rheumatoid arthritis

What is rheumatoid arthritis

Rheumatoid arthritis is a chronic inflammatory disease where your immune system mistakenly attacks the linings of your joints. This results in joint pain, stiffness, swelling, and destruction. Joints are where two or more bones join together, such as at your knees, hips, or shoulders. In some people, rheumatoid arthritis can also damage a wide variety of body systems, including the skin, eyes, lungs, heart and blood vessels.

Rheumatoid arthritis causes pain, swelling, and stiffness. If joints on one side of your body have rheumatoid arthritis, usually those joints on the other side do too. This disease often occurs in more than one joint. Rheumatoid arthritis can affect any joint in the body. In some people, rheumatoid arthritis can also cause the lining of the joints to become damaged and deformed. If you have this disease, you also may feel sick and tired, and sometimes get fevers.

  • Although rheumatoid arthritis can affect any joint in the body, rheumatoid arthritis is most commonly found in the hands, wrists, feet, and knees. Usually, if it is found in one hand, it will appear in the other as well.
  • Sometimes rheumatoid arthritis can cause problems with body parts other than your joints such as your heart, lungs, eyes, or mouth.
  • Rheumatoid arthritis usually lasts many years or an entire lifetime. For some people, rheumatoid arthritis can last for only a few months to a few years with treatment, although this is rare.
  • The symptoms of rheumatoid arthritis (pain, swelling, stiffness) can get worse for some periods of time (called a “flareup”) and then get better for some periods of time.

Figure 1. Rheumatoid arthritis

rheumatoid arthritis

How common is rheumatoid arthritis ?

  • Rheumatoid arthritis is less common than other kinds of arthritis such as osteoarthritis.
  • More than 1 million people in the United States have rheumatoid arthritis.
  • Women are more likely to have rheumatoid arthritis than men. About 7 out of every 10 people with rheumatoid arthritis are women.
  • Although rheumatoid arthritis can happen at any age, it usually develops between ages 30 and 50.

When to see a doctor

Make an appointment with your doctor if you have persistent discomfort and swelling in your joints.

Rheumatoid arthritis causes

The cause of rheumatoid arthritis is unknown, but researchers think the condition may be passed down in families. The pain and symptoms of rheumatoid arthritis happen when your immune system (the system of the body that helps defend you from germs) attacks the healthy lining of your joints. Doctors are not sure why the immune system in some people attacks their joints, although a genetic component appears likely. While your genes don’t actually cause rheumatoid arthritis, they can make you more susceptible to environmental factors — such as infection with certain viruses and bacteria — that may trigger the disease.

  • Rheumatoid arthritis occurs when your immune system attacks the synovium — the lining of the membranes that surround your joints.

The resulting inflammation thickens the synovium, which can eventually destroy the cartilage and bone within the joint.

The tendons and ligaments that hold the joint together weaken and stretch. Gradually, the joint loses its shape and alignment.

Risk factors

Factors that may increase your risk of rheumatoid arthritis include:

  • Your sex. Women are more likely than men to develop rheumatoid arthritis.
  • Age. Rheumatoid arthritis can occur at any age, but it most commonly begins between the ages of 40 and 60.
  • Family history. If a member of your family has rheumatoid arthritis, you may have an increased risk of the disease.
  • Smoking. Cigarette smoking increases your risk of developing rheumatoid arthritis, particularly if you have a genetic predisposition for developing the disease. Smoking also appears to be associated with greater disease severity.
  • Environmental exposures. Although uncertain and poorly understood, some exposures such as asbestos or silica may increase the risk for developing rheumatoid arthritis. Emergency workers exposed to dust from the collapse of the World Trade Center are at higher risk of autoimmune diseases such as rheumatoid arthritis.
  • Obesity. People who are overweight or obese appear to be at somewhat higher risk of developing rheumatoid arthritis, especially in women diagnosed with the disease when they were 55 or younger.

Complications of Rheumatoid arthritis

Rheumatoid arthritis increases your risk of developing:

  • Osteoporosis. Rheumatoid arthritis itself, along with some medications used for treating rheumatoid arthritis, can increase your risk of osteoporosis — a condition that weakens your bones and makes them more prone to fracture.
  • Rheumatoid nodules. These firm bumps of tissue most commonly form around pressure points, such as the elbows. However, these nodules can form anywhere in the body, including the lungs.
  • Dry eyes and mouth. People who have rheumatoid arthritis are much more likely to experience Sjogren’s syndrome, a disorder that decreases the amount of moisture in your eyes and mouth.
  • Infections. The disease itself and many of the medications used to combat rheumatoid arthritis can impair the immune system, leading to increased infections.
  • Abnormal body composition. The proportion of fat compared to lean mass is often higher in people who have rheumatoid arthritis, even in people who have a normal body mass index (BMI).
  • Carpal tunnel syndrome. If rheumatoid arthritis affects your wrists, the inflammation can compress the nerve that serves most of your hand and fingers.
  • Heart problems. Rheumatoid arthritis can increase your risk of hardened and blocked arteries, as well as inflammation of the sac that encloses your heart.
  • Lung disease. People with rheumatoid arthritis have an increased risk of inflammation and scarring of the lung tissues, which can lead to progressive shortness of breath.
  • Lymphoma. Rheumatoid arthritis increases the risk of lymphoma, a group of blood cancers that develop in the lymph system.

Signs and symptoms of rheumatoid arthritis

Signs and symptoms of rheumatoid arthritis may include:

  • Tender, warm, swollen joints
  • Joint stiffness that is usually worse in the mornings and after inactivity
  • Fatigue, fever and weight loss

Early rheumatoid arthritis tends to affect your smaller joints first — particularly the joints that attach your fingers to your hands and your toes to your feet.

As the disease progresses, symptoms often spread to the wrists, knees, ankles, elbows, hips and shoulders. In most cases, symptoms occur in the same joints on both sides of your body.

