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Types of Musculo-Skeletal disorders in elder(2)
3. Rheumatoid Arthritis
4. Polymalagia Arthritis
5. Cervical myleopathy and spinal canal stenosis
7. Low back pain
Rheumatoid Arthritis is defined a chronic disorder as a result of inflammation, affecting mostly the flexible (synovial) joints and tissues and organs in the body. The disease affects more women than men and generally occurs after the ages of 40, causing diminished quality of life of many elders(1). According to CDC, Musculoskeletal disorders (MSDs) affects over 52 millions of adults in the US alone, including 294,000 children under age 18 with some form of arthritis or rheumatic conditions(2). Rheumatoid Arthritis can induced bone loss through elevating bone resorption without increasing bone formation(4). A cross-sectional population-based study of 1042 patients with rheumatoid arthritis showed that RA patients had an increased risk of death from various causes(4a).
Signs and Symptoms
1. The feet and joints
2. The gait
Dr. Weiss RJ. and the research team at the Karolinska Institutet, showed that the kinematic and kinetic gait changes in rheumatoid arthritis (RA) patients are the result of a significant reduction in joint motions, joint moments, such as decreased hip flexion-extension range, hip abduction, knee flexion-extension range,...(9). The valgus deformities of the feet in patient withRA may be the main contribution to deformities of gait, including revealed decreases in velocity, stride length, and single-limb-support time(10). Used as characterise dysfunction of the lower limb and foot in people, gait also expressed its effects mainly in RA's patient with conditions of of a slower walk, longer double support time, and avoidance of extreme positions(11).
The affects of deformation of RA's hands can be described through the defects of bone ankylosis as a result of bone damage of the prolonged onset of the disease(12). These deformities of hand and wrist and small peripheral joints (such as fingers and wrist) due to chronic inflammation can be treated by transelectrical nerve stimulation, the University of Ottawa suggested(14).
According to the joint study lead by the University of Warwick, strengthening and stretching have been found effectively in reduced pain and dysfunction of the hands and/or wrists in RA patient with stable medication for at least 3 months(13)
4. The Muscle strength
The effects of muscle strength in patient with RA may contribute to the prevalence of functional limitations physically of that cdan effects daily living and quality of life. Dr. Häkkinen A and the research team at Jyväskylä Central Hospital, suggested that 2-year program of strength training showed a statistically significant improvement in clinical disease activity parameters, walking speed and physical function(15). Some researchers suggested that muscle strength was found inversely and independently associated with all-cause mortality, including the levels of physical activity or even cardiorespiratory fitness(16).
Dr. Brodin N and Dr. Swärdh said"... short-term land-based aerobic and strengthening exercise on moderate to high intensity results in positive effects on oxygen uptake and muscular strength, but not pain,..." (17).of that may be necessary for patient with RA.
5. Rheumatoid nodules
Rheumatoid nodules, lump on the skin, closed to the joint have been found to affect the joints of patients with rheumatoid nodules(18). Treatment of rheumatoid nodules are necessary in odd cases if the patient are experiencing pain or interference of mechanical function, according to Dr. Tilstra JS and Dr.Lienesch DW.(19). Use of methotrexate (MTX) in patient with RA may accelerate the occurance of nodulosis in the fingers. but nodules will be resolved after methotrexate was discontinued and recurred after methotrexate was reintroduced(20).
Although is rare in patients with rheumatoid arthritis, the appreance of the nodules may exhibit the
severity of the underlying disease, according to the Tehran University of Medical Sciences(21), including Pityriasis Lichenoides et Varioliformis Acuta(22), Epstein-Barr virus(23)
Morning stiffness, as a marker of inflammatory activity in reflecting functional disability and pain is a very common symptoms of patients in early rheumatoid arthritis(24). Use of glucocorticoid is found effectively in pain relief over 70 percent of patient with RA(25).
According to the Charité University Medicine, in a 12-week, multicentre, randomised, double-blind trial, 288 patients with active rheumatoid arthritis, treatment of modified-release prednisone exhibited a clinically relevant reduction of morningstiffness of the joint in comparison of immediate-release prednisone(26).
7.1. Physical disability
Although psychological distress and physical disability have been decreased with the cautious approach with respect to prescribing medication and physical exercise progressed toward RA patient(27), but tools necessary to measure RA disease activity are often incomplete, imprecise, or rely on a combination of physician and patient subjective evaluations(28)
Dr. Motl RW and Dr. McAuley E.said" The rationale and the associated onset of chronic disease conditions that influence function, disability, and quality of life (QOL) is embedded in the "Graying of America""(29), including patient with RA.
7.2. Concurrent psychiatric disorders
Concurrent psychiatric disorders, such as depression or anxiety in patient with Rheumatoid Arthritis is found to associate to poor quality of life, according to Dr. Mok C, and the scientists at the Tuen
Mun Hospital(30). Patients with RA is found to associate to Neurologic (N) and psychiatric (P) syndromes including depression and anxiety and symptoms of cognitive dysfunction, etc.,....of that induced poorer quality of life, according to the Lby the SF-36 and fatigue by a 10 point Likert scale(32).
Dr. Arnold LM said" Chronic widespread pain is associated with several medical and psychiatric disorders,....,careful and comprehensive differential diagnosis must be performed to ensure a correct diagnosis before an appropriate treatment can be selected"(31).
1. Abnormal autoimmune response
Scientists in the study of Abnormal networks of immune response-related molecules in bone marrow cells from patients with rheumatoid arthritis suggested that patients with abnormal gene expressions of interleukin (IL) -37,(32a), miR-573 on IL-6 production(33) and microRNA-203(34),... are associated to increased risk of rheumatoid arthritis.
Dr. Lee HM and the research team at the Osaka University said" Abnormal regulatory networks in the immune response and one marrow (BM) cells from RA patients, indicating that the BM is pathologically involved in RA"(35).
2. Abnormal lipid profile
Abnormal lipid profile in many cases is associated to the metabolic syndrome risk, especially in patient with type II diabetes(36). The University of California suggested that patient with rheumatoid arthritis are found to have a high expression of low-density lipoprotein (LDL) cholesterol driven by increases in cholesterol ester catabolism(37). Dr. Xue C and the research team at the People's Hospital of Peking University showed that the association of rheumatoid arthritis and an abnormal lipid profile may be contributed as a result of increased inflammation markers and autoimmune antibodies(38) or inflammatory changes in HDL-C and Lp(a) metabolisms(39).
Certain genetic variations inherited from a parent, may be involved in the expression of RA patient, some research insisted. The Immunochip custom SNP array of 11,475 individuals with rheumatoid arthritis (cases) of European ancestry and 15,870 controls for 129,464 markers found that people with certain gene of loci are found to have an increased risk of rheumatoid arthritis(40).
Chronic inflammation of the joint can result of thickens the synovium, of that affect the cartilage and bone within the joint. Dr. Liao F. and the the research team at the Wuhan University said" Rheumatoid arthritis (RA) is a common, systemic autoimmune disease which leads to destruction of the joint architecture and consequent disability"(46). According to Epidemiological studies, the prevalence of RA affects about 5% of the population are aged 50 years or older, involved the connection of infectious etiology with a complex inflammatory response(45).
T helper 17 cells (Th17), a major effector cells in several chronic inflammatory states, correlated with local and systemic parameters of inflammation may also be a causative link to the expression of patient with RA(47)
The prevalence of Rheumatoid arthritis is proportional with the progression of age. The University of Twente study suggests age is independently associated with the levels of both acute phase reactants in early RA.(48).
In a study of 950 RA patients, the median age at the time of onset of RA according to age of the young-onset RA (YORA) and late-onset RA (LORA) is 58(49).
According to the joint study lead by the Leiden University Medical Center, Zone, expression of gene IL7R gene expression associates with longevity and healthy ageing are also found to involved risk of immune-related disease, such as RA and reduced health(50).
2. Gender and body mass index
If you are women and overweight, you are at increased risk to develop Rheumatoid Arthritis(51)(52)(54), probably due to the association between body composition BMI and inflammatory activity of in rheumatoid arthritis(55). The Korea study suggests, Middle- and old-aged women accounted for the majority of the Korean RA population, of which interfere with daily activity and employment rate(53).
Genome-wide association studies and meta-analysis indicate that several genes/loci are consistently associated with rheumatoid arthritis (RA) in European and Asian populations(40). In treatment of RA, Dr. Constantinescu F and the research team at the Virginia Commonwealth University said " (there is) racial disparities in treatment preferences for rheumatoid arthritis(56). The University of Nebraska, Omaha suggests 52 percent of African American subjects were found to be risk averse compared with 12% of the white subjects. Race remained strongly associated with risk aversion in RA(57).
Smoking is considered as one of the environment risk factor in involvement of Rheumatoid arthritis (RA) development and severity(58). The Danish study insisted that smoking exhibits other risk factors including IgM-rheumatoid factor, anti-CCP and shared epitopes in contribution to the early onset of rheumatoid arthritis(59). In fact, the medical literature was reviewed from 1985 to 2001 with the assistance of a MEDLINE showed that cigarette smoking has been increasingly shown in epidemiologic and case-control studies to be an important risk factor for both the incidence and severity of RA, especially in seropositive men. The poor habit also induce mutations or alterations in p53, a suppressor gene found in patients with RA(60).
Rheumatoid arthritis (RA) is associated to greater risk in the first degree relatives in familial clustering, mothers confer susceptibility to RA on their offspring more often than fathers(61). According to the data on patients with RA were ascertained through the nationwide Swedish Patient Register of 88,639, the clinical Swedish Rheumatology Quality Register of 11,519, risk of RA are same in both sex but Familial factors is found to be overlap between seropositive RA and seronegative RA(62).
Certain vaccines may cause Rheumatoid Arthritis(65). But there is no statistically significant association between exposure to vaccine and onset of RA, according to the Kaiser Permanente Vaccine Study Center(64).
7. Other risk factors
Dr. Oliver JE and Dr. Silman AJ. in the study risk factors are that lead to the development of rheumatoid arthritis (RA). suggest diets high in caffeine, low in antioxidants, high in red meat, changes in the female hormonal environment such as in pregnancy, breastfeeding and the use of the oral contraceptive (OC) pill, cigarette smoking and passive inhalation of smoke may also contribute to an increased risk of RA(63).
If you are experience certain subtle symptoms, such as achy joints or a morning stiffness, etc,....you may be at the early stage onset of rheumatoid arthritis. If your doctor suspect that have develop RA because of some RA symptoms such as such as warmth, swelling and pain in the joints, after physical exam, certain blood tests may be necessary, including
1. Erythrocyte sedimentation rate
2. C-reactive protein
A group of "acute phase reactants" protein produced by liver and found in patient with rheumatoid arthritis.,tends to elevate in case of inflammation. According to the Copenhagen University Hospital, oral nonsteroidal antiinflammatory drugs (NSAIDs) does not effects the levels of protein but may be constituted to the influence of NSAIDs on cardiovascular complications in patient with RA(66).
According to statistic, the prevalence of mild anemia characterized by low serum iron concentration ranged between 33% and 60% are found in patient with rheumatoid arthritis(67), such as aplastic anemia and iron deficiency anemia. In fact, patient with combination of RA and amenia are mostly experience severe forms of joint disease and improvement of anemia is found to contribute to over all quality of life (QOL) and response to RA therapy(67).
Cyclic citrullinated peptides (CCP) in most cases is ordered in conjunction with the test of rheumatoid factor in patient with RA. The positive find of anti-citrullinated peptide/protein antibodies may contribute to the presence of the early event in the disease(68). Dr van Venrooij WJ and the research team at the Radboud University said"...., the presence of these antibodies was highly predictive of and specific for RA, and illustrating the importance of ACPA"(69).
