Arthritis: Symptoms and Diagnosis

  by Staff Editor

For the victim of rheumatoid arthritis, tangible evidence of the disease may not show up in a form that can be readily identified until it reaches its acute stage, with nodules at the joints and even disfigurement. But the physician who sees the patient in time can recognize the first symptoms far earlier, perhaps as much as a year and a half before these external physical changes occur.

What Doctors Tell Patients:

The first sign of rheumatoid arthritis is not pain, but fatigue with no good reason. The history of the fatigue and of what the patient does about it often follows a predictable patter. As a rule, when the victim realizes that he or she needs more and more sleep, the logical response is to see a family practitioner. Several tests are done, and the doctor usually reports that there is no apparent physical cause for the condition. He then asks the patient, “What's bothering you? You seem to be under a great deal of tension.”

The physician is on pretty safe ground. Every person who ever visited a doctor is under some kind of stress; that's the nature of modern living. The patient thinks about it for a moment, and then acknowledges that the doctor is right. In this brief exchange, for no other reason than that the doctor can't figure out what's wrong, some of the responsibility for the symptoms has been subtly shifted to the patient. The doctor nods in affirmation and says, "Well, you'll be all right. I think that's all it is."

One of the other symptoms of rheumatoid arthritis is depression. That takes a lot of the fight out of a person, so at this point, many patients meekly get up and go home. Others are unwilling to be dismissed that quickly, and they ask the doctor if there's anything he can do to make them feel better and restore their former energy. Sometimes the physician prescribes shots of vitamins, but as a rule he says no, that things will get better by themselves.

The next step, before there is any visible change, can be an unexplained anemia. This is something a little more tangible for the doctor, who now tells the patient he knows the cause of the problem and sets about curing it with shots of vitamin B-12, iron, and sometimes folic acid.

But the hemoglobin doesn't rise as it should, and the doctor asks the patient more questions: "Are you taking the medication I've given you?" and "Is there something you're not telling me?" The patient says yes to the first and no to the second, but the questions have served a secondary purpose: the seeds of uncertainty have been planted, and the patient wonders if the real root of the problem is something he is doing that he shouldn't, or not doing that he should.

Another preliminary symptom of rheumatoid arthritis can be unexplained weight change, and this takes two forms. In some cases, people who are slight of build will lose weight; when accompanied by severe fatigue this is often a precursor of the painful phase of the disease. In other cases, the patient is already overweight, and as the disease progresses the patient's weight increases, despite efforts to control it. We have observed this same phenomenon of weight abnormality in patients with other connective-tissue diseases, including scleroderma and lupus. But as any of these diseases go into remission, both extremes begin to move nearer to the mean; patients who are too thin start to gain, and those who are obese find that their efforts to reduce are becoming more productive.

Alternative Diagnoses:

It usually isn't long after these various symptoms appear before the patient begins to get some joint pain. There is still no visible external evidence of change, but the pain is a new symptom and calls for another trip to the doctor. At this stage, and even as long as a year later when the pain combines with some of the early signs of disfigurement, many doctors are still unwilling to diagnose the condition as arthritis. Favorite alternatives are sciatica, bursitis, lumbago, and synovitis; the apparent rationale is that any curable disorder is preferable to one that is not.

By the same token, if the doctor understands that rheumatoid arthritis can indeed be cured, then he also recognizes that all of these delays are detrimental to the patient and can greatly extend the degree and duration of treatment.

Proving the Presence of the Arthritic Infection:

If a patient comes to me with the earliest of these symptoms and nothing external yet shows, I start off with a test for the mycoplasma complement fixing reaction. It was through this means that I recently confirmed my suspicions about the eleven-year-old daughter of a woman I had been treating for several years.

