Primary localized cutaneous amyloidosis review: An update on immunopathogenesis and therapeutics

Summary: Abstract Body: Primary Localized Cutaneous Amyloidosis (PLCA) encompasses a group of disorders characterized by the deposition of amyloid proteins in the skin, with lichen amyloidosis (LA) and macular amyloidosis (MA) being the most common subtypes. These conditions often present with pruritic skin lesions that significantly impact patients' quality of life. Although PLCA is primarily sporadic, familial cases suggest a genetic predisposition, particularly involving mutations in the oncostatin M receptor-β (OSMRβ) and interleukin (IL)-31RA genes. Recent research has highlighted the IL-31 signaling pathway in PLCA's immunopathogenesis with IL-31 as a potential target due its role in mediating pruritus. Current treatment options, including topical and systemic therapies, offer varying degrees of efficacy, but there is no standardized treatment protocol. Emerging therapies, such as the aryl hydrocarbon receptor agonist, IL-4Rα inhibitor, IL-13 inhibitors, IL-31RA inhibitor, OSMRβ inhibitor, janus kinase (JAK) inhibitors, and phosphodiesterase 4 inhibitor offer promise in targeting the immunopathogenic mechanisms of PLCA. These novel treatments could potentially transform the management of PLCA, especially in recalcitrant disease refractory to conventional therapies. Further research is warranted to establish the efficacy and safety of these new therapeutic approaches, particularly in PLCA patients without atopic conditions. This review provides an updated overview of the immunopathogenesis of PLCA and explores the expanding therapeutic landscape to improve patient outcomes. Jiwon Park¹, Gabriela Soto-Canetti^{2, 3}, Jordan Talia² 1. The University of Texas Health Science Center at San Antonio Joe R and Teresa Lozano Long School of Medicine, San Antonio, TX, United States. 2. Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, United States. 3. Ponce Health Sciences University School of Medicine, Ponce, Puerto Rico. Clinical Research: Interventional Research