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Proteasome-associated autoinflammatory syndromes
Other Resources UpToDate PubMed

Proteasome-associated autoinflammatory syndromes

Contributors: Sabrina Popatia, Susan Burgin MD
Other Resources UpToDate PubMed


Proteasome-associated autoinflammatory syndromes (PRAAS) comprise a group of extremely rare conditions with overlapping clinical features. All are autosomal recessive conditions, and they most commonly result from different mutations of the PSMB8 gene, an essential component of proteasomes. Proteasomes are intracellular protease complexes that degrade polyubiquitinated proteins identified for disposal. They are involved in cell cycle regulation, gene repair, and activation of the NF-kappa B and IFN pathways.

PRAAS include chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome, Japanese autoinflammatory syndrome with lipodystrophy (JASL), joint contractures, muscular atrophy, microcytic anemia, and panniculitis-induced lipodystrophy (JMP syndrome), and Nakajo-Nishimura syndrome (NNS).

Patients with PRAAS typically present at birth or in early infancy with periodic fever, variable skin eruptions, lipodystrophy, hepatosplenomegaly, and muscular atrophy and myositis, accompanied by anemia of chronic disease and elevated acute phase reactants (ESR, C-reactive protein [CRP]). Flares and inflammatory symptoms are typically noted by 6 months of age, and patients accumulate progressive damage from chronic inflammation during childhood.


M04.8 – Other autoinflammatory syndromes

702449004 – Autoinflammation, lipodystrophy and dermatosis syndrome

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Diagnostic Pearls

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Differential Diagnosis & Pitfalls

PRAAS includes CANDLE syndrome, JASL, JMP syndrome, and Nakajo-Nishimura syndrome. Also consider:
  • Acute febrile neutrophilic dermatosis
  • Erythema nodosum
  • Urticarial vasculitis
  • Erythema annulare centrifugum
  • Juvenile dermatomyositis
  • Juvenile Systemic lupus erythematosus
  • Cryopyrin-associated periodic syndromes (CAPS)
  • Familial lipodystrophy syndromes – no fever, presents as young adult or in middle age
  • Leukemia cutis
  • Aicardi-Goutières syndrome (AGS)

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Last Reviewed:03/18/2018
Last Updated:07/20/2023
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Proteasome-associated autoinflammatory syndromes
A medical illustration showing key findings of Proteasome-associated autoinflammatory syndromes : Hepatosplenomegaly, Muscle atrophy, CRP elevated, ESR elevated, Periodic fever
Copyright © 2024 VisualDx®. All rights reserved.