Dr Brown's scleroderma protocol

Physicians' Protocol For Using Antibiotics in Rheumatic Disease (SCLERODERMA)
By Dr. Joseph Mercola

One of the main features of fibromyalgia is the morning stiffness, fatigue, and multiple areas of tenderness in typical locations. Most patients with fibromyalgia complain of pain over many areas of the body, with an average of six to nine locations. Although the pain is frequently described as being all over, it is most prominent in the neck, shoulders, elbows, hips, knees, and back.

Tender points are generally symmetrical and on both sides of the body. The areas of tenderness are usually small (less than an inch in diameter) and deep within the muscle. They are often located in sites that are slightly tender in normal people.

Patients with fibromyalgia, however, differ in having increased tenderness at these sites than normal persons. Firm palpation with the thumb (just past the point where the nail turns white) over the outside elbow will typically cause a vague sensation of discomfort. Patients with fibromyalgia will experience much more pain and will often withdraw the arm involuntarily.

More than 70% of patients describe their pain as profound aching and stiffness of the muscles. Often it is relatively constant from moment to moment, but certain positions or movements may momentarily worsen the pain. Other terms used to describe the pain are dull and numb.

Sharp or intermittent pain is relatively uncommon. Patients with fibromyalgia often complain that sudden loud noises worsen their pain. The generalized stiffness of fibromyalgia does not diminish with activity, unlike the stiffness of rheumatoid arthritis, which lessens as the day progresses.

Despite the lack of abnormal lab tests, patients can suffer considerable discomfort. The fatigue is often severe enough to impair activities of work and recreation. Patients commonly experience fatigue on arising and complain of being more fatigued when they wake up then when they went to bed. Over 90% of patients believe the pain, stiffness, and fatigue are made worse by cold, damp weather. Overexertion, anxiety and stress are also factors. Many people find that localized heat, such as hot baths, showers, or heating pads, give them some relief. There is also a tendency for pain to improve in the summer with mild activity or with rest.

Some patients will date the onset of their symptoms to some initiating event. This is often an injury, such as a fall, a motor vehicle accident, or a vocational or sports injury. Others find that their symptoms began with a stressful or emotional event, such as a death in the family, a divorce, a job loss, or similar occurrence.

Patients with fibromyalgia have pain in at least 11 of the following 18 tender point sites (one on each side of the body):

Base of the skull where the suboccipital muscle inserts.
Back of the low neck (anterior intertransverse spaces of C5-C7).
Midpoint of the upper shoulders (trapezius).
On the back in the middle of the scapula.
On the chest where the second rib attaches to the breastbone (sternum).
One inch below the outside of each elbow (lateral epicondyle).
Upper outer quadrant of buttocks.
Just behind the swelling on the upper leg bone below the hip (trochanteric prominence).
The inside of both knees (medial fat pads proximal to the joint line).

There is a persuasive body of emerging evidence that indicates that patients with fibromyalgia are physically unfit in terms of sustained endurance. Some studies show that cardiovascular fitness training programs can decrease fibromyalgia pain by 75%. Sleep is critical to the improvement. Many times, improved fitness will correct the sleep disturbance.

Allergies, especially to mold, seem to be another common cause of fibromyalgia. There are some simple interventions using techniques called Total Body Modification (TBM) 800-243-4826.

It is very important to exercise or increase muscle tone of the non-weight bearing joints. Experts tell us that disuse results in muscle atrophy and weakness. Additionally, immobility may result in joint contractures and loss of range of motion (ROM). Active ROM exercises are preferred to passive.

There is some evidence that passive ROM exercises increase the number of WBCs in the joint. If the joints are stiff, one should stretch and apply heat before exercising. If the joints are swollen, application of ten minutes of ice before exercise would be helpful.

The inflamed joint is very vulnerable to damage from improper exercise, so one must be cautious. People with arthritis must strike a delicate balance between rest and activity. They must avoid activities that aggravate joint pain. Patients should avoid any exercise that strains a significantly unstable joint.

A good rule of thumb is that if the pain lasts longer than one hour after stopping exercise, the patient should slow down or choose another form of exercise. Assistive devices are also helpful to decrease the pressure on affected joints. Many patients need to be urged to take advantage of these. The Arthritis Foundation has a book, Guide to Independent Living, which instructs patients about how to obtain them.

Of course, it is important to maintain good cardiovascular fitness. Walking with appropriate supportive shoes is also another important consideration.

