What is rheumatoid arthritis?
Rheumatoid arthritis is a chronic, systemic, generally progressive, autoimmune inflammatory disease, which chiefly affects the synovial membranes of multiple joints, and the connective tissue elements of tendons and ligaments. Of the inflammatory arthritis conditions, rheumatoid arthritis is the most common.
In severe disease, inflammatory degeneration of the organs may also occur, particularly involving the heart, lung and kidney, and exhibits a wide clinical spectrum with considerable variability in the joint and extra-articular manifestations.
Rheumatoid arthritis affects 1 to 3% of the general population. Before menopause women are three to four times more likely to develop the disease compared with men. The peak age of onset is between 20 to 40 years of age. How¬ever, acute onset may commence at any age and juvenile rheumatoid arthritis can develop in children.
The cause of this inflammatory polyarthritis remains ill defined. Genetic factors play a significant role. In the case of identical twins, if one twin develops rheumatoid arthritis the other twin will develop the disease in 40% of cases. A person whose identical twins has rheumatoid arthritis is five times more likely to develop rheumatoid arthritis compared with non-identical twins.
The disease appears to be strongly related to the immune response genes of the major histo compatibility complex that code for class II HLA. Population surveys reveal a strong association between specific alleles at the HLA-DRB1 locus and disease susceptibility, with relative risk varying from twofold for HLA-DR1 to more than sixfold for HLA-DR4.
Thus, in patients with severe seropositive erosive arthritis, more than 70% of patients are HLA-DR4 positive compared to a 25% incidence in the unaffected population. In the more severe forms of rheumatoid arthritis, the specific Dw4 subtype of DR4 shows an increased frequency, with the majority of DR4 homozygotes exhibiting a Dw4/Dw14 genotype.
The genetic contribution accounts for approximately 30% of the disease incidence. Environmental factors strongly influence initiation and maintenance of the autoimmune disease process. Many infectious disorders have shown the capacity to initiate immunologically mediated, inflammatory reactive arthritis, for example following gastroenteric infection with Chlamydia, Salmonella, Campylobacter, Shigella and Yersinia, or systemic viral infection, such as Ross River Virus, Barmah Forest Virus and Parvovirus. Thus, a variety of infectious agents have been postulated to cause rheumatoid arthritis, either by covert joint tissue infection, as for mycoplasma, rickettsiae and chlamydiae species, or immunological reactivity against organisms that exhibit tissue antigen molecular mimicry, as for proteus and Klebsiella organisms.
Pathologic examination of the joint tissues invariably demonstrates a severe inflammatory synovitis with hypertrophic tissue changes, called a pannus, which is infiltrated with large numbers of inflammatory cells including activated tissue macrophages, dendritic cells, plasma cells, and T and B lymphocytes – predominantly CD4-helper T lymphocytes.
Collagen autoimmunity has been implicated in the development of rheumatoid arthritis and, though circulating antibodies to type II collagen are detectable in rheumatoid patients, intra-articular cartilage and synovium contain a far greater prevalence of type II collagen antibodies than serum, which suggests an intra-articular antigen-driven immune process is responsible.
On a molecular level, the plasma cells secrete large quantities of immunoglobulins, mainly IgM and IgG rheumatoid factor, which react with self-IgG, activating complement proteins that initiate and maintain the inflammatory process. Complement breakdown products act as potent chemokines, attracting and activating polymorphonuclear leucocytes and stimulating release of proteases, lysosomal enzymes, collagenases, prostaglandins and TNF-alpha, which results in inflammatory erosion of cartilage and bone, breakdown of ligaments and tendons, and systemic cytokine-mediated inflammatory effects. Rheumatoid arthritis symptoms can include fever, energy loss, protein catabolism, myalgia and arthralgia.
During the acute phase, an inflammatory joint effusion will develop resulting in severe pain, redness and swelling. During the later stages, joint destruction, instability, and loss of function will develop resulting in secondary joint tissue fibrosis, misalignment of joints, and gross disturbance of joint movement.
Widespread inflammatory will often occur in other tissues, including myositis, tendonitis and tenosynovitis, endothelial vasculitis, and inflammatory granulomata in the subdermal connective tissues and organs, such as the heart, heart valves, lungs, spleen, and kidneys.
