Azathioprine-induced pancytopenia in a patient with pompholyx and deficiency of erythrocyte thiopurine methyltransferase

Introduction

Pompholyx is a form of acute dermatitis localised to the palms and soles, presenting as an itchy eruption with vesicles that can amount to bullae if severe. Chronic dermatitis may be hyperkeratotic, and secondary skin changes include uncomfortable desquamation, painful fissuring, and secondary infection. The functional consequences of chronic, severe palmoplantar dermatitis can be debilitating, with difficulty in walking or in using the hands. The mainstays of treatment are topical corticosteroids or preparations containing corticosteroids plus antimicrobials, with or without an occlusive dressing to aid penetration, but the response to treatment can be unpredictable and only partially successful. Second line treatments such as systemic corticosteroids, psoralen-UVA photochemotherapy, or ciclosporin have occasionally to be considered.

Azathioprine is a mercaptopurine immunosuppressive drug used widely across many medical specialties, probably most often as a steroid sparing agent. It is not often used as the sole treatment for pompholyx, but excellent responses have been described.1 The main problem with azathioprine is acute myelotoxicity manifesting as pancytopenia. Advances in the understanding of azathioprine metabolism have been made over recent years, and it is now known that the risk of acute myelotoxicity can be obviated by measuring, before treatment, the enzyme responsible for inactivating azathioprine (thiopurine methyltransferase (TPMT)). Publications on the measurement of erythrocyte TPMT activity first appeared as long ago as 1978 and on mercaptopurine pharmacogenetics in 1980.2 3 Others have since drawn attention to the importance of this in clinical practice,4^–8 and prior measurement of TPMT activity is now recognised as best practice in several authoritative guidelines in dermatology. …