Pompe disease is a rare hereditary glycogen storage disorder due to lysosomal acid alpha-glucosidase deficiency. Enzyme replacement therapy (ERT) is the only available treatment. Infusion-associated reactions (IAR) are challenging since there are no guidelines for ERT rechallenge after a drug hypersensitivity reaction (DHR) in Pompe disease. The objective of the present study was to describe IAR and their management in late-onset Pompe disease (LOPD) patients in France, and to discuss the various possibilities of ERT rechallenge. An exhaustive screening of LOPD patients receiving ERT between 2006 and 2020 from the 31-participating hospital-based or reference centers was performed. The patients who had presented at least one hypersensitivity IAR (=DHR) episode were included. Demographic characteristics of the patients, IAR onset and timing, were retrospectively collected from the French Pompe Registry. Fifteen patients among 115 treated LOPD patients in France presented at least 1 IAR; 80.0% were women. Twenty-nine IAR were reported; 18 (62.1%) IAR were Grade I reactions, 10 (34.5%) IAR were Grade II, and 1 (3.4%) IAR was Grade III. IgE-mediated hypersensitivity was found in 2/15 patients (13.3%). The median [IQR] time from ERT introduction to the first IAR was 15.0 months [11.0-24.0]. ERT was safely and effectively re-introduced either with premedication alone, or in combination with either modified regimen or desensitization protocol, in all 9 rechallenged patients; including in patients with IgE-mediated hypersensitivity, in the patient with the Grade III reaction, as well as in patients with very high anti-GAA titer. Based on the results herein and previous reports, we discuss premedication and modified regimen for Grade I reactions, and desensitization in Grade II and III reactions. In conclusion, ERT-induced IAR can be safely and effectively managed with a modified regimen or desensitization protocol in LOPD patients.

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. 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. 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. 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.

Idiopathic inflammatory myopathies (IIM) are rare, acquired muscle diseases; their diagnosis of is based on clinical, serological, and histological criteria. MHC-I-positive immunostaining, although non-specific, is used as a marker for IIM diagnosis; however, the significance of major histocompatibility complex (MHC)-II immunostaining in IIM remains debated. We investigated patterns of MHC-II immunostaining in myofibers and capillaries in muscle biopsies from 103 patients with dermatomyositis ([DM], n = 31), inclusion body myositis ([IBM], n = 24), anti-synthetase syndrome ([ASyS], n = 10), immune-mediated necrotizing myopathy ([IMNM], n = 18), or overlap myositis ([OM], n = 20). MHC-II immunostaining of myofibers was abnormal in 63/103 of patients (61%) but the patterns differed according to the IIM subgroup. They were diffuse in IBM (96%), negative in IMNM (83%), perifascicular in ASyS (70%), negative (61%) or perifascicular (32%) in DM, and either clustered (40%), perifascicular (30%), or diffuse heterogeneous (15%) in OM. Capillary MHC-II immunostaining also identified quantitative (capillary dropout, n = 47/88, 53%) and qualitative abnormalities, that is, architectural abnormalities, including dilated and leaky capillaries, (n = 79/98, 81%) in all IIM subgroups. Thus, MHC-II myofiber expression patterns allow distinguishing among IIM subgroups. We suggest the addition of MHC-II immunostaining to routine histological panels for IIM diagnosis.

Individuals living with neuromuscular disease (NMD) often face substantial financial strain due to the chronic and progressive nature of these conditions. Despite growing awareness, the extent and determinants of financial toxicity (FT) in this population remain poorly understood. We assessed FT among individuals with NMD or their caregivers in Canada using a validated patient-reported outcome measure. We conducted a national, cross-sectional survey of individuals with NMD or their caregivers registered with Muscular Dystrophy Canada (MDC). The survey, available in English and French, was completed online or by telephone with assistance from MDC personnel. FT was measured using the validated Comprehensive Score for Financial Toxicity (COST)-Functional Assessment of Chronic Illness Therapy questionnaire. Multivariable generalized linear models were used to identify factors associated with FT. A total of 1,426 participants (mean [SD] age, 52.0 [19.5] years; 52% female) completed the survey. Seventy-five percent reported household incomes below the national median, primarily because of reduced employment. The average COST score was 17.2 [10.4], significantly lower than scores reported in other chronic conditions, including cancer. Moreover, 70% of respondents had COST scores below 26, indicating moderate or severe FT. After adjusting for other factors, COST scores were significantly worse among caregivers than in adults with NMDs. Lower scores were also observed among individuals identified as racialized minority (rate ratio [RR] 0.74; 95% CI 0.64-0.87); those with lower household income (RR 0.59; 95% CI 0.51-0.69), those with lower education (RR 0.91; 95% CI 0.82-1.00), and those unable to work (RR 0.74; 95% CI 0.64-0.86); students (RR 0.54; 95% CI 0.34-0.86); or early retirees (RR 0.86, 95% CI 0.74-0.99). FT was also greater among those diagnosed with autoimmune myopathies (RR 0.82; 95% CI 0.73-0.92), spinal muscular atrophy (RR 0.79; 95% CI 0.66-0.96), and limb-girdle muscular dystrophy (RR 0.87; 95% CI 0.77-0.99). FT is highly prevalent among people living with NMDs, particularly caregivers and those with socioeconomic and clinical vulnerabilities. Policies to improve financial support and health care coverage for NMD-related needs could help alleviate this burden. Further research is required to understand the mechanisms contributing to FT within NMD subgroups.

Introduction: Neuromuscular diseases (NMDs) impose multifaceted challenges on individuals and their families, often resulting in significant medical and non‐medical expenses. While cost‐of‐illness (COI) studies provide valuable quantitative data, few explore the lived experience of financial strain. This study aims to identify the complex, often hidden, financial impacts experienced by individuals with NMDs and their families. Methods: We conducted a qualitative study involving four virtual semi‐structured focus groups, with 58 participants (76% patients and 24% caregivers). Participants were recruited from Muscular Dystrophy Canada's database and had previously completed the national BIND COI survey. Participants shared firsthand accounts of direct non‐medical costs, psychosocial burdens and opportunity costs, highlighting hidden expenses, substantial out‐of‐pocket costs, and the broader financial and emotional toll on families. Thematic analysis of the transcripts of the discussions was performed using an inductive approach, guided by a rare‐disease‐specific socio‐economic burden framework. Results: Four key themes emerged: informational costs (lack of awareness/support for navigating financial resources), time‐related costs (time spent advocating for supports), opportunity costs (loss of income or career advancement), and costs to independence (emotional toll and out‐of‐pocket costs for assistive devices and home modifications). Conclusion: This study identified four interconnected categories of hidden costs for people with NMDs and their families: informational burdens, administrative and advocacy demands, employment‐related opportunity costs, and reduced independence tied to out‐of‐pocket spending on equipment and home modifications. These findings reveal how financial and emotional pressures accumulate beyond what traditional COI estimates capture. Greater attention to these costs is critical for fostering equitable and sustainable healthcare systems. Patient or Public Contribution: This study was designed and conducted in partnership with individuals living with NMDs and caregivers. Three trained patient and family research partners contributed to the development of the focus group guide and interpretation of results. All participants contributed their lived experiences to inform and validate key findings. Their input was central to the design, analysis and preparation of this manuscript, ensuring alignment with community priorities.