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Sarcoidosis is a multisystemic disease characterized by non-caseating granuloma infiltrating various organs. The form with symptomatic muscular involvement is called muscular sarcoidosis. The impact of immune cells composing the granuloma on the skeletal muscle is misunderstood. Here, we investigated the granuloma–skeletal muscle interactions through spatial transcriptomics on two patients affected by muscular sarcoidosis. Five major transcriptomic clusters corresponding to perigranuloma, granuloma, and three successive muscle tissue areas (proximal, intermediate, and distal) around the granuloma were identified. Analyses revealed upregulated pathways in the granuloma corresponding to the activation of T-lymphocytes and monocytes/macrophages cytokines, the upregulation of extracellular matrix signatures, and the induction of the TGF-β signaling in the perigranuloma. A comparison between the proximal and distal muscles to the granuloma revealed an inverse correlation between the distance to the granuloma and the upregulation of cellular response to interferon-γ/α, TNF-α, IL-1,4,6, fibroblast proliferation, epithelial to mesenchymal cell transition, and the downregulation of muscle gene expression. These data shed light on the intercommunications between granulomas and the muscle tissue and provide pathophysiological mechanisms by showing that granuloma immune cells have a direct impact on proximal muscle tissue by promoting its progressive replacement by fibrosis via the expression of pro-inflammatory and profibrosing signatures. These data could possibly explain the evolution towards a state of disability for some patients.

Objective: Dermatomyositis associated with anti-MDA5 autoantibodies (DM-MDA5+) is a rare autoimmune disease usually characterized by skin involvement, often-severe lung involvement, and general features. Several reports of infections have been described, sometimes early after the introduction of immunosuppressive therapy. We studied the infection risk in a DM-MDA5+ population. Methods: A retrospective cohort study comparing the number and type of infections during the follow-up of 19 patients with DM-MDA5+ and 37 patients with another type of inflammatory myopathy was analyzed. Patients in both groups were matched on initial immunosuppressive therapy. We described and compared significant infectious complications (SIC) in each group. Results: Patients DM-MDA5+ had more SIC: 27 events in the DM-MDA5+ group versus 6 in the controls (HR 7.08, 95% CI 2.50–20.04, p < 0.0001). The number of SIC per patient was higher in DM-MDA5+ (1.4 ± 1.57 vs. 0.16 ± 0.44, p < 0.001). These were mainly lung (n = 13, 48%) and skin infections (n = 6, 22%), more often infections of an undetermined infectious agent (n = 11, 41%) or of bacterial origin (n = 9, 33%). A few cases of opportunistic infections were reported. The median duration of follow-up without SIC event in the DM-MDA5+ cohort was 3.5 months. Conclusion: Patients with DM-MDA5+ have an increased infection risk compared to others inflammatory myopathies irrespective of immunosuppressive therapy exposure. These results highlight the importance of monitoring for infection during patient follow-up.

Sarcoidosis is a systemic granulomatous disease of unknown cause characterized by a wide variety of presentations. Its diagnosis is based on three major criteria: a clinical presentation compatible with sarcoidosis, the presence of non-necrotizing granulomatous inflammation in one or more tissue samples, and the exclusion of alternative causes of granulomatous disease. Many conditions may mimic a sarcoid-like granulomatous reaction. These conditions include infections, neoplasms, immunodeficiencies, and drug-induced diseases. Moreover, patients with sarcoidosis are at risk of developing opportunistic infections or lymphoma. Reliably confirming the diagnosis of sarcoidosis and better identifying new events are major clinical problems in daily practice. To address such issues, we present seven emblematic cases, seen in our department, over a ten-year period along with a literature review about case reports of conditions misdiagnosed as sarcoidosis.

Sarcoidosis is a multi-system disease of unknown etiology characterized by the formation of granulomas in various organs. It affects people of all ethnic backgrounds and occurs at any time of life but is more frequent in African Americans and Scandinavians and in adults between 30 and 50 years of age. Sarcoidosis can affect any organ with a frequency varying according to ethnicity, sex and age. Intrathoracic involvement occurs in 90% of patients with symmetrical bilateral hilar adenopathy and/or diffuse lung micronodules, mainly along the lymphatic structures which are the most affected system. Among extrapulmonary manifestations, skin lesions, uveitis, liver or splenic involvement, peripheral and abdominal lymphadenopathy and peripheral arthritis are the most frequent with a prevalence of 25–50%. Finally, cardiac and neurological manifestations which can be the initial manifestation of sarcoidosis, as can be bilateral parotitis, nasosinusal or laryngeal signs, hypercalcemia and renal dysfunction, affect less than 10% of patients. The diagnosis is not standardized but is based on three major criteria: a compatible clinical and/or radiological presentation, the histological evidence of non-necrotizing granulomatous inflammation in one or more tissues and the exclusion of alternative causes of granulomatous disease. Certain clinical features are considered to be highly specific of the disease (e.g., Löfgren’s syndrome, lupus pernio, Heerfordt’s syndrome) and do not require histological confirmation. New diagnostic guidelines were recently published. Specific clinical criteria have been developed for the diagnosis of cardiac, neurological and ocular sarcoidosis. This article focuses on the clinical presentation and the common differentials that need to be considered when appropriate.