Abstract
Autoinflammatory diseases (AIDs) are characterized by recurrent, self-limiting systemic inflammation. Disorders include hereditary recurrent fever (HRF) syndromes such as hyperimmunoglobulinemia D and periodic fever syndrome (HIDS). To determine the incidence of HIDS and report clinical and genetic characteristics together with the underlying MVK genotypes in German children, a prospective active surveillance was conducted in Germany during a period of 3 years. Monthly inquiries were sent to 370 children’s hospitals by the German Paediatric Surveillance Unit (Clinic-ESPED, n1) and to two laboratories (Laboratory-ESPED, n2) performing genetic analyses. Inclusion criteria were a MVK mutation–positive patient ≤16 years of age with more than three self-limiting episodes of fever >38.5°C associated with increased inflammation markers. Clinical, epidemiological, and genetic data were assessed via questionnaires. Eight out of 16 patients were identified in Clinic-ESPED (n1) and 15 of 16 in Laboratory-ESPED (n2). Clinical and laboratory surveys overlapped in 7 of 16 cases. Incidence of HIDS was estimated to be 0.39 (95% CI: 0.22, 0.64) per 106 person-years. HIDS symptoms generally started in infancy with recurrent fever episodes lasting 3–12 (median, 4.5) days and recurring every 1–12 weeks. Fever was accompanied by abdominal pain, vomiting, diarrhea, cervical lymphadenopathy, and sometimes by headache, skin and joint symptoms. The patients carried 11 different MVK mutations mostly in compound heterozygosity (75%, 12 out of 16). The most frequent mutation was p.Val377Ile (81%, 13 out of 16). In Germany, the incidence of HIDS is very low with 0.39 per 106 person-years.
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Abbreviations
- AID:
-
Autoinflammatory disease
- MVK:
-
Mevalonate kinase
- HIDS:
-
Hyperimmunoglobulinemia D and periodic fever syndrome
- MKD:
-
MVK deficiency
- HRF:
-
Hereditary recurrent fever syndromes
- ESPED:
-
German Paediatric Surveillance Unit for rare paediatric diseases
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Acknowledgments
Additionally, the authors thank the following colleagues for their collaboration: Clinic-ESPED R. Ganschow, R. Lepler (Hamburg), J. Neubert (Düsseldorf), E. Holz (Eisenhüttenstadt), T. Kallinich (Berlin), C. Brandis (Schleswig), T. Hospach (Stuttgart), B. Belohradsky (München). Laboratory-ESPED H. Ruebsamen (Department of Clinical Chemistry—Großhadern, University of Munich, Munich), S. Burwinkel (Department of Molecular Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg). The authors thank U. Göbel and B. Heinrich from the ESPED registry. E. Lainka gratefully acknowledges the helpful discussions with and comments made by Oliver Weiergräber (Forschungszentrum Jülich, Germany).
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All authors declared no conflicts of interest.
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Lainka, E., Neudorf, U., Lohse, P. et al. Incidence and clinical features of hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) and spectrum of mevalonate kinase (MVK) mutations in German children. Rheumatol Int 32, 3253–3260 (2012). https://doi.org/10.1007/s00296-011-2180-8
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DOI: https://doi.org/10.1007/s00296-011-2180-8