Background Anaphylaxis after Hymenoptera stings has been reported in subjects with mastocytosis, but few data exist regarding disease prevalence in populations allergic to these insects. Objective ...The incidence of clonal mast cell (MC) disorders in subjects with both systemic reactions to Hymenoptera stings and increased serum baseline tryptase (sBT) levels was assessed by using bone marrow (BM) aspirates and biopsy specimens. Methods Subjects with a history of a systemic reaction caused by a Hymenoptera sting underwent the standard diagnostic work-up for Hymenoptera allergy, and sBT levels were measured. Subjects with an increased sBT level had BM evaluation that included histology/cytology, flow cytometry, and detection of KIT mutations. Results Forty-four (11.6%) of 379 subjects with systemic reactions had increased sBT levels (>11.4 ng/mL), and 31 (70.5%) of these had a history of anaphylaxis. Thirty-four subjects with increased sBT levels underwent a BM analysis. Histology detected diagnostic or subdiagnostic MC infiltrates in 22 (65%) of 34 patients. Abnormal MCs were identified by means of flow cytometry and cytology in 26 (78.8%) of 33 and 20 (58.8%) of 34 subjects, respectively. A KIT mutation was detected in 17 (54.8%) of 31 subjects. The diagnosis was indolent systemic mastocytosis in 21 (61.7%) of 34 subjects and monoclonal MC activation syndrome in 9 (26.5%) of 34 subjects. All subjects with anaphylaxis had one of those 2 disorders. Conclusion The concomitant presence of systemic reactions (especially anaphylaxis) after Hymenoptera stings and increased sBT levels strongly suggests that a BM examination is indicated for the diagnosis of clonal MC disease.
Background Systemic mastocytosis is a clonal mast cell (MC) disease that can lead to potentially fatal anaphylactic reactions caused by excessive MC mediator release. The prevalence of mastocytosis ...in patients with Hymenoptera venom allergy is high, and thus the disease should be suspected in patients with severe reactions caused by Hymenoptera stings and increased serum basal tryptase (SBT) levels. Objective We sought to evaluate the presence of clonal MC disorders in patients seen at our mastocytosis center with Hymenoptera sting–induced anaphylaxis, documented hypotension, absence of urticaria pigmentosa, and normal SBT levels. Methods Twenty-two patients with Hymenoptera sting–induced anaphylaxis, without skin lesions, and with tryptase levels of less than 11.4 ng/mL underwent bone marrow evaluation. Bone mineral density was assessed in those patients with ascertained mastocytosis. Results In 16 of 22 patients, a diagnosis of indolent mastocytosis could be established, and 1 patient had a monoclonal MC activation syndrome. Patients with mastocytosis had higher SBT levels ( P = .03) but only rarely had angioedema/urticaria associated with hypotension ( P = .004). Conclusions The absence of urticaria or angioedema in severe reactions to Hymenoptera stings with hypotension might represent the most relevant factor in identifying patients with mastocytosis, regardless of their serum tryptase levels.
Background Atopic dermatitis often has an allergic component, and immunotherapy may therefore prove beneficial. Objective To assess the effect of sublingual immunotherapy (SLIT) in children with ...atopic dermatitis. Methods Children age 5 to 16 years with atopic dermatitis (Scoring Atopic Dermatitis SCORAD > 7) and sensitization to dust mites alone, without food allergy or chronic asthma, were enrolled in a randomized, double-blind, placebo-controlled study and stratified according to disease severity. SLIT or placebo was given for 18 months in addition to standard therapy. SCORAD, visual analog scale, and rescue medication consumption were recorded at 3-month intervals. Results Fifty-six children were enrolled, and 28 were allocated to SLIT. Forty-eight completed the study, with 2 dropouts in the active and 6 in the placebo group. The difference from baseline in the SCORAD was significant ( P = .025) between the 2 groups starting from month 9. Similarly, there was a significant reduction in the use of medications only in the active group. A trend toward significance was seen for the visual analog score only in the active group versus baseline ( P = .07). A significant difference in the considered parameters was found only in patients with a mild-moderate disease, whereas severe patients had only a marginal benefit. SLIT had to be discontinued in 2 patients because of exacerbation of dermatitis. Conclusion Sublingual immunotherapy to dust mite improves mild-moderate atopic dermatitis. Clinical implications Sublingual immunotherapy may represent an additional therapeutic tool for the treatment of extrinsic atopic dermatitis in properly selected children.
