Analysis of cryopyrin-associated periodic syndromes (CAPS) in German children: epidemiological, clinical and genetic characteristics.
BACKGROUND
Cryopyrin-associated periodic syndromes (CAPS) are rare disorders belonging to the group of hereditary periodic fever (HPF)syndromes. These auto-inflammatory diseases(AID) are characterized by recurrent episodes of inflammation with attacks of fever variably associated with serosal, synovial and / or cutaneous inflammation, usually in a self-limiting manner, and with a mostly monogenic origin. The aims were to determine the incidence of CAPS and the spectrum of mutations in the NLRP3 (formerly= CIAS1) gene and to describe the clinical manifestations.


METHODS
A prospective surveillance of children with CAPS was conducted in Germany during a time period of 3 years(2003-2006). Monthly inquiries were sent to 370 children's hospitals by the German Paediatric Surveillance Unit (Clinic-ESPED, n1) and to 2 laboratories (Laboratory-ESPED, n2). Inclusion criteria were children ≤ 16 years of age, disease-associated NLRP3 mutation, more than 3 self-limiting episodes of fever > 38.5 ° C, and increased inflammation markers. Clinical, epidemiological and genetic data were evaluated via questionnaires.


RESULTS
6 out of 14 patients were identified in Clinic-ESPED (n1) and 13 / 14 in Laboratory-ESPED(n2). Clinical and laboratory surveys overlapped in 5 of 14 cases. The incidence of CAPS in German children was estimated to be 3.43 per 10⁷ person-years. The patients carried 11 different NLRP3 mutations and were classified as MWS(n = 6), CINCA (n = 4), FCAS (n = 1) and undefined CAPS (n = 3).


CONCLUSIONS
The incidence of CAPS in Germany is very low and corresponds to 2-7 newly diagnosed patients ≤ 16 years per year.
Department of Paediatric Rheumatology, Children's Hospital, University Duisburg-Essen, Hufelandstrasse 55, Essen, Germany. elke.lainka@uk-essen.de
E
E
Lainka
U
U
Neudorf
P
P
Lohse
C
C
Timmann
M
M
Bielak
S
S
Stojanov
K
K
Huss
R
R
von Kries
T
T
Niehues
D000293:Adolescent; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D056587:Cryopyrin-Associated Periodic Syndromes / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006580:Genetic Carrier Screening; D005858:Germany; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D011159:Population Surveillance; D011446:Prospective Studies