Ciprofloxacin-induced ANCA-negative cutaneous and renal vasculitis--resolution with drug withdrawal.

Sir, A 50-year-old male with a history of hypertension underwent cystoscopy for gross haematuria. A bladder tumour was resected cystoscopically, and subsequently proved to be benign. He presented one week later with fever, delirium and right-sided flank pain. He was admitted with a diagnosis of urosepsis, and treated with ampicillin and gentamicin intravenously. His clinical condition rapidly improved, and was discharged 4 days later on oral ciprofloxacin. Ten days after discharge, he developed a skin rash on his legs. The rash was an initially red, palpable purpura that progressed to purplish lesions that ultimately ulcerated. He had no other symptoms suggestive of systemic vasculitis. The patient was started on a tapering dose of oral prednisone for what was felt to represent a cutaneous vasculitis, and his ciprofloxacin was discontinued after 10 days of therapy. His rash improved significantly, with the ulcerative lesions healing over the course of the next 1 month, and the steroids were discontinued. Approximately 2 months after the course of ciprofloxacin, and as he was tapering off his steroids, he was noted to have worsening of his hypertension (180/110), which was previously well-controlled. A urinalysis showed >3 g/l protein and >50RBC/hpf. There was 24.1 g of protein in his 24 h collection. Bloodwork included normal electrolytes, urea 14.8mmol/l, creatinine 205 mmol/l, albumin 33 g/l, haemoglobin 140 g/l and erythrocyte sedimentation rate 66mm/h. A CT-guided renal biopsy was performed, and he was subsequently referred to nephrology. He was assessed in nephrology out-patient clinic 6 months after his course of ciprofloxacin and 4 months after the proteinuria was diagnosed. His only complaint was fatigue. In addition to quinapril 20mg OD which he had been on for 5 years, his medications now included methyldopa 250mg BID, furosemide 40mg OD, metolazone 2mg OD, and diltiazem 300mg OD. His blood pressure was 138/78, pulse 96 and weight 133.2 kg. His rash had completely resolved, with numerous depressed scars on his shins from healed ulcerations. He had oedema up to his knees bilaterally, but the rest of his exam was within normal limits. Further laboratory investigations at this time included normal electrolytes, creatinine 175 mmol/l, haemoglobin 136, negative hepatitis B and C serology, and negative antinuclear antibody, anti-neutrophil cytplasmic antibodies (ANCAs) and anti-glomerular basement antibodies. Complement levels had previously been normal. A repeat 24 h urine collection contained 9.25 g/day protein. His renal biopsy demonstrated glomeruli with diffuse, global proliferation (Figure 1). While necrosis was not seen, there were occasional crescents present (Figure 2). A moderate cellular infiltrate was seen within the interstitium, and red blood cell casts were seen within tubules. Immunofluorescence showed a trace of finely granular positivity for IgM, kappa and lambda, which was interpreted as being non-specific. There were no electron-dense deposits on electron microscopy. A diagnosis of ciprofloxacin-induced vasculitis was made based on the time course of his skin rash and renal biopsy findings. As he had already received 2 months of steroid therapy (albeit prior to the renal biopsy for his cutaneous vasculitis), it was decided to observe him closely and not to pursue further immunosuppression. Over the course of the next 6 months, his creatinine gradually improved to 105mmol/l, and his proteinuria decreased to 340mg/day. His blood pressure also improved, and his methyl-dopa and diltiazem were discontinued. Fig. 1. Renal biopsy showing diffuse cellular proliferation. Haematoxalin and eosin stain, magnification 400 .