Gene expression profiling of patients with latex and/or vegetable food allergy.

BACKGROUND: The prevalence of individuals allergic to latex, exhibiting cross-hypersensitivity with plant-derived food has been frequently reported as the so-called latex-fruit syndrome. Nonetheless, molecular mechanisms underlying allergy to latex and/or fruit are poorly understood. AIM: The aims of this study were to identify candidate genes that may be associated with the pathogenesis of allergy to latex and/or vegetable food, and to assess if similar molecular pathways are involved in both types of hypersensitivity. MATERIALS AND METHODS: DNA microarray analysis was performed to screen the molecular profiles of peripheral blood mononuclear cells isolated from patients with allergy to latex, to fruit, or with latex-fruit syndrome, and from control healthy subjects. RESULTS: Molecular profiling identified an overlapping dataset of genes commonly regulated in all the atopic patients enrolled in this study, suggesting that similar molecular mechanisms are involved in the pathogenesis of allergy to the fruit and/or latex. Several regulators of the innate and acquired immunity reported to polarize the immunological response towards a Th2-mediated immune response were overexpressed in the patients. Evidences suggested that the expression of T-regulatory cells might be defective in allergic patients, as a consequence of a dysregulation of some inflammatory cytokines. Finally, several transcription factors that may be responsible for the Th1/Th2 imbalance were modulated in allergic patients. CONCLUSIONS: This study identified relevant genes that may help to elucidate the molecular mechanisms underlying allergic disease. Knowledges of critical targets, along with transcription factors regulating gene activity may facilitate the development of new therapeutic options.

Allergic and non-allergic drug hypersensitivity reactions in children.

Adverse drug reactions (ADR) are an important medical problem. The aim of this study is to investigate the clinical characteristics of children with ADR and to assess the tolerability of alternative drugs in children (under 16 yrs of age) with a history of ADR. We studied 278 children (132 males and 146 females). Patients were studied by recording personal history and performing in vivo skin testing, in vitro laboratory tests and challenge tests. Patients who had experienced mild adverse reactions underwent challenge tests without any premedication; patients with a clinical history of moderate reactions, received a premedication with sodium chromolyn 30 min before the oral challenge; patients with a clinical history of severe reactions or undergoing parenteral challenges, were given an antihistamine 30 minutes before. A total of 660 adverse events were reported with 126 different drugs involved. Antimicrobial agents were the most involved drugs (51.7%). Non-steroidal anti-inflammatory drugs were involved in 22.7% of episodes. The most reported symptoms were cutaneous. Allergy testing was negative in 272 patients. A diagnosis of drug allergy was reported for 6 patients. A total of 669 challenge tests were performed. 639 were negative at first attempt while 22 were positive. Eight were repeated using a different premedication and resulted negative. Hypersensitivity drug reactions in children are mainly non-allergic. A premedication with sodium cromolyn or with oral H1-antihistamines may be useful in preventing ADR.

Cross-reactivity and tolerability of imipenem in patients with delayed-type, cell-mediated hypersensitivity to beta-lactams.

BACKGROUND: Administration of imipenem-cilastatin to patients with IgE-mediated hypersensitivity to beta-lactams has always been considered potentially harmful. Recent studies have demonstrated the tolerability of carbapenems (imipenem-cilastatin and meropenem) in patients with IgE-mediated hypersensitivity to beta-lactams; there are no studies on this topic regarding patients with cell-mediated allergy to beta-lactams. The aim of this study is to assess cross-reactivity and tolerability of imipenem in patients with cell-mediated allergy to beta-lactams. METHODS: From our database we selected 73 patients with cell-mediated allergy to beta-lactams, diagnosed by means of immediate-type skin tests, delayed reading intradermal tests, patch tests and detection of specific IgE. Patients with negative patch tests with imipenem-cilastatin underwent an intramuscular test dosing. RESULTS: Our patients had a total of 94 nonimmediate reactions to penicillins. All patients had positive patch tests and/or delayed reading intradermal tests for at least one of the penicillin reagent tested and negative immediate-type skin tests and specific IgE. Four patients out of 73 had a positive patch tests to at least one penicillin reagent and imipenem-cilastatin showing cross-reactivity. Sixty-four patients underwent the imipenem-cilastatin intramuscular test dosing and none of them had a clinical reaction. CONCLUSIONS: Our rate of cross-reactivity between imipenem-cilastatin and other beta-lactams was 5.5%. This result is different from previous findings and this may be explained by the fact that we investigated patients with cell-mediated allergy to beta-lactams. Patients with cell-mediated allergy to beta-lactams should undergo patch tests and a tolerance challenge test before treatment with imipenem-cilastatin.

