Full Dapsone Dose Made Possible by Control of Anaemia with Darbepoetin-alpha

Abstract

Sir, Dapsone is a first-line immunosuppressive treatment for many inflammatory diseases. Tolerance of the drug at higher doses is usually determined by its haematological side-effects, viz haemolysis and methaemoglobinaemia (1). These adverse effects are due entirely to hepatic Nhydroxylation of the drug to a hydroxylamine metabolite, some of which escapes from the liver and rapidly enters red cells (1). We describe here a case in which dapsoneinduced haemolysis was treated with darbepoetin-alpha. CASE REPORTAn 84-year-old man presented who had had symblepharon and entropion that had required multiple operations, but with poor results. He also had oral mucosal lesions and desquamative gingivitis, both of which affected his sleep and eating habits. His dentist referred him to us because he noticed a lesion in the skin. Linear IgA disease was suspected and confirmed by .typical histopathological changes showing subepidermal blistering with predominant neutrophilic infiltrate in the upper dermis and immunofluorescent staining showing linear deposition of IgA at the basal membrane zone. He was initiated cautiously on 25 mg of dapsone daily, due to his age. In a few days his haemoglobin level fell from 121 g/1 to 107 g/1. There was no therapeutic effect and the dose was increased to 50 mg dapsone daily, but his haemoglobin level fell further, to 98 g/1. The patient became pale with cyanotic lips, but not icteric (total bilirubin 12 Hmol/1, haptoglobin 2.07 g/1, se-lactate dehudrohenase (LDH) 266 U/1 (ref value 240-480 U/1), mean corpuscular volume (MCV) 98 fl, se-B12 375 pmol/1, erythrocyte folate 3596 nmol/1, se-iron 10 nmol/1 and se-total iron binding capasity (TIBC) 52 |imol/l). He experienced severe tiredness and instability when walking, and the lesions improved only minimally on that dose. We reduced the dose to an average daily dose of 37.5 mg (alternating 50 mg one day and 25 mg the next) and the lesions became worse. In order to treat the anaemia, we considered darbepoetin-alpha which is a hyperglycosylated derivative of erythropoietin (2) with a threefold longer terminal half-life (3). We administered 50 |ig s.