Immunoglobulin E-mediated Reactions Research Articles

FNDC5 Geni Polimorfizmleri, Serum İrisin Düzeyleri ve Alerjik Rinit Arasındaki İlişkinin Yokluğu

Aim: Allergic rhinitis (AR) is an inflammatory nasal mucosa disease caused by type 1 immunoglobulin E-mediated reactions to allergen exposure. Irisin is a hormone released by skeletal muscles in response to exercise. There are studies that demonstrate the relationship of irisin with inflammation. We aimed to investigate the potential association between irisin coding fibronectin type III domain 5 (FNDC5) gene polymorphisms, serum irisin levels, and AR. Method: A case-control study was designed, involving 100 AR patients and 100 healthy controls. Genotyping of rs726344 and rs1746661 SNPs within the FNDC5 gene was performed using PCR-RFLP method. Serum irisin levels were measured using ELISA. Results: Genotyping of rs726344 SNP in patients revealed 90% GG and 10% GA genotypes, while in controls, it was 94% GG and 6% GA. The AA genotype was not detected in any case. For rs1746661 SNP, patients had 57% GG, 39% GT, and 4% TT genotypes, while controls had 58% GG, 36% GT, and 6% TT genotypes. No significant difference was found in rs726344 and rs1746661 SNPs between the patients and the control group. Serum irisin level was 406.3±56.09 ng/ml in patients and 354.3±46.06 ng/ml in controls with no significant difference. Conclusion: This is the first study aiming to investigate the relationship between the irisin protein, its encoding gene, and AR. No significant association was identified between FNDC5 gene polymorphisms, serum irisin levels, and allergic rhinitis. While these findings suggest a limited role of these factors in AR, further studies are needed for more comprehensive understanding of the irisin-AR relationship.

Cyanocobalamin-Induced Anaphylactic Reaction

Abstract It is widely recognized that Vitamin B12, also known as cyanocobalamin, is a nutrient that keeps the body’s nerves and blood cells healthy and contributes in deoxyribonucleic acid synthesis. Megaloblastic anemia, a form of anemia that causes fatigue and weakness, can be prevented with Vitamin B12. The main objective of this case report was to draw attention to the rare hypersensitive reactions which can occur after injecting Vitamin B12 supplement therapy. The abovementioned reaction could be a result to an immunoglobulin E-mediated reaction or due to sensitization to the Vitamin B12 molecule itself. Here, we have reported the case of a 25-year-old female patient, a known case of pulmonary tuberculosis, who was hospitalized and on medication of fixed dose of directly observed treatment, short-course, nebulizer Combimist, tablet beclomethasone, and cyanocobalamin injection. We deduce that the anaphylactoid reaction to Vitamin B12 is a rare but serious side effect and that it should be vigilantly monitored while administering the drug to the patient, especially if the parenteral route is preferred.

A Case of Nonsteroidal Anti-Inflammatory Drug-Induced Anaphylaxis Confirmed by Skin Testing

Nonsteroidal anti-inflammatory drugs (NSAIDs) are collectively a major culprit of drug-induced hypersensitivity. No reliable diagnostic tests, other than a direct challenge, are available for detecting the hypersensitivity. Cross-reactivity among NSAIDs that inhibit cyclooxygenase-1 is common. However, in rare cases, the mechanism underlying hypersensitivity can be understood from the immunological point of view, without involving cross-reactivity of NSAIDs or even with a positive skin test for an NSAID. A 55-year-old woman was referred to the Emergency Department for anaphylaxis. She suffered from generalized hives, chest tightness, and hypotension a few minutes after intramuscular injection of diclofenac. One year ago, she had experienced a similar reaction after intramuscular injection of aceclofenac. Thereafter, she had been taking naproxen as needed to relieve her osteoarthritis pain, without having an adverse reaction. To confirm drug hypersensitivity and to find alternative drugs, provocation tests were performed with acetaminophen, celecoxib, and lysine-aspirin. All tests were negative, and a skin prick test with diclofenac was also negative. However, intradermal injection of 0.05 mL (37.5 mg/mL) diclofenac provoked an anaphylactic shock and resulted in her admission. Here, we report a rare case of single NSAID-induced anaphylaxis, which was only triggered by acetic acid derivatives of NSAIDs, presumably by an immunoglobulin E-mediated reaction.

