Tetracycline For Ra: Is It Safe?
by Alan R. Cantwell Jr., MD

Dr. Cantwell is a retired dermatologist who studied the infectious etiology of scleroderma and lupus for over 25 years. He published his findings in national and international dermatology journals between 1968 and 1985.

Thomas McPherson Brown, M.D. spent many years studying and researching the cause and treatment of rheumatoid arthritis (RA). In his classic book, The Road Back, he wrote about exceedingly tiny bacteria (in the form of mycoplasma) that he believed were the infectious microbes responsible for RA. He proposed long-term antibiotic therapy with tetracycline for RA, as well as for other "connective tissue diseases," such as scleroderma and lupus.

Originally he treated patients with 250 milligrams of tetracycline three times a week, usually on Monday, Wednesday, and Friday. Later, he gave the drug daily, even though some patients experienced a "Herxheimer reaction," which made their symptoms temporarily worse .

Dr. Brown, who died in 1989, was adamant that long-term tetracycline therapy was safe. In The Road Back, he claimed that he had "not seen any toxic effects in forty years in anybody." He explained: "The drug is used in low doses, widely spaced to avoid sensitization; the higher the physician has to go in dosage, the wider the spaces. Extreme cases can be treated intravenously, which avoids potential allergic responses by going into a part of the body where allergies don't take place. Tetracycline doesn't attack the part of organisms where immunity is formed, so it can be used virtually forever without giving rise to immune strains of the organism it is fighting."

As a dermatologist, my own published research into the cause of scleroderma and lupus similarly convinces me that bacteria, probably tiny microbes in the mycoplasma or cell-wall deficient form, are implicated in the cause of these connective tissue diseases which are also closely allied to RA.

Although I have no experience treating these diseases with tetracycline and minocycline, I have safely used long-term tetracycline over the past four decades in thousands of patients with severe acne. So have most other dermatologists; long-term antibiotics have been used routinely - and safely - for the treatment of acne for almost half a century. For severe cases, treatment can start with as much as 1000 mgs. tetracycline daily, and subsequently tapered down to 250-500 mgs. daily for months, even years. Even at those dosage levels, adverse effects are minor, infrequent and few in number.

Patients taking tetracycline are warned about possible sun-sensitivity. In women, antibiotic therapy may trigger a vaginal yeast infection, but this complication can be easily treated. There are contraindications to the use of these medications, and proper blood tests are required from time to time to ensure that no harm is being done to the body. But it's hard to believe that a therapy that is acceptable for a child with acne is not at least as safe in far lower doses for an adult with connective tissue disease.

When used properly and with care, I have never heard of anyone becoming seriously ill with tetracycline. The fact that many doctors do not believe in tetracycline therapy does not mean it is not helpful, at least in some cases. It is probable that physicians who deny patients treatment with such an application have never used the therapy. But if they call it dangerous, then they must apply the same standards equally to other drugs and admit the far greater, proven danger of steroids, NSAIDS and DMARDS routinely employed to manage chronic RA.

Naturally, all drugs must be prescribed with care and knowledge of their toxicity and other side effects. Despite precautions, hospital patients pay as much as $4 billion a year for treatment of adverse reactions to prescription drugs. "Up to half the problems could be avoided," according to Time magazine (2/3/97), "with simple measures-like better tracking of patients' allergies." And thousands of arthritics a year still die from the silent ulcers caused by the use of NSAIDS for the the management of their symptoms. Who ever heard of anyone dying from antibiotic therapy for acne?

At present, some physicians will not recommend tetracycline therapy for RA unless prodded by the patient, and some not even then. This choice of medication is far safer than steroids, aspirin, non-steroidal anti-inflammatory agents, gold and methotrexate currently in vogue for the treatment of this chronic and debilitating disease.

References:

Cantwell, AR Jr: Acid-fast bacteria in scleroderma and morphea. Arch of Derm

115: 449-452, 1971.

Cantwell, AR Jr, Kelso DW, Jones JE: Histologic observations of coccoid forms

suggestive of cell wall deficient bacteria in cutaneous and systemic lupus

erythematosus. Intl J Derm 21: 526-537, 1982.

Cantwell, AR Jr: The Cancer Microbe, Aries Rising Press, Los Angeles, 1990.

Collin J: Hold the Nystatin, Bring on the tetracycline! Townsend Letter for

Doctors, April 1995.

Hazenberg MP, Klasen IS, Kool J, et al: Are intestinal bacteria involved in the

etiology of rheumatoid arthritis? APMIS 100: 1-9, 1992.

Kligman AM: Tetracycline for acne (Letter): JAMA 229, August 5, 1974.

Paulus H: Minocycline treatment of rheumatoid arthritis (Editorial). Ann of Int

Med 122: 81-89, 1995.

Scammell H: The Arthritis Breakthrough (includes The Road Back with Thomas

McPherson Brown, M.D.) M. Evans & Co., Inc., New York, 1993.??

