Caspase recruitment domain 15 mutations and rheumatic diseases

Carlos D. Rose, Tammy M. Martin

Research output: Contribution to journalReview articlepeer-review

18 Scopus citations


Purpose of review: The purpose of this article is to review the foundational work and current developments on a group of rheumatic disorders associated with mutations in the caspase recruitment domain 15/nucleotide oligomerization domain 2 gene. Recent findings: To date, there are at least 10 arthritic conditions for which specific genetic mutations have been demonstrated. They include familial Mediterranean fever; tumor necrosis factor receptor associated periodic syndrome; hyper immunoglobulin D syndrome; neonatal onset multisystemic inflammatory disease; pyogenic arthritis pyoderma gangrenosum and acne; Muckle-Wells syndrome; familial cold autoinflammatory syndrome; immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome; Crohn's disease; and familial and sporadic sarcoid granulomatous arthritis. This review focuses on recent progress in the last two diseases and the caspase recruitment domain 15 genetic defects with which they are associated. Up to 50% of patients with familial granulomatous arthritis (Blau's syndrome), 90% of those with sporadic granulomatous arthritis (early-onset sarcoidosis), and 40% of individuals with Crohn's disease have documented mutations in the caspase recruitment domain 15 gene. Summary: Although histologically, Crohn's disease and familial and sporadic sarcoid granulomatous arthritis are distinct from rheumatoid arthritis because of the defining presence (albeit in not all cases) of non-caseating granulomata in the synovial and intestinal tissues, respectively, they still represent a promising model of both chronic synovitis and uveitis. In addition, once the actual mechanism is discovered by which defects of the caspase recruitment domain 15 gene product lead to chronic arthritis, it may uncover unsuspected biologic targets for therapeutics.

Original languageEnglish (US)
Pages (from-to)579-585
Number of pages7
JournalCurrent opinion in rheumatology
Issue number5
StatePublished - Sep 1 2005


  • Blau's syndrome
  • Caspase recruitment domain 15
  • Crohn's disease
  • Sarcoidosis

ASJC Scopus subject areas

  • Rheumatology


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