The following research from around the world, carried out over the course of 5-6 decades, focuses on streptococcus as a possible triggering element and causative factor in the progression of rheumatoid arthritis (RA).
Dr. Thomas McPherson Brown placed emphasis on the etiopathogenic role of streptococcal infections in RA, based on rheumatic fever, a classic infectious model of chronic arthritis that he saw frequently during his tenure as a practicing rheumatologist and clinical researcher. In the book, The New Arthritis Breakthrough, by Henry Scammell (p. 150), Dr. Brown describes using an anti-streptococcal approach to treating his rheumatic patients. This approach was administered in combination with mycoplasma treatment until strep titers had been lowered adequately, after which mycoplasma could be targeted more precisely. In these cases, treatment would involve ampicillin or similar penicillin antibiotic, sometimes pulsed with tetracycline antibiotics (spaced well apart or on tetracycline off-days), intermittent IV clindamycin, or just daily penicillin only in some patient cases.
An important clinical observation made by Dr. Brown was that patients with a greater frequency of rheumatoid nodules commonly had a history of streptococcal infection, accompanied by elevated strep antibodies, and that short-term treatment with penicillin derivatives would lead to nodule resolution. He also postulated that rheumatoid nodules are fibrous, skein-like tissue formations that form as a self-protective response to encapsulate and wall-off invading pathogens to prevent their spread.
Migrating Polyarthralgias. NEJM; Physicians-In-Training, Clinical Problem-Solving Review Series; July 5th, 2013.
The New England Journal of Medicine presented the case of an otherwise healthy 28-year old woman with fatigue and migrating joint pain and swelling. Such symptoms typically evolve 2-4 weeks after throat infection with group A streptococcal infection. Minor, early features of rheumatic fever involve fever, elevated CRP and SED rate, joint pain (no swelling) and elevated white blood cell counts (leukocytosis), and sometimes heart block. This report states, however, that these symptoms may be easily misdiagnosed as parvovirus B19, gout, post-infectious or reactive arthritis, gonococcal infection, and systemic rheumatic illnesses, such as, systemic lupus erythematosus, Lyme disease, or rheumatoid arthritis. In addition to migrating joint pain/swelling and fatigue, classic late stage major features of rheumatic fever include carditis, subcutaneous nodules, a skin rash called erythema marginatum, and Sydenham’s chorea (aka St. Vitrus’s Dance), involving rapid, involuntary facial and arm muscle movements, which help to delineate rheumatic fever from other rheumatic presentations. Treatment involves the administration of pencillin in a 10-day course or one intramuscular (IM) injection of penicillin G benzathine, along with anti-inflammatory pain and fever relievers, such as aspirin. Rheumatic fever can result in recurrent episodes if the patient is re-exposed to group A streptococcus. For this reason, rheumatic fever patients will be advised to receive monthly prophylactic IM penicillin G benzathine or twice daily oral penicillin indefinitely to prevent future rheumatic fever occurrences.
RBF Commentary: Strep throat, quickly and efficiently diagnosed today by clinicians with in-office throat swab testing, has resulted in a greatly reduced prevalence of rheumatic fever. Delayed treatment or misdiagnosis, however, can still result in the serious long-term consequences of rheumatic fever. Dr. Brown saw many rheumatic fever patients in the hospital setting, as described in The New Arthritis Breakthrough, by Henry Scammell, and this infection served as a classic model of reactive, infection-induced arthritis.
Pneumococcal polyarticular septic arthritis after a single infusion of infliximab in a rheumatoid arthritis patient: a case report. J Med Case Rep. 2012 Mar 9;6:81.
Case study of a 38-year old Japanese man with a 5-year history of seronegative rheumatoid arthritis (RA) that was resistant to methotrexate, folic acid, and low dose prednisolone. Eight days after receiving his first Remicade (infliximab) infusion, he became febrile (temp of 105.08f) with chills, polyarthritis (swollen, painful and warm joints), and significantly elevated inflammatory markers, and was diagnosed with bacterial septic arthritis as a result of Streptococcal pneumoniae infection. After surgical intervention due to joint sepsis and a month of intravenous antibiotic therapy, the patient recovered.
RBF Commentary: S. pneumoniae is a community-acquired form of pneumonia and resides in asymptomatic, healthy carriers, but can become pathogenic in immune-compromised individuals, spreading from the nasal cavity, sinuses, and respiratory tract to other locations in the body, such as the joints (septic arthritis), bones (osteomyelitis), heart (endocarditis), gut (peritonitis), skin (cellulitis), brain (abscess or meningitis), ears (otitis media), and eyes (conjunctivitis). Antistreptolysin O (ASO) titer is a blood test to measure antibodies against streptolysin O, a substance produced by Group A streptococcus bacteria. ASO testing of rheumatic patients should be routine and a reading of >200 units is considered significant. Dr. Brown would treat all rheumatic patients who had a history of strep with IV clindamycin followed by penicillin therapy until ASO titers and symptoms normalized.
Streptococcal cell wall induced arthritis: leukocyte activation in extra-articular lymphoid tissue. Inflammation. 2003 Apr;27(2):59-70.
Seeking better understanding of rheumatoid arthritis (RA) and the roles played by leukocytes and their subsets in this rheumatic disease, researchers in Louisiana used a streptococcal cell wall-induced arthritis model.
RBF Commentary: This study was included here to exemplify the universal acceptance that streptococcal antigens can induce arthritis for the purpose of studying various aspects of arthritis. By using this method of arthritis induction in the laboratory setting, these researchers were then able to confirm evidence of leukocyte activation in spleen, lymph node, and myeloid lineages, resulting in the production of specific antibodies, B cells, monocytes, T cells, and myeloid cells that are consistent with RA pathogenesis.
Tranilast suppresses the disease development of the adjuvant- and streptococcal cell wall-induced arthritis in rats. J Pharmacol Sci. 2007 Sep;105(1):48-56. Epub 2007 Sep 8.
Japanese researchers studied the effectiveness of Tranilast, an anti-allergy and anti-fibrotic medication used in the treatment of allergic disorders (e.g. asthma, allergic rhinitis, atopic dermatitis) in rats with streptococcal cell wall-induced arthritis. Results of this study concluded that Tranilast was superior to methotrexate in treating streptococcal cell wall-induced arthritis as compared to adjuvant-induced arthritis.
RBF Commentary: Dr. Brown described rheumatoid arthritis as a rheumatic disease that had all the characteristics of bacterial hypersensitivity (aka bacterial allergy) and, as a part of his antibiotic protocol treatment regimen, he would add an anti-histamine, such as Benedryl or Ateldrinspansule, to reduce the effects of bacterial die-off and the resulting tissue hypersensitivity caused by these antigenic endotoxins. The above Japanese study provides further evidence of the effectiveness of this approach.