Cutaneous vasculitis associated with rofecoxib

M. S. Lillicrap and P. Merry

Department of Rheumatology, Norfolk and Norwich University Hospital, Norwich NR4 7UZ, UK.

Correspondence to: M. S. Lillicrap. E-mail: mark.lillicrap{at}nnuh.nhs.uk

SIR, We read with interest the recent letter concerning a celecoxib-induced cutaneous vasculitis [1]. There are no such case reports concerning rofecoxib. There have now been several case reports recently documenting cutaneous vasculitis in association with the cyclooxygenase 2 (COX-2)-specific non-steroidal anti-inflammatory drug (NSAID) celecoxib [13]. One case of fatal allergic vasculitis, described in Lancet [2], raised the possibility that the sulphonamide moiety of celecoxib could be contributory. Rofecoxib differs from celecoxib in having a methylsulphone group rather than a sulphonamide. Cutaneous vasculitis has not been reported previously in association with rofecoxib. We report a case of cutaneous vasculitis that was apparently associated with rofecoxib.

In July 2002, a 62-yr-old Caucasian female was commenced on rofecoxib 12.5 mg/day for exacerbation of her osteoarthritic symptoms. She had presented with increasing pain and stiffness in her wrists, shoulders, knees and lumbar spine. She made a good response to the treatment but was troubled by pedal oedema. This resolved on discontinuation of the drug but due to exacerbation of her pain the treatment was recommenced. She subsequently developed an extensive palpable petechial rash on her lower legs and feet that extended to just above the knees. The rofecoxib was discontinued and she was admitted to hospital for further investigation.

Her past medical history included chronic suppurative lung disease secondary to alpha 1 antitrypsin deficiency and a left nephrectomy for reflux disease. Examination revealed no evidence of systemic vasculitis, but the extensive petechial rash was noted. Investigation revealed +++ blood and ++ protein on the urine dipstick, with mild renal impairment (creatinine 143 µmol/l). However, serum creatinine was not significantly changed from her previous measurements. Twenty-four-hour urinary protein excretion was increased to 1.06 g/24 h, although serum albumin was normal. Her erythrocyte sedimentation rate was elevated, at 22 mm/h, and the C-reactive protein concentration was 26 mg/l. The following tests were all normal or negative: complete blood count, complement levels, immunoglobulins, cryoglobulins, antinuclear antibodies, extractable nuclear antigens, antineutrophil cytoplasmic antibodies, rheumatoid factor, anticardiolipin antibodies and hepatitis serology.

A biopsy of involved skin showed a moderate perivascular lymphocytic infiltrate associated with widespread red-cell extravasation. No haemosiderin deposits were seen and there were only small collections of nuclear dust. The appearances were felt to be consistent with a lesion of cutaneous vasculitis that had been present for a few days and that was resolving.

She was managed conservatively by discontinuing rofecoxib and by observation. When reviewed in December 2002 the skin lesions had resolved, although the urine dipstick still showed ++ protein.

Given the temporal relationship of our patient’s symptoms to the ingestion of rofecoxib, and the resolution that occurred after discontinuation of the drug, this appears to be a case of rofecoxib-associated cutaneous vasculitis. Unlike the recent case described by Jordan et al. [1], our patient had evidence of renal involvement. In the retrospective study of cutaneous vasculitis undertaken by Garcia-Porrua et al. [4] in Spain, 15% of the patients with drug-induced cutaneous vasculitis had evidence of mild (6%) or severe (9%) renal impairment, and our patient would have met their criteria for mild impairment. In their cohort, persistent proteinuria or haematuria was seen in 7% of all the patients followed up after a median of 18 months.

The case described by Jordan et al. [1] was treated with oral prednisolone, but our case illustrates that it is possible to manage these patients conservatively. The study from Spain found that 79% of the cohort received no treatment, and this did not appear to alter the outcome.

Cutaneous vasculitis therefore appears to be a rare complication of the COX-2-specific NSAIDs, and the current case illustrates that this complication is not confined to celecoxib but can also be seen with rofecoxib. This suggests that the association is not due solely to the sulphonamide moiety of celecoxib.

The authors have declared no conflicts of interest.

References

  1. Jordan KM, Edwards CJ, Arden NK. Allergic vasculitis associated with celecoxib. Rheumatology 2002;41:1453–5[Free Full Text]
  2. Schneider F, Meziani F, Chartier C, Alt M, Jaeger A. Fatal allergic vasculitis associated with celecoxib. Lancet 2002;359:852–3[CrossRef][ISI][Medline]
  3. Skowron F, Berard F, Bernard N, Balme B, Perrot H. Cutaneous vasculitis related to celecoxib. Dermatology 2002;204:305[CrossRef][ISI][Medline]
  4. Garcia-Porrua C, Gonzalez-Gay MA, Lopez-Lazaro L. Drug associated cutaneous vasculitis in adults in northwestern Spain. J Rheumatol 1999;26:1942–4[ISI][Medline]
Accepted 27 February 2003