It is quite clear that autoimmunity plays a major role in the progression of rheumatoid arthritis. Most rheumatology investigators believe that an infectious agent causes rheumatoid arthritis. There is little agreement as to the involved organism. Investigators have proposed the following infectious agents: Human T-cell lymphotropic virus Type I, rubella virus, cytomegalovirus, herpesvirus, and mycoplasma. This review will focus on the evidence supporting the hypothesis that mycoplasma is a common etiologic agent of rheumatoid arthritis.

Mycoplasmas are the smallest self-replicating prokaryotes. They differ from classical bacteria by lacking rigid cell wall structures and are the smallest known organisms capable of extracellular existence. They are considered to be parasites of humans, animals, and plants.

In 1939, Dr. Sabin, the discoverer of the polio vaccine, first reported a chronic arthritis in mice caused by a mycoplasma. He suggested this agent might cause that human rheumatoid arthritis. Dr. Thomas Brown was a rheumatologist who worked with Dr. Sabin at the Rockefeller Institute. Dr. Brown trained at John Hopkins Hospital and then served as chief of medicine at George Washington Medical School before serving as chairman of the Arthritis Institute in Arlington, Virginia. He was a strong advocate of the mycoplasma infectious theory for over fifty years of his life.

Mycoplasmas have limited biosynthetic capabilities and are very difficult to culture and grow from synovial tissues. They require complex growth media or a close parasitic relation with animal cells. This contributed to many investigators failure to isolate them from arthritic tissue. In reactive arthritis immune complexes rather than viable organisms localize in the joints. The infectious agent is actually present at another site. Some investigators believe that the organism binding in the immune complex contributes to the difficulty in obtaining positive mycoplasma cultures.

Despite this difficulty some researchers have successfully isolated mycoplasma from synovial tissues of patients with rheumatoid arthritis. A British group used a leucocyte-migration inhibition test and found two-thirds of their rheumatoid arthritis patients to be infected with Mycoplasma fermentens. These results are impressive since they did not include more prevalent Mycoplasma strains like M salivarium, M ovale, M hominis, and M pneumonia.

One Finnish investigator reported a 100% incidence of isolation of mycoplasma from 27 rheumatoid synovia using a modified culture technique. None of the non- rheumatoid tissue yielded any mycoplasmas. The same investigator used an indirect hemagglutination technique and reported mycoplasma antibodies in 53% of patients with definite rheumatoid arthritis. Using similar techniques other investigators have cultured mycoplasma in 80- 100% of their rheumatoid arthritis test population.

Rheumatoid arthritis follows some mycoplasma respiratory infections. One study of over 1000 patients was able to identify arthritis in nearly 1% of the patients. These infections can be associated with a positive rheumatoid factor. This provides additional support for mycoplasma as an etiologic agent for rheumatoid arthritis. Human genital mycoplasma infections have also caused septic arthritis.

Harvard investigators were able to culture mycoplasma or a similar organism, ureaplasma urealyticum, from 63% of female patients with SLE and only 4% of patients with CFS. The researchers chose CFS as these patients shared similar symptoms as those with SLE, such as fatigue, arthralgias, and myalgias.

The full spectrum of human rheumatoid arthritis immune responses (lymphokine production, altered lymphocyte reactivity, immune complex deposition, cell-mediated immunity and development of autoimmune reactions) occurs in mycoplasma induced animal arthritis. Investigators have implicated at least 31 different mycoplasma species. Mycoplasma can produce experimental arthritis in animals from three days to months later. The time seems to depend on the dose given and the virulence of the organism.

There is a close degree of similarity between these infections and those of human rheumatoid arthritis. Mycoplasmas cause arthritis in animals by several mechanisms. They either directly multiply within the joint or initiate an intense local immune response. Mycoplasma produces a chronic arthritis in animals that is remarkably similar to rheumatoid arthritis in humans. Arthritogenic mycoplasmas cause joint inflammation in animals by many mechanisms. They induce nonspecific lymphocyte cytotoxicity and antilymphocyte antibodies as well as rheumatoid factor. Mycoplasma clearly causes chronic arthritis in mice, rats, fowl, swine, sheep, goats, cattle and rabbits. The arthritis appears to be the direct result of joint infection with culturable mycoplasma organisms.

Gorillas have tissue reactions closer to man than any other animal. Investigators have shown that mycoplasma can precipitate a rheumatic illness in gorillas. One study demonstrated mycoplasma antigens occur in immune complexes in great apes. The human and gorilla IgG are very similar and express nearly identical rheumatoid factors (IgM anti-IgG antibodies). The study showed that when mycoplasma binds to IgG it can cause a conformational change. This conformational change results in an anti-IgG antibody, which can then stimulate an autoimmune response.

