Atypical RNA Polymerase III phenotype with Rheumatoid Arthritis Overlap

Summary: Background Systemic sclerosis (SSc) is a complex autoimmune disorder characterized by vascular dysfunction, tissue fibrosis, and immune dysregulation. Key autoantibodies include anticentromere (ACA), anti-topoisomerase I (anti–topo I), and anti-RNA polymerase III (anti–RNAP III), aiding in diagnosis and prognosis. Anti–RNAP III is linked to diffuse cutaneous SSc with rapid progression, renal crisis, and an increased risk of cancer diagnosis, soon before or after disease onset5,6Approximately 2.5% of SSc patients have overlapping rheumatoid arthritis (RA), exhibiting distinct clinical features1,2.Our case highlights an atypical phenotype of RNA polymerase III positive diffuse systemic sclerosis combined with seropositive rheumatoid arthritis. Case Presentation  We present a 62-year-old male with diffuse cutaneous systemic sclerosis (dcSSc) with RNA polymerase III positivity and overlap seropositive RA. His initial symptoms consisted of wrist and knee synovitis at age 20. He was treated with methotrexate, sulfasalazine and hydroxychloroquine with some relief and achieved remission by his mid-20ss. In his early 40s he experienced recurrence of synovitis accompanied with muscle weakness after increasing the dose of atorvastatin. He was treated with steroids with mild improvement of the symptoms which later resolved with complete discontinuation of the statin. Alongside, he manifested Raynaud's phenomenon. Six months later a diagnosis of systemic sclerosis was confirmed due to sclerodactyly, telangiectasias, gastroesophageal reflux disease (GERD) and positive anti-RNA-Polymerase III antibodies. He did not develop malignancy or renal crisis.Initially, he responsed well to mycophenolate monotherapy until 2019 when persistent joint pain led to initiation of biologics, and he is currently doing well on adalimumab. Discussion  This case presents a unique phenotype of diffuse cutaneous systemic sclerosis (dcSSc) and overlap seropositive RA characterized by slow disease progression, primarily manifesting as sclerodactyly and synovitis without malignancy, rapid skin involvement or renal crisis. This atypical presentation challenges the traditional progression of the disease and management paradigms, underscoring the importance of recognizing individual variations in disease expression. Furthermore, the overlap with seropositive RA adds more complexity to the clinical picture and management. This case highlights the importance of investigating rare phenotypes to refine diagnostic criteria, optimize treatment strategies, and advance our understanding of disease phenotypes. Conclusion  Additional research is warranted to elucidate the clinical and serological features of various phenotypes of systemic sclerosis and overlap syndromes. Insights into such characteristics could contribute significantly to tailored treatment approaches, including the consideration of medications typically excluded, refinement of diagnostic criteria, and prognostic considerations for individuals with diffuse cutaneous systemic sclerosis (dcSSc) and overlap syndromes exhibiting similar phenotypes.