5. Rheumatoid factor
Rheumatoid factor test is a blood test to measure the antibody in patient with rheumatoid arthritis.
The study of 71 patients with rheumatoid arthritis and 25 control subjects. AIF-1 is found to associated with the pathogenesis of RA involved in the immunological process underlying RA(70).
6. X ray
1. Polyarticular gout
The condition of gradually loss of bone mineral density due to aging has found to be associate to the complication of rheumatoid arthritis. It mat be result of bone weakening induced by the progression of the disease.
Dr Lee SG, and the research team at the Pusan National University School of Medicine, suggest, the prevalence of osteoporosis in the RA patients was 1.9 times higher than in healthy subjects. Glucocorticoid use for treatment of osteoporosis was a risk factor for generalized bone loss in female RA patients(80). In the study of Italian Study Group on Bone Mass in patient with Rheumatoid Arthritis, Dr. Insignia L and his team concluded "... osteoporosis and its dramatic complications in RA the therapeutic challenge is to preserve functional capacity using the lowest possible dosage of corticosteroids"(81).
2. Lymphoproliferative diseases
The use of Methotrexate (MTX) as a first choice of medicine for treatment of RA has been found to induced complication of MTX-related lymphoproliferative diseases (MTX-LPDs). The joint study by the Niigata Rheumatic Center suggests the cytological examinations of the synovial fluid followed by knee operation are important and effective for early diagnosis of MTX-LPD(82). The study 589 RA outpatients examined at the National Center for Global Health and Medicine in the period from January 1990 to October 2010 conducted by the Osaka University Graduate School of Medicine also supported of the above claim and expressed the concern of the therapeutic challenge is to preserve functional capacity using the lowest possible dosage of corticosteroids.(83).
The Ipswich Hospital NHS Trust, of which insisted that Late-onset neutropenia (LON) occurs infrequently after treatment with RTX, but can present with infection(86).
4. Carpal tunnel syndrome
Carpal tunnel syndrome is defined as a condition of pressure on the nerve in the wrist that supplies Carpal tunnel syndrome caused by volar dislocation of the lunate, associated with median nerve neuropathy has found in a patient with rheumatoid arthritis(87).
Scabies is highly contagious skin disease caused by an infestation by the itch mite Sarcoptes is found to be another complication of medication use cause of disease(89).
6. Dry eye syndrome and Sjogren’s syndrome
According to 61 patients with rheumatoid arthritis recruited at Siriraj Hospital during March 2009-September 2010. the prevalence of secondary Sjogren's syndrome and dry eye were found with astonished rate of 28%(90). The awareness and detection of dry eye syndrome and secondary Sjogren’s syndrome in rheumatoid arthritis may has constituted the importantevaluation of their severity and proper management(91), the Mahidol University suggested.
7. Cerebral vasculitis
Cerebral vasculitis is a condition of inflammation of blood vessel wall involving the nervous system.
The diseases also share some characteristics with RA such as elevated levels of white blood cells, erythrocyte sedimentation rate, C-reactive protein, IgG-rheumatoid factor and immune complex(92). Dr. Ohno T and the reaserch team at the Ohtsu Red Cross Hospital reported that methotrexate is found effectively in treatment of long lasting rheumatoid cerebral vasculitis(93).
8. Other complications
According to 10 relevant studies out of 2326 bibliographic citations found by the University of Palermo, complication associate to RA, include ericardial effusion (OR 10.7; 95% CI 5.0-23.0), valvular nodules (OR 12.5; 95% CI 2.8-55.4), tricuspidal valve insufficiency (OR 5.3; 95% CI 2.4-11.6), aortic valve stenosis (OR 5.2; 95% CI 1.1-24.1), mitral valve insufficiency (OR 3.4; 95% CI 1.7-6.7), aortic valve insufficiency (OR 1.7; 95% CI 1.0-2.7), combined valvular alterations (OR 4.3; 95% CI 2.3-8.0), mitral valve thickening and/or calcification (OR 5.0; 95% CI 2.0-12.7), aortic valve thickening and/or calcification (OR 4.4; 95% CI 1.1-17.4), valvular thickening and/or calcification (OR 4.8; 95% CI 2.2-10.5), and mitral valve prolapse (OR 2.2; 95% CI 1.2-4.0)(88).
The Diseases associated to Rheumatoid Arthritis(Comorbidities)
1. Cardiovascular disease (CVD)
Cardiovascular disease (CVD), one the most leading cause of death in US, in particular Coronary artery disease, is found to associate to patient with RA(95). Dr.Goodson N said" Cardiovascular death is........ responsible for approximately half the deaths observed in RA(95). The study of 54 patients with RA :87% were women, with a mean age of 51 and 92% with rheumatoid factor positive showed that high homocysteine concentration is correlate to highest risk of CVD in RA patient(96).
Recent study by Dr. Kumar N and Armstrong DJ. insisted that traditional risk factors such as homocysteine, oxidised low-density lipoprotein, high-sensitivity C-reactive protein and leptin may contribute to the growing rates CVD death in RA patient(97).
The chronic, debilitating, autoimmune nature of RA affected directly or indirectly in almost all organ systems of RA patient, have shown to induced risk of infection(98) which is found to be responsible for death of 25% of RA patients(99). According to the joint study lead by Tampere University, in total of 10,994 patient-years, 341 serious infections were found in patient with RA(100).
3. Mental health issues
According to the study by National Institute for Science and Technology high prevalence of anxiety and depression and even suicide ideation has been found to associated to patient with RA(101) probably due to inflict of medicine(101). Dr. Rouse PC and the research team at the joint study lead by the University of Birmingham, Birmingham, suggested that depression is one most concern and positive psychological well-being in RA patients(102).
Dr. Ryan and Dr. McGuire B insisted that chronic pain associated to PA may constitute to psychological symptoms of depression and anxiety in patients with RA(103).
Use of TNF-alpha antagonists for treatment of inflammatory diseases may associate to risk of cancer, particular lung cancer(104). According Dr. Buchbinder R and the research team lead by the Monash University, "Malignancy incidence was low in this RA cohort and biologic exposure did not increase the risk of malignancy. Melanoma risk was increased in both TNFi-treated and biologic-naïve RA patients compared with the general population suggesting that RA status, and possibly methotrexate exposure, may be responsible"(105).
The do’s and do not’s list
2. Increase intake of fruit and vegetable
High glycemic index diets, which have low fiber content and are rich in trans fat cause the activation of the immune system, leading to excessive production of pro-inflammatory mediators(116). Dr. Kremer JM and Dr. Bigaouette J. of American diet in patients with RA said" Patients with RA ingest too much total fat and too little PUFA and fiber. Their diets are deficient in pyridoxine, zinc and magnesium vs the RDA and copper and folate vs the TAD"(115). Increase intake of fruits, vegetables, and whole grain consumption seem to be associated with the improvement in subclinical inflammatory condition(116).
4. Maintaining body weight
According to the joint study lead by the Philadelphia VA Medical Center and University of Pennsylvania, a low body mass index (BMI) has been associated with accelerated mortality in patients with rheumatoid arthritis (RA) and obesity showed no support a biologically protective role in RA patients(117). Patients with high BMI have lower mortality than thinner patients(118).
Foods sugar, dairy products, red meat and processed, meat, alcohol, artificial ingredients, refined products, etc. induced the production of pro inflammatory cytokine is associated to the expression and progression of Rheumatoid Arthritis(120) as Dr. Seaman DR. said" Nearly all degenerative diseases have the same underlying biochemical etiology, that is, a diet-induced proinflammatory state" and "treatment program must also include nutritional protocols to reduce the proinflammatory state"(119).
such as fresh vegetables and fruits, seeds and sprouts whole grain, fish, turkey, chicken, legumes, etc.
A high vegetable diet and fish oil are found to associate to reduce inflammation and progression of RA. Dr. Adam O and the research team at the Medizinische Klinik Innenstadt der LMU suggested that auch diet improved tender and swollen joints decreased caused by expression of pro inflammatory cytokines(121). Others in the study of 49 patients with active rheumatoid arthritis completed a 24-week, showed the intake of fish oil with olive oil is also associated with certain changes in immune function, probably through the health benefits from the presence of omega-3 fatty acids in olive(122).
Smoking are associated with increased of Rheumatoid Arthritis as it is considered as the most important extrinsic risk factors for the development and severity of Rheumatoid Arthritis, causing over expression of oxidative stress, inflammation, autoantibody formation and epigenetic changes(124).
According to the data of 2,800 adult patients included in the BARFOT early RA between 1992 and 2005study in Sweden. stop smoking after onset of RA did not change the poor prognosis of smokers with RA but reduced risk cardiovascular mortality and morbidity and the association of smoking with vasculitis and noduli in RA(123).
If you are in occupation of increased risk of Rheumatoid Arthritis(RA), such as farmers, upholsterers, lacquerers, concrete workers, and hair-dressers, you should take all precaution if necessary(124).
According to the Department of Occupational Health, Karolinska Hospital, in a register based cohort study of a total of 375,035 men and 140,139 women concluded "there were rather small differences in the relative risk of RA in different exposure groups and different occupations"(125).
Moderate exercise such as yoga(127)(128), taichi(128), qi kong(128),.....enhances immune function in fighting against inflammatory and infectious disease outcomes(128).
In the study of habitual physical activity levels of 29 female patients with RA, researchers at the joint study lead by University of the Witwatersrand showed that the exercise improved bone density and induced protective effects on bone health(126).
In animal model,
The Diet reduced risk of over expression of pro inflammatory cytokine is always important to prevent the early onset and patient with progression of the rheumatoid arthritis.
1. Organic Soy
Intake of soy protein can enhance the protective effect against Rheumatoid Arthritis(129). Genistein, an isoflavone derivative found in soy suppressed the proinflammatory cytokine production, through inhibiting the expression of accumulation of reactive oxygen species (ROS)(130).
3. Olive oil
Olive oil when used conjunction with fish oil is found to prevent the early development and protect against progression the diseases in patient with RA, in our earlier research(135). In other study of a total 145 RA patients and 188 control subjects, regular intake of of both cooked vegetables and olive oil was inversely and independently associated with risk of RA, probably through the consumption of n-3 fatty acids and nutrients effects(136). Dr. Rosillo MÁ and the research team lead by the University of Seville showed that phenolic compounds found in the extra virgin olive oil (EVOO) inhibited the levels of proinflammatory cytokines and prostaglandin E2 in the joint as well as down-regulation of the arthritic process(137).
Salmon containing high amount Omega 3 fatty acid which is found to decrease the risk of RA(138).
Salmon cartilage proteoglycan (PG), in animal model is found effective in suppressed excess inflammation in different mouse inflammatory diseases, including rheumatoid arthritis, through attenuated collagen-induced arthritis (CIA) pathogenesis by modulating immune response and local production inflammatory cytokines and chemokines in the joints(139).Salmon calcitonin, a hormone found in salmon and used as spray for treatment of osteoporosis exhibited anti inappropriate inflammatory responses contribute to the pathogenesis of rheumatoid arthritis (RA), according to the School of Food Science and Environmental Health(140).
Ginger (Zingiber officinale), one of traditional herbal medicine and spicy used in many Asian culture today, is being used as an anti-inflammatory in Chinese and Ayurvedic medicine. Crude dichloromethane extract from ginger, contained essential oils and more polar compounds, was found more efficacious in preventing both joint inflammation and destruction, according to Dr. Funk JL and scientists at the University of Arizona(141)).
Dr. Al-Nahain A and the research team at the University of Development Alternative said"..., phytochemicals( found in ginger) can form the basis of discovery of new drugs, which not only can provide symptomatic relief but also may provide total relief from RA by stopping RA-induced bone destruction"(142)
Curcumin is a phytochemical found abundantly in Turmeric, principal curcuminoid of the popular Indian spice
1.1. Anti-inflammatory agent
In rheumatoid arthritis patients, oral administration of curcumin sginificantly improved the American College of Rheumatology (ACR) DAS scores in reduction in tenderness and swelling of joint and and other arthritic conditions(147) such as dramatic amelioration of arthritis symptoms(148).