The daughter was always tired and wasn't doing well in school, and I suspected a combination of fatigue and depression, the classic early signs of rheumatoid arthritis. Like most children, she was unwilling to admit to much of anything that would aid in her diagnosis. This was partly because of a natural tendency for children to hide their feelings from adults as they seek to establish their own identities, and partly because of a lack of experience against which to make useful comparisons about how they should feel. Depression is particularly hard for adolescents to handle or for doctors to recognize; it doesn't show in children the way it does in adults, and is mixed in with a lot of psychological and physical changes that are normal parts of growing up. As a rule, it manifests itself as indifference. The child doesn't get out and play with others of the same age but is more inclined to read, watch television, or simply withdraw.

Despite the mother's insistence that her daughter probably had arthritis, because that was the way her own had begun when she was more or less the same age, the girl's doctors were not inclined to accept a lay diagnosis, especially when their own standard tests for the disease were negative. But when a sample of her blood was sent to our laboratory, the far more sensitive mycoplasma complement fixing reaction showed a high degree of activity, and I immediately wrote to her mother that the test, combined with the girl's other symptoms and her history, gave strong evidence of rheumatoid arthritis infection. We started her on a course of antibiotic therapy, and because it was still relatively early in the course of the disease, she picked right up and did very well.

At the end of the summer, however, my young patient hit a slump. Her spirits dropped again and she showed some of the earlier lethargy, though not as strongly. Her parents were prepared for this to happen. The mother knew from her own long experience that there are three flare periods in early stages of the treatment for rheumatoid arthritis: September, February, and May, the months in which the barometer is least stable. At those times, a doctor has to reassure his patient that it is normal for the recovery to slow down and even lose some ground for short periods, but that the slump won't last and that as the treatment continues the dips eventually stop occurring.

Up to the time of this writing, my patient, now fourteen, has had rheumatoid arthritis for three years and has been in treatment for two. Her energy levels have risen, her symptoms of depression have vanished, she gets along on a normal amount of sleep for a girl her age, her earlier outgoing nature has returned, and her grades in school are up to honor levels.

The mycoplasma complement fixing reaction by which she was initially diagnosed is a test for the antibody that develops in the bloodstream in response to a mycoplasma infection. In order to do the test, it is necessary to have strains of mycoplasma available in the laboratory. So far, no such strains are obtainable from commercial sources, so the Arthritis Institute propagates and stocks its own supply. However, it would be a simple enough matter for a pharmaceutical manufacturer to produce such a product. As mycoplasmas finally gain recognition as the cause of rheumatoid arthritis, laboratory testing kits should soon be appearing on the market.

Arthritis and Temperature:

There is one other symptom involved in rheumatoid arthritis, but it is a subtle one and easy to overlook in a diagnosis. That is a very slight temperature elevation. Lyme disease is a form of rheumatoid arthritis that in its early stages presents itself differently from other types, and a pronounced fever is one of its more dramatic features. (Lyme disease has played a key role in improving the medical community's understanding of rheumatoid arthritis as an infectious illness, and is discussed in detail in Chapter 16.) With other rheumatoid forms, the temperature is usually just a fraction above normal, and the few tenths or a single degree of abnormality will often escape detection. If the temperature is measured with an electronic thermometer, however, in a doctor's office or a hospital, the slight elevation can be seen easily. It isn't the response to an invading germ, as is the case with Lyme disease, but rather is a reaction to a substance which the germ produces. This small temperature difference is one of the most exact objective indicators of profound fatigue, and often of the depression that goes with it. Once the patient has begun treatment with an antibiotic, the temperature flattens right out at normal.

This small rise in temperature is less significant as a guide to diagnosis than it is as a further proof that rheumatoid arthritis is an infection, and it is a sensitive indicator to the effect of treatment. I often make use of it when I do patient rounds at the hospital. If I see from the chart that the small fever has disappeared, I'll tell the patient I am glad to see he or she is feeling better. It's a great trick, and until I explain it, the patients often feel I have a special diagnostic gift.

