{"id":44,"date":"2024-06-27T17:22:17","date_gmt":"2024-06-27T17:22:17","guid":{"rendered":"https:\/\/orthopaedicsone.com\/review\/orthopaedicsone-review-aetiology-of-ra\/"},"modified":"2024-06-27T17:22:17","modified_gmt":"2024-06-27T17:22:17","slug":"orthopaedicsone-review-aetiology-of-ra","status":"publish","type":"page","link":"https:\/\/www.orthopaedicsone.com\/review\/orthopaedicsone-review-aetiology-of-ra\/","title":{"rendered":"Aetiology of RA"},"content":{"rendered":"<p>Unknown trigger or triggers stimulate or activate a disturbed immunologic response in a genetically susceptible individual. Immune response genes congregated on the short arm of chromosome 6 in the segment called the major histo-compatibility complex. HLA antigens are the result of expression of genes in this segment.<\/p>\n<h4><strong>Class I<\/strong><\/h4>\n<ul>\n<li>Consists of 3 related types of molecules&nbsp;: HLA-A, B, C<\/li>\n<li>Antigens are identified on all cells (except RBC&nbsp;and early embryonic tissue)<\/li>\n<li>Their function is&nbsp;identification of self, development of tolerance and strong graft rejection responses<\/li>\n<\/ul>\n<h4><strong>Class II<\/strong><\/h4>\n<ul>\n<li>Code for molecules termed HLA-DR, DQ and DP<\/li>\n<li>These are involved in antigen presentation to T helper cells and are present on B cells, macrophages and activated T or killer cells<\/li>\n<li>Aberrant induction of Class II antigen expression on cells other than those normally evident&nbsp;causes inflammation in some auto immune diseases<\/li>\n<\/ul>\n<h4><strong>Class III<\/strong><\/h4>\n<ul>\n<li>Antigens are coded from a locus between Class I and II regions<\/li>\n<li>Consist of&nbsp;soluble proteins primarily involved in the complement cascade<\/li>\n<\/ul>\n<p><strong>Class I antigens<\/strong> are associated with arthropathies of the axial skeleton, e.g. Ankylosing Spondylitis (B27), Reiters (B27), Psoriatic arthropathy (B27 and B38)<\/p>\n<p><strong>Class II antigens<\/strong> have association with&nbsp;Rheumatoid arthritis (DR1 and DR4), Sjogrens&#8217; Syndrome (DR2 and DR3), JRA and&nbsp;SLE (DR2)<\/p>\n<ul>\n<li>The reason that more than one group of alleles can increase susceptibility to a disease is due to shared epitopes between molecules of each group<\/li>\n<li>For instance DR4 subgroup has 5 subtypes, of these only two, Dw4 and Dw14, promote susceptibility to RA<\/li>\n<li>They share a common epitope in their beta chain<\/li>\n<li>Rheumatoid arthritis is associated with HLA Dw4 locus and the HLA DR4 allotype in 60-80% of cases compared to only about 20-25% in the general population<\/li>\n<li>Sero-negative patients account for 24% of those with the HLA DR4 allotype and sero-positive patients 55%, indicating that they may be separate disease processes<\/li>\n<li>The immune response triggers production of auto antibodies which form immune complexes and trigger synovial proliferation and inflammation resulting in the typical pathological features of Rheumatoid Arthritis<\/li>\n<\/ul>\n<h3>Incidence<\/h3>\n<ul>\n<li>Affects 3% of the population<\/li>\n<li>Approximately 300,000 RA sufferers in Australia<\/li>\n<li>Usually presents in the 4th decade of life<\/li>\n<li>M:F incidence 1:3<\/li>\n<li>May affect any synovial joint and less commonly also cartilaginous joints and enthesies<\/li>\n<li>Increased incidence in first degree relatives of RA patients<\/li>\n<\/ul>\n<h3>Pathogenesis<\/h3>\n<ul>\n<li>Unknown stimulus&nbsp;activates immune system, with&nbsp;antibody \/ complement initiation of synovial inflammation and extra-articular manifestations in genetically susceptible individuals<\/li>\n<li>Viral (EB virus implicated), bacterial (component of bacterial cell wall may be stimulus), environmental, endogenous collagen or perhaps an emotional stimulus<\/li>\n<li>Stimulus&nbsp;causes formation of anti-IgG Ab (Rh factor)<\/li>\n<li>Activation of immune system, releases proteolytic enzymes and digests tissues<\/li>\n<li>Immune reaction&nbsp;leads to&nbsp;complement fixation and release of interleukin 1, phosphorylase A2, prostaglandin E2 and plasminogen and induces synthesis of collagenase<\/li>\n<li>The end result is&nbsp;degradation of matrix proteoglycan,&nbsp;chondrocyte death, cartilage breakdown, augmenting the process of irreversible joint destruction<\/li>\n<li>It is postulated that cartilage is a necessary factor for the chronic process to begin and be maintained, due to the fact that little recurrence is seen in artificial joint replacements<\/li>\n<li>Process blocked by early administration of cortisone, because&nbsp;proteoglycan synthesis is inhibited and existing proteoglycans are degraded<\/li>\n<\/ul>\n<h3>Pathology<\/h3>\n<ol>\n<li>Begins as non specific inflammatory synovitis&nbsp;<\/li>\n<li>Non specific increase in