Lyme Disease: A Portrait of Infectious Arthritis

  by Staff Editor

The formula for any good story is that it must have a beginning, a middle, and a conclusion, and at present Lyme disease is the form of arthritis that comes closest to meeting that requirement; the model it provides for future researchers should eventually lead to a full library of happy endings. For most people, including lovers of detective stories and romantics who like to see everything properly disposed of and explained in the end, the story of Lyme disease is a classic thriller. For diehard advocates of the metabolic theory of rheumatoid arthritis, however, the final chapter brings some very unsettling news.

The first reported cases of Lyme disease were in 1975, in the town on the eastern shore of the Connecticut River that gives the affliction its name. Two mothers called the state health department to say that their children had just been diagnosed as having rheumatoid arthritis, and they suspected an epidemic. Juvenile rheumatoid arthritis can be a very serious disease, and when the department looked into the situation they found that indeed there were several other cases in the vicinity, as well an inordinate number of adult cases reported in the same period.

The health authorities called Yale University School of Medicine and spoke with a postdoctoral fellow in rheumatology named Allen Steere. Steere took on the puzzle. He started by calculating that the thirty-nine children and twelve adult cases diagnosed to that date represented a rate of incidence a hundred times higher than normal for the size of the population. Moreover, in areas where cases of the disease clustered-heavily wooded rural sites-the rate was ten thousand times higher than it should have been.

Steere then identified several important features of the epidemic. From the pattern of dates on which families and neighbors showed their first symptoms, he concluded that it was a summertime affliction and that it was not highly contagious, which is to say that those afflicted were not catching it from one another but from some other source. A clue to that unknown source was found in the fact that a quarter of the victims recalled having an unusual rash a couple of days to a month before the first signs of arthritis, and the distribution and form of the rash suggested the bite of a crawling insect or spider.

Pattern Recognition:

Steere also discovered that the same skin rash pattern had been reported in Europe in 1909, although without the subsequent arthritis, and that it had been traced to the bite of a tick, Ixodes ricinus. Some decades later, cases of that same rash pattern in Europe were treated with penicillin and cured, from which scientists inferred that the active agent in 1909 had been a bacterial infection. Accordingly, an attempt was made to isolate bacteria from the synovial fluid of several victims of the Lyme epidemic, but nothing showed up.

A couple of years after he started, Steere had a piece of extraordinary luck: one of the people who came down with the disease in 1977 not only recalled having been bitten by a tick-but he had saved it. Steere sent the tick up to Harvard, where it was identified as Ixodes dammini, a close cousin of the European protagonist of seventy years earlier. Distribution studies subsequently established Ixodes dammini as the likely vector, or carrier, of Lyme disease.

Spirochete Infection:

That still didn't explain what Lyme disease was. Many ticks were gathered from the wild, but studies of their organs and digestive systems were no more productive than the earlier work with human joint fluid. Four years later, however, other scientists researching an outbreak of Rocky Mountain spotted fever opened the digestive system of an Ixodes dammini and found that it was filled with spirochete bacteria. They knew that the tick was the prime suspect in Lyme disease, and they guessed that the spirochete was the long-sought infectious agent. Subsequently the connection was proven. DNA studies showed the spirochete was a new species, which was named Borrelia burgdorferi after the researcher who first saw it.

Researchers who studied Lyme disease under a grant from the National Institutes of Health have identified three clinical stages, although not all patients demonstrate all stages. The first, showing up within a few days to a month after the bite, can include migratory rash, fatigue, fever, chills, and aches. The second stage can include irregular electrical activity in the heart muscle, showing up as shortness of breath, dizziness, and palpitations. The third stage is arthritis, sometimes accompanied by disorientation and memory loss. All three of those stages can vary widely, and Lyme disease is frequently misdiagnosed, often as Alzheimer's or multiple sclerosis.

Knocking it out:

Even if treatment waits until the third stage, either penicillin or tetracycline is still effective in knocking out most cases, although the NIH-sponsored researchers found that some entrenched incidents require that the antibiotics be administered intravenously. They also noted that several physicians treating the arthritic stage of the disease had encountered the Herxheimer effect, in which the symptoms became temporarily worse once treatment began, and they suspected that this reaction was another important clue. Subsequent laboratory tests showed that the Herxheimer effect probably results from the release of powerful agents from the walls of the dying bacteria as they are attacked by the antibiotic; these, in turn, stimulate the host body's immune defense mechanism.

That same chain reaction accounts for the Herxheimer effect in every other rheumatoid form of arthritis, whether the invading agent is a spirochete, streptococcus, or mycoplasma.

Of course, the chain reaction of rheumatoid arthritis doesn't begin or end with the Herxheimer effect. In the more common forms of arthritis, for example, we have known for a long time that mycoplasmas localize, and that if you can get them out of the joints, in most cases the condition will improve. We also know, even accounting for the Herxheimer effect, that if we're progressing at a good rate and the patient is getting better, it very often happens that some other bacterial antigen will enter the picture and make matters worse again. What has occurred in those instances is that the antigens from the mycoplasma or some other disease agent have sensitized the area in question, so that future incidents now have an easy place to happen.

When the stage is set in that way, lots of other factors can get into the act. Medication and foods can become serious problems, for example, as the sensitized body begins to reject them. Sinus troubles or kidney problems can appear. Antigens of many different types can enter the picture and create chaos.

Sleeper:

One of the sleeping antigens that is very hard to measure is streptococcus. It has been well established that the toxins from streptococci, as well as those from mycoplasmas, have an affinity for joints. We have found in the course of taking comprehensive histories of our patients that a tremendous number of them have had severe troubles with their sinuses or their tonsils or their ears, or have had scarlet fever or rheumatic fever-all streptococcal conditions. Strep is an organism that is very susceptible to penicillin, which is why rheumatic fever and scarlet fever are no longer the terrible menaces they were a generation ago. But even after it has been knocked out as a source of infection, streptococcus hangs on for years-in tonsils, around teeth, and in other hiding places-not causing infection, but serving as another source of antigen, or toxin, with that demonstrated specificity for joints.

In treating rheumatoid arthritis, when a physician gets to the point with tetracycline therapy that the mycoplasmas have been substantially reduced and further progress appears to be limited, it makes sense to probe the possibility that streptococcus is complicating the process. If a titer of streptococcal antibodies indicates that their levels are elevated, then both the mycoplasma and the strep can be treated at the same time, continuing tetracycline for the former and using ampicillin for the latter.

Nothing about rheumatoid arthritis is simple, and it doesn't necessarily stop there; the streptococcus often alters its form, which further compounds the problem. Treatment of the strep then takes one kind of medication, and treatment of the altered form requires yet another.

The Infectious Allergy:

All of these scenarios follow the pattern of infectious allergies, which is one of the central processes of all forms of rheumatoid arthritis and which must be addressed in their treatment. Lyme disease is harder to cure the longer it remains untreated; when the allergic reaction has been given enough time to become securely established, the resistance to therapy can be multiplied many times over. The same applies to all other forms of rheumatoid arthritis.

Finally, for those who like a moral with their short stories, it should be acknowledged that Lyme disease proves once again that there is no such thing as a panacea in dealing with mankind's oldest disease. Tetracycline may be all a doctor could ask for in treating many other forms of rheumatoid arthritis-even most of them-but by itself it is still not the whole answer.

The whole answer is in the one area that has received the least attention in the past forty years and that has finally been illuminated by the brilliant research which solved the puzzle of Lyme disease: a complete understanding of the causes of rheumatoid arthritis and of the mechanism by which it occurs.