Fixed Drug Eruption Induced by Pristinamycin and Amoxicillin–Clavulanic Acid: An Unusual Case of Cosensitization

To the Editor: Fixed drug eruption (FDE) is a cutaneous reaction triggered by several drugs.1 Although cross-reactivity between drugs with structural similarity has been reported, cosensitization between chemically unrelated agents was rarely described.2 We report the first case of FDE caused by pristinamycin and amoxicillin–clavulanic acid (AMC), confirmed by oral provocation tests (OPTs). A 75-year-old man, with a history of diabetes and hypertension, presented 2 itchy plaques in the left upper limb. Physical examination revealed 2 well-circumscribed erythematous plaques, in the external face of the arm (6-cm diameter) and in the palmar surface of the wrist (3-cm diameter; Fig. 1). He reported having taken 1000 mg of pristinamycin (Pyostacine), 6 hours before the onset of lesions. Two days later, the eruption resolved, after drug discontinuation, leaving hyperpigmentation. Examination of a skin biopsy specimen of the affected skin revealed lymphocyte exocytosis and several apoptotic keratinocytes in the epidermis, with a perivascular infiltrate of melanophages and eosinophils in the upper dermis. He experienced a similar event, 2 years before and 2 days after taking AMC (Augmentin, a cumulative dose of 3 g) with the same evolution. Patch tests to both drugs (10% in petrolatum) were successively performed on the residual lesions and were negative on days 2 and 4. After consent, he underwent an OPT to pristinamycin with gradual doses (5%, 15%, 30%, 50%) every hour until reaching a dose of 1000 mg. Four hours later, a flare-up at the same sites was observed. An OPT to AMC was performed according to the same protocol and gave positive results 3 hours after a cumulative dose of 2000 mg. Finally, we have tested colloidal silica and magnesium stearate, which are excipients involved in both drug formulations. They were negative.Figure 1: Erythematous plaques, 6 hours after the first drug intake of pristinamycin, in the external face of the arm (A, 6-cm diameter) and in the palmar surface of the wrist (B, 3-cm diameter).According to the Naranjo Causality Scale, the causality of both drugs was found to be probable. In literature, only 3 cases of FDE to pristinamycin were described, without confirmation by OPTs.2 β-Lactams are more likely to induce FDE, but only 2 cases induced by AMC have been reported.1 Because OPTs to excipients were negative, the event exhibited by our patient is likely to be considered as cosensitization to chemically unrelated active substances. The incidence of cosensitization in FDE is controversial; some suggest that it has been rarely described; for others, this was underdiagnosed.3 Few cases of FDE to unrelated drugs were described among antibiotics2 and anticonvulsants and between different classes.4 Pathogenesis seems to be triggered by nonspecific components of unrelated drugs activating resident memory T cells with release of cytokines by mast cells leading to a local inflammation.3 It can be also explained by the concept of immunocompromised district, sectorial immune dysregulation, and the tendency to develop FDE at the damaged skin site.5 Patch tests were falsely negative in our patient. Thus, an OPT remains the criterion standard to define the causative drug and alternatives.2 Cross-reactivity among β-lactams in FDE is rare1 and can be assessed by OPTs. However, our patient refused to complete the follow-up. Through this case, clinicians should be aware of such phenomenon that could be induced by chemically unrelated drugs. Helmi Ammar, MD Department of Pharmacology EPS Fattouma Bourguiba, Faculty of Medicine University of Monastir, Tunisia [email protected]Haifa Ben Romdhane, MDNajeh Ben Fadhel, MDZohra Chadli, MDNaceur A. Boughattas, PhDNadia Ben Fredj, MDKarim Aouam, PhD Department of Pharmacology EPS Fattouma Bourguiba, Faculty of Medicine University of Monastir, Tunisia

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