First-Dose Antimicrobial Infusion Reactions in Patients Enrolled in Outpatient Parenteral Antimicrobial Therapy Services.

After receiving a monitored first-dose antimicrobial infusion at an infusion center, 6 of 93 (6%) patients enrolled in outpatient parenteral antimicrobial therapy services experienced an immediate reaction, none of which were consistent with immunoglobulin E-mediated reactions. These findings suggest it would be reasonable to forgo monitoring for most patients receiving first-dose intravenous antimicrobials outpatient.

Beta-lactam hypersensitivity diagnosis in ambulatory and hospitalized settings require different approaches

Data on beta-lactam hypersensitivity (BLH) are mainly focused on immediate or mild nonimmediate reactions in the ambulatory setting, but limited in patients with concurrent illness and moderate-to-severe nonimmediate reactions in the hospitalized setting. To investigate the entire spectrum of BLH in Thai tertiary hospital. Clinical characteristics of 357 patients with suspected BLH were evaluated in a 7-year period. Culprit drug identification was performed in 335 patients by combined skin testing, in vitro testing, or drug provocation tests. The predominant BLH presentations were non-immunoglobulin (Ig)E-mediated reactions with severe cutaneous adverse reactions of 18.9%, and BLH status was definitively confirmed in 18.1%. The most common verified culprits were cephalosporins (34.8%), particularly in hypersensitivity type IV reactions. Natural penicillins were the main implicated drugs in 48.5% of ambulatory patients. In contrast, cephalosporins and carbapenems were the main implicated drugs in hospitalized patients. Non-IgE-mediated anaphylaxis and serum sickness-like reaction remained diagnostically challenged. New generations of beta-lactams, hospitalized patients, recent allergic history, and underlying malignancies or autoimmune diseases were associated with increased BLH risk. At present, cephalosporins are the leading causes of BLH, particularly in non-IgE-mediated reactions. More research on the verification of non-IgE hypersensitivity reactions from new generations of beta-lactams should be better emphasized. The registry was approved by the Ethics and Research Committee of the Faculty of Medicine, Chulalongkorn University, and listed on ClinicalTrials.gov (Identifier: NCT01667055; https://www. gov/ct2/show/NCT01667055).

Twenty-year comparison of delabeling pediatric patients with penicillin allergy with and without prior skin testing

Approximately 10% of the US population, including at least 5 million children, report a penicillin allergy though more than 90% of those individuals are found to have no allergy after evaluation.1,2 Less than 1% of patients with penicillin allergy have immunoglobulin (Ig)E-mediated reactions and approximately 80% of those patients will lose their sensitivity after 10 years.3 Inferior clinical outcomes, such as 50% increase in surgical site infections, prolonged hospitalization, use of less efficacious, more broad-spectrum antibiotics, and increased mortality, are associated with penicillin avoidance in adults with penicillin allergy.

Pharmacokinetic and Pharmacological Aspects of a Papain-Based Enzyme Solution for Rescuing Clogged Enteral Feeding Tubes.

Successful enteral feeding depends on patent enteral feeding tubes to permit trouble-free entry of nutritional formula into the alimentary tract. However, tube clogs can be a challenging complication of enteral feeding. This report addresses questions about using a papain-based enzyme solution to unclog enteral feeding tubes, including any effects that papain may have on patients and if solution use should be contraindicated in patients on ketogenic diets. The gastrointestinal tract is not permissive for significant papain activity and papain absorbed into the blood would likely be neutralized by antiproteases. In vitro examinations do not suggest toxic effects of papain in vivo, and those recognized in the latter setting are due to papain loads that exceed those used to unclog enteral feeding tubes. Allergies to papain occur infrequently and are probably attributable to an immunoglobulin E-mediated reaction to this enzyme. Although the amount of carbohydrate consumed upon single use of the unclogging solution is very low, a provider should decide whether using the papain-based enzyme solution for enteral feeding purposes is appropriate in patients who practice ketogenic diets. The benefits of using the papain-based enzyme solution to unclog enteral feeding tubes appear to outweigh any risks associated with its use.

