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Information on this web site is provided for informational purposes only and is not a substitute for professional medical advice. You should not use the information on this web site for diagnosing or treating a medical or health condition. You should carefully read all product packaging. If you have or suspect you have a medical problem, promptly contact your professional healthcare provider.  

Copyright © 2010, Children Allergy Center  Information Education Network. All rights reserved

Food allergies, defined as an adverse immune response to food proteins, affect as many as 6% of young children and 3%-4% of adults in westernized countries, and their prevalence appears to be rising. In addition to well-recognized acute allergic reactions and anaphylaxis triggered by IgE antibody-mediated immune responses to food proteins, there is an increasing recognition of cell-mediated disorders such as eosinophilic gastroenteropathies and food protein-induced enterocolitis syndrome. We are gaining an increasing understanding of the pathophysiology of food allergic disorders and are beginning to comprehend how these result from a failure to establish or maintain normal oral tolerance. Many food allergens have been characterized at a molecular level, and this knowledge, combined with an increasing appreciation of the nature of humoral and cellular immune responses resulting in allergy or tolerance, is leading to novel therapeutic approaches.

Food allergies, defined as an adverse immune response to food proteins, affect as many as 6% of young children and 3%–4% of adults in westernized countries, and their prevalence appears to be rising. In addition to well-recognized acute allergic reactions and anaphylaxis triggered by IgE antibody–mediated immune responses to food proteins, there is an increasing recognition of cell-mediated disorders such as eosinophilic gastroenteropathies and food protein–induced enterocolitis syndrome. We are gaining an increasing understanding of the pathophysiology of food allergic disorders and are beginning to comprehend how these result from a failure to establish or maintain normal oral tolerance. Many food allergens have been characterized at a molecular level, and this knowledge, combined with an increasing appreciation of the nature of humoral and cellular immune responses resulting in allergy or tolerance, is leading to novel therapeutic approaches.

Generally, introduction of allergens through the digestive tract is thought to induce immune tolerance. In individuals who are predisposed to developing allergies (atopic syndrome), the immune system produces IgE antibodies against protein epitopes on non-pathogenic substances, including dietary components. The IgE molecules are coated onto mast cells, which inhabit the mucosal lining of the digestive tract. Upon ingesting an allergen, the IgE reacts with its protein epitopes and release (degranulate) a number of chemicals (including histamine), which lead to oedema of the intestinal wall, loss of fluid and altered motility. The product is diarrhea. The eight most common food allergies in North America and Europe are to eggs, milk, peanuts, soy, fish, shellfish, tree nuts, and wheat. Any food allergy has the potential to cause a fatal reaction.

Currently, management of food allergies consists of educating the patient to avoid ingesting the responsible allergen and initiating therapy if ingestion occurs. However, numerous strategies for definitive treatment are being studied, including sublingual/oral immunotherapy, injection of anti-IgE antibodies, cytokine/anticytokine therapies, Chinese herbal therapies, and novel immunotherapies utilizing engineered proteins and strategic immunomodulators.

Patophysiology

• Allergic reactions are hyperactive responses of the immune system to generally innocuous substances. When immune cells encounter the allergenic protein, IgE antibodies are produced; this is similar to the immune system’s reaction to foreign pathogens. The IgE antibodies identify the allergenic proteins as harmful and initiate the allergic reaction. The harmful proteins are those that do not break down due to the strong bonds of the protein. IgE antibodies bind to a receptor on the on the surface of the protein, creating a tag, just as a virus or parasite becomes tagged. It is not entirely clear why some proteins do not denature and subsequently trigger allergic reactions and hypersensitivity while others do not.
• Hypersensitivities are categorized according to the parts of the immune system that are attacked and the amount of time it takes for the response to occur. There are four types of Hypersensitivity reaction: Type 1, Immediate IgE-mediated, Type 2, Cytotoxic, Type 3, Immune complex-mediated, and Type 4, Delayed cell-mediated.  The pathophysiology of allergic responses can be divided into two phases. The first is an acute response that occurs immediately after exposure to an allergen. This phase can either subside or progress into a “late phase reaction” which can substantially prolong the symptoms of a response, and result in tissue damage.
• Many food allergies are caused by hypersensitivities to particular proteins in different foods. Proteins have unique properties that allow them to become allergens, such as stabilizing forces in the tertiary and quaternary structure which prevent degradation during digestion. Many theoretically allergenic proteins cannot survive the destructive environment of the digestive tract and thus don’t trigger hypersensitive reactions
• Food allergies are primarily the result of immune responses to food proteins. Normally, noninflammatory immune responses develop to ingested foods in a process called oral tolerance. For reasons that remain unclear, but likely include environmental and genetic factors, tolerance may be abrogated, leading to adverse immune responses. While sensitization (eg, development of an immunoglobulin E [IgE] immune response) to an allergen has been primarily assumed to occur from ingestion, this may not always be the case. For example, oral allergy syndrome (pollen-food related syndrome) describes an allergic response to specific raw fruits or vegetables that share homologous proteins with pollens; the initial route of sensitization is respiratory exposure to pollen proteins rather than oral exposure to food proteins. The skin may be another potential route of sensitization. 
• IgE antibody – mediated responses are the most widely recognized form of food allergy and account for acute reactions. Patients with atopy produce IgE antibodies to specific epitopes (areas of the protein) of one or more food allergens. These antibodies bind to high-affinity IgE receptors on circulating basophils and tissue mast cells present throughout the body, including the skin, gastrointestinal tract, and respiratory tract.
• Subsequent allergen exposure binds and cross links IgE antibodies on the cell surface, resulting in receptor activation and intracellular signaling that initiates the release of inflammatory mediators (eg, histamine) and synthesis of additional factors (eg, chemotactic factors, cytokines) that promote allergic inflammation. The effects of these mediators on surrounding tissues result in vasodilatation, smooth muscle contraction, and mucus secretion, which, in turn, are responsible for the spectrum of clinical symptoms observed during acute allergic reactions to food.
• Cell-mediated responses to food allergens may also mediate allergic responses, particularly in disorders with delayed or chronic symptoms. For example, food protein – induced enterocolitis syndrome (FPIES), a gastrointestinal food allergy, appears to be mediated by T-cell elaboration of the cytokine tumor necrosis factor (TNF)-alpha. Persons with atopic dermatitis that flares with ingestion of milk have been noted to have T cells that, in vitro, express the homing receptor cutaneous lymphocyte antigen, which is thought to home the cell to the skin and mediate the response.  Celiac disease is the result of an immune response to gluten proteins in grains; this disorder is reviewed in the eMedicine Pediatrics article Celiac Disease.
• Food allergens are typically water-soluble glycoproteins resistant to heating and proteolysis with molecular weights of 10-70 kd. These characteristics facilitate the absorption of these allergens across mucosal surfaces. Numerous food allergens are purified and well-characterized, such as peanut Ara h1, Ara h2, and Ara h3; chicken egg white Gal d1, Gal d2, and Gal d3; soybean-Gly m1; fish-Gad c1; and shrimp-Pen a1. Closely related foods frequently contain allergens that crossreact immunologically (ie, lead to the generation of specific IgE antibodies detectable by skin prick or in vitro testing) but less frequently crossreact clinically. Recently, delayed allergic reactions to meat proteins have been attributed to reactions to carbohydrate moieties

Mechanism of Food Allergy

• Normally, there is a delicate balance of the gastrointestinal mucosal immune system distinguishing between potentially harmful pathogens, beneficial commensal bacteria, and harmless food allergens which do not induce active immune responses. The mechanisms by which ingested proteins are able to interact with unique populations of antigen presenting cells leading to suppression of cellular and humoral immune responses has been termed oral tolerance. This has been demonstrated in a murine model in which subcutaneous antigen exposure resulted in cell-mediated and humoral responses to the antigen in vitro, but mice that were first orally exposed to the antigen then immunized subcutaneously had decreased immune responses in vitro.  Transfer of T cells from the orally fed mice to naïve mice resulted in decreased immune responses as well. Different mechanisms of tolerance can occur depending on the dose of allergen exposure. Studies suggest that “high dose” tolerance is due to deletion of effector T cells, whereas “low dose” tolerance involves activation of regulatory T cells.
• Loss of oral tolerance can occur or may be bypassed by antigen presentation via alternative routes, such as through cutaneous exposures or via the respiratory tract. Using a murine model, epicutaneous or epidermal exposure to peanut was demonstrated to induce Th2 immune responses and promoted allergic sensitization. In addition, higher rates of peanut allergy have been found in children with atopic dermatitis who used topical creams containing peanut oil (OR 6.8). Respiratory exposures are seen in pollen-food syndrome (PFS), an IgE-mediated allergy that is due to cross-reacting proteins in pollens (the initial sensitizing allergen) and foods, which results in oropharyngeal symptoms to raw fruits and vegetables.
• Breakdown of oral tolerance can also occur as a result of defective regulatory T cells. The disorder of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is due to a mutation in the FOXP3 gene, a transcription factor on CD4+CD25+ regulatory T cells that has been implicated in blocking Th1 and Th2 responses. Atopic dermatitis and food allergies are known manifestations of this disorder.  The importance of T regulatory cells in tolerance was also demonstrated in a study of non-IgE milk allergy. The development of tolerance to milk was associated with higher numbers of circulating CD4+CD25+ regulatory T cells.

Host factors

• Several host factors can influence the development of food allergies. Different mouse strains are not equally susceptible to food allergies, suggesting that genetic predisposition is important. Furthermore, the age of exposure to food allergens can determine whether tolerance or allergy develops. In a murine model, sensitization occurred when mice were orally fed ovalbumin in the first week of life, however, tolerance was induced when the mice were orally exposed to ovalbumin at 2-3 weeks of age. In humans, epidemiologic studies show a higher rate of food allergies in young children as compared to adults,  suggesting that gut maturity may be a factor in the development of food allergies. On the other hand, population studies suggest that early introduction may be beneficial in some cases. In Israel, where infants are fed peanut proteins starting at an early age, there is a lower incidence of peanut allergy as compared to the UK where peanut is not introduced to children until a much later age.  The Learning Early About Peanut Allergies (LEAP) study is currently exploring the role of timing of peanut allergen exposure in the development of peanut allergy.
• Several studies suggest that disruption of normal gut barrier functions, such as gastric pH and commensal bacteria, can increase the risk of food allergies. Gastric digestion normally serves to breakdown food proteins, and in many cases destroys immunogenic epitopes in the process. The role of gastric acidity was investigated by Untersmayr et al. using a murine model. Mice fed caviar extract in combination with antacids had elevated specific IgE and demonstrated immediate skin reactivity to the protein after immunization. However, mice which were not fed antacids did not demonstrate these immunologic responses, suggesting that use of antacid medications increased the risk of food allergen sensitization. In a human study of 152 patients on antacid treatment for dyspepsia, increased food allergen sensitization was seen in 25% after 3 months.  Gastric enzymes can affect allergenicity of food proteins. Specifically, the allergenicity of ovomucoid has been demonstrated to be reduced after gastric digestion.  Additionally, commensal bacterial serve an important role. Mice raised in a germ-free environment do not develop normal tolerance,  and mice treated with antibiotics or those lacking in toll like receptor 4 (TLR4) are more easily sensitized to peanut than wild-type control mice.
• Additional host factors can modulate the clinical response of food allergy. For example, asthma has been shown to be a risk factor for more severe anaphylaxis. In a study of fatal food allergic reactions, the majority of victims had underlying asthma.  Host factors such as exercise, use of medication (alcohol, aspirin, beta-blockers, angiotensin converting enzyme inhibitors, monoamine oxidase inhibitors, tricyclic antidepressants), and concurrent infection may increase the severity of anaphylactic reactions or diminish the efficacy of epinephrine. Recently, low serum platelet-activating factor acetylhydrolase (PAF-AH) activity has been found to be a risk factor for more severe food-induced anaphylaxis.

• Food allergies can produce an array of clinical symptoms. The presence of specific IgE to sequential or conformational epitopes can distinguish between different phenotypes of milk and egg allergy. Several studies show that binding of conformational epitopes is associated with transient allergy to milk and egg whereas binding of sequential epitopes in these proteins is a marker for persistent allergy. Recent studies demonstrate that the majority of milk and egg allergic individuals can tolerate extensively heated or baked forms of these foods,  indicating that these individuals identify conformational epitopes that are disrupted by heating. Furthermore, studies show that different patterns of epitope recognition or epitope diversity may correlate with clinical manifestations of allergic reactions to peanut and milk.
• Although heating appears to render many proteins less allergenic, heating does not have the same effect on all food proteins. Roasting peanuts involves very high temperatures, and this causes a Maillard reaction leading to increased stability and allergenicity of peanut allergens. This finding may explain the differences in prevalence of peanut allergy in the U.S. where peanuts are primarily consumed in the roasted form and China where boiled or fried peanuts predominate.
• Additional properties of peanut make it a highly allergenic protein. Glycosylated Ara h 1, a major peanut allergen, has been shown to act as a Th2 adjuvant by activating dendritic cells to drive Th2 cell maturation.
• In contrast, deglycoslyated Ara h 1 did not activate dendritic cells. Recently, peanut proteins were shown to have the ability to induce production of complement (C3a) leading to increased platelet-activating factor and histamine production by macrophages, basophils, and mast cells

 Acute response and Late-phase response

• Acute response.  In the early stages of allergy, a type I hypersensitivity reaction against an allergen, encountered for the first time, causes a response in a type of immune cell called a T_H2 lymphocyte, which belongs to a subset of T cells that produce a cytokine called interleukin-4 (IL-4). These T_H2 cells interact with other lymphocytes called B cells, whose role is the production of antibodies. Coupled with signals provided by IL-4, this interaction stimulates the B cell to begin production of a large amount of a particular type of antibody known as IgE. Secreted IgE circulates in the blood and binds to an IgE-specific receptor (a kind of Fc receptor called FcεRI) on the surface of other kinds of immune cells called mast cells and basophils, which are both involved in the acute inflammatory response. The IgE-coated cells, at this stage are sensitized to the allergen.
• If later exposure to the same allergen occurs, the allergen can bind to the IgE molecules held on the surface of the mast cells or basophils. Cross-linking of the IgE and Fc receptors occurs when more than one IgE-receptor complex interacts with the same allergenic molecule, and activates the sensitized cell. Activated mast cells and basophils undergo a process called degranulation, during which they release histamine and other inflammatory chemical mediators (cytokines, interleukins, leukotrienes, and prostaglandins) from their granules into the surrounding tissue causing several systemic effects, such as vasodilation, mucous secretion, nerve stimulation and smooth muscle contraction. This results in rhinorrhea, itchiness, dyspnea, and anaphylaxis. Depending on the individual, the allergen, and the mode of introduction, the symptoms can be system-wide (classical anaphylaxis), or localized to particular body systems; asthma is localized to the respiratory system and eczema is localized to the dermis.
• Late-phase response After the chemical mediators of the acute response subside, late phase responses can often occur. This is due to the migration of other leukocytes such as neutrophils, lymphocytes, eosinophils, and macrophages to the initial site. The reaction is usually seen 2–24 hours after the original reaction. Cytokines from mast cells may also play a role in the persistence of long-term effects. Late phase responses seen in asthma are slightly different from those seen in other allergic responses, although they are still caused by release of mediators from eosinophils, and are still dependent on activity of T_H2 cells

Degranulation process in allergy.

1 – antigen;

2 – IgE antibody;

• 3 – FcεRI receptor;
• 4 – preformed mediators (histamine, proteases, chemokines, heparine);
• 5 – granules;
• 6 – mast cell;
• 7 – newly formed mediators (prostaglandins, leukotrienes, thromboxanes, PAF)

Protein structure, function  and organization

• Proteins are composed of amino acid monomers linked by peptide bonds.  The higher order structure of a protein depends on the sequence of amino acids which form its primary sequence, as various non-covalent interactions between these amino acids ensure proper protein folding. Proteins have specific amino acid sequences, which all identical proteins share.
• A protein’s secondary structure is created by hydrogen-bond interactions between the amide and carboxyl groups of the amino acid backbone. Secondary structure includes the formation of alpha helices and beta sheets.
•  The tertiary structure is the overall shape of the protein, and is usually driven by the protein’s tendency to orient hydrophobic amino acid side chains internally, although hydrogen bonding, ionic interactions and disulfide bonds also help to stabilize proteins in the tertiary state  Quaternary structure is the overall combination of polypeptide subunits to form the functional unit.
• Protein function. Protein folding is essential to the overall function of the individual protein; some protein structures allow them to resist degradation in the acidic environment of the digestive tract.Polypeptide chains are often very long and flexible, which leads to a wide variety of ways for a protein to fold. Non-covalent interactions control the shape and structure of the nascent protein. A protein’s proper amino acid sequence is absolutely required to induce proper folding into the quaternary structure. Two common folding patterns seen in proteins are the alpha helix and beta sheets.

• The gastrointestinal tract plays an important role in the mucosal immune response. While acting as a conduit allowing the transfer of nutrients from the intestinal lumen to the systemic circulation, it also protects against invasion by microbes and other antigens by the induction of an immune response. A downregulation of these immune responses to nonharmful antigenic substances is termed oral tolerance. A breakdown or underdevelopment of oral tolerance may therefore lead to the development of food allergy. Adverse immunologic reactions to food may be a consequence of both IgE- and non-IgE-mediated mechanisms. Although genetic factors play a major role in the development of allergic disease, other factors involved in an immature mucosal immune response have been implicated. Non-IgE-mediated allergic responses tend to involve a T cell-mediated delayed hypersensitivity reaction, and released cytokines act as determinants of the immune response. The “hygiene hypothesis” proposes that a reduction in infections in early infancy predisposes to allergic responses. Early childhood infections promote the induction of a T-helper type 1 response that protects against the development of allergy, which is predominantly a T-helper type 2 response. The role of B cells and T cells in the development of food allergy is incompletely under- stood, but advances in the evaluation and characterization of food allergens has opened exciting new avenues in this study.

Reference :

• Sicherer SH, Sampson HA. Food allergy. J Allergy Clin Immunol. Feb 2010;125(2 Suppl 2):S116-25.
• Scott H. Sicherer and Hugh A. Sampson. Food Allergy: Recent Advances in Pathophysiology and Treatment. Annual Review of Medicine Vol. 60: 261-277 (Volume publication date February 2009)
• Sampson H (2004). “Update on food allergy”. J Allergy Clin Immunol 113 (5): 805–819. http://www.jacionline.org/article/PIIS0091674904011455/fulltext.
• Julie Wang and Hugh A Sampson. Food allergy: recent advances in pathophysiology and treatment. Allergy Asthma Immunol Res. 2009 October; 1(1): 19–29.

Supported  by

Office : JL Taman Bendungan Asahan 5  Jakarta Pusat  Phone : (021) 70081995 – 5703646email :  judarwanto@gmail.com, www.childrenallergyclinic.wordpress.com/  

Information on this web site is provided for informational purposes only and is not a substitute for professional medical advice. You should not use the information on this web site for diagnosing or treating a medical or health condition. You should carefully read all product packaging. If you have or suspect you have a medical problem, promptly contact your professional healthcare provider.  

Copyright © 2010, Children Allergy Center  Information Education Network. All rights reserved

Asthma is an airway disorder that causes respiratory hypersensitivity, inflammation, and intermittent obstruction. Asthma commonly causes constriction of the smooth muscles in the airway, wheezing, and dyspnea. Asthma is a common chronic disorder of the airways that is complex and characterized by variable and recurring symptoms, airflow obstruction, bronchial hyperresponsiveness, and an underlying inflammation. The interaction of these features of asthma determines the clinical manifestations and severity of asthma and the response to treatment.

Asthma is a common chronic disease worldwide and affects 22 million persons in the United States. Asthma is the most common chronic disease in childhood, affecting an estimated 6 million children, and it is a common cause of hospitalization for children in the United States. Despite recent advances in the understanding of the pathophysiology, assessment, and treatment of asthma, the condition continues to have significant medical and economic impacts worldwide.

They defined asthma as follows: Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role, in particular, mast cells, eosinophils, T lymphocytes, macrophages, neutrophils, and epithelial cells. In susceptible individuals, this inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness and coughing, particularly at night or in the early morning. These episodes are usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment. The inflammation also causes an associated increase in the existing bronchial responsiveness to a variety of stimuli. Reversibility of airflow limitation may be incomplete in some patients with asthma.

Pathophysiology of Asthma

Asthma is a condition characterized by paroxysmal narrowing of the bronchial airways due to inflammation of the bronchi and contraction of the bronchial smooth muscle. The inflammatory component is central to the pathogenesis of symptoms: dyspnea, cough, and wheezing.

The pathophysiology of asthma is complex and involves the following components:

• Airway inflammation
• Intermittent airflow obstruction
• Bronchial hyperresponsiveness

Interactions between environmental and genetic factors result in airway inflammation, which limits airflow and leads to functional and structural changes in the airways in the form of bronchospasm, mucosal edema, and mucus plugs. Airway obstruction causes increased resistance to airflow and decreased expiratory flow rates. These changes lead to a decreased ability to expel air and may result in hyperinflation. The resulting overdistention helps maintain airway patency, thereby improving expiratory flow; however, it also alters pulmonary mechanics and increases the work of breathing.

• Hyperinflation compensates for the airflow obstruction, but this compensation is limited when the tidal volume approaches the volume of the pulmonary dead space; the result is alveolar hypoventilation. Uneven changes in airflow resistance, the resulting uneven distribution of air, and alterations in circulation from increased intraalveolar pressure due to hyperinflation all lead to ventilation-perfusion mismatch. Vasoconstriction due to alveolar hypoxia also contributes to this mismatch. Vasoconstriction is also considered an adaptive response to ventilation/perfusion mismatch.
• In the early stages, when ventilation-perfusion mismatch results in hypoxia, hypercarbia is prevented by the ready diffusion of carbon dioxide across alveolar capillary membranes. Thus, patients with asthma who are in the early stages of an acute episode have hypoxemia in the absence of carbon dioxide retention. Hyperventilation triggered by the hypoxic drive also causes a decrease in PaCO₂. An increase in alveolar ventilation in the early stages of an acute exacerbation prevents hypercarbia. With worsening obstruction and increasing ventilation-perfusion mismatch, carbon dioxide retention occurs. In the early stages of an acute episode, respiratory alkalosis results from hyperventilation. Later, the increased work of breathing, increased oxygen consumption, and increased cardiac output result in metabolic acidosis. Respiratory failure leads to respiratory acidosis.
• Chronic inflammation of the airways is associated with increased BHR, which leads to bronchospasm and typical symptoms of wheezing, shortness of breath, and coughing after exposure to allergens, environmental irritants, viruses, cold air, or exercise. In some patients with chronic asthma, airflow limitation may be only partially reversible because of airway remodeling (hypertrophy and hyperplasia of smooth muscle, angiogenesis, and subepithelial fibrosis) that occurs with chronic untreated disease.

The mechanism of inflammation in asthma may be acute, subacute, or chronic, and the presence of airway edema and mucus secretion also contributes to airflow obstruction and bronchial reactivity. Varying degrees of mononuclear cell and eosinophil infiltration, mucus hypersecretion, desquamation of the epithelium, smooth muscle hyperplasia, and airway remodeling are present

• Some of the principal cells identified in airway inflammation include mast cells, eosinophils, epithelial cells, macrophages, and activated T lymphocytes. T lymphocytes play an important role in the regulation of airway inflammation through the release of numerous cytokines. Other constituent airway cells, such as fibroblasts, endothelial cells, and epithelial cells, contribute to the chronicity of the disease. Other factors, such as adhesion molecules (eg, selectins, integrins), are critical in directing the inflammatory changes in the airway. Finally, cell-derived mediators influence smooth muscle tone and produce structural changes and remodeling of the airway.
• The presence of airway hyperresponsiveness or bronchial hyperreactivity in asthma is an exaggerated response to numerous exogenous and endogenous stimuli. The mechanisms involved include direct stimulation of airway smooth muscle and indirect stimulation by pharmacologically active substances from mediator-secreting cells such as mast cells or nonmyelinated sensory neurons. The degree of airway hyperresponsiveness generally correlates with the clinical severity of asthma
• Airflow obstruction can be caused by a variety of changes, including acute bronchoconstriction, airway edema, chronic mucous plug formation, and airway remodeling. Acute bronchoconstriction is the consequence of immunoglobulin E–dependent mediator release upon exposure to aeroallergens and is the primary component of the early asthmatic response. Airway edema occurs 6-24 hours following an allergen challenge and is referred to as the late asthmatic response. Chronic mucous plug formation consists of an exudate of serum proteins and cell debris that may take weeks to resolve. Airway remodeling is associated with structural changes due to long-standing inflammation and may profoundly affect the extent of reversibility of airway obstruction.
• Aspirin, a cyclooxygenase inhibitor, produces severe bronchospasm in sensitive individuals. Leukotriene inhibitors reverse this sensitivity, providing further evidence that leukotrienes are important mediators of asthma.
• A balance between the adrenergic and cholinergic systems controls bronchomotor tone. Beta-agonist stimulation induces bronchodilation, and beta-blockers cause bronchoconstriction. More specific beta2-agonists have been developed to avoid the tachycardia associated with nonspecific beta-agonist agents. Cholinergic stimulation may cause bronchoconstriction. Anticholinergic agents (eg, ipratropium) produce bronchodilation.
• The airway narrowing in acute asthma manifests itself most commonly in adults as wheezing; in children, nocturnal cough is a very common presentation. The initial component is generally rapidly reversible bronchospasm of the smooth muscles that develops into more refractory inflammation of the airways characterized by bronchial edema, tenacious viscid secretions, mucous plugging, and atelectasis. Common causes of acute asthma include viral upper respiratory infections; exposure to allergens (eg, dustmites, animal dander); smoke inhalation; and cold, dry weather. A strong association had been thought to exist in women between the perimenstrual phase of their cycle and asthma symptoms, but the latest data suggest a more complex association between female sex hormones and asthma.

Another important mechanism underlying acute asthma involves antigen-antibody interactions, which activate membrane phospholipase and result in production of arachidonic acid. Arachidonic acid is metabolized by cyclooxygenase to vasoactive prostaglandins (eg, thromboxanes, prostacyclins) or leukotrienes and their precursors. Several are potent smooth muscle contractors that produce airway hyperresponsiveness and inflammation. The pharmacologic inhibition of leukotriene synthesis and/or action has a beneficial effect on induced and spontaneous asthma, demonstrating that leukotrienes can be important mediators of acute asthma and reactive airway disease (RAD).

The 2007 Expert Panel Report 3 noted several key new differences in the pathophysiology of asthma, as follows:

• The critical role of inflammation has been further substantiated, but evidence is emerging for considerable variability in the pattern of inflammation, thus indicating phenotypic differences that may influence treatment responses.
• Of the environmental factors, allergic reactions remain important. Evidence also suggests a key and expanding role for viral respiratory infections in these processes.
• The onset of asthma for most patients begins early in life, with the pattern of disease persistence determined by early, recognizable risk factors including atopic disease, recurrent wheezing, and a parental history of asthma.
• Current asthma treatment with anti-inflammatory therapy does not appear to prevent progression of the underlying disease severity.

New insights in the pathogenesis of asthma suggest the role of lymphocytes. Airway inflammation in asthma may represent a loss of normal balance between two “opposing” populations of Th lymphocytes. Two types of Th lymphocytes have been characterized: Th1 and Th2. Th1 cells produce interleukin (IL)-2 and IFN-α, which are critical in cellular defense mechanisms in response to infection. Th2, in contrast, generates a family of cytokines (IL-4, IL-5, IL-6, IL-9, and IL-13) that can mediate allergic inflammation.

• The current “hygiene hypothesis” of asthma illustrates how this cytokine imbalance may explain some of the dramatic increases in asthma prevalence in Westernized countries. This hypothesis is based on the concept that the immune system of the newborn is skewed toward Th2 cytokine generation (mediators of allergic inflammation). Following birth, environmental stimuli such as infections activate Th1 responses and bring the Th1/Th2 relationship to an appropriate balance.
• Evidence suggests that the prevalence of asthma is reduced in association with certain infections (Mycobacterium tuberculosis, measles, or hepatitis A); country living, exposure to other children (eg, presence of older siblings and early enrollment in childcare); and less frequent use of antibiotics. Furthermore, the absence of these lifestyle events is associated with the persistence of a Th2 cytokine pattern.
• Under these conditions, the genetic background of the child, with a cytokine imbalance toward Th2, sets the stage to promote the production of immunoglobulin E (IgE) antibody to key environmental antigens (eg, dust mites, cockroaches, Alternaria, and possibly cats). Therefore, a gene-by-environment interaction occurs in which the susceptible host is exposed to environmental factors that are capable of generating IgE, and sensitization occurs. A reciprocal interaction is apparent between the two subpopulations, in which Th1 cytokines can inhibit Th2 generation and vice versa. Allergic inflammation may be the result of an excessive expression of Th2 cytokines. Alternately, the possibility that the loss of normal immune balance arises from a cytokine dysregulation in which Th1 activity in asthma is diminished has been suggested in recent studies.
• In preschool children with asthma, 2 years of inhaled corticosteroid therapy did not change the asthma symptoms or lung function during a third, treatment-free year. This suggests that no disease-modifying effect of inhaled corticosteroids is present after the treatment is discontinued.
• Evidence suggests that rhinovirus is a significant risk factor for the development of wheeze in preschool children and a frequent trigger of wheezing illnesses in children with asthma. In addition, some studies highlight the importance of genotypes.
• Attempts to identify clinical subtypes of asthma using cluster analysis resulted in the identification of 5 phenotypes of asthma that differ in multiple ways, including age of onset, gender, body weight, degree of flow limitation, and frequency of exacerbatio

Exercise-Induced Asthma

• The pathogenesis of exercise-induced bronchospasm is controversial. The disease may be mediated by water loss from the airway, heat loss from the airway, or a combination of both. The upper airway is designed to keep inspired air at 100% humidity and body temperature at 37°C (98.6°F). The nose is unable to condition the increased amount of air required for exercise, particularly in athletes who breathe through their mouths. The abnormal heat and water fluxes in the bronchial tree result in bronchoconstriction, occurring within minutes of completing exercise. Results from bronchoalveolar lavage studies have not demonstrated an increase in inflammatory mediators. These patients generally develop a refractory period, during which a second exercise challenge does not cause a significant degree of bronchoconstriction.
• Functional Anatomy. The problem in EIA occurs distal to the glottis, in the lower airway. Bronchoconstriction is involved that is distinguishable from laryngospasm, which can occur in other exercise-related conditions. One such example is the condition known as vocal cord dysfunction in which there is paradoxical narrowing of the vocal cords during inspiration, resulting in stridor that is often misconstrued as audible wheezing. Normally, the vocal cords open with inspiration. (See also the eMedicine article Vocal Cord Dysfunction.)
• Sport-Specific Biomechanics. EIA usually affects individuals who participate in sports that include an aerobic component. The condition can be seen in any sport, but EIA is much less common in predominantly anaerobic activities. This is likely due to the role of consistent and repetitive air movement through the airways (seen in aerobic sports), which affect airway humidity and temperature. EIA triggers an unknown biochemical and neurochemical pathway, resulting in the bronchospasm, which manifests as the symptoms of the disease.
• Although the exact mechanism of EIA is unknown, there are 2 predominant theories as to how the symptom complex is triggered. One is the airway humidity theory, which suggests that air movement through the airway results in relative drying of the airway. This, in turn, is believed to trigger a cascade of events that results in airway edema secondary to hyperemia and increased perfusion in an attempt to combat the drying. The result is bronchospasm.
• The other theory is based on airway cooling and assumes that the air movement in the bronchial tree results in a decreased temperature of the bronchi, which may also trigger a hyperemic response in an effort to heat the airway. Again, the result is a spasm in the bronchi.
• Many authors think that there may be a combination of the above 2 theories that takes place, but the biochemical or physical pathways that mediate these responses are unclear. Evidence may even exist to support the idea that the resulting cascades are not the inflammatory pathways to which we attribute allergic asthma.
• Likewise, certain sports and their environments predispose individuals with asthma to experience EIA. Sports played in cold and dry environments usually result in more symptom manifestation for athletes with this condition. On the other hand, when the environment is warm and humid, the incidence and severity of EIA decrease.

