Clinical bottom line
Palindromic rheumatism (PR) is a rare, episodic inflammatory arthritis characterized by sudden, recurrent attacks of joint pain and swelling that resolve completely between episodes. Management of refractory PR—cases unresponsive to conventional therapies such as nonsteroidal anti-inflammatory drugs (NSAIDs) and hydroxychloroquine—remains challenging. Emerging evidence suggests that B-cell targeted therapies, particularly rituximab, may offer clinical benefit in resistant PR, though data are limited and largely derived from case reports and small series. Clinicians should consider rituximab as a potential option for refractory PR after careful evaluation, while recognizing the need for further controlled studies to establish efficacy and safety.
What the evidence shows
Palindromic rheumatism is characterized by intermittent, self-limiting attacks of joint inflammation without permanent joint damage, but it can precede or overlap with rheumatoid arthritis (RA) in some patients (SpringerReference, 2022). Standard management typically involves NSAIDs and antimalarials such as hydroxychloroquine, which can reduce attack frequency and severity (Dictionary of Rheumatology, 2009). However, a subset of patients experiences refractory disease with frequent flares and inadequate response to these treatments (Joint Disease, 1987).
Rituximab, a monoclonal antibody targeting CD20-positive B cells, has been explored as a therapeutic option in refractory PR due to the suspected role of B cells and autoantibodies in disease pathogenesis (Rheumatology and Immunology Therapy, 2004). The first published report documenting rituximab efficacy in resistant PR described significant clinical improvement and reduction in flare frequency following treatment, with sustained remission in a patient unresponsive to conventional therapies (Raghavan et al., 2019). This case highlighted rituximab’s potential to modulate the underlying autoimmune process in PR.
Histopathological studies have suggested endothelial and synovial involvement in PR, with immune complex deposition and inflammatory cell infiltration implicating B-cell-mediated mechanisms (Arthritis & Rheumatism, 1972). These findings provide a biological rationale for B-cell depletion strategies. Nonetheless, the evidence remains limited to small case series and expert opinion, with no randomized controlled trials to date.
Caveats and uncertainty
The evidence supporting rituximab and other novel therapies in refractory PR is preliminary and largely anecdotal. The rarity of the condition and its episodic nature complicate clinical trial design and outcome assessment. Furthermore, the natural history of PR is variable, with some patients experiencing spontaneous remission, which may confound interpretation of treatment effects.
Potential risks of rituximab, including infusion reactions and immunosuppression-related infections, must be weighed against uncertain benefits in this population. Additionally, the relationship between PR and progression to RA remains incompletely understood; it is unclear whether early aggressive therapy alters this trajectory.
Current guidelines do not provide specific recommendations for refractory PR management beyond conventional agents, reflecting the paucity of high-quality evidence. Clinicians should exercise caution, individualize treatment decisions, and monitor patients closely when considering off-label use of biologics.
How this may change practice
For rheumatologists managing patients with refractory palindromic rheumatism, rituximab may represent a promising therapeutic option when standard treatments fail. This approach aligns with emerging understanding of PR as a B-cell-driven disorder in some cases. Incorporating rituximab could reduce flare frequency and improve quality of life for selected patients.
However, given the limited data, rituximab use should be reserved for carefully selected cases after thorough discussion of risks and benefits. Multidisciplinary collaboration and patient education are essential. Future research, including prospective registries and controlled trials, is needed to define optimal treatment algorithms and clarify long-term outcomes.