Rheumatoid arthritis – signs, symptoms & risk factors

Key statistics taken from a 2017 Arthritis Research report stated that:

• Over 400,000 people in the UK have rheumatoid arthritis.
• The cost of rheumatoid arthritis to the UK economy is estimated at £3.8 – 4.8 billion.
• 1/3 of people with rheumatoid arthritis will have stopped working within 2 years of onset.

In this week’s blog we look at some of the signs, symptoms and risk factors associated with rheumatoid arthritis; including diet, lifestyle and genetics.

What is rheumatoid arthritis?

Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic joint inflammation and destruction, and is characterised by activated T cells, persistent synovitis and the production of auto-antibodies, including rheumatoid factor (RF). (Synovitis is the medical term for inflammation of the synovial membrane. This membrane lines joints that possess cavities, known as synovial joints). Typically, RA manifests as sustained inflammation of the synovium, which leads to destruction of joints. It can cause ongoing pain, swelling, stiffness and limitations in terms of movements. For most people, RA symptoms tend to flare up at times, becoming worse when inflammation levels rise.

Key Takeaways

RA can put you at a higher risk of developing other conditions, particularly if it’s not well controlled such as:

• Joints – damage can occur to bone, cartilage and tendons.  Joint deformities may also materialise.
• Carpal tunnel syndrome – the result of compression of the nerve that controls sensation and movement in the hands and can cause symptoms such as aching, numbness, tingling in the thumbs, fingers and hand.

Because RA is an inflammatory condition, this can cause inflammation to develop in other parts of your body, such as the:

• Lungs – inflammation of the lungs or lung lining can lead to pleurisy or pulmonary fibrosis, which can cause chest pain, a persistent cough and shortness of breath.
• Heart – inflammation of the tissue around the heart can lead to pericarditis, which causes chest pain.
• Eyes – inflammation of the eyes can lead to scleritis or Sjogren’s syndrome. Scleritis can cause eye redness and pain, whereas Sjogren’s syndrome can cause dry eyes.
• Blood vessels – known as vasculitis – this can lead to the thickening, weakening, narrowing and scarring of blood vessel walls.
• Spinal cord – there is an increased risk of compression on the cervical spinal cord, a condition called cervical myelopathy.

Signs and Symptoms

• Joint pain – swelling in and around certain joints lasting for six weeks or more. Any joint can become damaged due to RA, but the wrists, feet, hands, ankles and knees are most commonly affected
• Redness, heat and tenderness near inflamed joints. Pain and tenderness are usually experienced in a symmetrical pattern
• Morning stiffness – many people experience morning stiffness for several hours in the morning
• Fatigue and muscle aches
• Trouble moving normally, including bending over, climbing stairs, walking or exercising
• Possible loss of appetite or low-grade fever

Risk Factors

Lifestyle

Several lifestyle factors have been shown to play a role in RA risk, including:

• Smoking—nicotine in the bloodstream can increase rheumatoid factor levels.^(1,2)

Evidence shows that cigarette smoking can cause the body to produce antibodies that are strongly associated with the development of RA.⁽³⁾  In addition, it has been found that smoking may reduce the effect of RA treatments including anti-TNF agents and disease-modifying anti-rheumatic drugs (DMARDs).^(4,5) Smoking has been shown to worsen RA symptoms and therefore increase the overall progression and severity of the disease.⁽⁶⁾

• Diet – A poor diet and food sensitivities (foods that contribute to inflammation including high sugar/refined carbohydrate consumption, dairy, gluten).
• Weight – It has been proposed that recent trends of increasing rates of RA found in some studies could potentially be related, at least in part, to the dramatic increase in rates of obesity. Study results, however, have been mixed, with some showing an increased risk of RA among obese individuals and others showing no association. Adipocytokines, because of their association with adiposity and their pro-inflammatory effects, have been proposed as potential mediators.  Studies to date, however, have not established adipocytokines as a direct link between obesity and the development of RA.  Additionally, insulin resistance leading to increased inflammation has been proposed as another potential mechanism.⁽⁷⁾

Genetics

The association of a particular human leukocyte antigen (HLA) with (RA) was first noted in the late 1970s, when the frequency of individuals with the HLA-Dw4 serotype was found to be increased among RA patients compared with healthy controls.⁽⁸⁾

Hormones

Women are more at risk for RA than men, and many experts think this is because women are more subject to hormone fluctuations. Specifically, RA risk seems to go up when hormone levels drop, such as right after pregnancy or at menopause.

Vitamin D Deficiency

Epidemiological evidence has shown increased prevalence of several autoimmune diseases, including inflammatory bowel disease, MS, type I diabetes and rheumatoid arthritis at Northern latitudes where sun exposure is reduced; therefore, it has been suggested that vitamin D may be protective against autoimmune conditions.⁽⁹⁾

This is likely to be due to anti-inflammatory and immune modulating effects that vitamin D has demonstrated, such as regulating the production of inflammatory cytokines and inhibiting the proliferation of pro-inflammatory cells, both of which are crucial for the development of inflammatory and autoimmune diseases.