About 40 percent of the people who have rheumatoid arthritis also experience signs and symptoms that don’t involve the joints. Rheumatoid arthritis can affect many non-joint structures, including:

  • Skin
  • Eyes
  • Lungs
  • Heart
  • Kidneys
  • Salivary glands
  • Nerve tissue
  • Bone marrow
  • Blood vessels

Rheumatoid arthritis signs and symptoms may vary in severity and may even come and go. Periods of increased disease activity, called flares, alternate with periods of relative remission — when the swelling and pain fade or disappear. Over time, rheumatoid arthritis can cause joints to deform and shift out of place.

How Rheumatoid arthritis is Diagnosed

Rheumatoid arthritis can be difficult to diagnose in its early stages because the early signs and symptoms mimic those of many other diseases. There is no one blood test or physical finding to confirm the diagnosis.

During the physical exam, your doctor will check your joints for swelling, redness and warmth. He or she may also check your reflexes and muscle strength.

Blood tests

People with rheumatoid arthritis often have an elevated erythrocyte sedimentation rate (ESR, or sed rate) or C-reactive protein (CRP), which may indicate the presence of an inflammatory process in the body. Other common blood tests look for rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) antibodies.

Imaging tests

Your doctor may recommend X-rays to help track the progression of rheumatoid arthritis in your joints over time. MRI and ultrasound tests can help your doctor judge the severity of the disease in your body.

Rheumatoid arthritis diet

With the increasing evidence of altered microbiota (gut microbiome) in the gut of rheumatoid arthritis patients being responsible for pathogenesis as well as disease progression 1), it should be desirable for doctors to advocate a supplemental “diet therapy” to rheumatoid arthritis patients. Various dietary plans for rheumatoid arthritis have been reported since 2) and are being repeatedly projected 3), such as medically supervised 7–10 days fasting 4), vegan 5) or Mediterranean diets 6). We hereby discuss the reported dietary interventions that clearly indicate clinically and statistically significant and beneficial long-term effects for relieving symptoms, delay in disease progression and associated damages in rheumatoid arthritis patients. The outcomes of published randomized clinical trials performed on rheumatoid arthritis patients to observe the effect of various dietary interventions have been summarized in Table 1. A pictorial representation of effects put by various factors on progression/remission of rheumatoid arthritis is depicted in Figure ​2.

Figure 2. Factors contributing to severity of rheumatoid arthritis

Factors contributing to severity of rheumatoid arthritis

Note: The picture summarizes various factors contributing to severity of rheumatoid arthritis (RA) and diets which cause remission of symptoms (left side of image). The effects of various factors on state of disease are shown at the right side of the image. The upper half of the image shows highly inflamed joints and synovial membrane, increased infiltration of immune cells in joints on exposure to environmental factors or food antigens. Lower half of the image shows effect of various diets in reducing inflammation, immune cell infiltration, and reducing the severity of disease.

[Source 7)]

Table 1. Summary of clinical trials of various dietary interventions in rheumatoid arthritis (RA)

