title: Pathophysiology of pruritus in primary localized cutaneous amyloidosis.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: National Skin Centre, 1 Mandalay Road, 308205, Singapore.|Lee Kong Chian School of Medicine, Singapore.
authors.forename: H L
authors.initials: HL
authors.lastname: Tey
authors.affiliation: National Skin Centre, 1 Mandalay Road, 308205, Singapore.
authors.forename: T
authors.initials: T
authors.lastname: Cao
authors.affiliation: Department of Dermatology and Temple Itch Center, Temple University School of Medicine, Philadelphia, PA, U.S.A.
authors.forename: L A
authors.initials: LA
authors.lastname: Nattkemper
authors.affiliation: National Skin Centre, 1 Mandalay Road, 308205, Singapore.
authors.forename: V W D
authors.initials: VW
authors.lastname: Tan
authors.affiliation: National Skin Centre, 1 Mandalay Road, 308205, Singapore.
authors.forename: Z A D
authors.initials: ZA
authors.lastname: Pramono
authors.affiliation: Department of Dermatology and Temple Itch Center, Temple University School of Medicine, Philadelphia, PA, U.S.A.
authors.forename: G
authors.initials: G
authors.lastname: Yosipovitch
mesh_terms: D000328:Adult; D000368:Aged; D028226:Amyloidosis, Familial / Q000150:complications*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000378:metabolism; D011537:Pruritus / Q000209:etiology*; D012684:Sensory Thresholds / Q000502:physiology; D012873:Skin Diseases, Genetic / Q000150:complications*; D013697:Thermosensing / Q000502:physiology; D055815:Young Adult
chemical_list: C502187:IL31 protein, human; D007378:Interleukins; C502240:NGF protein, human; D020932:Nerve Growth Factor