Prediction of adult-onset bronchial asthma in patients with metabolic syndrom in actual practice

Aim. Adult asthma diagnosis optimization for patients with metabolic syndrome using prognostic methods.
 Methods. The study included 46 patients with metabolic syndrome. Out of them, at the time of the study 31 subjects suffered from adult-onset bronchial asthma. All participants of the study had a history and complaints collected, and a clinical examination performed. Spirometry was used to assess the severity of bronchial obstruction syndrome. To assess the severity of metabolic syndrome components, glucose and fasting insulin concentrations, and lipid profile were determined, the homeostasis index of insulin resistance was calculated. Also in all participants the concentrations of leptin and endothelin-1 in the serum were determined.
 Results. Risk of adult-onset bronchial asthma in a typical patient with metabolic syndrome spikes with maximal blood pressure higher than 154/90 mm Hg, and immunoglobulin E and leptin level higher than 33 ME/ml and 3.7 ng/ml, respectively. Blood pressure level affects adult-onset bronchial asthma pathogenesis only in combination with other metabolic syndrome components. Immunoglobulin E-mediated reactions play an important role in the pathogenesis of adult-onset bronchial asthma, and leptin acts as a regulator of pathogenetic mechanism.
 Conclusion. Development of adult-onset bronchial asthma in patients with metabolic syndrome may be predicted on the basis of various variables; according to our data, those variables include maximum systolic and diastolic blood pressure levels, and levels of immunoglobulin E and leptin.

Wheat allergy: diagnosis and management

Triticum aestivum (bread wheat) is the most widely grown crop worldwide. In genetically predisposed individuals, wheat can cause specific immune responses. A food allergy to wheat is characterized by T helper type 2 activation which can result in immunoglobulin E (IgE) and non-IgE mediated reactions. IgE mediated reactions are immediate, are characterized by the presence of wheat-specific IgE antibodies, and can be life-threatening. Non-IgE mediated reactions are characterized by chronic eosinophilic and lymphocytic infiltration of the gastrointestinal tract. IgE mediated responses to wheat can be related to wheat ingestion (food allergy) or wheat inhalation (respiratory allergy). A food allergy to wheat is more common in children and can be associated with a severe reaction such as anaphylaxis and wheat-dependent, exercise-induced anaphylaxis. An inhalation induced IgE mediated wheat allergy can cause baker’s asthma or rhinitis, which are common occupational diseases in workers who have significant repetitive exposure to wheat flour, such as bakers. Non-IgE mediated food allergy reactions to wheat are mainly eosinophilic esophagitis (EoE) or eosinophilic gastritis (EG), which are both characterized by chronic eosinophilic inflammation. EG is a systemic disease, and is associated with severe inflammation that requires oral steroids to resolve. EoE is a less severe disease, which can lead to complications in feeding intolerance and fibrosis. In both EoE and EG, wheat allergy diagnosis is based on both an elimination diet preceded by a tissue biopsy obtained by esophagogastroduodenoscopy in order to show the effectiveness of the diet. Diagnosis of IgE mediated wheat allergy is based on the medical history, the detection of specific IgE to wheat, and oral food challenges. Currently, the main treatment of a wheat allergy is based on avoidance of wheat altogether. However, in the near future immunotherapy may represent a valid way to treat IgE mediated reactions to wheat.

