Practical guidelines for diagnosing hypersensitivity reactions to nonsteroidal anti-inflammatory drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the drugs most frequently involved in hypersensitivity reactions. These reactions include various clinical entities with different mechanisms leading to the release of inflammatory mediators. Characterization of patients based on clinical manifestations and suspected underlying mechanisms is critical for implementation of adequate diagnostic procedures and patient management. Our objectives were to prepare a systematic review of available scientific evidence and to provide general guidelines for the diagnosis and management of patients with hypersensitivity reactions to NSAIDs. We also propose a practical algorithm for the diagnosis of specific types of hypersensitivity to NSAIDs and provide recommendations for the management of hypersensitive patients.

Alternating Polistes-Vespula venom immunotherapy: a therapeutic strategy to resolve a diagnostic deficiency.

BACKGROUND: In Mediterranean regions, double sensitization to Polistes and Vespula species is frequent in patients reacting to an unidentified wasp sting. Since both genera are present, it is often difficult to determine which insect is responsible and, consequently, select venom for immunotherapy. When a specific diagnosis cannot be made, a new therapeutic strategy should be undertaken. METHODS: We performed a case-control study in which 37 patients who were allergic to venom from Vespula and Polistes species received a 3-year schedule of alternating immunotherapy. Twenty monosensitized patients (10 to Vespula and 10 to Polistes) received conventional venom immunotherapy (VIT) during the same period. All 57 patients received the same number of injections. The effectiveness of VIT was assessed by means of re-sting, which was performed yearly. Serum specific immunoglobulin (Ig) E and IgG4 were also studied, RESULTS: All the cases tolerated all the stings. One control patient developed a mild systemic reaction after the first-year Vespula sting but tolerated subsequent re-stings. Both cases and controls reached significant changes in levels of IgE and IgG4 after VIT (P < .04 at minimum). The cases developed a response as expected, although this was less intense than in the control group. In the Polistes control subgroup, sIgE to Polistes decreased to under baseline levels, after a marked initial increase; this decrease was not observed in the Vespula subgroup. CONCLUSION: An alternating VIT strategy is appropriate and provides protection to patients sensitized to Vespula and Polistes.

Allergenic profile of nasal polyposis.

BACKGROUND: Nasal polyposis is highly prevalent in the general population. Its exact origin is unknown, although several factors are involved in the etiology and development of this condition. Clinical patterns, a history of atopy, environmental exposure, eosinophil-mediated inflammation, the presence of inflammatory mediators, and sensitization to some allergens indicate that nasal polyposis is associated with allergic phenomena. The aim of this study was to identify the association between nasal polyposis and allergic factors by examining hypersensitivity reactions to common allergens and environmental exposure that could lead to the development of atopy. METHODS: We conducted a comparative study of 190 patients with nasal polyposis and 190 healthy individuals. The study included clinical and epidemiological variables, environmental exposure factors, and an allergology workup using skin prick tests with 18 inhaled allergens. RESULTS: A total of 121 patients (63.7%) of the 190 were male; 62.1% had a family history of allergy. The incidence of asthma was 48.9% among the patients and only 2.3% among the controls (P < .001). The factor most frequently involved in the patients' symptoms was weather changes (67.4%). Skin prick tests were positive in 63.2% of the patients and 31.1% of the controls. The allergens that most frequently elicited a reaction from the patients in the prick tests were Dermatophagoides pteronyssinus (27.7%), Dermatophagoides farinae (21.3%), and Olea europaea (21.1%). The difference between these results and those of the controls was statistically significant. CONCLUSIONS: Patients with nasal polyposis are sensitive to the most common allergens in our environment and exhibit a clear-cut correlation with other allergic factors, as confirmed by personal and family histories, the presence of chronic rhinitis, and the results of in vivo tests.

Fungal sensitization in nasal polyposis.

BACKGROUND: There are indications that polyposis is somehow related to allergic phenomena. Fungal sensitization in substantial proportions of patients has been cited as a trigger of inflammatory mechanisms involving either an immunoglobulin (Ig) E-mediated reaction to fungal colonization or fungal invasion of tissues. OBJECTIVE: To confirm whether fungi were involved in the development of polyposis by examining sensitivity to fungal allergens and potential local contamination by fungal species. METHODS: We performed a study of 190 patients with polyposis and 190 controls in which we compared the results of skin prick tests to 12 fungi, total IgE, and specific IgE to 15 fungal extracts and nasal fungal cultures. RESULTS: The specific fungi eliciting a reaction from the largest proportion of patients in the skin prick tests were Fusarium solani (13.7%), Penicillium frequentans (12.6%), Trichophyton mentagrophytes (11.1%), and Candida albicans (8.4%) (P < .001). The proportion of individuals that tested positive for fungal-specific IgE was 22.4% (38/170) for patients and 10.1% (19/189) for controls (P = .04). The respective proportions of positive responses to fungal cultures were 58.7% and 60%. Furthermore, no significant differences between patients and controls were found for the results of in vitro tests with cultured fungal allergens. CONCLUSIONS: Although the patients with polyposis exhibited sensitization to fungal allergens, we found that nasal colonization by fungi was similar in patients and the general population. We were also unable to find a correlation between a positive response to the cultures and the presence of fungal allergen-specific IgE. It therefore seems that nasal colonization by fungi does not induce fungal sensitization.

