Rheumatoid arthritis is an acquired disease, but the way people get it—and whether they get it—is determined by factors that are as complex as arthritis itself.
The principal complication is in the fact that rheumatoid arthritis involves a bacterial allergy. One of the characteristics of bacterial allergies is that the allergic process is so powerful, the body isolates the germ and keeps it from being transmitted to others.
A good model for that phenomenon is undulant fever, or brucellosis, a disease acquired from cattle or swine. Undulant fever is highly contagious among such livestock, and if one animal catches it, the disease spreads through the herd like wildfire. Man can contract undulant fever by drinking milk from an infected animal, but it has never been known in the history of medicine that the disease has been transmitted from one human to another. I believe the reason is that man, unlike cattle and swine, is so reactive to the antigens made by brucellae that the reactive state walls it off and keeps it highly localized, not allowing it to become a contagious entity. The same thing happens with mycoplasmas.
There are two main types of immunity: bloodstream immunity, in which certain factors in the blood protect us against particular diseases, and cellular immunity, in which the same protection is provided by the tissues of the body. The lack of cellular immunity is the reason children contract measles, whooping cough, chicken pox, mumps, and other so-called childhood disorders.
We know that mycoplasmas can be recovered from the genital tracts of women as a matter of routine. We look upon these organisms as parasites at that stage, but their presence at the end of the birth canal creates the possibility of a scenario in which the child can become infected and the relatively passive parasitic mycoplasma can eventually be transformed into an active agent of disease. If it happens that the mycoplasma enters the infant’s body, the parasite could escape into the bloodstream and be carried to the joints, where it would attach to the synovial cells. It could remain in the parasitic stage indefinitely, ticking away, awaiting its time to turn into something far more serious.
As the years go by, it is possible that these and other factors raise the body’s level of sensitivity until it finally reaches a point where, on a localized basis, the stage is set for an allergic reaction. The allergy would be the result of the body responding to the persistent presence of these organisms by raising a defense to surround them. How the reaction is triggered is the subject of speculation: it might be an accidental bump or contusion, or severe mental stress—or in some cases it might be the trauma of childbirth. I have treated a great many patients who never suspected they had any kind of arthritis until they had gone through some such seemingly unrelated shock or stress. Almost invariably they have associated their disease with the event that acted as the trigger.
If this linkage is correct, as I suspect it is, then the mycoplasma acts in the same way as a slow virus. Once the liberating event has set it off, it begins to create a reaction that walls it off even further to defend itself against attack by the body’s immune system. That would explain why as arthritis becomes more entrenched it also becomes more severe.
This scenario also supports the thesis that all the rheumatoid forms of arthritis derive from essentially the same causes, as I believe they do, and that the many variations in the disease are simply a result of differing levels of allergy and reactivity in the hosts. Similarly, people who suffer from asthmatic allergies may react to dust in one case and feathers and pollens in another, but the allergy itself, regardless of the source, is the cause of their distress.
The analogy with asthmatic allergies only holds up to a point, however; rheumatoid arthritis involves a living source of antigen which cannot be isolated from the patient in the way of ragweed or feathers. Bacterial antigens appear to have a physiological effect on things inside the body such as joints, muscles, nerves, the intestinal tract, and internal organs. The internal allergy is generally referred to as hypersensitivity to distinguish it from external allergies. Ordinary allergies affect the skin, the lungs, the eyes, and generally the outside of the body. Both can affect an intermediate ground, the gastrointestinal tract. External allergies come and go with changes in the environment, such as the seasons, or simply with cleaning the house or filtering the air. But internal hypersensitivities are built in and they persist, and the antigen from a bacterial source keeps coming, constantly or intermittently, and serves as a booster.
The reason housecleaning doesn’t work with internal allergies is that they are so inaccessible, and as these hypersensitivity conditions get worse they get even harder to reach because the walls around them rise progressively higher. When viewed under the microscope, the areas of inflammation in the affected tissues are seen to be spotty, as though the body had erected a series of tiny fortresses around the causative factor.
