Friday, November 12, 2010

Rheumatoid arthritis


At present 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

Consist of 3 related types of molecules - HLA-A, -B, -C .Antigens are identified on all cells (except RBC + early embryonic tissue) ® identification of self, development of tolerance and strong graft rejection responses.

Class II

Code for molecules termed HLA -DR, -DQ and -DP. These are involved in antigen presentation to T- helper cells and are present
on B cells, macrophages and activated T or killer cells.
Aberrant induction of Class II antigen expression on cells other than those normally evident ® inflammation in some auto immune diseases.

Class III

Antigens are coded from a locus between Class I and II regions ® soluble proteins primarily involved in the complement cascade.
Rheumatic diseases associated with Class I antigens include arthropathies of the axial skeleton eg Ank Spond B27
Reiters B27
Psoriatic arthropathy B27 and B38
Class II antigens have an association with
eg Rheumatoid arthritis DR1 and DR4
Sjogrens' Syndrome DR2 and DR3
The reason that more than one group of alleles can increase susceptibility to a disease is due to shared epitopes bw the molecules of each group.
eg the DR4 subgroup has 5 subtypes - of these only two - Dw4 and Dw14 promote susceptibility to RA - they share a common epitope in their beta chain
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
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
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.


Affects 3% of the population
Approximately 300,000 RA sufferers in Australia
Usually presents in the 4th decade of life
M:F incidence 1:3
May affect any synovial joint and less commonly also cartilaginous joints and enthesies
Increased incidence in first degree relatives of RA patients


An at present unknown stimulus ® activation of immune system ® antibody / complement initiation of synovial inflammation and extra-articular manifestations in genetically susceptible individuals.
? viral (EB virus implicated), bacterial (component of bacterial cell wall may be stimulus), environmental, endogenous collagen or perhaps an emotional stimulus.
? stimulus ® formation of anti IgG Ab (Rh factor)
Activation of immune system ® release of proteolytic enzymes and digestion of tissue.
Immune reaction ® complement fixation and release of interleukin 1, phosphorylase A2, prostaglandin E2 and plasminogen ® degradation of matrix proteoglycan, induces synthesis of collagenase® chondrocyte death, cartilage breakdown augmenting the process of irreversible joint destruction.
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.
Process blocked by early administration of cortisone ® proteoglycan synthesis is inhibited and existing proteoglycans are degraded.


Begins as non specific inflammatory synovitis
® Non specific increase in capillaries
® Proliferation of synoviocytes
® Hypertrophy of synovium ® villi formation
® Lymphocytic and plasma cell infiltrate mainly peri vascular and formation of lymphocytic nodules
® Focal fibrinoid deposition
® Cellular necrosis
Highly vascular reduplicated synovium covers articular surface ® pannus formation
At the cartilage-pannus junction macrophages and fibroblasts are the predominant cell types
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
These cells also secrete lysosomal enzymes such as proteases, cathepsin and elastase which are capable of degrading proteoglycan
RA artic cartilage specimens in a significant portion contain anti-collagen (Type II) antibodies
Pannus erodes the artic cartilage, Cartilage may fragment and ® intra-articular loose bodies
Subchondral bone is exposed and secondary osteoarthritis may result
There is associated local myositis

Rheumatoid Nodule

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. Peri vascular plasma cells and lymphocytes
Generally in Rh positive patients and usually implies more severe disease and vasculitis.
Seen on extensor surfaces, olecranon, lateral aspects of fingers, gluteal, Achilles, trochanters, ischial tuberosities, scapula, spine sacrum and occiput (if bedridden)
May become apparent before the actual onset of the arthritis
May persist indefinitely or regress

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