Pregnancy

• Pregnancy has a significant effect on the respiratory physiology of a woman. While the respiratory rate and vital capacity does not change in pregnancy, there is an increase in tidal volume, minute ventilation (40%), and minute oxygen uptake (20%) with resultant decrease in functional residual capacity and residual volume of air as a consequence of the elevated diaphragm. In addition, airway conductance is increased and total pulmonary resistance is reduced, possibly as a result of progesterone. 
• The result of all of these physiologic changes is a hyperventilatory picture as a normal state of affairs in the later half of pregnancy. This results in the picture of a chronic respiratory alkalosis during pregnancy with a decreased pCO₂, decreased bicarbonate, and increased pH. A normal pCO₂ in a pregnant patient may signal impending respiratory failure. The increased minute ventilation and improved pulmonary function in pregnancy promote more efficient gas exchange from the maternal lungs to the blood. Therefore, changes in respiratory status occur more rapidly in pregnancy than in the nonpregnant patient. Asthma is characterized by inflammation of the airways, with an abnormal accumulation of eosinophils, lymphocytes, mast cells, macrophages, dendritic cells, and myofibroblasts. This leads to a reduction in airway diameter caused by smooth muscle contraction, vascular congestion, bronchial wall edema, and thick secretions.

Reference : :

• Randolph C. Exercise-induced asthma: update on pathophysiology, clinical diagnosis, and treatment. Curr Probl Pediatr. Feb 1997;27(2):53-77.
• Busse WW, Calhoun WF, Sedgwick JD. Mechanism of airway inflammation in asthma. Am Rev Respir Dis. Jun 1993;147(6 Pt 2):S20-4. 
• Henderson WR Jr. Role of leukotrienes in asthma. Ann Allergy. Mar 1994;72(3):272-8. 
• Horwitz RJ, Busse WW. Inflammation and asthma. Clin Chest Med. Dec 1995;16(4):583-602. 
• Sears MR. Consequences of long-term inflammation. The natural history of asthma. Clin Chest Med. Jun 2000;21(2):315-29. 
• Anderson SD. How does exercise cause asthma attacks?. Curr Opin Allergy Clin Immunol. Feb 2006;6(1):37-42. 
• Hough DO, Dec KL. Exercise-induced asthma and anaphylaxis. Sports Med. Sep 1994;18(3):162-72. 
• Beaudouin E, Renaudin JM, Morisset M, et al. Food-dependent exercise-induced anaphylaxis–update and current data. Allerg Immunol (Paris). Feb 2006;38(2):45-51. 
• Mabie WC. Asthma in pregnancy. Clin Obstet Gynecol. Mar 1996;39(1):56-69. 
• Mays M, Leiner S. Asthma. A comprehensive review. J Nurse Midwifery. May-Jun 1995;40(3):256-68.
• Nelson-Piercy C, Moore-Gillon J. Asthma in pregnancy. Br J Hosp Med. Feb 7-20 1996;55(3):115-7. 
• Rey E, Boulet LP. Asthma in pregnancy. BMJ. Mar 17 2007;334(7593):582-5. 

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Information on this web site is provided for informational purposes only and is not a substitute for professional medical advice. You should not use the information on this web site for diagnosing or treating a medical or health condition. You should carefully read all product packaging. If you have or suspect you have a medical problem, promptly contact your professional healthcare provider.  

          Copyright © 2010, Children Allergy Center  Information Education Network. All rights reserved

Prevalence and Incidence

Adverse food reactions can be broadly classified into 2 categories. The first category consists of immunologically-mediated adverse reactions to foods that are termed food allergies. Food allergies can result in disorders with an acute onset of symptoms following ingestion of the triggering food allergen  and in chronic disorders. The second category is composed of adverse reactions that are not immune-mediated. An example is lactose intolerance caused by a deficiency of lactase. Adverse reactions to foods can also occur from toxic (eg, bacterial food poisoning) or pharmacologic (eg, caffeine) effects

In contrast to respiratory allergies, the epidemiology of food allergy has been little studied, and there is no strong evidence for an increasing incidence, either among infants and children or in adults. Neither are there any studies showing regional differences in prevalence. On the contrary, studies in many country indicate a similar prevalence during the first 2 years of life, both in verified food allergy and reported food intolerance. This is despite a low prevalence of respiratory allergies in the two former countries and a high prevalence in other country.

Food allergy is a large public health problem in the world  and the prevalence is growing. Awareness of the problem continues to grow and child day care, schools, and public institutions are developing protective policies and health programs to deal with the issue. A representative nationwide sample is needed, though, to get an accurate estimate of the prevalence of food allergies in the world wide. Population to help public health policy makers and care providers in planning and allocating resources for the recognition and treatment of food allergy.

The major problem with such epidemiological studies lies in the fact that there are no simple diagnostic criteria to verify the diagnosis. So far IgE determinations have been the only available diagnostic test, and their value is limited by poor sensitivity and the fact that at best they would only verify a small proportion of food intolerance, i.e. that caused by IgE-mediated reactions. A diagnosis of food allergy/intolerance must be based on a double-blind placebo-controlled food challenge, and not on the patient’s or doctor’s impression. More studies are required from different regions in order to identify similarities and differences in the patterns of food allergy. In particular, there is a need for properly conducted epidemiological studies in adults. Such studies should be interdisciplinary, as the cultural and social perceptions of food allergy and food intolerance would be expected to have a major impact on prevalence, perhaps even more than medical factors.

• The increasing prevalence of allergic diseases in westernized countries poses a significant health problem and a tremendous burden on quality of life and healthcare expenditure. Food allergy affects as many as 6% of young children and 3% to 4% of adults. While the majority of children outgrow their allergy to milk, egg, wheat and soy, allergies to peanut, tree nuts, fish and shellfish are often life-long. Currently, there are no treatments that can cure or provide long-term remission from food allergy.
• General surveys report that as many as 25-30% of households consider at least 1 family member to have a food allergy. This high rate is not supported by controlled studies in which oral food challenges (a medically supervised, gradual test feeding) are used to confirm patient histories. The actual prevalence of food allergies is estimated to be 5-6% in infants and children and 3.7 % in adults. However, comprehensive studies that include oral food challenges are few in number. Considering allergy to milk, egg, peanut, and seafood in a meta-analysis of 6 international studies using oral food challenges, estimated rates of 1-10.8% were obtained. In a meta-analysis including allergy to fruits and vegetables (excluding peanut), only 6 international studies included oral food challenges, and estimates of allergy varied widely from 0.1-4.3% for fruits and tree nuts to 0.1-1.4% for vegetables to under 1% for wheat, soy, and sesame.
• Studies in the United States and the United Kingdom indicate a rise in peanut allergy among young children in the past decade.
•  One study showed an increase of peanut allergy in children from 0.4% in 1997 to 0.8% in 2002. Recent studies from Canada and the United Kingdom indicate allergy rates to peanut of over 1% in children.
• Based upon available studies, estimations of the rate of food allergies in children have been summarized as follows for common food allergens: cow milk, 2.5%; eggs, 1.3%; peanuts, 0.8%; wheat, 0.4%; and soy, 0.4%.  Allergic reactions to non-protein food additives are uncommon
• An estimated 2.5% of the U.S. population has it; blacks, males and children are at increased risk for it, and it may be a factor in severe episodes of asthma.
  General surveys report that as many as 25-30% of households consider at least 1 family member to have a food allergy. This high rate is not supported by controlled studies in which oral food challenges (a medically supervised, gradual test feeding) are used to confirm patient histories.
• A recent report from the Centers for Disease Control and Prevention (CDC) indicated an 18% rise in food allergy among children in the past decade
• The actual prevalence of food allergies is estimated to be 5-6% in infants and children and 3.7 % in adults.
• Comprehensive studies that include oral food challenges are few in number. Considering allergy to milk, egg, peanut, and seafood in a meta-analysis of 6 international studies using oral food challenges, estimated rates of 1-10.8% were obtained.
• In a meta-analysis including allergy to fruits and vegetables (excluding peanut), only 6 international studies included oral food challenges, and estimates of allergy varied widely from 0.1-4.3% for fruits and tree nuts to 0.1-1.4% for vegetables to under 1% for wheat, soy, and sesame.
• A cross-sectional survey of data on food allergy among children <18 years of age, as reported in the 1997–2007 National Health Interview Survey, 2005–2006 National Health and Nutrition Examination Survey, 1993–2006 National Hospital Ambulatory Medical Care Survey and National Ambulatory Medical Care Survey, and 1998–2006 National Hospital Discharge Survey, was performed. Reported food allergies, serum immunoglobulin E antibody levels for specific foods, ambulatory care visits, and hospitalizations were assessed.
• In 2007, 3.9% of US children <18 years of age had reported food allergy. The prevalence of reported food allergy increased 18% (z = 3.4; P < .01) from 1997 through 2007. In 2005–2006, serum immunoglobulin E antibodies to peanut were detectable for an estimated 9% of US children. Ambulatory care visits tripled between 1993 and 2006 (P < .01). From 2003 through 2006, an estimated average of 317000 food allergy-related, ambulatory care visits per year (95% confidence interval: 195000–438000 visits per year) to emergency and outpatient departments and physician’s offices were reported. Hospitalizations with any recorded diagnoses related to food allergy also increased between 1998–2000 and 2004–2006, from an average of 2600 discharges per year to 9500 discharges per year (z = 3.4; P < .01), possibly because of increased use of food allergy V codes.
• Studies in the United States and the United Kingdom indicate a rise in peanut allergy among young children in the past decade.[16,17 ]One study showed an increase of peanut allergy in children from 0.4% in 1997 to 0.8% in 2002.
• Severe anaphylactic reactions, including death, can occur following the ingestion of food. Symptoms observed in a food-induced anaphylactic reaction may involve the skin, gastrointestinal tract, and respiratory tract. Frequently observed symptoms include oropharyngeal pruritus, angioedema (eg, laryngeal edema), stridor, dysphonia, cough, dyspnea, wheezing, nausea, vomiting, diarrhea, flushing, urticaria, and angioedema. Fatalities result from severe laryngeal edema, irreversible bronchospasm, refractory hypotension, or a combination thereof.
• Peanuts, tree nuts, fish, and shellfish are the foods most often implicated in severe food-induced anaphylactic reactions, though anaphylactic reactions have been reported to a wide variety of foods. Fatalities caused by reactions to milk are increasingly noted.
• Risk factors or associations for fatal food-induced anaphylaxis include: (1) the presence of asthma, especially in patients with poorly controlled disease; (2) previous episodes of anaphylaxis with the incriminated food; (3) a failure to recognize early symptoms of anaphylaxis; and (4) a delay or lack of immediate use of epinephrine to treat the allergic reaction. Teenagers and young adults appear to be overrepresented in registries of food allergy fatalities and present a special risk group.
• Among children, males appear to be more affected; among adults, females are more frequently affected.  In infants and children younger than 3 years, the prevalence of food allergy is approximately 5-6%. The estimated prevalence in adults is approximately 3.7%
• Recent studies from Canada and the United Kingdom indicate allergy rates to peanut of over 1% in children.
• Based upon available studies, estimations of the rate of food allergies in children have been summarized as follows for common food allergens: cow milk, 2.5%; eggs, 1.3%; peanuts, 0.8%; wheat, 0.4%; and soy, 0.4%. Allergic reactions to non-protein food additives are uncommon.
• A recent report from the Centers for Disease Control and Prevention (CDC) indicated an 18% rise in food allergy among children in the past decade.
• Severe anaphylactic reactions, including death, can occur following the ingestion of food.Symptoms observed in a food-induced anaphylactic reaction may involve the skin, gastrointestinal tract, and respiratory tract. Frequently observed symptoms include oropharyngeal pruritus, angioedema (eg, laryngeal edema), stridor, dysphonia, cough, dyspnea, wheezing, nausea, vomiting, diarrhea, flushing, urticaria, and angioedema. Fatalities result from severe laryngeal edema, irreversible bronchospasm, refractory hypotension, or a combination thereof.
• Peanuts, tree nuts, fish, and shellfish are the foods most often implicated in severe food-induced anaphylactic reactions, though anaphylactic reactions have been reported to a wide variety of foods. Fatalities caused by reactions to milk are increasingly noted.
• Risk factors or associations for fatal food-induced anaphylaxis include: (1) the presence of asthma, especially in patients with poorly controlled disease; (2) previous episodes of anaphylaxis with the incriminated food; (3) a failure to recognize early symptoms of anaphylaxis; and (4) a delay or lack of immediate use of epinephrine to treat the allergic reaction.
• Teenagers and young adults appear to be overrepresented in registries of food allergy fatalities and present a special risk group.
• Incidence of food allergy and related hospital visits increased significantly from 1997 to 2007, according to CDC researchers. However, officials remain uncertain as to whether the statistics represent actual increases in clinical disease or reflect parental and health care provider awareness.
• Data analysis from several nationally representative surveys revealed the following:  In 2007, 3.9% of all children reported having experienced a food or digestive allergy in the previous 12 months — an 18% increase from rates reported in 1997 (P<.01).
• Food allergy–related outpatient visits tripled between 1993 and 2006 (P<.01) and were estimated at about 317,000 during that period.
• Hospitalization with documented food-related diagnoses rose from an average of 2,600 discharges per year (1998-2000) to 9,500 discharges per year (2004-2006; P<.01).
• The adoption of diagnostic V codes in 2000, which record health issues not directly related to hospitalization, may play a part in the observed inflations, according to the researchers.
• Reported food allergy is increasing among children of all ages, among boys and girls and among children of different races/ethnicities.
• Blood test results revealed that immunoglobulin E antibody responses varied depending on race/ethnicity, with black children more likely to have detectable levels of antibody to peanut and milk compared with white children, and a four times greater likelihood of having detectable antibody to shellfish.
• Hispanic children were more likely than white children to experience food allergies but less likely than black children. This might demonstrate disparities in awareness and reporting among different demographic groups. Alternatively, racial differences between food-specific IgE levels and self-reported food allergies might be attributable to differences in dietary habits or other factors that differ among these racial/ethnic groups.”
• Among children, males appear to be more affected; among adults, females are more frequently affected.
• In infants and children younger than 3 years, the prevalence of food allergy is approximately 5-6%.
• The estimated prevalence in adults is approximately 3.7%.
• By the age of 3 years, 5-6% of children suffer from FHS based on food challenges and a good clinical history. There were large discrepancies between reported and diagnosed FHS. Comparing our data with a study performed in the USA more than 20 years ago, there were no significant differences in the cumulative incidence of FHS.
• The data from the nation-wide Surveying Canadians to Assess the Prevalence of Common Food Allergies and Attitudes towards Food Labelling and Risk (SCAAALAR) telephone survey, sponsored by Health Canada and the AllerGen research network, was presented at the American Academy of Allergy, Asthma & Immunology’s conference in March, 2009.
• While the information is not complete – it reflects about 90 per cent of the 9,000 individuals on whom data was collected: A greater prevalence of peanut allergy in Canadian children, and a greater prevalence of tree nut allergy overall, and in Canadian children.
• In Canada, 1.52 per cent of children are allergic to peanuts, based on a history of allergic reaction. The comparable figure in the U.S., from a 2002 survey, is .83 per cent, representing an 83 per cent higher rate in Canada. Similarly, the rate of tree nut allergy is about 120 per cent higher for Canadian children: 1.13 per cent have a history of reaction here, compared to .51 per cent in the United States.
• About 50 per cent higher rate of the allergy in U.S. adults compared to Canadian adults.
• That the differences come with a few caveats: the Canadian data was collected six years after the U.S. data, and some of the difference could be attributed to an increase in food allergies over that time. Also, the SCAAALAR team has not analyzed the demographics of the Canadian survey respondents yet, so it’s unclear if the studies represent the same socio-economic groups. This analysis will be done before the final results are published next year. (Updated U.S. statistics are also coming next year.)
• While the rates of allergy that Clarke and her team used to compare to U.S. figures are based on having a history of food allergy reactions, they also collected data on those who have had a medical diagnosis of food allergy, without a previous reaction. It might mean that the parent is going in with a child and saying, well, his brother has peanut allergies so I’m concerned he might be allergic, but he’s never eaten it.
• The physician then does a skin or blood test and makes a diagnosis based on the results. The SCAAALAR team is currently contacting all physicians who made the diagnoses in these cases to confirm that yes, that patient is deemed to have a true food allergy.
• The final figures for food allergy prevalence in Canada for individual foods, as well as overall incidence figures, will be based on those who have had a history of allergic reaction, as well as those who have a confirmed physician diagnosis
• Data from some study representative health and health care surveys indicate increases in reported food allergy estimates among world wide children . However, it cannot be determined how much of the increases in estimates are truly attributable to increases in clinical disease and how much are attributable to increased awareness by physicians, other health care providers, and parents. However, the consistent increases across surveys and among children in all age, gender, and race/ethnicity groups provide evidence that the increases are not limited to a certain setting, reporting mechanism, or demographic group.

Reference :

• Kagan RS, Joseph L, Dufresne C, Gray-Donald K, Turnbull E, Pierre YS, et al. Prevalence of peanut allergy in primary-school children in Montreal, Canada. J Allergy Clin Immunol. Dec 2003;112(6):1223-8. 
• Rona RJ, Keil T, Summers C, Gislason D, Zuidmeer L, Sodergren E, et al. The prevalence of food allergy: a meta-analysis. J Allergy Clin Immunol. Sep 2007;120(3):638-46. 
• Zuidmeer L, Goldhahn K, Rona RJ, Gislason D, Madsen C, Summers C, et al. The prevalence of plant food allergies: a systematic review. J Allergy Clin Immunol. May 2008;121(5):1210-1218.e4. 
• Sicherer SH, Munoz-Furlong A, Sampson HA. Prevalence of peanut and tree nut allergy in the United States determined by means of a random digit dial telephone survey: a 5-year follow-up study. J Allergy Clin Immunol. Dec 2003;112(6):1203-7. 
• Grundy J, Matthews S, Bateman B, Dean T, Arshad SH. Rising prevalence of allergy to peanut in children: Data from 2 sequential cohorts. J Allergy Clin Immunol. Nov 2002;110(5):784-9. 

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Office : JL Taman Bendungan Asahan 5  Jakarta Pusat  Phone : (021) 70081995 – 5703646email :  judarwanto@gmail.com, www.childrenallergyclinic.wordpress.com/  

Information on this web site is provided for informational purposes only and is not a substitute for professional medical advice. You should not use the information on this web site for diagnosing or treating a medical or health condition. You should carefully read all product packaging. If you have or suspect you have a medical problem, promptly contact your professional healthcare provider.  

Copyright © 2010, Children Allergy Center  Information Education Network. All rights reserved

 Google, Situs Pencarian Dunia Maya Yang Paling Handal

Para pengguna dunia maya pasti tidak akan pernah asing dengan google. Bahkan hampir semua toolbar yang ada di layar monito komputer google menjadi pilihan utama. Google Inc  merupakan sebuah perusahaan publik Amerika Serikat, berperan dalam pencarian Internet dan iklan online. Perusahaan ini berbasis di Mountain View, California, dan memiliki karyawan berjumlah 19.604 orang.  Filosofi Google meliputi slogan seperti “Don’t be evil”, dan “Kerja harusnya menantang dan tantangan itu harusnya menyenangkan”, menggambarkan budaya perusahaan yang santai.

Google didirikan oleh Larry Page dan Sergey Brin ketika mereka masih mahasiswa di Universitas Stanford dan perusahaan ini merupakan perusahaan saham pribadi pada 7 September 1998. Penawaran umum perdananya dimulai pada tanggal 19 Agustus 2004, mengumpulkan dana $1,67 milyar, menjadikannya bernilai $23 milyar. Melalui berbagai jenis pengembangan produk baru, pengambil alihan dan mitra, perusahaan ini telah memperluas bisnis pencarian dan iklan awalnya hingga ke area lainnya, termasuk email berbasis web, pemetaan online, produktivitas perusahaan, dan bertukar video.

Google menginginkan web ke depannya akan lebih berpengaruh besar dan persuasif kepada para pengguna.  Jejaring sosial berkembang sangat cepat di internet di seluruh dunia. Selain itu, sangat menarik karena makin maraknya konten yang dibuat sendiri oleh para pengguna. Strategi terbuka Google adalah untuk membuat web makin berpengaruh, misalnya melalui Google Chrome, Chrome OS, dan Android di ponsel,” ungkapnya. Selain itu, lanjutnya, Google juga memperkuat para pengembang web dengan peralatan yang efektif, seperti application engines, GWT, Chrome Tools, Chrome Search, dan Chrome Geo.

Google Chrome yang diklaim sebagai aplikasi yang sangat cepat dan sederhana untuk digunakan. Chrome merupakan platform terbaru untuk aplikasi web, yang memungkinkan kita melakukan hal-hal yang sebelumnya tidak bisa kita lakukan. Google juga merambah dunia mobile melalui Android. Setelah Android 2.1 atau yang biasa disebut Eclaire, Google sudah merilis versi baru Android yang lebih handal, yaitu Android 2.2 yang dikenal dengan sebutan Froyo.

Android sudah digunakan di sekitar 90 device, 21 manufaktur, 50 carrier, dan di 49 negara. Google juga menyediakan layanan Google Application Engine yang mudah dikembangkan, dijaga, dan diukur. Para pengembang dapat bergabung dalam komunitas para pengembang karena terbukti ide-ide segar lahir dari pertukaran gagasan di komunitas. Para pengembang juga dapat mengunjungi code.google.com untuk bisa memanfaatkan sejumlah aplikasi yang disediakan Google

Saat ini, Google mengklaim layanan Google Apps mengklaim telah digunakan 2 juta pengguna bisnis baik yang menggunakan veris gratis maupun berbayar. Sementara Microsoft maish jauh lebih besar dengan 500 juta pelanggan Microsoft Office.

Google Maps Indonesia

Google meluncurkan Google Maps Indonesia, sebuah platform pencarian lokal yang membantu pengguna menemukan informasi geografis seperti peta online, citra satelit, panduan arah berkendara, alamat dan daftar perusahaan, melalui PC dan telepon seluler. Google Maps Indonesia resmi diluncurkan dan siap digunakan untuk memudahkan kehidupan sehari-hari. Pengguna dapat dengan mudah mencari dan menemukan informasi suatu tempat yang diinginkan, kapan pun, dan di mana pun. Pengguna bisa mengaksesnya di alamat maps.google.co.id. Platform ini diharapkan menjadi peta online yang paling kaya konten dan paling relevan di Tanah Air.

Google Maps Indonesia memungkinkan pengguna, perusahaan, dan pengembang lokal untuk memberi sumbangan informasi mengenai Indonesia. Google menggandeng pelaku bisnis yang berniat mempromosikan serta membagi informasi tentang usaha mereka melalui platform ini. Sejumlah perusahaan yang telah menjadi mitra bisnis Google Maps Indonesia, antara lain urbanesia.com, Telkomsel, dan LewatMana.com  Selain lokasi, Google Maps Indonesia juga mampu menyajikan informasi tentang tempat yang dituju. Sebuah rumah makan di Jakarta, misalnya, si pengguna tidak hanya dapat mengetahui lokasi, tetapi juga mendapatkan informasi tentang restoran sushi tersebut.

Meski sudah menyediakan berbagai layananya dalam versi bahasa Indonesia, Google Maps merupakan produk kedua Google yang resmi diluncurkan di Indonesia. Sebelumnya, Google juga meluncurkan secara resmi browser Chrome. Namun, sampai saat ini Google belum membuka kantor perwakilan di Indonesia.

Produk

Google telah membuat layanan dan peralatan untuk lingkungan bisnis dan masyarakat; termasuk aplikasi web, jaringan periklanan dan solusi bagi bisnis.

Periklanan

Kebanyakan dari pendapatan Google berasal dari program periklanan. Untuk keuangan tahun 2006, perusahaan ini dilaporkan mendapat jumlah keuntungan periklanan sebesar $10,492 milyar dan hanya $112 juta pada pendapatan lisensi dan lainnya. Google AdWords membolehkan pengiklan web menampilkan iklannya dalam hasil pencarian Google dan Google Content Network, melalui sebuah sistem bayar-per-klik atau bayar-per-lihat. Pemilik website Google AdSense juga dapat menampilkan iklannya di situs mereka sendiri, dan mendapat untung setiap kali iklan diklik.

Aplikasi

Google dilaporkan bakal secara totalitas masuk ke bisnis aplikasi mulai Maret mendatang. Layanan Google Apps yang selama ini hanya menyediakan software-software buatannya, dalam waktu dekat akan berubah menjadi bursa yang menerima aplikasi buatan pihak ketiga yang memanfaatkan layanan-layanan yang telah dikembangkan Google. Menurut  Wall Street Journal,  layanan ini lebih ditujukan untuk konsumen bisnis. Para pengembang dapat menjual aplikasi buatannya dan berbagi keuntungan dengan Google. Selama ini, transaksi bisnis untuk memperoleh aplikasi-aplikasi sejenis dilakukan secara tak langsung melalui layanan Solutions Marketplace.

Google ke depan akan membebeaskan penggunanya untuk langsung mengakses aplikasi yang telah dibelinya melalui menu di atas tampilan layarnya lewat Gmail atau Google Docs. Namun, bagaimana skema penjualannya belum diungkapkan. Tujuan utama bursa aplikasi ini jelas menyaingi cengekaraman bisnis Microsoft. Selama ini, Google telah memperoleh pelanggan besar di layanan aplikasi berbasis cloud computing itu, antara lain dari Motorola dan Genentech Inc. Namun, banyak perusahaan masih memilih solusi offline Microsoft dengan alasan kelengkapan fitur dan keamanan data. Google membanderol seperangkat layanan aplikasi untuk bisnis dengan harga 50 dollar AS per pengguna per tahun.

Aplikasi yang ada dalam Google adalah :

•  Google dikenal luas karena layanan pencarian webnya, yang mana merupakan sebuah faktor besar dari kesuksesan perusahaan ini. Pada Agustus 2007, Google merupakan mesin pencari di web yang paling sering digunakan dengan saham pasaran sebanyak 53,6%, kemudian Yahoo! (19,9%) dan Live Search (12,9%). Google memiliki milyaran halaman web, sehingga pengguna dapat mencari informasi yang mereka inginkan, melalui penggunaan kata kunci dan operator. Google juga telah menggunakan teknologi Pencarian Web pada layanan pencarian lainnya, termasuk, Pencarian Gambar, Google News, situs perbandingan harga Google Product Search, arsip Usenet interaktif Google Groups, Google Maps dan lainnya.
• Tahun 2004, Google meluncurkan layanan email berbasis web gratisnya, disebut sebagai Gmail. Gmail memiliki fitur teknologi penyaringan spam dan kemampuan untuk menggunakan teknologi Google untuk mencari surel. Layanan ini mendatangkan keuntungan dengan menampilkan iklan dari layanan AdWords yang dimasukkan dalam isi pesan email yang ditampilkan di layar.
• Pada awal 2006, perusahaan ini meluncurkan Google Video, yang tidak hanya membolehkan pengguna untuk mencari dan melihat video secara gratis, tetapi juga membolehkan pengguna dan penyebar media menyebarkan isinya, termasuk acara-acara televisi CBS, pertandingan basket NBA, dan video musik.  Bulan Agustus 2007, Google mengumumkan bahwa mereka akan menghentikan program penyewaan dan penjualan videonya dan menawarkan pengembalian uang dan kredit Google Checkout bagi pengguna yang telah membeli video untuk sendiri.
• Google juga telah membuat beberapa aplikasi desktop, termasuk Google Earth, sebuah program pemetaan interaktif yang disediakan oleh satelit dan fotografi udara yang mencakup keseluruhan planet Bumi. Google Earth dianggap sangat akurat dan lebih mendetil. Beberapa kota besar memiliki gambar jelas yang dapat dibesarkan sedekat-dekatnya untuk melihat kendaraan dan pejalan kaki dengan jelas. Akibatnya, terdapat beberapa alasan mengenai keterlibatan dalam keamanan nasional. Secara spesifik, beberapa negara dan militer beranggapan perangkat lunak ini dapat digunakan untuk melihat dengan kejelasan dekat-jelas lokasi fisik infrastruktur yang rusak, bangunan komersial dan penghunian, pangkalan, agensi pemerintah, dan lainnya. Bagaimanapun, gambar satelit jarang diperbarui, dan semuanya tersedia gratis melalui produk lainnya dan bahkan sumber pemerintah (NASA dan National Geospatial-Intelligence Agency, sebagai contoh). Beberapa orang menilai argumen ini dengan menyatakan bahwa Google Earth mudah diakses juga saat mencari lokasi.
• Beberapa produk lainnya tersedia melalui Google Labs, yang mana merupakan sebuah koleksi aplikasi yang belum selesai dan masih dalam tahap ujicoba agar dapat digunakan publik.
• Google telah mempromosikan produk mereka dalam berbagai cara. Di London, Google Space didirikan di Bandar Udara Heathrow, menampilkan berbagai produk, termasuk Gmail, Google Earth dan Picasa. Juga, sebuah halaman yang sama diluncurkan untuk mahasiswa Amerika, dibawah nama College Life, Powered by Google.
• Tahun 2007, beberapa laporan menyatakan bahwa Google merencanakan peluncuran telepon genggam milik mereka, kemungkinan sebuah pesaing bagi iPhone Apple.Pada 5 November 2007, Google akhirnya mengumumkan Android, sebuah platformperangkat lunak dan sistem operasi bagi perangkat bergerak yang didukung Open Handset Alliance, sebuah konsorsium yang terdiri dari 34 perusahaan perangkat lunak, perangkat keras, dan telekomunikasi yang bertujuan mengembangkan standar terbuka bagi perangkat bergerak. Pada bulan September 2008, T-Mobile merilis ponsel pertama yang berjalan pada platform Android, yakni G1.
• Bulan Oktober 2007, layanan Google SMS diluncurkan di India dan membolehkan pengguna memperoleh daftar bisnis, jadwal pemutaran film dan informasi dengan mengirim pesan singkat.
• Google juga meluncurkan Google Chrome yaitu sebuah browser. Browser ini cukup cepat dan tampilannya minimalis. Browser web Chrome buatan Google agresif mengeruk kue di pasar pengguna internet. Hanya dalam waktu kurang dari dua tahun saja, Chrome berhasil menempus peringkat tiga dan mengalahkan browser Safari buatan Apple. Analisis terakhir yang dilakukan StatCounter menunjukkan, Chrome telah menguasai 9,4 persen pasar browser di dunia. Sementara Safari baru meraih 4 persen. Pasar terbesar tetap dipegang Internet Explorer buatan Microsoft dengan 53 persen diikuti Mozilla Firefox sebesar 31 persen. Statistik tersebut diambil dari smapel data 3,6 miliar pagiview di sleuruh dunia. Ini merupakan salah satu prestasi lagi dari Google mengingat mereka tumbuh dari nol. Hal ini juga menjadi pertaruhan baru dalam peta persaingan Google dan Apple yang juga sengit di platform perangkat smartphone antara iPhone dan Android. Google telah menyediakan versi final dari Google Chrome untuk pengguna Microsoft Windows maupun Apple Macintosh. pengguna Linux telah tersedia versi beta. Namun, sampai sekarang Chrome belum tersedia untuk ponsel/smartphone seperti halnya Safari. Chrome selama ini mengandalkan sebagai browser yang ringan. Tampilannya juga sederhana meski penggunanya tetap dapat menghias latar belakangnya dengan tema foto-foto pilihan maupun tambahan aplikasi yang disebut ekstensi. Chrome juga mendukung tab browsing yang tidak akan crash meskipun salah satu tab mengalami masalah. Fitur anti-crash ini belum ada pada browser lainnya.
• Dari segala browser beken seperti Internet Explorer 7, Mozilla FireFox 3, Opera, maupun Safari milik Apple, ternyata Chrome lebih mengkilap.  Menurut penilaian skor, Google Chrome adalah rajanya cepat. Chrome meraih 30 poin, di atas FireFox (20), dan Opera (10). 
  Selain menakar kecepatan, pengukuran yang dilakukan Brandon juga menganalisa bagaimana tiap browser menangani konten flash, javascript, serta kompatibiiltas coding.  Pengukuran tersebut menguji tiap browser berselancar ke situs-situs yang memiliki rich-content, seperti BBC, YouTube, Gamspot, Zoho Writer, dan Fark.com
• Google TV. Untuk memulai membangun website untuk Google TV, Google Code telah menyediakan dokumentasi baru dan Google TV forum web untuk membantu pengembang lebih terlibat dalam proses.Bisnis besar Google ini (selain pengembangan Android) sangat banyak menarik perhatian semua kalangan termasuk pengembang web. Anda bisa melihat situs-situs yang sudah dirilis di Google TV. Selain partner-partner yang sudah diumumkan sebelumnya ada Net-A-Porter : situs video dan shop fashion , Meegenius : situs bacaan buku anak-anak, Tuneln : situs radio TV dan The Onion : situs lawak. Google mengumumkan telah memberikan lebih dari 3000 buah perangkat Google TV bagi peserta konfrensi Adobe Max 2010 dan akan menjangkau ribuan pengembang dalam komunitas Google Code secara gratis. Dan Google berencana akan memberikan total 10,000 perangkat Google TV gratis bagi Web Developer yang beruntung dalam rangka membantu pengembang mulai membangun TV. Hal ini bertujuan untuk menjaring lebih banyak situs yang bisa dinikmati melalui Google TV
• Untuk Tuna Netra. Google kini mengembangkan aplikasi serupa ke dalam Android, sebuah layanan navigasi.
  Tidak tanggung-tanggung, dua aplikasi sekaligus digelontorkan oleh Google. Aplikasi-aplikasi tersebut dimaksudkan untuk menolong orang buta agar bisa berkeliling kota dengan lebih mudah.
• Tahun 2007, Google meluncurkan Google Apps Premier Edition, sebuah versi lain Google Apps yang difokuskan terutama pada pengguna bisnis. Produk ini memiliki beberapa tambahan seperti ruang disk lebih banyak untuk e-mail, akses API, dan penyokong utama, dengan harga USD50 per pengguna per tahun. Sebuah pertemuan besar Google Apps dengan 38.000 pengguna dilaksanakan di Universitas Lakehead di Thunder Bay, Ontario, Kanada.
• Pada 13 Desember 2007, Google mengumumkan peluncuran terbatas Knol sebuah situs web yang ditujukan sebagai sumber referensi pengetahuan. Knol dibuka bebas kepada semua pengguna pada 23 Juli 2008.

sumber : wikipedia dan berbagai sumber lainnya

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Children Allergy Center Yudhasmara Foundation JL Taman Bendungan Asahan 5 Bendungan Hilir Jakarta Pusat Phone :62 (021) 70081995 – 5703646   email : judarwanto@gmail.com  http://childrenclinic.wordpress.com/ email : judarwanto@gmail.com,

Copyright © 2010, Chil Allergy Center Information Education Network. All rights reserved.

