Sensitivity and specificity of skin tests in the diagnosis of clarithromycin allergy Francesca Mori, MD*; Simona Barni, MD*; Neri Pucci, MD*; Elisabetta Rossi, MD*; Chiara Azzari, MD, PhD*; Maurizio de Martino, MD, PhD*; and Elio Novembre, MD, PhD* Background: Clarithromycin is one of the most frequently prescribed oral macrolidic antibiotics in the pediatric population. Suspected adverse reactions to clarithromycin have been frequently described by parents of children examined in pediatric allergy units, but there is a lack of reliable methods available in detecting the presence of specific IgE antibodies. Objective: To investigate the prevalence of a clarithromycin allergy in children seen in a pediatric allergy unit using standardized skin tests and oral provocation tests (OPTs). Methods: Sixty-four children were referred with a history of a clarithromycin-associated adverse drug reaction. All these children underwent skin tests and OPTs. The nonirritating intradermal skin test concentration for clarithromycin was determined in a control group of 18 children who had tolerated clarithromycin in the previous month. Results: The threshold nonirritating intradermal concentration was established at the 10:2 dilution (0.5 mg/mL). Nine of the 64 children had an immediately positive intradermal response to the 10:2 dilution and only 1 child to the 10:3 dilution (0.05 mg/mL). None had positive skin prick test results or delayed skin responses to intradermal tests. Four of 64 children (6%) with previously described adverse reactions due to clarithromycin intake had a positive OPT reaction. When we correlated the intradermal skin test results to the OPT results, intradermal test sensitivity and specificity were 75% and 90%, respectively. Conclusion: Intradermal tests seem to be useful in allergologic workup in children with suspected clarithromycin hypersen- sitivity and may help reduce the need for OPTs. Ann Allergy Asthma Immunol. 2010;104:417– 419. INTRODUCTION Adverse reactions to antibacterial agents are not uncommon in children, especially reactions to -lactam drugs because of their widespread use and antigenic properties. Allergies to macrolide antibiotics may also occur (0.4%–3.0% of treatments), 1 as this group of drugs represents an old and well-established class of antimicrobial agents, accounting for 10% to 15% of the world- wide oral antibiotic market. 2 In Italy, clarithromycin is the most frequently prescribed oral macrolidic antibiotic in the pediatric population. 3 It belongs to the 14-membered macrolides category owing to the number of carbon atoms in the lactonic ring. In a study involving large numbers of children treated with clarithro- mycin, skin reaction rates were 2.8%. In other studies, cough, dyspnea, and bronchospasm immediately after clarithromycin intake 5 and nonimmediate reactions 6,7 were reported as well. The incidence of anaphylactic reactions provoked by clarithromycin is extremely low. 4 In general, adverse drug reactions may be both underdiag- nosed and overdiagnosed because of the lack of a specific allergologic workup. For an accurate diagnosis, a detailed history is of paramount importance. The European Network for Drug Allergy has recently updated standardized protocols for immediate and nonimmediate skin tests to -lactams, 8 but reliable methods available to diagnose clarithromycin allergy are still lacking. Skin tests have sometimes been used in diagnosing clarithromycin allergy, 7–9 but they have not been validated in terms of specificity and sensitivity. Because in vitro tests are less sensitive in drug hypersen- sitivity than in the inhalant allergy, 10 most authors still con- sider the oral provocation test (OPT) the gold standard for drug allergy diagnosis. 11 Suspected adverse reactions to cla- rithromycin were frequently described by parents of children examined in pediatric allergy units, and in many cases, an allergy evaluation was mandatory. Taking this fact into ac- count, we decided to investigate the prevalence of clarithro- mycin allergy using standardized skin tests and OPTs. METHODS Patients Between January 1, 2006, and June 30, 2008, 73 children were referred to our Allergy Unit of the A. Meyer Children’s Hospital, Florence, Italy, because of a history of reactions to clarithromycin. The patients all reported skin reactions (19% maculopapular eruptions, 62% urticarias, and 18% angioede- mas) during a 7-day treatment period. No children were reported to have anaphylactic reactions. According to their personal history, 49 children had late reactions (after 1 hour) and 20 had immediate reactions (within 1 hour) from the last antibiotic intake, most frequently after the second dose and Affiliations: * Paediatric Allergy and Immunology Unit, A. Meyer Chil- dren’s Hospital, Department of Paediatric, University of Florence, Florence, Italy. Disclosures: Authors have nothing to disclose. Funding Sources: This study was supported by the A. Meyer Children’s Hospital. © 2010 Published by Elsevier Inc. on behalf of American College of Allergy, Asthma & Immunology. doi:10.1016/j.anai.2010.03.010 VOLUME 104, MAY, 2010 417