Rheumatoid Arthritis

Rheumatoid arthritis is a chronic, inflammatory, systemic autoimmune disease that affects the joints, and often times other organs, with varying severity among patients.

It initially affects small joints, then progresses to larger joints, and eventually can attack the skin, eyes, heart, kidneys, and lungs.

Often, the bone and cartilage of joints get destroyed, and tendons and ligaments weaken [1].

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All this damage to the joints causes deformities and bone erosion, usually very painful to the patient.

Rheumatoid arthritis patients experience morning stiffness of the affected joints for 30 mins to a few hours, fatigue, fever, weight loss, tender, swollen, and warm joints, and small lumps of tissue that develop under the skin (also called “rheumatoid nodules”).

Identification of the disease at initial presentation and treatment at an earlier stage can positively affect the disease course, preventing the development of joint erosions or retarding the progression of erosive disease [23].

Early diagnosis and treatment may affect disease outcomes, even to a remission state [45].

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Otherwise, many complications can follow, such as permanent joint damage requiring arthroplasty, rheumatoid vasculitis (vascular inflammation), and Felty syndrome, possibly requiring splenectomy, if inadequately addressed.

Since rheumatoid arthritis affects not only the joints, but also internal organs, it may cause permanent disability in some instances.

The risk factors for rheumatoid arthritis include age, gender, genetics, and environmental exposure (cigarette smoking, air pollutants, and occupational).

The disease typically manifests between the age of 35 to 60 years, with alternating periods of remission and exacerbation.

The condition can also afflict young children, even before the age of 16 years.

In this case, it is referred to as juvenile rheumatoid arthritis, which is similar to the original rheumatoid arthritis, except that rheumatism is not present [678].

In the West, the prevalence of rheumatoid arthritis is believed to be 1–2% [89], and 1% worldwide [10].  

Epidemiology

Incidence rates of rheumatoid arthritis are higher in northern Europe and North America compared with southern Europe.

Incidence is 29 cases/100,000 in northern Europe, 38/100,000 in North America, and 16.5/100,000 in southern Europe.

In North America and northern Europe, the disease affects 0.4% to 1% of the population, while in southern Europe, it affects 0.3% to 0.7% of the population.

The female to male ratio is 2-3:1, and the prevalence of the condition increases with age [1112].

Causes

Genetic Factors

The causes of rheumatoid arthritis are unknown. It is thought to result from the interaction between the patient’s genotype and environment.

Twin studies have shown a concordance rate of 15% to 30% among monozygotic twins and 5% among dizygotic twins.

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The heritability of rheumatoid arthritis is approximately 40% to 65% for seropositive rheumatoid arthritis and 20% for seronegative rheumatoid arthritis.

The risk of developing rheumatoid arthritis has been associated with HLA-DRB1 alleles, particularly the HLA-DRB1*04, HLA-DRB1*01, and HLA-DRB1*10. 

It has also been suggested that polymorphism in signaling transducers and activators of transcription (STAT)-4 and interleukin (IL) -10 genes also confer susceptibility to rheumatoid arthritis (RA).

Additionally, single nucleotide polymorphism (SNP) in PSORS1C1, PTPN2, and MIR 146 A genes are associated with severe disease manifestation.

Environmental Factors

Cigarette smoking seems to be the strongest environmental risk factor associated with rheumatoid arthritis.

Studies have shown that in ACPA (anti-citrullinated protein antibody) positive individuals, there is an interaction between genes and smoking that increases the risk of rheumatoid arthritis.

Microbiome Alterations

Changes in the composition and function of the intestinal microbiome have been related to rheumatoid arthritis.

The composition of the gut microbiome is altered in patients with rheumatoid arthritis (dysbiosis); rheumatoid arthritis patients have decreased gut microbiome diversity when compared with healthy individuals.

In rheumatoid arthritis, there is an increase in specific bacterial genera: Actinobacteria, Collinsella, Eggerthalla, Faecalibacterium.

Collinsella, in particular, has been shown to alter gut mucosal permeability and is related to increased severity of the disease.

