Pathophysiology of pruritus in primary localized cutaneous amyloidosis

Br J Dermatol. 2016 Jun;174(6):1345-50. doi: 10.1111/bjd.14391. Epub 2016 Mar 15.

Abstract

Background: Primary localized cutaneous amyloidosis (PLCA) is a chronic pruritic dermatosis prevalent among Southern Chinese and South American populations. Pruritus is frequently present and can be debilitating; its pathophysiology is largely unknown.

Objectives: To investigate if small-fibre neuropathy (SFN), which results in a reduction of intraepidermal nerve fibres (IENF) and abnormalities in quantitative thermal sensory testing (QST), is present in PLCA.

Methods: Twenty Chinese patients (10 men) and 20 ethnicity-, sex- and age-matched controls underwent QST assessments. The patients' warm detection threshold (WDT) and heat pain threshold at the typical lesional sites were determined. Serum interleukin (IL)-31 levels were measured. Lesional biopsies were stained for IENF, IL-31 and its receptor's subunits [IL-31RA and oncostatin M receptor-β (OSMRβ)], and nerve growth factor (NGF) and its receptor [tropomyosin receptor kinase A (TrkA)], and were compared with normal skin obtained from archival paraffin-embedded specimens.

Results: WDT was significantly higher in patients at all sites and correlated with itch scores (r = 0·59; P < 0·01). Patient biopsies revealed lower IENF counts (P < 0·01 using protein gene product 9.5, β3-tubulin and Neurofilament 200 stains) and increased epidermal expression of OSMRβ (P < 0·01) and IL-31RA (P < 0·01). Cutaneous IL-31, NGF and TrkA stains were not significantly increased in patients. Serum IL-31 was not significantly higher in patients.

Conclusions: SFN is present in PLCA. Pruritus in PLCA is likely associated with hypersensitivity of cutaneous nerve fibres, which may be related to an increased expression of epidermal IL-31 receptors. Targeting IL-31 receptors is therefore a potential therapeutic approach.

MeSH terms

  • Adult
  • Aged
  • Amyloidosis, Familial / complications*
  • Case-Control Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Interleukins / metabolism
  • Male
  • Middle Aged
  • Nerve Growth Factor / metabolism
  • Pruritus / etiology*
  • Sensory Thresholds / physiology
  • Skin Diseases, Genetic / complications*
  • Thermosensing / physiology
  • Young Adult

Substances

  • IL31 protein, human
  • Interleukins
  • NGF protein, human
  • Nerve Growth Factor

Supplementary concepts

  • Amyloidosis, Primary Cutaneous