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

Abstract

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.

Keywords: Shulman syndrome; blood eosinophilia; eosinophils; idiopathic inflammatory myositis; muscle biopsy; myositis.

Figure 1.

Flowchart: identification, screening, eligibility and inclusion process for IEM and EF patients. Detailed histological and clinical screening of cases corresponding to ADICAP codes LM 7550, LM 7552, LM 7554 and LM 7556 possibly corresponding to idiopathic eosinophilic myositis patients, and of code LM 9387 possibly corresponding to eosinophilic fasciitis patients. Excluded patients and reasons for exclusion are detailed in the lateral boxes. IEM: idiopathic eosinophilic myositis

Figure 2.

IEM and EF histopathological and imaging features. Surgical fascia and muscle biopsy analysis (A–O, left panel). Schematic representation of eosinophil infiltration throughout the fascia and muscle. (A–H) Paired low and high magnification haematoxylin, phloxin, saffron (HPS)–stained muscle and fascia surgical biopsies of the different locations where eosinophilic infiltrates can be found, including the endomysium (A, B), perimysium (C, D), epimysium () and fascia (). (I–K) Low magnification of the different patterns of MHC-I expression using immunochemistry: diffuse, diffuse with perifascicular reinforcement (PFR) and perifascicular. (L–O) Low magnification of CD56 immunochemistry in all four subgroups [diffuse eosinophilic myositis (DEM), eosinophilic myofasciitis (EMF), EF, focal eosinophilic myositis (FEM)]: positive regenerating myofibres (arrows), unspecific staining of necrotic myofibres (stars), negative staining of immune cells. MRI and TEP-scanner imaging radiological patterns (P–T, right panel). (P–Q) Myositis pattern: STIR hypersignal of the gracilis (G), adductor (A), hamstring (I) and vastus lateralis (VL) muscles associated with hypersignal on T1-weighted sequence in favour of fat replacement on the sartorial (S), gracilis (G), adductor (A) and hamstring (I). A, associated myositis and fasciitis pattern: thickened fascia on T2STIR (arrow) coupled with hamstring muscle hypersignal (I). (S, T) Fasciitis pattern: thickened fascia on T2STIR-weighted image (S, arrows) and fascial hypermetabolism on TEP scan imaging (T, arrows). IEM: idiopathic eosinophilic myositis

Figure 3.

Disease course and therapeutic requirement for each subgroup. Values expressed in percentages of patients per subgroup with available follow-up data. Due to the small number of patients in the focal eosinophilic myositis subgroup, this subgroup is not represented. DEM: diffuse eosinophilic mysositis; EMF: eosinophilic myofasciitis

Figure 4.

Schematic representation of the clinical-pathological continuum from DEM to EF. Patients with DEM were about 70 years old and mainly female. They combined objective muscle impairment (muscle weakness, elevated CK level, myogenic aspects on EMG, myositis features on MRI), infiltration of eosinophils within the muscle (preferentially in endomysium and perimysium) but not in the fascia, and pathological features of myositis. IEM patients presented an increased risk of relapse. Patients with EMF were younger (about 50 years old) and mainly male. They combined myalgia, some skin lesions and no objective muscle impairment apart from the histological one (infiltration of eosinophils into the muscle, preferentially in the perimysium, epimysium and fascia, associated with myositis pathological features). MRI identified fasciitis, and patients presented elevated CRP levels and hypereosinophilia. They required longer CS treatment and showed some relapse. In comparison, no sex difference was noted in EF patients, who were also older (around 70 years old) than EMF patients. The latter presented important cutaneous lesions, particularly the groove sign which was absent from the other subgroups. Most EF patients did not display objective muscle impairment apart from histological abnormalities (myofibre MHC-I expression and myopathic changes) and myalgia. Inflammatory infiltrates were found only in the fascia, with or without eosinophils. Patients required shorter steroid treatment. DEM: diffuse eosinophilic mysositis; CK: creatine kinase; EMF: eosinophilic myofasciitis; IEM: idiopathic eosinophilic myositis