Gingerole, is also known as gingerol, a phytochemical of Flavonoids (polyphenols) found in fresh ginger.
2.1. Antioxidants and Anti-inflammatory effects
Quercetin is a member of flavonoids, found in fruits, vegetables, leaves and grains with anti inflammatory and antioxidant property(154)(155). which have been found effectively in reduce the early onset and stop the progression of rheumatoid arthritis.
In rheumatoid arthritis, Epigallocatechin-3-gallate (EGCG) may have a beneficiary effects for treatment of RA due to its suppressed autoimmune arthritis activity(160), also through vary antioxidant and anti inflammatory pathways.
Antioxidants found abundantly in fruits and vegetables can enhance the immune system fighting against forming of free radicals causes of irregular cell growth and foreign invasion of inflammation and infection.
1. Vitamin C
Vitamin C, one of most powerful free radical scavengers, played an important role in prevention of domino effects of imbalance of estrogen may be a potent antioxidant effectively in normalization of the impaired oxidant/antioxidant system and delayed complication of RA(161). Dr, Al-Okbi SY in the study of elevated oxidative stress and inflammatory biomarkers suggested that vitamin C can be used as as complementary medicine to manage rheumatoid arthritis due to its anti-inflammatory and antioxidant activities(162).
But Dr. Rosenbaum CC and the research team at the the Bethesda North Hospital Pharmacy iunsisted that more high quality research are necessary before supplements including vitamin C can be effectively and safely recommended to reduce nonsteroidal antiinflammatory drug or steroid usage"(163)
2. Vitamin E
Low intake of vitamin E and selenium have been found to the RA elder patient(166).Vitamin E, another free radical scavenger may also be effective for patient with RA due to its positive effect on autoimmune disease by decreasing proinflammatory cytokines and lipid mediator(164). Dr. Aryaeian N. in the investigation of the effectiveness of supplements in RA, showed that the procession of property in promoted immunity and involvement of inflammatory parameters may put vitamin E in front of other rheumatoid arthritis (RA)management supplements(165).
Glucosamine, a compound of the simple sugar glucose and the amino acid glutamine, is a precursor for glycosaminoglycans may be another antioxidant used for management of symptoms of patient with RA, according to the study of 25 patients in the glucosamine group and 26 patients in the placebo group(167). Dr. Matsuno H. and the research team at the Matsuno Clinic for Rheumatic Diseases, said" (oral administration of) glucosamine-chondroitin-quercetin glucoside (GCQG) for 3 months showed a significant improvement in pain symptoms, daily activities (walking and climbing up and down stairs), and visual analogue scale, and changes in the synovial fluid properties"(168) in patient of OA and RA. Further more, the supplement also found to consist the therapeutic potential for arthritis by exerting antioxidative and immunomodulatory effects(169).
Methylsulfonylmethane (MSM), an antioxidant with organosulfur compound has shown to involve in reduced the progression of inflammatory processes in RA patient(170). The Jazan University study in the comparison of the effectiveness of Echinacea extract and composite glucosamine, chondroitin and methyl sulfonyl methane supplements, showed that both ingredient exhibit anti inflammation, oedema and mild proliferation of synovial cells activities, through reduced cartilage damage and bone density of that may be a promising light on arthritis treatment(171)
A. In conventional medicine perspective
The aim of treatment is to stop the progression and relieve the symptoms of the diseases
1. Non Medication
1.1. Physical therapy
Relaxation and temperature biofeedback training as an adjunctive therapy has showed to alleviate both pain and stress-related symptoms as well as improvement of pain, tension, and sleep patterns. In fact, the therapy are found to induced higher physical/functional indices in comparison to physical therapy(174). Dr. Astin JA. and the research team at the University of Maryland School of Medicine suggested that psychological interventions such as relaxation, biofeedback, cognitive-behavioral therapy, may form an important part in may be important adjunctive therapies in the medical management of RA, especially for patients who have had the illness for shorter duration(175).In fact, a systematic review and meta-analysis of randomized controlled trials, also showed that psychological intervention improved both depressive symptoms and anxiety among patients with RA(176).
Low level laser therapy may be beneficiary in modulated inflammatory response both in early as well as in late progression stages of RA, through its effects in significantly improved mononuclear inflammatory cells(177) as well as modulating inflammatory mediators (IL-1β, IL-6)(178). The study of 132 patients at the age varying from 18 to 85 years presenting with rheumatoid arthritis by Dr.Kulova LA, and Dr. Burduli NM also found thatn the therapy showed an improvement of the endothelial function and the microcirculation indices in patient with rheumatoid arthritis(179). But according to a randomized double-blind controlled trial laser therapy using low-level aluminum gallium arsenide was not effective at the wavelength, dosage, and power studied for the treatment of hands among patients with rheumatoid arthritis(180).
1.4. Occupational therapy
According to the Canadian association of occupation therapy, it is form of treatment to solve the problems that interfere with your ability to do the things that are important to you. It can also prevent a problem or minimize its effects(181). According to the Netherlands Institute for Health Services Research, in controlled (randomized and non-randomized) and other than controlled studies (OD) addressing OT for RA patients showed that occupation therapy improved outcome on functional ability, social participation and/or health related quality of life(182). Rheumatologically, occupation therapy in many cases has successfully improved and maintained functional capacity, prevented progression of deformities, ......... of that may require for the engagement of the individual in meaningful occupations, favoring autonomy and independence in self-care activities, employment, educational, social and leisure(183)
Prosorba column apheresis therapy (PCT), a medical device containnig purified staphylococcal protein A covalently bound to a silica matrix has been used in many medical centers for treatment severerheumatoid arthritis (RA) since its approval in 1999(184) with some promising result(185).
The therapy showed a 52% improvement in joint tenderness, 40% improvement in swelling, 42% improvement in patient's pain, 38% improvement in patient's global response, and 48% improvement in physician's global scores 76% of responders, according to the study by Cypress Bioscience(184).
Medication or combined medication are used to stop the progression and relieve the symptoms of the diseases may include
2.1. Medication for reduced symptoms
Nonsteroidal anti-inflammatory drugs (NSAIDs)can be bought as over counter medicine for reduced pain and inflammation for patient with rheumatoid arthritis with an incidence of significant upper GI toxic effects, according to a total of 8059 patients (>/=18 years old) with osteoarthritis (OA) or rheumatoid arthritis (RA)(186). Dr. Wienecke T and Dr. Gøtzsche PC. in the comparison of NSAIDs and Paracetamol for treatment of RA said " There is a need for a large trial, with appropriate randomisation, double-blinding, test of the success of the blinding, and with explicit methods to measure and analyse pain and adverse effects"(187) due to favorable of onsteroidal anti-inflammatory drugs (NSAIDs) in general population.
d. JAK inhibitors
JAK inhibitors, the medication used in conventional doctors for inhibition of the activity of one or more of the Janus kinase family of enzymes, involving function in cytokine receptor signalling pathway, through interaction with signal transducers(transmission of molecularsignals from a cell's exterior to its interior) and activators of transcription proteins(a sequence-specific DNA-binding factor in controlling the rate of transcription of genetic information from DNA to messenger RNA)(200) is also known as a new subcategory of DMARDs. Dr. Norman P. said" JAK inhibitors differ in isoform specificity profiles, with good efficacy achievable by selective inhibition of either JAK1 (filgotinib or INCB-039110) or JAK3 (decernotinib)' of that contrite to the effective treatment of patient with rheumatoid arthritis)(201). According to the University of Occupational and Environmental Health, use of Tofacitinib, a new class of DMARDs orally available exhibited a strong clinical efficacy similar to biologic DMARDs through inhibited multiple cytokines and signaling pathways at clinical doses that are in contrast to biological DMARDs(202).
Here, we quoted the criteria of medication or combined medication is used to stop the progression and relieve the symptoms of RA by Dr. da Mota LM, and scientists at the Universidade de Brasília
1) The therapeutic decision should be shared with the patient;
2) Immediately after the diagnosis, a disease-modifying antirheumatic drug (DMARD) should be prescribed, and the treatment adjusted to achieve remission;
3) Treatment should be conducted by a rheumatologist;
4) The initial treatment includes synthetic DMARDs;
5) Methotrexate is the drug of choice;
6) Patients who fail to respond after two schedules of synthetic DMARDsshould be assessed for the use of biologic DMARDs;
7) Exceptionally, biologic DMARDs can be considered earlier;
8) Anti-TNF agents are preferentially recommended as the initial biologic therapy; 9) after therapeutic failure of a first biologic DMARD, other biologics can be used;
10) Cyclophosphamide and azathioprine can be used in severe extra-articular manifestations;
11) Oral corticoid is recommended at low doses and for short periods of time;
12) Non-steroidal anti-inflammatory drugs should always be prescribed in association with a DMARD; 13) clinical assessments should be performed on a monthly basis at the beginning of treatment;
14) Physical therapy, rehabilitation, and occupational therapy are indicated;
15) Surgical treatment is recommended to correct sequelae;
16) Alternative therapy does not replace traditional therapy;
17) Family planning is recommended;
18) The active search and management of comorbidities are recommended;
19) The patient’s vaccination status should be recorded and updated;
20) Endemic-epidemic transmissible diseases should be investigated and treated.
Surgery in some cases may be necessary to relieve severe pain and extensive joint deformities and with patient do not response to non and medical treatment. According to the Wrightington Hospital NHS Trust, in the study of postoperative infection or surgical complications occurring within one year of surgery in patient with RA found that the surgical procedure induced 27% of infection and complication for patient with different in the intake of Methotrexate(204), a synthetic compound used for treatment of some forms of cancers.
B. Treatment in herbal and traditional Chinese medicine
Life style modification has shown to be beneficiary for patients with Rheumatoid Arthritis to improve musculoskeletal and bone health and reduce disability. Dr. Jones G. and the research team at the joint study lead by University of Tasmania said" Lifestyle is of considerable importance in the first two and there is emerging evidence for rheumatoid arthritis despite it not traditionally being considered a lifestyle disease"(205). Modern herbal and TCM medicine specialists may suggest the following
B.1.1. Maintain balance weight
Maintain healthy weigh is important not only for reduce cost of treatment according to the study of retrospective analysis of 66 patients from a Spanish 1,000 beds-hospital Rheumatology Clinic Service(206) but also attenuate the risk of motility in patient with rheumatoid arthritis(207).
Dr. Baker JF and the research team at the joint study lead by Philadelphia VA Medical Center and University of Pennsylvania said" . Weight loss at an annualized rate of ≥3 kg/m(2) was associated with the greatest risk of death (HR 2.49, 95% CI 1.73-3.57, P < 0.001). Low BMI (<20 kg/m(2) ) in patients with a history of obesity (>30 kg/m(2) ) was associated with the greatest risk (HR 8.52, 95% CI 4.10-17.71, P < 0.001)(208).
In fact, many scientists have concerned for the rapidly increasing prevalence of obesity may contribute to recent increase in the incidence of rheumatoid arthritis(RA)(209).
Exercise, today is less popular leisure-time activity in many countries throughout the Western world, especially in the youth due to promotion of information collection through mobile phone. Exercise as medicine has been found to benefit to many forms of chronic diseases, including rheumatoid arthritis(210). Dr. Pedersen BK and Dr.Saltin B. Said" Considerable knowledge has accumulated in recent decades concerning the significance of physical activity in the treatment of a number of diseases,....... muscle, bone and joint diseases"(211).