Asthma is an airway disorder that causes respiratory hypersensitivity, inflammation, and intermittent obstruction. Asthma commonly causes constriction of the smooth muscles in the airway, wheezing, and dyspnea.  Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role, in particular, mast cells, eosinophils, T lymphocytes, macrophages, neutrophils, and epithelial cells. In susceptible individuals, this inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness and coughing, particularly at night or in the early morning. These episodes are usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment. The inflammation also causes an associated increase in the existing bronchial responsiveness to a variety of stimuli. Reversibility of airflow limitation may be incomplete in some patients with asthma.

Asthma Prevalence and Statistics

• Asthma is common in industrialized nations such as Canada, England, Australia, Germany, and New Zealand, where much of the asthma data have been collected. The prevalence rate of severe asthma in industrialized countries ranges from 2-10% and is estimated to affect 300 million persons worldwide. Trends suggest an increase in both the prevalence and morbidity of asthma, especially in children younger than 6 years. Factors that have been implicated include urbanization, air pollution, passive smoking, and change in exposure to environmental allergens.
• Asthma affects an estimated 300 million individuals worldwide. Evidence shows that the prevalence of asthma is increasing, especially in children. Annually, the World Health Organization (WHO) has estimated that 15 million disability-adjusted life-years are lost and 250,000 asthma deaths are reported worldwide. Approximately 500,000 annual hospitalizations (34.6% in individuals aged 18 y or younger) are due to asthma. The cost of illness related to asthma is around $6.2 billion. Each year, an estimated 1.81 million people (47.8% in individuals aged 18 y or younger) require treatment in the emergency department. Among children and adolescents aged 5-17 years, asthma accounts for a loss of 10 million school days and costs caretakers $726.1 million because of work absence.
• Worldwide, 130 million people have asthma. The prevalence is 8-10 times higher in developed countries (eg, United States, Great Britain, Australia, New Zealand) than in the developing countries. In developed countries, the prevalence is higher in low income groups in urban areas and inner cities than in other groups.
• Asthma prevalence varies from 1-30% across nations; the prevalence increases with increased urbanization and affluence. Over the past decade, asthma mortality has been stable in many countries, including Australia, Israel, New Zealand, and the United Kingdom
• Asthma is a common chronic disease worldwide and affects 22 million persons in the United States. Asthma is the most common chronic disease in childhood, affecting an estimated 6 million children, and it is a common cause of hospitalization for children in the United States. The overall prevalence rate of exercise-induced bronchospasm is 3-10% of the general population if persons who do not have asthma or allergy are excluded, but the rate increases to 12-15% of the general population if patients with underlying asthma are included. The rate of exercise-induced symptoms in persons with asthma has been reported to vary from 40-90%
• Approximately 34.1 million Americans have been diagnosed with asthma in their lifetime. The prevalence of asthma in the general population is 5%, and it has increased 40% in the past decade. Asthma accounts for more school absences and more hospitalizations than any other chronic illness. In most children’s hospitals in the United States, it is the most common diagnosis at admission. The current asthma prevalence is estimated to be 6.7% in adults and 8.5% in children.  According to the most recent US Centers for Disease Control and Prevention (CDC) Asthma Surveillance Survey, the burden of asthma has increased more than 75% from 1980-1999
• Most centres showed a change in prevalence of 1 or more SE for at least one disorder, with increases being twice as common as decreases, and increases being more common in the 6–7 year age-group than in the 13–14 year age-group, and at most levels of mean prevalence. An exception was asthma symptoms in the older age-group, in which decreases were more common at high prevalence. For both age-groups, more centres showed increases in all three disorders more often than showing decreases, but most centres had mixed changes. The rise in prevalence of symptoms in many centres is concerning, but the absence of increases in prevalence of asthma symptoms for centres with existing high prevalence in the older age-group is reassuring. The divergent trends in prevalence of symptoms of allergic diseases form the basis for further research into the causes of such disorders.
• The prevalence of asthma increased 75% from 1980-1994.
• Asthma rates in children under the age of five have increased more than 160% from 1980-1994.
• It is estimated that the number of people with asthma will grow by more than 100 million by 2025.
• Asthma accounts for approximately 500,000 hospitalizations each year.
• 13 million school days are missed each year due to asthma.
• Approximately 34.1 million Americans have been diagnosed with asthma by a health professional during their  lifetime.
• An estimated 300 million people worldwide suffer from asthma, with 250,000 annual deaths attributed to the disease
• Workplace conditions, such as exposure to fumes, gases or dust, are responsible for 11% of asthma cases worldwide.
• About 70% of asthmatics also have allergies.
• A study of UK schoolchildren has revealed that Black Africans, Indians and Bangladeshis have a similar or lower prevalence of asthma than White children, while Black Caribbean and Mixed Black Caribbean/White boys are more likely to have asthma. Researchers writing in the open access journal BMC Pediatrics studied the occurrence of asthma, investigating ethnic differences in risk factors. Melissa Whitrow and Seeromanie Harding from the Social and Public Health Sciences Unit of the Medical Research Council, UK, used data taken from 51 London schools to investigate a random selection of 11-13 year old pupils. The final sample for analysis included 1219 children who identified themselves as ‘White UK’, 933 ‘Black Caribbean’, 1095 ‘Black African’, 459 ‘Indian’, Globally, morbidity and mortality associated with asthma have increased over the last 2 decades. This increase is attributed to increasing urbanization. Despite advancements in our understanding of asthma and the development of new therapeutic strategies, the morbidity and mortality rates due to asthma definitely increased from 1980-1995.
• The prevalence of asthma is higher in minority groups (eg, blacks, Hispanics) than in other groups; however, findings from one study suggest that much of the recent increase in the prevalence is attributed to asthma in white children. Approximately 5-8% of all black children have asthma at some time. The prevalence in Hispanic children is reported to be as high as 15%. In blacks, the death rate is consistently higher than in whites
• In the United States, the mortality rate due to asthma has increased in all age, race, and sex strata. In the United States, the mortality rate due to asthma is more than 17 deaths per 1 million people (ie, 5000 deaths per year). From 1975-1993, the number of deaths nearly doubled in people aged 5-14 years. In the northeastern and midwestern United States, the highest mortality rate has been among persons aged 5-34 years. According to the most recent report from the CDC and the National Center for Health Statistics, 187 children aged 0-17 years died from asthma, or 0.3 deaths per 100,000 children compared with 1.9 deaths per 100,000 adults aged 18 or older in the year 2002.¹³  Non-Hispanic blacks were the most likely to die from asthma and had an asthma death rate more than 200% higher than non-Hispanic whites and 160% higher than Hispanics.215 ‘Pakistani’, 392 ‘Bangladeshi’ and 299 ‘Mixed White UK and Black Caribbean’
• Community influences of living in a low-educational area are associated with asthma, independently of subjects’ own educational level and social class.
• Asthma accounts for about 10.1 million missed work days for adults annually.
• Asthma was responsible for 3,384 deaths in the United States in 2005
• The annual economic cost of asthma is $19.7 billion. Direct costs make up $14.7 billion of that total, and indirect costs such as lost productivity add another $5 billion.
• Prescription drugs represented the largest single direct medical expenditure related to asthma, over $6 billion.
• Children from refugee camps appear to be at higher risk of asthma than children from neighbouring villages or cities. The prevalence of asthma and asthma symptoms in Palestine appears to be close to that of Jordan, but it is much lower than Israel, and lower than some other countries in the region, such as Kuwait and Saudi Arabia, and more developed countries. This initial study is a baseline for a study on lifestyle and environmental determinants for asthma among Palestinian children.
• In 2006, asthma prevalence was 20.1% higher in African Americans than in whites.
• The prevalence of asthma in adult females was 23% greater than the rate in males, in 2006.
• Approximately 40% of children who have asthmatic parents will develop asthma.
• In 2005, 8.9% of children in the United States currently had asthma.
• Nine million U.S. children under 18 have been diagnosed with asthma at some point in their lifetime.
• Nearly 4 million children have had an asthma attack in the previous year.
• More than 12 million people in the United States report having an asthma attack in the past year.
• In most children, asthma develops before age 5 years, and, in more than half, asthma develops before they age 3 years.
• Among infants, 20% have wheezing with only upper respiratory tract infections (URTIs), and 60% no longer have wheezing by age 6 years. Many of these children were called “transient wheezers” by Martinez et al. They tend to have no allergies, although their lung function is often abnormal. These findings have led to the idea that they have small lungs. Children in whom wheezing begins early, in conjunction with allergies, are more likely to have wheezing when they are aged 6-11 years. Similarly, children in whom wheezing begins after age 6 years often have allergies, and the wheezing is more likely to continue when they are aged 11 years
• Asthma accounts for 217,000 emergency room visits and 10.5 million physician office visits every year.
• The estimate of lost work and school time from asthma is approximately 100 million days of restricted activity. More than 1.8 million emergency department evaluations for asthma occur annually. The figures from the 1997 National Institutes of Health report¹ an estimated 500,000 hospitalizations and 5,000 deaths from asthma annually. International asthma mortality is reported as high as 0.86 deaths per 100,000 persons in some countries. US asthma mortality rates in 2002 were reported at 1.5 deaths per 100,000 persons. Mortality is primarily related to lung function, with an 8-fold increase in patients in the lowest quartile, but mortality has also been linked with asthma management failure, especially in young persons. Other factors that impact mortality include age older than 40 years, cigarette smoking more than 20-pack years, blood eosinophilia, forced expiratory volume in one second (FEV₁) of 40-69% predicted, and greater reversibility
• In 2006, almost 2.5 million people over the age of 65 had asthma, and more than 1 million had an asthma attack or episode.
• In a survey of U.S. homes, approximately one-quarter had levels of dust mite allergens present in a bed at a level high enough to trigger asthma symptoms.
• In 2007, 29% of children who had a food allergy also had asthma.
• Asthma increases the odds of healthcare use in obese people by 33%.
• About 23 million people, including almost 7 million children, have asthma.
• Approximately 2 million Hispanics in the U.S. have asthma.
• Asthma is the third-ranking cause of hospitalization among children under 15.
• Asthma is a common disorder that accounts for almost 2 million ED visits each year in the United States. In 2005, 1.8 million ED visits were for acute asthma. On average, this represents approximately 2% of all ED visits. In urban centers, however, acute asthma may comprise up to 10% of all ED visits.
• Incidence of acute asthma, defined as the number of persons who develop asthma within a specific time period, is approximately 0.2-0.4% annually. Childhood asthma persists into adulthood in approximately 50% of cases. Those with symptoms persisting into the second decade of life usually have asthma throughout adulthood. Asthma prevalence is 6-10% (ie, 20-25 million persons); one half of these cases are children (ie, 8-20% of all children). Overall, acute asthma represents about 2% of all ED visits with the national rate rising from 1993-1998 but stable from 1998-2005. The asthma epidemic seems to be plateauing.
• Children : 9-11%  children less than 18 years (9.5%) currently have asthma. 11.3% of male children currently have asthma. 7.7% of female children currently have asthma. This is not a statistically significant difference.
• Adults (≥ 18 Years): 9 -11%  adults 18 years and older  currently have asthma. The asthma prevalence for adults (9.5%) is higher than that for the United States (8.2%). The asthma prevalence in Michigan is significantly higher for adult females (11.0%) than adult males (7.9%).  The asthma prevalence is significantly higher for non-Hispanic black adults (12.9%) than non-Hispanic white adults. (8.7%).  Asthma prevalence for adults decreases with increasing household income.
• Asthma occurs in persons of all races worldwide. In the United States, asthma prevalence, especially morbidity and mortality, is higher in blacks than in whites.
• In children younger than 10 years, the male-to-female ratio is 2:1. Between the ages of 18 and 54 years, the ratio is reversed, with women being affected twice as often as men. Women visit the ED and are hospitalized for acute asthma twice as often as men. Previous data suggested that 40% of these hospitalizations occur during the premenstrual phase of the cycle; more recent data from larger studies have not borne out these initial findings. Indeed, some studies suggest a peak in asthma exacerbations shortly before ovulation, when estrogen levels are rising (and not falling).
• Although genetic factors are of major importance in determining a predisposition to the development of asthma, environmental factors play a greater role than racial factors in asthma onset. A national concern is that some of the increased morbidity is due to differences in asthma treatment afforded certain minority groups.
• The prevalence for those earning less than $20,000 is significantly higher than those earning $75,000 or more. 
• Among adults reporting a disability, 15.0 8.1% of non-Hispanic white children currently have asthma. 11.6% of non-Hispanic black children currently have asthma.  This is not a statistically significant difference.  An average of one out of every 10 school-aged child has asthma.
• Annual expenditures for health and lost productivity due to asthma are estimated at over $20 billion, according to the National Heart, Lung and Blood Institute.
• Over 92% of the 402 asthma deaths in 2006 were among people aged 45 years and over. Asthma in older Australians is distinct in many ways. The presence of comorbid conditions makes the management of asthma in older people more complex. The disease itself is also more persistent and severe than in the younger ages.
• Asthma predominantly occurs in boys in childhood, with a male-to-female ratio of 2:1 until puberty, when the male-to-female ratio becomes 1:1.
• Asthma prevalence is greater in females after puberty, and the majority of adult-onset cases diagnosed in persons older than 40 years occur in females.
• Boys are more likely than girls to experience a decrease in symptoms by late adolescence.
• Some 75% of asthmatic patients had associated rhinitis and this association was more frequent in atopic subjects. There is a positive correlation between the severity of rhinitis and asthma and between the number of asthma exacerbations and the presence of rhinitis. These results support the main message of ARIA and GEMA recommendations regarding the integral management of airways to improve the control of asthma.
• Before puberty, the prevalence is 3 times higher in boys than in girls. During adolescence, the prevalence is equal among males and females. Adult-onset asthma is more common in women than in men
• Asthma symptoms usually begin in early childhood (eg, 80-90% experience symptoms by age 6 y); however, asthma can present at any age, including elderly persons. Children younger than 10 years constitute approximately 50% of all cases.
• In 2003 asthma was the leading cause of burden of disease in Australian children, contributing 17.4% of total DALYs and the eleventh-leading contributor to the overall burden of disease in Australia, accounting for 2.4% of the total number of DALYs.
• Asthma and chronic obstructive pulmonary disease (COPD) can together be described as obstructive lung disease. This report examines recent data on deaths and hospitalisations among people aged 55 years and over when asthma or COPD are recorded as one of multiple causes of death or hospital diagnoses.
• The questionnaire demonstrated a greater prevalence of GER symptoms, RARS, and reflux-associated inhaler use in asthmatics. This excessive inhaler use may explain how GER indirectly causes asthma to worsen.
• Chronic respiratory diseases, such as asthma and emphysema, are very prevalent in the world. This report brings together data from a variety of sources to highlight the prevalence and impact of chronic respiratory diseases
• Asthma prevalence is increased in very young persons and very old persons because of airway responsiveness and lower levels of lung function.  Two thirds of all asthma cases are diagnosed before the patient is aged 18 years. Approximately half of all children diagnosed with asthma have a decrease or disappearance of symptoms by early adulthood.
• The assessment and diagnosis of exercise-induced bronchospasm is made more often in children and young adults than in older adults and is related to high levels of physical activity. Exercise-induced bronchospasm can be observed in persons of any age based on the level of underlying airway reactivity and the level of physical exertion.
• Parents of 5472 children aged 5-17 years from 3209 families were interviewed in a nationwide household survey. In the past year, 15.0% of children had wheezed, 2.2% had more than 12 attacks, and 2.3% had experienced a speech limiting attack. Altogether 4.3% were woken more than once a week by wheezing, 13.1% had doctor diagnosed asthma, and 13.6% had been prescribed antiasthmatic drugs in the past year. With increasing age, morbidity related to wheezing declined to a greater extent than annual period prevalence. The prevalence of wheeze varied little by socioeconomic group, but there were marked trends in all three indices of severity towards increased morbidity in poorer families. Diagnostic labelling and drug treatment of wheezy children did not differ substantially with socioeconomic status. Thus, a degree of socioeconomic equality exists in the process of medical care for childhood asthma in Britain. This does not appear to have resulted in equality of outcome
• 15 Years Prevalence. In 1973 a survey was conducted among 12 year old children living in a defined area of South Wales. In 1988 the survey was repeated in the same area, again among 12 year old children. Questionnaires were completed for all 965 children in the population sample; peak expiratory flow rates were performed on them all, and repeated (except for five children) after an exercise provocation test. The prevalence of a history of wheeze at any time had increased from 17% to 22%, while that of a history of asthma at any time had increased from 6% to 12%. Current asthma had increased from 4% to 9%, but wheezing in the past year not attributed to asthma had remained at 6%. The exercise provocation tests suggested that both mild and severe asthma had become more common. Increases had also occurred in the frequencies of a history of eczema (from 5% to 16%) and of hay fever (from 9% to 15%). It seems that the prevalence of asthma has risen, and that this cannot be wholly explained by a greater readiness to diagnose the disease.
• Prevalence of asthma in the general population is 4-5%. In pregnancy, the prevalence ranges from 1-4%.
• Morbidity and mortality rates of pregnant women with asthma are comparable to the general population.
• The mortality rate from asthma in the United States is currently 2.1 per 100,000. Death rates in the United States have been increasing from 0.8 per 100,000 in the general population in the late 1970s to 2.1 per 100,000 in 1994.
• Prevalence and mortality rates are significantly higher in African Americans and Hispanics when compared with whites.

source :

• World Health Organization. Global surveillance, prevention and control of chronic respiratory diseases: a comprehensive approach, 2007.
• American Lung Association. Epidemiology & Statistics Unit, Research and Program Services. Trends in Asthma Morbidity and Mortality, November 2007.
• Asthma Statistic http://www.aaaai.org/media/statistics/asthma-statistics.asp
• Centers for Disease Control. Surveillance for Asthma – United States, 1960-1995, MMWR, 1998; 47 (SS-1).

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• Del Giacco S, Rosenwasser LJ, Crisci CD, Crisci CD, Frew AJ, Kaliner MA, Lee BW, Guanghui L, Maspero J; Moon HB, Takemasa N, Potter PC, Singh AB, Valovirta E, Vervloet D, Warner JO, Henley K. What is an allergist? A Position Statement of the WAO Specialty and Training Council. World Allergy Organization J. 2008;1(1):19-20.
  Full text
• Kaliner MA, Del Giacco S, Crisci CD, Frew AJ, Liu G, Maspero J, Moon HB, Takemasa N, Potter PC, Rosenwasser LJ, Singh AB, Volovirta E, Van Cauwenberge P, Warner JO, on behalf of the WAO Specialty and Training Council. Requirements for Physician Competencies in Allergy: Key Clinical Competencies Appropriate for the Care of Patients with Allergic or Immunologic Diseases: A Position Statement of the World Allergy Organization. World Allergy Organization J 2008;1(2):42-6.
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• Canonica GW, Baena-Cagnani CE, Bousquet J, Bousquet PJ, Lockey RF, Malling H-J, Passalacqua G, Potter PC, Valovirta E. Recommendations for Standardization of Clinical Trials with Allergen Specific Immunotherapy for Respiratory Allergy: A Statement of a World Allergy Organization (WAO) Taskforce. Allergy. 2007;62(3):317-24.
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• Warner JO, Kaliner MA, Crisci CD, Del Giacco S, Frew AJ, Liu GH, Maspero J, Moon H-B, Takemasa N, Potter PC, Rosenwasser LJ, Singh AB, Valovirta E, Van Cauwenberge P. Allergy practice worldwide: a report by the World Allergy Organization Specialty and Training Council. Allergy Clin Immunol Int – J World Allergy Org. 2006;18:4-10; and Int Arch Allergy Immunol. 2006;139(2):166-74.
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• Fiocchi A, Brozek J, Schünemann H, Bahna S, von Berg A et al. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow’s Milk Allergy (DRACMA) Guidelines. World Allergy Organization Journal. 2010;3(4):57-161.
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• Fiocchi A, Brozek J, Schünemann H, Bahna S, von Berg A et al. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow’s Milk Allergy (DRACMA) Guidelines. Pediatric Allergy and Immunology. 2010 July;21(s21):1-125.
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• Canonica GW, Bousquet J, Casale T, Lockey R, Baena-Cagnani C et al. Sublingual Immunotherapy: World Allergy Organization Position Paper 2009. World Allergy Organization Journal. 2009;2(11):223-281.
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• Cox L, Larenas-Linnemann D, Lockey R, Passalacqua G et al. Speaking a Common Language in Grading Subcutaneous Immunotherpay Systemic Reactions: World Allergy Organization Subcutaneous Immunotherapy Systemic Reaction Grading System. J Allergy Clin Immunol. 2009 in press.
• Casale TB, Canonica, GW, Bousquet, J, Cox, L, Lockey, RF, Nelson, H, Passalacqua, G. Recommendations for appropriate sublingual immunotherapy clinical trials. J Allergy Clin Immunol. 2009;124(4):665-670.
  Abstract
• Zuberbier T et al., EAACI/GA²LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria. Allergy. 2009;64(10):1417-1426
  Abstract
• Zuberbier T, Asero R, Bindslev-Jensen C, Canonica GW, Church MK, Giménez-Arnau AM et al. EAACI/GA²LEN/EDF/WAO Guideline: Management of urticaria. Allergy, 2009; 64(10):1427-1443
  Abstract
•  
• Potter PC, Warner JO, Pawankar RS, Kaliner MA, Del Giacco A, Rosenwasser L, for the WAO Specialty and Training Council. Recommendations for Competency in Allergy Training for Undergraduates Qualifying as Medical Practitioners: A World Allergy Organization Position Paper. World Allergy Organization J. 2009;2(8):150-189.
  Abstract
• Kemp SF, Lockey RF, Simons FER; on behalf of the World Allergy Organization ad hoc
  Committee on Epinephrine in Anaphylaxis. Epinephrine: the drug of choice for anaphylaxis. A Statement of the World Allergy Organization. Allergy. 2008;63(8):1061-1070 and World Allergy Organization J, 2008;1(7):S18-S26,
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• Pawankar RS, Baena-Cagnani CE, Bousquet J, Canonica GW, Cruz, AA, Kaliner MA, Lanier BQ. State of World Allergy Report 2008: Allergy and Chronic Respiratory Diseases. World Allergy Organization J. 2008;1(6):S1-S17.
  Abstract

source :wao

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Recommendations for appropriate sublingual immunotherapy clinical trials

References and further reading may be available for this article. To view references and further reading you must purchase this article.

Thomas B. Casale MD^{a, ,} , G. Walter Canonica MD^b, Jean Bousquet MD^c, Linda Cox MD^d, Richard Lockey MD^e, Harold S. Nelson MD^f and Giovanni Passalacqua MD^b

source :wao

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Information on this web site is provided for informational purposes only and is not a substitute for professional medical advice. You should not use the information on this web site for diagnosing or treating a medical or health condition. You should carefully read all product packaging. If you have or suspect you have a medical problem, promptly contact your professional healthcare provider.  

        

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Allergy, Asthma : Theory, Practical and Related Diseases

