Introduction: The potential role of food hypersensitivity in the insurgence of inflammatory activity in arthritis such as Rheumatoid Arthritis (RA) has received intermittent attention, also supported by theoretical links involving mucosal immunity, mast-cell activation, and microbiome–immune interactions. Despite biological plausibility, the clinical significance of dietary antigens in RA remains uncertain. Methods: A systematic review was conducted following the PRISMA guidelines. Searches using PubMed, Scopus, and Web of Science identified studies exploring dietary interventions or food hypersensitivity in RA. Eligible articles included clinical trials, case reports, and observational studies, in English or Italian, up to the 10 December 2025. Data extraction and quality assessment were performed using the Newcastle–Ottawa Scale. Results: Eight studies met the inclusion criteria. Findings indicate that elimination or elemental diets occasionally yielded subjective improvements—such as a reduction in pain, morning stiffness, and functional improvements—yet objective inflammatory markers rarely changed. Small, highly selected, cohorts demonstrated immuno-histological alterations, including reduced mast-cell density, while long-term diets (e.g., gluten-free or vegan) have reduced specific IgG levels without altering radiographic progression. Conclusions: Evidence suggests that dietary interventions may offer symptomatic relief only in a minority of RA patients. Due to methodological constraints, inconsistent outcomes, and limited applicability to contemporary treatments, dietary approaches need further exploration and investigation. Rigorous trials in modern cohorts are warranted to clarify whether food hypersensitivity meaningfully influences RA pathophysiology.
Cofone et al. (Sat,) studied this question.