Immune-mediated comorbidities in multiple sclerosis: a scoping review

Background Immune-mediated comorbidities are increasingly recognized in people with multiple sclerosis (PwMS), but their frequency, recorded diagnostic sequence, and clinical relevance remain incompletely characterized. We aimed to characterize their co-occurrence with MS, diagnoses following MS, associations with subsequently diagnosed MS, and relationships with MS clinical outcomes. Methods We conducted a scoping review guided by the PRISMA-ScR checklist. PubMed, Embase, and Scopus were searched for studies published from January 1, 2001, through February 28, 2026. Eligible studies evaluated co-occurrence; immune-mediated diseases diagnosed following MS; associations between previously diagnosed immune-mediated diseases and subsequently diagnosed MS; or associations with MS activity, disability, or progression. Additional studies were identified through backward reference screening without publication-year restrictions. Results Autoimmune thyroid disease, type 1 diabetes (T1D), psoriasis, inflammatory bowel disease (IBD), and bullous pemphigoid showed some of the most recurrent evidence of higher co-occurrence with MS, whereas findings for rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), vitiligo, atopic dermatitis, asthma, and less frequently studied conditions were more variable. Studies investigating immune-mediated diseases diagnosed following MS reported heterogeneous, condition-specific associations, with higher subsequent occurrence for psoriasis, IBD, and bullous pemphigoid in some populations. Studies examining previously diagnosed immune-mediated diseases and subsequently diagnosed MS reported higher estimates for selected conditions, including T1D, psoriasis, IBD, bullous pemphigoid, systemic sclerosis, and primary Sjögren’s syndrome, although their magnitude, precision, and consistency varied. Evidence regarding associations between immune-mediated comorbidities and MS activity, disability, or progression was limited and heterogeneous. A small number of studies indicated adverse disability or MRI outcomes associated with T1D, whereas findings for other conditions were mixed, outcome-specific, or inconclusive. Conclusion Several immune-mediated diseases demonstrated recurrent co-occurrence with MS, while separate studies reported condition-specific associations with diagnoses following MS or with subsequently diagnosed MS. Findings varied across diseases, study designs, and temporal frameworks, and may indicate shared susceptibility, surveillance bias, diagnostic delay, treatment exposure, residual confounding, or coincidental coexistence. Current evidence is insufficient to establish an MS prodrome or biologically distinct MS subgroups. Longitudinal studies using standardized disease definitions, documented diagnostic chronology, treatment data, and appropriate confounder adjustment are needed to clarify clinical and prognostic relevance.