Scleritis and associated systemic diseases: contribution of systemic examination, follow-up, and additional investigations

Abstract Background Identifying underlying disease associations in patients with scleritis remains a clinical challenge. This study aimed to assess the contribution of systemic examination, longitudinal follow-up, and additional investigations to the identification of associated diseases in patients with scleritis. Methods We retrospectively reviewed 98 patients with scleritis in whom no associated disease had been identified at presentation, assessed in two internal medicine departments in Lyon between July 2011 and September 2023. Data were collected at the initial presentation, prior to the identification of any underlying disease. The primary outcome was the contribution of systemic examination to the identification of associated diseases. Results After a median follow-up of 42 months [15.5–100], an associated disease was identified in 37 patients (37.8%), including 23 systemic diseases (23.5%), 12 infectious diseases (12.2%), and 2 cases of drug-induced scleritis (2.0%). Systemic examination contributed to the identification of an associated disease in 20 patients (20.4%), mainly through ear, nose and throat (ENT) and dermatological assessments. In 70% of these patients, systemic manifestations preceded the first episode of scleritis, while in the remaining 30% they developed during follow-up. In three patients, scleritis was the initial and sole manifestation, and the diagnosis was established through additional investigations during follow-up. The positive predictive value (PPV) of non-specific anti-neutrophil cytoplasmic antibodies (ANCA) was 29%, with a negative predictive value (NPV) of 98%. When specific ANCA testing was performed, the PPV increased to 86%. Repeating laboratory investigations during follow-up did not yield additional diagnoses. Conclusion Systemic examination contributed to the identification of an associated disease in one-fifth of patients. Scleritis may be the first clinical manifestation of an underlying systemic disease, supporting the need for systematic and prolonged follow-up. These findings also underline the diagnostic value of specific ANCA testing, whereas repeating laboratory investigations after an initial negative assessment appears of limited utility.