Conventional medical treatment for rheumatoid arthritis
Unfortunately no cure for rheumatoid arthritis is available and only rarely does the problem goes away. Effective management of rheumatoid arthritis requires a multi disciplinary approach based on early and accurate diagnosis, which will enable appropriate therapy, patient education about joint protection, future planning to delay with potential disability, and adequate social support.
Medical treatment should include physical therapy, and pharmaceutical therapy, which usually work well, but most take several weeks to months to take full effect. In advanced disease, surgery may be necessary to replace a diseased joint, to enable improved mobility.
Physical therapy should emphasise:
- Joint protection measures ranging from merely resting affected joints to splinting of joints, particularly at night to avoid future joint deformity, or for joints that are too painful or unstable for use
- Local application of heat or cold or regular massage with analgesic or healing creams and lotions (topical NSAID creams, Dead Sea mud packs and sulphur baths)
- Stretching exercises to prevent joint contracture
- Active resistance exercise to maintain muscle strength and tone
- Supportive orthotic footwear to prevent foot deformity or enable the patient with deformed feet to maintain mobility
Pharmaceutical therapy that is focused on:
- Analgesia and anti-inflammatory relief – aspirin and aspirin derivatives; NSAIDS such as ibuprofen, piroxicam and sulindac; and the new COX-2 inhibitor medications celecoxib and rofecoxib
- Disease-modifying medications that are believed to influence the underlying rheumatoid pathology, though they exhibit substantial adverse effects, requiring careful patient monitoring. Drugs in this class include: gold salts; sulphasalazine; D-penicillamine and the antimalarial medication hydroxychloroquine.
- Steroidal anti-inflammatory therapy – substantially reduces inflammation and modifies disease progression, but adverse affects of iatrogenic Cushing’s syndrome, immune system depression and osteoporosis limit the use to short-term intervention preferably. Synthetic steroid prednisone and prednisolone are potent agents and cortisone acetate in low doses on an intermittent basis as required is preferable.
- Cytotoxic chemotherapy agents in low dose destroy lymphocytes and leucocytes and include: methotrexate, cyclophosphamide and azathioprine. In low-dose they exhibit little acute adverse effects, though acute infection due to secondary immune system depression is not uncommon, but long-term adverse effects are problematical.
- Novel immune-targeted therapies include: leflunomide, a lymphocyte suppression medication that shows good clinical efficacy but also exhibits serious adverse hepato¬toxic and bone marrow suppressive effects; and anti-TNF-alpha agents that are currently undergoing clinical trials.
Surgery is sometimes necessary to maintain function or reduce pain, and may include:
- Soft tissue procedures, as in repair of tendon rupture, tendon transfer, nerve decompression
- Synovectomy and excision arthroplasty to correct persistent synovitis and joint deformity
- Arthrodesis to fuse painful and unstable joints, particularly neck and foot joints
- Joint replacement arthroplasty, particularly of the hip and knee joints
Contemporary outcome studies report that pharmaceutical therapy has little beneficial impact on disease progression or overall mortality, with some reports that cytotoxic therapy may even reduce life expectancy.
Symptoms of rheumatoid arthritis may include painful swelling, inflammation, and stiffness in the fingers, arms, legs, and wrists occurring in the same joints on both sides of the body, especially upon awakening.
Nutritional medicine treatment for rheumatoid arthritis
For years people have believed that foods are an important trigger in the development of rheumatoid arthritis. Many sufferers notice an improvement in their condition when they avoid dairy products, citrus fruits, tomatoes, eggplant, meat, and sugar-rich and processed foods. For example omega-3 fatty acid supplements, and a gluten-free vegan diet have been show to benefit some people with rheumatoid arthritis.
From a nutritional medicine perspective, a variety of precipitating factors appear to be causally related to the development of the immune system hyper-reactivity, the prime characteristic of rheumatoid arthritis. These causal factors include both genetic and environ¬mental factors that interact to produce a hyper-inflammatory immunological state, with altered tissue macrophage antigen presentation, excessive production of cytokines and inflammatory mediators, and a shift in T-lymphocyte activity that results in production of autoimmune antibodies.