Adalimumab-associated pulmonary fibrosis

S ir , A small number of reports have implicated infliximab as an aetiological factor in the development of lung inflammation and fibrosis in patients with rheumatoid arthritis [ 1–5 ]. Etanercept has also been suggested to have been the cause of acute lung injury in one case in which non-caseating granulomas and birefringent particulate material were identified in transbronchial biopsy specimens [ 6 ]. Anti-tumour necrosis factor (TNF)-α drugs are being used with increasing frequency in the treatment of severe resistant rheumatoid arthritis. Current practice in most units is to perform a chest radiograph prior to commencing TNF blockade, primarily to rule out tuberculosis [ 7 ]. We report the case of an otherwise well 76-yr-old female patient with severe rheumatoid arthritis who was being treated with adalimumab and methotrexate. She had never smoked. Seropositive rheumatoid arthritis was diagnosed in 2003 and treatment with methotrexate was commenced within 6 months of diagnosis. She was tolerating a weekly dose of 22.5 mg of methotrexate, along with sulphasalazine 1G b.d. and hydroxychloroquine 200 mg o.d., but was still experiencing articular symptoms. In 2005, it was decided to commence adalimumab instead of sulphasalazine and hydroxychloroquine, whilst continuing methotrexate. A chest radiograph was performed prior to starting adalimumab and was reported as entirely normal. She had no respiratory symptoms. Initially there was a marked symptomatic improvement in her arthritis. However, within 10 weeks of starting adalimumab, she developed progressive shortness of breath on exertion. She was treated initially by her primary care physician for pulmonary oedema and a chest infection with no improvement and an echocardiogram showed good left ventricular function. Two weeks after the onset of shortness of breath, she deteriorated and became dyspnoeic at rest and was admitted to the hospital, requiring high-flow oxygen. Clinically, there were signs of pulmonary fibrosis. A high resolution CT scan of the lungs showed extensive confluent reticular and honeycomb shadowing in a basal and posterior distribution ( Figs 1 and 2 ). Lung function tests showed a carbon monoxide transfer factor (TLco) which was 30% of that predicted. Bronchoscopy was performed and the lavage showed a mixed infiltrate of alveolar macrophages with some lymphocytes and neutrophils. Culture for tuberculosis and analysis for Pneumocystis jiroveci and viruses were negative. Methotrexate and adalimumab were both discontinued and the patient was treated with oral prednisolone following which there was some improvement and she was discharged to receive home oxygen therapy. High resolution CT scan of the lungs showing widespread fibrosis. Chest radiograph showing reticulonodular shadowing. She was reviewed in clinic after a month and, in view of a further deterioration, it was decided to commence treatment with pulsed intravenous cyclophosphamide. However, prior to starting this treatment, she was readmitted to hospital with a mild intercurrent chest infection and unfortunately, because of her very poor respiratory reserve, the infection proved fatal. As far as we are aware, pulmonary fibrosis has not been reported previously in association with treatment with adalimumab. In this case, there are similarities with those which appear to link lung injury with infliximab treatment. While a cause and effect relationship cannot be proved, this case suggests that caution should be exercised with all of the anti-TNF drugs when treating rheumatoid patients who have pre-existing lung disease. Continuing vigilance is necessary as our experience in using these agents grows. The authors have declared no conflicts of interest.