A severe case of chronic infantile neurologic, cutaneous, articular syndrome treated with biologic agents

Arthritis Rheum. 2006 Jul;54(7):2314-20. doi: 10.1002/art.21965.


In this report we describe a case of severe chronic infantile neurologic, cutaneous, articular (CINCA) syndrome with a novel G307V cryopyrin mutation and all of the characteristic clinical and laboratory features of this autoinflammatory disease. There was no clear response to standard therapies, including human interleukin-1 (IL-1) receptor antagonist (anakinra) and soluble tumor necrosis factor receptor (etanercept). The patient finally had a partial clinical response (reduction in fever and irritability) and complete laboratory response (improved C-reactive protein and serum amyloid A levels) to humanized anti-IL-6 receptor antibody (MRA), but died from congestive heart failure and interstitial pneumonia 2 months after initiation of therapy. We serially measured the serum cytokine levels and expression of NF-kappaB activation in the patient's peripheral blood mononuclear cells before and during consecutive therapies. Pathologic examination of autopsy specimens was also performed. This case illustrates the continued difficulty in management of patients with CINCA syndrome and the complexity of the inflammatory pathways in this disorder.

Publication types

  • Case Reports

MeSH terms

  • Antibodies, Anti-Idiotypic / immunology
  • Antibodies, Anti-Idiotypic / therapeutic use*
  • Antirheumatic Agents / therapeutic use*
  • Autoimmune Diseases / blood
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / genetics
  • Carrier Proteins / genetics
  • Central Nervous System Diseases / drug therapy
  • Central Nervous System Diseases / physiopathology
  • Cytokines / blood
  • Etanercept
  • Exanthema / drug therapy
  • Exanthema / physiopathology
  • Fever / drug therapy
  • Fever / etiology
  • Humans
  • Immunoglobulin G / therapeutic use*
  • Infant
  • Interleukin 1 Receptor Antagonist Protein
  • Joint Diseases / drug therapy
  • Joint Diseases / physiopathology
  • Male
  • Mutation
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Receptors, Interleukin-6 / immunology
  • Receptors, Tumor Necrosis Factor / therapeutic use*
  • Sialoglycoproteins / therapeutic use*
  • Syndrome


  • Antibodies, Anti-Idiotypic
  • Antirheumatic Agents
  • Carrier Proteins
  • Cytokines
  • IL1RN protein, human
  • Immunoglobulin G
  • Interleukin 1 Receptor Antagonist Protein
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Receptors, Interleukin-6
  • Receptors, Tumor Necrosis Factor
  • Sialoglycoproteins
  • Etanercept