There are two major types of arthritis: osteoarthritis, also called degenerative arthritis, and various kinds of reactive arthritis such as rheumatoid arthritis. Osteoarthritis means that cartilage wears away and doctors don't have the foggiest idea why and therefore they have no effective treatment. Doctors usually prescribe non-steroidal pills that help to block pain but do not even slow down destruction of cartilage. Many serious scientists agree that an infection initiates the reactive arthritises, and many think that the germ is often still there when symptoms start. Short-term antibiotics are ineffective, but in some cases, if antibiotics are started before the joint is destroyed, they can prevent joint damage.
You are more likely to suffer reactive arthritis when you have: I) positive blood tests for arthritis; all tests used to diagnose arthritis are measures of an overactive immunity; II) swelling of the knuckles and middle joints of your fingers, causing them to look like cigars; III) a history of a long-standing infection such as a chronic cough, burning on urination or pain when the bladder is full, chronic diarrhea and belching and burning in the stomach; and IV) pain that starts at an age younger than 50.
Most rheumatologists refuse to treat their rheumatoid arthritis patients with antibiotics even though several controlled prospective studies show that minocycline drops the rheumatoid factor towards zero and helps to alleviate the pain and destruction of rheumatoid arthritis. The studies, referenced below, include: 1) First Netherlands study, 10 patients, J of Rheumatology 1990;17(1):43-46. 2) 2nd Netherlands Study, 80 patients, Arthritis and Rheumatism 1994;37(5):629-636. 3) Israel Study, 18 patients, J of Rheumatology 1992;19(10):1502-1504. 4) U.S.Mira Study, 219 patients, Annals of Internal Medicine. 1995(Jan15);122(2):81-89. 5) U.S. U of Nebraska Study, 40 patients, Arthritis and Rheumatism 1997;40(5):842-848.
I treated my reactive arthritis patients with Minocycline 100 mg twice a day, (sometimes azithromycin 500 mg twice a week), but this must still be considered experimental because most doctors are not ready to accept antibiotics as a treatment. There is also possibility of a rare serious side effect of lupus. Many patients do not feel better for the first few weeks after they start taking minocycline. If a patient does not feel better after taking 100 mg of minocycline twice day for two months, I add Zithromax 500 mg twice a week. If the patient does not feel better after taking the two antibiotics for six months, I do add the immune suppressants that most rheumatologists prescribe. But as soon as they feel better, I stop the immune supppressants and continue the antibiotics.
Other papers show that even osteoarthritis may respond to antibiotics (27). People who have chlamydia in their joints usually have no antibodies to that germ in their bloodstream and therefore cannot cure it (30). Reactive arthritis is characterized by pain in many muscles and joints and is thought to be caused by a person's own antibodies and cells attacking and destroying cartilage in joints. This type of arthritis may be triggered by infection and antibiotics may help to prevent and treat this joint destruction (1 to 10). Short-term antibiotics are ineffective (5). Doxycycline may prevent joint destruction by stabilizing cartilage (3) in addition to clearing the germ from the body.
How do germs cause arthritis? When a germ gets into your body, you manufacture cells and proteins called antibodies that attach to and kill that germ. Sometimes, the germ has a surface protein that is similar to the surface protein on your cells. Then, not only do the antibodies and cells attach to and kill the germ, they also attach to and kill your own cells that have the same surface membranes. Some people with arthritis have high antibody titre to E. Coli, a bacteria that lives normally in everyone's intestines (15). It has the same surface protein as many cells in your body (15). Normal intestines do not permit E. Coli to get into your bloodstream. Some people who get reactive arthritis may have intestines that allow E. coli to pass into the bloodstream and cause the immune reaction that destroys muscles and joints. The same type of reaction applies to several other bacteria and viruses that can pass into your bloodstream (15A). Venereal diseases, such as gonorrhea, chlamydia and ureaplasma have been found in the joint fluids of many people with arthritis (16). People with reactive arthritis are more likely to have staph aureus in their noses (17) and carry higher antibody titre against that germ (18). Many people with reactive arthritis have had chronic lung infections, caused by mycoplasma and chlamydia, prior to getting joint pains(20,21). Mycoplasma has been found in joint fluid of people with arthritis (28,29). The treatment of arthritis with antibiotics is controversial and not accepted by many doctors; discuss this with your doctor.
Auto-Immune Diseases and Inflammation
Osteoarthitis Linked to Inflammation
1A) O'dell et al. Minocycline therapy for early rheumatoid arthritis continued efficacy at three years. Annual meeting of the American College of Rheumatology. November 9, 1997.
1a) Higher doses more effective. M Kloppenburg, H Mattie, N Douwes, BAC Dijkmans, FC Breedveld. Minocycline in the treatment of rheumatoid arthritis: Relationship of serum concentrations to efficacy. Journal of Rheumatology 22: 4 (APR 1995):611-616.
