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Gaeta F.,Allergy Unit | Valluzzi R.L.,Allergy Unit | Alonzi C.,Allergy Unit | Maggioletti M.,Allergy Unit | And 2 more authors.
Journal of Allergy and Clinical Immunology | Year: 2015

Background Studies performed on samples larger than 100 subjects with a documented IgE-mediated hypersensitivity to penicillins have demonstrated a cross-reactivity rate of approximately 1% between penicillins and both imipenem and meropenem, whereas a single study found a cross-reactivity rate of 6.2% with aztreonam in 16 such subjects. Objective To assess the cross-reactivity and tolerability of aztreonam and 3 carbapenems (imipenem-cilastatin, meropenem, and ertapenem) in patients with documented IgE-mediated hypersensitivity to penicillins. Methods A total of 212 consecutive subjects with immediate reactions to penicillins and positive results on skin tests to at least 1 penicillin reagent underwent skin tests with aztreonam and carbapenems; subjects with negative results were challenged with escalating doses of aztreonam and carbapenems. Results All subjects displayed negative skin test results to both aztreonam and carbapenems; 211 accepted challenges and tolerated them. Challenges were not followed by full therapeutic courses. Conclusions These data indicate the tolerability of both aztreonam and carbapenems in penicillin-allergic subjects. In those who especially require these alternative β-lactams, however, we recommend pretreatment skin tests, both because rare cases of cross-reactivity have been reported and because negative results indicate tolerability. © 2014 American Academy of Allergy, Asthma & Immunology.


Romano A.,Allergy Unit | Gaeta F.,Allergy Unit | Valluzzi R.L.,Allergy Unit | Caruso C.,Allergy Unit | And 2 more authors.
Journal of Allergy and Clinical Immunology | Year: 2010

Background: There have been few studies regarding the cross-reactivity and tolerability of penicillins, aztreonam, and carbapenems in large samples of subjects with cephalosporin allergy. Objective: We sought to evaluate the possibility of using penicillins, monobactams, and carbapenems in subjects with cephalosporin allergy who especially require them. Methods: We conducted a prospective study of 98 consecutive subjects who had 106 immediate reactions (mostly anaphylactic shock) to cephalosporins and had positive skin test results for these drugs. To assess the cross-reactivity with penicillins, monobactams, and carbapenems and the tolerability of such alternative β-lactams, all subjects underwent skin tests and serum-specific IgE assays with penicillin reagents, as well as skin tests with aztreonam, imipenem/cilastatin, and meropenem. Subjects with negative test results were challenged with meropenem, imipenem/cilastatin, aztreonam, and amoxicillin. Results: Positive allergologic test results to penicillins were displayed by 25 (25.5%) subjects, including 1 with positive results to all reagents tested and another with a positive result to aztreonam. Another subject had positive results to both ceftazidime and aztreonam. A reaction to cephalosporins with side-chain structures similar or identical to those of penicillins was a significant predictor of cross-reactivity because of an increased 3-fold risk of positive results on allergologic tests with penicillin determinants. Challenges with alternative β-lactams were tolerated, with the exception of 1 urticarial reaction to imipenem/cilastatin. Conclusions: About 25% of subjects with cephalosporin allergy had positive results to penicillins, 3.1% to aztreonam, 2% to imipenem/cilastatin, and 1% to meropenem. In those who especially require alternative β-lactams, pretreatment skin tests are advisable because negative results indicate tolerability of the β-lactam concerned. © 2010 American Academy of Allergy, Asthma & Immunology.


Chiriac A.M.,Allergy Unit | Demoly P.,Allergy Unit | Demoly P.,Montpellier University
Current Opinion in Allergy and Clinical Immunology | Year: 2013

PURPOSE OF REVIEW: The multiple drug hypersensitivity syndrome (MDH) is a distinct clinical entity, different from cross-reactivity and flare-up reactions. Following its initial description in 1989 by Sullivan et al., several authors have addressed the issues surrounding this peculiar form of drug hypersensitivity. Whether this syndrome is single or can be further classified in several entities is still a matter of debate. RECENT FINDINGS: Case reports, case series or studies involving large populations on MDH are few. The use of this term in the literature is heterogeneous, and the definitions variable. Given the major advances in the study of drug hypersensitivities in general, and ongoing research regarding severe cutaneous adverse reactions in particular, careful study of the subgroup of patients with demonstrated immunological basis of MDH has enabled the generation of possible pathogenetic hypotheses. Together with the studies (despite their limitations) to estimate the prevalence of this syndrome in adult and paediatric patients these emerging data need confirmation through larger studies with well defined populations. SUMMARY: Bringing together the experience of groups involved in the field of drug allergy should help to move knowledge regarding this peculiar form of drug hypersensitivity forward. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Romano A.,Allergy Unit | Torres M.J.,Carlos Haya Hospital | Castells M.,Harvard University | Sanz M.L.,University of Pamplona | Blanca M.,Carlos Haya Hospital
Journal of Allergy and Clinical Immunology | Year: 2011

