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Current Opinion in Rheumatology Nov 2014To synthesize the current known data on pathogenesis and treatment of scleromyxedema. This review will also highlight the clinical presentation, systemic features and... (Review)
Review
PURPOSE OF REVIEW
To synthesize the current known data on pathogenesis and treatment of scleromyxedema. This review will also highlight the clinical presentation, systemic features and outcomes and distinguishing features between scleromyxedema and scleroderma, as a common mimic.
RECENT FINDINGS
Most recent publications have focused on describing treatment responses with novel therapies, with the majority of cases reporting success with intravenous immunoglobulin. However, other therapies suggest promise as well in case reports, including bortezomib, thalidomide and stem cell transplantation. There is little information on pathogenesis; however, focus has been on the relationship between the mucin deposition and the monoclonal immunoglobulins that are seen in almost all patients with scleromyxedema.
SUMMARY
Scleromyxedema is a rare mucinous deposition disorder that shares clinical features with scleroderma but has important distinguishing features in clinical presentation and major organ complications that should be recognized. Patients typically respond well to therapy as highlighted in several larger series, but poor outcomes are reported in a few cases.
Topics: Boronic Acids; Bortezomib; Humans; Immunoglobulins, Intravenous; Pyrazines; Scleromyxedema; Thalidomide; Treatment Outcome
PubMed: 25215418
DOI: 10.1097/BOR.0000000000000118 -
Rheumatology (Oxford, England) Jul 2022
Topics: Humans; Immunoglobulins, Intravenous; Scleromyxedema
PubMed: 34554227
DOI: 10.1093/rheumatology/keab718 -
Der Hautarzt; Zeitschrift Fur... Nov 2018Scleromyxedema is a rare disorder that frequently affects multiple extracutaneous organ systems and is usually associated with monoclonal gammopathy. The pathogenesis... (Review)
Review
Scleromyxedema is a rare disorder that frequently affects multiple extracutaneous organ systems and is usually associated with monoclonal gammopathy. The pathogenesis of scleromyxedema is unknown. The clinical course is chronic and progressive and can lead to marked morbidity or death. The skin findings consist of multiple waxy papules and indurated plaques. Progressive skin involvement can lead to decreased mobility of the mouth and joints. Extracutaneous manifestations occur in the musculoskeletal or cardiovascular system, in the gastrointestinal or respiratory tract, or in the kidneys. There are no approved or evidence-based treatment options available for scleromyxedema. High-dose immunoglobulins are considered the treatment of choice, followed by lenalidomide (or thalidomide) and systemic glucocorticosteroids, or in severe cases even autologous hematopoetic stem cell transplantation. Long-term maintenance treatment is usually required and close clinical follow-up is necessary as recurrence of scleromyxedema is common after withdrawal of an effective therapy.
Topics: Humans; Lenalidomide; Rare Diseases; Recurrence; Scleromyxedema
PubMed: 30135969
DOI: 10.1007/s00105-018-4257-8 -
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 -
Journal Der Deutschen Dermatologischen... Dec 2020Scleromyxedema is a rare, cutaneous deposition disorder from the group of mucinoses, which can affect multiple organs and is virtually always associated with a...
Scleromyxedema is a rare, cutaneous deposition disorder from the group of mucinoses, which can affect multiple organs and is virtually always associated with a monoclonal gammopathy. Cutaneous manifestations are usually generalized, 2 to 3 mm sized, dome-shaped or flat-topped, waxy, slightly red to skin-colored papules and sclerodermoid indurations. Neurological, rheumatological, cardiovascular, gastrointestinal, respiratory tract, renal and ophthalmologic manifestations can occur, with decreasing frequency. A serious and potentially lethal complication is the dermato-neuro syndrome which manifests with flu-like prodromes followed by fever, convulsions and coma. Untreated, scleromyxedema usually takes an unpredictable and potentially lethal progressive disease course over several years. According to a widely acknowledged classification by Rongioletti a diagnosis of scleromyxedema can be rendered when (1) generalized, papular and sclerodermoid eruption, (2) a histological triad of mucin deposition, fibroblast proliferation and fibrosis, and (3) monoclonal gammopathy are present, and (4) thyroid disease is absent. Apart from the classic microscopic triad, an interstitial granuloma annulare like pattern was also described. The pathogenesis of scleromyxedema is unknown. A potential role for various, as yet unknown serum factors has been discussed. An unequivocal causal relationship between paraproteinemia and disease manifestations could not be established to date. High dose intravenous immunoglobulins (IVIg) are the first-line treatment of choice according to the most recent European guidelines.
