New insight into mechanisms of pruritus from molecular studies on familial primary localized cutaneous amyloidosis

作者：Tanaka A; Arita K; Lai Cheong J E; Palisson F; Hide M; McGrath J A^*

来源：British Journal of Dermatology, 2009, 161(6): 1217-1224.

DOI：10.1111/j.1365-2133.2009.09311.x

• amyloid
• dorsal root ganglion
• interleukin-31
• oncostatin M
• pruritus

Macular and lichen amyloidosis are common variants of primary localized cutaneous amyloidosis (PLCA) in which clinical features of pruritus and skin scratching are associated with histological findings of deposits of amyloid staining on keratinous debris in the papillary dermis. Most cases are sporadic, but an autosomal dominant family history may be present in up to 10% of cases, consistent with a genetic predisposition in some individuals. Familial PLCA has been mapped to a locus on 5p13.1-q11.2 and in 2008 pathogenic heterozygous missense mutations were identified in the OSMR gene, which encodes oncostatin M receptor beta (OSMR beta), an interleukin (IL)-6 family cytokine receptor. OSMR beta is expressed in various cell types, including keratinocytes, cutaneous nerves and nociceptive neurones in dorsal root ganglia; its ligands are oncostatin M and IL-31. All pathogenic mutations are clustered in the fibronectin-III repeat domains of the extracellular part of OSMR beta, sites that are critical for receptor dimerization (with either gp130 or IL-31RA), and lead to defective signalling through Janus kinase-signal transducers and activators of transcription, extracellular signal-regulated protein kinase 1/2 and phosphoinositide 3 kinase/Akt pathways. Elucidating the molecular pathology of familial PLCA provides new insight into mechanisms of pruritus in human skin, findings that may have relevance to developing novel treatments for skin itching. This review provides a clinicopathological and molecular update on familial PLCA.

• 出版日期2009-12