Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of multiple malignancies by enhancing antitumor T-cell responses through blockade of immune regulatory pathways, including PD-1, PD-L1, and CTLA-4.1–3 These agents improve survival outcomes but may disrupt immune tolerance and induce immune-related Adverse Events (irAEs) affecting multiple organ systems.1,4,5

Cutaneous, musculoskeletal, and connective tissue irAEs are increasingly recognized in routine practice.5 Among these, eosinophilic fasciitis (EF) is a rare fibrosing disorder with prominent cutaneous and fascial manifestations, including skin induration and limb stiffness.5–8 First described by Shulman in 1974, EF is characterized by fascial inflammation, progressive fibrosis, peripheral eosinophilia, and peau d’orange-like changes, with diagnosis typically relying on full-thickness biopsy and/or characteristic Magnetic Resonance Imaging (MRI) findings.6–8

Although individual cases of ICI-associated EF have been reported, its overall clinical spectrum, diagnostic pathways, management strategies, and outcomes remain incompletely defined.9–26 The authors therefore conducted a systematic review to synthesize current evidence regarding ICI-associated EF, with a focus on features relevant to dermatology and onco-dermatology practice.

This systematic review identified 22 unique cases of eosinophilic fasciitis temporally associated with immune checkpoint inhibitor therapy, confirming that this is a rare but clinically relevant irAE with both dermatologic and connective tissue involvement. Nivolumab and pembrolizumab were the most frequently implicated agents, likely reflecting both their widespread use and accumulated post-marketing experience.9–26 Consistent with the patient-level data (Table 2), the extremities were the most frequently affected anatomical regions.

Compared with broader pharmacovigilance and multicenter cohorts, our strictly case-based approach captured fewer patients. For example, Biteau et al. reported three new cases within a larger French series of ICI-related EF, but many pharmacovigilance-derived or EF-like signals did not meet our requirement for confirmed EF and extractable patient-level data. 26 This stringent case definition, while restrictive, enhances diagnostic certainty and clinical interpretability. A detailed methodological appraisal of included studies is presented in Table 4.

The largest single case aggregation among the included reports was the series by Chan et al., which described four patients with biopsy-confirmed EF following checkpoint inhibitor therapy, underscoring the rarity of this complication even in high-volume centers.14 The available data suggest that ICI-associated EF shares pathophysiologic features with idiopathic EF, including immune dysregulation with eosinophilic infiltration and fibroblast activation.4–6 Management in published cases has largely mirrored that of conventional EF, with systemic corticosteroids as first-line therapy and escalation to steroid-sparing agents in refractory or relapsing disease.4–8 As detailed in Table 3, most patients demonstrated clinical improvement following corticosteroid therapy, with additional immunosuppressive agents required in selected cases.

Despite generally favorable outcomes, delayed recognition may permit progression to fixed fibrosis and persistent functional impairment. The presence of new or worsening skin induration, limb edema, or restricted mobility in patients receiving ICIs should therefore prompt early dermatologic and rheumatologic evaluation, with consideration of EF in the differential diagnosis. These findings highlight the importance of integrating dermatologic assessment into the multidisciplinary evaluation of patients receiving immune checkpoint inhibitors.

Immune checkpoint inhibitor–associated eosinophilic fasciitis is an uncommon but clinically important immune-related adverse event with both dermatologic and connective tissue involvement that should be recognized by dermatologists, oncologists, and rheumatologists. Early diagnosis and coordinated multidisciplinary management, with timely initiation of immunosuppressive therapy when indicated, appear crucial to limiting long-term functional impairment. Larger prospective and multicenter studies are needed to clarify predisposing factors, refine diagnostic pathways, and optimize therapeutic strategies.

Faisal Tobeigei: 0000-0003-3906-2017

Faris I. Alasiri: 0009-0009-0149-6531

CRD420251134379.

The entire dataset supporting the results of this study was published in this article.

This work was supported by King Khalid University's Deanship of Scientific Research [grant numbers GRP/122/44].

Yahya Argobi: Approval of the final version of the manuscript; critical literature review; data collection, analysis and interpretation; effective participation in research orientation; intellectual participation in propaedeutic and/or therapeutic management of studied cases; manuscript critical review; preparation and writing of the manuscript; statistical analysis; study conception and planning.

Faisal Tobeigei: Approval of the final version of the manuscript; critical literature review; data collection, analysis and interpretation; effective participation in research orientation; intellectual participation in propaedeutic and/or therapeutic management of studied cases; manuscript critical review; preparation and writing of the manuscript; statistical analysis; study conception and planning.

Faris I. Alasiri: Approval of the final version of the manuscript; critical literature review; data collection, analysis and interpretation; effective participation in research orientation; intellectual participation in propaedeutic and/or therapeutic management of studied cases; manuscript critical review; preparation and writing of the manuscript; statistical analysis; study conception and planning.