A cryopyrin-associated periodic syndrome with joint destruction

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.

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.

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.

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.