Arobic capacity and/or muscle strength training(212), physical training exercise(213) are recommended as routine practice in patients with RA. In fact, according to the Bowman Gray School of Medicine, therapeutic exercise performance in patient with rheumatoid arthritis have shown in improving aerobic capacity, strengthening muscles, improving endurance and increasing flexibility(214).
Smoking is a risk factor for RA,and heavy smokers, according to the Kobe University Graduate Schoolof Medicine(217)(218)
Smoking has been found to induce many forms of lung disease, and cancer,. According to statistic, smoking cause death of over 83% of patient with lung cancer. Recent study suggested of the associated of lung diseases suchas bronchiectasis and unexplained dyspnea as predictor for the future development of rheumatoid arthritis, due to inflammation induced by external triggers (such as smoking) (215).
In a total of 857 patients, for determination of the effects of cigarette smoking in RA disease severity,pack years of cigarette smoking was significantly associated with rheumatoid factor seropositivity and radiographic erosions but less severe radiographic disease seemed to be more strongly associated with cigarette smoking than more severe disease(216).
B.1.4. Reduced intake of coffee
Coffee, one of many flavor drink in many culture may be associate to risk of rheumatoid arthritis, as coffee drunk daily was found directly proportional to the prevalence of RF positivity in dose depend-manner, according to the National Public Health Institute in a cohort of 18 981 men and women who had neither arthritisnor a history of it at the baseline examination in 1973-76. Up to late 1989(218). Recent study by the University of Alabama at Birmingham also suggested that decaffeinated coffee intake is independently and positively associated with RA onset(219).
Other studies insisted of little evidence of an association between coffee, decaffeinated coffee, or tea consumption and the risk of RA among women, including the Harvard Medical School, and Brigham and Women's Hospital(220).
B.1.5. Moderate alcohol drinking
Intake of moderate alcohol has been found to induce diseases protection. According to the Brigham and Women's Hospital and Harvard Medical School, long term moderate alcohol drinking are also associate to reduce risk of RA(221) and study of 34,141 women born between 1914 and 1948, followed up from 1 January 2003 to 31 December 2009 by the Institute of Environmental Medicine(222).
Foods with anti pro inflammatory cytokines can be helpful to prevent and to protect against early
onset of rheumatoid arthritis. "Low grade inflammation has been found to play a pathophysiological role in RA" Dr. Jeppesen J. said (225) as the proinflammatory cytokines may affect synoviocyte proliferation caused by elevated interleukin-21 (IL-21) IL-21-induced proliferation and secretion of TNF-α and IL-6(226).
Garlic (Allium sativum) is a species in the onion genus, belongings to family Amaryllidaceae, native to central Asia, used popularly in traditional and Chinese medicine to treat common cold and flu(228), strengthen immunity(228), etc....The clinical trial of alisate--a garlic preparation produced in Russia showed the effectiveness of alisate used compunction with other and monotherapy in reduced symptoms of RA with little side effects(227). Dr. Majewski M. said" aged garlic extract (AGE), have a clear and significant biological effect in immune system improvement,...Clinically,garlic has been evaluated for a number of purposes, including treatment of .....rheumatoid arthritis,..."(228)
Ginger (Zingiber officinale) used in many Eastern culture as a cooking spice is best in the West for its treatment againts morning sickness in early stage of pregnancy. The herbal medicine is also found to relieve pain induced by inflammation due to its effects in inhibited pro inflammatory cytokines(229) of that may be beneficiary as pharmaceutical ingredient for treatment of Rheumatoid arthritis(230) when used in combination with others herbal medicine. DR. Al-Nahain A and the research team at the University of Development Alternative said, "(Ginger) not only can provide symptomatic relief but also may provide total relief from RA by stopping RA-induced bone destruction"(231).
Turmeric is a perennial plant used as spice in Indian and as herbal medicine for strengthening the overall energy of the body, relieving gas, dispelling worms, improving digestion, regulating menstruation, dissolving gallstones, etc.(232) may be a potential candidate for treatment of rheumatoid arthritis due of its phytochemical curcumin imilar to methotrexate(233). Dr. Ramadan G and Dr. El-Menshawy O. said, "mixture of ginger and turmeric rhizomes powder (1 : 1) suspended in distilled water (GTaq) in alleviating both articular and extra-articular manifestations in rat adjuvant-induced arthritis (AIA),.....may be effective against RA severity and complications"(234), probably due to the mixture anti-inflammatory and anti-oxidant properties(235).
1.4. Green tea
Green tea , a precious drink in traditional Chinese and many culture in Southeast Asia cultures used exceptional in socialization for more than 4000 thousand years has been found to consist the property of suppressed autoimmune arthritis(238) through its phytochemical epigallocatechin-3-Gallate
(EGCG) in upregulation of the Nrf-2 antioxidant pathway in -mediated immunoregulation and ameliorated experimental arthritis in animal study(236).
Dr. Riegsecker S and the research team at the University of Toledo said," (The) potential benefits of green tea polyphenol EGCG in the prevention and treatment of vascular inflammation in rheumatoid arthritis,.........., extensive clinical evidence of the 'synovial inflammation-systemic inflammation' link and the benefits of EGCG in regulating cytokine-driven inflammation in the pathogenesis of RA and its CV complication"(237).
1.5. Cooked tomato
Tomato, the edible vegetable is best known for its phytochemical lycopene found in skin for treatment of prostate health(239)(240). According to the University of Kerala, lycopene (all-trans) found in tomato may be a better natural source with increased activity and without side effects in the treatment of anti-inflammatory diseases, in the study on type II collagen induced arthritis in Sprague Dawley rats(241). In a total of 184,643 US women followed in the Nurses' Health Study and Nurses' Health Study II cohorts in 1980-2004 study showed that intake of antioxidants including lycopene, may protect against development of rheumatoid arthritis or systemic lupus erythematosus by combating oxidative stress(242).
Salmon, is a highly nutrition with best source of Omega 3 fatty acids found in fish for human consumption born in fresh water, migrate to the deep ocean, then travel thousands of miles in the deep sea cold water throughout their life cycle and within to five years returning to the exacted location where they were born to reproduce and die.
2. Omega-3 fatty acids
3. B vitamins
4. Vitamin D
is a potent antioxidant that stimulates the development of healthy fish nervous systems and enhances the fish's fertility and growth rate.
Intake of salmon calcitonin, a hormone extract from salmon or a synthetic polypeptide of the same sequence found in salmon, has shown to attenuate the pathogenesis of rheumatoid arthritis (RA, through reduced expression of a key of (orphan nuclear receptor, NR4A2) redulator and potential biomarker for inflammation(243). Dr. Tascioglu F and the research team at the Osmangazi University Faculty of Medicine, said." alendronate and intranasal salmon calcitonin (sCT) treatments,...produced significantly greater increases in the femoral neck BMD and greater decreases in bone turnover than intranasal sCT in RA patients receiving low dose glucocorticoids"(244). Furthermore, according to the multicenter study of 32 women with RA, intranasal salmon calcitonin (sCT) prevented bone loss at the proximal femur in patients with active RA induced by intake of low dose glucocorticoids for 12 months(245).
Salmon proteoglycan prepared from salmon nasal cartilage under nondenaturing conditions showed to improve autoimmune disease caused by chronic inflammation of connective tissues, through modulating immune response of splenocytes to CII stimulation and local production inflammatory cytokines and chemokines in the joints, the research lead by Dr. Yoshimura S. suggested.(246)
Olive is belongs to the the family Oleaceae, native to the coastal areas of the eastern Mediterranean Basin and south end of the Caspian Sea. Its fruit, is also called the olive and the source of olive oil.
Olive Oil: Fat Content
1. Saturated fats
a. Palmitic acid
b. Stearic acid
c. Arachidic acid
d. ehenic acid
e. Myristic acid
f. Lignoceric acid
2. Unsaturated fat3. Monounsaturated fats
a. Oleic acid
b. Palmitoleic acid
3. Polyunsaturated fats
a. Linoleic acid
b. Linolenic acid
Monounsaturated fatty acids found abundantly in extra virgin olive oil has found to inhibit proinflammatory cytokines in inducing the decreases lubricin expression and predisposes to cartilage degeneration(247). Intake of olive oil, according to the University of Athens Medical School and University of Seville, showed to reduce risk of risk of rheumatoid arthritis (RA) due to the effects of n-3 fatty acids through the antioxiant activity(248) as well as preventing inflammatory response and cartilage matrix degradation in murine collagen-induced rheumatoid arthritis(249), respectively.
Furthermore, in animal models of acute inflammation and rheumatoid arthritis, hydroxytyrosol, a phytochemical found in virgin olive oil, a primary source of fat in the Mediterranean diet, inhibited significant impact on chronic inflammation and acute inflammatory processes, through its antioxidant and anti-inflammatory properties, recent study suggested.(250).
In deed, dr. González Cernadas L and the research team at the Unidad de Fisioterapia Basada en la Evidencia del Departamento de Fisioterapia de la Universidad de A Coruña said," some dietetic elements (polyunsaturated fatty acids, mediterranean diet and antioxidants) with inflammatory markers reduction and oxidative stress inhibition have anti-inflammatory effects and decrease AR disease activity"(251)
1. Minerals for Immunity
Strengthen immunity plays an important role in regulating the free radical and other form of irregular cell growth causes of inflammation and auto immune diseases as well as attenuating the foreigner invasion. According to the study maintaining normal levels of Copper, Selenium and Zinc have found to improve immune function against morbidity, decrease antibody production, infection, impaired natural killing cells, etc......(252) in animal study. Also according to Dr. Kremer JM and Bigaouette J., deficiency of pyridoxine, zinc, copper, and magnesium may induce rheumatoid arthritis expression(253).
Epidemiological studies suggested that levels of copper may be influence to the risk of rheumatoid arthritis has produced inconclusive results, it probably due to the disease orgination(254)(255). According to the relevant published data were retrieved through PubMed, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biomedical Database (CBM) before September 20, 2014 of 1444 RA cases and 1241 healthy controls, above normal serum levels of copper (Cu) has found in patients with rheumatoid arthritis(254). Dr Li J and the research team at the joint study lead by Sichuan University, suggested patient with rheumatoid arthritis with B-lymphocyte dysfunction are associated to lower levels of copper, selenium and zinc levels(255). Other study insisted that the alternation of copper concentration may be a result of the changes of the immunoregulatory cytokines(256). Dr Percival SS said,"The immune system requires copper to perform several functions,.....interleukin 2 is reduced and T cell proliferation are reduced in copper deficiency"(257).
Dr. Minton K. in the study of mutation of Mutation of the magnesium transporter 1 (MAGT1) gene has been found to associate to immunodeficiency due to reduced levels of magnesium(258), inducing severe chronic viral infections and inflammations(259). Deficiency of magnesium is found in patient with RA(253), routine dietary supplementation with multivitamins and trace elements is appropriate in this population(253), Dr. Kremer JM1, Bigaouette J. suggested. The Ankara University study expressed only slight and statistically insignificant reductions of plasma and erythrocyte Mg levels of the RA patients showed when compared to controls, with a positive correlations between erythrocyte SOD activity and Mg level(260).
Selenium, is found to be one of most powerful antioxidant in enhancing immune system in fighting against inflammatory and immune-related diseases, including anti-viral immunity, autoimmunity, sepsis, allergic asthma, and chronic inflammatory disorders mainly through its incorporation into selenoproteins(261). Low serum Se concentration is found to associate in patient with RA(262). But according to the Free University of Brussels, in a in a double blind multi-centric placebo-controlled study showed no clinical benefit selenium treatment on RA but a significant improvement in arm movements and health feeling(263).
Recent study showed that lower than normal serum levels of Zinc (Cu) has found in patients with rheumatoid arthritis(254).
