Home

Rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic and disabling autoimmuneA condition or disease thought to arise from an overactive immune response of the body against substances and tissues normally present in the body disorder. Growing evidence suggests RA is caused by infections.

Pain is a symptom of RA and can be exacerbated by immunopathologyA temporary increase in disease symptoms experienced by Marshall Protocol patients that results from the release of cytokines and endotoxins as disease-causing bacteria are killed.. Marshall ProtocolA curative medical treatment for chronic inflammatory disease. Based on the Marshall Pathogenesis. (MP) patients should always use 40mg of olmesartan (Benicar)Medication taken regularly by patients on the Marshall Protocol for its ability to activate the Vitamin D Receptor. every four hours before resorting to pain medications. There are also other strategies for managing pain.

When the usual strategies for managing immunopathology are not enough to control pain, may patients rely upon pain medications. Except for corticosteroidsA first-line treatment for a number of diseases. Corticosteroids work by slowing the innate immune response. This provides some patients with temporary symptom palliation but exacerbates the disease over the long-term by allowing chronic pathogens to proliferate., there is no pain medication contraindicated specifically because a patient is on the Marshall Protocol. Opioids are the preferred method of dealing with extreme pain in the MP cohort.

Management

Pain medications

Studies have shown that people in hospitals given adequate pain control tend to heal faster and are able to be discharged sooner than those who are not given adequate pain medications.1) The physiologic consequences of uncontrolled pain are myriad, and should not be overlooked.

For many patients, the level of pain is truly incapacitating and these patients have to have pain control just to be able to get through the day.2) The “tough it out” mentality can backfire for times when the pain simply becomes too much. For these patients, choosing to use pain medication is the realistic and inevitable choice.

As one proceeds on the MP, one will eventually get to the point where the pain medications can be weaned down and then off.

TNF-alpha inhibitors

Main article: Anti-TNF drugs

Tumor necrosis factor-alphaA cytokine critical for effective immune surveillance and is required for proper proliferation and function of immune cells. or TNF-alphaA cytokine critical for effective immune surveillance and is required for proper proliferation and function of immune cells. is a cytokineAny of various protein molecules secreted by cells of the immune system that serve to regulate the immune system. critical for effective immune surveillance and is required for proper proliferation and function of natural killer cells, T cells, B cells, macrophages, and dendritic cells.3) Anti-TNF drugsDrugs which interfere with the body's production of TNF-alpha - a cytokine necessary for recovery from infection, also known as TNF blockers, are drugs which interfere with the body's production of TNF-alpha.4)

Anti-TNF drugs are expensive, ineffective at treating chronic disease and have a number of adverse effects. Also, anti-TNF inhibitors can make a patient feel temporarily less symptomatic, because they reduce immunopathologyA temporary increase in disease symptoms experienced by Marshall Protocol patients that results from the release of cytokines and endotoxins as disease-causing bacteria are killed., the bacterial die-off reaction.

→ Read more...

High-dose antibiotics

Related article: Pulsed low-dose antibiotics

A high-dose antibiotic therapy is any treatment which uses antibiotics at a large enough dose that the immune response is suppressed more than it is not.

Antibiotic protocols and treatments other than the Marshall ProtocolA curative medical treatment for chronic inflammatory disease. Based on the Marshall Pathogenesis. have been widely prescribed for certain Th1 diseasesThe chronic inflammatory diseases caused by bacterial pathogens. including rheumatoid arthritis and Lyme disease. However, the evidence for these treatments' efficacy is limited to short-term improvement and patients tend to relapse.

Although the Th1 diseases are caused by bacterial pathogens, these alternatives to the Marshall Protocol are ineffective for at least several reasons. For one, antibiotics given in high enough doses interfere with immune activity. With a weakened inflammatory response, a patient's symptoms may temporarily improve, but not because the pathogenic bacteria which drive the Th1 diseases have been eradicated.

Also, these protocols do not use olmesartan (Benicar)Medication taken regularly by patients on the Marshall Protocol for its ability to activate the Vitamin D Receptor. to activate the Vitamin D ReceptorA nuclear receptor located throughout the body that plays a key role in the innate immune response.. Protocols which do not generate sustained immunopathologyA temporary increase in disease symptoms experienced by Marshall Protocol patients that results from the release of cytokines and endotoxins as disease-causing bacteria are killed. are ultimately not effective against the Th1 diseases.

→ Read more...

