Divergence between initial and cumulative manifestations in systemic lupus erythematosus: effect of age and sex in a prospective lupus cohort from Pakistan.

Background: Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease that evolves over time. Understanding differences between initial and cumulative disease manifestations, as well as variations by age and sex, is critical for early recognition and management. Methods: This prospective cohort study enrolled 185 patients fulfilling ACR/EULAR SLE classification criteria, of whom 138 (74.6%) had complete datasets for analysis. Demographic, clinical, and laboratory data were collected at baseline and follow-up, with manifestations compared between pediatric-onset (<16 years) and adult-onset (≥17 years), as well as between sexes. Statistical analyses included McNemar's test for paired baseline-to-cumulative comparisons, chi-square and Fisher's exact tests for between-group comparisons, Results: The cohort was predominantly female, 132 (95%), and adult, 87 (83.7%). At onset, arthritis, 121 (87.7%), fever, 102 (73.9%), and mucocutaneous features like hair loss, 81 (58.7%), photosensitivity, 71 (51.4%), and oral ulcers, 70 (50.7%), were most frequent, while nephritis, 10 (7.2%), and neuropsychiatric SLE, 4 (≤4.3%), were rare. Over time, significant cumulative increases were observed in mucocutaneous involvement, 84 (63.2%) to 98 (71.0%), Conclusion: Arthritis and mucocutaneous features dominate early SLE, whereas sicca, vasculitis, and hematologic manifestations accumulate with disease progression. Pediatric and male patients may experience distinct risks, underscoring the importance of age- and sex-aware monitoring in long-term SLE care.