Dietary pyridoxine showed to improve immune responses(267) and reduced the expression of pro inflammatory cytokines of that may relate to the early onset of rheomatoid arthritis(268) but the deficiency was not severe enough to affect the immune system, according to the Instituto Nacional de Ciencias Médicas y Nutricion(269). Dr Chiang EP. and the research team of the National Chung-Hsing University said, " Suboptimal vitamin B6 status seen in rheumatoid arthritis can be corrected by 50 mg pyridoxine supplementation for 30 days,.... but (The pyridoxine supplementation) did not suppress pro-inflammatory cytokine production in patients with rheumatoid arthritis"(270).
Free radical scavengers such as vitamins plays an essential role in reduced risk of rheumatoid arthritis
due to their effects in attenuate the expression of free radical and pro inflammatory cytokines(271)(272)
2.1. Vitamin A
According to the Imam Reza Hospital of Tabriz University of Medical Sciences, antioxidant including vitamin A are found to consist a clinical outcomes and oxidative stress in RA(274).
Patient with rheumatoid arthritis are accompanied with the over expression of the levels of serum leptin and other related cytokines, Dr. Xiong RB and the research team at the Southern Medical Universit said, " VitA.....significantly reduced the levels of leptin, TNF-α, IL-6 and CRP and the ESR(Pro inflammatory cytokines) and significantly increased the levels of IL-10 ( limiting autoimmunity and inflammatory responses),.... (of that) may provide a novel approach for the treatment of RA"(273).. All-trans retinoic acid (ATRA), a biologic key metabolite of vitamin A, showed to suppress the clinical and histologic signs of arthritis in the collagen-induced arthritis (CIA) mice model through downregulated the expression of RANK and prevented white blood cell from differentiating into osteoclasts, causing RA( 275).
Dietary vitamin C did significantly influence on growth performance and immune response, according to epidemiological studies(276)(277).
Dr Al-Okbi SY said" the majority of nutraceuticals studied possess beneficial effect toward chronic inflammatory diseases,.....anti-inflammatory and antioxidant nutraceuticals may serve as complementary medicine for the management of RA(279).
2.3. Vitamin E
Vitamin A similar to vitamin A are found to consist a clinical outcomes and oxidative stress (274)which has been found to play an important role in the inflammation and parthenogenesis of RA(283).
According to studies, diets containing fish oil and vitamin E not only showed a significant pain reduction in patients but also induced a positive effect on autoimmune disease by decreasing proinflammatory cytokines and lipid mediator(280). In the rat model of collagen-induced arthritis (CIA), oral adminsitration of δ-tocotrienol (10 mg/kg) induced a significant impact in lowering paw edema, through it anti inflammatory effects(281).
Vitamin D receptor (VDR), best known for its function in variety of metabolic disorders and in regulation of inflammation, is found to associate to the risk of RA(284), through its expression on reduced risk for FLS-mediated cartilage and bone invasion and erosions by attenuating the pro inflammatory cytokines induced osteoclasts. Vitamin D deficiency is common in rheumatoid arthritis (RA) of which induced pain, fatigue, and limited physical activity as well as poor quality of life(285).
Dr. Kostoglou-Athanassioul and the research team at the Red Cross Hospital, said," vitamin D deficiency is highly prevalent in patients with RA, .......may be linked to disease severity in RA. As vitamin D deficiency has been linked to diffuse musculoskeletal pain, these results have therapeutic implications"(286).
Vitamin K, another vitamin is found to plays an important role as an anti-inflammatory nutrient in bone metabolism(287). According to the cross-sectional study of a total of 158 female RA patients (mean age 62.5 years), oral administration VitK2 significant decreased serum CRP, and inhibited the proliferation of fibroblast-like synoviocytes (FLSs) and the development of collagen-induced arthritis (CIA). in a dose-dependent manner(288)
Glucosamine, a compound of the simple sugar glucose and the amino acid glutamine, is a precursor for glycosaminoglycans(194,289), a major component of joint cartilage(195,290). In a randomized placebo-controlled study of 51 rheumatoid arthritis (RA) patients: 25 patients in the glucosamine group and 26 patients in the placebo group, Glucosamine hydrochloride at a daily dose of 1,500 mg showed to improve some symptomatic effects on RA(291).
The orally administered combination of a glucosamine-chondroitin-quercetin glucoside (GCQG) supplement also exerted a special effect on improving the synovial fluid properties in OA patients, according to the Matsuno Clinic for Rheumatic Diseases(292). Furthermore, a novel glucosamine analogue also showed to inhibit the development of RA through exerting antioxidative and immunomodulatory effects(293).
B.5. The Miracle Topical Remedy
Certain topical remedies used in traditional or folk medicine have found effective on attenuate persistent symptoms of rheumatoid arthritis
Electrostimulation has been applied to acupuncture to treat pain associate to the clips from the therapeutic device, are attached to the needles. This type of alternative application also was found in Ancient Egyptians and later the Greeks and Romans, dates back to thousands of years BC for treatment of pain, muscle dysfunction and sarcopenia(303).
Dr. Men'shikova IV. in the comment of combination of modern physiotherapeutic methods in rehabilitation said,"(Use of electrostimulation of smooth muscle) All patients(with RA) reported alleviation of pain and oedema in the affected joint. The rehabilitation period was 2-5 days shorter than after the traditional treatment(304).
1.1. Ice therapy
Ice therapy, using the techniques of compression and elevation basic principles for treatment of acute soft tissue injury, if applied correctly with repeated application of 10 minutes for avoiding side effects, and preventing possible further injury(306). According to Dr. van den Bekerom MP and the research team at the Orthopaedic Research Center Amsterdam, treatment of pain, swelling, ankle mobility or range of motion, must be made on an individual basis, carefully weighing the relative benefits and risks of each option, and must be based on expert opinions and national guidelines(307).
Unfortunately, according to the study of University of Ottawa, thermotherapy, including hot and ice packs application is found a significant effects on arthritic hands of patient with rheumatoid arthritis and most studies(308).
Heat therapy, is another form of thermotherapy with the use of heat in therapy for pain relief by alternative rehabilitation specialists. The review of studied that met the criteria of 328 subjects, by the University of Ottawa, superficial moist heat is found effective for relieved joint swelling, pain, reduced medication intake, improved range of motion (ROM), grip strength, hand function but limited by methodological considerations such as the poor quality of trials(309). In support of the above, the research team lead by Dr. found that in 17 with symmetrical rheumatoid arthritis (RA) applied heat to 1 hand twice daily for 2 years, heat therapy improve joint swelling, joint tenderness and grip strength with daily heat therapy did not accelerate the proliferative lesion in RA(310).
The most oldest form of medical treatment in traditional Chinese medicine has been known for its function in relief pain(383,313) and functional limitation(384,314) for chronic patient, including patient with moderate or severe chronic pain(383,313).
The Cochrane Field of Rehabilitation and Related Therapies and the Cochrane Musculoskeletal Review suggests the effectiveness of acupuncture as a rehabilitation of an adjunct therapy for the symptomatic treatment of rheumatoid arthritis showed to reduce symptomatic knee pain in patients with RA 24 hours and 4 months post treatment(315). According to Dr. Wang C and the research team at the Tufts Medical Center and Tufts University School of Medicine, acupuncture showed to decrease pain, significant reduced morning stiffness and inflammatory markers in comparison to controls in patients with rheumatoid arthritis(316).
Massage therapy used in traditional Chinese medicine over thousands of year for treatment of osteoarthritis (OA)(392,321) was effective in reduced pain of mild to moderate juvenile rheumatoid arthritis through mediation of children's anxiety and stress hormone (cortisol) levels(322).
Furthermore, in a forty-two adults with rheumatoid arthritis, light pressure massage therapy improved grip strength following the first and last massage sessions, reduced pain and promoted range of motion in their wrist and large upper joints (elbows and shoulders) by the end of the one month period(324).
Hydrotherapy, using water for the treatment of disease has shown some beneficiary for treating pain in patient with RA(329). In comparison to patient of RA with no treatment in the short term, hydrotherapy has a positive role in reducing pain and improving the health status of RA treated patients, through reducing pain, joint tenderness, mood and tension symptoms, and increasing grip strength(329), in knee range of movement (women only) as well as maintaining improvement in emotional and psychological state(330).
Oligomineral, homeothermic, low radioactive water hydrotherapy exhibited significant improvement of functional capacity, quality of life and positive influence on disease activity in the patients with RA, an study from Serbian suggested.
Tai chi, is an ancient form of mind-body technique used in Chinese with meditative movements that promote balance and healing of the mind and body(406, 331). But to use the technique for treatment of RA has produced conflict result.
According to the review of 4 trials including 206 participants, tai chi showed a statistically significant and clinically important improvements in ankle plantar flexion, benefits on lower extremity range of motion, in particular ankle range of motion, for people with RA but had no alternation of outcomes of disease activity(332). Contract to the study, Dr Lee MS and the research team at the Universities of Exeter & Plymouth, said, " Tai chi reported some positive findings for tai chi on disability index, quality of life, depression and mood for RA patients, (but) did not demonstrate effectiveness on pain reduction(333).
Other study in the assessment of patient with RA suggested that tai chi should be sued for treatment of people with a chronic debilitating disease such as RA due to its potential for physical and psychological improvements(334).
An ancient form of medical technique originated from India, is become a popular multimodal mind-body exercise in the Western world for promoted flexibility, strength, endurance, and balance(412, 335). According to university research conducted at a medical clinic, Yoga significantly decreased Health Assessment Questionnaire (HAQ) disability index, decreased perception of pain and depression, and improved balance in women with rheumatoid arthritis(336) and hand grip strength in normal persons and in patients with rheumatoid arthritis(337) as well as inducing positive changes in psychological or physiological outcomes(338).
But in the review of Eight RCTs with a total of 559 subjects, Dr. Cramer H and the research team at the Klinik für Naturheilkunde und Integrative Medizin, Knappschafts-Krankenhaus said" ,...there was very low evidence (of yoga) for effects on pain and disability,.... only weak recommendations can be made for the ancillary use of yoga in the management of....... RA at this point"(339)
Many herbal medicine have been found effectively for reduction of symptoms and treatment for patient with osteoarthritis(340), including
Furthermore combined treatment with ginger and stimulation at zusanli (ST 36) showed a significantly greater improvements in RA symptoms, laboratory outcomes, and gastrointestinal
symptom scores in comparison to anti-rheumatic drugs (ARDs), and acupoint stimulation at zusanli (ST 36) alone(343).
Dr. Hoffman T said," Ginger: an ancient remedy and modern miracle drug,.. (showed) "unclear" for treating rheumatoid arthritis, osteoarthritis, or joint and muscle pain)" (345), but Dr. Grzanna R and the research team at the RMG Biosciences, said,"ginger modulates biochemical pathways activated in chronic inflammation"(346).
2. Primrose oil
With a rich source of omega-6 essential fatty acids, primrose oil may be effective "use in the treatment of systemic diseases marked by chronic inflammation, such as atopic dermatitis and rheumatoid arthritis" Dr.Bayles B and Dr. Usatine R. said(348).
3. Willow bark
Unfortunately, according to randomized double-blind controlled trials, willow bark extract showed no relevant efficacy in patients with OA and with RA(353).
In support to above, study conducted by the Columbia University showed that ethanolic extracts from willow bark with daily doses up to 240 mg salicin over periods of up to six weeks exhibits no significant improvement in patients with rheumatoid arthritis(354).
Stinging nettle also known as Urtica dioica, a herbal medicine with long history for the effectiveness in treating of musculoskeletal pain(355).
Dr. Yang CL and the research team at the The University of Hong Kong in the study of scientific basis of botanical medicine as alternative remedies suggested that Urtica dioica demonstrated a strong anti-inflammatory and anti-arthritic effects and may may provide new treatment opportunities for RA patients(356).