At the very center of those fortresses are the mycoplasmas. Although their presence can be verified by other means such as protein fractionation, they usually can’t be seen with certainty even by an electron microscope; the particles are so tiny that they are indistinguishable from the parts of the cell to which they attach. Even when a tissue is deliberately inoculated with mycoplasmas and the physician examines electron-microscopic sections of the infected cells, it is difficult to determine which of the particles are derived from mycoplasmas and which represent normal cellular constituents. Little wonder that the mycoplasmas’ relationship to rheumatoid arthritis has eluded understanding for so long.
This near-invisibility is one more respect in which mycoplasmas are different from any other kind of disease agent. Even viruses, which are equally small, have what are called nuclear inclusions; the inclusion body in the nucleus of the cell for certain viruses is very distinctive, lining up in a crystalloid pattern of specks, and this “fingerprint” of one virus will be recognizably different from the pattern of another. Mycoplasmas don’t line up in the nucleus.
It is my belief that all of the rheumatic disorders, from the mildest arthritis to the most fatal form of lupus, involve mycoplasmas as a causative agent. There are two possible reasons for the same cause to produce such widely differing results: there are variations in how strongly the different tissues react against the organism, and there are some forms of mycoplasma that are more virulent than others.
There are other reasons for the immense number of variables in the arthritis family tree. Once the focus of sensitivity is established by the unique ability of the mycoplasma to attach to joints, other bacterial antigens can enter the picture and compound the problem. This is particularly true of the streptococcal antigen, which has a special affinity for sensitizing joints, as in rheumatic fever. Infected teeth, tonsils, sinuses, gallbladders, kidneys, and diverticula can contribute and often must be treated separately.
The most vicious strain of mycoplasma that has been isolated to date and one whose antibody is very commonly present in the blood of rheumatoid arthritics is Mycoplasma pneumoniae, which causes viral pneumonia. I don’t have any statistics on its incidence, but a lot of my patients over the years—far above the norm for the population as a whole—have suffered from walking pneumonia, an event which may well have supplied the trigger for a sudden upsurge in their arthritis.
Another dimension of the question about the causes of arthritis that deserves far more laboratory research is all the other L-forms of bacteria. The L-forms so closely resemble mycoplasmas in the laboratory that at one time all mycoplasmas were referred to as L-form bacteria. If a researcher grows streptococci on a laboratory medium, adds penicillin to the medium, and kills the strep or other bacteria, he may see tiny, microscopic colonies of what look like clusters of fried eggs emerging from the remains of the germ, in exactly the same manner as mycoplasmas produce such colonies.
Microbiologists claim these particular fried eggs are not identical to mycoplasmas, and indeed there are some chemical differences. But they are the same in form and structure, and are specifically suppressed by tetracycline derivatives, as are mycoplasmas. They behave the same way, growing on the surface of media. Protein fractionation, electrophoresis, and other study techniques are just now starting to provide valuable clues to their exact nature and relationship to the arthritic process.
The payoff on such research could be enormous. In rheumatic fever, for example, streptococcus splits off L-forms which very likely get into connective tissue in joints, the heart muscle, and even heart valves. One cannot grow the strep from the joints or heart muscle or valves, but it is possible the L-form is in these places, setting up a local sensitivity without the strep itself being present. If so, that would explain the chronic, destructive changes that go along with rheumatic fever. It is curious that the damage to the joints is not permanent, but clears up when the disease comes to an end. But the damage to the kidney or heart that has been caused by this unknown factor—a strep antigen or whatever—does not clear up, and it can shorten life.
I wouldn’t be at all surprised if research were to prove that when the L-form becomes fixed as a new entity, it becomes a mycoplasma. Phylogenetically, this could mean that back at the beginning of life, millions of years ago, there were only bacteria, and some of them evolved into the L-forms which later became mycoplasma, and some of them went in another direction to become parasites, amoebas, and other such organisms, adapting to changes in the environment.