Symptoms

The main symptoms of rheumatoid arthritis include achy, painful, stiff, tender, and swollen joints on both sides of the body (in opposition to classic osteoarthritis, which affects one side of the body), lack of appetite and weight loss, low-grade fever, fatigue, and weakness.

Rheumatoid arthritis patients harbor antibodies to citrullinated proteins (ACPAs).

Citrulline is an amino acid generated by post-translational modification of arginine residues by protein-arginine deaminases (a family of enzymes).

These antibodies are called anti-citrullinated protein antibodies (ACPAs) and are highly specific to rheumatoid arthritis.

ACPAs can be IgG, IgM, or IgA isotypes.

ACPAs can bind citrullinated residues on self-proteins, like vimentin, fibronectin, fibrinogen, histones, and type 2 collagen.

The binding of antibodies to proteins leads to complement activation (complement is a group of blood proteins that support the immune system).

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The presence of antibodies in rheumatoid arthritis is associated with severe disease, joint damage, and an increase in mortality.

ACPAs can be present in the serum up to 10 years before the onset of clinical symptoms, with time concentration of ACPAs and serum cytokine level increases.

In rheumatoid arthritis, the synovium (connective tissue that lines the inside of the joint capsule) is infiltrated by immune cells, which include innate immune cells (monocytes, dendritic cells, mast cells) and adaptive immune cells (Th1 (T helper 1), Th17 (T helper 17), B cells and plasma cells.

Cytokines and chemokines, like tumor necrosis factor (TNF), interleukin-6 (IL-6), granulocyte-monocyte colony-stimulating factors, oactivate endothelial cells and attract immune cells within the synovial compartment.

The fibroblast (most common type of connective tissue cell) in the rheumatoid synovium changes to an invasive phenotype.

Fibroblast and inflammatory cells lead to osteoclast (a type of bone cell that breaks down bone tissue) generation, resulting in bone erosion, which is the hallmark feature of rheumatoid arthritis.

During the early phase of the disease, the influx of inflammatory cells into the synovial membrane is apparent.

As the disease progresses, there is a proliferation of monocytes and thickening of the synovial membrane with small villous projections into the joint space, also known as rheumatoid nodules.

Rheumatoid nodules initially exhibit a small vessel vasculitis (inflammation of the blood vessels) phenomenon, followed by a chronic inflammatory granulomatous phase.

Rheumatoid nodules may be present in 20% of patients with rheumatoid arthritis and mainly occur over extensor surfaces at elbows, heels, and toes.

They’re usually not sensitive to pressure or touch.

Diagnosis

Rheumatoid arthritis can be challenging for doctors to diagnose in its initial stages, because the early signs and symptoms can mimic those of other diseases.

At an early stage (first few weeks and months), the symptoms are often very mild and may not be typical.

Someone who has had rheumatoid arthritis for a longer time, exhibits more dramatic joint alterations, that help with disease diagnosis.

During a medical appointment, the doctor or general physician will first ask about symptoms, such as painful joints, stiff joints in the morning, and general symptoms, like tiredness or exhaustion.

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It’s important that the patient will mention all his symptoms, not just the ones he/she thinks are important, as this will help the doctor to make the correct diagnosis.

If the doctor or general physician suspects that the patient has rheumatoid arthritis, they’ll refer him/her to a specialist (rheumatologist).

The typical diagnostic measures for rheumatoid arthritis include:

Physical examination

The doctor will feel the patient’s joints and check whether they are swollen, tender, or stiff.

It’s important to find out how many joints are affected and how long they’ve been inflamed.

The doctor will also look for other signs of rheumatoid arthritis, such as inflamed tear glands or rheumatoid nodules.

Blood tests

There is not one specific blood test to confirm the diagnosis, but several tests can show indications of the condition by detecting certain antibodies and signs of inflammation in the body.

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Some of the main blood tests used include erythrocyte sedimentation rate (ESR), which can help assess levels of inflammation in the body, C-reactive protein (CRP) – another indicator of inflammation, and full blood count (FBC), in order to rule out other possible causes of existing symptoms, as well as to provide an overview of the patient’s general health.