Stinging nettle leaf extracts, an Germany registered Germany for adjuvant therapy of rheumatic diseases by inhibiting the inflammatory cascade, including on NF-kappaB activation(358) in autoimmune diseases through its immunomodulating effect and mediating T helper cell derived cytokine patterns(357).
5. Devil’s claw
Devil’s claw is also one most popular herb used in alternative medicine for treatment of patient suffering from rheumatoid arthritis, probably through anti inflammatory activity and oxidative activity(359).
Dr. Wegener T. said, " Extracts of the secondary tubers of Devil's Claw , (showed)an improvement of motility and a reduction of pain sensation in several clinical studies,......Pharmacological experiments have shown analgesic, antiphlogistic and antiinflammatory actions,..(due to) its most important constituents iridoid glycosides"(360).
In the study of investigation of the efficacy of selected complementary and alternative medicine (CAM) therapies for pain from arthritis and related conditions, devil's claw, may be the best choice for relieved pain of rheumatoid arthritis (RA), but Dr. Soeken KL suggested that additional high quality research is necessary for its validation(361).
Licorice, one of most common Chinese herb used frequently in conjunction with other herbs in many herbal formulas is found to associate to the therapeutic effects on rheumatoid arthritis (RA) treatment through its phytochemicals glycyrrhizin (GL) and glycyrrhetinic acid (GA) in suppressing the anti-inflammatory cytokines(the COX-2/TxA2 pathway). The herbal medicine also decreases the adverse effects of conventional medicine NSAIDs or DMARDs(362).
Topical capsaicin, a neuromodulators, may be used for reduced pain in patients with RA. However, it is associated with a significant side effect, Dr. Richards BL and the research team at the Royal Prince Alfred Hospital suggested(367).
10. Green Tea
Green tea has been a precious drink in traditional Chinese culture and used exceptional in socialization for more than 4000 thousand years.
Turmeric, a cooking spice used in many culture in South East Asian, especially in India, also has been used as herbal medicine over thousands of year(373). Curcumin (CM), a yellow hydrophobic polyphenol derived from the herb turmeric, reduced inappropriate inflammatory responses through expression in inhibiting cell proliferation and metastasis and downregulating various factors, including the inflammatory cytokines and pathway(372) in animal model.
In acute and chronic inflammation, including Rheumatoid Arthritis, curcumin showed to inhibit inflammatory cell proliferation, invasion, and angiogenesis through multiple molecular targets and mechanisms of action, such as down-regulation of inflammatory transcription factors, cytokines,......related to expression of RA(374).
Bromelain, a group of protein digesting enzymes found in pineapples (Ananas comosus) used in traditional medicine as inflammatory agent and to treat pains, strains, and muscle aches and pains and ease back pain and chronic joint pain, skin diseases, etc.(467,376), through its the anti-inflammatory and analgesic properties may be the next potential target of pharmaceutical agent to reduce symptoms of rheumatoid arthritis(377). In the comparison for the effectiveness of cyclosporin A (5 mg/kg/day and 10 mg/kg/day orally); a mixture of enzymes containing pure substances (bromelain, trypsin, rutin) in the same ratio as in Phlogenzym (PHL, 150 mg/kg, twice daily, the mixture combined with cyclosporin A significantly inhibited both inflammation and destructive arthritis-associated changes, the Research Institute of Rheumatic Diseases suggested(378).
Furthermore, according to Dr. Bazzichi L and the research team at University of Pisa, bromelain may have a potential in activate autoreactive B cells induced the role of autoimmunity in the pathogenesis of rheumatoid arthritis, as self-perpetuing disorder(379).
Boswellia serrata used as incense in religious and cultural ceremonies and in medicine over thousands of year may be the potential source for treatment of RA through its abilities to inhibit proinflammatory cytokines and modulation of antioxidant status(380) as well as inhibition of TNF-α (a cell signaling protein (cytokine) involved in systemic inflammation) and nitric oxide (NO) production(381).
Dr. Ammon HP, said" autoimmune diseases - formation of oxygen radicals and proteases (for example elastase) play an important destructive role,......From the pharmacological properties of
Dan Shen with the pharmaceutical name of Radix Salvia miltiorrhizae, is a bitter and slightly cold herb, used mainly in traditional Chinese medicine for tonifying blood(494,383) has expressed the therapeutic effect on RA through its constituent ryptotanshinone (CTS),(384) through the inhibition of NF-κB signaling, the pro inflammatory cytokines.
The joint study lead by the West China Second Hospital, Sichuan University, injection of Salvia miltiorrhiza, a water‑soluble agent, derived from Salvia miltiorrhiza (SM), restores apoptosis of fibroblast-like synoviocytes and Bax mRNA expression levels of which related to the expression of synovial hyperplasia in RA(385).
Rheumatoid arthritis (RA) is a common worldwide public health problem especially in China, many RA formula has been used in the clinic and some of these TCM formulas have been existed over thousands of years in ancient China(388) with potential mechanisms such as inhibited osteoclast proliferation, suppressed fibroblast, decreased the expression of inflammatory cytokines, blocking signal pathways, etc.).
Kynurenic acid (KYNA), an endogenous neuromodulator and neuroprotector consisting anti-inflammatory, anti-oxidative and pain reliving properties, may be a propential herbal formula for prevention and treatment of Rheumatoid Arthritis due to activity involved in the synovial fluid of patients with rheumatoid arthritis(387).
Furthermore, application of Keishibukuryogan has shown to decreased tender joint count, swollen joint count and DAS(28) decreased significantly with CRP and inflammatory cytokines remained unchanged(391) in RA 's patient.
Furhtermore, the study from DR. Nanjundaiah SM and research team at the University of Maryland School of Medicine also found that the herbal formula expressed inhibition of symptoms of RA through a significant reduction in the levels of chemokines (RANTES, MCP-1, MIP-1α, and GRO/KC), MMPs (MMP 2 and 9), as well as cytokines (IL-6 and IL-17) by by suppressing the mediators of immune pathology(395)
4. Phytodolor (STW 1)
Phytodolor, a fixed herbal formulation containing alcoholic extracts of aspen leaves and bark (Populus tremula), common ash bark (Fraxinus excelsior), and golden rod herb (Solidago virgaurea),
may consist a potential effect on relieving symptoms of rheumatoid arthritis, the Australian Catholic University study suggested(396). DR Huber B said, " ....daily dose of either 3 x 30 drops of Phytodolor N .... administered over 3 weeks, ... improvements obtained were identical to those in the group receiving in part considerably higher doses of NSAIDs and placebo"(397)
In fact, the effectiveness of the herbal formula use for treatment of different subtypes of rheumatic diseases, such as painful inflammatory or degenerative rheumatic diseases(398), probably due to its antiinflammatory, antioedematous, antioxidative and analgesic properties(398).
5. Wu-tou decoction
Wu-tou decoction, containg 5 active herbs, Radix Aconiti (Wu Tou), Herba Ephedrae (Ma Huang), Radix Astragali (Huang Qi), Raidix Paeoniae Alba (Bai Shao) and Radix Glycytthizae (Gan Cao), has been used in traditional Chinese medicine for treatment of rheumatoid arthritis (RA), probably through anti-inflammatory and antioxidant activities(399), including effected on the expression of MMP-1 and MMP-13 in the joint of CIA rats and in human fibroblast-likesynoviocytes of rheumatoid arthritis(400).
(4a) Death rates and causes of death in patients with rheumatoid arthritis: a population-based study by Sihvonen S1, Korpela M, Laippala P, Mustonen J, Pasternack A(PubMed)
(7) We should not forget the foot: relations between signs and symptoms, damage, and function in rheumatoid arthritis by Baan H1, Drossaers-Bakker W, Dubbeldam R, van de Laar M.(PubMed)
(8) Pain and joint mobility explain individual subdimensions of the health assessment questionnaire (HAQ) disability index in patients with rheumatoid arthritis by Häkkinen A1, Kautiainen H, Hannonen P, Ylinen J, Arkela-Kautiainen M, Sokka T.(PubMed)
(9) Gait pattern in rheumatoid arthritis by Weiss RJ1, Wretenberg P, Stark A, Palmblad K, Larsson P, Gröndal L, Broström E.(PubMed)
(10) Valgus deformities of the feet and characteristics of gait in patients who have rheumatoid arthritis by Keenan MA1, Peabody TD, Gronley JK, Perry J.(PubMed)
(11) Gait analysis of the lower limb in patients with rheumatoid arthritis: a systematic review by Baan H1, Dubbeldam R, Nene AV, van de Laar MA.(PubMed)
(13) Strengthening And stretching for Rheumatoid Arthritis of the Hand (SARAH). A randomised controlled trial and economic evaluation by Williams MA1, Williamson EM1, Heine PJ1, Nichols V1, Glover MJ2, Dritsaki M2, Adams J3, Dosanjh S1, Underwood M1, Rahman A4, McConkey C1, Lord J1,Lamb SE1.(PubMed)
(14) Transcutaneous electrical nerve stimulation (TENS) for the treatment of rheumatoid arthritis in the hand by Brosseau L1, Judd MG, Marchand S, Robinson VA, Tugwell P, Wells G, Yonge K(PubMed)
(15) A randomized two-year study of the effects of dynamic strength training on muscle strength, disease activity, functional capacity, and bone mineral density in early rheumatoid arthritis by Häkkinen A1, Sokka T, Kotaniemi A, Hannonen P.(PubMed)
(16) Muscular strength as a strong predictor of mortality: A narrative review by Volaklis KA1, Halle M2, Meisinger C3.(PubMed)
(17) Personer med reumatoid artrit bör uppmanas till fysisk aktivitet.[Article in Swedish]by Brodin N1, Swärdh E1.(PubMed)
(18) Microchimerism in the rheumatoid nodules of patients with rheumatoid arthritis by Chan WF1, Atkins CJ, Naysmith D, van der Westhuizen N, Woo J, Nelson JL.(PubMed)
(19) Rheumatoid Nodules by Tilstra JS1, Lienesch DW2.(PubMed)
(26) Efficacy of modified-release versus standard prednisone to reduce duration of morning stiffness of the joints inrheumatoid arthritis (CAPRA-1): a double-blind, randomised controlled trial by Buttgereit F1, Doering G, Schaeffler A, Witte S, Sierakowski S, Gromnica-Ihle E, Jeka S, Krueger K, Szechinski J, Alten R.(PubMed)