In a recent study, both forms of vitamin D – 1,25(OH)2D3 and 25(OH)D3 exhibited anti-inflammatory actions by dose-dependently inhibiting lipopolysaccharide induced production of IL-6, and TNFα (pro-inflammatory cytokines) by human monocytes (immune cells).⁽¹⁰⁾

Microbiome and leaky gut

Research strongly suggests connections between intestinal permeability (leaky gut), dysbiosis in the gut microbiome, and arthritis.⁽¹¹⁾

Dysbiosis impacts the innate immunological pathways and leads to the production of pro-inflammatory cytokines IL-1, IL-18, IL-17, TNFα, and others. The signalling pathways involve an array of molecules that are produced by autoreactive T cells. The autoreactive T cells also migrate to the peripheral immune compartments to activate the B cells to form antibody producing plasma cells. The antibodies and the plasma cells then migrate to the synovial tissues to initiate an inflammatory cascade. Macrophages, fibroblasts, osteoclasts, and proteinases are the key components of the synovial inflammatory processes.^(12,13)

Healthy intestines are naturally permeable, allowing tiny nutrient particles to flow through their lining and enter the bloodstream. Problems arise if the intestinal lining becomes damaged.  For more information, please read our blog –  Leaky Gut Syndrome – The Signs and Symptoms.

It is understood that celiac disease, type 1 diabetes, multiple sclerosis, rheumatoid arthritis, Crohn’s and several other autoimmune diseases have all been associated with leaky gut that allows the passage of these antigens from the intestinal flora into the bloodstream and this then challenges the immune system to produce a response that can target any organ or tissue in people that are genetically predisposed.

Helpful foods

Mediterranean Diet

Some studies have reported a decrease in pain and disease activity with Mediterranean diet in RA.⁽¹⁴⁾ In a 12 week randomised trial in 51 patients with RA, Mediterranean diet intervention demonstrated reduction in inflammatory activity, an increase in physical function, and improved vitality.⁽¹⁵⁾

Gluten-Free Diet

Gluten, a food-derived antigen, is the driver of the autoimmunity seen in coeliac disease. The altered intestinal permeability found in coeliac patients, coupled with a genetic predisposition and altered immunological response, may result in a systemic immune response that is directed against sites other than the gut. Food or gut-derived antigens may have a role in the pathogenesis of other autoimmune disorders including rheumatoid arthritis.⁽¹⁶⁾

A gluten-free diet has been associated with benefits in patients with RA. A gluten-free vegan diet for 1 year was shown to significantly reduce levels of antibodies to β-lactoglobulin and gliadin and disease activity in patients with RA.⁽¹⁷⁾

Nutrient Support

Flavonoids

Flavonoids, found abundantly in foods and beverages of plant origin, such as fruits, vegetables, tea, cocoa and wine, possess antioxidant, antimicrobial, and anti-inflammatory properties of these agents in atherosclerosis, rheumatoid arthritis, and other inflammatory conditions.

Good Dietary Sources of flavonoids:

• Red, blue, and purple berries; red and purple grapes
• Teas (particularly white, green, and oolong), cocoa-based products
• Apples
• Onions, kale, broccoli, apples, berries, teas
• Parsley, thyme, celery, hot peppers
• Citrus fruit and juices, e.g., oranges, grapefruits, lemons
• Legumes

Omega-3 Fatty Acids

Long-term intake of fish and other sources of omega-3 fatty acids have been reported to be protective for development of RA.  Some studies support the role of omega-3 fatty acid supplementation as a valuable therapeutic option to improve symptoms, tender joint count, duration of morning stiffness, and the requirement for non-steroidal anti-inflammatories in RA.⁽¹⁸⁾

Good Sources of Omega-3 Fatty Acids:

• Wild caught salmon (tinned or fresh)
• Sardines (tinned in olive oil)
• Herring (tinned or fresh)
• Flaxseed oil
• Hempseeds

Vitamin D

Vitamin D has widely demonstrated activities on immune system and evidence suggests that low vitamin D status may be implicated in the pathogenesis of rheumatoid arthritis (RA). The relationship between vitamin D and RA is complex, also because deficient vitamin D status, which is very common in RA patients, can contribute to the increased risk of osteoporosis typical of RA.⁽¹⁹⁾

Low levels of vitamin D were associated with increased disease activity and corticosteroid dosage, and comorbidities in RA.⁽²⁰⁾

Sources of Vitamin D

Vitamin D dietary sources include butter, eggs, oily fish and fortified foods – these sources provide only low levels of vitamin D – most is produced in the skin following sun exposure. In the UK, vitamin D can be synthesised between April and September, 10.00 am to 2.00 pm, on sunny days (i.e. without cloud cover). Production also depends on genetics, age, sunscreen, clothing, and skin colour. Although vitamin D cannot be synthesised during the winter at our latitude, it can be stored in the body. Levels are likely to be lowest around March.

