Advances in understanding and treatment of scleromyxedema

ABSTRACT

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.

KEYWORDS:

• Autologous stem cell transplant
• bortezomib
• cutaneous mucinosis
• corticosteroids
• dermato-neuro syndrome
• intravenous immunoglobulin
• monoclonal gammopathy
• melphalan
• scleromyxedema
• thalidomide

Article highlights

• The pathogenesis of scleromyxedema remain a challenge: the primum movens, as well as the fine mechanisms causing skin mucinosis and fibrosis are uncovered. The associated monoclonal gammopathy might represent a negative prognostic rather than pathogenic factor.

• European guidelines have covered the lack of randomized trials, due to the rarity of the disease, supporting diagnostic criteria, and treatment recommendations. High-dose IVIg administration is confirmed as first line therapy, being substantially efficacious both on skin and systemic involvement, as well as in dermato-neuro syndrome, which remains the most unpredictable complications. Systemic steroids, thalidomide and/or lenalinomide, are useful in combination with IVIgs. Limited data on additional efficacy place as third lines options the autologous peripheral blood stem cell transplantation and bortezomib. Cytotoxic drugs, such as melphalan are no more recommended, except for very recalcitrant disease.

• Very mild disease, confined to limited areas of the skin without systemic manifestations might beneficiate of topical steroids or calcineurin inhibitors.

• Future perspectives are the definition of prognostic criteria, to distinguish rapidly evolving disabling disease from slow progression patients. Improvement of skin imaging and adoption of the modified Rodnan score system for scleromyxedema are valuable tools to increase standardization of management, and treatment response evaluation.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

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