(27) Change of psychological distress and physical disability in patients with rheumatoid arthritis over the last two decades by Overman CL1, Jurgens MS, Bossema ER, Jacobs JW, Bijlsma JW, Geenen R.(PubMed)
(28) Optimizing Rheumatoid Arthritis Therapy: Using Objective Measures of Disease Activity to Guide Treatment by Owens GM1(PubMed)
(29) Physical activity, disability, and quality of life in older adults by Motl RW1, McAuley E.(PubMed)
(30) Concurrent psychiatric disorders are associated with significantly poorer quality of life in patients with rheumatoid arthritis by Mok CC1, Lok EY, Cheung EF(PubMed)
(31) Pain and the brain: chronic widespread pain by Arnold LM1(PubMed)
(32) Neuropsychiatric syndromes in patients with systemic lupus erythematosus and rheumatoid arthritis by Hanly JG1, Fisk JD, McCurdy G, Fougere L, Douglas JA(PubMed)
(33) miR-573 is a negative regulator in the pathogenesis of rheumatoid arthritis by Wang L1, Song G2, Zheng Y3, Wang D4, Dong H4, Pan J1, Chang X3.(PubMed)
(34) Altered expression of microRNA-203 in rheumatoid arthritis synovial fibroblasts and its role in fibroblast activation by Stanczyk J1, Ospelt C, Karouzakis E, Filer A, Raza K, Kolling C, Gay R, Buckley CD, Tak PP, Gay S, Kyburz D.(PubMed)
(35) Abnormal networks of immune response-related molecules in bone marrow cells from patients with rheumatoid arthritis as revealed by DNA microarray analysis by Lee HM1, Sugino H, Aoki C, Shimaoka Y, Suzuki R, Ochi K, Ochi T, Nishimoto N.(PubMed)
(36) What is the consequence of an abnormal lipid profile in patients with type 2 diabetes or the metabolic syndrome? by Windler E1(PubMed)
(37) Potential mechanisms leading to the abnormal lipid profile in patients with rheumatoid arthritis versus healthy volunteers and reversal by tofacitinib by Charles-Schoeman C1, Fleischmann R, Davignon J, Schwartz H, Turner SM, Beysen C, Milad M, Hellerstein MK, Luo Z, Kaplan IV, Riese R, Zuckerman A,McInnes IB.(PubMed)
(38) [Association between systemic inflammation and autoimmunity parameters and plasma lipid in patients withrheumatoid arthritis].[Article in Chinese]by Xue C1, Liu WL, Sun YH, Ding RJ, Hu DY.(PubMed)
(39) Lp(a) lipoprotein and lipids in patients with rheumatoid arthritis: serum levels and relationship to inflammation by Dursunoğlu D1, Evrengül H, Polat B, Tanriverdi H, Cobankara V, Kaftan A, Kiliç M.(PubMed)
(40) High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis by
Eyre S, Bowes J, Diogo D, Lee A, Barton A, Martin P, Zhernakova A, Stahl E, Viatte S, McAllister K, Amos CI, Padyukov L, Toes RE, Huizinga TW, Wijmenga C,Trynka G, Franke L, Westra HJ, Alfredsson L, Hu X, Sandor C, de Bakker PI, Davila S, Khor CC, Heng KK, Andrews R, Edkins S, Hunt SE, Langford C, Symmons D; Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate; Wellcome Trust Case Control Consortium, Concannon P, Onengut-Gumuscu S,Rich SS, Deloukas P, Gonzalez-Gay MA, Rodriguez-Rodriguez L, Ärlsetig L, Martin J, Rantapää-Dahlqvist S, Plenge RM, Raychaudhuri S, Klareskog L,Gregersen PK, Worthington J.(PubMed)
(48) How age and sex affect the erythrocyte sedimentation rate and C-reactive protein in early rheumatoid arthritis by Siemons L1, Ten Klooster PM, Vonkeman HE, van Riel PL, Glas CA, van de Laar MA.(PubMed)
(49) Age at onset determines severity and choice of treatment in early rheumatoid arthritis: a prospective study by Innala L, Berglin E, Möller B, Ljung L, Smedby T, Södergren A, Magnusson S, Rantapää-Dahlqvist S, Wållberg-Jonsson S.(PubMed)
(50) IL7R gene expression network associates with human healthy ageing by Passtoors WM1, van den Akker EB2, Deelen J3, Maier AB4, van der Breggen R1, Jansen R5, Trompet S6, van Heemst D7, Derhovanessian E8, Pawelec G8, van Ommen GJ9, Slagboom PE3, Beekman M3.(PubMed)
(51) Gender, body mass index and rheumatoid arthritis disease activity: results from the QUEST-RA Study by Jawaheer D, Olsen J, Lahiff M, Forsberg S, Lähteenmäki J, da Silveira IG, Rocha FA, Magalhães Laurindo IM, Henrique da Mota LM, Drosos AA, Murphy E,Sheehy C, Quirke E, Cutolo M, Rexhepi S, Dadoniene J, Verstappen SM, Sokka T; QUEST-RA.(PubMed)
(52) Women, men, and rheumatoid arthritis: analyses of disease activity, disease characteristics, and treatments in the QUEST-RA study by Sokka T, Toloza S, Cutolo M, Kautiainen H, Makinen H, Gogus F, Skakic V, Badsha H, Peets T, Baranauskaite A, Géher P, Ujfalussy I, Skopouli FN, Mavrommati M, Alten R, Pohl C, Sibilia J, Stancati A, Salaffi F, Romanowski W, Zarowny-Wierzbinska D, Henrohn D, Bresnihan B, Minnock P, Knudsen LS, Jacobs JW,Calvo-Alen J, Lazovskis J, Pinheiro Gda R, Karateev D, Andersone D, Rexhepi S, Yazici Y, Pincus T; QUEST-RA Group.(PubMed)
(53) Socioeconomic and employment status of patients with rheumatoid arthritis in Korea by Kwon JM1, Rhee J, Ku H, Lee EK.(PubMed)
(54) Body mass index and the risk of rheumatoid arthritis: a systematic review and dose-response meta-analysis by Qin B1, Yang M2,3, Fu H4, Ma N5, Wei T6, Tang Q7, Hu Z8, Liang Y9, Yang Z10, Zhong R11.(PubMed)
(55) Association between body composition and inflammatory activity in rheumatoid arthritis. A systematic review.[Article in English, Spanish]by Alvarez-Nemegyei J1, Buenfil-Relloy FA2, Pacheco-Pantoja EL3.(PubMed)
(56) Racial disparities in treatment preferences for rheumatoid arthritis by Constantinescu F1, Goucher S, Weinstein A, Fraenkel L.(PubMed)
(57) The association of race and ethnicity with disease expression in male US veterans with rheumatoid arthritis by Mikuls TR1, Kazi S, Cipher D, Hooker R, Kerr GS, Richards JS, Cannon GW.(PubMed)
(58) Smoking and rheumatoid arthritis by Chang K1, Yang SM2, Kim SH3, Han KH4, Park SJ5, Shin JI2.(PubMed)
(59) [Smoking--a risk factor for rheumatoid arthritis development].[Article in Danish] by Christensen AF1, Lindegaard HM, Junker P.(PubMed)
(60) Cigarette smoking and rheumatoid arthritis by Albano SA1, Santana-Sahagun E, Weisman MH.(PubMed)
(61) Family history as a risk factor for rheumatoid arthritis: a case-control study by Koumantaki Y1, Giziaki E, Linos A, Kontomerkos A, Kaklamanis P, Vaiopoulos G, Mandas J, Kaklamani E.(PubMed)
(62) Familial risks and heritability of rheumatoid arthritis: role of rheumatoid factor/anti-citrullinated protein antibody status, number and type of affected relatives, sex, and age by Frisell T1, Holmqvist M, Källberg H, Klareskog L, Alfredsson L, Askling J.(PubMed)
(63) Risk factors for the development of rheumatoid arthritis by Oliver JE1, Silman AJ.(PubMed)
(64) Risk of rheumatoid arthritis following vaccination with tetanus, influenza and hepatitis B vaccines among persons 15-59 years of age by Ray P1, Black S, Shinefield H, Dillon A, Carpenter D, Lewis E, Ross P, Chen RT, Klein NP, Baxter R; Vaccine Safety Datalink Team.(PubMed)
(65) Can immunisation trigger rheumatoid arthritis? by D P Symmons and K Chakravarty(PubMed)
(64a) Comparative usefulness of C-reactive protein and erythrocyte sedimentation rate in patients with rheumatoid arthritis by Wolfe F1.(PubMed)
(65a) Erythrocyte sedimentation rate, C-reactive protein, or rheumatoid factor are normal at presentation in 35%-45% of patients with rheumatoid arthritis seen between 1980 and 2004: analyses from Finland and the United States by Sokka T1, Pincus T.(PubMed)
(66) Effect of nonsteroidal antiinflammatory drugs on the C-reactive protein level in rheumatoid arthritis: a meta-analysis of randomized controlled trials by Tarp S1, Bartels EM, Bliddal H, Furst DE, Boers M, Danneskiold-Samsøe B, Rasmussen M, Christensen R.(PubMed)
(67) Prevalence and outcomes of anemia in rheumatoid arthritis: a systematic review of the literature by Wilson A1, Yu HT, Goodnough LT, Nissenson AR.(PubMed)
(68) Anti-CCP antibodies: the past, the present and the future by van Venrooij WJ1, van Beers JJ, Pruijn GJ.(PubMed)
(69) Anti-citrullinated protein antibodies (ACPA) in early rheumatoid arthritis by Suwannalai P1, Trouw LA, Toes RE, Huizinga TW(PubMed)
(70) Expression of allograft inflammatory factor-1 in peripheral blood monocytes and synovial membranes in patients with rheumatoid arthritis by Pawlik A1, Kotrych D2, Paczkowska E3, Roginska D3, Dziedziejko V4, Safranow K4, Machalinski B5.(PubMed)
(71) Elevated expression of interleukin-7 receptor in inflamed joints mediates interleukin-7-induced immune activation in rheumatoid arthritis by Hartgring SA1, van Roon JA, Wenting-van Wijk M, Jacobs KM, Jahangier ZN, Willis CR, Bijlsma JW, Lafeber FP.(PubMed)
(72) Interferon-gamma-inducing activity of interleukin-18 in the joint with rheumatoid arthritis by Yamamura M1, Kawashima M, Taniai M, Yamauchi H, Tanimoto T, Kurimoto M, Morita Y, Ohmoto Y, Makino H.(PubMed)
(73) [Risk factors for bone mineral density changes in patients with rheumatoid arthritis and fracture risk assessment].[Article in Chinese] by Wang Y1, Hao YJ1, Deng XR1, Li GT1, Geng Y1, Zhao J1, Zhou W1, Zhang ZL1.(PubMed)
(74) The relationship between soft tissue swelling, joint space narrowing and erosive damage in hand X-rays of patients with rheumatoid arthritis by Kirwan J1, Byron M, Watt I.(PubMed)
(80) Increased frequency of osteoporosis and BMD below the expected range for age among South Korean women with rheumatoid arthritis by Lee SG1, Park YE, Park SH, Kim TK, Choi HJ, Lee SJ, Kim SI, Lee SH, Kim GT, Lee JW, Lee JH, Baek SH.(PubMed)
(81) A multicenter cross sectional study on bone mineral density in rheumatoid arthritis. Italian Study Group on Bone Mass in Rheumatoid Arthritis by Sinigaglia L1, Nervetti A, Mela Q, Bianchi G, Del Puente A, Di Munno O, Frediani B, Cantatore F, Pellerito R, Bartolone S, La Montagna G, Adami S.(PubMed)
(82) A case of rheumatoid arthritis with methotrexate related lymphoproliferative diseases of the knee by Abe A1, Wakaki K2, Ishikawa H1, Ito S1, Murasawa A1.(PubMed)
(83) Clinical characteristics and incidence of methotrexate-related lymphoproliferative disorders of patients withrheumatoid arthritis by Yoshida Y1, Takahashi Y, Yamashita H, Kano T, Kaneko H, Mimori A(PubMed)
(84) Neurologic complications of systemic lupus erythematosus, sjögren syndrome, and rheumatoid arthritis by Bhattacharyya S1, Helfgott SM2.(PubMed)
(85) Late-onset neutropenia after treatment with rituximab for rheumatoid arthritis and other autoimmune diseases: data from the AutoImmunity and Rituximab registry by Salmon JH1, Cacoub P2, Combe B3, Sibilia J4, Pallot-Prades B5, Fain O6, Cantagrel A7, Dougados M8, Andres E9, Meyer O10, Carli P11, Pertuiset E12, Pane I13, Maurier F14, Ravaud P13, Mariette X15, Gottenberg JE16.(PubMed)
