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Bilateral hydropneumothoraces in a patient with pulmonary rheumatoid nodules during treatment with methotrexate
  1. N Steeghs1,
  2. T W J Huizinga2,
  3. H Dik3
  1. 1Department of Internal Medicine, Rijnland Hospital, Leiderdorp, the Netherlands
  2. 2Department of Rheumatology, Leiden Medical Centre, Leiden, the Netherlands
  3. 3Department of Pulmonary Medicine, Rijnland Hospital, Leiderdorp, the Netherlands
  1. Correspondence to:
    MrsN Steeghs
    Department of Internal Medicine C1-R41, University Hospital, Albinusdreef 2, PO box 9600, 2300 RC Leiden, The Netherlands;

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Extra-articular manifestations in rheumatoid arthritis (RA), in particular rheumatoid nodules, are common. The most common pulmonary manifestations are pleural abnormalities and interstitial lung disease.1 Nodules observed on a chest x ray examination are a well known diagnostic dilemma in patients with RA, given the differential diagnosis of malignancy and rheumatoid nodules. Spontaneous pneumothorax secondary to pulmonary rheumatoid nodules is an uncommon complication of RA.2,3

A 73 year old female patient was admitted for cough, fever, and dyspnoea. She had had seropositive RA for 15 years, and had a history of chronic bronchitis, heart failure, diabetes mellitus, and hypothyroidism. She had been treated for 1 year with prednisone 7.5 mg/day and methotrexate (MTX), for active arthritis. The MTX dose was raised to 12.5 mg/week a month before presentation.

On admission, the patient was dyspnoeic and had a temperature of 39.3°C. She had clinical features of a right sided pneumothorax and destructive joint disease. No evidence of active arthritis or subcutaneous rheumatoid nodules was seen. The erythrocyte sedimentation rate was 73 mm/1st h and the white blood cell count 20.3×109/l. A chest x ray examination demonstrated a hydropneumothorax of the right lung.

Drainage by a chest tube produced chylous fluid and air leakage. Antibiotic treatment was started and the temperature normalised. Microbiological cultures and extensive examinations to locate an infection were all negative. A computed tomographic scan (CT scan) showed bilateral hydropneumothoraces with subpleural nodes and thickened pleura visceralis on the right side (fig 1). Ten days after admission the MTX was discontinued and steroid treatment was increased (30 mg/day) to control extra-articular disease (the nodulosis). The bilateral hydropneumothorax persisted. A week later a vigorous subcutaneous emphysema developed. A larger diameter chest tube was placed in the right pleural space. Continuing air leakage persisted. Thoracotomy was considered not to be an option in her condition. Ulcers and necrosis of the foot necessitated partial amputation of her right foot. Secondary infections occurred. Two months after admission the patient died.

Figure 1

 Thoracic CT scan showing bilateral pneumothoraces and pleural effusions. A large pulmonary rheumatoid nodule is located in the right lower lobe. A chest tube is placed in the right pleural space. The visceral pleural membrane is markedly thickened.

Postmortem analysis showed bilateral hydropneumothoraces, with multiple subpleural nodules on both sides. The largest nodule, 2 cm, was located in the right lower lobe and had disrupted the pleura visceralis at that place.

The causes of pleural effusion are various, but combination with a pneumothorax narrows the differential diagnosis. In patients with RA who develop bilateral hydropneumothoraces, extra-articular disease (for example, rheumatoid nodules) should be considered as the cause.

Pleural effusions develop as an inflammatory response to the presence of subpleural nodules. Pneumothoraces occur as a result of cavitation of necrobiotic nodules that rupture to the pleural space, as in our patient, and are rare complications of RA.3 The incidence of pulmonary nodules is <1% on chest x ray examination, and about 25% on high resolution CT scan.1 They are associated, in most cases, with longstanding seropositive RA, the male sex, and subcutaneous rheumatoid nodules.

Previous reports suggest that MTX might be involved in exacerbating extra-articular manifestations of RA.4 These reports describe exacerbation of subcutaneous rheumatoid nodules; pulmonary nodules were not investigated. A small number of case studies describe patients with pulmonary nodules, developing pneumothorax after the initiation or augmentation of MTX treatment, as in our patient.5 No definitive relationship could be established.

Given the fact that the cause of a pneumothorax can be extra-articular rheumatoid disease, one may consider that more intensive immunosuppressive treatment should be initiated earlier in patients with RA and pneumothorax due to necrosis in a pulmonary nodule. We recommend that necrosis of a pulmonary nodule is considered in the differential diagnosis of pleural effusion and pneumothorax in patients with RA. Given the adverse effects of cyclophosphamide and prednisone treatment, other causes should be excluded.


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