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Dermatologie (Heidelberg, Germany) Mar 2024Scleromyxedema or generalized diffuse lichen myxoedematosus is a rare mucinosis that is associated with monoclonal gammopathy and which frequently affects multiple... (Review)
Review
Scleromyxedema or generalized diffuse lichen myxoedematosus is a rare mucinosis that is associated with monoclonal gammopathy and which frequently affects multiple extracutaneous organ systems. The pathogenesis of scleromyxedema has not been fully elucidated, but includes stimulation of glycosaminoglycan synthesis. The clinical course of scleromyxedema is chronic and often progressive, leading to severe morbidity and even death. The characteristic skin findings encompass multiple waxy papules often on indurated plaques, while thickening of skin leads to conspicuous folds on glabella and dorsal aspects of finger joints. Microscopical manifestations are dermal deposits of glycosaminoglycans between collagen bundles in reticular dermis, increased numbers of fibroblasts and fibrosis as well as loss of elastic fibers. Progressive skin involvement results in decreased mobility of the mouth and joints and even contractures. Extracutaneous manifestations occur in the musculoskeletal or cardiovascular system, in the gastrointestinal or respiratory tract, in the kidneys or in the central and peripheral nervous system. There are no in-label or evidence-based treatments available for scleromyxedema, but by expert consensus high-dose immunoglobulins are considered as treatment of choice, followed in case of insufficient efficacy by systemic glucocorticosteroids and then lenalidomide or thalidomide. In severe and refractory cases, autologous hematopoietic stem cell transplantation has been performed. Long-term maintenance treatment is usually required to prevent recurrences. Close interdisciplinary follow-up is recommended.
Topics: Humans; Scleromyxedema; Skin; Lenalidomide; Thalidomide; Dermis
PubMed: 38363313
DOI: 10.1007/s00105-024-05303-0 -
Nature Communications Nov 2023Tissue-resident macrophages are critical for tissue homeostasis and repair. We previously showed that dermis-resident macrophages produce CCL24 which mediates their...
Tissue-resident macrophages are critical for tissue homeostasis and repair. We previously showed that dermis-resident macrophages produce CCL24 which mediates their interaction with IL-4 eosinophils, required to maintain their M2-like properties in the T1 environment of the Leishmania major infected skin. Here, we show that thymic stromal lymphopoietin (TSLP) and IL-5 type 2 innate lymphoid cells are also required to maintain dermis-resident macrophages and promote infection. Single cell RNA sequencing reveals the dermis-resident macrophages as the sole source of TSLP and CCL24. Generation of Ccl24-cre mice permits specific labeling of dermis-resident macrophages and interstitial macrophages from other organs. Selective ablation of TSLP in dermis-resident macrophages reduces the numbers of IL-5 type 2 innate lymphoid cells, eosinophils and dermis-resident macrophages, and ameliorates infection. Our findings demonstrate that dermis-resident macrophages are self-maintained as a replicative niche for L. major by orchestrating localized type 2 circuitries with type 2 innate lymphoid cells and eosinophils.
Topics: Animals; Mice; Immunity, Innate; Eosinophils; Interleukin-5; Lymphocytes; Cytokines; Thymic Stromal Lymphopoietin; Macrophages; Leishmaniasis, Cutaneous; Dermis
PubMed: 38030609
DOI: 10.1038/s41467-023-43588-2