Leuprolide acetate‐induced leukocytoclastic vasculitis

Leukocytoclastic vasculitis (LCV) is a distinct clinicopathological entity with cutaneous lesions from purpuric macules to necrotic ulcers, and the other systemic manifestations, such as fever, arthritis, gastrointestinal complaints, renal failure, etc. Although the exact cause cannot be established in more than half of the cases, various infections, connective tissue disorders, malignancies, cryoglobulinemia, and certain drugs are implicated (1). Leuprolide acetate is a synthetic analog of gonadotropin-releasing hormone that is used in the treatment of endo-metriosis, leiomyomas, and in the palliative treatment of advanced prostatic cancer. Adverse cutaneous reactions rarely occur with leuprolide acetate treatment (2). However, LCV associated with leuprolide acetate has not been reported until now. Here, a leuprolide acetate-induced LCV in a patient who had been treated for endometriosis by leuprolide acetate is presented. A 39-year-old woman was referred to the dermatology department with a 7-day history of progressively worsening purpuric eruption extending from the legs to the abdominal area in a symmetric pattern. The patient had been operated for ovarian endometriosis in June 2003 and monthly injections of leuprolide acetate (Lucrin Depot® Abbott Laboratories SA, Madrid, Spain) 3.75 mg had been administered afterwards. However, following the second administration of leuprolide, in a few numbers of scattered petechiae had been observed on the legs which regressed spontaneously in a week. As the injection of leuprolide acetate was not attributed as a trigger of this cutaneous reaction, the patient was allowed to receive the third injection which resulted in a recrudescence of her vasculitic rash. She denied receiving any other medication associated with the skin rashes. Skin examination revealed multiple ecchymotic rashes, 3-20 mm in size, predominantly on both thighs and gluteus and also scarcely on the abdomen and dorsa of the hands (Figure 1). There was no fever or other systemic complaints. Erythrocyte sedimentation rate was 35 mm/hr. Complete blood count, routine serum chemistry, and urine analyses were normal. The microbiologic investigation for infectious foci, viral serologic tests for hepatitis B and C viruses, and HIV were all negative. Serological tests for collagen diseases, antinuclear antibodies, antineutrophilic cytoplasmic antibodies, anticardiolipin antibodies, cryoglobulins, and cryofibrinogen were all negative. A skin biopsy revealed a cutaneous vasculitis with thickening of the endothelial walls, neutrophilic perivascular infiltration, and nuclear dusts – leukocytoclasia. A diagnosis of leuprolide-induced LCV was made based on the history, clinical, and laboratory findings. Considering the absence of systemic involvement, the bed rest and cessation of the leuprolide acetate injections were enough for the dramatic remission. Multiple ecchymotic rashes on both the thighs in a symmetric pattern are seen. Drug-based etiology is implicated in approximately 10–24% of cases of LCV (1). A variety of pharmacologic agents have been reported to cause LCV such as sulfonamides, penicillin, propylthiouracil (1), ibuprofen (3), and ritodrine (4). The precise mechanism of drug-induced vasculitis is unknown, but immune-mediated mechanisms are blamed in the etiology (1). Here, the production of immunocomplexes triggered by the subsequent exposures of leuprolide acetate, as well as activation of the complement cascade might have caused the development of LCV finally. There is no reliable laboratory or skin test to confirm a drug-induced vasculitis. The rechallenge test with the suspected drug provides more definitive evidence that the drug is the culprit (3). The close relationship between the administrations of leuprolide acetate and the appearance of vasculitis, especially recrudescence of the rash by subsequent administration, was the main clue to make the diagnosis in this case. Cutaneous adverse reactions of leuprolide acetate include pruritus, acne, urticaria, photosensitivity, injection site reactions (flare or subcutaneous nodules formation), and alopecia (2), (5). The cutaneous vasculitis (LCV) is a novel adverse effect of leuprolide acetate not previously reported. Therefore, physicians should be aware of the potentially life-threatening adverse effect of this widely used drug.