Cow's milk allergy (CMA) in children is a important problem in medical practice. Oral desensitization has been proposed as a therapeutic approach, but current protocols are time-consuming and ...impractical.
To establish a patient-friendly desensitization regimen with weekly up-dosing and to evaluate it in a randomized controlled trial.
Thirty children with IgE-mediated CMA confirmed by double-blind placebo-controlled food challenge were equally randomized to desensitization with CM or soy milk as control. The weekly up-dosing lasted 18 weeks. The occurrence and severity of reactions after each dose was evaluated, and the desensitization was stopped if severe reactions occurred. Specific IgE and IgG4 levels to CM were measured at baseline, after 8 weeks, and at the end of the study. The double-blind food challenge was repeated once the desensitization was completed or after premature discontinuation.
Two active and 1 control patient dropped out. Full tolerance to CM (200 mL) was achieved in 10 active patients and partial tolerance in 1. Two active patients discontinued the desensitization after experiencing severe reactions, whereas no reactions occurred in controls, whose sensitivity to CM remained unchanged. A significant increase in specific IgG4 levels was found only in the active group.
This weekly up-dosing desensitization protocol for CMA performed under medical supervision was effective and reasonably safe and induced consistent immunologic changes.
Oral immunotherapy (OIT) may be an effective treatment for food allergy in children. It is not clear if the OIT-induced effect is achieved by desensitization (transient state dependent on regular ...antigen exposure), or by tolerance (persistent condition where the ability to consume the food is retained even after a period of withdrawal).
The aim of this study was to investigate the efficacy of OIT-egg desensitization in a double-blind placebo-controlled study, and to evaluate if, after desensitization, tolerance can be maintained.
Children with egg allergy were randomized to OIT or placebo for 4 months. At the end of the controlled phase, a double-blind food challenge was repeated to confirm the achieved desensitization. Those subjects found to be desensitized were placed on an egg-containing diet for 6 months, followed by an egg avoidance phase for 3 months, when the food challenge was repeated to determine the maintained tolerance.
A total of 31 children were randomized to OIT with dehydrated egg white (n = 17) or placebo (n = 14). Of the 17 active patients (1 dropout), 16 achieved desensitization and started the 6-month egg-containing diet. After 3-month of egg avoidance, 31% remained tolerant. In the control group, only 1 passed the final food challenge. Egg-specific IgG4 increased only in the active group. Five active OIT patients had side effects.
Egg OIT results in desensitization in almost all subjects, although tolerance was maintained in only 1/3 of them after a 3-month period of withdrawal. Side effects were encountered, but the procedure appeared safe. In hen egg allergy, OIT is effective for desensitization.
Currently, testing for immunoglobulin E (IgE) sensitization is the cornerstone of diagnostic evaluation in suspected allergic conditions. This review provides a thorough and updated critical ...appraisal of the most frequently used diagnostic tests, both in vivo and in vitro. It discusses skin tests, challenges, and serological and cellular in vitro tests, and provides an overview of indications, advantages and disadvantages of each in conditions such as respiratory, food, venom, drug, and occupational allergy. Skin prick testing remains the first line approach in most instances; the added value of serum specific IgE to whole allergen extracts or components, as well as the role of basophil activation tests, is evaluated. Unproven, non-validated, diagnostic tests are also discussed. Throughout the review, the reader must bear in mind the relevance of differentiating between sensitization and allergy; the latter entails not only allergic sensitization, but also clinically relevant symptoms triggered by the culprit allergen.
Subcutaneous allergen immunotherapy (SCIT) is an effective treatment for allergic rhinitis, asthma and venom hypersensitivity and has the potential of producing serious life-threatening anaphylaxis. ...Adverse reactions are generally classified into 2 categories: local reactions, which can manifest as redness, pruritus, and swelling at the injection site, and systemic reactions (SRs). SRs can range in severity from mild rhinitis to fatal cardiopulmonary arrest. Early administration of epinephrine, which is the treatment of choice to treat anaphylaxis, may prevent the progression of an SR to a more serious life-threatening problem. Although there is little debate about using epinephrine to treat a SCIT SR, there is a lack of consensus about when it should be first used. A uniform classification system for grading SCIT SRs will be helpful in assessing more accurately when epinephrine should be administered. The primary purpose of this article is to discuss the proposed grading system for SCIT SRs.