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The full blood count test can also be used to check if the patient has anemia (condition in which the lack of red blood cells causes inadequate oxygen delivery to bodily tissues).

Anemia is common in people with rheumatoid arthritis, although having anemia does not mean you have rheumatoid arthritis.

Two other tests more specific to rheumatoid arthritis are rheumatoid factors and anti-cyclic citrullinated peptide (anti-CCP) tests.

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Imaging techniques

Changes in the joints can be seen in x-ray, ultrasound images, or MRI scans.

These can help to differentiate between the types of arthritis (i.e., osteoarthritis), and can be used to monitor the progress of the condition.

Osteoarthritis vs Rheumatoid Arthritis

Rheumatoid arthritis is often confused with osteoarthritis, but there are several differences between the two conditions:

  • Osteoarthritis is primarily a degenerative joint condition, while rheumatoid arthritis is an autoimmune condition.
  • Osteoarthritis is caused by the age-related breakdown of cartilage inside the joints, and not by inflammation.
  • Osteoarthritis affects almost exclusively the joints, while rheumatoid arthritis is a systemic disease, which can affect the entire body- lungs, heart, eyes, kidneys.
  • Osteoarthritis and rheumatoid arthritis affect different joints at first.
  • In osteoarthritis, moving the joint after resting it in the daytime is often painful at first. This pain may occur several times during the day, but doesn’t last long.
  • In osteoarthritis, the joints mainly hurt when you move them, and not when you rest them.

There are also major differences concerning both the treatment and course of the two diseases.

Treatment / Management

Conventional Treatments

There is currently no cure for rheumatoid arthritis.

Rheumatoid arthritis can be managed with medication, physical therapy, and occupational therapy.

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Various support aids may also make some everyday tasks easier.

Patients should be advised to engage in regular exercise or sports activities.

Treatment options depend on these factors:

  • How severe the inflammation and symptoms are
  • How far the disease has progressed
  • The predicted further course of the disease
  • How well previous treatments have worked

Medication

Medication can reduce inflammation and help stop the disease from getting worse, relieve symptoms like pain and swelling, and help people move their joints more easily again, or maintain joint mobility for as long as possible.

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The most commonly used medications are disease-modifying, anti-rheumatic drugs (DMARDs), which are initiated as soon as the diagnosis of rheumatoid arthritis is made.

Traditional or conventional DMARDs include methotrexate, leflunomide, sulfasalazine, and hydroxychloroquine.

Biologic DMARDs include TNF (tumor necrosis factor) inhibitors: Adalimumab (Humira), Etanercept (Enbrel), Infliximab (Remicade), Golilumab (Simponi), Certolizumab (Cimzia).

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And non-TNF inhibitors: Tocilizumab (Interleukin-6 inhibitor), Abatacept (inhibits T-cell co-stimulation), Rituximab (anti-B cell) [131415].

Physical Therapy and Sports

Physical therapy and sports can help improve or maintain mobility, strength, and joint function.

Physical activity strengthens the muscles around the aching joints, providing support.

Examples of suitable types of sports include cycling, brisk walking, dancing, gentle anaerobic exercises (e.g. gentle strengthening exercises), swimming, and aqua aerobics.

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Occupational Therapy

The main aim of occupational therapy is to maintain mobility and hand strength, and to learn how to get by with rheumatoid arthritis in everyday life.

Psychological Treatment

Psychological treatments are also sometimes used to help relieve pain and minimize the impact of the disease on everyday life.

They are also supposed to help relieve disease-related anxiety and depression that some people develop.

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In advanced arthritis, various aids can compensate for many physical limitations and help patients to carry out everyday activities.

These include orthopedic shoe inserts, grabbing aids, and specially designed cutlery.

Natural Treatments

Natural treatments can make a huge impact in terms of helping lowering pain, reduce swelling, prevent further joint damage, and increase the patient’s quality of life.

Natural treatments also won’t create any unwanted side effects, which are common with arthritis medication use, such as liver damage, anemia, low platelet count, hair loss, kidney issues, and heart problems.

