A role for ITPA variants in the clinical course of pulmonary Langerhans' cell histiocytosis?

Abstract

To the Editors: Interstitial lung diseases (ILD) comprise a number of clinical conditions, including sarcoidosis, pulmonary fibrosis and pulmonary Langerhans' cell histiocytosis (PLCH; histiocytosis X). The diagnostic workup for the classification of ILD is often complicated and tedious. PLCH is characterised by the proliferation of Langerhans' cells and their infiltration into pulmonary tissues. In disseminated LCH, additional tissues are affected. PLCH is strongly associated with smoking and the clinical outcome depends upon cessation of smoking 1. Treatment of ILD often requires corticosteroids and immunosuppressant drugs, including thiopurines and biologicals. It is mandatory to exclude genetic polymorphisms in genes involved in metabolism of thiopurine metabolism, because of the pharmacogenetic consequences of the use of thiopurines. The prospective measuring of erythrocyte enzyme activity of thiopurine S -methyltransferase (TPMT) and inosine triphosphatase (ITPase) or molecular analyses of the genes encoding these enzymes is recommended in clinical practice 2. Aberrant enzyme activity of either TPMT or ITPase gives rise to a broad spectrum of adverse drug reactions (ADR) associated with thiopurines, ranging from therapeutic failure to life-threatening leukopenia 3, 4. In order to avoid these ADR, we have incorporated pre-treatment screening of TPMT and ITPase of patients with ILD who are candidates for treatment with thiopurines in our hospital. An unexpectedly high number of decreased ITPase activities in patients with PLCH was found, all of which had an unfavourable outcome. We hypothesised about the role of the ITPA gene in relation to immunity, which might …