Chapter 18: Autoimmune Diseases, Rheumatoid Arthritis
Rheumatoid Arthritis is a multisystem chronic inflammatory disease particularly involving peripheral smaller joints and commonly leading to cartilage destruction. In cases, there is systemic involvement as well.
Age: 70% of the cases are seen in the second and third decades but may also be seen at any age. The peak age is 35-50 years.
Sex:- This is again the disease of females with male: female ratio of 1:3-5.
Distribution: RA has a worldwide distribution with a prevalence of 1% approximately.
Major Immunologic Features
- Presence of rheumatoid factor which may be IgM and IgG.
- The decrease in complement level.
- Increase the level of b-Microglobulin.
- There is a synovial fluid formation.
- Genetic Role: This is the role of the genetic component as there is familial clustering of the disease, more common in monozygotic twins than dizygotic twins, and more common in HLA DR1 and DR4.
- Unidentified environmental factors cause alteration in HLA-Ag and this may be due to viruses.
- The viruses may stimulate B-L which produce antibody against IgG and there is IgG + Anti IgG complex formation which leads to local arthritis reaction.
- Viral Role: Possibly EBV which may suppress Ts or give rise to polyclonal activation of B-L, other viruses blamed are Herpes, Rubella, and Mycoplasma.
- Synovial lymphocytes produce IgG which is recognized as foreign and give rise immune complex (IgG + Anti IgG).
Mechanism of Injury
Any stimulus maybe microbes, stimulate the synovial B-L against the Fc portion of IgG, and give rise to anti-IgG-Ab, predominantly IgM (Pentameric form). Other Ab IgG and IgA may also be found. Now immune complex forms (IgG + Anti IgG) which activate complement and leads to damage to cartilage with the formation of PANNUS and details are seen in the diagram.
Its formation is by hyperplasia and hypertrophy of the synovial lining with a microvascular injury with tissue edema. Synovial tissue protrudes into the synovial cavity are called Pannus. It consists of inflammatory exudates with the presence of mononuclear cells infiltrate surrounds vessels and the presence of T-L, macrophagic cells, and B-lymphocytes.
Rheumatoid Nodule: An extra-articular manifestations. It consists of central fibrinoid necrosis surrounded by palisading macrophagic cells and an outer zone of granulation tissue.
Signs and Symptoms
- These patients may have malaise, fever, and weight loss.
- Deformities of smaller joints (hand & feet) are commonly seen as “Swan-neck”.
- Skin: The rheumatoid nodules in the skin are seen in 20% of the cases.
- Cardiovascular system—Involvement is uncommon and may see as constrictive pericarditis.
- Lung: Coal-miners workers show involvement of lungs (pleuritis and diffuse fibrosing alveolitis) and polyarthritis is called Caplan’s syndrome.
- Felty’s syndrome: In these patients, there is splenomegaly, neutropenia, anemia, and thrombocytopenia.
- Lymphoreticular system often there is a regional enlargement of lymph nodes, and maybe enlarged liver and spleen.
- Ocular: Sometimes there is keratoconjunctivitis sicca.
- Blood vessels: There is vasculitis.
- Amyloidosis may be seen as a complication.
Criteria of a Patient for Rheumatoid Arthritis
Four of the seven criteria are required to classify the patient as having rheumatoid arthritis.
- Morning stiffness: This is present around joints in the morning and lasts one hour before the disease is maximum.
- Arthritis of three or more areas: At least 3 joints are observed by the physicians. There is possibly involvement of 14 joints area e.g.
- Right & left proximal interphalangeal, wrist, elbow, knee, ankle, and metatarsophalangeal joints.
- Arthritis of hand joints: This is arthritis of wrist metacarpophalangeal and proximal interphalangeal joints.
- Symmetric arthritis: – There is simultaneous involvement of the same joint area on both sides of the body.
- Rheumatoid nodule: – These subcutaneous nodules present over the prominence of bones are observed by the physician.
- Rheumatoid factor: – This rheumatoid factor is positive while in the control group only 5% show positive tests.
- Radiographic changes: – Typical changes in erosion are seen.
- A complete blood picture shows lymphocytosis, thrombocytosis, and raised ESR. There is normochromic and normocytic anemia.
- Synovial fluid examination shows mainly neutrophils (75%). The rheumatoid factor may be positive. Also, there is the presence of immune complex (IgG +Anti IgG).
- Radiological findings show a narrowing of the joint spaces.
- Immunological tests show rheumatoid factor (RF) positive in more than 70%. This is predominantly pentamer IgM but may see the presence of IgG, IgA, and IgM (monomer). Rheumatoid factor may be positive in SLE (30%) and Sjogren Syndrome (90%).
- This is simply symptomatic.
- The first line of defense is non-steroidal anti-inflammatory drugs. These drugs will control the symptoms by blocking cyclo-oxygenase, and the production of prostaglandin, prostacyclin, and thromboxane.
- There are drugs, which modify the course of diseases like anti-malarial, D-penicillamine, and gold salt.
- Corticosteroids are used for symptomatic improvement but there use is controversial.
- Cytotoxic drugs like azathioprine and cyclophosphamide may be used but avoided because of their side effects. Only useful in severe extra-articular manifestation.