Methotrexate

Main article: Methotrexate

Evidence of infectious cause

Scher's and Abramson's 2011 review “The microbiome and rheumatoid arthritis” offers a variety of evidence pointing to a key role of microbes in RA.5)

Rheumatoid factor is generated in response to infection

Related article: Autoimmune theory of disease

An increasing number of studies are providing support for the view that “autoantibodies” can be generated in response to the persistent presence of a pathogenic microbiotaThe bacterial community which causes chronic diseases - one which almost certainly includes multiple species and bacterial forms.. While high titers of rheumatoid factor (RF) are associated with severe rheumatoid arthritis, they also appear in a number of other diseases including viral, bacterial, and parasitic infections.6) Maturation of RF can be initiated by chronic infections.7)

Development during IRIS

During IRIS, HIV/AIDS patients experience the worsening or onset of systemic inflammatory clinical signs and symptoms following treatment with highly active antiretroviral therapy (HAART). This syndrome results when HAART allows for partial recovery of the immune response. This causes renewed and exuberant host immunological responses towards opportunistic infectious agents, agents that the host accumulated during prior periods of immunosuppression.8)

A number of well-known readily cultured pathogens have been conclusively linked to IRIS: the herpes viruses, cytomegalovirus, hepatitis B and C, M. tuberculosis, Mycobacterium avium complex and Cryptococcus neoformans.9) However, many more microbes likely contribute to the reaction since AIDS clinicians do not yet have access to the metagenomic tools. Certainly, the existence of IRIS in culture-negative HAART patients suggests that more microbes may be present than the few that have already been isolated.10)

Interestingly, patients experiencing IRIS often “develop” autoimmune conditions as a manifestation of immune restoration including rheumatoid arthritis,11) This suggests that patients with RA accumulated microbes that are directly involved in the pathogenesis of this disease state.

Other evidence

Vitamin D metabolism

Consistent with the Marshall PathogenesisA description for how chronic inflammatory diseases originate and develop., patients with RA tend to have higher than normal levels of 1,25-DPrimary biologically active vitamin D hormone. Activates the vitamin D nuclear receptor. Produced by hydroxylation of 25-D. Also known as 1,25-dihydroxycholecalciferol, 1,25-hydroxyvitamin D and calcitirol.. Mawer et al. found that 1,25-D levels were particularly elevated in the synovial fluid surrounding the joints of patients with rheumatoid arthritis (RA).16) In this study, median serum levels of 1,25-D at baseline was not elevated in the RA patients — only 24 pg/ml. Thus, the extrarenal synthesis of 1,25-D was not obvious from the routine blood test for 1,25-D. There is no reason to think that the metabolism of other diseases is any different. Mice without functional Vitamin D ReceptorA nuclear receptor located throughout the body that plays a key role in the innate immune response. signaling develop arthritic symptoms.17)

1,25-dihydroxyvitamin D3 (1,25(OH)2D3), has potent anti-inflammatory effects on T-cells. However the efficacy of vitamin-D in an inflammatory setting is unclear. D 1,25

Genetic predisposition

Evidence as to how human genes contribute to the development of RA has been weak. Genome-wide associations studies explain only 16% of disease variance.18) Moreover, the prevalence of RA concordance in monozygotic twins in European studies is ≤15%,19) 20) and it is unclear whether this level actually exceeds the risk of developing RA that exists in the general population.21)

Patients experiences

The following cases come from Autoimmunity Research FoundationNon-profit foundation dedicated to exploring a pathogenesis and therapy for chronic disease.'s peer-reviewed paper, “Immunostimulation in the era of the metagenome.”

B.G. is a 56-year old male who was first diagnosed with rheumatoid arthritis in June 2002. He also complained of fatigue and depression. In February 2004, B.G. was administered 200mg of minocycline every other day, 200mg of Celebrex daily, and Advil as needed. B.G. reported improvement in all major symptoms within weeks. In April 2005, Celebrex was lowered to 100mg every day. At this point, B.G. reported being “unaware” of rheumatoid arthritis symptoms. On a scale of 1-10, with 10 being the most severe, he rated his overall well-being as a 1. In September 2005, he was administered 40mg of olmesartanMedication taken regularly by patients on the Marshall Protocol for its ability to activate the Vitamin D Receptor. Also known by the trade name Benicar. four times daily. His symptom levels remained constant. After two weeks, 25mg of minocycline every other day was introduced. Within 48 hours, B.G. reported exquisite photosensitivityAbnormal sensitivity to sunlight and bright lights. Also referred to as "sun flare" or "light flare.", complaining that daylight “hurt his eyes” and “made him feel ill.” Over the course of several weeks, his symptoms increased greatly to the point where he rated his overall well-being as an 8.5. After five weeks, B.G. discontinued olmesartan and resumed 200mg of minocycline every other day. He reported immediate relief. In September 2005, B.G. resumed olmesartan four times daily and 25mg minocycline on alternate days. He experienced a spike in symptoms once more. Over a few months, immunopathology gradually decreased on this dose. At present, B.G. has been on the treatment for over 4 years. In September 2010, B.G. reported overall well-being at a 2.