Desensitization to co-trimoxazole in a patient with fixed drug eruption.

Although co-trimoxazole is a major cause of fixed drug eruption, there are no reports in the literature of desensitization protocols for co-trimoxazole in such patients. We present the case of an 85-year-old woman with a fixed drug eruption to co-trimoxazole. Since she needed co-trimoxazole therapy for treatment of infection of a prosthetic hip by Staphylococcus aureus, she underwent allergy testing with co-trimoxazole and its components sulfamethoxazole and trimethoprim. Allergy tests were all negative and a diagnosis of nonallergic hypersensitivity reaction to co-trimoxazole was made. Based on previous experience, we decided to attempt a desensitization protocol with co-trimoxazole. After 10 days, the patient could receive 800 mg of sulfamethoxazole and 160 mg of trimethoprim twice a day and no adverse reactions were observed. We suggest that desensitization protocols with co-trimoxazole be considered in patients with fixed drug eruption, especially when there are no alternative drugs.

Tolerability of aztreonam in patients with IgE-mediated hypersensitivity to beta-lactams.

Cross-reactivity between aztreonam and penicillins is poor, but clinical tolerance of aztreonam has been assessed, by means of tolerance challenge tests, only in a few groups of penicillin-allergic patients. The aim of this study is to evaluate the tolerability of aztreonam in a large group of beta-lactam-allergic patients. We studied all patients (greater than 14 years of age), with a clinical history of immediate reactions to any beta-lactam and with positive immediate-type skin tests and/or positive specific IgE to any of the studied beta-lactam; they were studied by means of: skin prick and intradermal tests with penicilloyl polylysine, minor determinant mixture, semisynthetic penicillins, cephalosporins, aztreonam and imipenem; detection of specific IgE to penicillin G, penicillin V, ampicillin, amoxicillin, cefaclor and ceftriaxone. Patients with negative immediate-type skin tests with aztreonam then underwent a graded intramuscular challenge. Forty-five patients (mean age 46.1 +/- 15.2 years), 27 females and 18 males, had positive skin tests and/or specific IgE to at least one of the studied beta-lactams. The most involved drugs were amoxicillin (23 cases), ampicillin (9 cases), penicillin G (8 cases) and other beta-lactams in the remaining cases. The most frequent reactions were anaphylaxis (27 cases) and urticaria (15 cases). All patients had negative intradermal tests with aztreonam and all patients tolerated the intramuscular graded challenge. Our data confirm the lack of cross-reactivity between beta-lactams and aztreonam. Immediate-type skin tests with aztreonam represent a simple and rapid diagnostic tool to establish tolerability in beta-lactam-allergic patients who urgently need this drug.

Sublingual-oral rush desensitization to mixed cow and sheep milk: a case report.

We attempted an oral rush desensitization with mixed cow and sheep milk in a 6-year-old boy who had had adverse reactions to cow and goat milks. Skin prick tests and specific immunoglobulin (Ig) E to cow, sheep and goat milks were positive. The double-blind, placebo-controlled food challenge with cow milk was positive too. He underwent a 12-day sublingual-oral desensitization treatment with mixed cow and sheep milk. Specific IgE and IgG4 were measured. Open oral challenges with cow milk, sheep milk and sheep cheeses were also performed after the desensitization. At the end of the desensitizing treatment our patient could tolerate 120 mL of mixed milk. Specific IgE levels did not vary, whereas an increase of specific IgG4 concentrations was observed. Open oral challenges with cow and sheep milks and sheep cheeses were negative. Oral rush desensitization may represent an alternative approach to the treatment of food allergy in children.