(86) Late-onset neutropenia in patients with rheumatoid arthritis after treatment with rituximab by Abdulkader R1, Dharmapalaiah C, Rose G, Shand LM, Clunie GP, Watts RA.(PubMed)
(87) Carpal tunnel syndrome caused by volar dislocation of the lunate in a patient with rheumatoid arthritis by Oka Y1, Tokunaga D, Fujiwara H, Hojo T, Takatori R, Kubo T.(PubMed)
(88) Heart involvement in rheumatoid arthritis: systematic review and meta-analysis by Corrao S1, Messina S, Pistone G, Calvo L, Scaglione R, Licata G.(PubMed)
(89) Scabies in a Patient with Rheumatoid Arthritis Treated with Adalimumab - A Case Report by Marković I, Pukšić S, Gudelj Gračanin A, Čulo MI, Mitrović J, Morović-Vergles J1.(PubMed)
(90) Prevalence of dry eye syndrome and Sjogren's syndrome in patients with rheumatoid arthritis by Kosrirukvongs P1, Ngowyutagon P, Pusuwan P, Koolvisoot A, Nilganuwong S.(PubMed)
(91) A study of the prevalence of sicca symptoms and secondary Sjögren's syndrome in patients with rheumatoid arthritis, and its association to disease activity and treatment profile by Haga HJ1, Naderi Y, Moreno AM, Peen E.(PubMed)
(92) [Multiple cerebral infarction associated with cerebral vasculitis in rheumatoid arthritis].[Article in Japanese]by Ohta K1, Tanaka M, Funaki M, Sakauchi M, Suzuki N.(PubMed)
(93) Recovery from rheumatoid cerebral vasculitis by low-dose methotrexate by Ohno T1, Matsuda I, Furukawa H, Kanoh T.(PubMed)
(109) Lower omega-3 fatty acids are associated with the presence of anti-cyclic citrullinated peptide autoantibodies in a population at risk for future rheumatoid arthritis: a nested case-control study by Gan RW1, Young KA1, Zerbe GO2, Demoruelle MK3, Weisman MH4, Buckner JH5, Gregersen PK6, Mikuls TR7, O'Dell JR7, Keating RM8, Clare-Salzler MJ9,Deane KD3, Holers VM3, Norris JM10.(PubMed)
(111) 4 Natural Remedies for Rheumatoid Arthritis(About health)
(112) Critical review: vegetables and fruit in the prevention of chronic diseases by Boeing H1, Bechthold A, Bub A, Ellinger S, Haller D, Kroke A, Leschik-Bonnet E, Müller MJ, Oberritter H, Schulze M, Stehle P, Watzl B.(PubMed)
(113) Greater variety in fruit and vegetable intake is associated with lower inflammation in Puerto Rican adults by Bhupathiraju SN1, Tucker KL.(PubMed)
(114) A pilot study of a Mediterranean-type diet intervention in female patients with rheumatoid arthritis living in areas of social deprivation in Glasgow by McKellar G1, Morrison E, McEntegart A, Hampson R, Tierney A, Mackle G, Scoular J, Scott JA, Capell HA.(PubMed)
(115) Nutrient intake of patients with rheumatoid arthritis is deficient in pyridoxine, zinc, copper, and magnesium by Kremer JM1, Bigaouette J.(PubMed)
(116) [Role of diet on chronic inflammation prevention and control - current evidences].[Article in Portuguese] by Geraldo JM1, Alfenas Rde C.(PubMed)
(117) Weight Loss, the Obesity Paradox, and the Risk of Death in Rheumatoid Arthritis by Baker JF1, Billig E2, Michaud K3, Ibrahim S1, Caplan L4, Cannon GW5, Stokes A6, Majithia V7, Mikuls TR8.(PubMed)
(118) Paradoxical effect of body mass index on survival in rheumatoid arthritis: role of comorbidity and systemic inflammation by Escalante A1, Haas RW, del Rincón I.(PubMed)
(119) The diet-induced proinflammatory state: a cause of chronic pain and other degenerative diseases? by Seaman DR.(PubMed)
(120) Osteoarthritis and rheumatoid arthritis pannus have similar qualitative metabolic characteristics and pro-inflammatory cytokine response by Furuzawa-Carballeda J1, Macip-Rodríguez PM, Cabral AR.(PubMed)
(121) Anti-inflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis by Adam O1, Beringer C, Kless T, Lemmen C, Adam A, Wiseman M, Adam P, Klimmek R, Forth W.(PubMed)
(122) Dietary fish oil and olive oil supplementation in patients with rheumatoid arthritis. Clinical and immunologic effects by Kremer JM1, Lawrence DA, Jubiz W, DiGiacomo R, Rynes R, Bartholomew LE, Sherman M.(PubMed)
(123) The Effect of Stopping Smoking on Disease Activity in Rheumatoid Arthritis (RA). Data from BARFOT, a Multicenter Study of Early RA by Andersson ML1, Bergman S, Söderlin MK.(PubMed)
(124) Rheumatoid arthritis and occupation by SNORRASON E.(PubMed)
(125) Occupation, occupational exposure to chemicals and rheumatological disease. A register based cohort study by Lundberg I1, Alfredsson L, Plato N, Sverdrup B, Klareskog L, Kleinau S.(PubMed)
(126) Habitual Physical Activity, Sedentary Behaviour and Bone Health in Rheumatoid Arthritis by Prioreschi A1, Makda MA2, Tikly M2, McVeigh JA1.(PubMed)
(162) Nutraceuticals of anti-inflammatory activity as complementary therapy for rheumatoid arthritis.
(175) Psychological interventions for rheumatoid arthritis: a meta-analysis of randomized controlled trials by Astin JA1, Beckner W, Soeken K, Hochberg MC, Berman B.(PubMed)
(176) Psychological interventions for rheumatoid arthritis: examining the role of self-regulation with a systematic review and meta-analysis of randomized controlled trials by Knittle K1, Maes S, de Gucht V.(PubMed)
(177) Low-level laser therapy in different stages of rheumatoid arthritis: a histological study by Alves AC1, de Carvalho PT, Parente M, Xavier M, Frigo L, Aimbire F, Leal Junior EC, Albertini R.(PubMed)
(178) Effect of low-level laser therapy on the expression of inflammatory mediators and on neutrophils and macrophages in acute joint inflammation by Alves AC, Vieira R, Leal-Junior E, dos Santos S, Ligeiro AP, Albertini R, Junior J, de Carvalho P.(PubMed)
(179) [The influence of intravenous laser therapy on the endothelial function and the state of microcirculation in the patients presenting with rheumatoid arthritis].[Article in Russian] by Kulova LA, Burduli NM.(PubMed)
(180) Assessment of the effectiveness of low-level laser therapy on the hands of patients with rheumatoid arthritis: a randomized double-blind controlled trial by Meireles SM1, Jones A, Jennings F, Suda AL, Parizotto NA, Natour J.(PubMed)
(181) What is occupation therapy(Canadian association of occupation therapy)
(182) Occupational therapy for rheumatoid arthritis by Steultjens EM1, Dekker J, Bouter LM, van Schaardenburg D, van Kuyk MA, van den Ende CH.(PubMed)
(183) [Occupational therapy in rheumatoid arthritis: what rheumatologists need to know?].[Article in Portuguese] by de Almeida PH1, Pontes TB2, Matheus JP2, Muniz LF3, da Mota LM3.(PubMed)
(184) Effects of Prosorba column apheresis in patients with chronic refractory rheumatoid arthritis by
(272) The antioxidant vitamins A, C, E and selenium in the treatment of arthritis: a systematic review of randomized clinical trials by Canter PH1, Wider B, Ernst E.(PubMed)
(302) Topical capsaicin in dermatologic and peripheral pain disorders by Rumsfield JA1, West DP.(PubMed)
(303) Neuromuscular electrostimulation techniques: historical aspects and current possibilities in treatment of pain and muscle waisting by Heidland A1, Fazeli G, Klassen A, Sebekova K, Hennemann H, Bahner U, Di Iorio B.(PubMed)
(304) [Combination of modern physiotherapeutic methods in rehabilitation of patients with osteoarthrosis andrheumatoid arthritis after arthroscopic surgery on the knee joint].[Article in Russian] by Men'shikova IV.(PubMed)
(307) What is the evidence for rest, ice, compression, and elevation therapy in the treatment of ankle sprains in adults? by van den Bekerom MP1, Struijs PA, Blankevoort L, Welling L, van Dijk CN, Kerkhoffs GM.(PubMed)
(308) Thermotherapy for treating rheumatoid arthritis by Robinson V1, Brosseau L, Casimiro L, Judd M, Shea B, Wells G, Tugwell P.(PubMed)(309) Thermotherapy for treating rheumatoid arthritis by Welch V1, Brosseau L, Shea B, McGowan J, Wells G, Tugwell P.(PubMed)
(310) Rheumatoid arthritis: failure of daily heat therapy to affect its progression by Mainardi CL, Walter JM, Spiegel PK, Goldkamp OG, Harris ED Jr.(PubMed)
(311) Treating arthritis with locally applied heat or cold by Oosterveld FG1, Rasker JJ.(PubMed)
(315) Acupuncture and electroacupuncture for the treatment of rheumatoid arthritis by Casimiro L1, Barnsley L, Brosseau L, Milne S, Robinson VA, Tugwell P, Wells G.(PubMed)
(316) Acupuncture for pain relief in patients with rheumatoid arthritis: a systematic review by Wang C1, de Pablo P, Chen X, Schmid C, McAlindon T.(PubMed)
(317)Acupuncture in the treatment of rheumatoid arthritis: a double-blind controlled pilot study.
Tam LS1, Leung PC, Li TK, Zhang L, Li EK.(PubMed)
(360) [Therapy of degenerative diseases of the musculoskeletal system with South African devil's claw(Harpagophytum procumbens DC)].[Article in German] by Wegener T1(PubMed)
(361) Selected CAM therapies for arthritis-related pain: the evidence from systematic reviews by Soeken KL1.(PubMed)
(362) Can active components of licorice, glycyrrhizin and glycyrrhetinic acid, lick rheumatoid arthritis by Huang QC1, Wang MJ2, Chen XM1, Yu WL2, Chu YL1, He XH1, Huang RY1.(PubMed)
(363) Ascidian tunicate extracts attenuate rheumatoid arthritis in a collagen-induced murine model. by Hong SH, Kwone JT, Lee JH, Lee S, Lee AY, Cho WY, Bat-Erdene M, Choi BD, Cho MH.(PubMed)
(364) Glycyrol suppresses collagen-induced arthritis by regulating autoimmune and inflammatory responses by Fu Y1, Zhou H1, Wang S1, Wei Q1.(PubMed)
(365) Nutraceuticals of anti-inflammatory activity as complementary therapy for rheumatoid arthritis by Al-Okbi SY1.(PubMed)
(366) Evaluation of disease modifying activity of Coriandrum sativum in experimental models by Nair V1, Singh S, Gupta YK.(PubMed)
(367) Neuromodulators for pain management in rheumatoid arthritis by Richards BL1, Whittle SL, Buchbinder R.(PubMed)
(368) Treatment of arthritis with topical capsaicin: a double-blind trial by Deal CL1, Schnitzer TJ, Lipstein E, Seibold JR, Stevens RM, Levy MD, Albert D, Renold F.(PubMed)
(370) Potential benefits of green tea polyphenol EGCG in the prevention and treatment of vascular inflammation inrheumatoid arthritis by Riegsecker S1, Wiczynski D, Kaplan MJ, Ahmed S.(PubMed)
(371) Green tea EGCG, T cells, and T cell-mediated autoimmune diseases by Wu D1, Wang J, Pae M, Meydani SN.(PubMed)
(372) The effect of curcumin and its nanoformulation on adjuvant-induced arthritis in rats by Zheng Z1, Sun Y2, Liu Z1, Zhang M1, Li C1, Cai H3.(PubMed)
(381) Inhibition of LPS-induced TNF-α and NO production in mouse macrophage and inflammatory response in rat animal models by a novel Ayurvedic formulation, BV-9238 by Dey D1, Chaskar S, Athavale N, Chitre D(PubMed)
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