Proal, et al., “Immunostimulation in the era of the metagenome”22)

L.Z. is a 58-year old female diagnosed with rheumatoid arthritis in 1996. In the 5 years that followed, she was administered high-dose antibiotics along with frequent cortisone injections. Despite treatment, her disease progressed and she had joint damage in hands and feet. In 2001, L.Z. began 2,000-5,000 IU of vitamin D daily, DHEA, armour thyroid, hydrocortisone, and bioidentical hormone supplementation. In August 2004, L.Z.’s measured levels of antinuclear antibodies (ANA) were 1:160. Following the test, patient stopped vitamin D and was administered 40mg olmesartan 4 times daily. Over the course of several years, she was prescribed rotating combinations of certain subinhibitory antibiotics including minocycline, azithromycin, and clindamycin. This caused transient increases in symptoms of depression, gastrointestinal distress, and joint pain. In March 2005, ANA antibodies were measured at 1:320 while in August of the same year, this measure declined to 1:160. By August 2006, L.Z. was able to discontinue both Celebrex and all hormone therapy. One year later, L.Z. reported being able to hike with reduced joint pain. In November 2006 and in 8 subsequent tests, the patient tested negative for ANA antibodies (Figure 1). In December 2007, L.Z. discontinued all antibiotics but continues to take olmesartan.

Proal, et al., “Immunostimulation in the era of the metagenome”23)

Patient interviews

Roy P.

sarcoidosis, rheumatoid arthritis

Read the interview

Ival Meyer

rheumatoid arthritis, dyslexia

Read the interview


Interviews of patients with other diseases are also available.

Notes and comments

If we ever have an article on JIA:

Do infections trigger juvenile idiopathic arthritis?24)

Aslan M, Kasapcopur O, Yasar H, Polat E, Saribas S, Cakan H, Dirican A, Torun MM, Arısoy N, Kocazeybek B.

Rheumatology International, published online before print December 13, 2009.

http://dx.doi.org/10.1007/s00296-009-1253-4

Abstract

Juvenile idiopathic arthritis (JIA) is a disease that was prominent with increased inflammation response in immune system, appeared mostly with peripheral arthritis and endogenous and exogenous antigens play a role in the pathogenesis of disease.

Two major reasons were thinking to be considerably important. First of them is immunological predisposition and the second one is environmental factors. Infections are considered to be the most important between environmental factors but also stress and trauma are also important in the etiology of the disease. However, the relation between JIA and infections is not clearly defined but the relation between adult chronic arthritis and infections was well-defined.

A total of 70 patients, 26 with primer JIA, 20 with recurrent JIA, 24 healthy control were included in this study. Mycoplasma pneumoniae, Chlamydophila pneumoniae and C. Jejuni were detected in 4, 1 and 1 of 10 (38.46%) patients with primer JIA, respectively. Salmonella enteritidis, EBV, M. pneumoniae, C. jejuni and Borrelia burgdorferi were detected in 1, 2, 2, 2, and 1 of the 8(40%) patients with recurrent JIA, respectively. S. enteritidis were isolated in feces culture and also identified by agglutination method. Infection was detected in total 18 (39.13%) of patient groups. C. pneumoniae and C. jejuni were detected in 1 and 1 of 2(8.33) healthy control groups, respectively. Throat culture positivity was not detected in any of the patient and healthy control groups.

In conclusion, etiopathogenesis of JIA is not clearly understood and suggested that various factors can trigger the disease and it is the most common rheumatoid disease of childhood. However, there are some studies focusing especially on one infectious agent but this is the first study including such a big range of infectious agents in the literature for the microorganisms that can be suggested to have a role in the etiopathogenesis of JIA. We have a conclusion in the light of our results and suggest that some microorganisms can trigger and increase the intensity of clinical situation according to the case. When we evaluate the primer and recurrent JIA groups; M. pneumoniae and C.

jejuni come forward and seen common in JIA cases. We also suggest that the pre-diagnosis of microorganisms, which can play a role as primarily or by intervening in the etiopathogenesis of JIA and adding specific antimicrobial therapy to the standard JIA therapy, it is possible to perform new, extended, especially molecular based serial case studies.

