Oral cyclophosphamide in a case of cyclosporin and steroid-resistant chronic urticaria showing autoreactivity on autologous serum skin testing

Patients with autoimmune chronic urticaria tend to be more severely affected than those with the idiopathic form of the disease,1 and may have a particularly severe impairment of their quality of life. The challenge of treating some of these subjects is even greater when their response to conventional therapies is insufficient. More than 75% of patients with unremitting urticaria show an excellent response to cyclosporin,2 but the problem remains what to do in nonresponders. A case of cyclosporin‐resistant chronic urticaria is reported here. A 50‐year‐old woman with a 12‐month‐history of severe, chronic urticaria unresponsive to antihistamines was seen recently. She could only partially control her symptoms by taking 25 mg of prednisone daily, but this had caused a 12 kg weight gain and the onset of osteoporosis. Laboratory investigations, including erythrocyte sedimentation rate, full blood count, electrophoresis, complement fractions, antinuclear antibodies, and thyroid autoantibodies were normal. The intradermal injection of 0.05 mL of autologous serum (ASST) induced a strong wheal‐and‐flare reaction (wheal 23 × 15 mm) whereas saline did not elicit any skin reaction. Strong reactivity on ASST has been associated with the presence of circulating auto‐antibodies to IgE or to the high affinity IgE receptor (FcɛRI).3 Cyclosporin 150 mg daily (2 mg/kg body weight) was started,2, 4 but after 2 months the patient was still unable to reduce prednisone dosage without experiencing a severe relapse of the disease. Cyclosporin was increased to 4 mg/kg but, again, after 2 months every attempt to withdraw prednisone was followed by the onset of severe, diffuse urticaria with angio‐oedema. On review, urticaria was still present despite daily therapy with prednisone 25 mg, cetirizine 10 mg, and cyclosporin. Cyclosporin was withdrawn. Oral cyclophosphamide (CTX) 100 mg (corresponding to 1.5 mg/kg body weight) 5 days/week associated with acetylcisteine 600 mg daily to reduce bladder toxicity was started after obtaining informed consent. The drug was well tolerated, as shown by laboratory investigations, and after 1 month the patient reported a 50% reduction of urticaria severity; prednisone was gradually discontinued, and the woman could now partially control her skin lesions by cetirizine 10 mg daily. After 6 months CTX was still well tolerated and the patient was virtually symptomless although she still had to take cetirizine 10 mg daily. One year after the start of CTX the patient remained well. A repeat ASST was negative. It is planned to reduce the CTX dose gradually.