Antibiotics for arthritis?

Research has pointed to a possible benefit of using antibiotics for the treatment of some types of arthritis. This article discusses some of the data.

The role of antibiotic therapy for the treatment of arthritis is controversial. However there is at least some evidence for effectiveness in two examples. Minocycline, a member of the tetracycline family, appears to suppress enzymes involved in the inflammatory process. Doxycycline is an antibiotic that also belongs to the tetracycline group and has shown to have positive benefits in osteoarthritis.

Minocycline

In 1949, at the International Congress on Rheumatic Diseases, a possible relationship between mycoplasmas and joint disease was described.

Thomas McPherson Brown, M.D. and his colleagues at the National Institutes of Health reported the following year that rheumatoid arthritis may be caused by an immunologic reaction of antigen and antibody (with mycoplasma as the suspected antigen).

In 1955, Brown reported that mycoplasmas, unlike bacteria and viruses, could live in tissue cell cultures without destroying the tissue cells. In 1964 a high incidence of mycoplasma antibodies in the blood of rheumatoid arthritis patients was found, indicating current or previous infection. Also noted was a four-fold higher incidence of mycoplasma antibodies in females suggesting a correlation with the higher incidence of rheumatoid arthritis in females.

Efforts to demonstrate the effectiveness of tetracycline therapy were initiated and first reported by Dr. Brown shortly thereafter. In 1989, NIH initiated controlled clinical trials of tetracycline therapy for rheumatoid arthritis. The preliminary results of the clinical trials, known now as MIRA or Minocycline in Rheumatoid Arthritis, were promising.

The result of the MIRA clinical trial were: “Patients who suffer from mild to moderate RA now have the choice of another therapeutic agent. Not only did the antibiotic significantly reduce symptoms, but side effects were minimal and less severe than observed for most other common rheumatoid treatments”.

Despite these findings, many rheumatologists remain skeptical. Other studies have failed to demonstrate clinically significant improvement.

According to the American College of Rheumatology, “Minocycline is prescribed for patients with symptoms of mild rheumatoid arthritis. It is sometimes combined with other medications to treat patients with persistent symptoms of this form of arthritis.”

Their formal position is stated in this fact sheet for patients:

…There is evidence minocycline may slow the progression of joint damage in arthritis and prevent disability like other drugs in the class known as DMARDs (disease-modifying antirheumatic drugs).

Minocycline is prescribed for patients with symptoms of mild rheumatoid arthritis, sometimes in combination with other medications to treat patients with persistent symptoms of this form of arthritis.

…Minocycline decreases the production of substances causing inflammation, such as prostaglandins and leukotrienes, while increasing production of interleukin-10, a substance that reduces inflammation.

Minocycline usually is given as a 100 milligram (mg) capsule twice a day. It may be taken with food, although it should not be taken with other medications such as antacids or iron tablets.

It may take 2 to 3 months before any improvement in arthritis symptoms is experienced and up to a year before maximum benefits are realized.

The most common side effects from this medicine are gastrointestinal symptoms, dizziness and skin rash. Some women who take minocycline develop vaginal yeast infections. While this can occur with other antibiotics, it seems more prevalent with minocycline and other tetracyclines. It is thought minocycline kills bacteria normally present in the body which protect against yeast infections.

Minocycline increases sensitivity to sunlight, resulting in more frequent sunburns or the development of rashes following sun exposure. It is recommended patients apply sunscreen (SPF 15 or greater) before outdoor activities or avoid prolonged exposure to the sun while taking minocycline.

More rarely, minocycline can affect the kidneys or liver. Doctors may recommend periodic blood tests for long-term users to check liver and kidney function. In equally rare cases, minocycline can induce lupus, but this condition usually improves after stopping the medication.

Minocyline use during pregnancy can slow the growth of teeth or bones in infants after birth as well as cause discoloration of the newborn’s teeth when taken during the last half of pregnancy. Minocycline may decrease the effectiveness of some birth control pills.

Minocycline is passed into breast milk, so mothers should avoid breast-feeding to prevent delayed development of teeth and bones in their infants. Minocycline can increase a nursing infant’s risk of fungal infections or dizziness in the newborn. Because minocycline may cause discoloration of teeth and problems with bone growth in young children, it is recommended that those younger than 8 years old not take this medication. This is not a problem in older children and adults.

Possible interactions with minocycline may occur when taking warfarin (Coumadin), antacids containing calcium, aluminum or magnesium (such as Tums, Rolaids, Maalox, or Mylanta), iron tablets and oral contraceptives (birth control pills).

To highlight one of the potential side effects of minocycline, a small study reported in the June 2006 issue of the Journal of Rheumatology indicated that skin discoloration (hyperpigmentation) appears to be a very common side effect of minocycline use. The study involved 27 patients. Forty-one percent (11 patients) reported developing skin discoloration after using minocycline for approximately one year. Four of the 11 patients stopped using minocycline because of hyperpigmentation (two had skin discoloration on their face and two had skin discoloration on their arms).

The use of minocycline for rheumatoid arthritis is rare nowadays because of the development of newer biologic therapies. Nonetheless, it remains a viable option for the rare person with extremely mild disease.

Doxycycline

Doxycycline, another tetracycline derivative, has been used to treat osteoarthritis. Study results reported in Arthritis & Rheumatism (July 2005 issue) suggest that treatment with the antibiotic doxycycline may slow the progression of this disease.

Researchers compared the use of doxycycline to placebo, using about 400 obese women with knee arthritis as study participants. Researchers analyzed the impact of doxycycline on the joint space of the affected knee.

The study participants were randomized into two groups, receiving either 100 mgs of doxycycline two times a day or placebo for up to two and a half years.

Following 16 months of treatment, results indicated that the average loss of joint space in the affected knee was 40% less among participants taking doxycycline than those who took placebo.

At the end of the two and a half year period, the loss of joint space was 33% less in the group who took doxycyline than in the group who took placebo.

Doxycycline treated patients also reported having marginally less joint pain.

Researchers said that this was the first major study of doxycycline as a potential treatment for osteoarthritis. More studies will be needed to confirm these results.

While the study did not clearly show that oral doxycycline was effective in reducing pain, there was evidence that there was less progression of osteoarthritis (i.e. less cartilage loss) in patients on the antibiotic. The authors felt doxycycline works through anti-inflammatory effect and not due to an anti-bacterial effect.

Based on this study, it is difficult to recommend long term doxycyline for relief of symptoms. (Although I admit, I’m a closet doxycycline user on occasion). On the other hand, it is possible that patients taking the antibiotic may be less likely to require joint replacement in the future due to a decrease in joint damage on x-ray.  Obviously, longer term studies are required. The problem, as it exists today, is that we have no other drugs with significant disease-modifying effects for osteoarthritis.

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