The patient was refractory to conventional immunosuppressive therapies including systemic corticosteroids, cyclophosphamide, mycophenolate mofetil, azathioprine, cyclosporine and intravenous immune globulin. He required multiple hospitalizations for acute respiratory failure requiring intubation, and he developed recurrent infections for which immunosuppressive therapy had to be discontinued.
In February 2013, the patient’s pulmonary status declined and his supplemental oxygen requirements increased. Physical examination showed 4.5/5 strength on hip flexors, 5/5 in all remaining major flexors and extensors with normal grip. The patient had hyperkeratotic skin lesions on his hands consistent with mechanic’s hands. Pulmonary function tests showed total lung capacity to be 62% of predicted. Forced vital capacity was 60% of predicted. DLCO was 29%, and FEV-1 was normal.
A CT of his chest demonstrated ground-glass opacities and honeycombing. An echocardiogram showed normal ejection fraction and diastolic function. His pulmonary artery systolic pressure was 25 mmHg.
Laboratory results included an erythrocyte sedimentation rate of 86 mm/h, CRP 181.0 mg/L and an elevated serum CPK level (1,500 U/L, normal ≤145 U/L).
The clinical picture was compatible with AS, which prompted the search for antisynthetase antibodies. Anti-Jo-1 antibodies were negative, but more specific testing (ImmunoDOT technique) revealed the presence of anti-PL-12 antibodies. To treat the ILD that had been refractory to all other immunosuppressive therapies, he was given two doses of 1,000 mg rituximab every two weeks, with the second dose given in November 2016.
He improved and had stable pulmonary function tests at his six-month outpatient follow-up appointment with our clinic.
This case emphasizes the need to consider AS in patients with ILD & undifferentiated connective tissue disease and to screen for ARS antibodies, particularly in the presence of typical clinical features (mechanic’s hands), a negative ANA & a positive anti-cytoplasmic signal.
Discussion
AS is a rare, chronic autoimmune disease of unknown etiology. It belongs to the subgroup of idiopathic inflammatory muscle diseases. It is a clinical entity characterized by interstitial lung disease (ILD), inflammatory myopathy, arthritis, Raynaud’s phenomenon, fever, mechanic’s hands and the presence of antisynthetase antibodies.
A diagnostic feature is the presence of serum autoantibodies that recognize the ARS antibodies. Antisynthetase antibodies are ARS antibodies that are directed against the enzymes that attach dedicated amino acids to their cognate tRNA in the process of polypeptide synthesis.
Theoretically, ARS antibodies could be targeting synthetases for all 20 existing amino acids. However, to date, only eight ARS antibodies have been identified, of which anti-Jo-1 is the most prevalent, comprising two-thirds of identified ARS antibodies.3 Others are less frequent and include anti-PL-12, anti-PL-7, anti-OJ, anti-EJ, anti-asparaginyl-tRNA synthetase, anti-phenylalanyl-tRNA synthetase and anti-tyrosyl tRNA synthetase.4