ReferenceSubjects, duration, and dietOutcome
Kjeldsen-Kragh et al. 8)Diet group—27 patients
7–10 days subtotal fasting (limited amount of nutritional supplements)
3.5 months on individually adjusted gluten-free vegan diet followed by lactovegetarian diet
Control group—26 patients
Ordinary diet throughout the study
After 1 month of diet
Reduction in number of tender (p < 0.0002) and swollen joints (p < 0.04), Ritchie articular index (RAI) (p < 0.0004), pain (p < 0.0001), morning stiffness duration (p < 0.0002), grip strength, HAQ score, erythrocyte sedimentation rate (ESR) (p < 0.002), C-reactive protein (CRP) (p < 0.005), and WBC count (p < 0.0001) which were maintained even after 1 year of administration of diet
Key note: Improvement can be maintained by continuing with individually adjusted diet
Kjeldsen-Kragh et al. 9)Diet group—27 patients
7–10 days subtotal fasting
3.5 months on individually adjusted gluten-free vegan diet followed by lactovegetarian diet
Control group—26 patients
Ordinary diet throughout the study
After 1 month of treatment
Significant decrease in leukocyte and platelet count (p < 0.003), IgM rheumatoid factors (p < 0.02), IgG, C3 (p < 0.04) and C4 complement components (p < 0.01), calprotectin (p < 0.03) and C3 activation products in diet responders in vegetarian diet group
Key note: Dietary interventions can help in improvement of disease in some RA patients
Peltonen et al. 10)Diet group—27 patients
7–10 days subtotal fasting
3.5 months on individually adjusted gluten-free vegan diet followed by 9 months lactovegetarian diet administration
Control group—26 patients
Ordinary diet throughout the study
Significant difference in fecal fatty acid profile at different times during the dietary intervention as compared to baseline in diet group was observed (p < 0.005). Fecal flora was significantly different between vegan diet (post 1 month treatment) and lactovegetarian diet period (p < 0.001). Significant difference in fecal flora was also observed between high improvement to low improvement groups (p < 0.001). This difference was also found at 1 month (vegan diet) and 13 months (lactovegetarian diet)
Key note: Study finds association between disease activity and intestinal flora indicating impact of diet on disease progression
Haugen et al. 11)Diet group—27 patients
7–10 days subtotal fasting
3.5 months on individually adjusted gluten-free vegan diet followed by lactovegetarian diet
Control group—26 patients
Ordinary diet throughout the study
Post 3.5 months of vegan diet
Significant reduction in plasma fatty acid 20:3n-6 (p < 0.0001) and 20:4n-6 (p < 0.01) was observed which reversed to baseline concentration after lactovegetarian diet
Significant reduction in 20:5n-3 post-vegan diet (p < 0.0001) and lactovegetarian diet (p < 0.01)
No significant difference in fatty acid concentration between diet responders and non-responders after vegan or lactovegetarian
Key note: Change in fatty acid profile could not explain disease improvement
Haugen et al. 12)Diet group—17 patients
7–10 days fasting
3.5 months on gluten-free vegan diet followed by 9 months lactovegetarian diet administration
Control group—17 patients
Ordinary diet throughout the study
After 1 month
Significant reduction in body mass index (BMI) and triceps skin fold thickness in diet group as compared with baseline (post 1 month) (p < 0.001) and controls (post study) (p = 0.04; p < 0.01)
Key note: One year of dietary intervention had a minor impact on nutritional status of patients. No significant differences in other clinical variables studied were observed between the two groups
Kjeldsen-Kragh et al. 13)Patients of above study were called for follow-up; 1 year post-trial. All responders and half non-responders were still on diet. Most of the patients eliminated those food which they thought aggravated their diseaseDiet responders showed greatest change in clinical variables including HAQ (p < 0.04) and RAI (p < 0.02) from the baseline. Significant improvements were observed in all clinical variables including pain (p < 0.005), morning stiffness duration (p < 0.005), tender joint (p < 0.0003), RAI (p < 0.0001) and swollen joints (p < 0.05) except grip strength as compared to non-responders and controls
Key note: Patients gained benefit from manipulation of diet which can be maintained for long term
Kjeldsen-Kragh et al. 14)Diet group—26 RA patients
7–10 days fasting followed by 3.5 months of gluten-free vegetarian diet
Agalactosyl IgG antibodies reduced in RA patients and correlated significantly (p = 0.04) with clinical improvement post fasting which was not observed after administration of vegetarian diet
Key note: IgG glycosylation may improve disease status during fasting
Fraser et al. 15)Diet group—10 patients
7 days subtotal fasting
13 patients—ketogenic diet for 7 days
All patients followed 2 weeks period of re-feeding on lactovegetarian diet
Post 7 days fasting
Significant decrease in serum IL-6 levels in fasting group (p < 0.03) on seventh day as compared to baseline and after re-feeding. Improvement was observed in ESR, CRP, and tender joint counts post 7 days fasting
Key note: Fasting improves disease activity in RA patients
Michalsen et al. 16)16 RA patients and 35 fibromyalgia patients
21 patients—vegetarian Mediterranean diet (MD)
30 patients—intermittent modified 8 days fasting therapy
No difference in the fecal bacterial counts, concentration of secretory immunoglobulin or pH of the stool within or between the two diet groups. Post 2 weeks of study, fasting RA patients showed more clinical improvement as compared to non-fasting patients
Key note: Clinical improvement is not related to intestinal flora
Abendroth et al. 17)22 patients—medical fasting for 7 days
28 patient—MD
Both groups observed significant decrease in disease activity score (DAS) (p < 0.001). Significantly higher decrease in pain in fasting group on seventh day (p = 0.049). No significant difference was observed in total fatty acid profile, butyrate and propionate but acetate increased significantly (p = 0.044) in fasting group and decreased significantly in MD group. No significant correlation between diet induced changes in short chain fatty acids and disease activity changes was observed
Key note: Change of intestinal microflora and relation with diet needs further studies
Sköldstam et al. 18)Diet group—26 patients—MD
Control group—25 patients
After 12 weeks of study, MD group showed significant reduction in DAS28 score (p < 0.001), decrease in HAQ (p = 0.020), and improvement in SF-36 health survey in two dimensions (p = 0.018). Out of 14 efficacy variables, 9 had shown improvement in diet group
Key note: MD administration reduced disease activity in RA patients
Hafström et al. 19)Diet group—38 patients—gluten-free vegan diet
Control group—28 patients
Vegan group showed higher response rate and significant improvement in all variables except CRP. The diet responders have significant improvement in CRP (p < 0.05). Levels of IgG anti-gliadin (p = 0.0183) and anti-β-lactoglobulin (p = 0.0162) levels have significantly reduced from baselines in vegan diet groups. After 6 and 12 months, there was significant increase in Larsen score, number of erosions and joint count in both groups
Key note: Diet change may reduce immunoreactivity to certain food antigens and some RA patients and may have certain clinical benefits
Peltonen et al. 20)Diet groupuncooked vegan diet rich in lactobacilli
Control group—normal omnivorous diet.
Diet group had significant change in fecal microflora from pre-test and post-test samples (p < 0.001) but not in control group. Significant difference was found on comparison of test group with control group at 1 month (p < 0.001). Significant difference in microflora was observed between low and high improvement index group after 1 month (p = 0.001) and after intervention (p = 0.029) but not in pre-test samples
Key note: Fecal microflora changes with diet and helps in improvement of RA
McDougall et al. 21)24 RA patients—very low fat vegan dietSignificant decrease in energy intake (p < 0.001), fats (p < 0.001) and proteins (p < 0.001) and significant increase in carbohydrate intake (p < 0.001) with decrease in weight. RA symptoms decreased including pain (p < 0.004), morning stiffness (p < 0.04), joint swelling (p < 0.02), and tenderness (p < 0.01) with increased joint mobility (p < 0.001)
Key note: RA symptoms significantly decrease in moderate or severe RA patients on administration of very low fat vegan diet
Elkan et al. 22)Diet group—38 patients—gluten-free vegan diet
Control group—28 patients
After 12 months, vegan group showed decreased BMI, LDL, and weight. DAS28 (p = 0.002) and HAQ scores (p = 0.010) decreased significantly in at least 3 months when compared to baseline and CRP decreased (p = 0.008) at 12 months. In vegan group, at least in 3 months, total cholesterol (p < 0.001), LDL (p < 0.001) and LDL/HDL ratio (p < 0.001) significantly decreased but TGs and HDL did not change. OxLDL significantly decreased (p = 0.021) after 3 months in responders group. IgM anti-phosphorylcholine increased significantly trend wise and was significant at twelfth month (p = 0.057)
Key note: Vegan diet (gluten free) is anti-inflammatory and atheroprotective
Sköldstam et al. 23)Study 1: Diet group—14 patients—lactovegetarian diet
Control group—10 patients
Study 2:
13 patients—control period of 2 months
7 patients—control period of 5 months followed by vegan diet for following 4 months
Study 3: Diet group—26 patients—Cretan MD
Control group—25 patients
Study 1: At end of study, diet group reported reduction in pain with a significant weight loss (p < 0.001) but no change in disease outcome and no change in control subjects were observed
Study 2: During vegan diet, all 20 patients were reported to have significant reduction in pain score, increased functional capacity, and significant weight loss (p < 0.001), which was not observed during the control period
Study 3: 9 out of 14 disease outcome measures were improved with a significant loss in weight (p < 0.001) and decreased pain when compared to controls