More Published Journal Articles on The Safety of Long-Term Tetracycline UseTetracycline for Acne

Albert M. Kligman, M.D., Ph.D.

Hospital of the University of Pennsylvania, Philadelphia

JAMA, 229, 6, 1974.

In a letter response to an earlier JAMA article (228:899, 1974), Dr. Kligman cites gynecologists as concluding that tetracycline causes very little trouble. An internist cited by the same article felt the benefits outweighed the risks.

It is Dr. Kligman's belief that "if dermatologists were restricted to a single drug, they would chose an antibiotic. . . (and that) tetracyclines are marvelously safe and effective in treating acne."

Tetracycline and Acne vulgaris: a clinical and laboratory investigation

WJ Cunliffe, RA Forster, ND Greenwood, C Hetherington, KT Holland, RL Holmes, S Kahn, CD Roberts, M Williams, B Williamson.

Gen. Infirmary at Leeds, Univ. of Leeds

Br. Med J, 1973, 4, 332-335.

Most dermatologists would agree that long-term oral tetracycline is one of the better treatments for acne vulgaris. In a three month trial, 13 patients were given one oral tetracycline 250 mg. once daily. Drug sensitivity tests were carried out which showed rather inconsistent changes, with no constant development of resistant strains.

Tetracyclines after 25 years

G. C. Ferguson

General Hospital, Northampton

Br Med J, 27 July 1974. (Letter to the Ed.)

In a recent article (25 May, p 400) the risks involved in the administration of tetracycline to patients with latent kidney disease, . . significant renal function was only found in patients with pretreatment blood urea values greater than 60 mg/100 ml.

Tetracyclines have been prescribed on a long-term basis for the treatment of chronic bronchitis and the risk of deterioration with a normal blood urea seems extremely slight and the frequency of frank renal insufficiency in this disease may in fact be quite low.

Clinical trial of an Amphotericin B-Tetracycline combination in pediatric patients

PJ Kozinn, JJ Burchall, A Katz, CT Taschdjian

Dept. of Pediatrics, Maimonides Hospital, Brooklyn, New York

AM&CT, Dec. 1960, 749-753.

Candida albicans is present in the mouth and GI tract of 18-50% of normal children and adults. A combination of Nystatin and tetracycline proved successful in the prevention of yeast proliferation in the intestine during and after antibiotic therapy, and was found to significantly reduce the incidence of GI disturbances. 53 pediatric patients, aged 1 month to 9 years were treated. The medication was well tolerated, with complete absence of toxic effects or allergic reactions. . . confirmed by blood counts and urinalysis.

Twenty-fifth anniversary of the discovery of Aureomycin: the place of the tetracyclines in antimicrobial therapy

Maxwell Finland, M.D.

Harvard Medical Unit, Boston City Hospital

Clin Pharm & Ther, 15:1, 1974, 3-8.

Sensitization of the organism and the acquisition of resistance by the organism during treatment did not seem to be a problem.

Minocycline was well tolerated in clinically useful doses, and yielded higher and better sustained antibacterial levels than either . . . doxycycline or tetracycline.

Although toxic side effects of tetracyclines are relatively few and sensitization reactions are rare, certain untoward effects place some limitations on their use in doses of more than 1 gm daily (1000 mg) of minocycline and doxycycline or 2 gm (2000 mg) of tetracycline daily, . . . but such larger doses are generally unnecessary.

Serious adverse reactions induced by minocycline: report of 13 patients & review of the literature

SR Knowles, L Shapiro, NH Shear

Dept. of Med, Sunnybrook Health Sci Ctr, Toronto, Canada

Arch Derm, 132, Aug. 1996

Minocycline has been reported to cause serious, albeit rare, adverse effects, including serum sickness-like reaction, hypersensitivity syndrome reaction, and drug-induced lupus (cases reported in literature developed 2 years after therapy began). More common and less serious side effects are nausea, dizziness, vomiting, photosensitivity, hyperpigmentation, and skin eruptions.

Neither tetracycline nor doxycycline contains the amino acid side chain that has the potential to form a reactive intermediate, and therefore, the HSRs associated with minocycline may be specific to this antibiotic.

Tetracyclines-how safe are they?

AL Wright, BGB Colver Dept of Derm, Edinburough, Scotland Clin & Exper Derm 1988; 13: 57-61

Tetracyclines have been used for nearly 40 years, . . courses of treatment may be for months-even years, and long-term follow-up studies suggest that tetracyclines are relatively safe even in high doses. Over many years of use by a large number of doctors, the drugs have a good safety record and the incidence of major side effects is low.

In antibiotic therapy, the drug is used in low doses, widely spaced to avoid sensitization; the higher the prescribed dosage, the wider the spaces between doses.

* The Keys to Treatment will become a regular feature of the Physician's Page and will highlight important or "key" aspects of antibiotic therapy.