Detection of tuberculosis by extensive screening in a patient with rheumatoid arthritis prior to anti-TNF-alpha therapy.

suggestive of UIP, with no ground-glass change. She presented with a 2-week-history of breathlessness after 12 injections (6 weeks) of etanercept, 25mg twice a week. There was no evidence of infection or heart failure. CXR showed new diffuse reticulonodular shadowing. CT pulmonary angiography (CTPA) confirmed widespread ground-glass change with no evidence of pulmonary embolism. She was treated with broad spectrum intravenous antibiotics. The etanercept and methotrexate were stopped. Despite this and adding methylprednisolone 500mg/day for 3 days and changing antibiotics, she developed worsening hypoxia and was intubated. Bronchoalveolar lavage showed no evidence of TB, bacterial or pneumocystis Carinii infection. She developed metabolic acidosis, progressive renal failure and later cardiac arrhythmias, and despite intensive treatment she died. Both our patients had pre-existing lung disease, they had enquiry into respiratory symptoms at 3 month intervals and annual CXR prior to the commencement of etanercept and were symptomatically stable. Also, both were on methotrexate and both developed acute respiratory symptoms within 3 and 6 weeks of commencing etanercept, respectively, which culminated in accelerated interstitial lung disease. The patient with COPD presented earlier and recovered quickly with oral steroids alone after discontinuing etanercept and subsequently was able to recommence methotrexate 25mg/week with adequate joint disease control but no recurrence of respiratory symptoms. The patient with poorer respiratory reserve developed progressive lung disease and died despite aggressive treatment. Lung disease is a well-known complication of methotrexate, and cases of accelerated methotrexate pneumonitis are also reported within 2–3 doses of infliximab. Our patient who survived restarted methotrexate safely, hence we do not postulate this as a cause [1]. Infliximab has been reported to accelerate lung nodulosis [2, 3], and it has been reported as causing a reversible, biopsy proven, non-caseating granulomatous lung disease in RA [4]. In both our patients, lung biopsies were taken, which may have been the histological change of the respiratory disease. Four further cases of reversible non-caseating granulomatous reaction temporally related to etanercept therapy have also been reported, two of which had previous pulmonary fibrosis [5]. Our two cases demonstrate a little-known complication of etanercept, one of which was fatal. It is noticeable that the patient who died also had rheumatoid lung disease, whilst the patient with COPD survived. Previously reports from the Biologics register [6], and published reports have raised the concern of increased mortality in patients with RA and pre-existing rheumatoid lung disease on azathiaprine when anti-TNF was added [7]. On the basis of these two cases caution needs to be extended to those with pre-existing lung disease, taking methotrexate when etanercept is added, particularly if the lung disease is due to rheumatoid involvement. Extra caution should be taken in patients with rheumatoid lung and poor respiratory reserve. Patients should be prompted to contact the rheumatology department if symptoms of acute breathlessness occur, especially soon after the introduction of etanercept.