Mycophenolate mofetil therapy for rapidly progressive interstitial lung disease in a patient with clinically amyopathic dermatomyositis

Rapidly progressive interstitial lung disease (ILD) associated with clinically amyopathic dermatomyositis (CADM) is often lethal despite corticosteroid therapy combined with cyclophosphamide and cyclosporine or tacrolimus. Several recent studies have described the treatment of ILD in patients with systemic sclerosis (SSc) or other connective tissue diseases with mycophenolate mofetil (MMF), a noncytotoxic immunosuppressant [1–9]. To our knowledge, this is the first report of MMF therapy as an alternative to intravenous pulses of cyclophosphamide (IVCY) for rapidly progressive ILD associated with CADM in combination with high-dose corticosteroids and oral tacrolimus. A 55-year-old female was admitted with a 1-week history of low-grade fever, muscle pain in the thigh, Gottron’s papules, and heliotrope rash. The white blood cell count was 3,230/ll with 75.9 % neutrophils, and C-reactive protein was 0.27 mg/dl (\ 0.3 mg/dl). The serum antinuclear antibody titre was not elevated and no anti-Jo-1 antibodies were detected. Anti-CADM 140 antibody was positive. She had no muscle weakness and her serum creatine kinase (156 IU/l; normal 45–163 IU/l) and aldolase (6.8 IU/l; normal 2.7–7.5 IU/l) levels were normal. Quadriceps magnetic resonance imaging and electromyography detected muscle inflammation. Slight fine crackles were audible bilaterally. Arterial blood gas analysis showed pH 7.472, PaO2 76.4 Torr, and PaCO2 34.5 Torr. The serum KL-6 was elevated at 695 U/ml (\ 499 U/ml). A chest X-ray revealed faint reticular shadows in both lower lung fields. Chest high-resolution computed tomography (HRCT) showed bilateral subpleural opacity with groundglass attenuation (GGA) (Fig. 1a). She was diagnosed with CADM and progressive ILD, and given intravenous pulse methylprednisolone therapy at 1 g/day for 3 days followed by oral prednisolone 1 mg/kg/day (50 mg/day). After 3 weeks, the muscle pain and skin manifestations had improved, while the chest images had deteriorated gradually with lung shrinkage on chest X-ray and increasing GGA with patchy consolidation on HRCT (Fig. 1b). Biweekly IVCY at 500 mg/body dose and oral tacrolimus were added immediately. The trough serum tacrolimus level was maintained at 8–10 ng/ml. Over the next 13 weeks, she received six sessions of IVCY therapy, the pulmonary lesion extended (Fig. 1c) and hypoxemia requiring oxygen therapy manifested. Intravenous pulse methylprednisolone therapy at 250 mg/day for 3 days was administrated followed by prednisolone 30 mg/day. Nevertheless, the chest images and her respiratory condition had not improved 4 weeks after these additional therapies. Furthermore, IVCY could not be continued because of sustained leukocytopaenia. We switched from IVCY to oral MMF, and gradual improvement of the hypoxemia and pulmonary lesions was obtained. Thirty-one weeks after starting MMF, when the prednisolone had been tapered to 10 mg/day, the lung GGA and exertional dyspnoea resolved (Fig. 1d) and the serum KL-6 level decreased from 4,837 to 563 U/ml (Fig. 2). During the combination therapy with MMF, she suffered from cytomegalovirus infection, which was successfully treated with ganciclovir. Her ILD and CADM have been well controlled without exacerbation for 2 years. H. Tsuchiya (&) H. Tsuno M. Inoue Y. Takahashi H. Yamashita H. Kaneko T. Kano A. Mimori Division of Rheumatic Diseases, National Center for Global Health and Medicine, 1-21-1 Toyama, shinjuku-ku, Tokyo 162-8655, Japan e-mail: elephantscale@yahoo.co.jp