Autoinflammatorische (Fieber-)Syndrome - Klinik, Genetik und Therapie

Zusammenfassung

Fieber ist ein häufiges Symptom im Kindesalter. Ursache sind meist banale Erkältungskrankheiten. Kehrt das Fieber jedoch über einen Zeitraum von mehr als sechs Monaten immer wieder, ohne dass eine Ursache offensichtlich ist, muss differenzialdiagnostisch auch an ein periodisches autoinflammatorisches oder Fieber-Syndrom gedacht werden. Charakteristisch ist eine multisystemische Entzündung mit Leukozytose, Beschleunigung der BSG und Erhöhung der Akute-Phase-Parameter CRP und SAA, die häufig von Bauchschmerzen, Myalgien, Arthralgien und Hautausschlägen begleitet ist. Das bei den Kindern zumeist vorhandene, plötzlich beginnende, zum Teil durch äußere Anlässe (Trauma, Impfung, Stress, Menstruation) getriggerte Fieber kann nur wenige Tage bis mehrere Wochen andauern und klingt dann ohne Therapie spontan wieder ab. Eine definitive Diagnosestellung anhand der klinischen Präsentation kann jedoch schwierig sein, da die begleitenden Symptome zum Großteil sehr unspezifisch sind und bei mehreren autoinflammatorischen Erkrankungen auftreten können. Als hilfreich erweist sich die molekulargenetische Analyse, die die Verdachtsdiagnose bestätigen oder mit hoher Wahrscheinlichkeit ausschließen kann. Untersucht werden können das familiäre Mittelmeerfieber (FMF), das Tumornekrosefaktor-Rezeptor-1-assoziierte periodische Syndrom (TRAPS), das Hyperimmunglobulinämie-D- und periodische Fieber-Syndrom (HIDS) und die Cryopyrin-assoziierten periodischen Syndrome (CAPS). Häufigstes Fieber-Syndrom im Kindesalter ist jedoch wahrscheinlich das zumeist transiente „periodische Fieberepisoden, aphthöse Stomatitis, Pharyngitis und zervikale Lymphadenitis”-(PFAPA-)Syndrom, das nach heutigem Kenntnisstand keine genetische Ursache hat.

Abstract

Fever is frequent during infancy and childhood. The cause is usually a common cold. In cases where the fever reoccurs at intervals for more than six months without an obvious reason, one has to consider the possibility that the child suffers from an autoinflammatory syndrome which is commonly also known as a periodic fever syndrome. This group of diseases is characterised by a multisystemic inflammation with leukocytosis, an elevation of the erythrocyte sedimentation rate, and increased C-reactive protein and amyloid A serum concentrations. Common symptoms of an attack are abdominal pain, myalgia, arthralgia, and skin rash. Fever is almost always present in children. The attack starts abruptly and can be triggered by external factors such as trauma, vaccination, stress, and menstruation. The fever persists for several days up to weeks and spontaneously resolves without therapy. It is, however, often difficult to make a definitive diagnosis based solely on the clinical presentation, because the symptoms accompanying the fever are mostly rather unspecific and typical for more than one of the autoinflammatory syndromes. It is therefore helpful to perform a genetic analysis to either confirm the suspicion or to rule out a specific diagnosis. Hereditary fever syndromes, for which gene defects are known, include familial Mediterranean fever (FMF), tumor necrosis factor receptor 1-associated periodic syndrome (TRAPS), hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS), and the cryopyrin-associated periodic syndromes (CAPS). The most frequently observed fever syndrome in childhood is, however, the mostly transient periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome which appears not to be inherited.

Schlüsselwörter

Autoinflammation - Fieber unbekannter Ursache - hereditäres periodisches Fiebersyndrom - Diagnostik - Mutation

Key words

autoinflammation - fever of unknown origin - hereditary periodic fever - recurrent fever - diagnosis, mutation

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