The present article addresses the advances in the diagnosis and management of drug hypersensitivity reactions that were discussed in the 4th Drug Hypersensitivity Meeting held in Rome in April 2010. Such reactions can be classified as immediate or nonimmediate according to the time interval between the last drug administration and onset. Immediate reactions occur within 1 hour, and nonimmediate reactions occur after more than 1 hour. Clinical and immunologic studies suggest that type-I (IgE-mediated) and type-IV (T cell-mediated) pathogenic mechanisms are involved in most immediate and nonimmediate reactions, respectively. In diagnosis prick, patch, and intradermal tests are the most readily available tools. Determination of specific IgE levels is still the most common in vitro method for diagnosing immediate reactions. New diagnostic tools, such as the basophil activation test, the lymphocyte activation test, and enzyme-linked immunospot assays for analysis of the frequency of antigen-specific, cytokine-producing cells, have been developed for evaluating either immediate or nonimmediate reactions. The sensitivity of allergologic tests is not 100%; therefore in selected cases provocation tests are necessary. In the diagnosis of nonallergic hypersensitivity reactions to nonsteroidal anti-inflammatory drugs, the provocation test with the suspected drug still represents the "gold standard." However, there was no consensus regarding the use of this test in subjects with histories of hypersensitivity reactions to 1 (single reactors) or more (multiple reactors) nonsteroidal anti-inflammatory drugs. With regard to management, desensitization allows patients to be treated with irreplaceable chemotherapy agents, such as taxanes, platinum salts, and mAbs, to which they have presented hypersensitivity reactions. Desensitization also permits the use of aspirin in aspirin-sensitive patients undergoing revascularization and in subjects with aspirin-exacerbated respiratory disease. © 2011 American Academy of Allergy, Asthma & Immunology.


Romano A.,Allergy Unit | Romano A.,Instituto Of Ricovero E Cura A Carattere Scientifico Oasi Maria Ss | Caubet J.-C.,University of Geneva
Journal of Allergy and Clinical Immunology: In Practice | Year: 2014

Hypersensitivity reactions to β-lactam and non-β-lactam antibiotics are commonly reported. They can be classified as immediate or nonimmediate according to the time interval between the last drug administration and their onset. Immediate reactions occur within 1 hour after the last drug administration and are manifested clinically by urticaria and/or angioedema, rhinitis, bronchospasm, and anaphylactic shock; they may be mediated by specific IgE-antibodies. Nonimmediate reactions occur more than 1 hour after the last drug administration. The most common manifestations are maculopapular exanthems; specific T lymphocytes may be involved in this type of manifestation. The diagnostic evaluation of hypersensitivity reactions to antibiotics is usually complex. The patient's history is fundamental; the allergic examination is based mainly on in vivo tests selected on the basis of the clinical features and the type of reaction, immediate or nonimmediate. Immediate reactions can be assessed by immediate-reading skin tests and, in selected cases, drug provocation tests. Nonimmediate reactions can be assessed by delayed-reading skin tests, patch tests, and drug provocation tests. However, skin tests have been well validated mainly for β-lactams but less for other classes of antibiotics. © 2014 American Academy of Allergy, Asthma & Immunology.


Romano A.,Allergy Unit | Gaeta F.,Allergy Unit | Valluzzi R.L.,Allergy Unit | Maggioletti M.,Allergy Unit | And 3 more authors.
Journal of Allergy and Clinical Immunology | Year: 2015

Background Studies regarding the cross-reactivity and tolerability of alternative cephalosporins in large samples of subjects with an IgE-mediated hypersensitivity to cephalosporins are lacking. Objective We sought to evaluate the possibility of using alternative cephalosporins in subjects with cephalosporin allergy who especially require them. Methods One hundred two subjects with immediate reactions to cephalosporins and positive skin test results to the responsible drugs underwent serum specific IgE assays with cefaclor and skin tests with different cephalosporins. Subjects were classified in 4 groups: group A, positive responses to 1 or more of ceftriaxone, cefuroxime, cefotaxime, cefepime, cefodizime, and ceftazidime; group B, positive responses to aminocephalosporins; group C, positive responses to cephalosporins other than those belonging to the aforementioned groups; and group D, positive responses to cephalosporins belonging to 2 different groups. Group A subjects underwent challenges with cefaclor, cefazolin, and ceftibuten; group B participants underwent challenges with cefuroxime axetil, ceftriaxone, cefazolin, and ceftibuten; and group C and D subjects underwent challenges with some of the aforementioned cephalosporins selected on the basis of their patterns of positivity. Results There were 73 subjects in group A, 13 in group B, 7 in group C, and 9 in group D. Challenges with alternative cephalosporins (ceftibuten in 101, cefazolin in 96, cefaclor in 82, and cefuroxime axetil and ceftriaxone in 22 subjects) were well tolerated. Conclusions Cephalosporin hypersensitivity does not seem to be a class hypersensitivity. Subjects with cephalosporin allergy who especially require alternative cephalosporins might be treated with compounds that have side-chain determinants different from those of the responsible cephalosporins and have negative pretreatment skin test responses. © 2015 American Academy of Allergy, Asthma & Immunology.


