Polyarticular osteoarthritis - Two major phenotypes hypothesized

ArthroCare Pty Ltd, P.O. Box 6, Mount Lawley, and Department of Medicine, University of Western Australia, Australia.
Medical Hypotheses (Impact Factor: 1.07). 02/2006; 66(2):315-8. DOI: 10.1016/j.mehy.2005.08.028
Source: PubMed


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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    • "Most definitions state that GOA involves at least three joints [31], although this again is questioned [27]. The group of joints most often incorporated in definitions are the hands, neck, lower back, knees and hips [7,56,57], whereas other definitions postulate that the involvement of atypical joints [25,26] or hallux valgus [25,58] is essential for GOA. To date, two specific phenotypes of GOA have been established [28], however, these phenotypes are far from useful in daily practice as these phenotypes only represent a very small proportion of patients with OA-like complaints in multiple joints. "
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    ABSTRACT: Non-pharmacological treatment (NPT) is a useful treatment option in the management of hip or knee osteoarthritis. To our knowledge however, no studies have investigated the effect of NPT in patients with generalized osteoarthritis (GOA). The primary aim of this study is to compare the effectiveness of two currently existing health care programs with different intensity and mode of delivery on daily functioning in patients with GOA. The secondary objective is to compare the cost-effectiveness of both interventions. In this randomized, single blind, clinical trial with active controls, we aim to include 170 patients with GOA. The experimental intervention consist of six self-management group sessions provided by a multi-disciplinary team (occupational therapist, physiotherapist, dietician and specialized nurse). The active control group consists of two group sessions and four sessions by telephone, provided by a specialized nurse and physiotherapist. Both therapies last six weeks. Main study outcome is daily functioning during the first year after the treatment, assessed on the Health Assessment Questionnaire. Secondary outcomes are health related quality of life, specific complaints, fatigue, and costs. Illness cognitions, global perceived effect and self-efficacy, will also be assessed for a responder analysis. Outcome assessments are performed directly after the intervention, after 26 weeks and after 52 weeks. This article describes the design of a randomized, single blind, clinical trial with a one year follow up to compare the costs and effectiveness of two non-pharmacological interventions with different modes of delivery for patients with GOA. Dutch Trial Register NTR2137.
    BMC Musculoskeletal Disorders 07/2010; 11(1):142. DOI:10.1186/1471-2474-11-142 · 1.72 Impact Factor
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    ABSTRACT: Previous studies of patients with primary hand and ankle osteoarthritis (OA) have suggested the presence of two major polyarticular OA (POA) phenotypes, designated Type 1 and Type 2. The former, characterised by sentinel distal interphalangeal (IP) (DIP) or proximal IP (PIP) joint OA resembles generalised OA (GOA), whereas the latter characterised by sentinel metacarpophalangeal (MCP)2,3 OA, resembles the arthropathy associated with hereditary haemochromatosis (HH). The aim of this study was to validate these putative phenotypes and to further investigate their clinical and genetic characteristics. Newly referred patients had X-rays if pre-determined clinical criteria for OA in hand and other joints were met. Subjects were assigned to the putative Type 1 POA (T1POA) or Type 2 POA (T2POA) phenotypes if radiological criteria were satisfied. Human haemochromatosis (HFE) gene mutations were determined in buffy-coat DNA by polymerase chain reaction amplification, followed by restriction enzyme cleavage and analysis on a 3% agarose gel. The significance of differences was determined by Chi-square test or by Fisher's exact test. Sixty-seven patients fulfilled criteria for inclusion in this study; 39 (6M, 33F) for T1POA and 28 (18M, 10F) for T2POA. A statistically significant difference in gender was observed (64% male in the T2POA subset, P<0.0001). Heberden's nodes (HNs) were found in 34 of the 39 Type 1 subjects, but in only nine of the 28 Type 2 subjects (P<0.0001). HFE gene mutations were found in nine of the 39 Type 1 subjects (23%), whereas 21 of the 28 Type 2 subjects had a single HFE gene mutation (75%, P<0.0001). These findings confirm the hitherto hypothetical proposition of a T1POA phenotype conforming to nodal GOA (NGOA) and a T2POA phenotype closely resembling the arthropathy described in haemochromatosis (HH).
    Osteoarthritis and Cartilage 07/2009; 17(7):891-5. DOI:10.1016/j.joca.2009.01.003 · 4.17 Impact Factor
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    ABSTRACT: The 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. In 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. GOA 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. GOA 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.
    Zeitschrift für Rheumatologie 08/2010; 69(6):544-9. · 0.61 Impact Factor
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