Predicting patients at high-risk of systemic reactions to cluster allergen immunotherapy: a pilot prospective observational study.

OBJECTIVE: The purpose of this study was to identify factors associated with increased risk of adverse systemic reactions to cluster allergen immunotherapy and to create a preliminary predictive clinical model. METHODS: In a prospective observational study, the tolerance of 611 patients with seasonal respiratory diseases who were receiving cluster immunotherapy was monitored and all systemic reactions were recorded. Associations between potential prognostic factors (sex, age, respiratory disease, severity, duration of disease, previous immunotherapy, nonseasonal symptoms, skin prick test, total immunoglobulin (Ig) E, specific IgE, treatment schedule, allergenic composition, batch, date of treatment, habitat, place of residence) and systemic reactions were estimated. Multivariate stepwise logistic regression analysis was used to build a predictive clinical model and estimate the probability of systemic reactions to cluster immunotherapy. RESULTS: Sixty-five patients (10.6%) suffered systemic reactions. Only 7 independent risk factors were retained in the final model: age over 14 years (odds ratio [OR], 2.6), previous immunotherapy (OR, 0.3), skin prick test positive to Chenopodium album (white goosefoot) (OR, 3.0), elevated specific IgE to grass pollen (OR, 2.3), elevated specific IgE to olive pollen (OR, 4.1), olive pollen 100% composition (OR, 2.6) and treatment schedule (OR, 1, 1.6 or 7.1, depending on the cluster immunotherapy schedule). CONCLUSIONS: This predictive model, derived from simple clinical variables, has excellent ability to assess individual risk of suffering systemic reactions to cluster allergen immunotherapy. Detecting high-risk patients can help clinicians to prevent and eliminate many severe adverse reactions to cluster immunotherapy.

Efficacy and quality of life with once-daily sublingual immunotherapy with grasses plus olive pollen extract without updosing.

OBJECTIVE: The purpose of this randomized, double-blind, placebo-controlled study was to evaluate the clinical efficacy and tolerance of once-daily sublingual immunotherapy without updosing. Reduction in symptoms and medication use was the primary endpoint. METHODS: One hundred five patients with rhinitis and/or asthma due to grass and olive sensitization were randomized to be treated with placebo or active sublingual immunotherapy with the SLITone grass mix plus olive pollen extract for 6 months before the 2005 pollen season. Patients recorded symptoms and medication intake for 8 weeks during the pollen seasons in 2004 (n=37) and 2005 (n=85). RESULTS: Allergic symptoms were significantly decreased in the active immunotherapy group (P = .004) but not in the placebo group. There were no differences in scores between groups during the 2005 pollen season. Subjective assessments on a visual analog scale and a quality-of-life questionnaire indicated an improvement in actively treated patients with significant differences in both symptoms and medication use (P = .006). The rate of systemic adverse reactions was comparable in the 2 groups. No anaphylactic or severe adverse reactions were reported. Local adverse reactions, which were more common in the active immunotherapy group, were mostly immediate, were limited to the lips and mouth, and did not require treatment. CONCLUSION: Once-daily sublingual immunotherapy without updosing was well tolerated. The actively treated patients showed a significant reduction in symptom and medication scores and an improvement in their quality of life although there were no significant differences between the groups probably due to the low allergen season in which the study was evaluated.

Tolerance of a cluster schedule on the treatment of seasonal allergic respiratory disease with pollen extracts quantified in mass units.

In order to evaluate the tolerance of a cluster schedule on specific immunotherapy (SIT), 306 patients were included in a multicenter study. The patients were suffering from rhinoconjunctivitis with/without asthma, caused by sensitization to olive and/or grass pollen. SIT was administered subcutaneously according to a cluster schedule in which the maintenance dose is reached after four visits (3 weeks). The extracts were biologically standardized with major allergens quantified in mass units. Local reactions appeared in 7.2% of the patients and 1.3% of the doses. Systemic reactions (SR) were recorded in 1.2% of the doses administered to 9.5% of the patients. No anaphylactic shock was registered, and all the SR responded fully and rapidly to treatment. There was no difference in SR according to diagnosis or allergen extract used. The majority of SR occurred with the administration of vial of higher concentration (Vial 2: 7 SR (22%), Vial 3: 32 SR (78%), p < 0.05). Of the 32 SR recorded with Vial 3, 13 (41%) were immediate, with no existing association between dose administered and appearance of SR. However, of the 18 delayed SR (56%), 14 occurred after the administration of the first two doses of Vial 3 and four occurred after administration of the second two doses (78% vs 22%, p < 0.05). On the other hand, this regime realized an important saving in cost and time compared to the conventional schedule (1581 fewer doses and 2754 fewer visits were necessary to reach the optimal dose). Considering all these factors, the clinical profile of the proposed regime may be qualified as good. However, future studies are necessary in order to better adjust the schedule to avoid the delayed SR that occurred after the administration of the first two doses of Vial 3.