• The Asthma Educator’s Handbook
  Reviewed by Pavana Beerelli, MSIV, George Washington University, School of Medicine
• Asthma: An Atlas of Investigation and Management
  Reviewed by Mathew Varghese, MD, First Year Fellow in Allergy & Immunology, Dept. Internal Medicine, Division of Allergy and Immunology, University of South Florida College of Medicine
• Allergic Diseases: Diagnosis and Treatment, 3rd Ed.
  Reviewed by Josh Phillips, MD, Division of Allergy & Immunology, University of South Florida College of Medicine
• Litt’s Drug Eruption Reference Manual, 13th Edition; Including Drug Interactions
  Reviewed by James Young Joon Choi, MB BS, FRACP, Clinical Immunologist and Allergist, Dermatology Registrar, Westmead Hospital, Sydney, Australia
• PARASITES & ALLERGY
  Reviewed by Peter DeBuse FRACP, FRCP (LOND.), Royal Children’s Hospital, Brisbane, Australia
• STRUCTURAL BIOLOGY of the COMPLEMENT SYSTEM
  Reviewed by Dr Olga Patricia MARTINEZ, MB BS, FRACP, FRCPA, PhD, Royal Perth Hospital, PathWest, School of Surgery and Pathology, University of Western Australia
• Lung Function Testing
  Reviewed by Dr Janet Rimmer, MBBS, MD, FRACP, Woolcock Institute, University of Sydney, Australia
• Allergy and Asthma in Modern Society: A Scientific Approach
  Reviewed by Dr David Sutherland, FRACP, Nineways Specialist Clinic, Broadmeadow NSW 2292
• Pediatric Dermatology
  Reviewed by Dr. Preeti Joshi, Staff Specialist, The Children’s Hospital at Westmead, NSW, Australia
• HIV Second Edition
  Reviewed by Dr Lucinda Berglund MB BS
  Advanced Trainee, Immunology Registrar, Westmead Hospital, NSW Australia
• Allergy: An Atlas of Investigation and Management
  Reviewed by Steven L. Cole, DO
  Division of Allergy and Immunology, University of South Florida College of Medicine
• Mechanisms of Epithelial Defense
  Reviewed by Gary R. Hellermann
  University of South Florida College of Medicine, Tampa, Florida
• Osteoporosis: An Evidence-based guide to Prevention and Management
  Reviewed by Dr. Constance H. Katelaris
  Deputy Director (Clinical) Institute of Immunology and Allergy Research, Westmead Hospital, Sydney, Australia
• Color Atlas of Air-Borne Pollens and Plants in China
  Reviewed by Dr. Hong Li
  Allergy Department, Peking Union Medical College Hospital, Beijing, 100730, China
• Headache
  Reviewed by Mark C. Glaum, MD, PhD
  Assistant Professor of Medicine and Pediatrics, Division of Allergy and Immunology, University of South Florida College of Medicine
• Neonatal Immunity
  Reviewed by Mark C. Glaum, MD, PhD
  Assistant Professor of Medicine and Pediatrics, Division of Allergy and Immunology, University of South Florida College of Medicine
• Allergologie. Le guide.
  Reviewed by Professor Gabrielle Pauli
  President of the French Society of Allergology and Clinical Immunology
  Hôpitaux Universitaires – Strasbourg (France).
• Skin Immune System: Cutaneous Immunology and Clinical Immunodermatology
  Reviewed by Salvador Gala, PhD
  University of Sydney, Westmead Hospital, Westmead, NSW, Australia.
• Atlas of Immunology
  Reviewed by L.L. Wallman
  Staff Specialist, Department of Clinical Immunology and Allergy, Westmead, Hospital, Westmead, Australia
• Traité d’Allergologie
  Reviewed by Professor Gabrielle Pauli Z
  President of the French Society of Allergology and Clinical Immunology
  Hôpitaux Universitaires – Strasbourg (France).
• Current therapy in Allergy, Immunology and Rheumatology
  Reviewed by Constance H. Katelaris
  Clinical Associate Professor
  Institute for Immunology and Allergy Research
  Westmead Hospital, Westmead, Australia.
• Encyclopedia of Medical Genomics and Proteomics
  Reviewed by Gary R. Hellermann, PhD
  University of South Florida College of Medicine
  Dept. of Internal Medicine/Div. of Allergy-Immunology
  Tampa, Florida
• Immunobiology. The immune system in health and disease.
  Reviewed by Dr Kenneth Tang
  Immunopathology registrar
  Westmead Hospital
  Sydney, Australia
• Monograph on Insect Allergy.
  Reviewed by Constance H Katelaris
  Associate Professor
  Department of Clinical Immunology and Allergy
  Westmead Hospital, NSW
• Prevention of Allergy and Allergic Asthma. World Allergy Organization Project Report and Guidelines.
  Reviewed by Ronald S. Walls, MD PhD
  University of Sydney, Concord Hospital
  Concord, NSW. Australia.
• “Allergy. Your questions answered”
  Reviewed by Constance H Katelaris
  Associate Professor
  Department of Clinical Immunology and Allergy
  Westmead Hospital, NSW
• Allergens and Allergen Immunotherapy, 3rd Edition, revised and expanded
  Reviewed by Philip Lieberman, MD
  University of Tennessee College of Medicine
  Memphis, Tennessee USA
• Urticaria and Angioedema
  Reviewed by Michael A. Kaliner, MD
  Institute for Asthma and Allergy
  Bethesda, Maryland USA
• Middleton’s Allergy Principles and Practice Textbook 6th edition
  Reviewed by Bob Q. Lanier, MD
  North Texas Institute for Clinical Trials
  Fort Worth, Texas USA
• Applying Genomic and Proteomic Microarray Technology in Drug Discovery
  Reviewed by Gary Hellermann, University of South Florida College of Medicine, Tampa, Florida
• New Perspectives in Monitoring Lung Inflammation: Analysis of Exhaled Breath Condensate
  Reviewed by Mark C. Glaum, MD, PhD, Assistant Professor of Medicine and Pediatrics, University of South Florida
• Immunity; The Immune Response in Infectious and Inflammatory Disease
  Reviewed by Brad Frankum, Clinical Immunologist, and Professor of Clinical Education, University of Western Sydney, Campbelltown, NSW, Australia
• Lippincott’s Illustrated Reviews: Immunology
  Reviewed by Josh Phillips, MD, Division of Allergy & Immunology, University of South Florida College of Medicine
• Nonallergic Rhinitis
  Reviewed by Ronald S. Walls MD, PhD, University of Sydney, Department of Immunology & Allergy, Concord Hospital, Sydney
• Parasites And Allergy (Chemical Immunology and Allergy Vol. 90)
  Reviewed by Steven L. Cole, DO, Division of Allergy and Immunology, Department of Internal Medicine, University of South Florida College of Medicine and James A. Haley Veterans’ Hospital, Tampa, FL
• Superantigens and Superallergens, Vol. 93 in Chemical Immunology and Allergy
• Roitt’s Essential Immunology, 11th Edition
  Reviewed by Byol Shin, DO, University of South Florida College of Medicine, James A. Haley Veterans Hospital, Tampa, FL, USA
• Quantitative Skin Testing for Allergy: IDT and MQT
  Reviewed by Dr. David C Sutherland, FRACP, Nineways Specialist Clinic, Broadmeadow, NSW, Australia
• Handbook of Atopic Eczema: 2nd edition
  Reviewed by Dr Janet Rimmer, MBBS, MD (UNSW), FRACP, St. Vincent Clinic, Darlinghurst, NSW, Australia
• Current Problems in Dermatology, Vol. 33: Biofunctional Textiles and the Skin
  Reviewed by James Young Joon Choi, MBBS FRACP, Allergist and Clinical Immunologist, Westmead Hospital Dermatology Registrar
• Mayo Clinic Atlas of Immunofluorescence in Dermatology: Patterns and Target Antigens
  Reviewed by Andrew Bagg, MD, Division of Allergy and Immunology, University of South Florida College of Medicine, Tampa Florida
• The Year in Allergy, Volume 3
  Reviewed by Steven L. Cole, DO, Division of Allergy and Immunology, University of South Florida College of Medicine
• Oxford Handbook of Clinical Immunology and Allergy, Second Edition
  Reviewed by Richard F. Lockey, M.D., Distinguished University Health Professor, Professor of Medicine, Pediatrics, and Public Health, Joy McCann Culverhouse Professor of Allergy and Immunology, Director, Division of Allergy and Immunology, University of South Florida College of Medicine
• Atopic Dermatitis: Second Edition
  Reviewed by Robbie Pesek, MD, Division of Allergy and Immunology, Department of Internal Medicine, University of South Florida College of Medicine, James A. Haley Veterans Hospital, Tampa, Florida USA
• New Generation Vaccines, Fourth Edition
  Reviewed by Dr. Michael S. Gold, MbCHB, DCH, MD, FCP, FRACP, Discipline of Paediatrics, Adelaide University, Adelaide, South Australia
• Handbook of Drug Metabolism, Second Edition
  Drugs and the Pharmaceutical Sciences
  Reviewed by James J. Yun, MBBS, Immunology Registrar, Liverpool Hospital, Australia
• Immunology: A Short Course, 6th Edition
  Reviewed by Karuna Keat, MBBS, Campbelltown Hospital, University of Western Sydney, Cambelltown, NSW Australia
• Clinical Allergy: Diagnosis and Management
  Reviewed by Catherine Toong, B Med(Hons), Immunology and Allergy Advanced Trainee, Royal Prince Alfred Hospital, Australia
• Respiratory Diseases in the Elderly
  Reviewed by Monroe James King, DO, Division of Allergy and Immunology, University of South Florida, College of Medicine, Tampa, Florida, USA
• Handbook of Sleep Disorders
  Reviewed by Michel Alkhalil, MD, First Year Fellow in Allergy and Immunology, Division of Allergy and Immunology, Department of Internal Medicine, University of South Florida College of Medicine, James A. Haley Veterans’ Hospital, Tampa, Florida USA
• Sleep and Breathing in Children: Developmental Changes in Breathing during Sleep Second Edition (Lung Biology in Health and Disease)
  Reviewed by Michel Alkhalil, MD, First Year Fellow in Allergy and Immunology, Division of Allergy and Immunology, Department of Internal Medicine, University of South Florida College of Medicine, James A. Haley Veterans’ Hospital, Tampa, Florida USA
• Clinical Management of Chronic Obstructive Pulmonary Disease Second Edition (Lung Biology in Health and Disease)
  Reviewed by Dr. Girish Patel, MBBS, MD (Respiratory Medicine), Advanced Trainee, Respiratory Medicine, Cambelltown Hospital, Campbelltown, New South Wales, Australia
• Chronic Obstructive Pulmonary Disease Exacerbations
  Reviewed by Dr. Graeme A. Thompson, M.B.B.S. (Hons1), FRACP, Respiratory Physician and Conjoint Lecturer, Campbelltown Hospital and University of Western Sydney, Australia
• Urticaria and Angioedema, Second Edition
  Reviewed by Roger W. Fox, MD, Professor of Medicine and Pediatrics, University of South Florida College of Medicine, Division of Allergy, Tampa, Florida USA
• Airway Smooth Muscle in Asthma and COPD: Biology and Pharmacology
  Reviewed by Dr Janet Rimmer MD, FRACP, St. Vincent’s Clinic, Darlinghurst, Sydney, Australia
• Nonallergic Rhinitis
  Reviewed by Dennis Kim, First year fellow, Division of Allergy and Immunology, University of South Florida College of Medicine and VA Hospital, Tampa, Florida
• Cancer Vaccines and Tumor Immunity
  Reviewed by Veronica A Preda, MB BS BSc (Hon), Campbelltown Hospital, Sydney, New South Wales, and Skin & Cancer Foundation Australia, Darlinghurst, New South Wales, Australia
• “T cell regulation Allergy, Asthma and Atopic Skin Diseases”, Chemical Immunology and Allergy, Vol 94
  Reviewed by Constance H. Katelaris, MB BS PhD FRACP, Professor of Immunology and Allergy, University of Western Sydney and Campbelltown Hospital, New South Wales, Australia
• Eosinophilic Esophagitis
  Reviewed by Alyson Kakakios MB BS, FRACP, Department of Allergy and Immunology, The Children’s Hospital at Westmead, Westmead, Sydney, New South Wales, Australia
• Dictionary of Contact Allergens
  Reviewed by Dr Veronica A Preda, MB BS BSc (Hons), Conjoint Associate Lecturer, Faculty of Medicine, University of New South Wales, Australia, Sydney South Western Area Health Service Campbelltown Hospital, Skin & Cancer Foundation Darlinghurst and St Vincent’s Hospital.
• Bronchial Asthma: A Guide for Practical Understanding and Treatment
  Reviewed by Dr David C Sutherland, FRACP, Nineways Specialist Clinic, Broadmeadow, NSW, Australia
• Oxford Handbook of Clinical Immunology and Allergy
  Reviewed by Thomas Chacko, MD, Division of Allergy and Immunology, University of South Florida College of Medicine, Tampa, FL, USA
• Kendig’s Disorders of the Respiratory Tract in Children
  Reviewed by Peter van Asperen MD FRACP, Head, Department of Respiratory Medicine, The Children’s Hospital at Westmead & Macintosh Professor of Paediatric Respiratory Medicine, University of Sydney, Australia.
• From Genes to Phenotypes – The Basis of Future Allergy Management
  Reviewed by John B. Ziegler MB BS, FRACP, MD, DipHEd, FAAAAI Head, Department of Immunology & Infectious Diseases
• Allergy in Practice
  Reviewed by Ron Purcell, MD, University of South Florida College of Medicine and James A. Haley Veterans Hospital, Tampa, FL, USA
• Allergy in Practice
  Reviewed by Salvador Gala, MB BS PhD, University of Sydney
• Concise Clinical Immunology for Healthcare Professionals
  Reviewed by Thomas Chacko, MD, 2nd year Fellow, University of South Florida College of Medicine, Tampa, FL
• Cystic Fibrosis in the 21st Century
  Reviewed by Dr RG Stirling BSc(Hons), MBBCh(Hons), MRCPI, FRACP,
  Department of Allergy Immunology & Respiratory Medicine; Alfred Hospital & Monash University; Melbourne, Australia
• Ultrastructure of Mast Cells and Basophils
  Reviewed by Ross Boadle, Institute of Clinical Pathology and Medical Research and Westmead Millennium Institute, Westmead, NSW, Australia
• Asthma in the Workplace, 3rd Edition
  Reviewed by Mark Glaum, University of South Florida College of Medicine, Tampa, FL, USA

Immunology

• Immunogenomics and Human Disease
  Reviewed by Gary Hellermann, PhD, University of South Florida College of Medicine, Tampa, FL, USA
• Immunology, infection and immunity
  Reviewed by James J. Yun, MBBS, Advanced trainee, Immunology & Allergy, Campbelltown Hospital, New South Wales, Australia
• Janeway’s Immunobiology, Seventh Edition
  Reviewed by Dr Sandhya Limaye, MBBS FRACP FRCPA, Department of Immunology, Liverpool Hospital, Liverpool, New South Wales, Australia
• Immunology, Infection and Immunity
  Reviewed by James J. Yun, MBBS, Immunology & Allergy, Campbelltown Hospital, Cambelltown, New South Wales, Australia
• Problem-based immunology
  Reviewed by Dr Jane Peake MBBS, FRACP, DTM&H, University of Queensland, Herston, Queensland, Australia
• Microbial Subversion of Immunity: Current Topics
  Reviewed by Gary Hellermann PhD
• Contributions to Microbiology vol. 15: Trends in Innate Immunity
  Reviewed by James J. Yun, MBBS, Immunology Registrar, Campbelltown Hospital, New South Wales, Australia
• Handbook of Human Immunology, Second Edition
  Reviewed by Salvador Gala, MB BS PhD
• Janeway’s Immunobiology 7th Edition
  Reviewed by Dr Denise C. Hsu, BscMBBS(UNSW), Immunology Registrar, Campbelltown Hospital, NSW, Australia
• The Immune System, Third Edition
  Reviewed by Dr. Frederick J. Lee, BSc MBBS (Hons I), Senior Registrar, Clinical Immunology and Allergy, Campbelltown Hospital, Campbelltown, New South Wales, Australia
• The Immune Response: Basic and Clinical Principles
  Reviewed by Sam Mehr, MBBS, BMedSci, The Children’s Hospital at Westmead, Westmead, NSW, Australia
• Mast cells in allergic diseases. Chemical Immunology and Allergy. Vol. 87
  Reviewed by Ron Walls MD, PhD, University of Sydney, Sydney, NSW, Australia
• Immune System Disorders Sourcebook (Second Edition)
  Reviewed by Roger W. Fox, MD, University of South Florida Health Sciences Center, Tampa, FL, USA
• Mast Cells and Basophils: Development, Activation and Roles in Allergic/Autoimmune Disease
  Reviewed by Mark C. Glaum, MD, PhD, University of South Florida College of Medicine, Division of Allergy & Immunology
• Primary Immunodeficiency Diseases—a Molecular and Genetic Approach, 2nd Ed.
  Reviewed by Gary Hellermann, PhD, University of South Florida Division of Allergy and Immunology

source : WAO

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Office : JL Taman Bendungan Asahan 5  Jakarta Pusat  Phone : (021) 70081995 – 5703646email :  judarwanto@gmail.com,

Information on this web site is provided for informational purposes only and is not a substitute for professional medical advice. You should not use the information on this web site for diagnosing or treating a medical or health condition. You should carefully read all product packaging. If you have or suspect you have a medical problem, promptly contact your professional healthcare provider.  

        Copyright © 2010, Children Allergy Center  Information Education Network. All rights reserved

Worldwide Allergy Meetings Congress

2010 American College of Allergy, Asthma and Immunology (ACAAI) Annual Meeting

Mainzer Allergie-Workshop (23rd Allergy Workshop in Mainz)

Tuesday, March 1, 2011 | 13:00 – 14:00 Location: University Clinic Mainz, Germany Meeting Type: Non-Annual Meeting Host(s): German Society for Allergology and Clinical Immunology Year: 2011 City: Mainz Country: Germany Region: Europe     67th American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting Friday, March 18 – Tuesday, March 22, 2011 Meeting Type: Annual Meeting Host(s): American Academy of Allergy, Asthma & Immunology (AAAAI) Year: 2011 City: San Francisco, California Country: United States Region: North America   1Oème CONGRES INTERNATIONAL de L’ANAP Thursday, April 7 – Saturday, April 9, 2011 Location: SHERATON HOTEL – ALGIERS Host(s): ANAP ALGERIA City: ALGIERS Country: Algeria Region: Middle East/Africa IV World Asthma and COPD Forum Saturday, April 30 – Tuesday, May 3, 2011 Meeting Type: Non-Annual Meeting Host(s): CIS Society of Allergology and Immunology & World Immunopathology Organization Year: 2011 City: Paris Country: France Region: Europe American Thoracic Society (ATS) International Conference Friday, May 13 – Wednesday, May 18, 2011 Meeting Type: Annual Meeting Host(s): American Thoracic Society (ATS) Year: 2011 City: Denver, Colorado Country: United States Region: North America Spring Meeting of the Japanese Society of Allergology Saturday, May 14 – Sunday, May 15, 2011 Meeting Type: Non-Annual Meeting Host(s): Japanese Society of Allergology Year: 2011 City: Chiba Country: Japan Region: Asia Pacific   Annual Spring Meeting of the Korean Academy of Asthma, Allergy and Clinical Immunology Friday, June 3 – Saturday, June 4, 2011 Meeting Type: Annual Meeting Host(s): Korean Academy of Asthma, Allergy and Clinical Immunology Year: 2011 City: Seoul Country: South Korea Region: Asia Pacific   source : wao   Supported  by Widodo judarwanto, pediatrician  Children’s Allergy Center Online   www.childrenallergyclinic.wordpress.com/   Picky Eaters Clinic, Klinik Kesulitan makan Pada Anak  www.mypickyeaters.wordpress.com/   Office : JL Taman Bendungan Asahan 5  Jakarta Pusat  Phone : (021) 70081995 – 5703646email :  judarwanto@gmail.com, Information on this web site is provided for informational purposes only and is not a substitute for professional medical advice. You should not use the information on this web site for diagnosing or treating a medical or health condition. You should carefully read all product packaging. If you have or suspect you have a medical problem, promptly contact your professional healthcare provider.            Copyright © 2010, Children Allergy Center  Information Education Network. All rights reserved

Maternal consumption of peanut during pregnancy is associated with peanut sensitization in atopic infants.

Sicherer SH, Wood RA, Stablein D, Lindblad R, Burks AW, Liu AH, Jones SM, Fleischer DM, Leung DY, Sampson HA.

Jaffe Food Allergy Institute, Mount Sinai School of Medicine, New York, NY.

Supported  by

• Children’s Allergy Center Online http://childrenallergyclinic.wordpress.com
• Picky Eaters Clinic, Klinik Kesulitan makan Pada Anak   http://mypickyeaters.wordpress.com

Children with allergic and nonallergic rhinitis have a similar risk of asthma.

Chawes BL, Bønnelykke K, Kreiner-Møller E, Bisgaard H.

Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen, and the Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Copenhagen, Denmark.

respurces :  American Academy of Allergy, Asthma & Immunology. Published by Mosby

Supported  by

• Children’s Allergy Center Online http://childrenallergyclinic.wordpress.com
• Picky Eaters Clinic, Klinik Kesulitan makan Pada Anak   http://mypickyeaters.wordpress.com

Cause of Stuttering is generally unknown. But few researchers have claimed about the connection between food allergies and stuttering.

Stuttering
Stuttering (alalia syllabaris), also known as stammering (alalia literalis or anarthria literalis), is a speech disorder in which the flow of speech is disrupted by involuntary repetitions and prolongations of sounds, syllables, words or phrases, and involuntary silent pauses or blocks in which the stutterer is unable to produce sounds.The term stuttering is most commonly associated with involuntary sound repetition, but it also encompasses the abnormal hesitation or pausing before speech, referred to by stutterers as blocks, and the prolongation of certain sounds, usually vowels and semivowels. The term “stuttering”, as popularly used, covers a wide spectrum of severity: it may encompass individuals with barely perceptible impediments, for whom the disorder is largely cosmetic, as well as others with extremely severe symptoms, for whom the problem can effectively prevent most oral communication. The impact of stuttering on a person’s functioning and emotional state can be severe. Much of this goes unnoticed by the listener, and may include fears of having to enunciate specific vowels or consonants, fears of being caught stuttering in social situations, self-imposed isolation, anxiety, stress, shame, or a feeling of “loss of control” during speech. Stuttering is sometimes popularly associated with anxiety but there is actually no such correlation (though as mentioned social anxiety may actually develop in individuals as a result of their stuttering). Despite popular perceptions to the contrary, stuttering does not affect and has no bearing on intelligence.Stuttering is generally not a problem with the physical production of speech sounds or putting thoughts into words. Apart from their speech impediment, people who stutter may well be ‘normal’ in the clinical sense of the term. Anxiety, low self-esteem, nervousness, and stress therefore do not cause stuttering per se, although they are very often the result of living with a highly stigmatized disability and, in turn, exacerbate the problem in the manner of a positive feedback system.The disorder is also variable, which means that in certain situations, such as talking on the telephone, the stuttering might be more severe or less, depending on the anxiety level connected with that activity. Although the exact etiology of stuttering is unknown, both genetics and neurophysiology are thought to contribute.

Allergy and Stuttering
A particular food allergy can activate our Sympathetic Nervous System instead of the Para-sympathetic Nervous System. Thus, our levels of anxiousness increases. This condition stimulates stuttering.Sympathetic Nervous System is a type of nervous system present in our body, which operates on its own. It becomes more active when our body is under stress. It follows the mechanism of ‘Fight-or-Flight’. Para-sympathetic Nervous System also performs on it own. It follows the mechanism of ‘Rest and Digest’ and hence opposite in action to Sympathetic Nervous System.

Till now no scientific evidence is available. So most stutterers are unaware of this. But certain instances are convincing where stutterers have felt improvement by avoiding certain food items. These instances increase our intesrest in finding details on how certain food can worsen the stuttering conditions in a stutterer. So we advise all stutterers to consult a gastroenterologist to ensure if any food allergic reaction is making you stutter more. All stutterers may not be suffering from food allergic-stuttering but few may experience.Most common food allergen which can cause stuttering is found to be ‘Gluten’. Gluten is found in wheat, so present in most bakery items like – bread. When a stutterer is allergic to gluten, can experience high level of stuttering. The stutterer may not be able to complete even a sentence. His stuttering condition can get normal once he stops consuming products having gluten.

Foods rich in Dopamine can also cause extreme stuttering in stutterers. Dopamine is present in caffeine. Some may also be allergic to peanut butter or sugar. The allergic products are needed to be identified properly and should not be included in the diet. Extreme stuttering caused due to food allergy can be checked only by avoiding the foods in your diet that cause allergy. There are many treatments and speech therapy techniques available that may help increase fluency in some stutterers to the point where an untrained ear can not identify a problem; however, there is essentially no “cure” for the disorder at present.

Reference :

• Robert E. Card. A Study of Allergy in Relation to Stuttering.Journal of Speech and Hearing Disorders Vol.4 223-230 September 1989.
• Howell P. Behavioral effects arising from the neural substrates for atypical planning and execution of word production in stuttering. Exp Neurol. 2010 Sep;225(1):55-9. Epub 2010 Jun 23.
• Horga G, Horga A, Baeza I, Castro-Fornieles J, Lázaro L, Pons A. Genetics & Medicine⁠ Drug-induced speech dysfluency and myoclonus preceding generalized tonic-clonic seizures in an adolescents. J Child Adolesc Psychopharmacol. 2010 Jun;20(3):233-4. ⁠
• Büchel C, Watkins KE. Genetic susceptibility to. Genetic susceptibility to persistent stuttering. M N Engl J Med. 2010 Jun 10;362(23):2226;
• Leahy MM, Walsh IP. 27. Paying attention to therapy discourse: identifying therapy processes and practice in talk about talk. Semin Speech Lang. 2010 May;31(2):98-110. Epub 2010 Jun 2.
• Howell P, Bailey E, Kothari N.Clin Linguist Phon. 2010 Jun;24(7):556-75.Changes in the pattern of stuttering over development for children who recover or persist.⁠

Supported  by

Challenge Tes (Eliminasi Provokasi Makanan) : Diagnosis Pasti Alergi Makanan dan Hipersensitifitas Makanan

Food allergy is a matter of concern because it affects about 0.5-3.8% of the paediatric population and 0.1-1% of adults, and as well may cause life-threatening reactions. Skin prick testing with food extracts and with fresh foods, the measurement of food-specific IgE, elimination diets and a double-blind, placebo-controlled food challenge are the main diagnostic procedures; many non-validated procedures are available, creating confusion among patients and physicians. Oral food challenges are indicated for the diagnosis of food allergy and the double-blind, placebo-controlled oral food challenge is considered the gold standard diagnostic method in patient with suspected food allergy and food hypersensitivity.

Meski masih banyak diperdebatkan tetapi berbagai fakta ilmiah berupa laporan kasus dan penelitian ilmiah menunjukkan berbagai gangguan tubuh dan sistem tubuh terutama gangguan fungsional tubuh yang belum dapat dipastikan penyebabnya seringkali berkaitan dengan reaksi akibat  makanan yang dikonsumsi. Diagnosis alergi atau hipersensitif makanan dibuat bukan dengan tes alergi tetapi berdasarkan diagnosis klinis, yaitu anamnesa (mengetahui riwayat penyakit penderita) dan pemeriksaan yang cermat tentang riwayat keluarga, riwayat pemberian makanan, tanda dan gejala alergi makanan sejak bayi hingga dewasa dan dengan eliminasi provokasi makanan. Intervensi diet atau Challenge test adalah untuk mencari penyebab dan memastikan bahwa berbagai gangguan penyakit yang ada berkaitan dengan alergi dan hipersensitifitas makanan sekaligus memperbaiki atau mengurangi gangguan yang ada.

 Latar Belakang :

• Tidak semua gangguan asma, gangguan kulit adalah alergi makanan. Bila tidak diperantarai oleh Imunoglobulin E biasanya di sebut hipersensitifitas Makanan.
• Untuk mendiagnosis dan memastikan makanan penyebab alergi dan hipersensitifitas makanan harus menggunakan Provokasi makanan secara buta (Double Blind Placebo Control Food Chalenge = DBPCFC). DBPCFC adalah gold standard atau baku emas untuk mencari penyebab secara pasti alergi makanan. Cara DBPCFC tersebut sangat rumit dan membutuhkan waktu, tidak praktis dan biaya yang tidak sedikit. Tes alergi tidak bisa memastikan penyebab alergi makanan karena meski sensitifitasnya baik tetapi spesifitasnya terhadap alergi makanan rendah.
• Beberapa pusat layanan alergi anak melakukan modifikasi terhadap cara itu. Children Allergy Clinic Jakarta melakukan modifikasi dengan cara yang lebih sederhana, murah dan cukup efektif. Modifikasi DBPCFC tersebut dengan melakukan “Modifikasi Eliminasi Provokasi Makanan Terbuka” atau disebut sebagai Intervensi Diet atau challenge Test.
• Bila setelah dilakukan eliminasi beberapa penyebab alergi makanan selama 3 minggu didapatkan perbaikan , maka dapat dipastikan penyebabnya adalah penyebab berbagai gangguan yang ada adalah berkaitan dengan  alergi makanan dan hipersensitifitas makanan.
• Gangguan metabolisme tubuh, gangguan endokrin, gangguan autoimun dan berbagai gangguan genetik lainnya (seperti Lupus, rematoid artritis, AUTISM, ADHD, Psoriasi, Vitiligo, dan lain-lain) ternyata menurut penelitian kekambuhan gangguan  diperberat oleh alergi dan hipersensitifitas makanan. Pada gangguan tersebut alergi makanan dan hipersensitifitas makanan bukan sebagai penyebab tetapi hanya sebagai faktor yang memperberat.
• Berbagai gangguan fungsional khususnya gangguan saluran cerna dan susunan sataf pusat sering berkaitan dengan gangguan alergi makanan dan hipersensitifitas makanan. Ciri khasnya biasanya terdapat keluhan berulang seringkali dokter mengatakan kedaan tubuhnya normal karena dalam pemeriksaan darah, USG, endoskopi, CT scan, EEG semuanya normal. Karakteristik lainnya adalah penggunaan obat jangka panjang tanpa bisa menjelaskan penyebabnya atau tanpa disertai gangguan organ tubuh.
• Banyak kontroversi dan perbedaan pendapat tentang pengaruh makanan dan gangguan fungsi tubuh karena dasar penilaian yang bebeda. Pada penelitian yang menunjang dilakukan dengan intervensi eliminasi provokasi makanan dan pengamatan secara klinis. Tetapi bagi penentangnya biasanya melakukan penelitian dengan penilaian laboratorium atau tes alergi tanpa dilakukan intervensi eliminasi provokasi.
• Kontroversi pihak yang tidak sependapat dengan alergi dan hipersensitifitas makanan berkaitan dengan berbagai gangguan tubuh karena hanya mengamati kaitan makanan dengan berbagai riwayat yang ada hanya dengan anamnesa (mengetahui riwayat gangguan penderita), tes alergi ataupun berbagai pemeriksaan alergi lainnya tanpa melakukan challenge test dengan benar.
• Bila anak anda mengalami gangguan alergi dan hipersensitifitas makanan, biasanya salah satu orangtua ada yang mengalami juga (biasanya anak dan orangtua dengan nwajah yang sama). Bila ini terjadi tidak ada salahnya lakukan intervensi diet dengan saat yang sama karena akan mempermudah pelaksaannnya dalam penyajian makanan.



Program Intervensi Diet atau “Modifikasi Eliminasi Provokasi Makanan Terbuka” atau Challenge test

1. LANGKAH PERTAMA : identifikasi berbagai gangguan yang ada pada tubuh anda dan anak anda
2. LANGKAH KE DUA : identifikasi minimal satu gejala yang ada dalam gangguan fungsi saluran cerna yang selama ini kadang tidak disadari
3. LANGKAH KE TIGA : Lakukan program intervensi diet atau eliminasi provokasi atau  Challenge test dengan hanya mengkonsumsi makanan yang relatif aman dan menghindari beberapa makanan yang dicurigai sebagai penyebab selama 3 minggu.
4. LANGKAH KE EMPAT : lakukan evaluasi dengan cermat berbagai gangguan yang ada dan cermati berbagai faktor yang berpengaruh , biasanya akan membaik secara bersamaan
5. LANGKAH KE LIMA  : Bila ingin mengetahui penyebabnya lakukan provokasi satu persatu makanan yang dicurigai mulai dari daftar makanan step 2 terus ke high risk intervention.
6. LANGKAH KE ENAM : lakukan diet pemeliharaan (maintenance dietary) dengan melakukan tahapan dan jenis khusus tidap harinya



LANGKAH PERTAMA : identifikasi berbagai gangguan yang ada pada tubuh dan sistem organ tubuh

LANGKAH KE DUA : Identifikasi minimal satu gejala yang ada dalam gangguan fungsi saluran cerna yang selama ini kadang tidak disadari

LANGKAH KE EMPAT : lakukan evaluasi dengan cermat berbagai gangguan yang ada dan cermati berbagai faktor yang berpengaruh , biasanya akan membaik secara bersamaan

LANGKAH KE LIMA  : Bila ingin mengetahui penyebabnya lakukan provokasi satu persatu makanan yang dicurigai mulai dari daftar makanan step 2 terus ke high risk intervention.

• Dilakukan trial and error satu persatu makanan dan diamati gejala yang timbul sambil diamati berbagi faktor yang berpengaruh
• Melakukan provokasi makanan harus dilakukan dalam keadaan sehat tidak rewel malam, nafsu makan baik, berat badan naik, tidak panas, batuk, pilek dan tidak ada gangguan saluran cerna atau gangguan alergi dan hipersensitifitas lainnya.

LANGKAH KE ENAM : lakukan diet pemeliharaan (maintenance dietary) dengan melakukan tahapan dan jenis khusus tiap harinya

 Bila dalam keadaan sehat seperti  tidak rewel malam, nafsu makan baik, berat badan naik, tidak panas, batuk, pilek dan tidak ada gangguan lainnya pada usia tertentu atau orang dewasa boleh dicopba konsumsi makanan beresiko.

• Pada anak usia di atas 1 tahun daftar makanan  DIETARY  INTERVENTION : STEP TWO boleh dikonsumsi 1 -2 kali perminggu, di atas usia 3-5 tahun boleh dikonsumsi 2-3 kali perminggu.  Pada usia di atas usia 2-5 tahun daftar makanan HIGH RISK DIETARY  INTERVENTION boleh dikonsumsi 1-2 kali per bulan. Dengan semakin bertambahnya usia permasalahan alergi berkurang dapat dikonsumsi lebih sering.
• Pada saat sakit , ujian sekolah (berkaitan dengan mengganggu konsentrasi), batuk lama, makan minum kurang, berat badan sulit naik,  sulit makan dan timbul gejala alergi lainya sebaiknya harus kembali ke diet eliminasi awal selama 2-3 minggu dan makanan yang beresiko ditunda lagi.

 End Point :

• Intervensi Diet/Challenge Tes atau Eliminasi Provokasi adalalah diagnosis pasti untuk memngetahui seseorang mengalami alergi makanan dan hipersensitifitas makanan. Tes alergi dan pemeriksaan lainnya belum memastikan penyebab alergi atau hipersensitifitas makanan.
• Penderita yang harus dicurigai mengalami gangguan alergi makanan dan hipersensitifitas makanan adalah yang mengalami gangguan fungsi saluran cerna
• Ketidakberhasilan intervensi diet ini tidak disiplin dan tidak ketat dalam menghindari makanan pantangan atau karena terganggu Infeksi saluran napas atau infeksi virus lain yang tidak disadari
• Berdasarkan berbagai penelitian selain mengakibatkan gangguan fungsional organ tubuh ternyata juga memperberat berbagai gangguan organik dan gangguan auto imun, gangguan endokrin dan metabolisme dan berbagai gangguan genetik lainnya.
• Kekawatiran tentang kekurangan gizi saat melakukan tes eliminasi ini sebenarnya tidak berdasar, karena setiap makanan yang sementara dihindari selalu ada makanan pengganti yang tidak kalah gizinya. Justru setelah dilakukan intervensi diet bila dilakukan secara benar dan tanpa dipengaruhi faktor infeksi maka keberhasilannya ditandai dengan berat badan yang meningkat. bila BB tidak meningkat sebagai faktor penentu ketidak berhasilan program intervensi diet.
• Bila dalam melakukan Intervensi Diet/Challenge Tes atau Eliminasi Provokasi dengan benar dan berhasil maka penderita harus percaya faktanya bahwa selama ini berbagai gangguan yang ada disebabkan karena reaksi simpang makanan. Meski berbagai pendapat menentang atau tidak mempercayainya. Pihak yang tidak sependapat ini harus dimaklumi karena untuk memastikan penyebab alergi dan hipersensitifitas makanan tidak mudah.
• Intervensi Diet/Challenge Tes atau Eliminasi Provokasi hanya dilakukan selama 3 minggu bukan selamanya setelah itu dilakukan provokasi makanan atau mantenance diet.

