INTRODUCTION
Antisynthetase syndrome (ASS) is a systemic autoimmune syndrome characterized by the presence of autoantibodies to aminoacyl-transfer RNA (tRNA) synthetases (antisynthetase antibodies) (1). Antibodies to anti-histidil (anti-Jo-1) antibodies are the most commonly detected antisynthetase autoantibodies (2). The clinical presentation typically includes: constitutional symptoms, myositis, arthralgias or arthritis, Raynaud phenomenon, mechanic’s hands, and interstitial lung disease (ILD). ASS makes up about 30% of inflammatory myopathies (3). The presence of anti-aminoacyl-tRNA synthetase antibodies and two major or one major and two minor criteria are necessary for a diagnosis. Major criteria are ILD, polymyositis, or dermatomyositis, while minor criteria are arthritis, Raynaud phenomenon, and mechanic’s hands (4). Initial treatment are glucocorticoids, but if necessary, they are combined with immunosuppressive agents such as cyclophosphamide, azathioprine, or mycophenolate mofetil (3).
CASE REPORT
A 45-year-old man presented with a two-month history of general weakness, exhaustion, and chest pain. He had been treated at the Department for Respiratory Diseases under the diagnosis of bilateral pneumonia. The symptoms of general weakness were associated with long-lasting inactivity and bed rest. On discharge, 20-milligram prednisolone tablets once daily were prescribed for further home treatment. At the next follow-up with the pulmonologist one month after discharge from the hospital, an intensification of the previous symptoms with occasional dyspnea was reported. On that occasion, ILD was verified and the chest X-ray showed characteristics of pulmonary fibrosis. Prednisolone was excluded from the therapy. The patient was examined by a rheumatologist who indicated hospitalization for additional diagnostic workup. At the time of hospitalization, pain in the muscles of the pelvis and shoulders occured. The physical examination revealed tachycardia, weak handshake, and difficulty standing up from the squatting position (Gower sign). The initial laboratory workup showed leukocytosis 17x109/l (3.4-9.7 109/L), as well as elevated aspartate-aminotransferase (AST) 177 U/L (<50U/L), alanine-aminotransferase (ALT) 188U/L (<50U/L), lactate-dehydrogenase (LDH) 548 U/L (<248), creatine kinase (CK) 3184 U/L (0-171 U/L), creatine kinase-MB 112 U/L (0-24 U/L), and C-reactive protein (CRP) 27.2 mg/L (0-5 mg/L). In the urinanalysis total 24-hour urine protein was 0.238 g/24h (<0.15 g/24h). The immunological workup showed negative rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibody, antinuclear antibody (ANA), anti-double stranded DNA (anti-dsDNA) antibody, anti-ribonuclear protein (RNP) antibody, anti-Smith (Sm) antibody, and anti-topoisomerase I (anti-Scl-75) antibody, but positive anti-histidil (anti-Jo-1) antibodies, which were 200 (<1 U/l). Spirometry showed a mild restrictive ventilatory disorder, and carbon monoxide diffusing capacity (DLCO) was mildly reduced as well. Serum tumor markers, high-resolution chest CT (HRCT), and ultrasound of the heart and musculoskeletal system were normal. Electromyoneurography showed a small percentage of low-voltage polyphasic action potentials.
The patient was treated with high doses of corticosteroids, methylprednisolone 1 mg/kg/day, and methotrexate tbl a 15 mg once a week. An improvement was observed in the clinical and laboratory parameters. The corticosteroid dose was gradually reduced and switched to oral prednisolone 60 mg per day, divided in two doses (30 mg + 30 mg). On the last follow-up, six months after hospitalization, the laboratory findings were: CK 66, CK-MB 10.7, AST 14, and ALT 18. The other parameters were within the reference limits, and the prednisolone dose was reduced to 15 mg daily with the same metothrexate dose.
DISCUSSION
ASS is a rare systemic autoimmune disease that affects multiple organs. The prevalence is 1.5 per 100,000 population. The mean age at diagnosis is 50 years, with a predominance in females (2: 1) (5). Myositis, ILD, and polyarthritis followed by fever and skin involvement are the classic clinical manifestations of ASS (6). The hallmark of the disease are antibodies against aminoacyl-tRNA synthetase, most commonly anti-Jo-1 antibodies, in 80% of cases (3). ILD occurs in more than 60% of cases and is the major cause of morbidity (7). Routine testing for ASS antibodies in all patients with ILD without an obvious etiology is important because they have implications regarding the choice of therapy (8). Myositis occurs in 90% of cases, but it is of note that it may not be part of the initial clinical presentation of ASS. In one series of ILD patients with ASS, myositis as an initial symptom was present in only 31% of them. Myositis can occur months and even years after ILD (9). In our case, ILD preceded myositis. A literature review shows that it occurs at a percentage of 10-30%, which is not negligible (10). In our patient, in the initial stages of the disease ILD presented on X ray as fibrosis according to the radiologist’s report, but clinically it was more consistent with interstitial pneumonitis, as an early stage of ILD. Because of that, we started treatment with prednisolone, with a favorable response verified by the chest HRCT done after admission to the Rheumatology Department, which was normal. Pulmonary function tests showed a mild restrictive ventilation disorder, supporting the initial findings (FVC 78%; FEV1 73%; DLCO 65%).
Joint involvement occurs in more than 50%, mechanic’s hands in 30%, and Raynaud phenomenon in 40% of ASS cases (6).
A similar case report was published by Priyangika et al. In that case the patient initially presented with progressive exertional dyspnea. HRCT was performed, as well as transbronchial lung biopsy, and the diagnosis of organizing pneumonia was made. Two years later the patient presented with muscle pain, and the diagnosic workup revealed elevented CK and CRP with positive anti-Jo-1 antibodies, but without arthritis or arthralgias, Raynaud phenomenon, or mechanic’s hands. With high-dose prednisolone and azathioprine, the patient’s CK and inflammatory markers normalized (11). He had positive anti-Jo-1 antibodies with ILD and muscle involvement, but without Raynaud phenomenon, joint involvement, and mechanics hands, which does not exclude the possibility of their occurrence in the future.
In conclusion, our case shows that in patients with ILD without a known etiology the presence of ASS must be considered. Early diagnosis and the adequate treatment are essential for optimal patient care.