If mycoplasma were a causative factor in rheumatoid arthritis, one would expect tetracycline type drugs to provide some sort of improvement in the disease. Collagenase activity increases in rheumatoid arthritis and probably has a role in its cause. Investigators demonstrated that tetracycline and minocycline inhibit leukocyte, macrophage, and synovial collagenase.

There are several other aspects of tetracyclines that may play a role in rheumatoid arthritis. Investigators have shown minocycline and tetracycline to retard excessive connective tissue breakdown and bone resorption while doxycycline inhibits digestion of human cartilage. It is also possible that tetracycline treatment improves rheumatic illness by reducing delayed-type hypersensitivity response. Minocycline and doxycycline both inhibit phosolipases which are considered proinflammatory and capable of inducing synovitis.

Minocycline is a more potent antibiotic than tetracycline and penetrates tissues better. These characteristics shifted the treatment of rheumatic illness away from tetracycline to minocycline. Minocycline may benefit rheumatoid arthritis patients through its immunomodulating and immunosuppressive properties. In vitro studies demonstrated a decreased neutrophil production of reactive oxygen intermediates along with diminished neutrophil chemotaxis and phagocytosis.

Investigators showed that minocycline reduced the incidence of severity of synovitis in animal models of arthritis. The improvement was independent of minocycline's effect on collagenase. Minocycline has also been shown to increase intracellular calcium concentrations that inhibit T-cells.

Individuals with the Class II major histocompatibility complex (MHC) DR4 allele seem to be predisposed to developing rheumatoid arthritis. The infectious agent probably interacts with this specific antigen in some way to precipitate rheumatoid arthritis. There is strong support for the role of T cells in this interaction.

Minocycline may suppress rheumatoid arthritis by altering T cell calcium flux and the expression of T cell derived from collagen binding protein. Minocycline produced a suppression of the delayed hypersensitivity in patients with Reiter's syndrome. Investigators also successfully used minocycline to treat the arthritis and early morning stiffness of Reiter's syndrome.

In 1970 investigators at Boston University conducted a small, randomized placebo-controlled trial to determine if tetracycline would treat rheumatoid arthritis. They used 250 mg of tetracycline a day. Their study showed no improvement after one year of tetracycline treatment. Several factors could explain their inability to demonstrate any benefits.

Their study used only 27 patients for a one-year trial, and only 12 received tetracycline. Noncompliance could have been a factor. Additionally, none of the patients had severe arthritis. Patients were excluded from the trial if they were on any anti-remittive therapy.

Finnish investigators used lymecycline to treat the reactive arthritis in Chlamydia trachomatous infections. The study compared the effect of the medication in patients with two other reactive arthritis infections Yersinia and Campylobacter.

Lymecyline produced a shorter course of illness in the Chlamydia induced arthritis patients, but did not affect the other enteric infections-associated reactive arthritis. The investigators later published findings that suggested lymecycline achieved its effect through non-antimicrobial actions. They speculated it worked by preventing the oxidative activation of collagenase.

Breedveld published the first trial of minocycline for the treatment of animal and human rheumatoid arthritis. In the first published human trial, Breedveld treated ten patients in an open study for 16 weeks. He used a very high dose of 400 mg per day. Most patients had vestibular side effects resulting from this dose.

However, all patients showed benefit from the treatment. All variables of efficacy were significantly improved at the end of the trial. Breedveld concluded an expansion of his initial study and observed similar impressive results. This was a 26-week double-blind placebo-controlled randomized trial with minocycline for 80 patients. They were given 200 mg twice a day. The Ritchie articular index and the number of swollen joints significantly improved (p < 0.05) more in the minocyline group than in the placebo group.

Investigators in Israel studied 18 patients with severe rheumatoid arthritis for 48 weeks. These patients had failed two other DMARD. They were taken off all DMARD agents and given minocycline 100 mg twice a day. Six patients did not complete the study, three withdrew because of lack of improvement, and three had side effects of vertigo or leukopenia. All patients completing the study improved. Three had complete remission, three had substantial improvement of greater than 50% and six had moderate improvement of 25% in the number of active joints and morning stiffness.

Radiological changes typical of rheumatoid arthritis on PA hand and wrist X-rays, which must include erosions or unequivocal bony decalcification localized to or most marked adjacent to the involved joints (osteoarthritic changes alone do not count).

Note: Patients must satisfy at least four of the seven criteria listed. Any of criteria 1-4 must have been present for at least 6 weeks. Patients with two clinical diagnoses are not excluded. Designations as classic, definite, or probable rheumatoid arthritis is not to be made.

Presented at the 32nd International Congress of the Great Lakes College of Clinical Medicine. Baltimore, Maryland, September 25, 1999