Ocular Syphilis and Tuberculosis in Mixed Connective Tissue Disease

Background: Visual loss in patients with mixed connective tissue disease is often attributed to disease activity or drug toxicity. However, infections can present with similar symptoms, sometimes concurrently, complicating diagnosis and management. Methods: A 54-year-old female with mixed connective tissue disease (systemic lupus erythematosus, Sjögren’s syndrome, and rheumatoid arthritis), maintained on hydroxychloroquine and methotrexate, presented with progressive visual blurring described as cloudy, with difficulty seeing fine details and focusing of the eyes associated with eye pain and sandy gritty foreign body sensation then later metamorphosia. She was referred to ophthalmology service for consideration of SLE retinitis or hydroxychloroquine toxicity. Result: Ophthalmologic examination revealed acute granulomatous posterior uveitis (Figure 1). Differential diagnosis expanded to consider ocular syphilis and tuberculosis. Further work up revealed positive rapid plasma regain (RPR) and fluorescent treponemal antibody absorption (FTA-ABS). Chest radiograph and interferon-gamma release assay were negative, but sputum GeneXpert was positive. These findings confirmed dual infection with syphilis and tuberculosis. She was then treated with intravenous penicillin G and standard anti-tuberculosis therapy which led to improvement in her visual acuity. This case illustrates the investigative challenge of disentangling overlapping etiologies in complex autoimmune patients. Attribution bias toward autoimmune flare or hydroxychloroquine toxicity could have delayed recognition of infections. Early recognition and treatment in this case preserved vision and improved clinical outcomes. Conclusion: Ocular infections must be considered among immunosuppressed patients with visual disturbances. A structured diagnostic approach—including ophthalmologic evaluation, syphilis serologies (RPR, FTA-ABS), and tuberculosis testing—can unmask infectious mimics, ensuring timely and effective therapy.