Nakajo-Nishimura syndrome: an autoinflammatory disorder showing pernio-like rashes and progressive partial lipodystrophy

Allergol Int. 2012 Jun;61(2):197-206. doi: 10.2332/allergolint.11-RAI-0416. Epub 2012 Mar 25.

Abstract

Nakajo-Nishimura syndrome (ORPHA2615; also registered as Nakajo syndrome in OMIM#256040) is a distinct inherited inflammatory and wasting disease, originally reported from Japan. This disease usually begins in early infancy with a pernio-like rash, especially in winter. The patients develop periodic high fever and nodular erythema-like eruptions, and gradually progress lipomuscular atrophy in the upper body, mainly the face and the upper extremities, to show the characteristic thin facial appearance and long clubbed fingers with joint contractures. So far about 30 cases have been reported from Kansai, especially Wakayama and Osaka, Tohoku and Kanto areas. At present, about 10 cases are confirmed to be alive only in the Kansai area, including one infant case in Wakayama. However, more cases are expected to be added in the near future. Although cause of the disease has long been undefined, a homozygous mutation of the PSMB8 gene, which encodes the β5i subunit of immunoproteasome, has been identified to be responsible in 2011. By analyses of the patients-derived cells and tissues, it has been suggested that accumulation of ubiquitinated and oxidated proteins due to immunoproteasome dysfunction causes hyperactivation of p38 mitogen-activated protein kinase and interleukin-6 overproduction. Since similar diseases with PSMB8 mutations have recently been reported from Europe and the United States, it is becoming clear that Nakajo-Nishimura syndrome and related disorders form proteasome disability syndromes, a new category of autoinflammatory diseases distributed globally.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Age of Onset
  • Animals
  • Antigen Presentation / genetics
  • Autoimmunity / genetics
  • Chilblains / epidemiology
  • Chilblains / etiology
  • Chilblains / genetics
  • Chilblains / immunology*
  • Erythema Nodosum / complications
  • Erythema Nodosum / epidemiology
  • Erythema Nodosum / genetics
  • Erythema Nodosum / immunology*
  • Exanthema / epidemiology
  • Exanthema / etiology
  • Exanthema / genetics
  • Exanthema / immunology*
  • Fingers / abnormalities
  • Humans
  • Infant
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / genetics
  • Japan
  • Lipodystrophy / epidemiology
  • Lipodystrophy / etiology
  • Lipodystrophy / genetics
  • Lipodystrophy / immunology*
  • MAP Kinase Signaling System / genetics
  • MAP Kinase Signaling System / immunology
  • Mutation / genetics
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / immunology
  • Proteasome Endopeptidase Complex / metabolism*

Substances

  • Interleukin-6
  • LMP7 protein
  • Proteasome Endopeptidase Complex

Supplementary concepts

  • Nakajo syndrome