Familial primary localized cutaneous amyloidosisE85.4

Localized (primary) cutaneous amyloidosis is a chronic skin disease caused by deposition of amyloid in the upper dermis. While primary cutaneous amyloidosis is mainly sporadic, familial clustering with autosomal dominant inheritance can be observed in some cases (about 10% of cases).

The male-to-female ratio in patients with a homozygous OSMR mutation (0.29) was significantly lower than in patients with a heterozygous OSMR mutation (1.08; P < 0.05) and in patients with wild-type OSMR (1.75; P < 0.01).

Familial autosomal dominant PLCA is due in part to mutations in the OSMR gene , which encodes the oncostatin M receptor-beta subunit (OSMR-beta) (Arita K et al. 2008). OSMR-beta belongs to the cytokine receptors of the interleukin-6 family and has two ligands:

• Oncostatin M
• and
• Interleukin-31.

Cultured keratinocytes from patients with familial primary localized cutaneous amyloidosis showed decreased activation of Jak-STAT, MAPK, and PI3K/Akt signaling pathways after OSM or IL-31 cytokine stimulation. The pathogenic amino acid substitutions are located in the extracellular fibronectin type III-like (FNIII) domains, regions critical for receptor dimerization and function (Arita K et al. 2008). Saeedi M et al. 2014 detected a C/T substitution at position 613 in his clientele by sequencing the mutant gene. This mutation leads to a change in the amino acid L613S (leucine 613 to serine).

The cytokines oncostatin especially interleukin-31 (itch cytokine) play a biological role in inflammation and proliferation, differentiation and apoptosis of keratinocytes.

First manifestation between the ages of 20 and 50. Familial primary cutaneous amyloidosis occurs particularly within certain geographical regions, such as South America and Southeast and Northwest Asia (Saeedi M et al. 2014).

The shins, forearms and/or back are typically affected.

The clinical findings correspond to the classic macular or lichenoid (lichen amyloidosus) primary cutaneous amyloidosis associated with pruritus.

Most cases of macular and lichenoid cutaneous amyloidosis (see below cutaneous amyloidoses) occur sporadically. However, in up to 10% of cases, an autosomal dominant family history is present, suggesting a genetic predisposition. The mutant genes in "Familial Primary Localized Cutaneous Amyloidosis" have been assigned to a locus on 5p13.1-q11.2. In 2008, pathogenic heterozygous missense mutations were identified in the OSMR gene, which encodes oncostatin M receptor beta (OSMRbeta), a cytokine receptor of the interleukin (IL)-6 family. OSMRbeta is expressed in several cell types, including keratinocytes, cutaneous nerves, and nociceptive neurons in the dorsal root ganglia; its ligands are oncostatin M and IL-31. Elucidation of the molecular basis of familial PLCA provides new insights into the mechanisms of itch in human skin and may lead to new therapeutic targets for itch.

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