Polyarticular osteoarthritis--two major phenotypes hypothesized.
ABSTRACT Osteoarthritis is the commonest form of arthritis, at least amongst Caucasians and is frequently polyarticular. Genetic factors are now considered pivotal in the aetiopathogenesis of polyarticular osteoarthritis (POA). This document proposes a nexus between the gene most commonly mutated amongst Caucasian peoples, notably the HFE gene and an appreciable subset of POA patients who have a clinically recognisable OA phenotype. It is hypothesised that there are at least 2 major POA phenotypes each of which is associated with discrete genotypes. Type 1 POA characterized by Heberden's or Bouchard's nodes with prominent DIP, PIP, knee joint (medial compartment) and Great toe MTP joint involvement corresponds to the putative nodal generalized form of OA or NGOA (proposed Type 1 POA phenotype). As yet no genetic marker has been defined for this POA subset. The second is a hitherto less well recognized phenotype characterized by involvement of the index and/or middle finger metacarpophalangeal (MCP2,3) joints and the elbows, ankles and possibly the intertarsal and tarsometatarsal joints. The hip and knee joints may sometimes also be involved. This different joint distribution corresponds closely to the pattern observed in the arthropathy that often accompanies hereditary haemochromatosis. It is predicted that mutations in the HFE gene will associate strongly with the proposed Type 2 POA phenotype and serve as a genetic marker for this clinically recognisable subset.
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ABSTRACT: HintergrundDie generalisierte Osteoarthrose (GOA) wird in der Literatur unterschiedlich definiert. Ebenso kontrovers ist die Diskussion über die Zusammenhänge zwischen GOA und Heberden-Arthrose (HA). Beide Fragestellungen wurden daher an einem Patientengut überprüft, für das in einer genealogischen Studie an 931 Familienmitgliedern eine familiäre Disposition nachgewiesen werden konnte. Material und MethodenAn 106 Patienten mit einer HA und 109 Kontrollpersonen wurden je Patient 70Gelenke bzw. Wirbelsäulensegmente mittels charakteristischer funktioneller und 44Gelenke bzw. Wirbelsäulenabschnitte mittels röntgenologischer Parameter untersucht. ErgebnisseDie GOA betrifft sowohl die kleinen und großen Gelenke als auch die Wirbelsäule. Dieses Phänomen ist umso ausgeprägter, je mehr Fingergelenke im Sinne einer Heberden- und Bouchard-Arthrose verändert sind. SchlussfolgerungDie GOA betrifft den gesamten Bewegungsapparat. Die unterschiedliche Manifestation an einzelnen Gelenken und Wirbelsäulenabschnitten ist wahrscheinlich auf multifaktorielle lokale und systemische Faktoren zurückzuführen. In einer früheren Untersuchung konnte für die untersuchte Population eine genetische Disposition mit einer maximalen Prävalenz der HA von 30% gesichert werden. Da die HA als genetischer Marker für die GOA angesehen werden kann, ist die gleiche Aussage für die Häufigkeit der GOA anzunehmen. BackgroundThe definition of generalized osteoarthritis in the literature is just as controversial as the discussion about correlations between GOA and Heberden’s nodes (HN). Therefore, both questions were investigated in patients with proven heredity in a genealogical study of 931 family members. Material and methodsIn 106 patients with HN and 109 control subjects, 70 joints and spinal segments were investigated with respect to characteristic functional parameters. In addition, 44 joints and spinal segments were investigated radiologically. ResultsGOA affects both the small and large joints as well as the spine. This phenomenon is the more pronounced the more finger joints are affected by Heberden’s and Bouchard’s nodes. ConclusionsGOA affects the entire musculoskeletal system. The varying manifestation in individual joints and spinal segments is probably attributable to multifactorial local and systemic factors. In an earlier study, a genetic disposition with a maximum HA prevalence of 30% was identified in the study population. Since HA is considered a genetic marker for GOA, it can be assumed that the same is true of GOA prevalence. SchlüsselwörterGeneralisierte Arthrose-Heberden-Arthrose-Bouchard-Arthrose-Arthrosedisposition-Polyarthrose KeywordsGeneralized osteoarthritis-Heberden’s nodes-Bouchard’s nodes-Disposition to osteoarthritis-PolyarthritisZeitschrift für Rheumatologie 01/2010; 69(6):544-549. · 0.45 Impact Factor
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ABSTRACT: In view of the clinical similarities between polyarticular osteoarthritis (POA) with metacarpophalangeal (MCP) joint involvement and the arthropathy that occurs in hereditary haemochromatosis (HH), it was hypothesized that osteochondral damage in both disorders may be due to localized iron overload. Accordingly, it was predicted that the concentration of ferritin in synovial fluid (SF) would be higher in OA patients with HFE gene mutations than in HFE wild-type (wt) OA patients. The aim of this study was to test this proposition. Sequential patients with physician-diagnosed OA and, for comparison, diverse inflammatory diseases of the joints, who required diagnostic or therapeutic arthrocentesis, were studied. Participants underwent HFE genotyping. SF samples were assayed for ferritin and also for selected cytokines and matrix metalloproteinases (MMPs). Seventy-three patients with diverse rheumatic disorders were recruited. Of the 29 patients who had knee OA, 15 were wt and 14 were heterozygous for HFE mutations (C282Y or H63D). Mean SF ferritin concentrations in the wt and heterozygous OA groups were 273 and 655 ng/mL, respectively (p = 0.0146). A predicted difference in SF ferritin concentrations in patients with knee OA was confirmed. Concentrations of ferritin in the SF were found to be two- to threefold higher in knee OA patients with HFE gene mutations compared to wt patients. This finding is consistent with the possibility that, in OA patients with HFE gene mutations, localized iron overload may contribute either directly or indirectly to osteochondral damage, possibly in a similar way to that which occurs in the arthropathy that complicates HH.Scandinavian journal of rheumatology 01/2010; 39(5):413-20. · 2.51 Impact Factor
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ABSTRACT: Hereditary Haemochromatosis is a common inherited disorder, which primarily affects populations of northern European origin. Individuals homozygous for the C282Y mutation in the HFE gene product have up to a 30 percent chance of developing significant disease as a result of iron overload. Arthropathy is arguably the most disabling complication of iron overload in this disorder. Here we review the clinical and pathophysiological aspects of arthropathy in Hereditary Haemochromatosis. © 2011 by the American College of Rheumatology.Arthritis care & research. 05/2011; 64(1):9-14.