Statistically significant correlation was found between diet and three disease outcome variables including ΔAcute-Phase Response (p = 0.007), ΔPain Score (p = 0.005), and ΔPhysical Function (p = 0.002)
Key note: Improvement of RA on administration of Vegan, Mediterranean, or lactovegetarian diet is not related to reduction of body weight
Ågren et al. 24)Diet group—16 patients—vegan diet
Control group—13 patients
Significant reduction (p < 0.001) of serum total, LDL cholesterol, and phospholipid concentrations were observed in vegan diet group. Sitosterol concentration increased and that of campesterol decreased giving a significant greater ratio of sitosterol: campestrol (p < 0.001) in vegan diet group when compared to control group
Key note: Serum cholesterol, cholestanol, phospholipids, and lathosterol decrease in uncooked vegan diet
Hänninen et al. 25)42 patients divided in two groups—Uncooked vegan diet for 3 months and omnivorous control groupsThe RA symptoms reduced in diet group and reverted on restarting omnivorous diet. There was a significant negative correlation between degree of subjective adaptation system and decreased activity of RA (p = 0.003)
Key note: Vegan diet rich in fibers, antioxidants, and lactobacilli improved RA in some patients
Vaghef-Mehrabany et al. 26)Diet group—22 patients—108 colony-forming unit (CFU) of Lactobacillus casei 01 for 8 weeks
24 patients—placebo with maltodextrin for 8 weeks
Number of tender and swollen joints, serum hs-CRP levels, DAS, visual analog scale (VAS) score, tumor necrosis factor (TNF)-α, and IL-12 decreased significantly in probiotic group. Significant increase in IL-10 (p = 0.02), IL-10/IL-12 (p = 0.01), and IL-10/TNF-α (p = 0.03) was observed in the probiotic group
Key note: Disease activity and inflammatory status improved in patients on L. casei 01 supplementation
Vaghef-Mehrabany et al. 27)Diet group—22 patients—108 CFU of L. casei 01 for 8 weeks
24 patients—placebo with maltodextrin for 8 weeks
No significant difference was observed within or between probiotic and placebo group in serum malondialdehyde, total antioxidant capacity, and catalase activity. Erythrocyte superoxide dismutase activity decreased significantly in probiotic group and glutathione peroxidase activity decreased in both groups. Difference between two groups was insignificant for both groups at the end of the study
Key note: Probiotic supplementation does not have significant effect on oxidative status of RA patients
Hatakka et al. 28)Diet group—8 patients—L. rhamnosusGG (LGG) (≥5 × 109 CFU/capsule), twice a day for 12 months
13 patients—placebo group
Mean number of tender and swollen joints decreased in probiotic group. A 71% reduction in disease activity was observed in probiotic group and 30% in placebo group. Serum IL-1β increased in probiotic group and decreased in placebo group. At the end of the study, fecal recovery of LGG was increased from 25 to 86% in probiotic from baseline and decreased from 23 to 0% in placebo group
Key note: More patients administered with LGG reported subjective well-being
Zamani et al. 29)Diet group—30 patients—L. acidophilus (2 × 109 CFU/g), L. casei (2 × 109 CFU/g), and Bifidobacterium bifidum (2 × 109 CFU/g)
30 patients—placebo group received capsule filled with cellulose
Probiotic group observed significant decrease in DAS28 score (p = 0.01), serum insulin levels (p = 0.03), HOMA-B (p = 0.03), serum hs-CRP concentrations (p < 0.001), LDL cholesterol (p = 0.07), and total cholesterol (p = 0.09) compared to placebo group. No significant effect was observed in tender and swollen joints, VAS pain, glucose homeostasis parameters, biomarkers of oxidative stress, and lipid profiles after probiotic administration
Key note: Patients had significant benefit by incorporating probiotic supplements in diet
Vaghef-Mehrabany et al. 30)Diet group—22 patients—108 CFU of L. casei 01
24 patients—placebo group received similar capsules with maltodextrin
No significant difference within or between group for anthropometric and demographic parameters, physical activity was observed. Serum lipid did not change within any group significantly or in between the groups
Key note: L. casei 01 could not improve serum lipid in patients
Alipour et al. 31)Diet group—22 patients—108 CFU of L. casei 01
24 patients—placebo group
Probiotic decreased serum high sensitivity CRP levels (p = 0.009), counts of swollen (p = 0.003) and tender joints (p = 0.03), DAS (p < 0.05), and global health score (p = 0.00). Global health score decreased significantly in placebo group as well. At the end of study, more patients in probiotic group showed moderate response to the supplementation according to EULAR criteria but all were non-responders in placebo group. The difference of IL-6, IL-12 (0.00), TNF-α (p = 0.002), and IL-10 (p = 0.007) cytokines between the two groups was statistically significant
Key note: Probiotic can be an adjunct therapy for relieving symptoms
de los Angeles Pineda et al. 32)Diet group—15 patients—L. rhamnosus GR-1 and L. reuteri RC-14 with 2 billion CFU viable bacteria
14 patients—placebo
Significant difference was observed in HAQ score (p = 0.02) in probiotic group when compared to baseline but not between groups. The pro-inflammatory cytokines including GM-CSF, IL-6, IL-1α, TNF-α, and IL-15 decreased but not significantly in the probiotic group. No difference was observed in cytokine levels and DAS
Key note: Probiotics did not improve RA but functional improvements were reported
Mandel et al. 33)Diet group—22 patients—Bacillus coagulans GBI-30, 6086 (2 billion CFU) with green tea extract, methylsulfonylmethane, and vitamins and minerals (including vitamins A, B, C, D, E, folic acid, and selenium)
22 patients—placebo group received microcrystaline cellulose
Probiotic group showed statistically significant improvement in patient pain assessment score (p = 0.052) and pain scale (p = 0.046) as compared to baseline. Improvement was observed in patient global assessment, patient self-assessed disability, and reduction in total CRP but statistical difference was not found in physician global assessment or physician assessment of painful and swollen joints. Ability to walk 2 miles was marginally significant (p = 0.072) and ability to participate in daily activities was more in probiotic group
Key note: Adjunctive therapy with probiotics serves effective for RA patients
Kavanagh et al. 34)Diet group—24 patients—elemental diet 028 (E028) (4 weeks) followed by food reintroduction where food unlikely to cause intolerance were introduced first followed by those which were known to cause intolerance one at a time. Food worsening RA was eliminated
23 patients—control groups were given E028 as a substitute to any drink along with normal diet
After 4 weeks of elemental diet, the diet group showed significant increase in grip strength (p = 0.008), decrease in RAI (p = 0.006), and loss of weight as compared to control diet group. CRP concentrations were different between the two groups but not significant. Statistically significant correlation was observed between loss of weight and grip strength at 1 week (p = 0.009) and 4 weeks (p = 0.027) in the diet group
Key note: Elemental diet may improve some parameters in RA patients
Podas et al. 35)Diet group—21 patients—elemental diet E028
9 patients—oral prednisolone 15 mg/day
All clinical parameters of RA including early morning stiffness, VAS, RAI, and HAQ improved significantly (p < 0.05) in both groups. Clinical parameters were improved by 20% in 72% patients in elemental diet group as compared to 78% in steroid group
Key note: A 2 week treatment with elemental diet is as effective as 15 mg/day of prednisolone in improvement of clinical parameters. RA may start within the intestine due to reaction to various food antigens
Holst-Jensen et al. 36)Diet group—15 patients—commercial liquid diet (TU). TU contains hydrolyzed soy protein, triglycerides and carbohydrates, methionine, tryptophan, vitamins, and trace elements and is lactose free
Control group—15 patients
4 weeks of treatment caused statistical significant improvements in pain (p = 0.02), HAQ score (p = 0.03) and reduction in BMI (p = 0.001). After the study, the number of swollen joints, ESR and General assessment of health, average during the last week lowered but not statistically significant. No difference was observed in the control group. Only one patient in the diet group achieved complete remission
Key note: Peptide diet can improve some subjective and objective parameters of the disease. This diet may help those patients who have diet aggravated RA
Van de Laar and Van der Korst 37)Diet group—45 patients—allergen free diet
49 patients—allergen restricted with lactoproteins and yellow dyes
During first 4 weeks, patients followed their normal diets followed by 4 weeks of assigned diets and then administration of normal diet for 4 weeks
No significant difference could be found in clinical effects between the allergen free and allergen restricted diet. Only 9 out of 94 patients enrolled in the study showed favorable response but the disease relapsed after readministration of usual diets
Key note: Some patients have food-aggravated RA, and they can be controlled by administering allergen-free food
Karatay et al. 38)20 patients—positive skin prick test (SPT) to food extracts
20 patients—negative SPT
All patients first fasted to most common allergenic food for 12 days. Food challenge was performed for PPG with allergenic food and for PNG with corn and rice for 12 days. Followed which allergenic foods were removed from respective groups
On food challenge in PPG, ESR (p < 0.05), CRP (p = 0.001), TNF-α (p < 0.01), and IL-1β (p < 0.05) increased and was also observed on re-elimination of food. In PNG, pain decreased significantly (p < 0.05) on food challenge. At end of re-elimination phase, differences were observed in between two groups in pain, duration of stiffness, number of tender and swollen joints, CRP levels, and RAI but not in HAQ and ESR levels. 72% patients in PPG group and 18% in PNG group suffered from disease aggravation on food challenge which continued in re-elimination phase
Key note: Diet changes on individual level may change disease activity in patients
[Source 39)]

