A 52-year old previously healthy male is admitted to the hospital for a one month history of fever and progressive dyspnea. He has failed two courses of outpatient oral antibiotics for a presumed community-acquired pneumonia. Review of systems is positive for new polyarticular joint pain and muscle aches.

On examination he is febrile to 102º F. He appears ill and uncomfortable. His respiratory rate is 30 and the use of accessory muscles of respiration with speech is noted. Pulse oximetry on room air is 88% and he is placed on supplemental oxygen. On lung exam, fine diffuse bilateral crackles are heard loudest in the bases but extending up to the level of the scapular tip. Cardiac and abdominal examinations are normal.

Bilateral interstitial infiltrates are seen on chest X-ray. CT scan of the chest demonstrates ground glass opacities and diffuse interstitial changes. Laboratory studies are notable for a mild anemia consistent with chronic disease. WBC count is 11,000/cu mm with a normal differential. AST and ALT are elevated at twice the upper limits of normal. CT and ultrasound of the liver are normal. Viral hepatitis and HIV studies are negative. Cultures of blood and sputum are negative, including cultures obtained by bronchoscopy. ANA, rheumatoid factor and anti-CCP antibodies are negative. 

He is initially treated with broad-spectrum IV antibiotics with no improvement. He has continued fever and progressive worsening of his respiratory status. Open-lung biopsy is obtained. Pathology demonstrates non-specific interstitial pneumonitis with no organisms identified.

Because of worsening joint complaints, rheumatology is consulted post-operatively. 

His physical examination is notable for mild synovitis in the MCP and wrist joints, and knees. On skin examination he has roughening along the edges of his fingers consistent with mechanic's hands. He denies Raynaud symptoms but dilated capillaries are found on nailfold capillaroscopy. On muscle strength testing there is subtle weakness proximally. He is able to resist against pressure, but only with difficulty and is not able to stand-up from a squatting position. The strength in distal muscle groups and reflexes are intact.  CK obtained at that time is elevated at 900 U/L (reference range: 30 – 220 U/L).

What disorder can tie the above findings together? 

The constellation of muscle abnormalities (proximal weakness with an elevated CK, AST and ALT), fever, mechanic's hands, inflammatory arthritis, and interstitial lung disease is characteristic of the well-classified anti-synthetase syndrome, a subset of the inflammatory myopathies.

What further work-up is indicated, and which antibody is classically seen?

• Subsequent EMG and STIR MRI of the thighs are consistent with an inflammatory muscle process. Anti-Jo-1 (anti-histidyl tRNA synthetase antibody) is positive. An incisional muscle biopsy further confirms the diagnosis of dermatomyositis. High dose steroids are instituted, initially with IV pulse due to the progressive lung function deterioration, followed by high-dose oral daily therapy.
• Because the constellation of clinical findings is so characteristic for an inflammatory myopathy it is debatable whether a muscle biopsy would actually be necessary. Even with active disease, a muscle biopsy may not demonstrate the inflammation since involvement is often patchy within the muscle. Since the antigen for Jo-1 is located in the cell cytoplasm rather than the nucleus, it does not produce nuclear immunofluorescence on ANA testing, and the ANA is not required for diagnosis.