2) Lancet, July 11, 1992.
3) AA Cole, S Chubinskaya, LJ Luchene, K Chlebek, MW Orth, RA Greenwald, KE Kuettner, TM Schmid: Doxycycline disrupts chondrocyte differentiation and inhibits cartilage matrix degradation.(39 references and summary) Arthritis and Rheumatism 37: 12 (DEC 1994):1727-1734.
4) Barbara Tilley, Henry Ford Health Science Center in Detroit. Annals of Internal Medicine. January 14, 1995.
5) Short-term antibiotic treatment has no effect in manifest ReA, whereas a tendency to improvement has been seen with treatment over months, at least after chlamydia infection. B Svenungsson. International Journal of STD & AIDS 6: 3:(MAY-JUN 1995):156-160.
6) Kloppenburg et al. Minocycline double blind for RA. Arthritis and Rheumatism 1994;37:629-636.
7) Langevitz et al. RA with Minocycline. J.Rheumatlogy 1992;19:1502-1504.
8) Breedveld et al. J Rheumatology 1990;17:43-46.
9) Good summary in Lancet, 1995(May 27);345:1319-1322.
10) Kloppenburg et al. Minocycline double blind for RA. Arthritis and Rheumatism 1994;37:629-636.
11) Langevitz et al. RA with Minocycline. J.Rheumatlogy 1992;19:1502-1504.
12) Breedveld et al. J Rheumatology 1990;17:43-46.
13) Good summary in Lancet, 1995(May 27);345:1319-1322.
14) Kloppenburg M et al. Minocycline in Rheumatoid arthritis. Clin Immunother 1996(Jan);5(1):1-4. 14A) Keystone et al. Nature Medicine. April, 1995.
15) S Aoki, K Yoshikawa, T Yokoyama, T Nonogaki, S Iwasaki, T Mitsui, S Niwa. Role of enteric bacteria in the pathogenesis of rheumatoid arthritis: Evidence for antibodies to enterobacterial common antigens in rheumatoid sera and synovial fluids. Annals of the Rheumatic Diseases 55: 6 (JUN 1996):363-369. 15A) LB Siegel, EP Gall. Viral infection as a cause of arthritis. American Family Physician 54: 6 (NOV 1 1996):2009-2015. (parvovirus, chronic hepatitis B virus and hepatitis C) virus infections.
16) F Li, R Bulbul, HR Schumacher, T Kieberemmons, PE Callegari, JM Vonfeldt, D Norden, B Freundlich, B Wang, V Imonitie, CP Chang, I Nachamkin, DB Weiner, WV Williams. Molecular detection of bacterial DNA in venereal-associated arthritis. Arthritis and Rheumatism 39: 6 (JUN 1996):950-958.
17) D Tabarya, WL Hoffman. Staphylococcus aureus nasal carriage in rheumatoid arthritis: Antibody response to toxic shock syndrome toxin-1. Annals of the Rheumatic Diseases 55: 11 (NOV 1996):823-828.>
18) T Origuchi, K Eguchi, Y Kawabe, I Yamashita, A Mizokami, H Ida, S Nagataki. Increased levels of serum IgM antibody to staphylococcal enterotoxin B in patients with rheumatoid arthritis. Annals of the Rheumatic Diseases 54: 9 (SEP 1995):713-720.
19) M Calguneri, S Kiraz, I Ertenli, M Benekli, Y Karaarslan, I Celik. The effect of prophylactic penicillin treatment on the course of arthritis episodes in patients with Behcet's disease: A randomized clinical trial. Arthritis and Rheumatism 39: 12 (DEC 1996):2062-2065.
20) J Despaux, JC Polio, E Toussirot, JC Dalphin, D Wendling. Rheumatoid arthritis and bronchiectasis - A retrospective study of fourteen cases. Revue du Rhumatisme 63: 11 (DEC 1996):801-808.
21) H Lena, B Desrues, A Lecoz, C Belleguic, ML Quinquenel, J Kernec, G Chales, P Delaval. Rheumatoid arthritis and bronchial dilatation: A little recognised association. Revue Des Maladies Respiratoires 14: 1 (JAN 1997):37-43.
22) IC Tracey, GM Strand, K Singh, M Macaluso. Survival and drug discontinuation analyses in a large cohort of methotrexate treated rheumatoid arthritis patients. Annals of the Rheumatic Diseases 54: 9 (SEP 1995):708-712.
23) M Jones, D Symmons, J Finn, F Wolfe. Does exposure to immunosuppressive therapy increase the 10 year malignancy and mortality risks in rheumatoid arthritis? A matched cohort study. British Journal of Rheumatology 35: 8 (AUG 1996):738-745.