Topics: Granuloma Annulare; Humans; Immunoglobulins, Intravenous; Scleromyxedema; Seizures; Skin
PubMed: 33373143
DOI: 10.1111/ddg.14319 -
Journal of Neurology Aug 2019Scleromyxedema is a chronic, idiopathic disorder associated with monoclonal gammopathy, and characterized by dermal mucin deposition. However, systemic manifestations... (Review)
Review
Scleromyxedema is a chronic, idiopathic disorder associated with monoclonal gammopathy, and characterized by dermal mucin deposition. However, systemic manifestations are frequent, including neuromuscular symptoms. We herein present a 71-year-old man who developed a vacuolar myopathy in a context of a known scleromyxedema, and we compare our observation with the nineteen other cases found in the medical literature. Such an association (especially with suggestive skin abnormalities) has to be known for two reasons. First, this diagnosis might be quite challenging because the myopathy may precede the typical skin changes. Secondly, conversely to other forms of vacuolar myopathy, some of the symptoms may respond (even partially) to immunomodulatory and/or immunosuppressant therapeutics.
Topics: Aged; Humans; Immunoglobulins, Intravenous; Lysosomal Storage Diseases; Male; Muscular Diseases; Scleromyxedema
PubMed: 31115676
DOI: 10.1007/s00415-019-09379-w -
The New England Journal of Medicine Nov 2023
Topics: Humans; Immunoglobulins, Intravenous; Scleromyxedema
PubMed: 37991858
DOI: 10.1056/NEJMicm2302207 -
Clinics in Dermatology 2006Scleromyxedema is a rare cutaneous mucinous disease characterized by a generalized papular sclerodermoid eruption and systemic manifestations that can lead to... (Review)
Review
Scleromyxedema is a rare cutaneous mucinous disease characterized by a generalized papular sclerodermoid eruption and systemic manifestations that can lead to significant morbidity and mortality. Although its etiology remains unknown, most theories focus on a pathogenic role by paraproteins; it must be noted, however, that nonparaprotein factors have been suggested to cause fibroblast proliferation and increased mucin production. Several treatment modalities including melphalan, cyclophosphamide, interferon alfa, and plasmapheresis have been suggested; however, further research is needed to prove treatment efficacy.
Topics: Disease Progression; Humans; Scleromyxedema; Skin
PubMed: 17113967
DOI: 10.1016/j.clindermatol.2006.07.011 -
International Journal of Dermatology Oct 2020Scleromyxedema is a chronic disease with high morbidity and mortality and no definitive therapeutic guidelines. (Review)
Review
IMPORTANCE
Scleromyxedema is a chronic disease with high morbidity and mortality and no definitive therapeutic guidelines.
OBJECTIVE
To review all available data on the efficacy and the safety of the available treatments of scleromyxedema and suggest a possible therapeutic approach.
EVIDENCE REVIEW
We performed a systematic literature review in Pubmed/Medline, Embase, and Cochrane collaboration databases, searching for all articles since 1990 on the treatments of scleromyxedema, with no limits on participant age, gender, or nationality.
FINDINGS
Ninety-seven studies were included in this systematic review, of which one prospective, two retrospective, 70 case reports/case series, and 24 letters/correspondence/clinical image. Intravenous immunoglobulin (IVIG) was the most used first-line therapy based on its efficacy and its generally well-tolerated nature; most patients require continued treatment to remain in remission. Thalidomide and systemic glucocorticoids were mostly considered as second-line therapies and were given alone or in association with IVIG. Patients with severe or refractory disease were treated with autologous bone marrow transplantation, melphalan, or bortezomib with dexamethasone.
CONCLUSIONS AND RELEVANCE
Consideration of patient comorbidities, disease distribution, clinician experience, and treatment accessibility is mandatory in every therapeutic approach of scleromyxedema.
Topics: Bortezomib; Humans; Prospective Studies; Retrospective Studies; Scleromyxedema; Thalidomide
PubMed: 32358980
DOI: 10.1111/ijd.14888 -
Journal of Scleroderma and Related... Jun 2019Scleromyxedema is a rare fibromucinous disorders, with several clinical and pathological overlaps with scleroderma and scleredema. Etiopathogenesis remains uncovered,... (Review)
Review
Scleromyxedema is a rare fibromucinous disorders, with several clinical and pathological overlaps with scleroderma and scleredema. Etiopathogenesis remains uncovered, and no explanation has been provided either for the origin of mucin deposition or for the paraprotein role. The disease does not show gender predilection and affects mainly middle-age adults. The course is unpredictable, and prognosis remains guarded for renal, cardiac, and neurologic complications, especially in the setting of dermato-neuro syndrome. A valuable recent progress is the consensus definition of diagnostic criteria and lines of treatment, which hold the promise to improve the early recognition and management of this rare condition worldwide. High-dose intravenous immunoglobulin has been suggested as the first-line treatment either alone or associated with systemic steroids and/or thalidomide. In very recalcitrant cases, adjunctive bortezomib and/or autologous stem cell transplant might be considered. Melphalan treatment was associated with very toxic side effects and actually is no longer recommended.
PubMed: 35382389
DOI: 10.1177/2397198318824929