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Page: Pathophysiology
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Causes
The cause of RA is still unknown to this day, but has long been suspected to be infectious. It could be due to food allergies or external organisms. Mycoplasma, Erysipelothrix, Epstein-Barr virus, parvovirus B19 and rubella have been suspected but never supported in epidemiological studies. As in other autoimmune diseases, the "mistaken identity" theory suggests that an offending organism causes an immune response that leaves behind antibodies that are specific to that organism. The antibodies are not specific enough, though. They begin an immune attack against, in this case, the synovium, because some molecule in the synovium "looks like" a molecule on the offending organism that created the initial immune reaction - this phenomenon is called molecular mimicry.
But physical and emotional effects, stress and improper diet could play a role in the disease. It is suspected that susceptibility to rheumatoid arthritis is an inherited trait.
Autoimmune diseases require that the affected individual have a defect in the ability to distinguish self from foreign molecules. There are markers on many cells that confer this self-identifying feature. However, some classes of markers allow for RA to happen. 90% of patients with RA have the cluster of markers known as the HLA-DR4/DR1 cluster, whereas only 40% of unaffected controls do. Thus, in theory, RA requires susceptibility to the disease through genetic endowment with specific markers and an infectious event that triggers an autoimmune response.
Once triggered, the immune response causes inflammation of the synovium. Early and intermediate molecular mediators of inflammation include tumor necrosis factor alpha (TNF-?), interleukins IL-1, IL-6, IL-8 and IL-15, transforming growth factor beta, fibroblast growth factor and platelet-derived growth factor. Modern pharmacological treatments of RA target these mediators. Once the inflammatory reaction is established, the synovium thickens, the cartilage and the underlying bone begins to disintegrate and evidence of joint destruction accrues.
Bacteria/antibiotic hypothesis
Thomas McPherson Brown along with other researchers and patient groups believe that it can be demonstrated that RA is caused by a bacterial infection, in particular mycoplasma that localizes to joints.
Thomas McPherson Brown used tetracycline antibiotics to treat rheumatoid arthritis, and concluded that improvement in symptoms was evidence that the antibiotic must be killing a bacterium that caused the arthritis. The tetracycline antibiotics that he used, however also "exhibit immunomodulatory properties, which may contribute significantly to their beneficial effects in rheumatoid arthritis". In other words, the same drug can both kill bacteria and suppress the immune system, and the latter may be responsible for its benefits in rheumatoid arthritis. That said, there are thousands of documented cases of remission of RA and other related auto-immune diseases using antibiotics on file at the National Hospital in Washington, D.C., where Dr. Brown practiced, and many other reports from rheumatologists worldwide that judicious use of minocycline, sometimes combined with clindamycin, along with diet change, nutritional supplements, and vigorous exercise, and various other immune-strengthening alternative therapies, such as acupuncture, hyperbaric oxygen, and infra-red sauna, can retard or remit the disease. Tumor necrosis factor inhibitors are a class of drugs that markedly reduce resistance to certain types of bacterial infection (including the mycobacteria that were hypothesised to be to blame for rheumatoid arthritis by McPherson Brown). They are, however very effective in treating RA. In fact, they are one of the most effective treatments for rheumatoid arthritis in widespread use. If rheumatoid arthritis were caused by bacteria, we would expect the disease to worsen, not improve, when tumour necrosis factor inhibitors are used, contrary to what is widely observed. The bacteria/antibiotic hypothesis therefore has very little support amongst the majority of rheumatologists and researchers, but is seen by a small number of integrative physicians and caregivers as part of the web of factors that produce the disease. Several large, long-term studies in the last ten years, both in the United States and Europe, have convinced these integrative healers that antibiotics have an important role to play in the armamentarium of weapons against RA, and an evolved form of the antibiotic protocol originally devised by Dr. Brown at the National Hospital has now been officially sanctioned as a DMARD (disease-modifying anti-rheumatic drug) by the AMA and recognized by the Arthritis Foundation.
Rheumatoid arthritis, ankylosing spondylitis, systemic and discoid lupus, Sjogren's disease, celiac disease, dermatitis herpetiformis, Crohn's disease, ulcerative colitis and scleritis have been associated with the genetic porphyrias. Lupus, transient and sustained autoantibody production have been reported with both neurovisceral and cutaneous porphyrias since the early 1950s.
Physicians should be on high alert for porphyrias in families with autoimmune diseases since porphyrinogenic drugs can lead to acute porphyria attacks and further medical complications. Pericarditis, syndrome of inappropriate antidiuretic hormone, focal and systemic neuropathy, and pancreatitis have been reported with the highly drug sensitive porphyrias.
Testing should be appropriate for all neurovisceral and cutaneous porphyrias. The urine screening test used to detect acute neurovisceral porphyria attacks is an unreliable test and inappropriate for hereditary coproporphyria, variegate porphyria and children.
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Important notice:
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