capillaries&nbsp;<\/li>\n<li>Proliferation of synoviocytes, then hypertrophy of synovium, then villi formation&nbsp;<\/li>\n<li>Lymphocytic and plasma cell infiltrate mainly perivascular and formation of lymphocytic nodules&nbsp;<\/li>\n<li>Focal fibrinoid deposition&nbsp;<\/li>\n<li>Cellular necrosis<\/li>\n<li>Highly vascular reduplicated synovium covers articular surface, leading to&nbsp;pannus formation<\/li>\n<li>At the cartilage-pannus junction macrophages and fibroblasts are the predominant cell types<\/li>\n<li>Presence of macrophages and collagenase markers within cells and the subsequent collagenolysis of the eroded bone matrix suggest that these cells may be responsible for a major portion of the bone erosion<\/li>\n<li>These cells also secrete lysosomal enzymes such as proteases, cathepsin and elastase which are capable of degrading proteoglycan<\/li>\n<li>RA articular cartilage specimens in a significant portion contain anti-collagen (Type II) antibodies<\/li>\n<li>Pannus erodes the articular cartilage, cartilage may fragment and&nbsp;make intra-articular loose bodies<\/li>\n<li>Subchondral bone is exposed and secondary osteoarthritis may result<\/li>\n<li>There is associated local myositis<\/li>\n<\/ol>\n<p><strong>Rheumatoid Nodule<\/strong><\/p>\n<ul>\n<li>Central fibrinoid necrosis (fibrin, degraded collagen and cellular fragments), surrounded by a radially disposed palisades of local histiocytes and beyond that by inflammatory granulation tissue, which is vascular and later becomes fibrotic.<\/li>\n<li>Perivascular plasma cells and lymphocytes<\/li>\n<li>Generally in Rh positive patients and usually implies more severe disease and vasculitis.<\/li>\n<li>Seen on extensor surfaces, olecranon, lateral aspects of fingers, gluteal, Achilles, trochanters, ischial tuberosities, scapular spine, sacrum and occiput (if bedridden)<\/li>\n<li>May become apparent before the actual onset of the arthritis<\/li>\n<li>May persist indefinitely or regress at any time<\/li>\n<\/ul>\n<p><strong>Neuropathies<\/strong><\/p>\n<ul>\n<li>Vasculitic&nbsp;causes motor and sensory peripheral neuropathy&nbsp;<\/li>\n<li>May be&nbsp;due to entrapment or compression<\/li>\n<li>Affects\n<ul>\n<li>Median at wrist (carpal tunnel)<\/li>\n<li>Ulna at&nbsp;elbow<\/li>\n<li>Radial&nbsp;(posterior interosseous nerve)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p><strong>Tendon Rupture<\/strong><\/p>\n<ul>\n<li>Proteolytic enzymes from the hypertrophic synovitis<\/li>\n<li>Direct synovial invasion of the tendon<\/li>\n<li>Intratendinous nodules may prevent free gliding of a tendon<\/li>\n<li>Attrition, where the tendon is abraded running over sharp bony prominences<\/li>\n<li>Extensor tendon rupture is more common than flexor and ulnar tendons before radial tendons<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"<p>Unknown trigger or triggers stimulate or activate a disturbed immunologic response in a genetically susceptible individual. Immune response genes congregated on the short arm of chromosome 6 in the segment called the major histo-compatibility complex. HLA antigens are the result of expression of genes in this segment. Class I Consists of 3 related types of [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_lmt_disableupdate":"","_lmt_disable":"","_o1_cross_site_relations":[],"_o1_disable_knowledge_graph":"","footnotes":""},"tags":[],"o1_subspecialty":[],"o1_anatomic_region":[],"o1_article_type":[],"class_list":["post-44","page","type-page","status-publish","hentry"],"_links":{"self":[{"href":"https:\/\/www.orthopaedicsone.com\/review\/wp-json\/wp\/v2\/pages\/44","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.orthopaedicsone.com\/review\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.orthopaedicsone.com\/review\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.orthopaedicsone.com\/review\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.orthopaedicsone.com\/review\/wp-json\/wp\/v2\/comments?post=44"}],"version-history":[{"count":0,"href":"https:\/\/www.orthopaedicsone.com\/review\/wp-json\/wp\/v2\/pages\/44\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.orthopaedicsone.com\/review\/wp-json\/wp\/v2\/media?parent=44"}],"wp:term":[{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.orthopaedicsone.com\/review\/wp-json\/wp\/v2\/tags?post=44"},{"taxonomy":"o1_subspecialty","embeddable":true,"href":"https:\/\/www.orthopaedicsone.com\/review\/wp-json\/wp\/v2\/o1_subspecialty?post=44"},{"taxonomy":"o1_anatomic_region","embeddable":true,"href":"https:\/\/www.orthopaedicsone.com\/review\/wp-json\/wp\/v2\/o1_anatomic_region?post=44"},{"taxonomy":"o1_article_type","embeddable":true,"href":"https:\/\/www.orthopaedicsone.com\/review\/wp-json\/wp\/v2\/o1_article_type?post=44"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}