A cryopyrin-associated periodic syndrome with joint destruction.
OBJECTIVE
Describe four generations (11 members) of a family with a cryopyrin-associated periodic syndrome (CAPS), including joint destruction, associated with a CIAS1-gene mutation and good responses to anakinra.


METHODS
In addition to detailed questioning and physical examination, six family members underwent haematological, immunological and biochemical testing. Exon 3 of the CIAS1 gene was sequenced in search of a mutation in the 1q44 region.


RESULTS
During childhood or adolescence, four family members developed different combinations of the following CAPS manifestations: deafness (3/4); arthritis (4/4) with joint destruction for two of them; nervous (cerebral demyelinization, 2/4), cutaneous (livedo and/or urticaria, 3/4) and eye lesions (episcleritis and/or papilloedema, 4/4); IgA hypergammaglobulinaemia (4/4) and inflammatory syndrome (3/4). Sequencing of six family members' CIAS1-gene exon 3 identified a heterozygous mutation, c.1043C > T. Pertinently, this CAPS is distinct from chronic infantile neurological cutaneous and arthritis syndrome/neonatal onset multisystemic inflammatory disease syndrome and Muckle-Wells syndrome (MWS), which also result from exon 3 mutations in this gene. Moreover, this family did not have the usual neurological manifestations, typical morphological features and frequent amyloidosis of MWS.


CONCLUSIONS
We describe a previously unreported form of CAPS with atypical neurological signs, joint destruction and livedo. This observation extends the clinical spectrum associated with CIAS1 mutations. Anakinra, an interleukin-1-receptor antagonist, prescribed to two family members, was highly effective.
Lequerré
T
T
Department of Rheumatology, Rouen University Hospital, 76031 Rouen, Cedex, France. thierry.lequerre@univ-rouen.fr
Vittecoq
O
O
Saugier-Veber
P
P
Goldenberg
A
A
Patoz
P
P
Frébourg
T
T
Le Loët
X
X
D000293:Adolescent; D017668:Age of Onset; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001168:Arthritis / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics*; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D010505:Familial Mediterranean Fever / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use; D008297:Male; D009154:Mutation; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010375:Pedigree; D011859:Radiography; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D002352:Carrier Proteins; D053590:Interleukin 1 Receptor Antagonist Protein; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human