Based on findings discussed in Khanna et al review 40), they have designed an anti-inflammatory food chart (Table ​2) that may aid in reducing signs and symptoms of rheumatoid arthritis. This may not cure the patients; however, an effective incorporation of these food items in the daily food plan may help to reduce their disease activity, delay disease progression, and reduce joint damage, and eventually a decreased dose of drugs administered for therapeutic treatment of patients. The believe that an ideal meal can include raw or moderately cooked vegetables (lots of greens, legumes), with addition of spices like turmeric and ginger 41), seasonal fruits 42), probiotic yogurt 43); all of which are good sources of natural antioxidants and deliver anti-inflammatory effects. The patient should avoid any processed food, high salt 44), oils, butter, sugar, and animal products 45). Dietary supplements like vitamin D 46), cod liver oil 47), and multivitamins 48) can also help in managing rheumatoid arthritis. This diet therapy with low impact aerobic exercises can be used for a better degree of self-management of rheumatoid arthritis with minimal financial burden 49). A better patient compliance is, however, always necessary for effective care and management of rheumatoid arthritis.

Table 2. Recommended anti-inflammatory food chart

FruitsDried plums, grapefruits, grapes, blueberries, pomegranate, mango (seasonal fruit), banana, peaches, apples
CerealsWhole oatmeal, whole wheat bread, whole flattened rice
LegumesBlack soybean, black gram
Whole grainsWheat, rice, oats, corn, rye, barley, millets, sorghum, canary seed
SpicesGinger, turmeric
HerbsSallaki, ashwagandha
OilsOlive oil, fish oil, borage seed oil (in encapsulated form)
MiscellaneousYogurt (curd), green tea, basil (tulsi) tea
[Source 50)]

Rheumatoid arthritis treatment

Although there is no cure for rheumatoid arthritis, treatment can:

  • Relieve pain and swelling
  • Slow down or stop joint damage
  • Help lower the number of symptom “flareups” (times when pain or swelling is the worst)
  • Improve your ability to do daily activities such as bathing, getting dressed, doing chores, reaching, and lifting

Rheumatoid arthritis medications

The types of medications recommended by your doctor will depend on the severity of your symptoms and how long you’ve had rheumatoid arthritis.

