Trisomie 21 und Juvenile Idiopathische Arthritis – die Bedeutung chromosomaler Aberrationen bei der Abklärung einer Arthritis

Zusammenfassung

Hintergrund: Bei verschiedenen chromosomalen Störungen wird ein erhöhtes Risiko für eine Juvenile Idiopathische Arthritis (JIA) vermutet. Vor allem bei Patienten mit einem Morbus Down (Trisomie 21) und einer JIA besteht darüber hinaus eine Unsicherheit bezüglich der geeigneten Therapie mit DMARDs, weil auch das Risiko bezüglich einer AML erhöht ist.

Methode: In einer retrospektiven Fall-Kohorte eigener Patienten wurde das typische Verteilungsmuster und die Entzündungsaktivität bei Patienten mit Trisomie 21 und JIA (T21-JIA) sowie deren Ansprechen und Nebenwirkungen von MTX im Vergleich zu JIA-Patienten mit seronegativer polyartikulärer JIA (SNP-JIA) untersucht.

Ergebnisse: Die elf eingeschlossenen T21-JIA Patienten (6 weibl./5 männl.) hatten bei Diagnosestellung JIA ein mittleres Alter von 6 Jahren (1–13 Jahre). 9 T21-JIA Patienten (82%) hatten einen polyartikulären Verlauf und wurden mit MTX behandelt. T21-JIA Patienten hatten bei Diagnosestellung eine signifikant höhere Anzahl aktiver und schmerzhafter Gelenke (T-21 JIA 19,9 (± 10,9) vs. SNP-JIA 15,5 (± 6,5)) und präsentierten sich in 7 von 10 (70%) Fällen als SNP-JIA (gemäß ILAR-Klassifikation, erwartet: 13–15%). Ein T21-JIA Patient hatte eine systemische, einer eine persistierende- und 2 eine extended oligoartikuläre JIA. Im Verlauf entwickelten 81% der T21-JIA Patienten Gelenkskontrakturen. Kein T21-JIA Patient hatte im Verlauf eine Uveitis. Das Ansprechen auf MTX und die Frequenz von unerwünschten Arzneimittelwirkungen (UAW) war bei T21-JIA Patienten mit denen einer gematchten Vergleichstichprobe vergleichbar.

Schlussfolgerung: T21-JIA Patienten zeigen gehäuft einen polyartikulären Verlauf mit einer höheren Anzahl betroffener Gelenke und ausgeprägteren Bewegungseinschränkungen im Erkrankungsverlauf. Das Ansprechen und die UAW einer MTX-Therapie bei Patienten mit T21-JIA entspricht dem von JIA-Patienten mit einem normalen Karyotyp. Auch bei anderen chromosomalen Aberrationen namentlich Turner- (Monosomie XO), Klinefelter- (Poly-X, XXY) und Di George Syndrom (del 22q11.2) wird ein erhöhtes Risiko für das Auftreten einer JIA vermutet.

Abstract

Rationale: Various chromosomal disorders have been suspected to increase the risk of juvenile idiopathic arthritis (JIA). In addition, especially in children with Down syndrome (trisomy 21), there is uncertainty regarding treatment with DMARDs as these patients are also at a higher risk of developing AML.

Methods: In a retrospective case series of our own patients, we evaluated the typical distribution pattern and inflammatory activity of patients with trisomy 21 and JIA (T21-JIA) and their response to methotrexate as well as adverse drug reactions as compared to other patients with seronegative polyarticular JIA (SNP-JIA).

Results: Eleven T21-JIA patients were included in the study (6 female/5 male) with a median age at diagnosis of 6 years (range 1–13 years). 9 T21-JIA patients (82%) had a polyarticular course of arthritis and were treated with methotrexate. T21-JIA patients had a significantly higher total joint count of active and painful arthritis at the time of diagnosis (T-21 JIA 19.9 (± 10.9) vs. SNP-JIA 15.5 (± 6.5)). 7 out of 10 (70%) T-21-JIA patients presented with SNP-JIA, which is above the expected frequency (expected percentage according to the ILAR classification: SNP 13–15%). One T21-JIA patient had systemic, one had persistent and 2 had extended oligoarticular JIA. During the follow-up period, 81% of T21-JIA patients developed joint contractures. Notably there was no T21-JIA patient with JIA-associated uveitis. Response rates to methotrexate and frequency of adverse drug reactions (ADR) were comparable between T21-JIA patients and a matched comparative sample.

Conclusion: T21-JIA patients frequently have a higher joint count of active arthritis at the time of diagnosis and a decreased range of motion in the course of disease, but there is no difference in response to methotrexate and adverse drug reactions compared to patients with a normal caryotype. Patients with other chromosomal aberrations, especially Turner (monosomy XO), Klinefelter (poly-X, XXY) and Di George syndrome (del 22q11.2), are suspected to have an increased risk for JIA as well.

Schlüsselwörter

Juvenile idiopathische Arthritis - Morbus Down - Di George Syndrom - Klinefelter Syndrom - Turner Syndrom

Key words

Juvenile idiopathic arthritis - down syndrome - Di George syndrom - Klinefelter’s syndrom - turner syndrom

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