Daftar Pustaka

• Fleischer DM, Bock SA, Spears GC, Wilson CG, Miyazawa NK, Gleason MC, Gyorkos EA, Murphy JR, Atkins D, Leung DY. Oral Food Challenges in Children with a Diagnosis of Food Allergy. J Pediatr. 2010 Oct 27.
• Lins MG, Horowitz MR, da Silva GA, Motta ME. Oral food challenge test to confirm the diagnosis of cow's milk allergy. J Pediatr (Rio J). 2010 Jul-Aug;86(4):285-9. Epub 2010 May 27. English, Portuguese.
• Pestana S, Moreira M, Olej B. Safety of ingestion of yellow tartrazine by double-blind placebo controlled challenge in 26 atopic adults. Allergol Immunopathol (Madr). 2010 May-Jun;38(3):142-6. Epub 2010 Jan 27.
• Rincón de Arellano IR, Vázquez-Cortés S, Sinaniotis AC, Fernández-Rivas M. False positive placebo reaction in a double-blind placebo-controlled food challenge. J Investig Allergol Clin Immunol. 2009;19(3):241-2. No abstract available.
• Asero R, Fernandez-Rivas M, Knulst AC, Bruijnzeel-Koomen CA. Double-blind, placebo-controlled food challenge in adults in everyday clinical practice: a reappraisal of their limitations and real indications. Curr Opin Allergy Clin Immunol. 2009 Aug;9(4):379-85. Review.
• Vlieg-Boerstra BJ, Duiverman EJ, van der Heide S, Bijleveld CM, Kukler J, Dubois AE. Should children with a history of anaphylaxis to foods undergo challenge testing?  Clin Exp Allergy. 2008 Dec;38(12):1935-42. Epub 2008 Sep 3.
• Lieberman JA, Sicherer SH. Diagnosis of Food Allergy: Epicutaneous Skin Tests, In Vitro Tests, and Oral Food Challenge. Curr Allergy Asthma Rep. 2010 Oct 5.
• Pestana S, Moreira M, Olej B. Safety of ingestion of yellow tartrazine by double-blind placebo controlled challenge in 26 atopic adults. Allergol Immunopathol (Madr). 2010 May-Jun;38(3):142-6. Epub 2010 Jan 27.
• Patriarca G, Schiavino D, Pecora V, Lombardo C, Pollastrini E, Aruanno A, Sabato V, Colagiovanni A, Rizzi A, De Pasquale T, Roncallo C, Decinti M, Musumeci S, Gasbarrini G, Buonomo A, Nucera E. Food allergy and food intolerance: diagnosis and treatment. Intern Emerg Med. 2009 Feb;4(1):11-24. Epub 2008 Aug 16. Review.
• Scibilia J, Pastorello EA, Zisa G, Ottolenghi A, Ballmer-Weber B, Pravettoni V, Scovena E, Robino A, Ortolani C. Maize food allergy: a double-blind placebo-controlled study. Clin Exp Allergy. 2008 Dec;38(12):1943-9. Epub 2008 Sep 4
• Reese I, Zuberbier T, Bunselmeyer B, Erdmann S, Henzgen M, Fuchs T, Jäger L, Kleine-Tebbe J, Lepp U, Niggemann B, Raithel M, Saloga J, Vieths S, Werfel T. Diagnostic approach for suspected pseudoallergic reaction to food ingredients. J Dtsch Dermatol Ges. 2009 Jan;7(1):70-7. Epub 2008 Nov 24. Review.
• Rancé F, Deschildre A, Villard-Truc F, Gomez SA, Paty E, Santos C, Couderc L, Fauquert JL, De Blic J, Bidat E, Dupont C, Eigenmann P, Lack G, Scheinmann P; SFAIC and SP2A Workgroup on OFC in Children. Oral food challenge in children: an expert review. Eur Ann Allergy Clin Immunol. 2009 Apr;41(2):35-49.
• Lee S, Noh GW, Lee KY. Clinical application of histamine prick test for food challenge in atopic dermatitis. J Korean Med Sci. 2001 Jun;16(3):276-82.
• Vatn MH, Grimstad IA, Thorsen L, Kittang E, Refnin I, Malt U, Løvik A, Langeland T, Naalsund A. Adverse reaction to food: assessment by double-blind placebo-controlled food challenge and clinical, psychosomatic and immunologic analysis. Digestion. 1995;56(5):421-8.
• Asero R, Fernandez-Rivas M, Knulst AC, Bruijnzeel-Koomen CA. Double-blind, placebo-controlled food challenge in adults in everyday clinical practice: a reappraisal of their limitations and real indications. Curr Opin Allergy Clin Immunol. 2009 Aug;9(4):379-85. Review.
• Fleischer DM, Bock SA, Spears GC, Wilson CG, Miyazawa NK, Gleason MC, Gyorkos EA, Murphy JR, Atkins D, Leung DY. Oral Food Challenges in Children with a Diagnosis of Food Allergy. J Pediatr. 2010 Oct 27. [Epub ahead of print]
• Pastorello EA, Pravettoni V, Stocchi L, Bigi A, Schilke ML, Zanussi C. Are double-blind food challenges necessary before starting an elimination diet? Allergy Proc. 1991 Sep-Oct;12(5):319-25.
• Vatn MH, Grimstad IA, Thorsen L, Kittang E, Refnin I, Malt U, Løvik A, Langeland T, Naalsund A.  Adverse reaction to food: assessment by double-blind placebo-controlled food challenge and clinical, psychosomatic and immunologic analysis. Digestion. 1995;56(5):421-8.
•  Wüthrich B. [Food allergy, food intolerance or functional disorder?] Praxis (Bern 1994). 2009 Apr 1;98(7):375-87. German.

• Gangguan Hormonal, Alergi Makanan dan Hipersensitifitas Makanan
• Benarkah Aku Tidak alergi makanan ? Kontroversi tentang Alergi dan Hipersensitifitas Makanan
• Gangguan Mata dan Alergi Makanan
• Gangguan Kesehatan Gigi, Kesehatan Mulut dan Alergi Makanan
• Sakit Kepala atau Migren Disebabkan Alergi -Hipersensitifitas Makanan ?
• Gangguan Kulit Pada Anak, Karena Pengaruh Alergi atau Hipersensitif Makanan
• Diare Berkepanjangan dan Berak Darah berulang Pada Anak, Karena Pengaruh Alergi atau Hipersensitif Makanan
• Gangguan Tidur Pada Anak Karena Pengaruh Alergi atau Hipersensitif Makanan ?
• Gastrooesepageal Refluks (GER) atau Sering Muntah Pada Anak, Karena Pengaruh Alergi atau Hipersensitif Makanan
• Gangguan Buang Air Besar (Konstipasi) Pada Anak, Karena Pengaruh Alergi atau Hipersensitif Makanan
• Rheumatoid Arthritis, Food Allergy and Adverse Food Reaction
• Alergi Debu dan “Fobia Alergi Debu”
• Alergi Hewan Peliharaan dan “Fobia Alergi Binatang”
• Sulitnya Mencari Penyebab Alergi
• Benarkah aku tidak alergi makanan ? Kontroversi tentang Alergi dan Hipersensitifitas Makanan
• Benarkah Debu sebagai Penyebab Alergi yang Utama
• Waspadai Diagnosis TBC (“Fleks”) yang tidak benar pada penderita Alergi
• Waspadai bahaya dan Komplikasi operasi amandel dan Kontroversi Kapan sebaiknya Harus Dilakukan operasi Amandel
• Kenali dan Cermati Irritable Bowel Syndrome (Gangguan Pencernaan Jangka Panjang) Berkaitan dengan Alergi Makanan

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• Berbagai Kumpulan Artikel Berkaitan dengan Gangguan Mata
• Berbagai Kumpulan Artikel Alergi makanan berkaitan dengan Gangguan Jantung dan Pembuluh Darah
• Berbagai kumpulan Artikel Alergi makanan berkaitan dengan gangguan Otot dan Tulang
• Berbagai kumpulan Artikel Berkaitan dengan Gangguan Organ tubuh lainnya
• Berbagai Kumpulan Artikel Alergi makanan berkaitan denmgan Gangguan Tidur
• Berbagai Kumpulan Artikel Alergi makanan Berkaitan dengan gangguan saluran cerna
• Reaksi Simpang Makanan dan Gangguan Neurologi
• Waspadai Makanan Penyebab Gangguan Otak dan Perilaku Anak
• Kejang, Epilepsi, Nonsiezure episode, Nonepilepticseizure, Nonepileptic paraxysmal disorders atau nonepileptic attack disorders dan Alergi-Hipersensitifitas Makanan

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Widodo judarwanto, pediatrician

 Copyright © 2010, Children Allergy Center  Information Education Network. All rights reserved

Feeding disorders, ALTE syndrome, Sandifer syndrome and gastroesophageal reflux disease in the course of food hypersensitivity in 8-month old infant

[Article in Polish]

Iwańczak B, Mowszet K, Iwańczak F.

Akademia Medyczna we Wrocławiu, II Katedra i Klinika Pediatrii, Gastroenterologii i Zywienia. barbara@iwanczak.com

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Office : JL Taman Bendungan Asahan 5  Jakarta Pusat  Phone : (021) 70081995 – 5703646email :  judarwanto@gmail.com, www.childrenallergyclinic.wordpress.com/  

Information on this web site is provided for informational purposes only and is not a substitute for professional medical advice. You should not use the information on this web site for diagnosing or treating a medical or health condition. You should carefully read all product packaging. If you have or suspect you have a medical problem, promptly contact your professional healthcare provider.  

Copyright © 2010, Children Allergy Center  Information Education Network. All rights reserved

No To Hattatsu. 2010 Sep;42(5):367-71.

An autopsy case of child with severe motor and intellectual disabilities showing hyper IgE subsequent to food allergy

[Article in Japanese]

Miwa N, Tanuma N, Hayashi M.

Department of Pediatrics, Tokyo Metropolitan Fuchu Medical Center for the Disabled, Fuchu, Tokyo. Naho_Miwa@member.metro.tokyo.jp

Reference :

• Hadjivassiliou M, Rao DG, Wharton SB, Sanders DS, Grünewald RA, Davies-Jones AG. Sensory ganglionopathy due to gluten sensitivity. Neurology. 2010 Sep 14;75(11):1003-8.

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Office : JL Taman Bendungan Asahan 5  Jakarta Pusat  Phone : (021) 70081995 – 5703646email :  judarwanto@gmail.com, www.childrenallergyclinic.wordpress.com/  

Information on this web site is provided for informational purposes only and is not a substitute for professional medical advice. You should not use the information on this web site for diagnosing or treating a medical or health condition. You should carefully read all product packaging. If you have or suspect you have a medical problem, promptly contact your professional healthcare provider.  

Copyright © 2010, Children Allergy Center  Information Education Network. All rights reserved

An autopsy case of child with severe motor and intellectual disabilities showing hyper IgE subsequent to food allergy

[Article in Japanese]

Miwa N, Tanuma N, Hayashi M.

Department of Pediatrics, Tokyo Metropolitan Fuchu Medical Center for the Disabled, Fuchu, Tokyo. Naho_Miwa@member.metro.tokyo.jp

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Office : JL Taman Bendungan Asahan 5  Jakarta Pusat  Phone : (021) 70081995 – 5703646email :  judarwanto@gmail.com, www.childrenallergyclinic.wordpress.com/  

Information on this web site is provided for informational purposes only and is not a substitute for professional medical advice. You should not use the information on this web site for diagnosing or treating a medical or health condition. You should carefully read all product packaging. If you have or suspect you have a medical problem, promptly contact your professional healthcare provider.  

Copyright © 2010, Children Allergy Center  Information Education Network. All rights reserved

Dietary intake in adolescents with asthma – potential for improvement.

Bueso AK, Berntsen S, Mowinckel P, Andersen LF, Lødrup Carlsen KC, Carlsen KH.

Voksentoppen, Department of Paediatrics, Oslo University Hospital, Rikshospitalet, Norway Department of Paediatrics, Oslo University Hospital, Ullevål, Norway Department of Sports Medicine, Norwegian School of Sport Sciences, Oslo, Norway Faculty of Medicine, University of Oslo, Oslo, Norway.

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Office : JL Taman Bendungan Asahan 5  Jakarta Pusat  Phone : (021) 70081995 – 5703646email :  judarwanto@gmail.com, www.childrenallergyclinic.wordpress.com/  

Information on this web site is provided for informational purposes only and is not a substitute for professional medical advice. You should not use the information on this web site for diagnosing or treating a medical or health condition. You should carefully read all product packaging. If you have or suspect you have a medical problem, promptly contact your professional healthcare provider.  

Copyright © 2010, Children Allergy Center  Information Education Network. All rights reserved

Should breastfeeding mothers avoid allergenic foods?

List BA, Vonderhaar KJ.

Betsy A. List is a Guidelines Program Administrator at Cincinnati Children’s Hospital Medical Center, Cincinnati, OH. She can be reached via e-mail at Betsy.list@cchmc.org. Karen J. Vonderhaar is a Guidelines Program Administrator at Cincinnati Children’s Hospital Medical Center, Cincinnati, OH.

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Office : JL Taman Bendungan Asahan 5  Jakarta Pusat  Phone : (021) 70081995 – 5703646email :  judarwanto@gmail.com, www.childrenallergyclinic.wordpress.com/  

Information on this web site is provided for informational purposes only and is not a substitute for professional medical advice. You should not use the information on this web site for diagnosing or treating a medical or health condition. You should carefully read all product packaging. If you have or suspect you have a medical problem, promptly contact your professional healthcare provider.  

Copyright © 2010, Children Allergy Center  Information Education Network. All rights reserved

Source : associated news
Some people have recently discovered that they have a food allergy to cinnamon, which took them years to diagnose. A cinnamon allergy is also a difficult allergy to have this time of year with all of the cinnamon spiced baked good around, but even more difficult is the swollen throat, itchy eyes, and runny nose that they have for hours after accidentally eating something with cinnamon in it,

Why Cinnamon Allergies are Hard to Detect

While cinnamon is a common food allergen, most people are not aware they have it, because as a spice, and not a food, it is difficult to pinpoint as the irritating cause of their symptoms. Also, much of the “cinnamon” we purchase in our store is actually cassia, which is a member of the cinnamon family, but true cinnamon. Once again making it difficult to pinpoint exactly what is causing the symptoms. While the apple pie someone ate may be laced with cinnamon, causing an allergic reaction, the churro the same person ate, may have used cassia, not causing a reaction at all, causing the person to rule out cinnamon as the allergen.

Another reason people fail to identify cinnamon as the cause of their allergies is that cinnamon does not have to be individually mentioned on food labels. It can fall under the generic label of “spices.”

Cinnamon Allergy Symptoms and Treatment

While allergic reactions to cinnamon vary from person to person, the most common symptoms are irritation of the throat or tongue, lip and tongue swelling, runny nose, watery and sore eyes, eczema, hives, disturbed sleep, and nausea.

The most common treatment for any allergic reaction is to take an over the counter antihistamine as soon as possible. Benadryl is a common allergy medication that can be purchased at any drug store. A doctor can prescribe a stronger medication for life threatening reactions, including anaphylactic shock.

Cinnamon Substitutes

The best defense to a cinnamon allergy is to avoid cinnamon altogether. Cinnamon can be found in chai drinks, cinnamon rolls (of course), pumpkin breads and pies, apple pies and other apple baked goods, spiced cider, cinnamon schnapps (such as Goldschlager), and some granolas and cereals. Mexican, Moroccan, and Indian cuisines can contain cinnamon in their savory dishes

Substituting other spices in baked goods and breads allows cinnamon allergy sufferers to enjoy their favorite baked goods without suffering any side effects. I have had good luck substituting nutmeg and ground cloves for cinnamon. Most people don’t even notice the difference.
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Office : JL Taman Bendungan Asahan 5  Jakarta Pusat  Phone : (021) 70081995 – 5703646email :  judarwanto@gmail.com, www.childrenallergyclinic.wordpress.com/  

Information on this web site is provided for informational purposes only and is not a substitute for professional medical advice. You should not use the information on this web site for diagnosing or treating a medical or health condition. You should carefully read all product packaging. If you have or suspect you have a medical problem, promptly contact your professional healthcare provider.  

Copyright © 2010, Children Allergy Center  Information Education Network. All rights reserved

• Sulitnya Mencari Penyebab Alergi
• Benarkah Aku tidak Alergi makanan ?
• Memastikan penyebab alergi makanan harus dengan chalenge tes atau eliminasi provokasi makanan bukan dengan tes alergi.

Banyak kasus penderita alergi sering frustasi karena hilang timbulnya keluhan dan tanpa diketahui secara pasti penyebabnya. Sehingga berbagai dokter telah dikunjungi namun seringkali semakin bingung karena pendapat berbagai dokter tersebut tidak ada yang sama. Seorang dokter mengatakan makanan tidak berkaitan dengan berbagai gejala yang ada. Tetapi kelompok dokter lain mengatakan bahwa makanan berperanan dengan gangguan yang ada. Hal ini wajar tejadi karena sumber kontroversi tersebut sampai saat ini adalah penentuan diagnosis alergi makanan dan banyak faktor yang berpengaruh. Untuk memastikan makanan sebagai penyebab alergi adalah dengan diagnosis klinis bukan dengan pemeriksaan laboratorium atau tes alergi. Bukan hanya perbedaan pendapat antara klinisi, hasil penelitian tentang alergi makanan berkaitan dengan manifestasi berbagai organpun seringkali tidak sama karena sebagian peneliti mengandalkan diagnosis bukan dengan diagnosis klinis tetapi dengan pemeriksaan laboratorium atau tes alergi. Bila kesalahan dasar ini terjadi maka perbedaan pendapat dan kontroversi tersebut akan terjadi semakin besar dalam penanganan berbagai kasus alergi.

Ilustrasi Kasus :

• Berbagai klinisi dan penelitian banyak yang mengungkapkan bahwa alergi berkaitan dengan berbagai gangguan tubuh dan gangguan perilaku. Hal ini terjadi karena klinisi dan dokter tersebut menentukan tanda dan gejala alergi dengan melakukan diagnosis klinis dengan eliminasi provokasi. Sedangkan dokter lain dan peneliti lain mengungkapkan bahwa alergi tidak berkaitan dengan berbagai manifestasi yang ada karena menggunakan dasar laboratorium atau tes alergi.  Padahal dalam menentukan diagnosis alergi makanan yang paling penting adalah diagnosis klinis bukan laboratorium atau tes alergi.
• Seorang bayi yang sudah minum susu sapi selama 6 bulan tidak ada manifestasi alergi tetapi saat kemudan divonis alergi susu sapi. Selanjutnya setelah 6 bulan orangtua frustasi mencari berbagai susu yang cocok karena susu yang paling amanpun ternyata menimbulkan alergi. Kasus ini terjadi karena klinisi hanya memfokuskan penyebab alergi karena alergi susu sapi, padahal banyak faktor lain juga mempengaruhi timbulnya alergi seperti infeksi virus atau makanan lain yang dikonsumsi. Dan ternyata memang penderita tidak mengalami alergi susu sapi ketika dilakukan eliminasi provokasi susu sapi.
• Seorang dokter pernah diklaim oleh dokter lainnya ketika menulis bahwa tes alergi tertentu tidak direkomendasikan dan tidak akurat sebagai pengobatan atau diagnosis. Bahkan perbedaan pendapat tersebut berpotensi akan memasuki meja hijau, tetapi dengan komunikasi ilmiah yang dilakukan ternyata perbedaan pendapat tersebut dapat diperbaiki.
• Seorang dokter ahli dipermasalahkan oleh sebagian dokter ahli lainnya mengungkapkan berbagai tanda dan gejala alergi yang ada berkaitan dengan makanan. Padahal ungkapan tersebut disampaikan ditunjang dengan fakta ilmiah dari berbagai penelitian yang ada. Akhirnya perbedaan pendapat  ini masuk dalam ranah komite etik profesi.  Dalam pertemuan tersebut juga masih terjadi perbedaan pendapat tajam. Seorang nara sumber bidang yang berkopeten mengatakan bahwa bisa saja pengaruh histamin dapat menganggu berbagai organ tubuh lainnya meski insidennya tidak banyak. Tetapi yang pihak lain bependapat bahwa berbagai pakar dari berbagai keahlian tidak setuju dengan berbagai tanda dan gejala tersebut dikaitkan dengan alergi makanan. Tetapi akhirnya salah satu pihak mengalah untuk tidak mempanjang kontroversi ini demi kesejawatan.
• Seorang penderita kejang yang berlangsung selama sepuluh tahun dengan minum berbagai obat anti kejang tidak membaik. Dalam pemeriksaan laboratorium, CT scan dan EEG dalam batas normal. Berbagai dokter ahli persarafan di Indonesia bahkan di Singapura di bidangnyapun masih terjadi beda pendapat. Sebagian menyarankan minum obat kejang sebagian dokter lainnya obat kejang tidak perlu.  Ketika dilakukan evaluasi ternyata penderita mengalami gangguan alergi makanan dan dicurigai bahwa sangat mungkin gangguan kejang karena berkaitan dengan alergi makanan. Saat dilakukan elminasi provokasi makanan terbukti gejala alergi saluran cerna membaik dan keluhan kejang membaik tanpa pengobatan anti kejang. Saat itu penderita melakukan elminansi provokasi makanan dengan ketat selama 2 bulan. Tetapi saat mendengar informasi dari dokter ahli lainnya bahwa makanan tidak berkaitan dengan gejala tersebut penderita melepas lagi program eliminasi provokasi makanan. Ketika melakukan konsultasi ulang ternyata setelah 2 bulan paska menarik diri dari program elimnasi provokasi tersebut gejala kejang tersebut hilang timbul lagi dengan berganti-ganti obat tetapi responnya tidak membaik seperti yang diharapkan.

Berdasarkan beberapa fakta ilmiah termasuk berbagai penelitian ilmiah belakangan telah terungkap bahwa alergi makanan menimbulkan komplikasi yang cukup mengganggu, karena alergi dapat mengganggu semua organ atau sistem tubuh kita termasuk gangguan fungsi otak. Karena gangguan fungsi otak itulah maka timbul gangguan perkembangan dan perilaku pada anak seperti gangguan konsentrasi, gangguan tidur, gangguan emosi, gangguan konsentrasi hingga memperberat gejala ADHD dan autism. Meskipun sebenarnya alergi bukan penyebab ADHD atau Autism tetapi hanya memperberat gangguan perilaku yang sudah ada tersebut. Meski berbagai peneilitian klinis juga mengungkapkan hal tersebut ternyata terdapat juga sebagian penelitian klinis yang tidak sependapat bahwa berbagai kelainan tersebut tidak berkaitan dengan alergi.

Memang sampai saat ini bahkan di negara sudah majupun banyak gangguan alergi tidak disadari bahkan oleh sebagian dokter. Sejauh ini banyak orang tidak mengetahui bahwa berbagai keluhan yang dia alami atau yang dialami anaknya itu adalah gejala alergi.  Resource (Marketing Research) Limited  melakukan penelitian di Inggris bagian selatan, tahun 2000  dilaporkan  lebih dari 50% orang dewasa menderita alergi makanan. Sekitar 70% penderita  alergi baru mengetahui kalau ia mengalami  alergi setelah lebih dari 7 tahun. Sekitar 50% orang dewasa mengetahui penyebab gejala alergi setelah 5 tahun, bahkan terdapat 22% baru mengetahui setelah lebih 15 tahun mengalami gangguan alergi tersebut. Sebanyak 80% penderita alergi mengalami gejala seumur hidupnya. Hal ini menunjukkan bahwa di negara maju seperti Inggrispun para dokter terlambat mendiagnosis alergi apalagi di Indonesia. Ternyata para dokter di Inggrispun menganggap bahwa selama ini berbagai gangguan yang ada tidak berkaitan dengan alergi.

Berbagai gangguan alergi atau hipersensitifitas makanan tersebut adalah gangguan fungsional sehingga dianggap normal dan dikatakan dengan pertambahan usia akan membaik. Mungkin saja saja sebagian pendapat tersebut benar. Memang penderita alergi makanan terutama yang mengganggu saluran cerna dan ssusunan saraf pusat mengalami gangguan fungsional. Gangguan alergi makanan khususnya gangguan pada saran cerna dan susunan saraf pusat adalah gangguan fungsi bukan gangguan organnya. Hal inilah yang melatarbelakngi mengapa semua gangguan yang berkaitan dengan alergi makanan dan hipersensitifitas makanan sering dianggap normal. Karena, memang manifestasi yang ada tidak didapatkan kelainan organ dengan pemeriksaan USG, foto kontras dan CT scan. Karena pemeriksaan tersebut tidak didapatkan kelainan maka dianggap penderita tidak punya kelainan, tetapi anehnya keluhan penderita hilang timbul. Bahkan beberapa dokter menganggap bahwa gangguan tersebut dipengaruhi karena stres. Saat dilakukan eliminasi provokasi makanan ternyata gangguan yang dianggap normal itu bisa membaik. Memang gangguan fungsional pada umumnya adalah masalah imaturitas atau ketidakmatangan sistem tubuh, karena dengan pertambahan usia setelah usia 2 hingga 7 tahun akan membaik. Meski ada yang masih mengalami hingga usia 12 tahun dan sebagian masih mengalami hingga dewasa meski dengan tingkat gangguan yang berkurang. Tetapi bukan berarti harus menunggu sampai usia tertentu membaik karena bila dilakukan elminasi provokasi makanan untuk mencari penyebab makanan penyebabnya gangguan tersebut akan membaik.

Dengan semakin berkembangnya ilmu pengetahuan kedokteran dan teknologi kedokteran, namun kejadian alergi justru meningkat pesat, dan semakin banyak yang masih misterius belum terungkap. Banyak klinisi memvonis alergi pada penderita tetapi tidak bisa mengadviskan dengan pasti penghindaran penyebab karena kesulitan terbesar penanganan alergi adalah mencari penyebabnya.

Alergi dan hipersensitifitas makanan pada anak tidak sesederhana seperti yang pernah kita ketahui. Sebelumnya kita sering mendengar dari dokter spesialis penyakit dalam, dokter anak, dokter spesialis yang lain bahwa alergi itu gejala adalah batuk, pilek, sesak dan gatal. Padahal dapat menyerang semua organ tanpa terkecuali mulai dari ujung rambut sampai ujung kaki dengan berbagai bahaya dan komplikasi yang mungkin bisa terjadi. Belakangan terungkap bahwa menimbulkan komplikasi yang cukup berbahaya, karena alergi dan hipersensitivitas makanan dapat mengganggu semua organ atau sistem tubuh kita termasuk gangguan fungsi otak. Karena gangguan fungsi otak itulah maka timbul gangguan perkembangan dan perilaku pada anak seperti gangguan konsentrasi, gangguan emosi, keterlambatan bicara, gangguan konsentrasi hingga memperberat gejala ADHD dan Autism.

Bila melihat demikian luasnya gangguan yang terjadi dan banyaknya organ yang terganggu, tampaknya alergi dan hipersensitivitas makanan adalah suatu “gangguan sistemik”. Dapat dimaklumi bila ada pendapat, bahwa ungkapan itu terlalu berlebihan karena semua keluhan selalu dikaitkan dengan alergi dan hipersensitifitas makanan. Namun pendapat ini akan sirna, bila banyak penderita alergi dan hipersensitivitas makanan mengungkapkan, memang benar bahwa gangguan dan keluhan tersebut memang terjadi pada dirinya.  Secara ilmiahpun hal ini didukung oleh penelitian ilmiah dan laporan ilmiah dari berbagai disiplin ilmu yang mengaitkan bahwa berbagai gejala tersebut penyebabnya adalah alergi. Habnya seringkali terjadi kontroversi yang berlebihan antara sesama dokter dan orangtua karena alergi dan hipersensitivitas makanan hanya bisa ditegakkan diagnosisnya dengan diagnosis klinis bukan dengan pemeriksaan laboratorium. Diagnosis klinis adalah mengamati secara cermat tanda dan gejala yang timbul berkaitan dengan pemberian makanan yang diberikan melalui anamnesa (menanyakan secara cermat semua keluhan) dan pemeriksaan fisaik oleh dokter.

Dalam beberapa puluh tahun lamanya mungkin sering dihadapi oleh masyarakat pada umumnya, masih sering terjadi kontroversi tentang penyakit alergi dan hipersensitifitas makanan. Sering terjadi bukan hanya pada orang awam di kalangan dokterpun masih banyak terjadi perbedaan pendapat. Seorang penderita alergi dan hipersensitivitas makanan mendapat advis dari seorang dokter untuk menghindari makanan tertentu untuk mengurangi keluhan penyakitnya. Tetapi dokter lainnya mengatakan tidak perlu menghindari makanan tersebut, karena makanan tidak berhubungan dengan penyakitnya. Sebagian dokter berpendapat, bahwa gejala alergi dan hipersensitivitas makanan jarang ditemukan.  Ada pendapat alergi dan hipersensitivitas makanan hanya berkaitan dengan sedikit penyakit dan sangat jarang menyangkut bahan makanan.

Makanan yang diakui sebagai penyebab alergi masih sangat terbatas misalnya gluten susu dan ikan. Sedangkan kubu dokter lain berpendapat alergi dan hipersensitivitas makanan sangat umum dan bersembunyi dibalik berbagai kelainan yang hingga sekarang tak dapat disembuhkan, seperti radang sendi (artritis), eksim (dermatitis atau alergi kulit), migren (sakit kepala sebelah). Mereka ingin mengungkapkan bahwa seluruh permasalahan kesehatan dapat dicetuskan dan disembuhkan dengan penanganan alergi dan hipersensitivitas makanan. Timbul pendapat bahwa penyebab alergi makanan tidak dibatasi, semua jenis makanan atau minuman dapat dianggap sebagai penyebab alergi.

Bahkan bahan bukan makanan dapat menyebabkan alergi seperti semprotan rambut, uap obat nyamuk, uap bensin, plastik dan semua bahan kimia yang potensial mengganggu dalam lingkungan kita. Penyebab alergi lainnya yang sudah lama diyakini dan tidak disangsikan lagi adalah debu, kutu, bulu binatang, serbuk sari atau bulu unggas lainnya.

Suasana perbedaan pendapat tersebut jauh dari suasana kekeluargaan. Ungkapan dari berbagai pihak seperti “tak terbukti”, “berbahaya”, “orientasi obat”, “berpikiran sempit”, “tidak ilmiah” atau “tidak kompeten” secara tak sadar secara langsung diterima oleh pasien. Jika para pakar medis sudah berbeda pendapat secara tajam, maka orang awam menjadi bingung karena pendapat berbagai dokter berlainan. Dalam menghadapi kontroversi ini tidak heran bila masyarakat semakin bingung tak tahu harus minta bantuan kemana. Fakta ilmiah dan data penelitian telah banyak menunjukkan bahwa ternyata makanan tertentu dapat menyebabkan berbagai gangguan yang selama ini tidak diperkirakan banyak orang. Ternyata, makanan yang bergizi setinggi apapun dan selezat apapun ternyata dapat merugikan mengganggu tubuh manusia yang sebaliknya dapat mengakibatkan berbagai gangguan fungsi tubuh.

Berbagai gangguan dan sistem tubuh telah disepakati sebagai akibat pengaruh makanan. Tetapi sebaliknya justru telah menjadi kontroversi baik masyarakat awam maupun sesama dokter bahwa ternyata berbagai makanan sebagai penyebab gangguan tubuh manusia. Hal itu terjadi karena untuk memastikan pengaruh makanan terhadap tubuh bukan berdasarkan tes alergi atau pemeriksaan laboratorium semata tetapi berdasarkan diagnosis klinis yang di bidang medis di sebut chalenge test atau eliminasi provokasi makanan.

