Abstract Side effects such as cutaneous vasculitis, which occur during prolonged levamisole treatment, may discourage the utilization of the drug in relapsing neph- rotic syndrome. We describe a child who developed dis- seminated vasculitis during prolonged treatment with le- vamisole. The acute phase was characterized by hepato- splenomegaly, hemolytic anemia, IgM anticardiolipin and p-antineutrophil cytoplasmic antibodies. One month after withdrawal of therapy all symptoms had disap- peared and tests normalized. This case report, together with other reports on cutaneous vasculitis, suggest cau- tion and close monitoring during prolonged levamisole therapy. Key words Nephrotic syndrome · Levamisole · Vasculitis Introduction Levamisole is an immunomodulatory agent that has been used as adjuvant therapy for frequently relapsing nephrot- ic syndrome [1, 2] and adenocarcinoma of the colon [3]. In children with nephrotic syndrome, long-term levami- sole treatment is a good alternative to major immunosup- pressives [4]. However, treatment is hampered by side ef- fects such as vasculitis, typically localized in the ear lobe, with anticardiolipin and p-antineutrophil cytoplasmic (ANCA) antibodies occurring in some cases [5, 6]. We report a child treated for 2 years with levamisole for relapsing nephrotic syndrome who developed dis- seminated autoimmune disease characterized by hepato- splenomegaly, hemolytic anemia, and leukopenia with high titers of IgM anticardiolipin and p-ANCA antibod- ies. While vasculitis has previously been reported as a major side effect of levamisole therapy, this is the first patient with disseminated disease and without skin le- sions. Case report From the age of 3 years an 8-year-old boy had suffered from fre- quently relapsing nephrotic syndrome responsive to steroids. Nephrotic syndrome began in January 1993, and became steroid dependent in August 1994. At this stage, the child showed no side effects of the prolonged steroid regimen. In accordance with the accepted practice in our institution no biopsy was performed at this stage. From January 1995 the child was treated with levami- sole (2.5 mg/kg on alternate days) for 1 year. There was no pro- teinuria during levamisole therapy, but after its withdrawal, neph- rotic syndrome recurred. This was treated with steroids (Interna- tional Study of Kidney Diseases in Children scheme) and, based on the previous good response to levamisole, we decided not to perform a biopsy but to reintroduce levamisole treatment that was continued for 2 years. In January 1998, while taking levamisole, the child developed hepatosplenomegaly and hemolytic anemia (Table 1) with low haptoglobin levels, hyperbilirubinemia, and leukopenia. Coombs’ test was negative. He appeared pale and re- ported fatigue during exercise. His body temperature was always in the normal range. His lungs appeared normal on physical exam- ination and the abdomen was normal except for the liver and spleen enlargement. No skin changes were observed. During the acute episode, the anticardiolipin IgM titer was high, pANCA an- tibodies were positive, C3 was moderately low, and antinucle- ar/anti-DNA antibodies were persistently negative. Renal function and urinalyses remained normal. Two weeks after withdrawal of levamisole therapy, clinical parameters had normalized and 1 month later, the liver had returned to a normal size. After 1 month, the child had persistent pANCA antibodies, while the anticardio- lipin IgM titer had returned to the normal range. After 6 months splenomegaly was the only physical symptom of the acute epi- sode, and proteinuria was absent without therapy. Discussion This is the sixth and most-serious case of an autoimmune disease developing after protracted levamisole treatment. Vasculitis has been reported in five other children treated with levamisole at three Italian pediatric nephrology cen- ters and has been described in detail elsewhere [5, 6]. In this patient the clinical course was more serious than in G. Barbano ( ✉ ) · F. Ginevri · G.M. Ghiggeri · R. Gusmano Department of Nephrology, G. Gaslini Children’s Hospital, Largo G. Gaslini, 5, I-16148 Genoa, Italy e-mail: Labnefro@tin.it Tel.: +39-010-380742, Fax: +39-010-395214 Pediatr Nephrol (1999) 13:602–603 © IPNA 1999 BRIEF REPORT Giancarlo Barbano · Fabrizio Ginevri Gian M. Ghiggeri · Rosanna Gusmano Disseminated autoimmune disease during levamisole treatment of nephrotic syndrome Received: 24 June 1998 / Revised: 17 November 1998 / Accepted: 20 November 1998