All diseases of the connective tissue are related to the same process that controls the rheumatoid forms of arthritis, and all respond, in greater or lesser degrees, to the same antibiotic approach to treatment. Lupus, which is a disease whose mortality figures are extremely unreliable because of a lack of continuity in observation, may kill as many as 75 percent of those who contract it. I have had consistently positive results in treating even very advanced cases with tetracycline, including several patients who have now reached what appears to be permanent remission.
One connective-tissue disease that proves the case for tetracycline even more incontrovertibly is scleroderma. It is a chronic hardening and shrinking of the connective tissues in which the skin turns to leather and, because the blood vessels are involved as well, the extremities become numb and cold. It affects the ectodermal portion of the esophagus so that eventually the patient loses the peristaltic motion that permits swallowing, and it can even invade the lungs and intestinal tract. It is a slow, progressive, inevitable death.
During the past few years, I have been sent a number of scleroderma patients from Athens, Alabama. They have all tested high for mycoplasma antibody levels—just as patients with lupus or rheumatoid arthritis or mixed osteo-rheumatoid arthritis or dermatomyositis do—and I have treated every one of them with tetracycline, just as I treat everyone who is suffering from these or any other disease of the connective tissues. And the scleroderma patients have all improved, some dramatically.
In the case of scleroderma, any improvement at all is dramatic, but these improvements are truly remarkable. The patients have increased their ability to swallow. The skin on their face and hands has started to loosen up and become supple again. Those who have been caught early don’t have any further progression of the disease, and those who started late have begun to reverse their condition. The most striking result has been the reversal of widespread sclerodermatous pulmonary lesions.
A lot of doctors like to explain away any progress in rheumatoid arthritis or lupus by calling it natural remission. But they can’t explain what happens with scleroderma as a natural remission because with that disease there isn’t any such thing: under any other form of treatment the disease only goes one way, downward, and it doesn’t stop until the patient is dead.
All these different types of connective-tissue disorders involve a circulating antibody against mycoplasma, but that is not to say that every patient proves positive for those antibodies every time he or she is tested. In those cases where the results are negative, as a rule all that is required to get a positive result is to follow the patient for a period until the antibody pops up again. The process of antibody circulation in rheumatoid arthritis or other such diseases is very similar to that in undulant fever, which is often very difficult to diagnose because of the wavelike periodicity of the antibody. The cyclical appearance and disappearance of a disease antibody is a widely recognized phenomenon of immunology. The Herxheimer effect, which is a toxic surge that follows the onset of treatment for mycoplasmic disorders, brings out the antibody in patients who have tested negative prior to treatment; as the treatment progresses, the antibody eventually tests negative again.
Eventually there will be a test for the antigen of mycoplasmas as well as for the antibody; diagnosticians will be able to look for the disease factor that creates the condition, rather than seeking an indication of the body’s response. This is an area of research in which the Arthritis Institute is vigorously active. We have also noted a greater concentration of both antigen and antibody in joint fluid compared to the blood serum from the same patient.
In order to identify the antigen, it is first necessary to break down tissue, joint fluid, or blood into its serial protein fractions. Blood has any number of different proteins in it, one of which turns out to derive from mycoplasma. We have been measuring the direct signs of mycoplasma in the blood—either its toxins, particles of the germ, or the entire disease organism—to see whether it goes away when the patient is treated intravenously with tetracycline. And we have shown that it does.
We have also been collecting and analyzing data to look for a correlation between the dropoff of the antigen and the status of the symptoms as the patient is treated. Preliminary data are not sufficient to prove anything significant, but there is enough positive evidence to encourage further effort. One of the benefits of such a correlation, if it is proven, will be to provide an alternative to double-blind testing.
Not all of the information that has developed from fifty years of research and practice with connective-tissue disorders is of a kind that lends itself to statistical summary. In fact, I often feel that the source that has weighed most heavily over the long term, in helping me to understand what is involved in these diseases and in recognizing their patterns, is the kind of data that scientists characterize as anecdotal. In time, as it repeats itself over and over again, anecdotal data becomes progressively more substantive and meaningful. Perhaps more than any other aspect of learning, it has provided the deepest insights into the process by which arthritis happens to people.
That is the principal reason for the approach we have taken in the writing of this book.