Abstract
A 72-year-old patient was admitted to the intensive care unit with respiratory failure due to rapidly progressive interstitial lung disease (ILD). All cultures and PCRs focused on ILD were negative and a paraneoplastic phenomenon was deemed unlikely after screening for malignancy. Inflammatory myositis was suspected as the patient also presented fever, progressive pitting oedema and arthritis in both hands and feet. A myositis blot revealed high titres of anti-Jo-1 antibodies: the patient was diagnosed with antisynthetase syndrome and was treated with high-dose corticosteroids, cyclophosphamide and intravenous immunoglobulins with a gradual full recovery. Antisynthetase syndrome should be considered in patients with idiopathic or rapidly progressive ILD.

Case
A 72-year-old man without relevant medical history presented to the emergency department with dyspnoea, cough and fever. He reported pain in both wrists and ankles and progressive pitting oedema around these joints in the last few weeks. His medical history did not reveal any relevant comorbidities, no recent travel, no exposure to potential sources of infectious diseases, no allergies and no use of any medication. On physical examination, a fever of 39.2°C, fine crackles upon pulmonary auscultation and extensive pitting oedema in hands and feet were found. Laboratory analysis showed CRP 142 mg/l, leukocytes 12.3/nl but no other abnormalities. Urine analysis was normal. On the chest X-ray, several consolidations were seen (figure 1A). SARS-CoV-2 PCR was negative. An atypical pneumonia was suspected and the patient was admitted after blood cultures were drawn and a throat swab for PCR of the most common respiratory pathogens was taken, and empirical antibiotic treatment with ceftriaxone and doxycycline was initiated awaiting these results. To investigate the cause of the pitting oedema, a cardiac ultrasound was done which excluded cardiac failure. Nephrotic syndrome and thyroid dysfunction were also ruled out.

The respiratory symptoms and fever did not resolve in the following days and a CT scan was performed which showed extensive ground glass opacities (COVID-19 Reporting and Data System class 5)[1] and subpleural nodular infiltrates that could match interstitial lung disease (ILD) (figure 1B). A second negative PCR ruled out SARS-CoV-2. Subsequently, bronchoalveolar lavage was performed with minor signs of inflammation, and absence of pneumocystis, fungi or signs of viral pneumonitis. As all microbial cultures and PCR on
common respiratory pathogens were negative, a daily dose of 40 mg prednisolone was started. Three days after starting prednisolone, the respiratory symptoms progressed to respiratory failure and the patient was admitted to the intensive care unit (ICU) where he was intubated and supported with invasive mechanical ventilation. We started 1 mg/kg intravenous prednisolone and continued the diagnostic work up. To look further for the cause of this respiratory failure, rheumatoid factor, ANA, ANCA serology and screening for connective tissue diseases were tested but all were negative. We performed age and sex appropriate screening for a malignancy to assess the presence of a paraneoplastic phenomenon, but all tests were negative. Because of generalised pitting oedema and arthritis, inflammatory myositis was suspected and analysis for autoimmune disease was further extended with myositis blot screening for associated autoantibodies. This revealed an anti-Jo-1 titre of 1147 cubic units (ref. <20). Combined with a creatine kinase (CK) concentration of 2021 U/L and the ILD, the diagnosis antisynthetase syndrome (ASS) was confirmed.

The patient was supported by mechanical ventilation for five weeks. Initially, high PEEP and inspiratory pressure was needed due to low pulmonary compliance. After approximately two weeks, pulmonary function improved significantly with decreasing PEEP and inspiratory pressure levels.