http://dx.doi.org/10.1007/s00296-009-1253-4

Notes and comments

References

1)
Systemic lidocaine shortens length of hospital stay after colorectal surgery: a double-blinded, randomized, placebo-controlled trial.
Herroeder S, Pecher S, Schönherr ME, Kaulitz G, Hahnenkamp K, Friess H, Böttiger BW, Bauer H, Dijkgraaf MG, Durieux ME, Hollmann MW
Ann Surg246p192-200(2007 Aug)
2)
Pain management: a fundamental human right.
Brennan F, Carr DB, Cousins M
Anesth Analg105p205-21(2007 Jul)
3)
TNF blockade: an inflammatory issue.
Aggarwal BB, Shishodia S, Takada Y, Jackson-Bernitsas D, Ahn KS, Sethi G, Ichikawa H
Ernst Schering Res Found Workshopp161-86(2006)
5)
The microbiome and rheumatoid arthritis.
Scher JU, Abramson SB
Nat Rev Rheumatol7p569-78(2011 Aug 23)
6)
When do microbes stimulate rheumatoid factor?
Posnett DN, Edinger J
J Exp Med185p1721-3(1997 May 19)
8)
Immune reconstitution inflammatory syndrome and cerebral toxoplasmosis.
Cabral RF, Valle Bahia PR, Gasparetto EL, Chimelli L
AJNR Am J Neuroradiol31pE65-6(2010 Aug)
10)
Immune reconstitution inflammatory syndrome in HIV-associated cryptococcal meningitis: a prospective study.
Bicanic T, Meintjes G, Rebe K, Williams A, Loyse A, Wood R, Hayes M, Jaffar S, Harrison T
J Acquir Immune Defic Syndr51p130-4(2009 Jun 1)
11)
A case of immune reconstitution rheumatoid arthritis.
Bell C, Nelson M, Kaye S
Int J STD AIDS13p580-1(2002 Aug)
12)
Changing paradigms in Whipple's disease and infection with Tropheryma whipplei.
Moos V, Schneider T
Eur J Clin Microbiol Infect Dis30p1151-8(2011 Oct)
13)
Fecal microbiota in early rheumatoid arthritis.
Vaahtovuo J, Munukka E, Korkeamäki M, Luukkainen R, Toivanen P
J Rheumatol35p1500-5(2008 Aug)
14)
Jejunoileal bypass arthritis.
Ross CB, Scott HW, Pincus T
Baillieres Clin Rheumatol3p339-55(1989 Aug)
15)
Induced apoptosis of chondrocytes by Porphyromonas gingivalis as a possible pathway for cartilage loss in rheumatoid arthritis.
Röhner E, Detert J, Kolar P, Hocke A, N'Guessan P, Matziolis G, Kanitz V, Bernimoulin JP, Kielbassa A, Burmester GR, Buttgereit F, Pischon N
Calcif Tissue Int87p333-40(2010 Oct)
16)
Evidence for nonrenal synthesis of 1,25-dihydroxyvitamin D in patients with inflammatory arthritis.
Mawer EB, Hayes ME, Still PE, Davies M, Lumb GA, Palit J, Holt PJ
J Bone Miner Res6p733-9(1991 Jul)
18)
Characterizing the quantitative genetic contribution to rheumatoid arthritis using data from twins.
MacGregor AJ, Snieder H, Rigby AS, Koskenvuo M, Kaprio J, Aho K, Silman AJ
Arthritis Rheum43p30-7(2000 Jan)
19)
Occurrence of rheumatoid arthritis in a nationwide series of twins.
Aho K, Koskenvuo M, Tuominen J, Kaprio J
J Rheumatol13p899-902(1986 Oct)
20)
Twin concordance rates for rheumatoid arthritis: results from a nationwide study.
Silman AJ, MacGregor AJ, Thomson W, Holligan S, Carthy D, Farhan A, Ollier WE
Br J Rheumatol32p903-7(1993 Oct)
22) , 23)
Immunostimulation in the era of the metagenome.
Proal AD, Albert PJ, Blaney GP, Lindseth IA, Benediktsson C, Marshall TG
Cell Mol Immunol8p213-25(2011 May)
24)
Do infections trigger juvenile idiopathic arthritis?
Aslan M, Kasapcopur O, Yasar H, Polat E, Saribas S, Cakan H, Dirican A, Torun MM, Arısoy N, Kocazeybek B
Rheumatol Intp(2009 Dec 13)
home/diseases/rheumatoid_arthritis.txt · Last modified: 06.21.2017 by sallieq
© 2015, Autoimmunity Research Foundation. All Rights Reserved.