COMPARATIVE STUDY OF SECOND GENERATION ANTI HISTAMINE (Cetirizine Hydrochloride 10mg) ALONE VERSUS ANTIHISTAMINE IN COMBINATION WITH LEUKOTRIENE RECEPTOR ANTAGONISTS (Montelukast Sodium 10mg) IN THE TREATMENT OF ALLERGIC RHINITIS

Background: Allergic rhinitis is an inflammatory disease of the nasal mucosa, induced by an immunoglobulin Emediated reaction in allergen-sensitized subjects. Allergen avoidance and pharmacotherapy are the cornerstones of allergic rhinitis management. Pharmacotherapy is individualized to the patient based on type of symptoms, their duration and severity, co-morbidities, response to prior treatment and patient preference. Classes of drugs used to treat allergic rhinitis include antihistamines, corticosteroids, mast cell stabilizers, decongestants, nasal anticholinergics, and leukotriene-receptor antagonists.
 Objective: The objective of the study was to compare the Second Generation Antihistamine (Cetirizine) alone versus Antihistamine with Leukotriene Receptor Antagonist-LTRA (Montelukast Sodium) in the treatment of Allergic Rhinitis AR.
 Method: It was single blind hospital-based study in which 200 patients were included. The patients were divided into two equal groups (Group-A and Group-B). Group-A was treated with Cetirizine hydrochloride 10mg/day alone while Group-B was treated with Cetirizine hydrochloride 10mg/day along with Montelukast Sodium 10mg/day.
 Results: Among 100 Group-A patients, 35.0% were 15-20 years old and among 100 Group-B patients, 34.0% were 15-20 years old. 57.0% Group-A and 55.0% Group-B patients had seasonal allergy. Among Group-A patients, 26.0% had nasal mucosa pale on revisit and 79.0% patients had any remarkable sedation with dispensed medicine. But among Group-B patients, only 5.0% had nasal mucosa pale and swollen on revisit and only 5.0% patients had any remarkable sedation with dispensed medicine.
 Conclusion: Study concluded that combination of cetirizine hydrochloride 10mg/day & montelukast sodium 10mg/day is more efficacious in the treatment of allergic rhinitis than cetirizine hydrochloride 10mg/day alone.

Recognition and First-Line Treatment of Anaphylaxis

The International Classification of Diseases (ICD)-9 included a code only for anaphylactic shock. The improved ICD-10 coding defines the different symptoms and types of anaphylaxis and includes coding for anaphylaxis without shock. This new coding is consistent with the efforts of the National Institute of Allergy and Infectious Diseases (NIAID) and the Food Allergy and Anaphylaxis Network (FAAN), who convened a panel to formulate a definition of and the diagnostic criteria for anaphylaxis. Anaphylaxis is a serious reaction that has a rapid onset and may cause death. It is a systemic immunoglobulin E-mediated reaction resulting from the sudden release of multiple mediators from mast cells and basophils. Foods are the most common triggers for anaphylactic reactions, followed by drugs, insect stings, and idiopathic anaphylaxis (anaphylaxis of unknown cause). If the NIAID/FAAN criteria are met and anaphylaxis is diagnosed, epinephrine administration is mandatory. Delays in epinephrine administration have been associated with fatalities. Patients should have ready access to >1 epinephrine autoinjector in the outpatient setting. An individualized emergency action plan should be developed for each patient at risk for anaphylaxis.

An Experimental Biological Test to Diagnose Hypersensitivity Reactions to Carboplatin: New Horizons for an Old Problem

Carboplatin, a second-generation platinum compound, is a chemotherapeutic drug effective in many types of cancers. Its use is limited by the development of systemic allergic reactions in up to 30% of the cancer patients. Therefore, it is very important to make a correct diagnosis of true carboplatin allergy, for the crucial clinical implications. In this regard, no biological test is actually available to detect specific immunoglobulin E in the sera of patients allergic to carboplatin. We evaluated a new experimental biological test in patients with suspected immunoglobulin E-mediated reactions to carboplatin. Three patients with suspected hypersensitivity reactions to carboplatin underwent skin tests with an undiluted aliquot (10 mg/ml) of carboplatin preparation planned for infusion. Total serum immunoglobulin E and specific immunoglobulin E to the two platinum salts carboplatin and cisplatin were determined with the ImmunoCAP system (Phadia AB, Uppsala, Sweden). We detected specific immunoglobulin E to carboplatin in all three patients, whereas specific immunoglobulin E to cisplatin was observed in one patient. The positivity of specific immunoglobulin E against carboplatin in these three patients is a new and encouraging observation for the development of a new important instrument that can help clinicians in their therapeutic decisions, after a hypersensitivity reaction to a platinum salt.

