Cryopyrin-assoziierte periodische Syndrome – Erkennung und Behandlung

Zusammenfassung

Die Cryopyrin-assoziierten periodischen Syndrome (CAPS) gehören zu den seltenen Autoinflammatorischen Erkrankungen (AID). CAPS sind ein Spektrum von Erkrankungen unterschiedlichen Schweregrades, obwohl die zugrunde liegenden Mutationen zumeist im NLRP3-Gen liegen. Die Diagnose kann bei Vorliegen von mindestens 2 von 6 definierten CAPS-spezifischen Symptomen (Urtikaria-ähnlicher Ausschlag, Kälte-/Stress-getriggerte Episoden, Hörverlust, muskuloskeletale Symptome (Arthritis, Arthralgie, Myalgie), chronische aseptische Meningitis, Skelettveränderungen (prominente Stirn, Epiphysenhypertrophie)) verknüpft mit einer Erhöhung der Entzündungsparametern (CRP, SAA) gestellt und durch genetischen Nachweis der Mutation bestätigt werden. Eine besondere Herausforderung sind Patienten ohne Mutationsnachweis oder mit Varianten niedriger Penetranz. Die Behandlung mit IL-1 Inhibitoren ist mittlerweile der Goldstandard in der Behandlung von CAPS. Aktuell sind die IL-1-Inhibitoren Anakinra, Rilonacept und Cankinumab für die Therapie von CAPS zugelassen, davon in Europa Anakinra und Cankinumab. Für alle IL-1-Inhibioren konnte eine gute Wirksamkeit in Bezug auf die täglichen Symptome wie Fieber, Exanthem, Arthralgie, Fatigue usw. nachgewiesen werden, in einigen Fällen war eine Amyloidose rückläufig und das Hörvermögen verbesserte sich. Durch Anpassung bzw. Erhöhung der Anfangsdosierung des IL-1 Inhibitors bei nicht vollständigem Ansprechen („treat-to-target“-Strategie) lassen sich Remissionsraten von über 90% erreichen. Das Monitoring der Krankheitsaktivität durch die Patienten selbst, die klinische Beurteilung durch den Arzt und die Kontrolle der Entzündungsparameter sind erforderlich um die Therapie effektiv zu steuern und das Behandlungsziel einer kompletten Remission zu erreichen.

Abstract

Cryopyrin-associated periodic syndromes (CAPS) belong to the group of rare autoinflammatory diseases. CAPS are a spectrum of diseases of varying severity, although the mutations causing the disease are located in the NLRP3 gene in most cases. The diagnosis can be made if at least 2 out of 6 defined CAPS-specific symptoms are present (urticaria-like rash, cold or stress-triggered episodes, hearing loss, musculoskeletal symptoms (such as arthritis, arthralgia and myalgia), chronic aseptic meningitis, and skeletal deformities (such as epiphyseal overgrowth and protuberant forehead)), combined with elevated inflammatory parameters (ESR, CRP). The diagnosis may be confirmed by genetic testing. Patients without confirmation of NLRP3 mutation and those with low-penetrance variants are particularly challenging. Today the application of IL-1 inhibitors is considered to be the gold standard in the treatment of CAPS. The IL-1 inhibitors Anakinra, Rilonacept and Canakinumab have been approved for CAPS therapy. Anakinra and Canakinumab are available in Europe. All IL-1 inhibitors have demonstrated good efficacy in respect to daily symptoms like fever, rash, arthralgia and fatigue. In some cases amyloidosis and hearing loss have improved as well. When increasing the starting dose in cases with incomplete response (“treat-to-target” strategy), rates of complete response may be increased to over 90%. Monitoring of disease activity by the patient, clinical evaluation by the physician and control of inflammatory parameters are essential for effective management of therapy and to achieve the goal of complete remission.

Schlüsselwörter

CAPS - Cryopyrin-assoziierte periodische Syndrome - Interleukin-1 Inhibition - NLRP3-Gen - Autoinflammation

Key words

CAPS - cryopyrin-associated periodic syndromes - interleukin-1 inhibition - NLRP3-gene - autoinflammation

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