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Editor,—Levamisole along with prednisolone has been used in the treatment of steroid dependent minimal change nephrotic syndrome (MCNS) for many years. The only important side effect cited in the study of levamisole in the treatment of MCNS by the British Association for Paediatric Nephrology (BAPN) is neutropenia.1
Laux-End et al report a case of vasculitis with circulating autoantibodies in an 11 year old girl with nephrotic syndrome treated with levamisole.2 Raised levels of aspartate aminotransferase (ALT) have been reported in two out of 11 patients given levamisole for recurrent pyoderma. I wish to report a patient with nephrotic syndrome who developed liver toxicity after four weeks’ treatment with levamisole.3 As far as I am aware there are no reports of liver toxicity in children with nephrotic syndrome treated with levamisole.
A 14 year old boy who has had frequently relapsing steroid sensitive MCNS from the age of 18 months relapsed after a two year treatment free remission. Once again he was steroid sensitive but relapsed three times in seven months and rapidly developed steroid toxicity with cushingoid features with striae and could not be weaned off steroids. His height was 170 cm (on the 97th centile) and weight 78 kg (> 97 th centile). After a steroid induced remission the dose of prednisolone was reduced to 20 mg on alternate days. Blood counts and liver function tests done two weeks previously were normal. Levamisole 50 mg three times a day on alternate days was added to the treatment. Blood counts monitored weekly remained normal.
The remission continued. After four weeks the patient complained of pruritis. There was no skin rash. Liver function tests done at this stage showed an ALT 103 U/l (normal range up to 40), total protein 63 g/l (normal range 60–80), albumin 42 g/l (normal range 35–45), bilirubin 11 μmol/l (normal range 3–20), γ-glutamyltransferase (GGT) 12 U/l (normal range up to 45), alkaline phosphatase 196 U/l (normal range 100–800). The treatment was continued. Two weeks later liver function tests showed ALT 126 U/l, total protein 65 g/l, albumin 43 g/l, bilirubin 12 μmol/l, GGT 27 U/l, and alkaline phosphatase 311 U/l. After a further two weeks on the same treatment ALT had risen to 156 U/l. There were no significant changes in the other liver enzymes or bilirubin. The pruritis had cleared up. At this stage levamisole was stopped and prednisolone reduced to 15 mg on alternate days. Liver function tests done two weeks after stopping levamisole showed ALT 64 U/l, total protein 60 g/l, albumin 40 g/l, bilirubin 12 μmol/l, GGT 14 U/l, and alkaline phosphatase 370 U/l. Prednisolone was gradually tapered off. The patient remains well in remission.
It is fair to assume that the raised levels of ALT on this patient were the result of treatment with levamisole, as liver function tests two weeks before starting treatment were normal and two weeks after cessation the ALT had returned to near normal. The toxicity is likely to relate to the cumulative dose as ALT continued to rise until levamisole was stopped. Because of his size this patient received the adult dose of levamisole. This was, however, less than the 2 mg/kg alternate day dose recommended in the study by the BAPN. The adult dose of 150 mg/day of levamisole is generally well tolerated when given in short courses not exceeding two days for the treatment of worm infections. However when levamisole is used for a long period, even intermittently, as an immunomodulater side effects have been more frequent and diverse.4
As treatment of nephrotic syndrome with levamisole would normally last several months, it is important to define a safe upper limit of the dose. Those receiving larger doses of levamisole, as in the patient described, may develop liver toxicity after some time. It is important to monitor liver function tests in such patients.