Department of Medicine III, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan
SIR, The interstitial lung disease associated with rheumatoid arthritis (RA) is characterized by slow and insidious progression up to 10 yr [1]. However, it infrequently shows rapid progression, resulting in death within a short time after the onset of pulmonary symptoms [2]. This form of the disease is known as acute interstitial pneumonitis (AIP). Although oral corticosteroids have been used as the standard treatment for AIP, high-dose steroid therapy is frequently associated with serious side-effects without any improvement of the lung disease [3]. In this report, we describe a patient with AIP due to RA, who was successfully treated with the combination of cyclosporin A (CyA) and corticosteroids.
A 60-yr-old woman with a 15-yr history of seropositive RA developed low-grade fever and a dry cough in December 1998. She had been treated successively with gold injections and bucillamine for 10 yr; these were discontinued in 1994 because the disease became inactive. Six months before admission, she developed a sustained flare of her arthritis, she underwent treatment with loxoprofen sodium (120 mg/day), indomethacin (50 mg/day, suppository) and prednisolone (0.1 mg/kg per day; 5 mg/day). She was admitted to the community hospital on 4 January 1999 because of worsening symptoms, including high fever, cough and exertional dyspnoea. The chest X-ray showed a fine reticular shadow in both lung fields that had developed during the last 2 weeks. The patient was a non-smoker and reported no history of exposure to hazardous chemicals or dust. Since pulse therapy with 1000 mg methylprednisolone i.v. produced no effect, the patient was referred to our hospital for further evaluation and treatment. On admission, the patient complained of general fatigue and dyspnoea. No finger-clubbing, peripheral cyanosis, heart murmur or lymphadenopathy were noted, but fine crackles were audible over both sides of the chest. Laboratory data showed a white blood cell count of 14.7x103/mm3 (neutrophils 89%, lymphocytes 10%), haemoglobin 9.2 g/dl, platelet count 287x103/mm3, aspartate aminotransferase 30 IU/l, lactate dehydrogenase (LDH) 848 IU/l (normal range; 236455), creatine kinase 13 U/l, C-reactive protein 3.9 mg/dl and erythrocyte sedimentation rate 87 mm/h. The rheumatoid factor level was 64 IU/ml by nephelometry (normal range 018), and antinuclear antibodies were not detectable. A tuberculin skin test was negative. Arterial blood gas analysis on breathing oxygen (12 l/min) showed a partial pressure of arterial oxygen (PaO2) of 71.1 torr and PaCO2 of 43.4 torr, with pH 7.42. The chest X-ray (Fig. 1, top left) demonstrated reticular shadows in both lung fields. High-resolution computed tomography (CT) of the chest (Fig. 1
, lower left) showed bilateral and patchy high density areas and partial pleural thickening, but no obvious honeycombing. The interstitial ground-glass appearance suggested active inflammation of the lungs. Cultures for bacteria and mycoplasmas were negative. No cytomegalovirus antigenaemia was detected. A diagnosis of AIP was made on the basis of the acute clinical course, laboratory data, chest CT findings and the resistance to steroid pulse therapy. Her condition deteriorated, including worsening of the interstitial shadow on the chest X-ray, progression of hypoxaemia and hypercapnia, and a progressive rise in serum LDH up to 889 IU/l. Accordingly, treatment was begun with cyA at a dose of 5 mg/kg per day (250 mg/day) was begun on 7 January 1999, wih an increasing dose of prednisolone up to 1.2 mg/kg per day (60 mg/day). This treatment resulted in a dramatic improvement, within 3 weeks, in her symptoms and clinical findings such as serum LDH and PaO2. In April, the abnormal shadow on chest X-ray had disappeared (Fig. 1
, top right), and only irregular thickening of the pleura without obvious honeycombing was still noted on the high-resolution chest CT (Fig. 1
, lower right). Shortness of breath improved further and stabilized, and CyA was tapered to 2 mg/kg per day (100 mg/day) 3 months later, because the trough level of whole blood was maintained between 100 and 200 ng/ml. Prednisolone was also tapered gradually during the same period. Soluble interleukin (IL)-2 receptor, which is a marker of activated T cells [4], was reduced from 2080 to 589 U/ml (normal range 220530 U/ml) after initiation of CyA therapy. These findings indicated a good response to immunosuppressant therapy with CyA. The patient was discharged on April 19, 1999, and was followed up in the outpatient clinic of our hospital. She remains well without any symptoms. One year after the initiation of the combination therapy, the patient was still being treated with CyA (100 mg/day) and prednisolone (5 mg/day).
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