Diagnosis and assessment of food allergy in children and young people in primary care and community settings: NICE clinical guideline

Food allergy is recognised as a major paediatric health problem in western countries. The true prevalence is unknown but Europe and the US report ranges from 6% to 8% in children aged up to 3 years. The National Institute for Health and Clinical Excellence (NICE) has developed a guideline on the symptoms that should prompt consideration of food allergy when a child or young person presents in primary or community care.1 Food allergy is an adverse immune response to food allergens. Reactions can be classified into those that are immunoglobulin E (IgE) mediated or non-IgE mediated. Some children may have both IgE and non-IgE mediated reactions to food; in this guideline, these are referred to as mixed reactions. In both IgE and non-IgE reactions, there is a response by the immune system to a protein within food. IgE mediated reactions are immediate type 1 hypersensitivity reactions while non-IgE mediated reactions usually occur several hours after allergen exposure. The exact mechanism is not clearly understood but, in both reactions, elimination of the allergenic food protein is required to prevent symptoms. The correct diagnosis of food allergy should decrease the incidence of adverse food reactions that are a result of true food allergies; and help prevent the unnecessary exclusion of foods that are safe and that should be eaten as part of a normal, healthy diet. This guideline does not cover children and young people with food intolerances (such as intolerance to lactose), reactions to pharmacological agents (such as salicylates), or reactions to those substances that naturally occur in foods (such as benzoic acid). When to suspect food allergy Food allergy should be suspected when the following are present: persistent eczema, gastro-oesophageal reflux disease and bowel symptoms, including constipation, that do not respond to normal …

Allergic Contact Dermatitis from Carmine

A 28-year-old woman developed allergic contact dermatitis within 6 to 24 hours exclusively after using carmine-containing eyeshadows and lipsticks. She had both a positive patch test result and a positive antecubital repeated open application test result with carmine 2.5% in petrolatum. Thirty other patients had negative patch test results. Carmine is a widely used pigment derived from gravid cochineal insects. Carminic acid is the source of its color. Only two previous publications describing allergic contact dermatitis from carmine could be found. The ingredient in carmine causing these delayed hypersensitivity reactions has not been studied. In contrast, there are numerous reports of immediate hypersensitivity reactions from carmine, mostly from its use in foods and beverages but also from cosmetics and pharmaceuticals. These are immunoglobulin E-mediated reactions directed against cochineal proteins.

Antihistamine and sodium cromoglycate medication for food cold water exercise-induced anaphylaxis

