Advances in understanding and treatment of scleromyxedema

Introduction: Scleromyxedema is a rare fibromucinosis, associated with monoclonal gammopathy, and other comorbidities with unpredictable prognosis. It usually affects middle-aged adults, without gender predilection. Incomplete understanding of the pathogenesis depends on the limited number of cases, but consolidated multicenter experience has produced the European guidelines for clinical management of isolated cases. Areas covered: A synthesis of current knowledge on pathogenesis and treatment of scleromyxedema is retrieved from PubMed database. Expert opinion: Understanding of scleromyxedema remains a challenge, without substantial progress in the explanation of mucin deposition origin, paraprotein role and factors primarly implicated in the disease progression. However, the definition of diagnostic criteria and lines of treatment have increased the awareness and early recognition of the disease in recent years. Timely treatment with high dose immunoglobulin has proven efficacy and tolerability, becoming first line treatment, eventually associated with thalidomide and/or systemic steroids. Very aggressive treatment, such as melphalan are no more recommended, while bortezomib and/or autologous stem cell transplant are considered in very recalcitrant cases. No promising new options are under evaluation. Future perspectives, besides etiopathogenesis improvements, are definition of prognostic criteria, to distinguish rapidly disabling disease from slow progression, and improvement of imaging, to support the diagnosis and management protocols