Rituximab Therapy for Severe Cutaneous Leukocytoclastic Angiitis Refractory to Corticosteroids, Cellcept and Cyclophosphamide
A 39-year-old Lebanese woman presented with progressive skin rash with ulcerations in both lower limbs for 2 months. She denied fever, weight loss, chest or abdominal pain. She had mild low back discomfort at the left sacroiliac region, yet no peripheral joint pain or swelling. The patient is a school teacher and had never dealt with paints or lived in an area of industrial fumes. She did not have previous medical disease, allergy, and surgery nor had used medications especially in the past few months prior to the skin rash. On her initial physical examination, the patient was in clear discomfort from her leg ulcers. Blood pressure was 110/70 mm Hg, temperature was normal and body weight was 70 kg. She did not have lymphadenopathy, goiter, jugular venous distension or edema. Systemic examination did not show abnormality. Lower extremities showed bilateral maculopapular rash with ulcerations and livida reticularis (fig. ).\nLaboratory investigations showed normal peripheral leukocytic and platelet counts. Hemoglobin was 110 g/l with normal MCV. ESR was 90 mm/h. Serum sugar, urea, creatinine, electrolytes, CPK, liver functions, cholesterol and TSH were normal. Urine routine and microscopy was normal except for isolated hematuria (25 RBCs/HPF). Blood culture was negative. Serum complements (C3 and C4) and protein electrophoresis were normal. ANA, anti-ds DNA, ANCA, RA, cryoglobulins, hepatitis B surface antigen and anti-HCV antibodies were negative. Twenty-four-hour urine collection showed normal creatinine clearance and protein excretion. Stool testing for ova, parasites and occult blood was normal. Chest X-ray and ECG were normal. Abdominal and pelvic ultrasound did not show abnormality. Skin biopsy showed leukocytoclastic vasculitis with predominantly lymphocytic infiltrate in the subepidermal layer only with extravasated fragmented erythrocytes indicating vascular leaks (fig. ). Immunofluorescent stains were negative. Since she had hematuria, percutaneous kidney biopsy as well as celiac and renal arteriography were done. Both tests were normal. The patient was previously treated with 6 weeks of corticosteroids (1 mg/kg/day) but the lesions persisted. Hence, she was treated with pulse steroids (1 g i.v. daily for 3 days) followed by prednisone oral corticosteroids in addition to cyclophosphamide monthly infusions at a dose of 1 g in 200 ml of normal saline over 2 h. The latter was continued for 3 months, then was reduced to every 3 months with a maintenance daily dose of 5 mg of prednisone for a total period of 18 months. The lesions disappeared after the first month of therapy. However, 6 months after discontinuation of cyclophosphamide therapy, her lesions reappeared. Again, systemic examination and investigations did not show evidence of systemic disease. At this time, she was treated with 4 weekly infusions of rituximab (mabthera). The patient was premedicated with two 500-mg paracetamol and one piriton tablet followed by an infusion of 125 mg of solumedrol in 50 ml of D5W over 30 min before infusions. The 500 mg of rituximab were diluted in 450 ml of NS leading to a concentration of 1 mg/ml. The first infusion rate was 20 ml/h for the first 30 min followed by 20-ml increments/h every 30 min till the total dose is achieved. The second infusion was started at 40 ml/h, the third at 80 ml/h and the fourth at 120 ml/h. Flow cytometry showed that her CD19 lymphocytes dropped to zero after 1 week of therapy and remained <0.5% for 8 months. Interestingly, the patient is asymptomatic and up to 12 months after normalization of her CD19, i.e. a total of 32 months following the start of rituximab therapy.