NSAIDs. Nonsteroidal anti-inflammatory drugs (NSAIDs) can relieve pain and reduce inflammation. Over-the-counter NSAIDs include ibuprofen (Advil, Motrin IB) and naproxen sodium (Aleve). Stronger NSAIDs are available by prescription. Side effects may include ringing in your ears, stomach irritation, heart problems, and liver and kidney damage.

Steroids. Corticosteroid medications, such as prednisone, reduce inflammation and pain and slow joint damage. Side effects may include thinning of bones, weight gain and diabetes. Doctors often prescribe a corticosteroid to relieve acute symptoms, with the goal of gradually tapering off the medication.

Disease-modifying antirheumatic drugs (DMARDs). These drugs can slow the progression of rheumatoid arthritis and save the joints and other tissues from permanent damage. Common DMARDs include methotrexate (Trexall, Otrexup, Rasuvo), leflunomide (Arava), hydroxychloroquine (Plaquenil) and sulfasalazine (Azulfidine).

Sometimes DMARDs and corticosteroids are taken together to treat rheumatoid arthritis.

What are DMARDs ?

Disease-modifying antirheumatic drugs (DMARDs) are a family of medicines that stop your body’s immune system from attacking and destroying joints. If you have severe rheumatoid arthritis symptoms or are not getting enough relief from pain relievers or corticosteroids, your doctor may suggest a disease-modifying antirheumatic drug (DMARD). Disease-modifying antirheumatic drugs (DMARDs)s may be taken with each other or together with pain relievers and corticosteroids.

There are two kinds of Disease-modifying antirheumatic drugs (DMARDs): nonbiologic and biologic.

Nonbiologic Disease-modifying antirheumatic drugs (DMARDs)

Like most medicines, nonbiologic DMARDs are produced from chemicals. They are usually taken daily or weekly as pills, but some can also be given as shots. Nonbiologic DMARDs include:

  • Hydroxychloroquine (Plaquenil®)
  • Leflunomide (Arava®)
  • Methotrexate (Folex®, Rheumatrex®, Trexall®)
  • Sulfasalazine (Azulfidine EN-Tabs®, Sulfazine®)

What does research say about nonbiologic DMARDs ?

How well they work to treat rheumatoid arthritis:

  • Methotrexate (Folex®, Rheumatrex®, Trexall®) and sulfasalazine (Azulfidine EN-Tabs®, Sulfazine®) work about the same to reduce symptoms, reduce the number of joints affected, improve the ability to do daily activities, and slow down or stop joint damage.
  • Leflunomide (Arava®) appears to work about as well as methotrexate, but there is not enough research to know this for certain.

Side effects:

  • All nonbiologic DMARDs appear to cause about the same amount of side effects, but there is not enough research to know this for certain.

Biologic Disease-modifying antirheumatic drugs (DMARDs)

Biologic agents also known as biologic response modifiers, this newer class of DMARDs includes abatacept (Orencia), adalimumab (Humira), anakinra (Kineret), certolizumab (Cimzia), etanercept (Enbrel), golimumab (Simponi), infliximab (Remicade), rituximab (Rituxan), tocilizumab (Actemra) and tofacitinib (Xeljanz).

These drugs can target parts of the immune system that trigger inflammation that causes joint and tissue damage. These types of drugs also increase the risk of infections.

Biologic DMARDs are usually most effective when paired with a nonbiologic DMARD, such as methotrexate.

Biologic DMARDs are proteins similar to those made in your body, but these proteins are created in laboratories. Biologic DMARDs must be given as shots or through an IV (intravenous) tube into a vein in your arm. Biologic DMARDs include:

  • Abatacept (Orencia®)
  • Adalimumab (Humira®)
  • Anakinra (Kineret®)
  • Certolizumab pegol (Cimzia®)
  • Etanercept (Enbrel®)
  • Golimumab (Simponi®)
  • Infliximab (Remicade®)
  • Rituximab (Rituxan®)
  • Tocilizumab (Actemra®)

Some biologic DMARDs such as infliximab (Remicade®), rituximab (Rituxan®), and tocilizumab (Actemra®) must be given through an IV tube at a doctor’s office or clinic. This could take up to 2 hours. Other biologic DMARDs come in injection pens that you can use at home.

Most biologic DMARDs are given once a month, once every other week, or once a week. Your doctor may change your schedule depending on how well you are doing.

Side effects vary but may include liver damage, bone marrow suppression and severe lung infections.

What does research say about biologic DMARDs ?

How well they work to treat rheumatoid arthritis:

  • Biologic DMARDS work to decrease or completely stop symptoms, improve the ability to do daily activities, and slow down or stop joint damage.

Side effects:

  • Taking a biologic DMARD increases the risk of developing serious infections.
  • Taking biologic DMARDs for long periods of time does not increase the risk of having serious side effects.

What does research say about how nonbiologic and biologic DMARDs compare to each other ?

How well they work to treat rheumatoid arthritis:

  • The biologic DMARDs adalimumab (Humira®) and etanercept (Enbrel®) help decrease symptoms about the same as the nonbiologic DMARD methotrexate.

Side effects:

  • There is not enough research to know if certain side effects happen more often with nonbiologic or biologic DMARDs.