Some natural ways to manage rheumatoid arthritis symptoms and prevent complications include :

1. Eating an Anti-inflammatory Diet 

High-antioxidant foods and foods that are whole, unrefined, and unprocessed can help control symptoms of rheumatoid arthritis by minimizing inflammation.

A healthy “arthritis diet” should include healthy fats, like organic extra virgin olive oil and coconut oil, plenty of raw, fresh vegetables and fruits (and their juices), wild-caught fish, especially those rich in omega-3s (salmon, sardines, herring, mackerel, halibut), pasture-raised eggs, organic meats (including organ meats, such as liver), and bone broth.

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Fish, in particular, has been shown to offer some unique benefits in rheumatoid arthritis (RA) patients.

A 2018 human study revealed that rheumatoid arthritis (RA) patients who consumed fish more than twice a week experienced lower RA activity [16].

For each additional serving of fish, patients reported even lower RA activity levels.

Additionally, a lot of promising evidence concerns the beneficial anti-oxidative effects of plant polyphenols contained in fresh fruits, vegetables, and spices, for rheumatoid arthritis (RA) patients.

An example of a dietary element rich in polyphenols that may be beneficial in rheumatoid arthritis is the dried plum.

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In a study on transgenic mice overexpressing TNF (tumor necrosis factor) designed as a rheumatoid arthritis genetic model, the effects of dried plum on joint destruction were evaluated.

Month-long supplementation with dried plum not only slowed the onset of arthritis, but also reduced joints’ bone erosions compared with mice on a regular diet.

Polyphenols and neochlorogenic acid are basic components of the dried plum, and some of their known beneficial effects at the molecular level include the inhibition of TNF-induced formation of osteoclasts (a type of bone cell that breaks down bone tissue).

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The favorable anti-arthritic effect of dried plum may also be due to lowering the number of tartrate-resistant acid phosphatase (TRAP) positive cells, which are responsible for osteoclastogenesis (creation of osteoclasts).

Furthermore, nutritionally speaking, it’s very important for rheumatoid arthritis (RA) patients to completely remove foods that trigger inflammation- such as added sugar, processed food, hydrogenated/trans fats, fast food, and common allergens like gluten or pasteurized dairy.

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2. Staying Active

Although rheumatoid arthritis (RA) can cause flare-ups of pain along with limited range of motion, staying generally active is very important for managing symptoms and controlling joint inflammation.

Joint pain associated with rheumatoid arthritis (RA) tends to be worse after periods of inactivity (which is why sleeping causes morning stiffness), so exercise is helpful and beneficial [17].

The best type of physical activity for people with rheumatoid arthritis is low-impact exercise that doesn’t overly-stress sensitive joints, such as cycling, walking, water aerobics, and yoga.

An ideal exercise routine should combine a form of aerobic activity with strength training, along with stretching to improve flexibility, muscle strength, and cardiovascular health.

When symptoms worsen, extra rest can be helpful and often is necessary, however, stretching can also help manage inflammation.

3. Managing Stress and Getting Enough Sleep

Getting enough sleep and limiting emotional stress allow joints to heal optimally, so these habits are especially important during episodes of heightened inflammation, pain, swelling, and stiffness.

Fatigue and stressful episodes exacerbate inflammation and may also contribute to complications, such as muscle pains, low immunity, infections, overeating, inactivity, and weight gain.

Studies have found that incorporating relaxation techniques- such as guided meditation, yoga or stretching, deep breathing, guided imagery, and visualization — offers protection against painful episodes, since these techniques help the muscles to relax, balance hormones, decrease cortisol and strengthen the immune system.

Stress-relieving activities, having a positive mental outlook, and receiving family/friend/spouse support, have been linked with pain reduction in rheumatoid arthritis [1819]

4. Controlling Pain Naturally

Research shows that natural pain-relieving techniques, including massage therapy, acupuncture or acupressure, essential oils used on the skin, and heat/ice treatments (like ice packs or warm baths) all help manage rheumatoid arthritis symptoms.

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Many of these can also act as natural stress relievers, since they promote body awareness, help patients stay active, improve sleep, and ease stress or anxiety.

Essential oils for arthritis include eucalyptus, orange, ginger, turmeric, myrrh, and frankincense oils.