24) EM Veys, CJ Menkes, P Emery. A randomized, double-blind study comparing twenty-four-week treatment with recombinant interferon-gamma versus placebo in the treatment of rheumatoid arthritis. (Doesn't work) Arthritis and Rheumatism 40: 1 (JAN 1997):62-68.
25) C Wilson, A Thakore, D Isenberg, A Ebringer. Correlation between anti-Proteus antibodies and isolation rates of P-mirabilis in rheumatoid arthritis. Rheumatology International 16: 5 (JAN 1997):187-189.
26) JR Odell, CE Haire, W Palmer, W Drymalski, S Wees, K Blakely, M Churchill, PJ Eckhoff, A Weaver, D Doud, N Erikson, F Dietz, R Olson, P Maloley, LW Klassen, GF Moore. Treatment of early rheumatoid arthritis with minocycline or placebo: Results of a randomized, double-blind, placebo-controlled trial. Arthritis and Rheumatism 40: 5 (MAY 1997):842-848. In patients with early seropositive RA, therapy with minocycline is superior to placebo.
27) F Blotman, E Maheu, A Wulwik, H Caspard, A Lopez. Efficacy and safety of avocado/soybean unsaponifiables in the treatment of symptomatic osteoarthritis of the knee and hip - A prospective, multicenter, three-month, randomized, double-blind, placebo-controlled trial. Revue du Rhumatisme 64: 12 (DEC 1997):825-834.
27a) GN Smith, LP Yu, KD Brandt, WN Capello. Oral administration of doxycycline reduces collagenase and gelatinase activities in extracts of human osteoarthritic cartilage. Journal of Rheumatology 25: 3 (MAR 1998):532-535.
28) T Schaeverbeke, M Clerc, L Lequen, A Charron, C Bebear, B Debarbeyrac, B Bannwarth, J Dehais, C Bebear. Genotypic characterization of seven strains of Mycoplasma fermentans isolated from synovial fluids of patients with arthritis. Journal of Clinical Microbiology 36: 5 (MAY 1998):1226-1231.
29)TV Poggio, N Orlando, L Galanternik, S Grinstein. Microbiology of acute arthropathies among children in Argentina: Mycoplasma pneumoniae and hominis and Ureaplasma urealyticum. Pediatric Infectious Disease Journal 17: 4 (APR 1998):304-308.
30) NZ Wilkinson, GH Kingsley, J Sieper, J Braun, ME Ward. Lack of correlation between the detection of Chlamydia trachomatis DNA in synovial fluid from patients with a range of rheumatic diseases and the presence of an antichlamydial immune response. Arthritis and Rheumatism 41: 5 (MAY 1998):845-854.>
31) NS Lai, JL Lan. Treatment of DMARDs-resistant rheumatoid arthritis with minocycline: a local experience among the Chinese. Rheumatology International 17: 6 (APR 1998):245-247.
32) GS Alarcon. Minocycline for the treatment of rheumatoid arthritis. Rheumatic Disease Clinics of North America 24: 3(AUG 1998):489.
33) JG Kuipers, B Jurgenssaathoff, A Bialowons, J Wollenhaupt, L Kohler, H Zeidler. Detection of Chlamydia trachomatis in peripheral blood leukocytes of reactive arthritis patients by polymerase chain reaction. Arthritis and Rheumatism 41: 10 (OCT 1998):1894-1895.
34) M Wuorela, K Granfors. Infectious agents as triggers of reactive arthritis. American Journal of the Medical Sciences 316:4(OCT 1998):264-270.
34a) S Nikkari, K Rantakokko, P Ekman, T Mottonen, M Leirisalorepo, M Virtala, L Lehtonen, J Jalava, P Kotilainen, K Granfors, P Toivanen. Salmonella-triggered reactive arthritis - Use of polymerase chain reaction, immunocytochemical staining, and gas chromatography mass spectrometry in the detection of bacterial components from synovial fluid. Arthritis and Rheumatism 42: 1 (JAN 1999):84-89.
35) E Veillard, P Guggenbuhl, S Bello, F Lamer, G Chales. Reactive oligoarthritis in a patient with Clostridium difficile pseudomembranous colitis - Review of the literature. Revue du Rhumatisme 65: 12 (DEC 1998):795-798.
36) R Oliker, BA Cunha. Streptococcus pneumoniae septic arthritis and osteomyelitis in an HIV-seropositive patient. Heart & Lung 28: 1(JAN-FEB 1999):74-76.
37) AA Butt, A Janney. Arthritis due to Mycobacterium fortuitum. Scandinavian Journal of Infectious Diseases 30: 5(1998):525-527.37) JR Odell. Is there a role for antibiotics in the treatment of patients with rheumatoid arthritis? Drugs, 1999, Vol 57, Iss 3, pp 279-282.
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