1 Rheumatology Department, Southampton General Hospital and
2 MRC Environmental Epidemiology Unit, Southampton General Hospital, Southampton, UK
SIR, The new cyclooxygenase 2 (COX-2)-specific non-steroidal anti-inflammatory drugs (NSAIDs) are being used with increasing frequency. Cutaneous vasculitis associated with the COX-2-specific NSAID celecoxib (Celebrex) is not well documented. Following the recent report of fatal allergic vasculitis associated with celecoxib described in Lancet [1], we report a case of non-fatal allergic vasculitis associated with celecoxib.
In March 2002, a 69-yr-old Caucasian lady had been prescribed celecoxib for knee osteoarthritis; she took a daily dose of 200 mg for 1 week with no problems and then discontinued the drug as her pain had improved significantly. She then re-introduced the medication herself approximately 10 days later for the same pain. Seven days after re-introduction of celecoxib, she developed a maculopapular rash affecting both lower legs and feet. Celecoxib was discontinued. The rash developed into non-blanching purpuric lesions that ulcerated (Fig. 1), particularly over the feet, and the patient also developed necrotic ulcers on the posterior aspect of her right calf and on her feet. She was admitted to hospital at this stage for investigation.
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Full examination revealed no systemic features of vasculitis other than that of her rash.
Investigations performed revealed no signs of sepsis or chronic inflammatory disorders. Full blood count, inflammatory markers, liver function tests and urea and electrolytes were normal. Blood and urine cultures were sterile. A wound swab of the necrotic ulcer on her posterior right calf grew Staphylococcus aureus and the patient was treated with erythromycin for 7 days. Blood testing for cryoglobulins, immunoglobulins, complement (C3 and C4), rheumatoid factor, antineutrophil cytoplasmic antibody, antinuclear antigen, extractable nuclear antigens, CA 125 (carbohydrate antigen 125) and hepatitis B and C serology were normal. An echocardiogram did not show valvular abnormalities or vegetations. No biopsy was performed as the patient was taking warfarin.
She was started on 30 mg oral prednisolone daily and within 24 h her rash had improved, with partial resolution of the blistering and necrotic areas. Her total in-patient stay was 7 days.
Our case differs somewhat from that of the case of fatal allergic vasculitis described by Schneider et al. [1] in that our patient had no systemic features of vasculitis and the rash our patient developed was confined to her legs and feet. However, features of the rash described in both of the patients were consistent with the presence of a maculopapular rash initially, which then developed into purpuric lesions that ulcerated and became necrotic.
This appears to be a case of allergic vasculitis associated with celecoxib, given the temporal relationship between the introduction of celecoxib and the onset of the rash. Immediate withdrawal of the drug and prompt treatment with corticosteroid resulted in recovery in this case. However, the situation was complicated by the presence of an ovarian carcinoma and recent chemotherapy.
Cutaneous vasculitis has been reported in association with malignancies, most commonly with myelodysplastic syndromes [2, 3] and lymphoproliferative malignancy [4, 5]. It has also been associated with solid tumours [6, 7], predominantly lung cancer, colon carcinoma, renal, prostate, head and neck cancer and breast cancer. There has only been one case of ovarian carcinoma and cutaneous vasculitis described in the literature, and this was at tumour presentation [8]. When in association with tumours, skin symptoms typically run a parallel course with the cancer. Most paraneoplastic dermatoses disappear when the primary tumour is removed and reappear in the case of recurrence or metastases of the cancer [5]. In our patient there was no history of any rash occurring during the 6 yr course since the diagnosis of her ovarian cancer. Paclitaxel has been associated with various skin rashes but not vasculitis.
There is little in the current literature regarding the prevalence and incidence of cutaneous vasculitis associated with NSAID use. There are, however, case reports describing cutaneous reactions with various NSAIDs, including ibuprofen [9] and naproxen [10]. A retrospective study from northwestern Spain examined the incidence of biopsy-proven cutaneous vasculitis associated with drug treatment over a 10 yr period. One hundred and thirty-eight patients had cutaneous vasculitis, and 11 (8%) of the were associated with analgesic or NSAID use. None of these patients had systemic vasculitis and complete recovery with no sequelae was observed in most cases [11]. The annual incidence of analgesic and NSAID-induced, biopsy-proven cutaneous vasculitis in this cohort was 5.83 cases/million population.
Given the widespread use of these drugs, cutaneous vasculitis as a complication is rare but may well be under-reported.
Notes
Correspondence to: K. M. Jordan, MRC Environmental Epidemiology Unit, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK.
References