Tidak hanya dalam alergi makanan, tampaknya kontroversi itu adalah hal yang biasa seperti hal penyakit lainnya di bidang kedokteran. Biasanya bila untuk memastikan diagnosis suatu penyakit atau kelainan hanya berdasarkan diagnosis klinis seringkali akan menimbulkan banyak kontroversi krena subyektifitasnya sangat tinggi. Contoh tersebut adalah dalam diagnosis Autism, ADHD, dan diagnosis gangguan fungsional lainnya yang dalam pemeriksaan imunopatobiologis normal. Hal ini mengakibatkan bahwa ADHD adalah wrong doagnosis terbesar di Amerika Serikat. Kondisi tersebut juga mengakibatkan mengapa seorang gangguan perilaku yang sama didiagnosis yang berbeda oleh 5 dokter yang berbeda. Beragamnya diagnosis kepada anak yang sama tersebut seperti diagnosis Autis, Autism Ringan, Bukan Autis, PDD NOS atau ADHD. Padahal klinisi yang mendiagnosisnya adalah sudah berkopeten di bidangnya. Tetapi bila dasar diagnosis tersebut parameternya disertai laboratorium dan pemeriksaan penunjang maka perbedaan pendapat tersebut semakin jarang. Misalnya diagnosis Hepatitis B, Hipertensi, Sindrom Nefrotik (klainan ginjal) atau Diabetes Melitus maka dalam mendiagnosisnya relatif tidak menimbulkan perbedaan persepsi. 

Sumber Kontroversi

• Di bidang ilmu kedokteran telah disepakati secara ilmiah bahwa untuk memastikan penyebab alergi adalah dengan eliminasi provokasi makanan bukan dengan tes alergi. Tes alergi hanya membantu diagnosis bukan memastikan penyebab alergi. Tetapi kesepakatan ilmiah yang seharusnya tidak terbantahkan ini sering diabaikan dan menjadi sumber berbagai kontroversi yang ada
• Penyebab lain perbedaan pendapat ini adalah sulitnya untuk memastikan penyebab alergi dengan melakukan eliminai provokasi makanan. Gold Standart atau standar baku emas diagnosis alergi makanan adalah DBPCFC (Double Blind Placebo Chalenge Food Control). Tetapi karena relatif rumit timbul beberapa modifikasi Chalenge test atau eliminasi provokasi makanan yang kelihatan mudah tetapi sulit ini seringkali tidak pernah dilakukan oleh klinisi dan sebagian ahli alergi untuk memastikan penyebab alergi makanan.
• Gangguan alergi makanan khususnya gangguan pada saran cerna dan susunan saraf pusat adalah gangguan fungsi bukan gangguan organnya. Hal inilah yang melatarbelakngi mengapa semua gangguan yang berkaitan dengan alergi makanan dan hipersensitifitas makanan sering dianggap normal. Karena, memang manifestasi yang ada tidak didapatkan kelainan organ dengan pemeriksaan USG, foto kontras dan CT scan. Karena pemeriksaan tersebut tidak didapatkan kelainan maka dianggap penderita tidak punya kelainan, tetapi anehnya keluhan penderita hilang timbul. Saat dilakukan eliminasi provokasi makanan ternyata gangguan yang dianggap normal itu bisa membaik.
• Penelitian berbagai manifestasi klinis dan pengaruh alergi makanan masih belum banyak terungkap jelas. Sampai saat ini keterkaitan berbagai manifestasi klinis gangguan fungsi tubuh dengan alergi makanan dan hipersensitifitas lainnya masih relatif sulit dibuktikan secara ilmiah. Dalam penelitian ilmiah penelitian klinis adalah mempunyai kualitas penelitian yang tidak lebih baik dibandingkan penelitian yang diukur dengan parameter imunopatobiologis. Padahal diagnosis alergi makanan dan hipersensitifitas lainnya berdasarkan diagnosis klinis bukan dengan pemeriksaan laboratorium imunopatobiologis Hal inilah yang mengakibatkan bahwa keterkaitan manifestasi klinis dengan alergi makanan sulit dibuktikan dengan standard ilmiah yang lebih baik. Pada umumnya dasar diagnosis penelitian alergi makanan dan hipersensitifita lainya yang membuktikan ketidakbermaknaannya hubungan tersebut dibuat bukan berdasarkan eliminasi provokasi tetapi berdasarkan parameter tes alergi dan laboratorium penunjang. Sehingga kesimpulan yang dibuatpun menjadi lemah. Seharusnya penelitian dampak alergi makanan atau manifestasi alergi makanan berdasarkan eliminasi provokasi makanan bukan berdasarkan parameter laboratorium atau pemeriksaan ts alergi. Di masa datang permasalahan alergi makanan dan hipersensitifitas makanan akan lebih terungkap dengan jelas bila penelitian klinis eliminasi provokasi makanan disertai perubahan klinis dan perubahan biomolekular.
•  Sebagian dokter bahkan masih mendewakan tes alergi sebagai cara untuk mencari memastikan penyebab alergi makanan dan hipersensitifitas makanan. Hal ini tampak dengan banyak pendapat dari beberapa dokter bahwa ketika seseorang dipastikan menderita alergi makanan dan hipersensitifitas makanan dengan eliminasi provokasi masih disangsikan ketika belum dilakukan tes alergi. Padahal justru angka kejadian alergi makanan lebih sedikit dibandingkan hipersensittifitas makanan lainnya. Secara umum penderita alergi makanan adalah berkisar 4-9% tetapi diduga angka kejadian hipersensitifita makanan lainnya sepuluh kali lipat dibandingkan penderita alergi makanan. Tes alergi memang diperlukan untuk diagnosis tetapi untuk memastikannya harus dikonfirmasi lagi dengan eliminasi provokasi atau chalenge test.

Sumber Kontroversi lainnya

• Pada umumnya gangguan reaksi simpang makanan karena alergi atau hipersensitifitas makanan merupakan gangguan fungsional sistem tubuh. Gangguan fusngsional sistem tubuh mempunyai karakteristik oragan tubuh yag terlibat sering dianggap normal dan dalam pemeriksaan penunjangpun tidak ditemukan kelainan. Sehingga saat dilakukan pemeriksaan penunjang apapun seperti USG, CT Scan, MRI, EEG atau pemeriksaan lainnya pada organ tubuh adalah normal. Bila dikatakan normal sering timbul pertanyaan pada penderta. Mengapa dikatakan normal, padahal saya sangat menderita setiap hari dan berlangsung demikian lama. Dalam kedaan seperti ini biasanya setiap dokter yang memeriksa akan memeberikan pendapat yang bebeda tentang penyebabnya, bahkan sebagian dokter mengatalkan jujur tidak tahu penyebabnya. Beberapa dokter yang mencoba berspekulasi memberikan penilaian tentang penyebab kelainan tersebut biasanya jawaban seputar stres, masuk angin, terlalu capek dan masih bayak penyebab lainnya yang secara ilmiah kadang tidak sesuai. Sehingga saat wajar ketika pasien mengeluhkan gangguan yang selama ini diderita kepada tiga atau lima dokter pendapatnya akan berbeda. Hal ini akan membuat penderita semakin frustasi. Bila penyebabnya masih simpang siur maka akan berimbas pada terapinya akan juga tidak akan pernah fokus pada penyebabnya. Hal inilah yang juga mengakibatkan penderita gangguan reaksi simpang makanan karena alergi atau hipersensitifitas makanan menjadi berkepanjangan hilang timbul terus menerus dengan berpindah-pindah dokter.
• Berdasarkan beberapa fakta ilmiah belakangan terungkap bahwa alergi menimbulkan komplikasi yang cukup menggaggu, karena alergi dapat mengganggu semua organ atau sistem tubuh kita termasuk gangguan fungsi otak. Karena gangguan fungsi otak itulah maka timbul gangguan perkembangan dan perilaku pada anak seperti gangguan konsentrasi, gangguan tidur, gangguan emosi, keterlambatan bicara, gangguan konsentrasi hingga memperberat gejala ADHD dan autism. Meskipun sebenarnya alergi bukan penyebab ADHD atau Autism tetapi hanya memperberat gangguan perilaku yang sdah ada tersebut.
• Resiko dan tanda alergi dapat diketahui sejak anak dilahirkan bahkan sejak dalam kandunganpun mungkin sudah dapat terdeteksi. Alergi dapat dicegah sejak dini dan diharapkan dapat mengoptimalkan pertumbuhan dan perkembangan Anak secara menyeluruh. Sehingga “overtreatment” dan “overdiagnosis” yang diberikan terhadap penderita alergi dapat dicegah sedini mungkin. Akhirnya komplikasi yang ditimbulkan khususnya dalam ganguan otak dan gangguan perilaku juga dapat dicegah lebih dini. 

Berbagai pendapat dalam kontroversi itu adalah Kesulitan memastikan penyebab alergi makanan dan hipersensitifitas makanan yang seharusnya berdasarkan klinis ini mengakibatkan melebarnya perbedaan pandangan di bidang lainnya. Kontroversi tersebut adalah :

• Pendapat ekstrim sebagian dokter yang mengatakan bahwa belum di tes dan diperiksa laboratorium tetapi sudah dipastikan alergi
• Beberapa dokter berulang kali mengatakan bahwa penyebab alergi makanan terbesar di Jakarta adalah udang dan ikan laut, karena berdasarkan tes kulit alergi. Padahal tes kulit bukan untuk memastikan penyebab alergi makanan. Seharusnya yang benar adalah “kemungkinan” penyebab alergi adalah udang. Karena, belum tentu berbagai hasil tes kulit yang negatif adalah bukan penderita alergi makanan bahan yang di tes tersebut.
• Setiasp ada tanda dan gejala alergi pada bayi selalu saja anak langsung dianjurkan pemberian susu hipoalergenik parsial, padahal belum tentu anak alergi susu sapi. Hal lain yang tidak berkaitan bahwa pemberian susu hipoalergenik parsial bukan sebagai pemgobatan alergi susu sapi tetapi sebagai pencegahan alergi. Pencegahan adalah bila anak tidak ada gejal;a alergi untuk mencegah alergi harus menggunakan susu hipoalergenik parsial, tetapi kalau ada gejala harus diamati apakah alergi susu sapi atau tidak.
• Setiap ada tanda dan gejala alergi bahkan beberapa dokter langsung memvonis alergi susu sapi dan diadviskan dengan pemberian susu hipoalergeenik ekstensif atau soya, padahal 6 bulan sebelumnya menggunakan susu sapi tidak masalah.
• Pemeriksaan alergi dengan tes alternatif yang tidak diakui oleh berbagai institusi kesehatan internasional dan tidak terbukti secara ilmiah seperti bioresonansi, IgG4 (yang dikirim ke Amerika) dan berbagai tes unproven lainnya
• Penanganan langkah awal penderita alergi adalah mendeteksi penyebab dan menghindarinya. Tetapi karena berbagai kesulitan langkah awal ini diabaikan tetapi langsung masuk ke langkah berikutnya dengan pengobatan dan pencegahan alergi dengan obat-obatan.
• Berbagai hal gejala dan gangguan fungsi tubuh disebabkan alergi dan hipersensitifitas makanan lainnya sering disangkal. Tetapi justru penyangkalan tersebut tanpa data ilmiah untuk membuktikan memang tidak berhubungan. Tetapi justru penelitian awal yang sudah semakin banyak bahkan tetap masih dipandang sebelah mata karena memang didoinasi penelitian klinis.
• Pemakaian obat-obatan untuk profilaksis alergi makanan baik dengan ketotifen (profilas) atau obat alergi lainnya yang tidak terbukti sebagai pencegahan.
• Sebenarnya fakta makanan dapat mengakibatkan berbagai manifestasi penyakit sudah diyakini beberapa praktisi kesehatan sejak lama. Hanya karena keterkaitan masalah tersebut belum dapat dibuktikan secara klinis tentang penyebabnya maka juga timbul berbagai perbedaan pandangan.
• Berbagai pendekatan diet yang dianggap tidak seuai manifestasi imunopatobiologis bidang kedokteran di antaranya adalah :

1. Diet berdasarkan Golongan darah
2. Diet rotasi
3. Diet Asam basa

Angka kejadian alergi dan hipersensitifitas makanan terus meningkat tajam dalam dekade terakhir ini. Terdapat kecenderungan alergi pada anak, merupakan kasus yang mendominasi kunjungan penderita di klinik rawat jalan pelayanan Kesehatan Anak. Perhatian dan penanganan alergi pada anak masih belum optimal, bahkan sering terjadi keterlambatan penanganan. Tampak pada orang tua penderita alergi baru menyadari bahwa anaknya menderita alergi setelah sekian tahun lamanya anaknya menderita sakit yang berulang dan telah berganti-ganti dokter. 

 Cara menyikapinya

• Kontroversi yang sangat tajam tersebut bukan hanya membingungkan para dokter tetapi pastipun akan lebih bingung dalam menerima perbedaan pendapat para dokter tersebut. Untuk menyikapi hal tersebut sebenarnya buklan dengan langsung memvonis dokter satu paling benar atau dokter lain salah. Tetapi dipihak klinisi atau organisasi profesi harus membuat forum disikusi dan kalau perlu membuat workshop atau debat ilmiah untuk menyelesaikan masalah ini. Kala sudah sepakat maka para klinisi tersebut melalui organisasi profesi mengeluarkan rekomendasinya. Kebenaran ilmiah adalah kebenaran fakta ilmiah sesuai Evidance Base Medicine. Bukan berdasarkan opini pakar atau profesor tanpa mempertimbagkan fakta klinis yang ada.
• Bagi klinisi yang berseberang pendapat memang wajarerjadi tetapi harus berdasarkan fakta ilmiah dari pengalaman klinis berbasis bukti dengan didasari oleh berbagai penelitian. Tetapi sebaiknya bila klinisi tersebut tidak berbekal data ilmiah tetapi langsung membuat kontroversi semakin panas sangat disayangkan karena penyelesaian perbedaan pendapat tersebut harus diselesaikan dengan cara ilmiah bukan dengan debat tidak ilmiah.
• Sedangkan di pihak pasien atau orangtu pasien dalam menyikapi hal ini harus secara obyektif. Bila orangtua atau pasien ragu dengan berbagai kontroversi tersebut maka sebaiknya ikuti langkah eliminasi provokasi atau chalenge test di bawah pengawasan dokter ahli. Bila berbagai gangguan yang ada membaik maka sebaiknya penderita harus percaya dengan fakta yang ada, bahwa alergi dapat mengganggu berbagai organ tubuh yang ada. Bila fakta tersebut ada, bukan berarti harus menyalahkan pendapat dokter lainnya bahwa dokter yang lain salah. Bahwa memang kebenaran ilmiah tersebut akan terjadi seiring dengan berjalannya waktu yang membutuhkan proses ilmiah alamiah yang panjang.

Provided by
children’s ALLERGY CLINIC , Yudhasmara Foundation  htpp://www.childrenallergyclinic.wordpress.com/ 

JL Taman Bendungan Asahan 5 Bendungan Hilir jakarta Pusat Jakarta Indonesia 10210, phone : (021) 70081995 – 5703646   

Clinical and Editor in Chief :   

Widodo Judarwanto   

email : judarwanto@gmail.com,   

Information on this web site is provided for informational purposes only and is not a substitute for professional medical advice. You should not use the information on this web site for diagnosing or treating a medical or health condition. You should carefully read all product packaging. If you have or suspect you have a medical problem, promptly contact your professional healthcare provider.   

Copyright © 2010, Children Allergy Clinic Information Education Network. All rights reserved.

Alergi adalah penyakit kronis yang sangat mengganggu hilang dan timbul tidak menentu, sulit dideteksi penyebabnya. Berbagai pendekatan terapi pada alergi telah dilakukan salah satu diantaranya adalah imunoterapi. Imunoterapi atau  desensitisasi atau allergy injection therapy  adalah suatu terapi yang memerlukan proses panjang dari suatu suntikan yang berulang dari ekstrak alergen yang disuntikkan pada pasien dengan penyakit alergi, yang jelas faktor alergen pencetusnya, dengan tujuan untuk mengurangi gejala penyakitnya. Pengobatan ini efektif pada penyakit alergi derajat ringan dan yang tidak responsif terhadap terapi standar. Imunoterapi merubah pejalanan penyakit, dan menghambat terjadinya asma pada anak dengan rinitis alergika. Imunoterapi spesifik masih merupakan pengobatan pilihan untuk reaksi sistemik pada sengatan tawon dan lebah. Mekanisme yang jelas pada kegunaan imunoterapi masih belum jelas. Diduga efek pada Sel T regulator, berkaitan dengan  pergeseran sel B dalam produksi IgG4. Efek imunoterapi memerlukan waktu lama, tetapi begitu tercapai, memberikan perbaikan klinis yang berlangsung lama, sedangkan farmakoterapi, bermanfaat selagi pemberian berlangsung. Tehnik baru imunoterapi saat ini sedang dikembangkan meliputi alergen rekombinan, alergen hipoalergenik, vaksin peptida Sel T, stimulan Th1, dan anti-IgE, yang hasilnya cukup menjanjikan untuk digunakan pada penyakit alergi. Terapi ini direkomendasikan pada penyakit alergi saluran pernafasan, terutama asma dan rinitis bersama dengan penghindaran alergen dan penggunaan obat-obatan.

• Imunoterapi sebagai terapi tambahan selain menghindari pajanan alergen dan sebagai pengobatan pasien rhinitis yang diinduksi alergen
• Imunoterapi harus dimulai sejak dini untuk mengurangi risiko efek samping dan untuk mencegah perkembangan penyakit menjadi lebih berat. Argumen untuk melakukan imunoterapi adalah sebagai berikut :

1. respons terhadap farmakoterapi tidak maksimal
2. terjadi efek samping obat
3. penolakan tatalaksana dengan menggunakan farmakoterapi
4. imunoterapi spesifik secara injeksi (subkutan) dapat digunakan pada rhinitis berat dan berkepanjangan (biasanya berhubungan dengan asma)

• imunoterapi spesifik secara lokal (intranasal dan sublingual-oral) dapat digunakan pada pasien tertentu dengan riwayat terjadi efek samping dan menolak suntikan.

Prinsip Klinis Imunoterapi

Prinsip pertama dari imunoterapi adalah bahwa efektifitas klinis tergantung dosis, dosis minimal tertentu dari ekstrak alergen harus diberikan untuk mendapatkan suatu kontrol gejala yang efektif. Ekstrak alegen ini dibuat dengan proses yang khusus dengan mencampurkan sumber material alergen (pollen, mold spores, dust mites, or animal pelts)  pada cairan buffer untuk mengekstraksi komponen yang larut dalam air. Pada saat ini banyak ekstrak alergen komersial dibawah lisensi FDA yang dijual di pasaran. Penggunaan alergen yang dimurnikan, sebagian dimurnikan atau yang tidak dimurnikan, ternyata memberi hasil yang sama.

Efek terapi meningkat bersamaan dengan lamanya pengobatan. Perbaikan yang nyata biasanya baru tampak setelah terapi diberikan 6 bulan atau lebih. Belum jelas kenapa diperlukan waktu yang sedemikian lama, baru kelihatan efeknya. Mungkin oleh karena diperlukan waktu yang cukup panjang untuk menaikkan dosis alergen yang terkecil yang di toleransi sampai konsentrasi 10.000 kali untuk mencapai kadar yang memberi efek klinis dan imunologis. Efek klinis terus meningkat sampai beberapa tahun setelah suntikan dihentikan. Lamanya penyuntikan ini perlu dibicarakan dengan pasien atau keluarganya sebelum memulai terapi.

Sebagian besar gejala pasien berkurang, dan imunoterapi hanya mengurangi beratnya gejala tetapi tidak menghilangkannya. Sejumlah 25% pasien tidak menunjukkann perbaikan yang berarti, hal ini perlu dibicarakan terlebih dahulu sebelum memulai terapi.

Reaksi anafilaksis yang bersifat sistemik sering dilaporkan. Reaksi ini biasanya ringan dan tidak mengancam kehidupan, tetapi mungkin membutuhkan epinefrin untuk mengatasinya, biasanya cukup dengan satu dosis epinefrin. Reaksi ini sangat mungkin terjadi oleh karena pasien diberikan alergen yang berdasarkan pemeriksaan RAST dan tes kulit memang sensitif, serta diberikan penyuntikan secara berulang. Jadi untuk mengantisipasi terjadinya reaksi anafilaksis pasien harus menunggu 20-30 menit, baru boleh pulang. Dokter harus mempunyai kemampuan untuk mengatasi reaksi anafilaksis dan mempunyai obat-obatan dan peralatan yang memadai.       

Penelitian sedang dilakukan dengan penambahan ajuvan untuk meningkatkan efektivitas dari imunoterapi, dan memodifikasi alergen untuk mengurangi risiko reaksi anafilaksis yang berat. Rute lain untuk memberikan ekstrak alergen tanpa suntikan juga sedang dikembangkan, yang mulai dilakukan sekarang adalah rute secara sublingual.

Mekanisme Kerja

Mekanisme dan cara kerja yang pasti dari imunoterapi belum diketahui.  Beberapa mekanisme imunoterapi telah dikemukakan untuk menerangkan keberhasilan imunoterapi yaitu

• Induksi pembentukan IgG (blocking antibody)
• Penurunan produksi IgE
• Penurunan pengerahan sel efektor
• Perubahan keseimbangan sitokin (pergeseran dari Th2 ke Th1)
• Anergi sel T
• Induksi terjadinya Sel T regulator

Imunoterapi untuk hioersensitifitas terhadap sengat

Sengatan lebah dapat menyebabkan anafilaksis yang dapat menyebabkan kematian. IgE spesifik terhadap sengat dapat ditemukan pada 30-40% individu yang tersengat dan menghilang setelah beberapa bulan. Pada beberapa penderita, IgE ini bertahan beberapa tahun, pada golongan ini sengatan berikutnya akan menyebabkan anafilaksis dan beberapa akan menyebabkan kematian.

Keputusan untuk memberikan imunoterapi pada penderita semacam ini harus berdasarkan pemeriksaan yang akurat dan pendalaman yang baik mengenai perjalanan penyakit. Penggunaan sengat murni dalam imunoterapi sengat menunjukkan perbaikan efektifitas imunoterapi untuk hipersensitifitas terhadap sengat. Preparat yang lama menggunakan ekstrak seluruh badan lebah menunjukkan hasil yang sama dengan plasebo. Setelah menggunakan ekstrak sengat murni, terdapat 10% reaksi sistemik ringan terhadap sengatan lebah.

Imunoterapi untuk rinitis alergika

Imunoterapi spesifik sangat efektif untuk Rinitis Alergika terutama jika penyebabnya terbatas. Seperti penggunaan untuk penyakit lain, sangat penting dilakukan pemilihan pasien yang tepat. Efektifitas imunoterapi terhadap Rinitis Alergika musiman (Seasonal Allergic Rhinitis) terutama yang gagal dengan pengobatan konvensional, telah banyak dibuktikan pada beberapa penelitian. Data yang telah ada menunjukkan bahwa pemberian imunoterapi selama 3 tahun pada Rinitis Alergika cukup efektif memberi penyembuhan, dan kasiatnya masih bertahan sampai 6 tahun setelah imunoterapi dihentikan. Hal ini sangat kontras dengan pengobatan konvensional yang biasanya berhenti kasiatnya begitu pengobatan dihentikan.

Kegunaan imunoterapi untuk rinitis alergi perrenial kurang memuaskan dibanding rinitis alergika musiman. Hal ini mencerminkan lebih kompleksnya faktor penyebab rinitis alergi perrenial. Selain alergi, ada penyebab lain yaitu instabilitas vasomotor, infeksi, dan sensitifitas terhadap aspirin. Beberapa penelitian membuktikan adanya perbaikan toleransi terhadap paparan dengan bulu kucing, baik melalui uji provokasi maupun klinis.

Respons antibodi dan imunoterapi

Terdapat peningkatan kadar IgG spesifik terhadap alergen dalam bulan-bulan pertama imunoterapi. Diperkirakan alergen-spesifik IgG ini berfungsi sebagai blocking antibody dengan menghalangi antigen berikatan dengan IgE, atau menghalang IgE berikatan dengan reseptor FcERI  pada permukaan sel mast atau basofil.

Efek pada sel T

Imunoterapi berperan pada keseimbangan aksis Th1/Th2, dengan bergeser ke arah Th1. Seperti diketahui fenotipe interleukin Th2 dihubungkan dengan peningkatan penyakit alergi, dan produksi interleukin Th1 berpengaruh pada proteksi.

Efek pada sel inflamasi

Dapat dibuktikan bahwa imunoterapi mempunyai pengaruh pada sel mast, basofil dan eosinofil. Terdapat penurunan yang sangat menyolok dari sel mast dan basofil. Juga terjadi penurunan eosinofil dari sekresi nasal dan spesimen bronkial.

PENYAKIT ALERGI YANG DIINDIKASIKAN UNTUK IMUNOTERAPI

Walaupun telah dibuktikan imunoterapi efektif untuk pasien dengan gigitan serangga, rinitis alergi dan asma, tetapi pemilihan pasien dengan hati-hati untuk memulai imunoterapi sangat penting.

Imunoterapi untuk bisa ular dan serangga memberikan efektivitas lebih dari 95%. Tetapi pada anak, imunoterapi terhadap gigitan serangga tidak begitu penting, karena reaksi sistemik yang terjadi biasanya tidak begitu berat. Oleh karena itu untuk anak dengan alergi gigitan serangga, imunoterapi hanya diberikan pada anak dengan riwayat terjadi reaksi yang mengancam kehidupan bila digigit serangga.        

Pada rinitis alergi, imunoterapi hanya diberikan bilamana telah dilakukan penghindaran alergen dan iritan secara maksimal, dan pemberian medikamentosa secara benar dan optimal, terutama oleh karena lamanya terapi. Imunoterapi pada rinitis alergi telah terbukti sangat efektif baik untuk rinitis yang intermiten maupun yang persisten. Lamanya terapi biasanya antara 3-5 tahun, dan  biasanya gejala tetap membaik walaupun pengobatan telah dihentikan.

Pada asma alergi banyak penelitian yang telah membuktikan manfaatnya. Tetapi karena pada asma anak reaksi alergi tipe I hanya merupakan sebagian dari patofisiologinya, imunoterapi harus dipertimbangkan dengan hati-hati, terutama setelah dilakukan penghindaran alergen dan terapi medikamentosa secara maksimal. Kunci dari suksesnya imunoterapi pada pasien asma anak adalah kehati-hatian memilih pasien. Imunotarapi hanya dilakukan terhadap alergen yang bila terpapar jelas menimbulkan serangan, dan juga diperkuat dengan hasil pemeriksaan IgE spesifik. Walaupun imunoterapi tidak di rekomendasikan pada alergi makanan, pilihan imunoterapi terhadap alergi makanan sedang banyak diteliti.

• Anak dibawah usia 5 tahun, untuk menghindari kesulitanpenatalaksanaan pasien pada saat terjadi reaksi anafilaksis usia tua, karena efek samping imunoterapi terhadap sistem kardiovaskular dapat ireversibel
• Keadaan hamil sebaiknya tidak dimulai imunoterapi, akan tetapi bila imunoterapi telah dilakukan sebelum kehamilan, maka dapat diteruskan
• Penyakit imunopatologik seperti pneumonitis hipersensitif termasuk aspergilosis bronkopulmoner alergi
• Keadaan imunodefisiensi yang berat
• Keganasan
• Kelainan psikiatri yang berat
• Pengobatan dengan penyekat beta, karena reaksi anafilaksis keadaan akan memberat dan sulit diatasi dengan cara konvensional
• Pasien tidak patuh
• Pasien mengalami efek samping yang berat yang berulang selama terapi
• Asma berat yang tidak terkontrol dengan farmakoterapi
• Penyakit kronik saluran pernapasan dengan volume eks- pirasi paksa detik 1 (VEP1) < 70% prediksi walaupun telah mendapatkan farmakoterapi yang optimal
• pasien dengan penyakit kardiovaskular berat yang disebabkan oleh efek anafilaksis terhadap miokardium. Hipotensi dan vasokontriksi pulmoner akan menambah beban jantung juga perfusi miokardium sendiri akan berkurang

Prosedur Pemberian

• identifikasi pasien, kehadiran, memanggil nama lengkap dan mencocokkan tanggal lahir atau nomor pasien
• Riwayat  pasien apakah gejala asma telah terkontrol
•  Apakah ada riwayat terjadi reaksi pada pemberian terakhir
• terapkan aturan “3 benar”, yaitu : kartu (chart) yang benar, antigen benar, pasien benar
• triple check antigen, yakni : label, nama pasien, isi pengenceran, tanggal kadaluarsa, tanggal penyuntikan terakhir

Sebelum melakukan imunoterapi, harus memenuhi syarat sebagai berikut:

• Observasi pasien dalam 15 menit dan lakukan spirometri atau pengukuran arus puncak ekspirasi (APE). Bila hasil peng- ukuran 20% di bawah nilai tertinggi yang pernah dicapai maka penyuntikan imunoterapi tidak dilakukan.
• Ekstrak alergen inhalasi
• Diberikan dengan cara suntikan subkutan pada regio deltoid secara bergantian pada periode imunoterapi. Dengan menggunakan semprit 0,5-1,0 ml untuk pengukuran yang akurat jumlah antigen yang masuk dan jarum 27G untuk kenyamanan pasien. Jarum disuntikkan dan setelah masuk pada posisi subkutan jarum diaspirasi. Apabila darah teraspirasi maka semprit tersebut harus dibuang dan prosedur dimulai lagi dari awal. Semprit yang digunakan harus berbeda untuk setiap pasien untuk mencegah penularan penyakit infeksi. Setelah penyuntikan pasien diminta menunggu selama 20-30 menit untuk mengantisipasi reaksi sistemik yang mungkin muncul dalam periode tersebut. Pasien dengan derajat hipersensitivitas tinggi harus diobservasi selama 30 menit atau lebih.
• Lakukan penilaian ulang spirometri atau APE 30 menit setelah suntikan dan bila terjadi penurunan 10% akan menjadi dasar untuk mengurangi dosis pada suntikan berikutnya.
• Ekstrak alergen dapat diberikan secara tunggal atau dicampur (idealnya kurang dari 10 jenis alergen), akan tetapi campuran ini akan mengencerkan kadar setiap alergen dan dapat mengurangi respons terhadap imunoterapi.
• Jenis alergen yang diberikan tergantung penilaian klinisi didasarkan pada jenis alergen yang memberi hasil positif pada uji kulit dan yang menimbulkan gejala klinis bila terpajan. Jenis alergen yang dapat diberikan secara injeksi subkutan adalah bermacam jenis serbuk sari (pollen), tungau debu rumah dan bulu kucing.
• Imunoterapi dapat diberikan satu sampai dua kali seminggu dengan dosis awal dimulai dengan 0,05 ml alergen konsentrasi 1:10.000 sampai 1:1.000.000 berat/volume (wt/vol) ditingkatkan sampai tercapai dosis pemeliharaan yaitu 0,05 ml alergen konsentrasi 1:100. Lama penyuntikan 6-10 bulan untuk
  mencapai dosis pemeliharaan.
• Dosis pemeliharaan diberikan dalam interval 2-4 minggu selama 3-5 tahun dan berdasarkan penelitian, cukup untuk memberikan perlindungan jangka pan-
  jang pada hampir semua pasien (cara lambat).
• Imunoterapi dengan durasi yang lebih panjang ternyata tidak berguna.
• Pemberian imunoterapi dengan cara cepat, dilakukan dengan menyuntikkan alergen 4 kali sehari dengan interval 1/2 jam dan diulang setelah 2 minggu. Respons antibodi yang diinginkan terjadi setelah 5 kali kunjungan.
• Cara Cluster merupakan modifikasi cara lambat dan cepat dengan memberikan 2-4 kali suntikan dalam sehari, diulang setelah 1-2 minggu sampai dosis maksimal dan dipertahankan dengan dosis pemeliharaan.
• Secara umum dalam pemberian imunoterapi harus memahami :

1. cara penyesuaian dosis untuk meminimalkan reaksi
2. cara penatalaksanaan reaksi lokal dan sistemik
3. telah mendapat pelatihan resusitasi jantung paru
4. memiliki alat resusitasi termasuk stetoskop, sfigmomano-meter, turniket, jarum suntik, epinefrin, antihistamin, steroid, oksigen, oral airway, cairan intravena, set infus, set trakeos-tomi, nebulizer dan obat bronkodilator inhalasi.

