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ANTIBIOTIC, MINOCYCLINE, CURES ARTHRITIS

Report #7266

A press release from the American College of Rheumatology states that "An antibiotic commonly used to treat acne also provides significant improvement for people with early rheumatoid arthritis." (1)

Aspirin and nonsteroidals (such as ibuprofen) reduce pain but they do not stop the relentless destruction of cartilage caused by rheumatoid arthritis. So doctors prescribe four poisons (methotrexate, prednisone, azathioprine and hydroxychloroquine to slow destruction of the joints. The most recent study presented at the annual meeting of the American College of Rheumatology supports several previous studies that show that antibiotics can reduce pain, slow joint destruction and often return blood levels of the rheumatoid factor to normal, but it may take several months before people with arthritis feel better. The people who benefit the most and have a chance to be cured are those who start antibiotic treatment soon after the disease starts and before the cartilage is damaged. Most doctors do not treat rheumatoid arthritis with antibiotics, but those who do usually prescribe Minocycline 100 mg twice a day. Research is now being conducted to see if a more effective regimen may be doxycycline 100 mg once a day plus azithromycin 500 mg twice a week.

By Gabe Mirkin, M.D., for CBS Radio News

1) Paper presented at the American College of Rheumatology meetings November 9, 1997 by J. O'dell at the University of Nebraska Medical Center and VA Medical Center in Omaha, Nebraska.

2) 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.

3) Lancet July 11, 1992.

4) 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.

5) Barbara Tilley, Henry Ford Health Science Center in Detroit. Annals of Internal Medicine. January 14, 1995.

6) 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.

7) Kloppenburg et al. Minocycline double blind for RA. Arthritis and Rheumatism 1994;37:629-636.

8) Langevitz et al. RA with Minocycline. J.Rheumatlogy 1992;19:1502-1504.

9) Breedveld et al. J Rheumatology 1990;17:43-46.

10) Good summary in Lancet 1995(May 27);345:1319-1322.

11) Kloppenburg et al. Minocycline double blind for RA. Arthritis and Rheumatism 1994;37:629-636.

12) Langevitz et al. RA with Minocycline. J.Rheumatlogy 1992;19:1502-1504.

13) Breedveld et al. J Rheumatology 1990;17:43-46.

14) Good summary in Lancet 1995(May 27);345:1319-1322.

15) Kloppenburg M et al. Minocycline in Rheumatoid arthritis. Clin Immunother 1996(Jan);5(1):1-4.

16) Keystone E. et al. Nature Medicine. April, 1995.

17) 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.

18) 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.

19) 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.

20) 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.

21) 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.

22) 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.

23) 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.

24) 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.

25) 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.

26) 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.

27) 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.

28) 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.

29) 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.

30) C Bologna, P Viu, MC Picot, C Jorgensen, J Sany. Long-term follow-up of 453 rheumatoid arthritis patients treated with methotrexate: An open, retrospective, observational study. British Journal of Rheumatology 36: 5 (MAY 1997):535-540. 59.3% had side-effects. A Ritchie's index less than or equal to 10, a lower polymorphonuclear cell count and the absence of RF were predictive of side-effects. The probability of being on MTX at 5 yr was 73%. This study confirms the high efficacy of MTX in RA.

31) 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.

32) RW Hoffman, FX Osullivan, KR Schafermeyer, TL Moore, D Roussell, R Watsonmckown, MF Kim, KS Wise. Mycoplasma infection and rheumatoid arthritis: Analysis of their relationship using immunoblotting and an ultrasensitive polymerase chain reaction detection method. Source Arthritis and Rheumatism 40: 7(JUL1997):1219-1228.

33) A Franz, ADB Webster, PM Furr, D Taylorrobinson. Mycoplasmal arthritis in patients with primary immunoglobulin deficiency: Clinical features and outcome in 18 patients. British Journal of Rheumatology 36: 6 (JUN 1997):661-668.

34) E Toussirot, J Despaux, D Wendling. Do minocycline and other tetracyclines have a place in rheumatology? Revue du Rhumatisme 64: 7-9 (JUL-SEP 1997):474-480. address D Wendling, Chu Besancon, Hop Jean Minjoz, Serv Rhumatol, Blvd a Fleming, F-25030 Besancon, France.

35) M Aoyagi, T Sasaki, NS Ramamurthy, LM Golub. Tetracycline/flurbiprofen combination therapy modulates bone remodeling in ovariectomized rats: Preliminary observations. Bone 19: 6 (DEC 1996):629-635.

36) S Williams, A Wakisaka, QQ Zeng, J Barnes, G Martin, WJ Wechter, CT Liang. Minocycline prevents the decrease in bone mineral density and trabecular bone in ovariectomized aged rats. Bone 19: 6 (DEC 1996):637-644.

37) 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. Arthritis and Rheumatism 37: 12 (DEC 1994):1727-1734. Best summary article with 39 references.

38) Kloppenburg et al. Minocycline double blind for RA. Arthritis and Rheumatism 1994;37:629-636.

39) Langevitz et al. RA with Minocycline. J.Rheumatlogy 1992;19:1502-1504.

40) Breedveld et al. J Rheumatology 1990;17:43-46.

41) Good summary in Lancet 1995(May 27);345:1319-1322.

42) Kloppenburg M et al. Minocycline in Rheumatoid arthritis. Clin Immunother 1996(Jan);5(1):1-4.

43) 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.

44) 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.

45) 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.

46) 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.

47) 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.

48) E Toussirot, J Despaux, D Wendling. Do minocycline and other tetracyclines have a place in rheumatology? Revue du Rhumatisme 64: 7-9 (JUL-SEP 1997):474-480. address D Wendling, Chu Besancon, Hop Jean Minjoz, Serv Rhumatol, Blvd a Fleming, F-25030 Besancon, France."Minocycline therapy has given sufficient proof of its efficacy to make it an attractive alternative in rheumatoid arthritis.

49) LE Shapiro, SR Knowles, NH Shear. Comparative safety of tetracycline, minocycline, and doxycycline. Archives of Dermatology 133: 10 (OCT 1997):1224-1230.

50) SR Knowles, L Shapiro, NH Shear. Serious adverse reactions induced by minocycline: Report of 13 patients and review of the literature. Archives of Dermatology 132: 8 (AUG 1996):934-939. serum sickness-like reaction, hypersensitivity syndrome reaction, and drug-induced lupus.

51) RA Sabroe, CB Archer, D Harlow, JW Bradfield, RDG Peachey. Minocycline-induced discolouration of the sclerae. British Journal of Dermatology 135: 2 (AUG 1996):314-316.

52) A Malcolm, TR Heap, RP Eckstein, MR Lunzer. Minocycline-induced liver injury. American Journal of Gastroenterology 91: 8 (AUG 1996):1641-1643. intrahepatic cholestasis with bile duct depletion.

53) O Elkayam, M Yaron, D Caspi. Minocycline induced arthritis associated with fever, livedo reticularis, and pANCA. Annals of the Rheumatic Diseases 55: 10(OCT 1996):769-771. All three fever, arthritis/arthralgia and livedo reticularis.

54) L Xenard, JL George, T Maalouf, T Malet, P Lesure. Adverse effects of tetracyclines. A report of two cases. Semaine Des Hopitaux 72:29-30 (NOV 7 1996):924-927. benign intracranial hypertension and palpebral photosensitization.

55) excellent review on safety. Joshi N, Miller DQ. Doxycycline revisited. Archives of Internal Medicine 1997(July);157:1421-1428.

Checked 8/9/05; see report #J159.