Hämochromatose-assoziierte Arthropathie – moderne Diagnostik für eine altmodische Therapie?

Zusammenfassung

Die genetische Hämochromatose ist bei einer geschätzten Allelfrequenz von ca. 0,04 für die HFE-Genvariante die häufigste genetisch determinierte Erkrankung in Mitteleuropa. Neben einer autosomal-rezessiv wirkenden Mutation mit Aminosäureaustausch C 282Y im HFE-Genprodukt existieren in diesem und in anderen Genen noch zahlreiche andere, weitaus seltenere Mutationen, die allesamt die Expression des die Eisenaufnahme hemmenden Hepcidins stören. Folge ist eine gesteigerte Eisenresorption und Störungen der Eisenretention im retikulo-endothelialen System. Die Manifestationen am Bewegungsapparat sind häufig. Sie betreffen vor allem Arthropathien der Grundgelenke des 2. und 3. Fingers, gefolgt von den Hand- und Hüftgelenken. Hier finden sich zystische Knochenveränderungen zunächst neben erweiterter, und später reduzierter Gelenkspaltweite, sowie charakteristischen Osteophyten, seltener aseptische Knochennekrosen, ferner eine generalisierte Osteoporose. Strukturelle Veränderungen der Arthropathie müssen bislang als irreversibel gelten. Von der Korrektur des Eisenstatus ist jedenfalls keine wesentliche Änderung der Symptomatik zu erwarten. Die rechtzeitige Diagnose ist dennoch wichtig, erlaubt sie Vermeidung schwerer endokrinologischer, kardialer und hepatischer Komplikationen. Die Diagnose basiert primär auf Screeningtests mit über 55 % Sättigung der Eisenbindungskapazität und erhöhten Ferritinspiegeln. Der Nachweis der Genmutation ist bislang nicht zwingend, erleichtert aber die Suche nach Genträgern in der Familiendiagnostik. Ohne Möglichkeiten zur Korrektur des Hepcidinmangels stellt die Phlebotomie zur Normalisierung der Eisenspeicher zurzeit die am ehesten kausale Behandlungsform dar. Die symptomatische Behandlung der Arthropathie besteht primär aus Analgetika und bedarfsweise Antiphlogistika, die Behandlung der GH-Osteopathie erfolgt analog zur Osteoporosebehandlung.

Abstract

Genetic hemochromatosis, with an allelic frequency of approximately 0.04 of HFE gene mutations, is the most prevalent inherited disorder in central Europe. Besides this most prevalent autosomal recessive mutation with exchange of the amino acids C 282Y, several other mutations in this and in other genes have been discovered. They all cause an impaired expression of hepcidin, an antimicrobial peptide predominantly expressed in the liver, which blocks iron uptake in the gut, and iron release from the reticulo-endothelial system. Disease manifestations of the locomotor system are frequent. Cystic arthropathy of metacarpophalangeal joints of the second and third digit are most frequent, followed by involvement of the wrist and hip joints. The typical changes of the joints include bone cysts, an initially enlarged joint space width followed by joint space narrowing in the later course, hook-like osteophytes, less frequent aseptic necrosis in the metaphyses, and generalised osteoporosis. Structural changes of the joints are irreversible under current treatment options. Correction of the iron status does not influence many of the joint-related complaints. However, an appropriate diagnosis is important since correction may avoid the endocrine, cardiac, and hepatic complications of iron overload. The diagnosis should be considered on basis of more than 55 % saturated iron binding capacity and increased ferritin plasma concentrations. Genotyping is still facultative for diagnosis, but may help in the screening of families for gene conductors. Phleobotomy is currently the most causative treatment option, until hepcidin substitution may become available. Symptomatic treatment of the arthropathic complaints includes analgesics and intermittent anti-inflammatory agents. Treatment of hemochromatosis osteopathy should be done in analogy to that of generalised osteoporosis.

Schlüsselwörter

Hämochromatose - Eisen - Hepcidin - Arthropathie - Aderlass

Key words

hemochromatosis - iron - hepcidin - arthropathy - phlebotomy

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