Comment on: Psoriasis under B-cell depleting therapies in multiple sclerosis: a retrospective multicenter analysis

Dear Editor,

We read with great interest the recent study by Kirschner et al., which provides a rigorous multicenter evaluation of psoriasis in multiple sclerosis (MS) patients treated with B-cell depleting therapies (BCDT). ¹ Among 3228 patients, 7 developed new-onset psoriasis and 10 experienced exacerbation of preexisting disease, corresponding to a rare overall incidence of 0.49%, with a median onset of 13 months (range 3–83 months). While the overall frequency is low, the clinical implications of even isolated events are substantial, given the need to balance MS disease control with the emergence of autoimmune skin disease.

The study highlights that most cases were controlled with topical therapy, but some required systemic anti-IL17A intervention or MS therapy modification. This raises a crucial question: how should clinicians prioritize competing immunological targets when BCDT successfully controls MS yet potentially triggers Th17-mediated psoriasis? Is there a predictable patient profile—based on prior therapy, cytokine milieu, or regulatory B-cell function—that identifies those at risk for autoimmune flare upon B-cell depletion?

Mechanistically, the proposed pathway—BCDT-induced depletion of regulatory B cells leading to Th17 hyperactivation and psoriatic inflammation —is compelling. Yet it also prompts further inquiry: to what extent does B-cell depletion unmask latent autoimmune predisposition versus directly triggering de novo pathology? Moreover, in cases where systemic anti-IL17A therapy is initiated, what are the implications for MS disease activity, particularly in patients with high inflammatory burden?

Finally, the retrospective design leaves open additional uncertainties: the contribution of prior disease-modifying therapies (e.g., dimethyl fumarate), subclinical psoriasis underreporting, and the absence of quality-of-life measures. Future prospective studies are urgently needed to define predictive biomarkers, clarify causality, and optimize integrated therapeutic strategies for patients with dual autoimmune risk.

We propose moving beyond static biomarkers toward dynamic immune reconstitution surveillance. Recent single-cell RNA sequencing (scRNA-seq) has revealed that anti-CD20 therapy induces cell-type-specific functional changes in CSF macrophages and peripheral monocytes, detectable before clinical psoriasis emerges. ² Spatial transcriptomics could further identify early psoriasiform signatures. Additionally, the gut–skin axis—wherein gut dysbiosis promotes IL-23-mediated Th17/γδ T-cell activation—represents an overlooked upstream event.^3,4 We therefore advocate a prospective multi-omics model incorporating: (1) longitudinal scRNA-seq of PBMCs at 3, 6, and 12 months post-BCDT; (2) skin spatial transcriptomics at baseline and first erythema; and (3) gut metagenomic sequencing. This framework would distinguish unmasked latent autoimmunity from de novo immune deviation, providing testable biomarkers for future validation.

The therapeutic dilemma—suppressing Th17-driven psoriasis without destabilizing MS—is compounded by conflicting safety data on anti-IL-17A agents. A 2025 systematic review reported secukinumab discontinuation in 9 of 15 comorbid MS patients over 12.5 months, including 3 due to neurological relapse. However, early-phase trials showed reduced MRI lesions without major safety signals, suggesting discontinuations may reflect dermatologic rather than neurologic deterioration. ⁵ We propose a tiered algorithm informed by the gut–immune–skin circuit:

• Tier 1 (mild): Continue BCDT plus topical therapy; monitor serum IL-17A, IL-23, and CLA+ memory T-cells quarterly.

• Tier 2 (moderate–severe, MS stable): Transition to natalizumab or S1P modulators before initiating systemic anti-IL-17.

• Tier 3 (anti-IL-17 required): Implement a 3-month MRI surveillance window with CSF IL-17A monitoring at baseline and month 6.

Looking ahead, RORγt inhibitors (bypassing IL-17A directly) may offer a distinct CNS safety profile, whereas JAK inhibitors carry a class demyelination warning, limiting their use outside controlled trials. This tiered approach shifts from reactive IL-17 blockade to proactive risk stratification grounded in individual immune–gut profiling (Figure 1).

Figure 1.

Integrated multi-omics surveillance and tiered therapeutic algorithm for BCDT-associated psoriasis in multiple sclerosis.

In summary, Kirschner et al. provide valuable evidence that psoriasis under BCDT is rare and largely manageable, but their findings also expose critical mechanistic and clinical questions. Addressing these uncertainties is essential to guide rational, patient-centered therapy in MS with comorbid autoimmune disease.