Ekstrak alergen untuk imunoterapi  

Ekstrak alergen didapatkan dengan mengekstraksi material alergen dalam bentuk yang besar dalam cairan buffer. Beberapa produk menggunakan standar alergen dalam mikrogram per milliliter, hal ini sangat penting sebagai pegangan untuk menentukan dosis minimal dan maksimal yang dapat diberikan.

Penyimpanan

Kekuatan alergen berkurang dengan waktu, oleh karena itu harus diperhatikan tanggal kadaluwarsanya, terutama setelah dilarutkan. Tanggal kadaluwarsa ini berdasarkan asumsi bahwa ekstrak alergen disimpan dalam refrigerator dengan suhu dibawah 5° C, karena kekuatan alergenisitas akan lebih cepat berkurang pada suhu > 5° C.

Peraturan penyuntikan dan regimen yang tersedia     

Keputusan untuk memulai imunoterapi harus berdasarkan hasil pemeriksaan IgE spesifik, yang diperkuat dengan anamnesis. Penentuan ini sangat penting dan kompleks, dan sebaiknya dilakukan oleh seorang dokter ahli alergi, dan tidak hanya berdasarkan pada tes kulit. Biasanya satu set regimen terdiri dari satu vial dengan konsentrasi 1:10, dan 3 atau 4 vial lainnya dengan konsentrasi kelipatan 10 (misal 1:100, 1:1000 dan seterusnya). Setiap vial harus dilabel dengan nama pasien, nama ekstrak alergen dan tanggal kadaluwarsa.

Dosis dan cara pemberian

Prinsip dasarnya adalah dosis permulaan yang diberikan adalah 1/10 dari dosis yang menimbulkan reaksi tes kulit positif, dan dosis dinaikkan sedikit demi sedikit setiap minggunya sampai mencapai 1000-10.000 kali dosis awal yang masih ditoleransi. Biasanya memerlukan waktu sedikitnya 6 bulan deangan penyuntikkan 1 minggu sekali untuk mencapai dosis pemeliharaan. Kalau terjadi reaksi sistemik, maka dosis yang lebih rendah menjadi dosis maksimum yang dapat di toleransi .      

Prosedur aturan  ekstrak alergen

(Nelson HS, 1998)

Lamanya imunoterapi   

Sekali dosis pemeliharaan tercapai, biasanya terapi akan dilanjutkan dalam waktu 3 tahun atau lebih. Kalau seorang anak sudah dapat mentoleransi paparan alergen tanpa menimbulkan serangan, maka imunoterapi dapat dihentikan.

Reaksi samping yang dapat terjadi

Reaksi samping terhadap imunoterapi biasanya ringan dan tidak membahayakan. Suatu penelitian melaporkan bahwa 3 sampai 7% pasien dapat mengalami reaksi sistemik, dan dapat terjadi pada setiap 250 sampai 1600 penyuntikan. Reaksi dapat terbatas pada urtikaria, tetapi 40-70% dapat mengenai saluran pernafasan (stridor, rinitis, mengi) dan hampir 10% disertai hipotensi. Reaksi yang fatal dapat terjadi pada 1:2 juta atau 1:3 juta suntikan. Reaksi yang tersering terjadi pada waktu pemberian dosis pemeliharaan. Reaksi lebih sering terjadi pada anak remaja dan pada waktu pajanan terhadap alergen tinggi. Faktor risiko untuk terjadinya reaksi berat antara lain asma berat, usia kurang dari 5 tahun dan penggunaan β bloker. Untuk alasan ini, penyuntikan harus dilakukan di fasilitas kesehatan dan oleh orang yang mengetahui dan dapat mengenali dan mengatasi reaksi sistemik anafilaksis. Harus tersedia fasilitas minimal untuk resusitasi. Setelah penyuntikan, pasien harus menunggu selama 30 menit, dan diawasi bila tampak tanda reaksi alergi. Penyuntikan sebaiknya tidak dilakukan dirumah.

Standard peralatan dan obat  resusitasi yang harus tersedia saat  pemberian imunoterapi

MASA DEPAN DARI IMUNOTERAPI

Alergoid dan ajuvan 

Alergoid diproduksi dengan modifikasi secara kimia atau denaturasi alergen asli, dengan tujuan tetap mempertahankan alergenisitasnya, tetapi mengurangi risiko reaksi anafilaksisnya. Ajuvan digunakan bersama dengan ekstrak alergen untuk meningkatkan respon imunologik dari alergen dan efektivitas dari imunoterapinya.

Peptida dan rekombinan alergen   

Pada era modern dari cloning dan sequenzing, banyak alergen dapat dikarakterisasi pada tingkat molekular. Dengan demikian rekombinan alergen dan peptida alergen dapat diproduksi dan mungkin nanti akan memegang peran penting dalam imunoterapi.

Imunomodulator

Beberapa jenis imunomodulator banyak diteliti dalam strategi terapi penyakit alergi, termasuk imunomodulator terhadap IgE maupun yang berperan terhadap sitokin. Anti IgE telah dievaluasi sebagai pengobatan pada asma dan rinitis alergi. Terapi anti sitokin layak dan mungkin untuk masa depan dapat merupakan terapi yang efektif untuk asma dan rinitis alergi.

Alternatif rute pemberian

Alternatif rute pemberian imunoterapi juga sedang banyak diteliti. Beberapa penelitian klinis membuktikan efektivitas dari imunoterapi secara sublingual. Mekanisme dari imunoterapi dengan rute yang berbeda ini belum diketahui, dan mungkin berbeda dengan rute yang konvensional.

Imunoterapi sebagai preventif

Imunoterapi biasanya ditujukan untuk terapi tidak untuk pencegahan. Tetapi banyak hal membuktikan bahwa spesifik imunoterapi dimasa depan mungkin memegang peran sebagai pencegahan sekunder pada penyakit alergi. Anak yang mendapat imunoterapi untuk rinitis alergi, dapat tercegah dari serangan asma. Walaupun masih banyak memerlukan penelitan, tetapi tampaknya intervensi imunologik dini pada stadium permulaan perkembangan sistem imun, mungkin dapat mengubah fenotipe alergi pada seseorang.

Sebagai terapi Kanker

Imunoterapi digunakan untuk merangsang sistem kekebalan tubuh melawan kanker. Misal, vaksin yang terdiri dari antigen diperoleh dari sel tumor bisa menaikkan fungsi tubuh pada antibodi atau sel kekebalan (t limpiosit). Ekstrak bakteri tuberkolosis yang dilemahkan, yang diketahui untuk menaikkan reaksi kekebalan, telah berhasil ketika ditanamkan ke dalam kandung kemih untuk mencegah kambuhnya tumor kandung kemih.

Terapi antibodi Monoclonal memerlukan penggunaan antibodi yang dihasilkan secara eksperimental untuk menjadikan protein khusus di atas permukaan sel kanker sebagai sasaran. Trastuzumab adalah salah satu antibodi, yang menyerang HER-2/neu receptor yang hadir di atas permukaan sel kanker pada 25% wanita dengan kanker payudara. Trastuzumab meningkatkan efek obat kemoterapi. Rituximab sangat efektif mengobati lymphoma dan leukemia limfositik kronis. Rituximab yang dihubungkan dengan isotop radioaktif bisa digunakan untuk mengantarkan radiasi secara langsung ke sel lymphoma. Gemtuzumab ozogamicin, antibodi dan obat gabungan, efektif pada beberapa orang dengan leukemia myelocytic kronis.

Pemodifikasi reaksi biologis memperbaiki kemampuan sistem kekebalan tubuh untuk menemukan dan menghancurkan sel kanker, seperti dengan merangsang sel normal untuk menghasilkan utusan kimia (penengah). Interferon (diantaranya ada beberapa macam) adalah yang diketahui terbaik dan sangat luas pemodifikasi reaksi biologis yang digunakan. Hampir semua sel manusia menghasilkan interferon secara alami, tetapi juga bisa dibuat lewat bioteknologi. Walaupun mekanisme tepat pada tindakan tidak benar-benar jelas, interferon mempunyai tugas di dalam pengobatan beberapa kanker, seperti Kaposi’s sarcoma dan melanoma ganas. Interleukin 2, yang dihasilkan pada sel darah putih tertentu, juga bisa membantu sel karsinoma dan metastatic melanoma di ginjal.

Imunoterapi mungkin berpengaruh menekan gejala alergi melalui modifikasi dari respons antibodi, respons limfosit atau respons target sel terhadap alergen. Sedang diteliti untuk mengetahui apakah modifikasi dari reagen imunoterapi atau perubahan rute pemberian akan meningkatkan efektifitas dan dapat mengurangi risiko reaksi anafilaksis. Banyak bukti yang menunjukkan bahwa imunoterapi dapat mengubah perjalanan alamiah dari penyakit alergi, disamping untuk pengobatan mungkin dimasa depan dapat digunakan untuk pencegahan.

Point of Interest :

• Efektivitas klinis terjadi setelah dosis pemeliharaan tercapai
• Terdapat efek plasebo yang bermakna
• Sekitar 75% pasien mempunyai respons dengan imunoterapi
• Risiko utama adalah reaksi sistemik
• Efikasi merupakan dose dependent
• Imunoterapi hanya efektif pada penyakit yang diperantarai IgE, seperti anafilaksis akibat gigitan serangga, rinitis alergi dan asma
• Pasien harus dipilih, pasien yang menunjukkan IgE spesifik dan pasien yang tatalaksana medisnya tidak cukup dalam mengontrol penyakit
• Terapi yang sukses membutuhkan pemberian dosis toleransi maksimal ekstrak alergen dan membutuhkan waktu berbulan-bulan sampai bertahun-tahun untuk mencapai keuntungan maksimal
• Dengan adanya risiko anafilaksis selama terapi, injeksi harus dilakukan di tempat dokter atau fasilitas kesehatan yang dapat menunjang resusitasi kardiorespiratorius. Pasien ajrus dipantau selama 30 menit setelah injeksi

End Point :

• Imunoterapi merupakan pengobatan yang sangat efektif pada pasien dengan alergi gigitan serangga, asma dan rinitis alergi .
• Imunoterapi juga sebagai imunomodulator, hal ini cukup penting berperanan dalam mengurangi resiko infeksi berulang pada penderita alergi yang masih merupakan masalah utama.
• Bila prosedur pemberian baik dan digunakan pada pasien yang tepat, imunoterapi sangat efektif dan aman, tetapi harus tetap memperhatikan adanya efek samping. Perlu seorang yang ahli dalam memberikan imunoterapi dan siap dalam penanggulangan efek samping.
•  Pengembangan masa depan seperti pengembangan ekstrak yang terstandardisasi lebih baik, dan penggunaan ekstrak rekombinan akan memberikan pola keamanan yang sangat baik. Pengembangan ekstrak alergen yang bersifat lebih mengarah modulator imun dengan tujuan pendekatan yang lebih umum untuk penderita yang sensitif terhadap alergen multiple.   

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Alergi Makanan Dapat Berpengaruh Meningkatkan Perilaku kriminal Seseorang

Dr Widodo Judarwanto SpA

Kejadian kriminal di kalangan anak sekolah semakin hari semakin meningkat pesat, baik kualitas dan kuantitasnya. Seiring dengan itu angka kejadian alergi di dunia semakin hari semakin meningkat pesat. Ternyata peningkatan kedua fenomena sosial dan kesehatan tersebut berkaitan. Dalam berbagai penelitian menunjukkan bahwa pengaruh alergi makanan dapat meningkatkan perilaku kriminal seseorang. Bahkan dalam sebuah penelitian telah ditemukan bahwa dengan melakukan intervensi diet alergi maka pelaku kriminal dapat ditekan.

Beberapa penelitian psikososial dan psikobiologis telah mengungkapkan faktor lingkungan sangat berpengaruh  terhadap perilaku kriminal pada seseorang. Lingkungan tersebut bisa berupa fisik, biologis dan sosial. Tetapi kebanyakan orang-orang beresiko biasanya memasuki lingkungan yang sama sehingga berpotensi terjadinya perilaku berbagai kejahatan tersebut.

Faktor lingkungan fisik dan sosial yang beresiko berkembangnya seorang menjadi kriminal adalah tekanan ekonomi yang buruk, perlakuan kasar dan keras sejak usia anak, penelantaran anak, perceraian orang tua, kesibukan orangtua, faktor pemberian nutrisi tertentu, dan kehidupan keluarga yang tidak mematuhi etika hukum, agama dan sosial. Lingkungan yang beresiko lainnya adalah hidup ditengah masyarakat yang dekat dengan perbuatan lriminal seperti pembunuhan, penyiksaan, kekerasan dan lain sebagainya.

Sedangkan lingkungan biologis salah satunya yang saat ini banyak diteliti adalah pola makan apakah berpengaruh terhadap tindak kriminal tersebut. Adanya penelitian yang dilakukan Peter C dkk tahun 1997 cukup mengejutkan. Didapatkan kaitan diet, alergi makanan, intoleransi makanan dan perilaku kriminal di usia muda cukup menjadi informasi dan fakta ilmiah yang menarik dan sangat penting, Meskipun demikian masih belum dapat dijelaskan mengapa beberapa faktor tersebut berkaitan.

Sedangkan Bentin dalam menelitiannya telah mengungkapkan bahwa intervensi dan penghindaran diet tertentu dapat brtprngaruh pada perilaku antisosial, perbuatan bunuh diri dan perbuatan kriminal.

Penelitian lain yang diungkapkan oleh Benneth adalah penanganan penderita alergi makanan dapat mencegah perilaku lriminal dalam kelompok masyatakat tertentu.

Bahkan penulis telah mengadakan penelitian terhadap kelompok anak penderita alergi dengan gangguan saluran cerna setelah dilakukan intervensi diet selama 3 minggu didapatkan beberapa penurunan perilaku emosi, agresif, gangguan tidur dan gangguan konsentrasi seorang anak.

Terdapat beberapa faktor resiko untuk terjadi tindak kekerasan dan kriminal yang dapat diamati sejak usia dini pada seorang anak. Beberapa perilaku tersebut meliputi peningkatan agresifitas, emosi, impulsifitas, hiperaktif, gangguan tidur dan sebagainya. Ternyata banyak faktor resiko tersebut juga terjadi pada penderita alergi dan hipersensitifitas makanan. Belakangan terungkap bahwa alergi atau hipersensitifitas makanan tertentu menimbulkan komplikasi yang cukup berbahaya, karena dapat mengganggu semua organ atau sistem tubuh kita termasuk gangguan fungsi otak. Gangguan fungsi otak itulah maka timbul gangguan perkembangan dan perilaku pada anak seperti gangguan konsentrasi, gangguan emosi, agresifitas, gangguan tidur, gangguan konsentrasi, impulsifitas hingga memperberat gejala penderita Autism dan ADHD.

Bila faktor genetik, gangguan fungsi otak, dan diikuti oleh lingkungan fisik, biologis dan sosial yang negatif maka tindak kriminal pada seorang individu lebih gampang terjadi.

Sehingga sangatlah penting untuk mengetahui faktor resiko dan gangguan perilaku pada usia anak untuk dilakukan pencegahan sejak dini. Bila hal ini dikaitkan dengan berbagai penelitian tersebut tampaknya dengan melakukan deteksi sejak dini gangguan alergi dan hipersensitifitas makanan mungkin saja dapat mencegah perilaku antisosial dan perilaku kriminal pada seseorang di masa depan.

Agresifitas, gangguan tidur, gangguan emosi dan gangguan anti sosial lainnya adalah faktor resiko terjadi prilaku kriminal pada seseorang. Ternyata dalam berbagai penelitian telah terungkap bahwa berbagai faktor resiko terjadinya perilaku kriminal tersebut juga seringkali di sebabkan karena alergi dan hipersensitifitas makanan.

Diperlukan penelitian lebih lanjut secara holistik melalui kajian biomolekular, pola genetik, psikobiologis dan psikososial lainnya untuk menyikapi temuan-temuan penting tersebut. Bila nantinya temuan penting tersebut saling melengkapi maka dengan perbaikan pola diet dan perbaikan gejala alergi pada kelompok masyarakat dapat membuat dunia ini lebih aman di masa depan.

Deteksi Dini Gangguan Perilaku Pada Penderita Alergi dan Hipersensitifitas makanan

• GERAKAN MOTORIK BERLEBIHAN Mata bayi sering melihat ke atas. Tangan dan kaki bergerak terus tidak bisa dibedong/diselimuti. Senang posisi berdiri bila digendong, sering minta turun atau sering menggerakkan kepala ke belakang, membentur benturkan kepala. Sering bergulung-gulung di kasur, menjatuhkan badan di kasur (“smackdown”}. ”Tomboy” pada anak perempuan : main bola, memanjat dll.
• GANGGUAN TIDUR  (biasanya MALAM-PAGI) gelisah/bolak-balik ujung ke ujung, bila tidur posisi “nungging”, berbicara/tertawa/berteriak dalam tidur, sulit tidur, malam sering terbangun/duduk, gelisah saat memulai tidur, gigi gemeretak (beradu gigi), tidur ngorok 
• AGRESIF MENINGKAT sering memukul kepala sendiri, orang lain. Sering menggigit, menjilat, mencubit, menjambak (spt “gemes”)
• GANGGUAN KONSENTRASI: cepat bosan sesuatu aktifitas kecuali menonton televisi,main game, baca komik, belajar. Mengerjakan sesuatu  tidak bisa lama, tidak teliti, sering kehilangan barang, tidak mau antri, pelupa, suka “bengong”, TAPI ANAK TAMPAK CERDAS
• EMOSI TINGGI (mudah marah, sering berteriak /mengamuk/tantrum), keras kepala, negatifisme (sering membantah)
• GANGGUAN KESEIMBANGAN KOORDINASI DAN MOTORIK : Terlambat bolak-balik, duduk, merangkak dan berjalan. Jalan terburu-buru, mudah terjatuh/ menabrak, duduk leter ”W”. 
• GANGGUAN SENSORIS : sensitif terhadap suara (frekuensi tinggi) , cahaya (mudah silau), perabaan telapak kaki dan tangan sensitif  (jalan jinjit, flat foot, mudah geli, mudah jijik, tidak suka memegang bulu, boneka dan bianatang berbulu)
• IMPULSIF : banyak bicara,tertawa berlebihan, sering memotong pembicaraan orang lain

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Abstract

There is evidence from several well documented case reports that occasional patients with rheumatoid arthritis (RA) may develop aggravation of their arthritis as a result of allergy to some ingredient in the diet. A variety of foodstuffs have been implicated including milk and milk products, corn and cereals. Total fasting results in improvement in rheumatoid arthritis, but appears to be mediated by diminution in production of chemical mediators of inflammation, rather than by elimination of a dietary allergen. There is conflicting evidence from studies using various intestinal probes that patients with rheumatoid arthritis may have a ‘leaky’ intestinal mucosa allowing food allergens to be more easily absorbed. Clinical therapeutic trials of exclusion diets have employed the standard strategy of the double-blind randomized method. However, this presupposes that patients entered into such a study are capable of improvement with dietary manipulation

Artritis Reumatoid  merupakan penyakit yang terjadi pada saat tubuh diserang oleh sistem kekebalan tubuhnya sendiri) yang mengakibatkan peradangan dalam waktu lama pada sendi. Penyakit ini menyerang persendian, biasanya mengenai banyak sendi, yang ditandai dengan radang pada membran sinovial dan struktur-struktur sendi serta atrofi otot dan penipisan tulang. Berbagai penelitian menunjukkan bahwa manifestasi klionis atau gangguan rematoid artritis berhubungan dengan alergi makanan dan hipersesitifitas makanan

Artritis reumatoid (Rheumatoid Arthritis, RA) merupakan penyakit autoimun (penyakit yang terjadi pada saat tubuh diserang oleh sistem kekebalan tubuhnya sendiri) yang mengakibatkan peradangan dalam waktu lama pada sendi. Penyakit ini menyerang persendian, biasanya mengenai banyak sendi, yang ditandai dengan radang pada membran sinovial dan struktur-struktur sendi serta atrofi otot dan penipisan tulang. Pada Gambar 1, ditunjukkan bahwa RA dapat mengakibatkan nyeri, kemerahan, bengkok dan panas di sekitar sendi. Berdasarkan studi, RA lebih banyak terjadi pada wanita dibandingkan pria dengan rasio kejadian 3 : 1.

Umumnya penyakit ini menyerang pada sendi-sendi bagian jari, pergelangan tangan, bahu, lutut, dan kaki. Pada penderita stadium lanjut akan membuat si penderita tidak dapat melakukan aktivitas sehari-hari dan kualitas hidupnya menurun. Gejala yang lain yaitu berupa demam, nafsu makan menurun, berat badan menurun, lemah dan kurang darah. Namun kadang kala si penderita tidak merasakan gejalanya. Diperkirakan kasus Rheumatoid Arthritis diderita pada usia di atas 18 tahun dan berkisar 0,1% sampai dengan 0,3% dari jumlah penduduk Indonesia.

Artritis Reumatoid Juvenil (ARJ) adalah salah satu penyakit Reumatoid yang paling sering pada anak, dan merupakan kelainan yang paling sering menyebabkan kecacatan. Ditandai dengan kelainan karakteristik yaitu sinovitis idiopatik dari sendi kecil, disertai dengan pembengkakan dan efusi sendi. Ada 3 tipe ARJ menurut awal penyakitnya yaitu: oligoartritis (pauciarticular disease), poliartritis dan sistemik.

Penyakit reumatik merupakan sekelompok penyakit yang sebelumnya dikenal sebagai penyakit jaringan ikat. Menurut kriteria American Rheumatism Association (ARA) artritis reumatoid juvenil (ARJ) merupakan penyakit reumatik yang termasuk ke dalam kelompok penyakit jaringan ikat yang terdiri lagi dari beberapa penyakit. Penderita RA selalu menunjukkan gejala ritme sirkadia dari sistem kekebalan neuroindokrin.

Tanda dan Gejala Penyakit reumatik Pada dewasa

RA umumnya ditandai dengan adanya beberapa gejala yang berlangsung selama minimal 6 minggu, yaitu :

1. Kekakuan pada dan sekitar sendi yang berlangsung sekitar 30-60 menit di pagi hari
2. Bengkak pada 3 atau lebih sendi pada saat yang bersamaan
3. Bengkak dan nyeri umumnya terjadi pada sendi-sendi tangan
4. Bengkak dan nyeri umumnya terjadi dengan pola yang simetris (nyeri pada sendi yang sama di kedua sisi tubuh) dan umumnya menyerang sendi pergelangan tangan

Pada tahap yang lebih lanjut, RA dapat dikarakterisasi juga dengan adanya nodul-nodul rheumatoid, konsentrasi rheumatoid factor (RF) yang abnormal dan perubahan radiografi yang meliputi erosi tulang.

Manifestasi Klinis Artritis Reumatoid Juvenil (ARJ)

• Artritis  adalah gejala klinis utama yang terlihat secara obyektif. Ditandai dengan salah satu dari gejala pembengkakan  atau efusi sendi, atau paling sedikit 2 dari 3 gejala peradangan yaitu gerakan yang terbatas, nyeri jika digerakkan dan panas. Nyeri atau sakit biasanya tidak begitu menonjol. Pada  anak kecil, yang lebih jelas adalah kekakuan sendi pada pergerakan, terutama pada pagi  (morning stiffness).
• Tipe onset poliartritis   Terdapat pada penderita yang menunjukkan gejala arthritis pada lebih dari 4 sendi, sedangkan tipe onset oligoartritis 4 sendi atau kurang. Pada tipe oligoartritis sendi besar lebih sering terkena dan biasanya pada sendi tungkai. Pada tipe poliartritis lebih sering terdapat pada sendi-sendi jari dan biasanya simetris, bisa juga pada sendi lutut, pergelangan kaki, dan siku.
• Tipe onset sistemik  Ditandai dengan demam intermiten dengan puncak tunggal atau ganda, lebih dari 39^o C selama 2 minggu atau lebih, artritis disertai kelainan sistemik lain berupa ruam rematoid serta kelainan viseral misalnya hepatosplenomegali, serositis atau limfadenopati

Amati Tanda dan gejala gangguan saluran cerna yang lain karena alergi dan hipersensitif makanan (Gastrointestinal Hipersensitivity) (Gejala Gangguan Fungsi saluran cerna yang ada selama ini sering dianggap normal)

Pada anak yang lebih besar :

1. Mudah MUNTAH bila menangis, berlari atau makan banyak. MUAL pagi hari.
2. Sering Buang Air Besar (BAB)  3 kali/hari atau lebih, sulit BAB sering ngeden kesakitan saat BAB (obstipasi). Kotoran bulat kecil hitam seperti kotoran kambing, keras, warna hitam, hijau dan bau tajam. sering buang angin, berak di celana. Sering KEMBUNG, sering buang angin dan bau tajam. Sering NYERI PERUT, tidur malam nungging (biasanya karena perut tidak nyaman)
3. Nyeri gigi, gigi berwarna kuning kecoklatan, gigi rusak, gusi mudah bengkak/berdarah. Bibir kering dan mudah berdarah, sering SARIAWAN, lidah putih & berpulau, mulut berbau, air liur berlebihan.  

• SALURAN NAPAS DAN HIDUNG : Batuk / pilek lama (>2 minggu), ASMA, bersin, hidung buntu, terutama malam dan pagi hari. MIMISAN, suara serak, SINUSITIS, sering menarik napas dalam.
• KULIT : Kulit timbul BISUL, kemerahan, bercak putih dan bekas hitam seperti tergigit nyamuk. Warna putih pada kulit seperti ”panu”. Sering menggosok mata, hidung, telinga, sering menarik atau memegang alat kelamin karena gatal. Kotoran telinga berlebihan, sedikit berbau, sakit telinga bila ditekan (otitis eksterna).
• SALURAN CERNA : Mudah MUNTAH bila menangis, berlari atau makan banyak. MUAL pagi hari. Sering Buang Air Besar (BAB)  3 kali/hari atau lebih, sulit BAB (obstipasi), kotoran bulat kecil hitam seperti kotoran kambing, keras, sering buang angin, berak di celana. Sering KEMBUNG, sering buang angin dan bau tajam. Sering NYERI PERUT.
• GIGI DAN MULUT : Nyeri gigi, gigi berwarna kuning kecoklatan, gigi rusak, gusi mudah bengkak/berdarah. Bibir kering dan mudah berdarah, sering SARIAWAN, lidah putih & berpulau, mulut berbau, air liur berlebihan.
• PEMBULUH DARAH Vaskulitis (pembuluh darah kecil pecah) : sering LEBAM KEBIRUAN pada tulang kering kaki atau pipi atas seperti bekas terbentur. Berdebar-debar, mudah pingsan, tekanan darah rendah.
• OTOT DAN TULANG : nyeri kaki atau kadang  tangan, sering minta dipijat terutama saat malam hari. Kadang nyeri dada
• SALURAN KENCING : Sering minta kencing, BED WETTING (semalam  ngompol 2-3 kali)
• MATA : Mata gatal, timbul bintil di kelopak mata (hordeolum). Kulit hitam di area bawah kelopak mata. memakai kaca mata (silindris) sejak usia 6-12 tahun.
• HORMONAL : rambut berlebihan di kaki atau tangan, keputihan, gangguan pertumbuhan tinggi badan.
• Kepala,telapak kaki/tangan sering teraba hangat. Berkeringat berlebihan meski dingin (malam/ac). Keringat  berbau.
• FATIQUE :  mudah lelah, sering minta gendong

• SUSUNAN SARAF PUSAT : sakit kepala, MIGRAIN, TICS (gerakan mata sering berkedip), , KEJANG NONSPESIFIK (kejang tanpa demam & EEG normal).
• GERAKAN MOTORIK BERLEBIHAN Mata bayi sering melihat ke atas. Tangan dan kaki bergerak terus tidak bisa dibedong/diselimuti. Senang posisi berdiri bila digendong, sering minta turun atau sering menggerakkan kepala ke belakang, membentur benturkan kepala. Sering bergulung-gulung di kasur, menjatuhkan badan di kasur (“smackdown”}. ”Tomboy” pada anak perempuan : main bola, memanjat dll.
• AGRESIF MENINGKAT sering memukul kepala sendiri, orang lain. Sering menggigit, menjilat, mencubit, menjambak (spt “gemes”)
• GANGGUAN KONSENTRASI: cepat bosan sesuatu aktifitas kecuali menonton televisi,main game, baca komik, belajar. Mengerjakan sesuatu  tidak bisa lama, tidak teliti, sering kehilangan barang, tidak mau antri, pelupa, suka “bengong”, TAPI ANAK TAMPAK CERDAS
• EMOSI TINGGI (mudah marah, sering berteriak /mengamuk/tantrum), keras kepala, negatifisme
• GANGGUAN KESEIMBANGAN KOORDINASI DAN MOTORIK : Terlambat bolak-balik, duduk, merangkak dan berjalan. Jalan terburu-buru, mudah terjatuh/ menabrak, duduk leter ”W”. 
• GANGGUAN SENSORIS : sensitif terhadap suara (frekuensi tinggi) , cahaya (mudah silau), perabaan telapak kaki dan tangan sensitif  (jalan jinjit, flat foot, mudah geli, mudah jijik, tidak suka memegang bulu, boneka dan bianatang berbulu)
• GANGGUAN ORAL MOTOR : TERLAMBAT BICARA, bicara terburu-buru, cadel, gagap. GANGGUAN MENELAN DAN MENGUNYAH, tidak bisa  makan makanan berserat (daging sapi, sayur, nasi) Disertai keterlambatan pertumbuhan gigi.
• IMPULSIF : banyak bicara,tertawa berlebihan, sering memotong pembicaraan orang lain
• AUTIS dan ADHD (Alergi dan hipersensititas makanan bukan penyebab Autis atau ADHD tetapi hanya memperberat gejalanya)

• Daya tahan menurun sering sakit demam, batuk, pilek setiap bulan bahkan sebulan 2 kali. (normal sakit seharusnya 2-3 bulan sekali)
• Karena sering sakit berakibat Tonsilitis kronis (AMANDEL MEMBESAR) hindari operasi amandel yang tidak perlu  atau mengalami Infeksi Telinga
• Waspadai dan hindari efek samping PEMAKAIAN OBAT TERLALU SERING. 
• Mudah mengalami INFEKSI SALURAN KENCING.  Kulit di sekitar kelamin sering kemerahan 
• SERING TERJADI OVERDIAGNOSIS TBC  (MINUM OBAT JANGKA PANJANG PADAHAL BELUM TENTU MENDERITA TBC / ”FLEK ”)  KARENA GEJALA ALERGI MIRIP PENYAKIT TBC. BATUK LAMA BUKAN GEJALA TBC PADA ANAK BILA DIAGNOSIS TBC MERAGUKAN SEBAIKNYA ”SECOND OPINION” DENGAN DOKTER LAINNYA  
• MAKAN BERLEBIHAN KEGEMUKAN atau OBESITAS
• INFEKSI JAMUR (HIPERSENSITIF CANDIDIASIS) di lidah, selangkangan, di leher, perut atau dada, KEPUTIHAN

• Diagnosis Gangguan gejala  Artritis Reumatoid yang  dipengaruhi alergi atau hipersensitif makanan dibuat bukan dengan tes alergi tetapi berdasarkan diagnosis klinis, yaitu anamnesa (mengetahui riwayat penyakit penderita) dan pemeriksaan yang cermat tentang riwayat keluarga, riwayat pemberian makanan, tanda dan gejala alergi makanan sejak bayi dan dengan eliminasi dan provokasi.
• Untuk memastikan makanan penyebab alergi dan hipersensitifitas makanan harus menggunakan Provokasi makanan secara buta (Double Blind Placebo Control Food Chalenge = DBPCFC). DBPCFC adalah gold standard atau baku emas untuk mencari penyebab secara pasti alergi makanan. Cara DBPCFC tersebut sangat rumit dan membutuhkan waktu, tidak praktis dan biaya yang tidak sedikit.
• Beberapa pusat layanan alergi anak melakukan modifikasi terhadap cara itu. Children Allergy clinic Jakarta melakukan modifikasi dengan cara yang lebih sederhana, murah dan cukup efektif. Modifikasi DBPCFC tersebut dengan melakukan “Eliminasi Provokasi Makanan Terbuka Sederhana”. Bila setelah dilakukan eliminasi beberapa penyebab alergi makanan selama 3 minggu didapatkan perbaikan dalam gangguan muntah tersebut, maka dapat dipastikan penyebabnya adalah alergi makanan.
• Pemeriksaan standar yang dipakai oleh para ahli alergi untuk mengetahui penyebab alergi adalah dengan tes kulit. Tes kulit ini bisa terdari tes gores, tes tusuk atau tes suntik. PEMERIKSAAN INI HANYA MEMASTIKAN ADANYA ALERGI ATAU TIDAK, BUKAN UNTUK MEMASTIKAN PENYEBAB ALERGI. Pemeriksaan ini mempunyai sensitifitas yang cukup baik, tetapi sayangnya spesifitasnya rendah. Sehingga seringkali terdapat false negatif, artinya hasil negatif belum tentu bukan penyebab alergi. Karena hal inilah maka sebaiknya tidak membolehkan makan makanan penyebab alergi hanya berdasarkan tes kulit ini.  
• Dalam waktu terakhir ini sering dipakai alat diagnosis yang masih sangat kontroversial atau ”unproven diagnosis”. Terdapat berbagai pemeriksaan dan tes untuk mengetahui penyebab alergi dengan akurasi yang sangat bervariasi. Secara ilmiah pemeriksaan ini masih tidak terbukti baik sebagai alat diagnosis. Pada umumnya pemeriksaan tersebut mempunyai spesifitas dan sensitifitas yang sangat rendah. Bahkan beberapa organisasi profesi alergi dunia tidak merekomendasikan penggunaan alat tersebut. Yang menjadi perhatian oraganisasi profesi tersebut bukan hanya karena masalah mahalnya harga alat diagnostik tersebut tetapi ternyata juga sering menyesatkan penderita alergi yang sering memperberat permasalahan alergi yang ada
• Namun pemeriksaan ini masih banyak dipakai oleh praktisi kesehatan atau dokter. Di bidang kedokteran pemeriksaan tersebut belum terbukti secara klinis sebagai alat diagnosis karena sensitifitas dan spesifitasnya tidak terlalu baik. Beberapa pemeriksaan diagnosis yang kontroversial tersebut adalah Applied Kinesiology, VEGA Testing (Electrodermal Test, BIORESONANSI), Hair Analysis Testing in Allergy, Auriculo-cardiac reflex, Provocation-Neutralisation Tests, Nampudripad’s Allergy Elimination Technique (NAET), Beware of anecdotal and unsubstantiated allergy tests.