Background Data on the long-term effects of sublingual immunotherapy (SLIT) are sparse, and the optimal duration of treatment is a matter of debate. Objective We sought to prospectively evaluate the ...long-term effect of SLIT given for 3, 4, or 5 years and to compare the effect of those different durations. Methods In this prospective open controlled study we followed up patients with respiratory allergy who were monosensitized to mites for 15 years. The subjects were divided in 4 groups receiving drug therapy alone or SLIT for 3, 4, or 5 years. Clinical scores, skin sensitizations, methacholine reactivity, and nasal eosinophil counts were evaluated every year during the winter months. The clinical effect was considered to persist until clinical scores remained at less than 50% of the baseline value, and then patients underwent another course of SLIT. Results Seventy-eight patients were enrolled, and 59 completed the study. In the 12 control subjects no relevant change in clinical scores was seen throughout the study. In the patients receiving SLIT for 3 years, the clinical benefit persisted for 7 years. In those receiving immunotherapy for 4 or 5 years, the clinical benefit persisted for 8 years. New sensitizations occurred in all the control subjects over 15 years and in less than a quarter of the patients receiving SLIT (21%, 12%, and 11%, respectively). The second course of vaccination induced a benefit more rapidly than the first course. The behavior of bronchial hyperreactivity and nasal eosinophils paralleled the clinical score. Conclusion Under the present conditions, it can be suggested that a 4-year duration of SLIT is the optimal choice because it induces a long-lasting clinical improvement similar to that seen with a 5-year course and greater than that of a 3-year vaccination.
Sublingual immunotherapy (SLIT) is increasingly used worldwide. Despite its safety being well ascertained, there is no universally accepted system to grade and classify its adverse events (AEs). ...According to the literature, it seems reasonable to classify and grade systemic side effects by using the previously published World Allergy Organization recommendations. On the other hand, local side effects are the most frequent with SLIT, sometimes leading to its discontinuation. Therefore grading of the severity of local side effects was perceived as necessary for the purpose of uniform reporting, classification, and quantification of this aspect. A World Allergy Organization Taskforce, after examining the available literature and the postmarketing surveillance data, proposed a clinically based grading of the severity of local AEs caused by SLIT. The use of the Medical Dictionary for Regulatory Activities nomenclature for AEs was also included in this context. The proposed grading system for SLIT-induced local reactions is expected to improve and harmonize surveillance and reporting of the safety of SLIT.
The Allergic Rhinitis and its Impact on Asthma document was first published in 2001. Since then, new data on specific immunotherapy have appeared. This review is intended as an update to the original ...document. MedLine (2001 to June 2006) was searched with appropriate key words, and panelists were asked to identify further relevant articles. Randomized controlled trials were considered for the evaluation of efficacy. For the evaluation of safety and additional effects, studies with lower grades of evidence were included. The clinical efficacy of injection immunotherapy in rhinitis and asthma was confirmed, as well as the safety, provided that recommendations are followed. Studies have demonstrated the long-term efficacy and the preventive effect of immunotherapy in reducing the onset of new sensitizations. One randomized open trial demonstrated that in children with allergic rhinitis, injection immunotherapy may reduce the risk of developing asthma. There is strong evidence that sublingual immunotherapy is effective in allergic rhinitis in adults. Recent meta-analyses demonstrated its efficacy in allergic rhinitis in children and in asthma, although more definitive trials are required. Current data indicate that sublingual immunotherapy is safe and the rate of adverse reactions is not greater below 5 years of age. One randomized open trial showed that in children with allergic rhinitis, sublingual immunotherapy reduced the onset of asthma. Further studies are needed to identify the optimal maintenance dose and to elucidate the mechanism of action. Novel approaches for immunotherapy are currently under evaluation, including the use of adjuvants, peptides, and DNA-conjugated and recombinant allergens.
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