Importance of repeat testing in the diagnosis of penicillin allergy.
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Biomedical subjects
Publications and source records attributed to V Matheu.
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In subjects not developing allergy, inhalation of nonpathogenic protein antigens causes no harm and is associated with tolerance induction. Repeated exposure to aerosolized ovalbumin (OVA) likewise does not evoke airway inflammation and induces inhalation tolerance in experimental animals. The present study explored the role of the inhibitory T-cell receptor CTLA-4, in preventing inflammation and in establishing inhalation tolerance in response to a protein antigen. Naive BALB/c mice were injected intraperitoneally with anti-CTLA-4 monoclonal antibody or control immunoglobulin G (IgG) and exposed daily to aerosolized saline or OVA over 10 or 20 consecutive days. OVA-specific IgE levels and the inflammatory response in airway tissues were assessed 2 days after last exposure. The OVA-specific IgE response was also evaluated in mice subjected to a subsequent immunogenic OVA challenge 18 days after last aerosol exposure. Additional mice were made tolerant by 10 days of OVA aerosol exposure and were then subjected to an immunogenic OVA challenge combined with CTLA-4 blockade or control IgG treatment. Repeated inhalation of aerosolized OVA alone did not cause a pulmonary inflammatory response. In contrast, 10 days of OVA exposure combined with blockade of CTLA-4 led to development of eosinophilic lung infiltrates, BAL fluid eosinophilia, goblet cell hyperplasia and increased OVA-specific IgE. By 20 days of OVA exposure and blockade of CTLA-4, the inflammatory response remained. Mice exposed to aerosolized OVA for 10 days exhibited greatly reduced OVA-specific IgE responses to subsequent immunogenic OVA challenge. Blockade of CTLA-4 during the period of OVA aerosol exposure did not prevent this suppression of the OVA-specific IgE response. Neither did blockade of CTLA-4 during immunogenic OVA challenge alter the allergen-specific IgE response. Our results indicate that in vivo blockade of CTLA-4 modulates the initial immune response to a protein antigen allowing the development of allergen-induced airway inflammation in naive mice. However, this initial exaggerated immune response is followed by the induction of inhalation tolerance, demonstrating that CTLA-4 signalling is not decisive in this process. Our findings also show that once inhalation tolerance is established it may not be disrupted by blockade of CTLA-4.
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BACKGROUND: Diagnostic methods for the study of allergic reactions to Anisakis simplex (A.s.) based on whole-body extracts of the larva are clearly insufficient. OBJECTIVES: To study the allergenicity of the proteins secreted by the parasite. Comparison with somatic antigens and determination of their clinical importance in allergic patients were also addressed. METHODS: An excretory/secretory (E/S) extract was produced by culturing third-stage A.s. larvae. It was used to perform immediate skin tests and to determine specific IgE in 10 patients diagnosed with allergy to A.s. Both tests were compared with the results obtained with the whole-body extract (somatic (S)). The molecular weight (MW) of their allergens was determined by immunoblotting, and a single-blind placebo-controlled oral challenge with E/S proteins was performed. Finally, allergens' resistance to gastric pepsin and acid pH was explored. RESULTS: A.s. larvae secreted allergens more potent than those present in the S extract. The skin prick test wheal area produced by E/S molecules and the absorbance obtained in the determination of specific IgE with these allergens (ELISA) were 5.8 times bigger than those obtained with S extract. MW allergens of 72 and 56 kDa in E/S extracts and those of 56, 48 and 43 kDa in S extract were recognized by more than 50% of the patients. Partial cross-reactivity between them was revealed by immunoblotting inhibition studies. Oral challenge with E/S extract (up to 479 microg) was negative in all the patients. Treatment of E/S proteins with gastric pepsin inhibited the binding of the E/S allergens for specific IgE. The acid pH did not affect the overall binding of IgE to E/S extract. It decreased by 15.23% and 19.96% at pH 4 and 2, but the difference was not statistically significant. CONCLUSION: A.s. secretes allergens more potent than somatic antigens and should be used in the diagnostic procedures. These allergens are inactivated by the pepsin, which supports the theory that live larva is necessary to induce an allergic reaction in most of the patients.
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BACKGROUND: Anisakis simplex (A.s.) allergy is an emerging disease. The third-stage larvae of this nematode are a source of hidden allergens in fish. There are no clear guidelines concerning dietary restrictions for patients with serum-specific IgE to this parasite. OBJECTIVE: To follow up the clinical data and immunological parameters of patients sensitized to A.s. during 6 to 23 months. METHODS: The clinical symptoms and serologic status of 17 patients with specific IgE and positive skin prick test results to A.s. were studied prospectively. Six of these had anaphylaxis (ANA) attributed to A.s. and 11 patients experienced concomitant chronic urticaria (CU). All patients were advised not to eat fish for 6 months. RESULTS: Four patients from the ANA group excluded fish, and ANA did not recur. Two other patients with ANA refused to exclude fish; one remained free of symptoms and the other experienced several urticarial episodes. During this 6-month period total IgE levels decreased in all six ANA patients; specific IgE for A.s. decreased in four patients and increased in two. Two patients from the CU group did not exclude fish, and symptoms persisted in these two patients. Clinical improvement was observed in 78% of the patients with CU who excluded fish. Total and specific IgE levels decreased in all the patients with CU. CONCLUSIONS: Because ANA symptoms are very severe, patients should always be advised to exclude fish until specific food allergens are identified. However, in patients with CU and specific IgE to A.s., only the clinical response to fish ingestion will determine the need for strict fish avoidance.