Table 3. Possible Side Effects of Disease-modifying antirheumatic drugs (DMARDs)

Nonbiologic DMARDsBiologic DMARDs
  • Upset stomach
  • Nausea
  • Diarrhea
  • Hair loss
  • Mouth sores
  • Rash or serious skin reactions
  • Liver, kidney, or lung problems
  • Redness, swelling, itching, bruising, or pain in the area where the shot was given
  • Sinus infection (sore throat, runny nose, hoarseness)
  • Headache
  • Nausea
  • Diarrhea
Possible Serious Side Effects
  • In rare cases, the nonbiologic DMARD methotrexate and some biologic DMARDs (including adalimumab [Humira®], etanercept [Enbrel®], golimumab [Simponi®], and infliximab [Remicade®]) have been associated with:
    • Serious infections such as tuberculosis (called “TB”), fungal infections such as yeast, pneumonia, or food-borne illnesses such as listeria
    • Cancer, usually lymphoma (cancer in the lymph glands, which are part of the immune system)
  • The risk of serious infections or cancer is increased by taking two or more biologic DMARDs together or by taking a biologic DMARD with a nonbiologic DMARD. The exact risk to people with RA who are taking a DMARD is not known.
  • Rituximab (Rituxan®) can cause a severe reaction the first time you take it. It could also cause a life-threatening rash.

 What are corticosteroids ?

Corticosteroids are a kind of medicine that works like a certain type of hormone in your body. Corticosteroids can help reduce swelling and stop the body’s immune system from attacking healthy joints. Corticosteroids are taken as pills, liquids, or shots and include:

  • Methylprednisolone (Depo Medrol®, Medrol®, Solu-Medrol®)
  • Prednisolone (Delta-Cortef ®, Econopred®, Orapred®, Pediapred®, Prelone®)
  • Prednisone (Liquidpred®, Deltasone®, Sterapred®)

What are the possible side effects of corticosteroids ?

Possible side effects of corticosteroids listed by the FDA include:

  • Swelling in the lower legs
  • Weight gain
  • Increased blood pressure
  • Mood swings
  • Increased pressure in the eyes

Possible side effects from taking corticosteroids for longer than a few days or weeks include:

  • High blood sugar, which can cause or worsen diabetes
  • Increased risk of infections
  • Loss of calcium from bones, which can make it easier to break a bone
  • Irregular menstrual periods
  • Thin skin that bruises easily
  • Longer time for wounds to heal.

What does research say about combining medicines ?

How well they work to treat rheumatoid arthritis:

  • If treatment with one DMARD does not relieve symptoms, taking a biologic DMARD together with the nonbiologic DMARD methotrexate works better than taking only one to improve the ability to do daily activities and slow down or stop joint damage.
  • Adding a corticosteroid to treatment with a nonbiologic DMARD improves the ability to do daily activities more than taking a nonbiologic DMARD alone.
  • Adding a corticosteroid may also slow down or stop joint damage more than taking a nonbiologic DMARD alone, but there is not enough research to know this for certain.
  • For people who have had rheumatoid arthritis for less than 3 years, taking two or three nonbiologic DMARDs plus a corticosteroid works better than taking only one nonbiologic DMARD.
  • For people who have had rheumatoid arthritis for less than 3 years, taking the nonbiologic DMARD methotrexate together with a biologic DMARD decreases or completely stops symptoms and slows down or stops joint damage in people whose rheumatoid arthritis was quickly getting worse.
  • For people who have had rheumatoid arthritis for a long time without any improvement, taking three nonbiologic DMARDs together reduces symptoms and the number of joints affected more than taking one or two nonbiologic DMARDs.

Side effects:

  • Taking a nonbiologic DMARD with a biologic DMARD does not cause more side effects than taking the biologic DMARD alone.
  • Taking two or more biologic DMARDs together can cause more serious side effects than taking only one.
  • Taking a corticosteroid together with a nonbiologic DMARD does not make treatment more difficult to tolerate.
  • In people who have had RA for less than 3 years, taking two or three nonbiologic DMARDs plus a corticosteroid does not make treatment more difficult to tolerate than taking only a nonbiologic DMARD.

What should you think about when deciding which medicine is right for you ?

More research is needed to know which rheumatoid arthritis medicines might work best for different people. There are several things to consider when choosing a medicine to treat your rheumatoid arthritis:

  • The trade-offs between the possible benefits and side effects for each medicine
  • Which medicine best fits your lifestyle, what is important to you (your values), and your preferences
  • You may want to think about how comfortable you are with taking pills, getting shots, or taking the medicine through an IV tube. You may also want to consider how often you are able to go to the doctor’s office or clinic and how much time you are able to spend there.
  • The cost of each medicine

What are the trade-offs ?

Only you and your doctor can decide whether taking a DMARD for your rheumatoid arthritis is worth the risk of possible side effects. You and your doctor should discuss:

  • The amount of pain or joint damage you have and whether treatment with a DMARD can help
  • The risk of serious side effects from DMARDs
  • Signs to look for to help you notice serious side effects so they can be treated or so your medicine can be changed
  • Whether adding a corticosteroid to your treatment with DMARDs might help
  • Other options besides DMARDs that might help your rheumatoid arthritis

What are the costs of rheumatoid arthritis medications ?

The costs to you for nonbiologic and biologic DMARDs and corticosteroids depend on:

  • Your health insurance plan
  • The amount (dose) you need
  • Whether you take the medicine as a pill, as a shot, or through an IV tube
  • Whether a generic form of the medicine is available
  • Whether the company that makes the medicine offers financial help to lower the cost

Corticosteroids can be taken for short periods of time (30 days) or longer, depending on your specific needs. The cost for corticosteroids is around $3 to $15 a month. The cost to you depends on how much of the medicine you need and how long you will need to take it.