Live Native Bacteria

Current evidence supports the role of probiotics as adjunctive therapy in RA. Rheumatoid arthritis is an autoimmune disease in which probiotics appear to have an immune modulating action along with decreasing the inflammatory process. In one study, probiotics lowered pro-inflammatory cytokines IL-6 in RA.⁽²¹⁾ Probiotics are an appealing therapeutic strategy in RA due to potential interactions with the microbiome.

Other anti-inflammatory nutrients

Herbs such as Boswellia serrrata and turmeric have been shown to inhibit pro-inflammatory processes through effects on inflammatory enzymes (such as the cyclooxygenase enzymes), suppression of NF-KB activation and the reduction of pro-inflammatory cytokines.

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If you have any questions regarding the health topics that have been raised, please don’t hesitate to get in touch with Jackie via phone; 01684 310099 or e-mail jackie@cytoplan.co.uk

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References

1. Chang, K. et al. (2014) ‘Smoking and rheumatoid arthritis’, International journal of molecular sciences. Multidisciplinary Digital Publishing Institute (MDPI), 15(12), pp. 22279–95.
2. Heliövaara, M. et al. (1993) ‘Smoking and risk of rheumatoid arthritis’, The Journal of rheumatology, 20(11), pp. 1830–5.
3. Klareskog L. et al. (2006) A New Model for an Etiology of Rheumatoid Arthritis. Arthritis & Rheumatism, 54;38-46
4. Saevarsdottir et al. (2011) Patients with early rheumatoid arthritis who smoke are less likely to respond to treatment with methotrexate and tumour necrosis factor inhibitors: Observations from the epidemiological investigation of rheumatoid arthritis and the Swedish rheumatology register cohorts: Arthritis & Rheumatism,63:26-36.
5. Abhishek et al. (2010) Anti-TNF-[alpha] agents are less effective for the treatment of rheumatoid arthritis in current smokers: Journal of Clinical Rheumatology, 16:15-18.
6. Masdottir B. et al. (2000) Smoking, rheumatoid factor isotypes and severity of rheumatoid arthritis Rheumatology, 39:1202-1205.
7. George, M. D. and Baker, J. F. (2016) ‘The Obesity Epidemic and Consequences for Rheumatoid Arthritis Care.’, Current rheumatology reports. NIH Public Access, 18(1), p. 6.
8. McMichael, A. J. et al. (1977) ‘Increased frequency of HLA-Cw3 and HLA-Dw4 in rheumatoid arthritis’, Arthritis and rheumatism, 20(5), pp. 1037–42.
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10. Calton EK, Keane KN, Newsholme P, Soares MJ. (2015) The Impact of Vitamin D Levels on Inflammatory Status: A Systematic Review of Immune Cell Studies, 10(11):e0141770.
11. Campbell, A. W. (2014) ‘Autoimmunity and the gut’, Autoimmune diseases. Hindawi Limited, p. 152428.
12. Scher J.U., Abramson S.B. (2011) The microbiome and rheumatoid arthritis. Nat. Rev. Rheumatol. 7(10):569–578.
13. Badsha, H. (2018) ‘Role of Diet in Influencing Rheumatoid Arthritis Disease Activity.’, The open rheumatology journal. Bentham Science Publishers, 12, pp. 19–28.
14. González Cernadas, L., Rodríguez-Romero, B. and Carballo-Costa, L. (2014) ‘[Importance of nutritional treatment in the inflammatory process of rheumatoid arthritis patients; a review].’, Nutricion hospitalaria, 29(2), pp. 237–45.
15. Sköldstam, L., Hagfors, L. and Johansson, G. (2003) ‘An experimental study of a Mediterranean diet intervention for patients with rheumatoid arthritis’, Annals of the rheumatic diseases. BMJ Publishing Group, 62(3), pp. 208–14.
16. Warjri, S. B. et al. (2015) ‘Coeliac Disease With Rheumatoid Arthritis: An Unusual Association.’, Gastroenterology research. Elmer Press, 8(1), pp. 167–168.
17. (El-Chammas and Danner, 2011) El-Chammas, K. and Danner, E. (2011) ‘Gluten-Free Diet in Nonceliac Disease’, Nutrition in Clinical Practice, 26(3), pp. 294–299.
18. (Navarini et al., 2017) Navarini, L. et al. (2017) ‘Polyunsaturated fatty acids: any role in rheumatoid arthritis?’, Lipids in health and disease. BioMed Central, 16(1), p. 197.
19. Bellan, M., Sainaghi, P. P. and Pirisi, M. (2017) ‘Role of Vitamin D in Rheumatoid Arthritis’, in Advances in experimental medicine and biology, pp. 155–168.
20. Hajjaj-Hassouni, N. et al. (2017) ‘Evaluation of Vitamin D Status in Rheumatoid Arthritis and Its Association with Disease Activity across 15 Countries: "The COMORA Study".’, International journal of rheumatology. Hindawi Limited, 2017, p. 5491676.
21. Mohammed, A. T. et al. (2017) ‘The therapeutic effect of probiotics on rheumatoid arthritis: a systematic review and meta-analysis of randomized control trials’, Clinical Rheumatology, 36(12), pp. 2697–2707.

Last updated on 16th August 2021 by cytoffice