Macrolide allergy: which tests are really useful?

Clarithromycin or azithromycin is not infrequently used as empiric treatment for upper respiratory tract infections. When patients develop a rash after several days of treatment, one is often faced with the diagnostic dilemma of whether this is a drug eruption or viral exanthema. Most times, if the temporal sequence is in keeping with a drug eruption, this patient will be peremptorily labelled with a macrolide allergy as the literature has little to guide us through a diagnostic pathway for macrolide allergies. Macrolides are characterised by a large lactone ring, which makes up the main structure, and can vary from 12 to 16 atoms. Although commonly thought of as a class of antibiotics, there are also non-antibiotic macrolides such as tacrolimus and sirolimus. Macrolide antibiotics are used for a wide variety of infections, but are particularly useful for upper respiratory tract infections. They are recommended by the British Thoracic Society as a first-line treatment together with amoxicillin for hospitalised patients with moderate to severe community acquired pneumonia, and are also an important component of the treatment regimen of Helicobacter pylori (HP) infection. It would be wrong to deny a patient the future use of such a useful drug when the aetiology of the rash might be infectious or due to another concurrent drug. However, unlike the case of beta-lactams, skin prick tests and intra-dermal tests for macrolide antibiotics have not been widely performed and validated, and some of the macrolide antibiotics are not available in injectable forms amenable for skin testing. Lymphocyte transformation tests and histamine release tests for the diagnosis of macrolide allergy have been reported, but give inconsistent results. In this issue of Allergologia et Immunopathologia, Seitz et al. examine the results of allergy testing in a large cohort of patients (n = 125) with suspected macrolide allergy and prove that 87.2% of patients in their series could have been unnecessarily labelled as allergic to macrolides and hence disallowed appropriate medication or an effective treatment regimen for HP eradication. So what lessons can we learn from this study? History and physical examination may not always yield the answer