Table 2. Wholesale Prices: Nonbiologic and Biologic DMARDs

Drug NameBrand NamePrice per MonthFormDose
Nonbiologic DMARDs
HydroxychloroquineGeneric$35–$75Tablet200–400 mg daily
LeflunomideGeneric$490Tablet20 mg daily
MethotrexateGeneric$45–$90Tablet7.5–15 mg weekly
Folex®, Rheumatrex®, Trexall®$125–$140
SulfasalazineGeneric$40Tablet2,000 mg daily
Azulfidine EN-Tabs®$120
Biologic DMARDs(Generic versions of these medicines are not available.)
AbataceptOrencia®$1,430–$2,860IV500–1,000 mg monthly
$2,530Shot125 mg weekly
AdalimumabHumira®$2,450Shot40 mg twice a month
AnakinraKineret®$2,760Shot100 mg daily
Certolizumab pegolCimzia®$2,360Shot400 mg monthly
EtanerceptEnbrel®$2,475Shot50 mg weekly
GolimumabSimponi®$2,650Shot50 mg monthly
InfliximabRemicade®$3,725–$9,300IV200–500 mg twice a month (depending on your weight)
RituximabRituxan®$15,180IV1,000 mg twice a month
TocilizumabActemra®$1,660–$3,320IV400–800 mg monthly (depending on your weight)
*Prices are the average wholesale prices from RED BOOK Online® rounded to the nearest $5. Generic prices are the middle value in the range of prices listed from different manufacturers. The actual prices of the medicines may be higher or lower than the prices listed here, depending on your health insurance and the manufacturer used by your pharmacy.
IV = intraveneous

Ask your doctor

  • Do you think a DMARD could help my rheumatoid arthritis ?
  • What serious side effects should I look for?
  • Would adding a corticosteroid to a DMARD help my rheumatoid arthritis ?
  • How long will it take until I start to feel better?
  • Is there a less expensive medicine that I could take?
  • What else can I do to help my rheumatoid arthritis ?
  • Are there specific lifestyle changes you can suggest that might help?
Physical and Occupational Therapy

Your doctor may send you to a physical or occupational therapist who can teach you exercises to help keep your joints flexible. The therapist may also suggest new ways to do daily tasks, which will be easier on your joints. For example, if your fingers are sore, you may want to pick up an object using your forearms.

Assistive devices can make it easier to avoid stressing your painful joints. For instance, a kitchen knife equipped with a saw handle helps protect your finger and wrist joints. Certain tools, such as buttonhooks, can make it easier to get dressed. Catalogs and medical supply stores are good places to look for ideas.


If medications fail to prevent or slow joint damage, you and your doctor may consider surgery to repair damaged joints. Surgery may help restore your ability to use your joint. It can also reduce pain and correct deformities.

Rheumatoid arthritis surgery may involve one or more of the following procedures:

  • Synovectomy. Surgery to remove the inflamed synovium (lining of the joint). Synovectomy can be performed on knees, elbows, wrists, fingers and hips.
  • Tendon repair. Inflammation and joint damage may cause tendons around your joint to loosen or rupture. Your surgeon may be able to repair the tendons around your joint.
  • Joint fusion. Surgically fusing a joint may be recommended to stabilize or realign a joint and for pain relief when a joint replacement isn’t an option.
  • Total joint replacement. During joint replacement surgery, your surgeon removes the damaged parts of your joint and inserts a prosthesis made of metal and plastic.

Surgery carries a risk of bleeding, infection and pain. Discuss the benefits and risks with your doctor.

Lifestyle and home remedies for rheumatoid arthritis

You can take steps to care for your body if you have rheumatoid arthritis. These self-care measures, when used along with your rheumatoid arthritis medications, can help you manage your signs and symptoms:

  • Exercise regularly. Gentle exercise can help strengthen the muscles around your joints, and it can help fight fatigue you might feel. Check with your doctor before you start exercising. If you’re just getting started, begin by taking a walk. Try swimming or gentle water aerobics. Avoid exercising tender, injured or severely inflamed joints.
  • Apply heat or cold. Heat can help ease your pain and relax tense, painful muscles. Cold may dull the sensation of pain. Cold also has a numbing effect and decreases muscle spasms.
  • Relax. Find ways to cope with pain by reducing stress in your life. Techniques such as guided imagery, distraction and muscle relaxation can all be used to control pain.

Alternative medicine

Some common complementary and alternative treatments that have shown promise for rheumatoid arthritis include:

  • Fish oil. Some preliminary studies have found that fish oil supplements may reduce rheumatoid arthritis pain and stiffness. Side effects can include nausea, belching and a fishy taste in the mouth. Fish oil can interfere with medications, so check with your doctor first.
  • Plant oils. The seeds of evening primrose, borage and black currant contain a type of fatty acid that may help with rheumatoid arthritis pain and morning stiffness. Side effects may include nausea, diarrhea and gas. Some plant oils can cause liver damage or interfere with medications, so check with your doctor first.
  • Tai chi. This movement therapy involves gentle exercises and stretches combined with deep breathing. Many people use tai chi to relieve stress in their lives. Small studies have found that tai chi may reduce rheumatoid arthritis pain. When led by a knowledgeable instructor, tai chi is safe. But don’t do any moves that cause pain.

Coping and support

The pain and disability associated with rheumatoid arthritis can affect a person’s work and family life. Depression and anxiety are common, as are feelings of helplessness and low self-esteem.

The degree to which rheumatoid arthritis affects your daily activities depends in part on how well you cope with the disease. Talk to your doctor or nurse about strategies for coping. With time you’ll learn what strategies work best for you. In the meantime, try to:

  • Take control. With your doctor, make a plan for managing your arthritis. This will help you feel in charge of your disease.
  • Know your limits. Rest when you’re tired. Rheumatoid arthritis can make you prone to fatigue and muscle weakness. A rest or short nap that doesn’t interfere with nighttime sleep may help.
  • Connect with others. Keep your family aware of how you’re feeling. They may be worried about you but might not feel comfortable asking about your pain.
  • Find a family member or friend you can talk to when you’re feeling especially overwhelmed. Also connect with other people who have rheumatoid arthritis — whether through a support group in your community or online.
  • Take time for yourself. It’s easy to get busy and not take time for yourself. Find time for what you like, whether it’s time to write in a journal, go for a walk or listen to music. Use this time to relieve stress and reflect on your feelings.

References   [ + ]