You can also try using topical treatments on the skin containing salicylates or capsaicin, which some studies show help reduce joint pain [20].

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5. Reducing Inflammation with Supplements

Anti-inflammatory supplements that can act as natural analgesics and help reduce arthritis pain include:

Conclusion

Rheumatoid arthritis (RA) is a chronic, progressive, autoimmune, rheumatic disease affecting both articular (joint-related) and extra-articular (non-joint-related) structures.

In the West, the prevalence of rheumatoid arthritis is believed to be 1–2%, and 1% worldwide.

RA affects more women than men at a ratio of 2-3:1.

The exact cause of the disease remains unknown, but it is believed to be a combination of genetics, age, environment, gut microbiota alterations affecting host immunity, and lifestyle (i.e., smoking).

Its main symptoms include joint pain, heat, redness, inflammation, morning stiffness, movement difficulties, fatigue, and low-grade fever.

Currently, there is no cure for RA, rather, symptoms are addressed on an individual basis.

All individuals have multiple exacerbations and remissions.

Close to 50% of patients with the disease become disabled within 10 years.

Besides the joint disease, individuals can suffer from many extra non-joint-related problems, which can significantly alter the quality of life.

Concerning disease diagnosis, RA can be difficult to diagnose because many other conditions cause joint stiffness and inflammation, and there is no one particular test that can pinpoint that a person has it.

Blood panel tests, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) provide the best information about the acute phase response. 

The goals of treatment for RA are to reduce joint inflammation and pain, maximize joint function, and prevent joint destruction and deformity.

Treatment regimens consist of combinations of pharmaceuticals, physical therapy, occupational therapy, educating patients about the disease, and rest.

Treatments are generally customized to a patient’s needs and depend on their overall health.

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Natural ways to treat RA symptoms include eating anti-inflammatory foods, staying active, managing stress and getting enough sleep, controlling pain naturally, and reducing inflammation through specific supplementation.

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About George Kelly

George Kelly M.Sc is a Sports Nutritionist, Functional Nutritional Therapy Practitioner (FNTP), and Metabolic Type expert. He is the CEO and lead author of Metabolic Body.


References

[1] https://pubmed.ncbi.nlm.nih.gov/28581281/
[2] https://pubmed.ncbi.nlm.nih.gov/17139662/
[3] https://pubmed.ncbi.nlm.nih.gov/17371885/
[4] https://pubmed.ncbi.nlm.nih.gov/18668546/
[5] https://pubmed.ncbi.nlm.nih.gov/19339921/
[6] https://pubmed.ncbi.nlm.nih.gov/22150039/
[7] https://pubmed.ncbi.nlm.nih.gov/27080040/
[8] https://pubmed.ncbi.nlm.nih.gov/26203933/
[9] https://pubmed.ncbi.nlm.nih.gov/17045630/
[10] https://pubmed.ncbi.nlm.nih.gov/18783739/
[11] https://pubmed.ncbi.nlm.nih.gov/30226016/
[12] https://pubmed.ncbi.nlm.nih.gov/30207568/
[13] https://pubmed.ncbi.nlm.nih.gov/30239912/
[14] https://pubmed.ncbi.nlm.nih.gov/30200078/
[15] https://pubmed.ncbi.nlm.nih.gov/30137623/
[16] https://pubmed.ncbi.nlm.nih.gov/28635117/
[17] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3042669/
[18] https://pubmed.ncbi.nlm.nih.gov/14635321/
[19] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6159751/
[20] https://pubmed.ncbi.nlm.nih.gov/19332972/


MEDICAL DISCLAIMER

This content is for informational and educational purposes only. It is not intended to provide medical advice or to take the place of such advice or treatment from a personal physician. All readers/viewers of this content are advised to consult their doctors or qualified health professionals regarding specific health questions. Neither Metabolic Body nor the publisher of this content takes responsibility for possible health consequences of any person or persons reading or following the information in this educational content. All viewers of this content, especially those taking prescription or over-the-counter medications, should consult their physicians before beginning any nutrition, supplement or lifestyle program.