Novel Treatment of Rapidly Progressive ILD in Anti-Pl7 Associated Antisynthetase Syndrome: A Case Report

Background Antisynthetase syndrome (ASS) is a rare autoimmune disorder characterized by the presence of antisynthetase antibodies and variable clinical features, including myositis, arthritis, Raynaud’s phenomenon, and interstitial lung disease (ILD).[1] Among its subtypes, PL-7-associated ASS, representing approximately 3-4% of cases, is particularly associated with rapidly progressive ILD (RP-ILD) and poor prognosis.[1] Corticosteroids remain the mainstay of therapy; however, steroid-resistant disease is common, and evidence guiding optimal adjunctive immunosuppressive strategies remains limited.[2] In the absence of randomized trials, treatment is often extrapolated from other connective tissue disease-related ILDs. Data from anti-MDA5-associated ILD suggest that early, aggressive combination therapy with corticosteroids, cyclophosphamide, and tacrolimus can improve survival compared to stepwise escalation.[3] Case Report We describe a 77-year-old man with atrial fibrillation and prior stroke who presented with a 3-week history of progressive dyspnea, dry cough, and fatigue unresponsive to outpatient therapy. He had no relevant exposures but reported a 2-year history of Raynaud’s phenomenon. High-resolution CT revealed right-predominant ground-glass opacities with early fibrosis (Figure 1). Serology demonstrated high-titer anti-PL7 and anti-Ro52/TRIM21 antibodies, confirming ASS. Despite initial corticosteroids, his oxygen requirements worsened to 10 L via non-rebreather, prompting escalation to pulse methylprednisolone (250 mg IV x 3 days), cyclophosphamide (500 mg/m 2 IV monthly), and tacrolimus (target trough 5-10 ng/mL). His respiratory status improved, and by discharge, he required oxygen only with exertion. During admission, workup revealed rectal adenocarcinoma with a hepatic metastasis, for which neoadjuvant FOLFOX chemotherapy was initiated with curative intent. Cyclophosphamide was discontinued to minimize toxicity, while tacrolimus and prednisone were continued. Within 10 weeks, he no longer required supplemental oxygen. Conclusion To our knowledge, this represents the first reported case of colorectal cancer-associated anti-PL7/anti-Ro52-positive ASS presenting with rapidly progressive ILD successfully treated with early triple-agent immunosuppression. This case highlights 2 key observations: (1) early combination therapy with corticosteroids, cyclophosphamide, and tacrolimus may be lifesaving in severe, steroid-refractory anti-PL7/anti-Ro52-positive RP-ILD; and (2) The coexistence of metastatic colorectal cancer raises the possibility of a paraneoplastic variant of ASS, a rare but described phenomenon. New-onset ASS should prompt evaluation for underlying malignancy, even in amyopathic presentations. References [1.] Shi J. J Rheumatol 2017;44:1051-7. [2.] Marie I. Eur J Intern Med 2013;24:474-9. [3.] Tsuji H. Arthritis Rheumatol 2020;72:488-98.