We report a case of a 5-year-old child who suffered an oral allergy syndrome and lip angiedema after eating grapes. We obtained a positive prick test with commercial grape extract and a positive prick-by-prick test with pulp and peel of fresh white grape (Moscatel variety) and pulp and peel of blue grape. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis followed by immunoblotting revealed specific immunoglobulin E (IgE) antibodies in the patient's serum against a 94,000 molecular-weight antigenic band. Lip open challenge was positive.
We report a case of a patient who suffered generalized urticaria, chest tightness, wheezing, nausea, vomiting, hypotension, and loss of consciousness. Two hours earlier she had taken Eulitop Retard following lunch. She had tolerated all the implicated food after the reaction. Allergy evaluation revealed intense positive responses to intradermal tests with bezafibrate active component and Eulitop Retard (skin tests in control subjects were negative). Specific IgE tests (RAST) to Eulitop Retard were negative. An IgE mechanism is suggested to be responsible for this adverse reaction on the basis of the positive skin tets. The delayed onset (two hours) of this anaphylactic shock is unusual. Although infrequent, it may be caused by the specific pharmacokinetic characteristics of this drug, which is a slow releasing agent, mainly absorbed in the gut. The drug was taken just after lunch, and this concomitant food ingestion could also have produced a delay in gastric drainage and a retarded drug absorption. An IgE-mediated accelerated type reaction could also explain this delay. Apparently the patient reacted after the first contact to the drug, and the absence of a sensitization period is not usual in this type of immune reponse. Finally, we recommend the performance of prick and intradermal skin tests prior to any systemic challenge when allergic reactions to fibric acid derivatives are suspected.
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BACKGROUND: Legumes are one of the most common foods causing allergic reactions in children and adults. Cross-reacting antibodies are frequently demonstrated in this family but the real clinical cross-reactivity is uncommon. OBJECTIVE: To report a case of lupine-induced anaphylaxis and to elucidate in vivo and in vitro cross-reactivity with some legumes. METHODS: Skin prick test (SPT) with some legumes were performed. Cap-IgE, ELISA-IgE, and immunoblotting were carried out. Open oral challenges with some legumes were performed. Cross-reactivity was studied by ELISA and immunoblotting inhibition. RESULTS: The results demonstrated type-I hypersensitivity reactions with lupine and some other legumes. Cap-IgE with peanut was positive but the SPT and ELISA-IgE were negative and the patient tolerated a peanut challenge. ELISA inhibition revealed a partial inhibition (62%) using lupine as the solid phase. Partial inhibition was demonstrated by immunoblotting inhibition. Open oral challenge with peanut and green bean were negative but positive with pea. CONCLUSION: We present a lupine sensitized patient with positive SPT and in vitro cross-reactivity with other legumes. Clinical cross-reactivity progressively developed over a 5-year period. Discrepancies were found between the clinical aspect and in vitro study of peanut allergy. Factors determining the wide variability in cross-reactivity among individuals are still obscure.
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The case is presented of a child who developed rhinoconjunctivitis, angioedema and asthma by sensitization to Sapelli wood, which was used in his father's carpentry. Positive skin-prick test, high levels of specific immunoglobulin E by ELISA and a positive conjunctival challenge test suggest a type I hypersensitivity mechanism to this wood. This is the first case report of sensitization to Sapelli wood and it confirms that occupational allergen exposure as Sapelli wood may also cause sensitization in a child.
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BACKGROUND: Anisakis simplex, a fish parasite, causes allergic urticaria, angioedema and anaphylactic shock through an IgE-mediated hypersensitivity mechanism. Consensus on the dietary recommendations that should be given to allergic patients is lacking. Our objective was to evaluate the usefulness of different types of diets in preventing further reactions in patients allergic to A. simplex. METHODS: Twenty-eight adult patients, who had suffered an allergic episode caused by A. simplex were asked to follow one of the following three diets for a mean period of 13.16 months: a fish-free diet (diet 1; n = 19), a diet including fish frozen for more than 48 hours (diet 2; n = 9) and a diet with fresh fish (diet 3; n = 12). In all patients raw fish was excluded. Relapse rates and changes in total serum IgE and specific IgE to A. simplex were studied during the follow up. RESULTS: During the 13-month follow-up none of the patients developed anaphylaxis. Urticaria symptoms were present in 5.8 %, 11.1 % (n.s) and 33.3 % (p = 0.016) of patients following diets 1, 2 and 3, respectively. Total IgE decreased by 64 % (p < 0.05), 48 % (p < 0.05) and 39.4 % (p < 0.05), respectively. Specific IgE to A. simplex decreased by 50.7 % (p < 0.05), 54.1 % (p < 0.05) and 23.6 % (p < 0.05) after diets 1, 2 and 3, respectively. No statistically significant differences were found among the groups in variations in total and specific IgE. CONCLUSIONS: Patients allergic to A. simplex can eat fish that has been frozen at -20 C for 48 hours without risk of a severe allergic reaction. Long term decreases in specific and total IgE may not be good markers of eventual contact with A. simplex.
Indapamide is a nontiazidic sulfonamide diuretic which has not been previously reported as a cause of fixed drug eruption. We describe a patient who experienced several episodes of fixed drug eruption during treatment with indapamide. The diagnosis was confirmed by positive controlled oral challenge test. The possible existence of cross-reactivity with other sulfonamide derivatives was investigated by controlled oral challenge test with sulfamethoxazole, sulfadiazine and furosemide, with the tests with sulfamethoxazole and sulfadiazine resulting positive.