Revisiting idiopathic eosinophilic myositis: towards a clinical-pathological continuum from the muscle to the fascia and skin.

OBJECTIVES: Idiopathic inflammatory myopathies are mainly defined by inflammatory infiltrates within the muscle (lymphocytes and macrophages). Eosinophil muscle infiltration has been described in idiopathic eosinophilic myositis (IEM) and rarely in EF. This study aimed to further delineate the nosological frame of idiopathic eosinophil muscle infiltration through the exhaustive analysis of IEM and EF patients. METHODS: This multicentre retrospective case series included IEM patients diagnosed between 2000 and 2022. IEM inclusion criteria were eosinophilic muscle infiltration with myositis pathological features, after the exclusion of differential diagnoses. An additional group of EF patients diagnosed between 2016 and 2022 was constituted. Inclusion criteria were an EF diagnosis and fascia thickening with inflammatory infiltrate. RESULTS: A total of 20 IEM cases and 10 EF cases were included. The median (interquartile range) age at diagnosis was 65 (49-70) years; there were 18 males. Data analysis delineated four subgroups: focal EM (FEM, n = 3), diffuse EM (DEM, n = 6), eosinophilic myofasciitis (EMF, n = 11) and EF (n = 10). FEM represented a limited and benign form of myositis. DEM cases presented objective muscle impairment with eosinophilic muscle infiltration. EMF patients presented subjective muscle impairment (myalgia, 55%), fasciitis (on histology and/or imaging), eosinophilic muscle infiltration and frequent hypereosinophilia (55%). EF patients presented myalgia (50%), muscle lesions on histology with fascia-restricted inflammatory infiltrates with (60%) or without (40%) eosinophils. CONCLUSIONS: The analysis of IEM and EF patient characteristics delineates four subgroups (FEM, DEM, EMF and EF) in terms of clinical, laboratory, imaging, pathological and outcome specificities, and proposes an adapted diagnostic and care management approach.

Identification of Multidimensional Phenotypes Using Cluster Analysis in Sarcoid Uveitis Patients.

PURPOSE: To identify multidimensional phenotypes of sarcoid uveitis patients. DESIGN: Retrospective cohort. METHODS: Consecutive patients with biopsy-proven, presumed, or probable sarcoid uveitis between December 2003 and December 2020 in Lyon were recruited. Data were collected from the clinical notes, and consisted in laboratory and imaging findings, systemic treatments and outcome. Systemic sarcoidosis was diagnosed according to the Abad's modified criteria and uveitis was classified according to the Standardization of Uveitis Nomenclature. A hierarchical cluster analysis was performed. The main outcome measure was identification of different phenotypes of sarcoid uveitis patients. RESULTS: A total of 299 patients were included. Three clusters were identified: (1) younger non-Caucasian patients who presented acute (75.3%), anterior (55.6%) uveitis, and systemic manifestations (87.8%), requiring oral corticosteroids (75.3%) along with immunosuppressive therapy (17.2%) and who were more prone to experience complete visual recovery (84.1%); (2) middle-aged Caucasian patients who presented chronic (91.7%), panuveitis (79.5%), and isolated uveitis at diagnosis (74.8%), requiring systemic treatment with corticosteroids (74.0%) but less frequently immunosuppressive therapy (9.8%) and a worse prognosis (45.3% complete visual recovery); and (3) middle-aged Caucasian patients, without preferential chronic or acute uveitis, isolated uveitis at diagnosis (81.4%), more homogenous in terms of eye involvement repartition, requiring less corticosteroids or immunosuppressive therapy (respectively 54.1% and 13.1%) and having a prognosis close to cluster 2 patients (55.3% complete visual recovery). CONCLUSIONS: This retrospective study suggested the existence of several phenotypes of sarcoid uveitis patients with different progressions and prognoses. Further studies are needed to determine the genetic and environmental factors that could explain these results.

Involvement of Type I Interferon Signaling in Muscle Stem Cell Proliferation During Dermatomyositis.

BACKGROUND AND OBJECTIVES: The idiopathic inflammatory myopathy dermatomyositis is an acquired disease that involves muscle, lung, and skin impairments. Patients with dermatomyositis show a wide range of severity of proximal skeletal muscle weakness, associated with inflammatory infiltrates, vasculitis, capillary dropout, and perifascicular myofiber atrophy. Muscles of patients with dermatomyositis show signs of muscle regeneration. Because muscle stem cells (MuSCs) are responsible for myofiber repair, we wondered whether the proliferative properties of MuSCs are altered in dermatomyositis muscle. We investigated the role of type I interferon (IFN-I) in this process because dermatomyositis is associated with sustained inflammation with high IFN-I levels. METHODS: MuSCs isolated from normal muscles and those from adult and juvenile patients with dermatomyositis were grown in culture and analyzed in vitro for their proliferating properties, myogenic capacities, and senescence. Gain- and loss-of-function experiments were performed to assess the role of IFN-I signaling in the proliferative capacities of MuSCs. RESULTS: MuSCs derived from 8 adult patients with dermatomyositis (DM-MuSCs) (5 severe form and 3 mild form, established from histologic evaluation), from 3 patients with juvenile dermatomyositis, and from normal muscle were used to analyze their myogenesis in vitro. DM-MuSCs exhibited strongly reduced proliferating capacities as compared with healthy MuSCs (-31% to -43% for mild and severe dermatomyositis, respectively), leading to poor myotube formation (-36% to -71%). DM-MuSCs were enriched in senescent, ß-galactosidase-positive cells, partly explaining the proliferation defect. Gain- and loss-of-function experiments were performed to assess the role of IFN-I on the proliferative capacity of MuSCs. High concentrations of IFN-I decreased the proliferation of healthy MuSCs. Similarly, conditioned medium from DM-MuSCs decreased the proliferation of healthy MuSCs (-15% to -22%), suggesting the delivery of an autocrine effector. Pharmacologic blockade of IFN signaling (using ruxolitinib or anti-IFN receptor antibodies) in DM-MuSCs rescued their proliferation up to the control values. DISCUSSION: These results show that autocrine IFN-I signaling prevents MuSC expansion, leading to muscle repair deficit. This process may explain the persistent muscle weakness observed in patients with severe dermatomyositis.

Idiopathic eosinophilic myositis: a systematic literature review.

Eosinophilic myositis belong to the idiopathic inflammatory myopathies and are defined by an inflammatory infiltrate composed of eosinophils within the muscle. To date, no consensus exists for diagnosis and care of such patients. The aim of this review was to describe clinical and histological presentation, treatment, and outcome of eosinophilic myositis based on a systematic review of all published histologically proven cases of eosinophilic myositis. A total of 453 records were identified in MEDLINE until November 2020. A total of 69 published cases were identified. The analysis of these allowed the distinction of the 3 previously described pathological subtypes: focal eosinophilic myositis (n = 17); diffuse eosinophilic myositis (n = 36); and eosinophilic perimyositis (n = 16). We propose a simple algorithm for diagnosis and treatment strategy for the care of patient with muscular symptoms and blood eosinophilia. This work also highlights eosinophilic myositis pathogenesis and the need for careful investigations in order to rule out differential diagnoses.