Hypersensitivity:

One of the central concepts for understanding how rheumatoid arthritis works is that of the "sensitized host." Hypersensitivity is really the same thing as an allergy, but it occurs in a system where it doesn't produce a standard allergic display, such as hives or the rash from poison ivy.

The human body is made up of three sections. The ectoderm includes the skin, part of the eyes, the lungs, and part of the trachea and esophagus. The entoderm is the gastrointestinal tract and its attachments. The mesoderm includes the connective tissue, bone and cartilage, muscles, nerves, blood and blood vessels, the lymph system, and the remaining glands and organs.

Each of these sections is separate in the embryo, and although they combine in later stages of development, each retains its own unique status all through life, each reacting differently and each the target of various allergies, although
the entoderm can include some ectodermal and some mesodermal features.

It has occurred to me over the years that the mesoderm is primarily the focus for bacterial allergy, while the ectoderm is more the target of chemical allergy. Obviously bacteria are chemical as well, but I am referring more to such irritants as ragweed, dust, and smoke. The distinction is not complete, because we can get hives from a vaccination or from a food reaction, but the three sections do react differently even to the same stimuli.

Mesodermal allergies don't show on the surface, and because of that we don't generally call them allergies; for that matter, for a long time we didn't even call them hypersensitivities. But as time has passed, I have become convinced that one of the major pathogenic components of rheumatoid arthritis is the fact that the mesoderm is reacting in a truly allergic sense to the agents for which it is the particular target. These agents include mycoplasma, streptococcus, brucella (the agent of undulant fever, which gives rise to arthritis), tubercle bacillus, and others.

Nodules:

The most pronounced and classic symptom of rheumatoid arthritis is the nodule, which appears at the joints as the first external evidence of arthritic disfigurement. Because this is so widely recognized for what it represents, some victims of the disease are actually relieved when the first rheumatoid nodule appears; now, at last, the patient has something tangible to take to the doctor. Nodules usually arise at the site of some injury, such as a sprain or bump, and although it is possible to have one or two without necessarily having arthritis, it is likely that all such nodules are the result of disease activity at the site.

Nodules are unlike malignant lesions that keep on spreading, however, and they can come and go. Sometimes a patient will detect one on an elbow or wrist and make an appointment with the doctor, only to discover that the nodule has receded and perhaps even disappeared by the time the appointment is kept. Or it can vanish in one place and reappear later in another.

The most likely explanation for these nodules is that they contain fibrous tissue that forms in a skein around the small lesions where the mycoplasmas are located. The tissue is a protective response by the body to contain the infection and keep it from spreading. If the mycoplasma antigen stops coming out for some reason, either because the body's defense puts it down for a while or a medicine suppresses it, then the scar tissue surrounding the germ is no longer needed and the nodule goes away. The process by which this occurs is one of natural attrition; cells are periodically replaced, and if the cause for defense is no longer there, the body will remove the old cells without sending in new ones.

The Role of Streptococcus:

People who have the most rheumatoid nodules are frequently the ones who have had a streptococcal infection, perhaps in childhood, and in whom there is evidence that the streptococcal antibodies are still present along with the mycoplasmas. The drugs for streptococci are not the same as the ones used for mycoplasmas. If I detect streptococcal antibodies, I will combine an antistreptococcal approach with the treatment for the mycoplasma at the outset, and once the streptococcal level has been lowered, I will focus the attack more precisely on the mycoplasma.

The standard treatment for streptococcus is penicillin or one of its many derivatives. Penicillin has no value in treating the forms of rheumatoid arthritis that are caused by mycoplasmas-the vast majority of such cases. (They do work on the form known as Lyme disease, however, which evidence indicates is caused by a spirochete bacterium.) Conversely, the tetracyclines aren't as effective as penicillin in treating streptococcal infections. The problem in using penicillin-based antibiotics is that they tend to create drug allergies after a certain amount of time, so there is an incentive to limit the duration of their use. After a short term of treatment with penicillin derivatives, the rheumatoid nodules tend to disappear in patients who have the history of streptococcal infection.