Bonadonna P.,Allergy Unit | Lombardo C.,Allergy Unit
Immunology and Allergy Clinics of North America | Year: 2014

Drugs are known triggers of anaphylaxis in patients with mastocytosis even to the association between drug anaphylaxis and mastocytosis does not appear frequently appear. Nevertheless, mast cell disorders might be ruled out in cases of severe systemic reactions. Careful examination of the skin should accompany measurement of basal serum tryptase levels. The data published about drug anaphylaxis in patients with mast cell disorders are scarce, and it is not currently possible to provide clear recommendations. Most papers report cases of anaphylaxis during surgical procedures or radiocontrast media exposure. There are no specific recommendations to prevent severe reactions during such procedures, although some specialists suggest performing premedication with antihistamines and corticosteroids before anesthesia or radiocontrast media administration. © 2014 Elsevier Inc.


Bonadonna P.,Allergy Unit | Zanotti R.,Azienda Ospedaliera Universitaria Integrata of Verona | Muller U.,Bern Medical
Current Opinion in Allergy and Clinical Immunology | Year: 2010

Purpose of Review: To analyse the association of systemic allergic hymenoptera sting reactions with mastocytosis and elevated baseline serum tryptase and to discuss diagnosis and treatment in patients with both diseases. Recent findings: In recent large studies on patients with mastocytosis a much higher incidence of severe anaphylaxis following hymenoptera stings than in the normal population was documented. In patients with hymenoptera venom allergy, elevated baseline tryptase is strongly associated with severe anaphylaxis. Fatal sting reactions were reported in patients with mastocytosis, notably after stopping venom immunotherapy. During venom immunotherapy most patients with mastocytosis are protected from further sting reactions. Based on these observations immunotherapy for life is recommended for patients with mastocytosis and venom allergy. The incidence of allergic side-effects is increased in patients with mastocytosis and elevated baseline tryptase, especially in those allergic to Vespula venom. Premedication with antihistamines, or omalizumab in cases with recurrent severe side-effects, can be helpful. Summary: In all patients with anaphylaxis following hymenoptera stings, baseline serum tryptase should be determined. A value above 11.4 μg/l is often due to mastocytosis and indicates a high risk of very severe anaphylaxis following re-stings. Venom immunotherapy is safe and effective in this situation. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Savi E.,G Da Saliceto Hospital | Peveri S.,G Da Saliceto Hospital | Senna G.,Allergy Unit | Passalacqua G.,University of Genoa
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2013

Sublingual immunotherapy (SLIT) is often discontinued, and many patients do not renew the prescription. We evaluated the reasons for discontinuation and set up an educational/follow-up plan to improve the adherence. In a first phase, the adherence at 4 months was directly assessed. Based on those results, an action plan (education, frequent contacts, and strictly scheduled visits) was developed and tested in other patients. A group of matched patients did not undergo the follow-up plan (controls). In the first phase, involving 252 subjects, at 4 months, there were 30% dropouts, mainly due to side-effects. In the second phase, 149 patients underwent education/follow-up and 90 received no intervention. In the first group, discontinuations at 4 months were 5%, vs 18% in the controls (P = 0.01). After one year, 12% of patients were lost in the first group and 35% in the control group (P < 0.001). An adequate education and a strict follow-up can significantly reduce SLIT's discontinuations. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Brockow K.,TU Munich | Bonadonna P.,Allergy Unit
Current Opinion in Allergy and Clinical Immunology | Year: 2012

PURPOSE OF REVIEW: Mastocytosis in adults is associated with a history of anaphylaxis in 22-49%. In addition, monoclonal mast cell activation syndrome has been described presenting with anaphylaxis, especially in patients with hymenoptera venom anaphylaxis. Data on patients with drug hypersensitivity and mast cell diseases are scarce. RECENT FINDINGS: Drugs are elicitors of anaphylaxis in patients with mastocytosis. Drug hypersensitivity is only seldom described as associated with undetected mast cell disease in the literature. Together with a single-centred retrospective study, this data suggests that from all patients with drug-induced anaphylaxis, probably only a minority are associated with mast cell disease. Most of these cases in the literature are related to general anaesthesia. Thus, for patients with mastocytosis, general anaesthesia appears to be a procedure associated with risk of mast cell degranulation, and special precautions should be considered. SUMMARY: The association between immediate drug hypersensitivity and undetected mast cell diseases appears to be moderate, but nevertheless basal serum tryptase determination and examination for skin signs of mast cell disorders are recommended. An ongoing European multicenter study by the European Network for Drug Allergy will provide more information on this topic. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

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