Depot leuprorelin acetate-induced granulomas manifested as persistent suppurative nodules.

) is a synthetic agonist analogue of gonadotrophin-releasing hormone (Gn-RH or luteinizing hormone-releasing hormone), administered as intramuscular or subcutaneous injections, and indicated for the treatment of advanced prostate cancer. In the last decade, sustained release parenteral depot formulations have been developed, by entrapping the hydrophilic leuprorelin in biodegradable highly lipophi-lic synthetic polymer microspheres. Depending on the type of polymer being used, the peptide drug is released from these depot formulations at different constant rates. Polylactic and glycolic acids (PLGA) are used for a one-month depot injections, and polylactic acid (PLA) for depot injections longer than 2 months. Cutaneous adverse events to leuprorelin acetate are rare, but several cases of local reactions at the injection sites have been reported in urology or paediatric journals (1–5). These reactions have been described as erythematous ma-cules, infiltrated plaques, subcutaneous nodules and sterile abscesses. A possible role of either leuprorelin acetate itself or lipophilic synthetic polymer used in depot injections has been postulated as responsible for such reactions (6). A 78-year-old man was referred to our department for evaluation of a persistent inflammatory suppurative subcutaneous nodule on his right arm. Past medical history disclosed a familial protein C deficiency (treated with acenocoumarol and without any vascular complication) and advanced prostate cancer diagnosed in 1988. During the last months, the patient was receiving injections with 3-month depot formulation of leuprorelin acetate. Since he was receiving treatment with oral anticoagulants, the injections were administered subcutaneously instead of intra-muscularly (the recommended route). Four months before consultation, the patient noticed a painful erythematous subcutaneous papule-nodule developing at the injection site of the third dose of leuprorelin acetate. The lesion had appeared a few days after the injection, and had enlarged progressively, developing a central ulcer. Treatment with oral antibiotics (amoxicillin/clavulanic acid) was prescribed without any clinical improvement. Physical examination disclosed an apparently healthy man presenting a fistulated subcutaneous nodule, 3 cm in diameter, on the lateral aspect of his right arm. It was a painful lesion that drained a dense serous material. No fever, malaise, regional enlarged lymph nodes or hepatosplenomegaly were noted. Several bacteriological, mycobacteriological and fungal cultures from swabs obtained from the exudate yielded negative results. Treatment with oral tetracycline and clarithromycin, as well as topical cures with mupirocin, was prescribed and the lesion resolved in 2 months. During the following months, the patient developed two additional similar lesions on the left buttock (Fig. 1) and on …