Langerhans cell histiocytosis (LCH) is a group of disorders characterised by monoclonal proliferation of histiocytic cells (Langerhans cells) producing tumour-like masses in multiple organs including the bone, skin, lymph nodes and central nervous system. In contrast to multiorgan LCH, pulmonary LCH (PLCH) usually involves only a single organ and presents as an infiltrative lung disease. PLCH is strongly correlated with smoking and presumably reflects reactive Langerhans cell proliferation triggered by some inhaled agent.1 In early cellular PLCH, Langerhans cells aggregate in multiple small bronchiolocentric granulomas which may further cavitate to form inflammatory thick-walled cysts, usually predominating in the upper lobes. With disease progression, PLCH may evolve towards irreversible lung destruction by cicatricial fibrotic thin-walled cysts, respiratory insufficiency and death or lung transplantation.1

No treatment has hitherto proved effective in PLCH. Tumour-like LCH has been reported to respond to cladribine (2-chlorodeoxyadenosine),2^–4 a chemotherapeutic agent cytotoxic for lymphocyte and monocyte cells. Cladribine was also observed to have an effect in one case of tumour-like LCH involving the lung.5 One patient with PLCH improved after multiple treatments including cladribine, but the effect of this agent could not be clearly established.6 Whether cladribine as a single agent is effective in PLCH presenting as infiltrative lung disease is currently unknown. We report the effect of cladribine chemotherapy in one patient with PLCH presenting as infiltrative lung disease with progressive lung function impairment.

A 39-year-old woman presented with dry cough, dyspnoea class II NYHA, fatigue and weight loss. She had smoked 1.5 packs/day between the ages of 25 and 27 years, then reduced her consumption to 1 cigarette/day and had maintained it unchanged since then. Between the ages of 22 and 31 years she was exposed to passive smoking while working as a nurse in a psychiatric hospital. Clinical examination was unremarkable. There were no features of extrathoracic disease. Lung function tests were normal except for reduced residual volume. A presumptive diagnosis of PLCH was made based on a typical chest high-resolution CT (HRCT) scan showing diffuse thick-walled cavitary nodules (fig 1). Prednisone 0.5 mg/kg/day was administered for 5 months but her lung function worsened. Positron emission tomography (PET) showed diffuse 18-fluorodeoxyglucose uptake limited to the lungs. The diagnosis of PLCH was confirmed by surgical lung biopsy showing typical cavitary granulomas with abundant Langerhans cells and no fibrosis. In the following months her dyspnoea worsened to class II–III NYHA and lung function tests further deteriorated (fig 1).

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Figure 1 (A) High-resolution computed tomography (HRCT) scan of the chest showing reticulonodular infiltrative lung disease with multiple solid and cavitary lung nodules. (B) Decrease in number and size of lung nodules and decrease in thickness of the walls of the cavitary lesions after cladribine treatment. (C) Sustained deterioration in forced expiratory volume in 1 s (FEV₁), forced vital capacity (FVC), total lung capacity (TLC), arterial oxygen tension (Pao₂) and carbon monoxide transfer factor (Tlco) with no benefit with prednisone 0.5 mg/kg/day for 5 months. A marked improvement in lung volumes was observed after two cycles of cladribine and further confirmed after the fourth cycle. Pao₂ and Tlco also improved markedly.

A treatment decision was taken based on sustained deterioration in lung function predicting a poor prognosis and the active and cellular nature of the disease suggested by lung histopathology and PET. After receiving informed consent from the patient, four cycles of cladribine were administered at, respectively, 3, 4, 5 and 5 mg/m2 every 4 weeks, with pegfilgrastim to prevent neutropenia. Self-limited gastroenteritis and sinusitis were the only side effects. Lung volumes improved markedly (fig 1). The HRCT scan showed reduced thickness of the walls of the cavitary nodules and reduction in the size and number of nodules (fig 1). PET showed disappearance of abnormal 18-fluorodeoxyglucose uptake in the lungs and dyspnoea improved to class I NYHA. Her smoking habits and exposure had remained unchanged during the 8 years preceding the diagnosis and over the entire follow-up period.

We conclude that single-agent cladribine chemotherapy might constitute a therapeutic option for PLCH presenting as infiltrative lung disease in patients with sustained deterioration in lung function and active Langerhans cells proliferation, before the occurrence of late-stage cicatricial cystic pulmonary disease. A clinical trial is warranted to further evaluate the role of cladribine in PLCH.