Eosinophilic fasciitis (Shulman syndrome)—recognition of the histological spectrum allows for new insights into possible pathomechanisms

Abstract

Abstract Objectives EF is a rare disease characterized by fibrosis and inflammation of the fascia, scleroderma-like skin indurations and optional blood eosinophilia. We aimed to expand the knowledge about its aetiology and pathogenesis. Methods Biopsy specimens from 16 EF patients were assessed by histology, immunohistochemistry and quantitative reverse transcription PCR in comparison with anti-Mi-2+ DM patients and non-disease controls. Results Histologically, EF shows mild to severe inflammation at the muscle–fascia interface, with frequent involvement of the underlying muscle tissue, though varying in degree. CD206+ macrophages predominate and eosinophils are detected within the fascia in the majority of cases, however in quite small numbers, and seen infrequently within the muscle. Activators of the so-called Th2–M2 pathway like STAT6 and IL-4 are upregulated leading to high expression levels of CD206. Activators of the so-called Th1–M1 pathway like STAT1 and IFN-γ (IFNG) are also upregulated, though not translating into a significant upregulation of the effector molecule COX2. Interestingly, activators or chemoattractants of eosinophils show no significant upregulation in EF compared with DM. EF shows features of perifascicular pathology comparable to DM, with upregulation of MHC class I and II; however, this is not accompanied by perifascicular atrophy or any signs of a type I IFN response or hypoxia-mediated processes. Conclusions Our findings highlight a specific immune phenotype of leucocyte infiltrates in EF along features of perifascicular pathology similar to DM, while there is no evidence of hypoxia-mediated or type I IFN–associated processes with perifascicular fibre atrophy, indicating different pathomechanisms of muscle involvement.