Food exercise-induced anaphylaxis (FEIA) is an uncommon but well described immunoglobulin (Ig) E-mediated reaction potentially causing severe anaphylaxis (1) after ingestion of a specific food, most often wheat flour, exclusively when followed by exercise (2). The patient reported here suffered from FEIA, exclusively when exercising in cold water. He is a 17-year-old man playing national league water-polo, swimming every day for at least 1 h. He was experiencing in the last 2 years monthly anaphylactic reactions ranging from diffuse urticaria to acute asthma when swimming up to 6 h after eating wheat. The reactions appeared in various swimming pools as well as in a lake (water temperature between 18 and 25 C) but not when doing other types of exercise (e.g. running) indoors or outdoors. Oral antihistamines alone failed to prevent the reactions but no reaction occurred on a wheat avoidance diet for 8 h prior to swimming. His medical history revealed polleninduced allergic rhinitis. He never suffered from atopic dermatitis, asthma or any type of physical urticaria, and had no sign of systemic disease. Skin prick tests showed sensitization to celery, nuts and various pollens (weed, rye and mugwort) and negative results for various cereals including wheat and soy. Serum-specific IgE (by UniCAP, Phadia, Uppsala, Sweden) were positive at 0.8 kU/l for wheat, 3.96 kU/l for rye, 1.22 kU/l for barley, 3.67 kU/l for maize and 1.69 kU/l for buckwheat flour. Basal serum tryptase level was normal. Further diagnostic work-up included food challenges without and with exercise as summarized in Table 1. The challenge tests were conducted in the morning, in a fasting state or 90 min after ingestion of 3.5 g of cooked wheat protein. The patient remained asymptomatic after running 20 min on a treadmill. After ingestion of wheat, the patient developed diffuse pruritus and urticaria on his trunk after 15 min of brisk swimming in the cold swimming pool (24 C). The challenge was stopped and the symptoms resolved spontaneously. Interestingly, no symptoms appeared in the warm swimming pool (31 C) after a similar effort. Diet was the major drawback for the patient s sport activity. Therefore, a protective treatment with oral antihistamine (fexofenadine, Telfast 360 mg, once a day; sanofi-aventis, Geneva, Switzerland) and oral sodium cromoglycate (Nalcrom 200 mg; sanofi-aventis) prior to every meal was started. The efficacy of this treatment was assessed by a negative wheat challenge followed by swimming in the cold water pool. Two weeks later, on protective medicine, the patient was progressively reintroduced to wheat without reaction. The food and exercise challenge tests demonstrated that our patient suffered from FEAI to wheat but exclusively in cold water with a temperature below 31 C, with a threshold between 25 and 31 C. Food exercise-induced anaphylaxis is usually manageable with avoidance diet only. However, restrictive diet or exercise avoidance can be difficult and impair quality of life, particularly in athletes. Cromoglycate, a mast cell stabilisator, was studied earlier in food allergy but failed to be effective in egg allergic patients (3). However, we could show that the addition of antihistamine and cromoglycate abrogated the symptoms, allowing our patient to keep on his high level training programme while eating a nonrestricted diet. This confirms an earlier case report of a successful prevention of FEIA with sodium cromoglycate (4). Only larger trials could demonstrate if antihistamines combined with sodium cromoglycate could avoid restrictive diet in selected patients with this condition. P. A. Eigenmann has consulting arrangements with Phadia and is on the speakers bureau for Phadia, Trimedal, Milupa, UCB Pharma, Mead Johnson, Fujisawa, Novartis, Abbot and Essex. The other authors report no potential conflict of interest.

Autism spectrum disorders – Exogenous protein insult

The immune-response perspective described herein is intended to explore how certain environmental proteins may affect neuro-cognitive development in children. Specifically, proteins inherent in natural rubber latex are known to cause severe and pervasive immune responses. More specifically, the Hevea Brasiliensis proteins in natural rubber latex may trigger immunoglobulin-E mediated reaction antibodies and influence cross-react immune responses to other exogenous/endogenous proteins. In adults, repeated exposure to the Hevea Brasiliensis proteins has been shown to cause an increased incidence of sensitization, adverse allergic reactions, and even death through anaphylactic shock. Natural rubber latex has seen a dramatic increase in usage over the last 30-years (e.g., health care industry, consumer products). The timing, frequency, intensity, and type of exposure to such proteins may influence the incidence, degree of atypicality, and prevalence of autism spectrum disorders. Therefore, research efforts should be directed at exploring how immune responses to such proteins affect lymphocyte sensitivity, enzyme regulation, and neural formation during prenatal/neonatal development.

Desensitization for drug allergy

Desensitization for drug allergy is the induction of temporary clinical unresponsiveness to drug antigens. Gradual reintroduction of small doses of drug antigen at fixed time intervals allows for the delivery of full therapeutic doses, protecting patients from anaphylaxis. Rapid desensitizations permit the use of essential antibiotics in severely infected allergic patients or aspirin in aspirin-sensitive cardiac patients undergoing revascularization. We review the indications and outcomes of recent protocols for desensitization to antibiotics and aspirin. Despite the success of rapid desensitizations, the cellular and molecular inhibitory mechanisms are incompletely understood. In-vitro mast cell and basophil models implicate molecular signaling molecules syk and STAT6. Rapid desensitization protocols treat type I mast cell/IgE dependent reactions, such as anaphylaxis, as seen with sensitization to penicillin, cephalosporins, and other antibiotics. Anaphylactoid reactions induced upon initial drug exposure and with similar clinical presentation as immunoglobulin E-mediated reactions, as seen with aspirin, vancomycin and taxenes, can also be treated with rapid desensitizations. Successful rapid desensitization protocols for treating adverse reactions to antibiotics and aspirin allow for treatment of critically infected patients and aspirin-sensitive cardiac patients. Standardized protocols with high success rates should be implemented as the standard of care.