 PENATALAKSANAAN 

• Penanganan  Gangguan gejala  Artritis Reumatoid yang dipengaruhi alergi dan hipersensitifitas makanan pada anak haruslah dilakukan secara benar, paripurna dan berkesinambungan. Pemberian obat terus menerus bukanlah jalan terbaik dalam penanganan gangguan tersebut tetapi yang paling ideal adalah menghindari penyebab yang bisa menimbulkan keluhan alergi tersebut.    
• Penghindaran makanan penyebab alergi pada anak harus dicermati secara benar, karena beresiko untuk terjadi gangguan gizi. Sehingga orang tua penderita harus diberitahu tentang makanan pengganti yang tak kalah kandungan gizinya dibandingklan dengan makanan penyebab alergi. Penghindaran terhadap susu sapi dapat diganti dengan susu soya, formula hidrolisat kasein atau hidrolisat whey., meskipun anak alergi terhadap susu sapi 30% diantaranya alergi terhadap susu soya. Sayur dapat dipakai sebagai pengganti buah. Tahu, tempe, daging sapi atau daging kambing dapat dipakai sebagai pengganti telur, ayam atau ikan. Pemberian makanan jadi atau di rumah makan harus dibiasakan mengetahui kandungan isi makanan atau membaca label makanan.  
• Obat-obatan anti histamine (AH1 dan AH2), ketotifen, ketotofen, kortikosteroid, serta inhibitor sintesaseprostaglandin hanya dapat mengurangi gejala sementara bahkan dlamkeadaan tertentu seringkali tidak bermanfaat, umumnya mempunyai efisiensi rendah. Sedangkan penggunaan imunoterapi dan natrium kromogilat peroral masih menjadi kontroversi hingga sekarang.  
• Pengobatan Gangguan gejala  Artritis Reumatoid yang dipengaruhi alergi dan hipersensitifitas makanan pada anak yang baik adalah dengan menanggulangi penyebabnya. Bila gangguan sulit makan yang dialami disebabkan karena gangguan alergi dan hipersensitifitas makanan, penanganan terbaik adalah menunda atau menghindari makanan sebagai penyebab tersebut.    
• Konsumsi obat-obatan saluran cerna atau pencahar, pola makan serat, buah dan air putih banyak, terapi tradisional ataupun beberapa cara dan strategi untuk menangani Gangguan Buang Air Besar (Konstipasi) Pada Anak tidak akan berhasil selama penyebab utama  alergi dan hipersensitifitas makanan tidak diperbaiki.

PENATALAKSANAAN KHUSUS

• Pengobatan utama adalah suportif. Tujuan utama adalah mengendalikan gejala klinis, mencegah deformitas, meningkatkan kualitas hidup.
• Garis besar pengobatan  Meliputi :

1. Program dasar yaitu pemberian : Asam asetil salisilat; Keseimbangan aktifitas dan istirahat; Fisioterapi dan latihan; Pendidikan keluarga dan penderita; Keterlibatan sekolah dan lingkungan;
2. Obat anti-inflamasi non steroid yang lain, yaitu Tolmetindan Naproksen
3. Obat steroid intra-artikuler;
4. Perawatan Rumah Sakit
5. Pembedahan profilaksis dan rekonstruksi.

• Asam asetil salisilat   Obat anti-inflamasi non steroid (NSAID) terpenting untuk ARJ, bekerja menekan inflamasi, aman untuk pemakaian jangka panjang. Dosis yang efektif adalah 75-90mg/kgBB/ hari dibagi   3-4 dosis, diberikan 1-2 tahun setelah gejala klinis hilang.
• Analgesik lain.  setaminofen bermanfaat untk mengontrol nyeri atau demam terutama pada tipe sistemik, tidak boleh dipakai dalam jangka waktu lama karena menimbulkan kelainan ginjal.
• NSAID yang lain.  ebagian besar NSAID yang baru tidak boleh diberikan pada anak, pemakaiannya hanya untuk mengontrol nyeri, kekakuan, dan inflamasi pada anak yang tidak responsif terhadap asam asetil salisilat atau sebagai pengobatan awal. Tolmetin diberikan dengan dosis 30 mg/kgBB/hari ternyata cukup efektif. Selain itu Naproksen dengan dosis 10-15mg/kgBB/hari memberikan hasil pengobatan yang cukup baik.
• Obat-obat yang dapat memodifikasi perjalana penyakit (DMARDs)  Pengobatan ARJ kadang-kadang memerlukan waktu cukup lama sehingga menimbulkan keputusasaan dan ketidakpercayaan pada penderita maupun orang tuanya. DMRAIDs akan memperpendek perjalanan penyakit dan masa rawat inap. Obat-obat ini hanya boleh diberikan pada poliartritis progresif yang tidak responsif terhadap Asam Asetil Salisilat Tabel 4 menunujukkan DMRAIDs, efek samping dan pemantauannya.

 Obat Anti Rematik

• Hidroksiklorokuin  Bermanfaat pada anak yang cukup besar dengan dosis awal 6-7mg/kgBB/hari, setelah 8 minggu diturunkan menjadi 5mg/kgBB/hari. Bila setelah 6 bulan pengobatan tidak diperoleh perbaikan hidroksiklorokuin harus dihentikan. Ketika memulai jangan lupa meyakinkan bahwa tidak ada defisiensi G₆PD karena bisa terjadi hemolisis.
• Kortikosteroid   Digunakan bila terdapat gejala sistemik,uveitis kronik atau untuk suntikan intra-artikular. Dosis awal adalah 0,25-1 mg/kgBB/hari dosis tunggal, atau dosis terbagi pada kasus berat. Bila terjadi perbaikan klinis maka dosis diturunkan pelan-pelan (tappering of).
• Imunosupresan   Hanya diberikan dalam protokol eksperimental untuk keadaan berat yang mengancam jiwa, walaupun beberapa pusat kesehatan sudah memakai untuk pengobatan baku. Yang paling banyak digunakan adalah metotreksat dengan indikasi untuk poliartritis berat atau gejala sistemik yang tidak membaik dengan NSAID, hidroksiklorokuin atau garam emas. Dosis awal metotreksat adalah 5mg/m²/minggu dapat dinaikkan menjadi 10mg/m²/minggu setelah 9 minggu tidak ada perbaikan. Lama pengobatan adalah 6 bulan.
• Obat-obat ARJ yang lain :  Naproksen 10-20 mg/kg bb/hari 2 x sehari; Tolmetin 25 mg/kg bb/hari 4 x sehari; dan Ibuprofen 35 mg/kg bb/hari 4 x sehari.

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• Gangguan Hormonal, Alergi Makanan dan Hipersensitifitas Makanan
• Gangguan Mata dan Alergi Makanan
• Gangguan Kesehatan Gigi, Kesehatan Mulut dan Alergi Makanan
• Sakit Kepala atau Migren Disebabkan Alergi -Hipersensitifitas Makanan ?
• Gangguan Kulit Pada Anak, Karena Pengaruh Alergi atau Hipersensitif Makanan
• Diare Berkepanjangan dan Berak Darah berulang Pada Anak, Karena Pengaruh Alergi atau Hipersensitif Makanan
• Gangguan Tidur Pada Anak Karena Pengaruh Alergi atau Hipersensitif Makanan ?
• Gastrooesepageal Refluks (GER) atau Sering Muntah Pada Anak, Karena Pengaruh Alergi atau Hipersensitif Makanan
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Sistem imun tubuh terdiri dari banyak komponen. Semua komponen tersebut akan bekerja secara serentak manakala tubuh mendapatkan serangan dari penyakit yang berasal dari luar tubuh maupun dari dalam tubuh kita sendiri. Mempertahankan kekebalan tubuh diperlukan agar tubuh senantiasa sehat. Meningkatkan dengan menjaga pola hidup sehat, yaitu istirahat/tidur yang cukup, konsumsi makanan bergizi yang mengandung vitamin dan mineral, dan bila perlu menggunakan imunomodulator. Imunomodulator adalah imunostimulasi atau imunopotensiasi, yaitu cara memperbaiki fungsi sistem imun tubuh dengan menggunakan bahan yang merangsang atau meningkatkan kerja sistem tersebut.

Kerja sistem imun tubuh kita secara sederhana terbagi dalam 3 kelompok :

1. Sistem pertahan tubuh awal : contohnya, kulit, rambut di kulit, air mata
2. Sistem pertahanan tubuh non spesifik (alamiah) : adalah sistem yang paling cepat bereaksi ketika ada serangan virus, bakteri atau mikroba dari luar.
3. Sistem pertahanan spesifik (dapatan) : sistem ini baru bekerja ketika perlawanan sistem imun alami kita tidak cukup dan bekerja menurut jeniis serangan virus atau  bakteri yang terjadi. Yang bekerja pada sistem ini adalah Limfosit T & B. Hasil kerja sistem inilah yang berbentuk antibodi (IgG dan IgM)

Sistem imun berkembang sesuai dengan perkembangan tubuh kita, pada waktu bayi umumya sistem imun masih belum banyak berkembang, beberapa komponen masih belum dapat bekerja optimal. Dengan bertambahnya usia dari anak-nak menuju remaja hingga dewasa, sistem imun berkembang untuk bekerja lebih optimal. Tetapi memasuki usia tua, sistem imun menurun kemballi. Oleh karena itu, anak-anak dan lansia mudah sekali terkena penyakit.

Pada prinsipnya, orang dengan kondisi sistem imun dalam keadaan prima, tidak mudah terkena infeksi, akan tetapi jika pada saat tertentu sistem imunterganggu atau tidak bekerja dengan baik, maka infeksi oleh bakteri, virus atau jamur mudah masuk ke dalam tubuh. Banyak faktor yang dapat mengakibatkan sistem imun terganggu, di antaranya: stress, kurang gizi, terlalu lelah, dsb. Untuk mengatsinya diperlukan pola hidup sehat, antara lain : cukup istirahat, makan bergizi seimbang, tidak stress, menghindari lingkungan yang dapat mengakibatkan sakit dan bila perlu mengkonsusmsi obat atau suplementasi yang dapat menguatkan sistem imun (daya tahan) tubuh.

Terapi imunopotensiasi atau Imunomodulator

Terapi Imunopotensiasi adalah upaya pengobatan untuk memperbaiki fungsi sistem imun dengan menggunakan bahan yang merangsang sistem imun. Imunomodulator adalah senyawa tertentu yang dapat meningkatkan mekanisme pertahanan tubuh baik secara spesifik maupun non spesifik, dan terjadi induksi non spesifik baik mekanisme pertahanan seluler maupun humoral. Pertahanan non spesifik terhadap antigen ini disebut paramunitas, dan zat berhubungan dengan penginduksi disebut paraimunitas. Induktor semacam ini biasanya tidak atau sedikit sekali kerja antigennya, akan tetapi sebagian besar bekerja sebagai mitogen yaitu meningkatkan proliferasi sel yang berperan pada imunitas. Sel tujuan adalah makrofag, granulosit, limfosit T dan B, karena induktor paramunitas ini bekerja menstimulasi mekanisme pertahanan seluler. Mitogen ini dapat bekerja langsung maupun tak langsung (misalnya melalui sistem komplemen atau limfosit, melalui produksi interferon atau enzim lisosomal) untuk meningkatkan fagositosis mikro dan makro (Gambar 1). Mekanisme pertahanan spesifik maupun non spesifik umumnya saling berpengaruh. Dalam hal ini pengaruh pada beberapa sistem pertahanan mungkin terjadi, hingga mempersulit penggunaan imunomodulator, dalam praktek.

Imunostimulan
Imunostimulan ditunjukan untuk perbaikan fungsi imun pada kondisi-kondisi imunosupresi. Kelompok obat ini dapat memperngaruhi respon imun seluler maupun humoral. Kelemahan obat ini adalah efeknya menyeluruh dan tidak bersifat spesifik untuk jenis sel atau antibodi tertentu. Selain itu efekumumnya lemah. Indikasi imunostimulan antara lain AIDS, infeksi kronik, dan keganasan terutama yang melibatkan sistem limfatik

Karakteristik imunomodulator dan metode penguji

Aktivitas suatu senyawa yang dapat merangsang sistem imun tidak tergantung pada ukuran molekul tertentu. Efek ini dapat diberikan baik oleh senyawa dengan berat molekul yang kecil maupun oleh senyawa polimer. Karena itu usaha untuk mencari senyawa semacam ini hanya dapat dilakukan dengan metode uji imunbiologi saja. Metode pengujian yang dapat dilakukan adalah metode in vitro dan in vivo, yang akan mengukur pengaruh senyawa kimia terhadap fungsi dan kemampuan sistem mononuklear, demikian pula kemampuan terstimulasi dari limfosit B dan T.

Metode uji aktivitas imunomoduator yang dapat digunakan,yaitu:

1. Metode bersihan karbon (“Carbon-Clearance”) Pengukuran secara spektrofluorometrik laju eliminasi partikel karbon dari daerah hewan. Ini merupakan ukuran aktivitas fagositosis.
2. Uji granulosit Percobaan in vitro dengan mengukur jumlah sel ragi atau bakteri yang difagositir oleh fraksi granulosit yang diperoleh dari serum manusia. Percobaan ini dilakukan di bawah mikroskop.
3. Bioluminisensi radikal Jumlah radikal 02 yang dibebaskan akibat kontak mitogen dengan granulosit atau makrofag, merupakan ukuran besarnya stimulasi yang dicapai.
4. Uji transformasi limfosit T Suatu populasi limfosit T diinkubasi dengan suatu mitogen. Timidin bertanda ( 3 H) akan masuk ke dalam asam nukleat limfosit 1. Dengan mengukur laju permbentukan dapat ditentukan besarnya stimulasi dibandingkan dengan fitohemaglutinin A (PHA) atau konkanavalin A (Con A).

Persyaratan imunomodulator

Menurut WHO, imunomodulator haruslah memenuhi persyaratan berikut:

1. Secara kimiawi murni atau dapat didefinisikan secara kimia.
2. Secara biologik dapat diuraikan dengan cepat.
3. Tidak bersifat kanserogenik atau ko-kanserogenik.
4.  Baik secara akut maupun kronis tidak toksik dan tidak mempunyai efek samping farmakologik yang merugikan.
5. Tidak menyebabkan stimulasi yang terlalu kecil ataupun terlalu besar.

Dasar fungsional paramunitas

1. Terjadinya peningkatan kerja mikrofag dan makrofag serta pembebasan mediator.
2. Menstimulasi limfosit (yang berperan pada imunitas tetapi belum spesifik terhadap antigen tertentu), terutama mempotensiasi proliferasi dan aktivitas limfosit.
3. Mengaktifkan sitotoksisitas spontan.
4. Induksi pembentukan interferon tubuh sendiri.
5. Mengaktifkan faktor pertahanan humoral non spesifik (misalnya sistem komplemen properdin-opsonin).
6. Pembebasan ataupun peningkatan reaktivitas limfokin dan mediator atau aktivator lain.
7. Memperkuat kerja regulasi prostaglandin.

Bahan atau obat yang merangsang fungsi imun tersebut imunostimulan, terdiri dari imunostimulan biologik dan imunostimulan sintetik.

Imunostimulan biologik

• Nukleotida  
 
• Nukleotida terdapat pada air susu ibu. Akhir-akhir ini banyak susu formula yang diberi suplementasi nukleotida. Pada penelitian uji banding kasus yang dilakukan pada bayi, satu kelompok diberikan susu ibu atau susu formula yang disuplementasi nukleotida, dibandingkan dengan kelompok yang diberikan susu formula tanpa nukleotida, ternyata terdapat peningkatan aktifitas sel NK pada bayi-bayi yang diberi susu ibu dan formula dengan nukleotida dibandingkan bayi-bayi yang diberi susu formula tanpa nukleotida. Peneliti yang sama mendapatkan peningkatan produksi IL-2 oleh sel monosit pada kelompok yang diberi susu formula dengan nukleotida. Nukleotida juga mengaktifkan sel T dan sel B.

  

• Kolostrum  
• Kolostrum mengandung  “interferon like substance”, dapat menyebabkan aktifasi sitotoksisitas leukosit. Kolostrum juga mengandung makrofag yang berfungsi sebagai penyimpan dan pengangkut imunoglobulin. 
• Gonadotropin-releasing hormone’ (GnRH)  
• Gonadotropin-releasing hormone meningkatkan pertumbuhan makrofag, sel T dan merangsang sumsum tulang, serta meningkatkan GM-CSF. Pada percobaan binatang yang mengalami imunodefisiensi dengan meningkatkan CD4 T limfosit dan kadar serum IgG total, sedangkan  growth hormone
• Hormon timus 
• Hormon timus berperan dalam sel T dan modulasi sel T yang sudah matang. Ada empat macam hormon timus, yaitu timosin a, timolin, timopoietin, dan faktor timus humoral. Hormon tersebut digunakan untuk memperbaiki gangguan fungsi sistem imun pada keadaan usia lanjut, kanker, autoimun, dan kegagalan sistem imun pada pengobatan dengan imunosupresan. Pada kasus tersebut pemberian hormon timus menimbulkan peningkatan jumlah dan fungsi reseptor sel T serta beberapa aspek imunitas selular. Efek samping yang mungkin timbul seperti pemberian hormon yang lain adalah reaksi alergi lokal maupun sistemik.
• Limfokin
• Limfokin atau sitokin dihasilkan oleh limfosit yang mengalami aktivasi. Ada beberapa limfokin antara lain faktor aktivasi makrofag (MAF), faktor pertumbuhan makrofag (MGF), faktor pertumbuhan sel T (IL-2), faktor stimulasi koloni (CSF), interferon gamma. Faktor yang dihasilkan oleh makrofag misalnya faktor nekrosis tumor (TNF). IL-2 dan TNF telah dapat dibuat dengan bioteknologi genetika. TNF pada percobaan dapat menyembuhkan beberapa tumor pada tikus. Gangguan sintesis IL-2 ada kaitannya dengan kanker, AIDS, usia lanjut dan penyakit autoimun.
• Interferon
• Ada tiga macam interferon, interferon alfa (IFN-α) yang dihasilkan leukosit, interferon beta (IFN-β) yang dihasilkan fibroblast, dan interferon gama (IFN-γ =  interferon imun) yang dihasilkan oleh sel T yang teraktivasi. Interferon mempunyai khasiat dapat menghambat replikasi DNA dan RNA virus, sel normal dan sel ganas, dapat memodulasi sistem imun. Interferon dalam dosis tinggi menghambat penggandaan sel B dan sel T sehingga menurunkan respons imun selular dan humoral, dan dalam dosis rendah mengatur produksi antibodi serta merangsang sistem imun yaitu meningkatkan aktivitas membunuh sel NK, makrofag dan sel T. Efek sampingnya adalah demam, malaise, mialgia, mual, muntah, mencret, leukopenia, trombositopenia, dan aritmia.
• Antibodi monoklonal 
• Antibodi monoklonal diproduksi secara rekayasa bioteknologi. Dengan cara ini akan dihasilkan antibodi dalam jumlah banyak terhadap epitop tunggal antigen yang dikehendaki. Penggunaannya bersama radioisotop, toksin atau obat lain terutama pada pengobatan neoplasma. Antibodi monoklonal dapat mengikat komplemen untuk membunuh sel tumor manusia dan tikus pada percobaan in vivo.
• Bahan dari jamur 
• Bahan yang dapat diisolasi dari jamur antara lain lentinan, krestin dan schizophyllan. Efek imunostimulasinya adalah meningkatkan fungsi makrofag. Krestin dan lentinan sebagai imunostimulator nonspesifik telah banyak digunakan pada pengobatan kanker.
• Bahan dari bakteri
  1. Corynebacterium parvum  Corynebacterium parvum adalah kuman Gram positif. Digunakan sebagai imunostimulator dalam bentuk suspensi kuman yang telah dimatikan dengan pemanasan. Dalam klinik digunakan untuk mencegah pertumbuhan tumor dan mengurangi metastasis.
  2. Lactobacillus acidophilus  Dalam penelitian merupakan dapat menyebabkan pergeseran pola Th-2 ke arah Th-1 walaupun hanya secara lemah meningkatkan IFN-g.
  3. Endotoksin  Endotoksin merupakan lipopolisakarida, komponen dari dinding sel bakteri gram negatif seperti E. coli, shigela, dan salmonela. Sebagai imunomodulator diketahui dapat merangsang penggandaan sel B maupun sel T dan mengaktifkan makrofag. Masih bersifat eksperimen karena bersifat pirogenik dan imunogenik.

Imunostimulan sintetik

Echinacea
• Farmakodinamik Echinacea adalah peningkatan fagositosis sel granulosit manusia  in vitro 
• Levamisol  Dalam klinik lazim dipakai sebagai obat cacing, dan sebagai imunostimulan levamisol berkhasiat untuk meningkatkan penggandaan sel T, menghambat sitotoksisitas sel T, mengembalikan anergi pada beberapa kanker (bersifat stimulasi nonspesifik), meningkatkan efek antigen, mitogen, limfokin dan faktor kemotaktik terhadap limfosit, granulosit dan makrofag. Penggunaan klinisnya untuk mengobati artritis reumatoid, penyakit virus, lupus eritematosus sistemik, sindrom nefrotik. Diberikan dengan dosis 2,5 mg/kgBB per oral selama 2 minggu, kemudian dosis pemeliharaan beberapa hari per minggu. Efek samping yang harus diperhatikan adalah mual, muntah, urtikaria, dan agranulositosis.



• Isoprinosin  Sebagai imunostimulator isoprinosin berkhasiat meningkatkan penggandaan sel T, meningkatkan toksisitas sel T, membantu produksi IL-2 yang berperan dalam diferensiasi limfosit dan makrofag, serta meningkatkan fungsi sel NK. Diberikan dengan dosis 50 mg/kgBB. Perlu pemantauan kadar asam urat darah karena pemberian isoprinosin dapat meningkatkan kadar asam urat.
• Muramil dipeptida (MDP)  MDP adalah komponen aktif terkecil dari dinding sel mikobakterium. Bahan tersebut kini dapat dibuat secara sintetik. Sebagai imunostimulan berkhasiat meningkatkan sekresi enzim dan monokin, serta bersama minyak dan antigen dapat meningkatkan respons selular maupun humoral. Dalam klinik telah banyak digunakan untuk pencegahan tumor dan infeksi sebagai ajuvan vaksin.
• Vaksin BCG  Dalam penelitian pada tikus, BCG mengurangi sensitisasi dan mengurangi pembentukan IgE spesifik dan respons eosinofil terhadap rangsangan alergen dan menginduksi produksi IFN-g. BCG adalah Mycobacterium bovis yang dilemahkan. Penggunaan BCG dalam imunopotensiasi bermula dari pengamatan bahwa penderita tuberkulosis kelihatan lebih kebal terhadap infeksi oleh jasad renik lain. Dalam imunomodulasi BCG digunakan untuk mengaktifkan sel T, memperbaiki produksi limfokin, dan mengaktifkan sel NK.
• Toksin kolera Toksin kolera subunit B yang berikatan dengan antigen presenting cell mengaktifasi produksi sitokin oleh sel T.
• LW50020  LW50020 adalah suatu imunomodulator bakteria yang kini sedang dalam penelitian, merupakan preparat beberapa bacteria yang biasanya menyebabkan infeksi saluran nafas, bila diberikan per oral dapat meningkatkan mekanisme pertahanan paru dengan meningkatkan migrasi limfosit lamina propria dan limfosit Peyer’s patch. Penelitian ini dilakukan pada hewan coba BALG/c mice.
• N,N’-Diacetyl-1 Cystein  N,N’-Diacetyl-1 Cystein adalah suatu dimmer disulfit dari N-acetylcystein pada penelitian dengan hewan percobaan BALB/c meningkatkan sel CD8⁺  dan sensitifitas kontak.
• Acemannan  Acemannan adalah suatu b(1,4)-linked acetylated mannan, mempunyai kasiat antivirus, diketahui menyebabkan aktivasi makrofag dan dengan IFN-g menyebabkan apoptosis sel RAW264.7 melalui mekanisme inhibisi ekspresi bcl-2. Pada penelitian lain acemannan meningkatkan sintesis NO. Kenaikan ini didahului dengan peningkatan ekspresi mRNA NO synthase. Diduga prosesnya melalui peningkatan NO synthase pada tingkat transkripsi. 
• Polifenol  Polifenol adalah zat aktif dari teh hitam Cammelia sinensis assamica mempunyai khasiat imunopotensiator yaitu menaikkan aktifitas makrofag, sel  blast dan limfosit T sitotoksisitas.
• Vitamin A  Pada percobaan binatang vitamin A meningkatkan aktifitas sel neutrofil CD116, T CD8⁺, meningkatkan sekresi IL-2, IL-4, IL-10, IFN-g.
• Imunoterapi spesifik.    Imunoterapi spesifik adalah pemberian alergen dalam dosis rendah meningkat berjenjang dengan ekstrak alergen yang sensitif terhadap penderita. Saat ini yang diberikan adalah ekstrak alergen hirupan dan bisa/sengat. Modulasi imun yang ditimbulkan adalah merubah keseimbangan Th-1/Th-2 kearah Th-1. Pada beberapa penelitian imunoterapi meningkatkan IL-2 dan IFN-g, menurunkan IL-4, IL-5 dan IL-13. Penelitian lain menunjukkan peningkatan IgG4 dan menurunkan IgE. Kombinasi imunoterapi dengan kortikosteroid menimbulkan modulasi imun lebih kuat ke arah Th-1. Kortikosteroid menurunkan IL-5 lebih banyak, menyebabkan modulasi imun peningkatan IL-2 lebih kuat. 

Waspadai Penggunaan berlebihan pada Penderita Alergi

 Bahaya penggunaan imunomodulator berlebihan masih belum diketahui secara pasti. Karena hingga kini belum ada penelitian tentang akibat penggunaan imunomodulator berlebihan. Namun harus diwaspadai  tubuh akan sangat rentan terhadap alergi. Bila sistem  kekebalan tubuh normal dirangsang terus, seseorang akan tambah jadi sensitif dan meningkatkan stimulasi alergi. Nanti kekebalannya jadi berlebihan.  Sebaiknya penggunaan imunomodulator bukan sebagai suplemen tetapi memang diperlukan di kala tubuh membutuhkannya seperti saat daya tahan tubuh menurun atau terkena infeksi.

Imunomodulator,  berbeda dengan vitamin yang dapat dikeluarkan tubuh saat tidak lagi diperlukan atau berlebihan. Bila kekebalan tubuh terlalu berlebih, tubuh menjadi terlalu sensitif dan keseimbangan sel-sel limfosit menjadi terganggu. Dalam tubuh itu ada keseimbangan sel-sel limfosit yakni sel limfosit T-helper1 yang  dan limfosit T-helper 2. Sel T helper 1 lebih berperan kepada kekebalan tubuh terhadap infeksi sedangkan T helper 2 berperan pada antibodi.  Pada orang yang reaksi kekebalan tubuhnya berlebihan akan mudah alergi karena sel limfosit T-helper 2 menjadi terlalu dominan.

Daftar Pustaka :

• N.V. Bulkina, A.P. Glybochko.Clinico-Immunological Estimation of Application of Immunomodulatory Medicine «Gepon» in Complex Therapy of Inflammatory Periodontium Diseases. Saratov Journal of Medical Scientific Research. 2009, volume 5Issue:№2Pages: 238-242
• Spelman K, Burns J, Nichols D, Winters N, Ottersberg S, Tenborg M (June 2006). “Modulation of cytokine expression by traditional medicines: a review of herbal immunomodulators”. Alternative Medicine Review11 (2): 128–50. PMID 16813462. http://www.thorne.com/altmedrev/.fulltext/11/2/128.pdf.
• Jaffe HS, Sherwin SA. Immunomodulation. In: Stites DP, Terr AI, editor. Basic and clinical immunology; edisi ke-7. Norwalk: Appleton & Lange; l99l.p.780-5.
• Bone K, Mills S. Echinacea: Structures and biological activity. Phytochem 1994:27:278-84.
• Broxmeter HE, Smithyman A, Eiger RR,et al. Identification of lactoferrin as the granulocyte-derived inhibitor of colony stimulating-activity production. J Exp Med 1978:148:1052-68.
• Carver JD, Primentel B, Cox WI, Barnes IA. Dietary nucleotide effects upon immune function in infants. Pediatrics 1991:83:359-63.
• Carver JD. Dietary nucleotides: Cellular immune, intestinal and hepatic system effects. J Nutr 1994:124:1445-85.

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