Advances in Current and Emerging Therapies for Challenging Cutaneous Mucinoses with Substantial Morbidity and Therapeutic Complexity: A Narrative Review.

BACKGROUND

Cutaneous mucinoses are a heterogeneous group of disorders characterized by dermal accumulation of glycosaminoglycans, leading to a wide spectrum of clinical manifestations. Among these, pretibial myxedema (PTM), scleredema, scleromyxedema, and obesity-associated lymphedematous mucinosis represent clinically relevant and therapeutically challenging entities with substantial morbidity.

SUMMARY: A narrative review of the literature was conducted using PubMed, MEDLINE, and Google Scholar to identify studies. Articles reporting clinical, pathogenetic, and therapeutic data were included, with emphasis on treatment efficacy, safety, and a focus on emerging mechanism-based treatments.

KEY MESSAGES: Advances in the understanding of disease mechanisms - including autoimmune dysregulation, paraproteinemia-driven fibroblast activation, and lymphatic or metabolic impairment - have led to the development of targeted therapies. Intravenous immunoglobulin remains central in scleromyxedema, while phototherapy is a mainstay in scleredema. In PTM, targeted approaches such as insulin-like growth factor-1 receptor inhibition and B-cell-directed therapies show promising results. In obesity-associated forms, management is primarily based on metabolic and mechanical interventions. The therapeutic landscape of cutaneous mucinoses is evolving toward mechanism-based, multimodal strategies. Despite promising advances, high-quality evidence remains limited, highlighting the need for further studies to establish standardized treatment algorithms.