Acute onset of neutrophilic dermatosis in patients after therapy with a COX-2-specific inhibitor.

Case 1 A 31-year-old black woman with an 8-year history of Crohn's disease (CD) presented with multiple, erythematous, tender, leg nodules. She had started to develop these areas approximately 2 weeks earlier. About 1 week prior to the development of these areas, the patient had gone to her primary care physician because of increasing joint pains. She was given rofecoxib, 50 mg/day. A few months earlier, the patient had stopped taking the medication that had been prescribed for CD: sulfasalazine and prednisone. Since stopping sulfasalazine and prednisone, her gastrointestinal symptoms had increased. After starting rofecoxib, the patient did not notice any significant change in her gastrointestinal symptoms, although her arthritic symptoms improved. Earlier on the day of presentation, the patient's gastroenterologist had instructed her to stop rofecoxib, and to re-start sulfasalazine and prednisone. On physical examination, the patient had multiple erythematous nodules on both legs, predominantly on the lower legs anteriorly and posteriorly (Fig. 1a). Some of the nodules showed central pustules and some showed superficial epidermal ulceration (Fig. 1b). A biopsy was performed on an indurated lesion that had not yet ulcerated. Figure 1. Multiple, erythematous nodules on the legs of a patient with Crohn's disease (Case 1). Biopsy specimens from some lesions showed subepidermal pustule formation with or without epidermal ulceration Download figure to PowerPoint The epidermis was intact. Within the dermis, beginning at the mid-reticular dermis and extending to the subcutaneous fat, there was a central area of abscess formation with infiltration of neutrophils into the surrounding dermis (Fig. 2a and 2b). Within the lower reticular dermis and the subcutaneous fat, these abscess areas were surrounded by an epithelioid granulomatous reaction with necrobiotic changes in the surrounding stroma. Special stains, including Fite, Ziehl–Neelsen, Gomori methenamine silver, and tissue Gram stain, were negative, and no birefringent material was seen with polarization microscopy. Figure 2. Low-power views of a biopsy specimen from a lesion in Case 1 that had not yet ulcerated, showing an intact epidermis with a dermal abscess extending into the subcutaneous fat with a peripheral granulomatous infiltrate (× 15 and × 100) Download figure to PowerPoint When the patient returned to dermatology 10 days later, she had stopped rofecoxib, but was reluctant to re-start sulfasalazine and prednisone. The patient reported that she stopped developing new lesions shortly after stopping rofecoxib. In addition, the existing lesions showed decreased induration, redness, and pain, and the ulcerated lesions had stopped draining. The patient returned 5 weeks later, 3 weeks after re-starting sulfasalazine and prednisone, with resolution of her leg lesions and improvement in her gastrointestinal and arthritic symptoms. Case 2 A 38-year-old white woman presented with multiple, tender, erythematous nodules of the lower legs. The patient carried a diagnosis of rheumatoid arthritis (RA), but had been off medication for a number of years with quiescence of her disease. Approximately 1 month earlier, she developed myalgias and bilateral joint pains involving the hands and knees with morning stiffness, and was given rofecoxib, 50 mg/day. Within 2 weeks, she developed multiple, slightly tender, subcutaneous nodules over both legs and some mild swelling in both ankles. Although the patient had some improvement in her joint symptoms, she developed more lower leg lesions with ankle swelling and areas of ulceration. On physical examination, the patient had multiple, hyperpigmented, erythematous papules to nodules on both the anterior and posterior lower extremities. A few lesions showed focal areas of ulceration; two showed epidermal ulceration with purulent drainage. A biopsy was performed. The biopsy specimen showed a focus of epidermal ulceration with overlying scale crust. Within the dermis, there was a mixed inflammatory infiltrate, with abundant neutrophils and nuclear dust in the superficial to the upper reticular dermis, and deeper areas of early necrobiotic change with a more mixed infiltrate containing neutrophils and a lymphohistiocytic infiltrate (Fig. 3a). Peripheral to the area of necrobiosis, there was a more granulomatous infiltrate (Fig. 3b). Features of vasculitis were not seen. Special stains, including Fite, Ziehl–Neelsen, Gomori methenamine silver, and tissue Gram stain, were negative, and no birefringent material was seen with polarization microscopy. Figure 3. Higher power views at the edge of the biopsy specimen from Case 1, showing an area with a mixed neutrophilic and lymphohistiocytic infiltrate with surrounding stromal necrobiosis, and a peripheral area of granulomatous inflammation (× 30 and × 200) Download figure to PowerPoint Three days later, the patient's primary care physician was given a diagnosis of neutrophilic dermatitis consistent with pyoderma gangrenosum, and he instructed the patient to discontinue rofecoxib. Her significant laboratory findings included a rheumatoid factor of 810 IU/mL (normal, < 20 IU/mL), with a normal complete blood count and differential count, and negative rapid plasma reagin, anti-streptolysin titer, antinuclear antibody, extractable nuclear antigens (ENA), serum protein electrophoresis, and chest X-ray. The patient was referred to a rheumatologist with the diagnosis of RA. She showed resolution of the cutaneous eruption before starting oral prednisone therapy 4 weeks later.