Food allergy: manifestations, diagnosis and management

Adverse reactions to food are common but only a fraction of them are due to hypersensitivity (or allergy). Of the latter, immunoglobulin (Ig)E-mediated reactions appear to be the most common and best understood. A wide variety of manifestations may affect various body systems, particularly the gastrointestinal tract, skin and respiratory tract. Diagnosis depends primarily on thorough medical history, often supplemented by skin testing or specific serum IgE antibody measurement. Verification would require appropriately designed challenge testing. At present, treatment is primarily strict avoidance of the offending food, together with crossreacting other foods. Several immunomodulatory therapeutic agents are being explored. A few studies demonstrated a potential benefit of probiotics for prophylaxis and treatment. A multicenter study is currently investigating the efficacy and safety of anti-IgE in subjects with peanut allergy. Experimental studies in mice revealed preliminary findings that promise vaccine development using novel approaches, such as modified food allergen epitopes, immunostimulatory sequence-conjugated allergens and chimeric proteins capable of complexing with IgE or its receptors.

Immunoglobulin e-mediated reactions to corticosteroids

Allergic reactions to steroids are rare, but are becoming more commonly recognized by clinicians. Although many reactions are thought to be IgE mediated, most are adverse drug reactions caused by nonallergic mechanisms, some related to additives in the steroid preparation being administered. Provocative challenge with the suspected offending agent, serologic tests for allergen-specific IgE, and skin testing are the most reliable methods for assessing hypersensitivity to steroids, although none is infallible. Therapeutic options for patients with documented steroid allergy include the use of alternative steroid preparations, desensitization, and, possibly, the use of monoclonal anti-IgE antibodies.

Immediate allergy to tetanus toxoid vaccine: determination of immunoglobulin E and immunoglobulin G antibodies to allergenic proteins

Adverse reactions to tetanus toxoid (TT) vaccine are mostly mild and limited to the injection site. However, immunoglobulin (Ig)E-mediated reactions may occur, and the incidence of anaphylactic responses to TT immunization is 0.001%. When TT induces an allergic reaction, the potential causative agents can be TT antigens, thimerosal or aluminum phosphate. We studied four children who developed immediate urticaria after TT vaccine, soon after the reaction and 5 years later. Skin tests were performed separately with TT vaccine and two vaccine components, thimerosal and aluminum phosphate, and the diagnosis was confirmed by provocation test. IgE and IgG antibodies to TT and their specificities were determined. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting were performed to characterize the antigenic proteins. All four children were immediate skin test-positive to TT, but negative to thimerosal and aluminum phosphate; 3 developed a reaction after intramuscular provocation using increasing doses of TT vaccine; and 1 refused to be tested. All these tests were negative in five controls, all of whom received TT vaccine and developed only local swelling at the site of application 24 hours after vaccine administration. After 5 years the IgG antibodies were still high in all cases and the IgE antibody values fell by 50%. Patients allergic to TT vaccine produced IgE and IgG antibodies, which decreased at different rates but remained for at least 5 years. The pattern of antibody decrease was confirmed by radioallergosorbent test, enzyme-linked immunoadsorbent assay, or immunoblotting assay. IgE and IgG antibodies recognized two proteins derived from TT, of 150 and 50 kDa, corresponding to the intracellular form and to a chain of the extracellular form of the tetanus neurotoxin. In children with immediate allergic reactions to TT vaccine, antibodies may persist for at least 5 years, requiring evaluation by skin and/or in vitro tests before subsequent treatment.