INTRODUCTION:

Rheumatoid Arthritis, the name is based on the term “Rheumatic fever”, an illness which includes joint pain and is derived from the Greek word rheuma (nom), rhematos (“flow, current”), the suffix –oid (“resembling”) translating as joint inflammation that resembles rheumatic fever¹

Rheumatoid arthritis is the most common inflammatory arthritis and is a major cause of disability². Cytokines regulate a broad range of inflammatory processes that are implicated in pathogenesis of rheumatoid arthritis. In rheumatoid joints, it is well known that an imbalance between pro-and anti- inflammatory cytokine activities favours the induction of autoimmunity, chronic inflammation and thereby joint damage³. More women are effected by rheumatoid arthritis than me, the ratio is 3:1 respectively⁴.

The first recognizable description of rheumatoid arthritis was made in 1800 by Dr. Augustin Jacob Landre-Beauvais (1772-1840) of Paris⁵. The disease earned a proper name, when Sir Alfred Garrod, a London physician, coined the clinical term 'rheumatoid arthritis' in 1859 and the first reference came to be made in medical literature⁶.

Types of rheumatoid arthritis

1. seropositive:

Rheumatoid arthritis patients who are classified as seropositive have the presence of anti-cyclic citrullinated peptides (anti-CCPs) in their blood test results. These are also referred to as anti-citrullinated protein antibodies (ACPAs). These are the antibodies that attack the body and produce the symptoms of rheumatoid arthritis.

Between 60 and 80 % of rheumatoid arthritis patients test positive for the presence of anti-CCPs, meaning it is a reliable indicator for diagnosis. The presence of these antibodies can be detected as early as 5 to 10 years before clinical rheumatoid arthritis symptoms appear.

2.seronegative:

It’s still possible for patients to develop rheumatoid arthritis without the presence of antibodies in their blood. This is referred to as seronegative type rheumatoid arthritis. Seronegative patients are those who do not test positive for the anti-CCPs or another antibody called rheumatoid factor.

Though seronegative patients lack the antibodies that help doctors diagnose the condition, they can still be diagnosed with rheumatoid arthritis in a number of ways. These include the demonstration of clinical rheumatoid arthritis symptoms, as well as X-ray results indicating patterns of cartilage and bone deterioration.

3.juvenile rheumatoid arthritis:

Juvenile rheumatoid arthritis is another type that affects patients under the age of 17 years old. It is also known as juvenile idiopathic arthritis. It is the most common type of arthritis for this age group and symptoms can be persistent. Swelling, stiffness and pain the joints can last months for those suffering from juvenile rheumatoid arthritis. Some patients may experience rheumatoid arthritis symptoms for the rest of their lives⁷.

JRA may cause fever and anemia, and can also affect the heart, lungs, eyes, and nervous system. Arthritic episodes can last for several weeks and may recur, although the symptoms tend to be less severe during later recurrent attacks. Treatment is similar to that for adults, with an additional heavy emphasis on physical therapy and exercise to keep growing bodies active. Many of the strong medicines used for adults, though, aren't usually needed for JRA. Permanent damagefrom juvenile rheumatoid arthritis is now rare, and most affected children recover from the disease fully without experiencing any lasting disabilities.

Causes of rheumatoid arthritis:

Hormonal factors:

An early menarche, favoured by a "rich" diet and body fat, increases the risk of developing RA, as well as very irregular menstrual cycles; oral contraceptives, instead, protect against severe forms; while pregnancy causes a remission of RA⁸.

Do not smoke or quit as soon as possible:

Cigarettes are an important risk factor for RA, especially for the seropositive form. A revision on available researches showed that RA increases with years of smoking and the amount of cigarettes smoked: e.g. RR doubles in those who smoke a pack daily for 20-30 years⁹.

Breastfeeding:

Breastfeeding protects women against RA in proportion to its duration.Нis is one more reason to promote it and to support all mothers during breastfeeding¹⁰.

Cytokines in pathogenesis of rheumatoid arthritis:

Cytokines regulate inflammation, autoimmunity and articular destruction in the joints of patients with rheumatoid arthritis. In particular, tumour-necrosis factor (TNF) has proved to be of particular utility as a therapeutic target.

T-cell activation particularly towards a T helper 1 (T_H1)-cell and/or a T_H17-cell phenotype is associated with the presence in the synovial tissue of interleukin-15 (IL-15), IL-1, IL-6, transforming growth factor-β (TGFβ), IL-12 and IL-23. In turn, T cells drive inflammation via IL-17 release and by cognate interactions with adjacent macrophages.

B cells have a critical role in synovitis, acting in part via antigen presentation and cytokine release. B-cell differentiation and expansion, in turn, is supported in the synovial tissue by IL-6, IL-10, B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL).

Macrophage-derived cytokines including TNF, IL-1, IL-6, IL-15 and IL-18 drive many of the pro-inflammatory pathways in synovial tissue.

Cytokines are responsible for osteoclast maturation and activation. There appears to be a hierarchical role for receptor activator of nuclear factor-κB ligand (RANKL) in this process together with TNF, IL-17 and IL-1.

Early intervention, for example with TNF-blocking agents, appears to offer higher clinical response rates and improved chances of achieving clinical remission. Clinical studies are ongoing targeting IL-6, IL-15, IL-18, IL-17, granulocyte/macrophage colony-stimulating factor (GM-CSF) and others, with the objective of further improving clinical outcomes¹¹.

symptoms of rheumatoid arthritis

sleep disturbances:

An alpha frequency (7 to 11.5 Hz) EEG sleep anomaly, an overnight increase in tenderness in their peripheral joints and in "fibrositic" regions, as well as increased weakness and diminished energy¹². Cross-sectional findings indicate that pain and depression play significant roles in self-reported sleep disturbance among patients with RA¹³

Morning stiffness:

Slowness or difficulty moving the joints when getting out of bed or after staying in one position too long, which involves both sides of the body and gets better with movement¹⁴.

Warm reddneses:

Joint inflammation can lead to symptoms of joint redness and warmth. These symptoms should be evaluated by your doctor because they can also be suggestive of a joint infection. However, it is not uncommon for the inflammation associated with arthritis to lead to redness and warmth of the joint¹⁵.

Grinding joints:

As joint cartilage is worn away, the smooth lining covering the rough bone is lost. When the bone is exposed, the joint may not move smoothly. You may feel or even hear a grinding sensation. Place your hand on the joint as you bend back and forth and feel for a grinding sensation of the joint¹⁵

Treatment for rheumatoid arthritis:

In patients with rheumatoid arthritis, combination therapy with methotrexate, sulfasalazine, and hydroxychloroquine is more effective than either methotrexate alone or a combination of sulfasalazine and hydroxychloroquine¹⁶. the dose in the methotrexate-plus-azathioprine group was only half the dose in the methotrexate-alone group¹⁷.

CTLA4Ig is a promising new therapy for rheumatoid arthritis¹⁸.

REFERENCE:

1. Ramachandran et al. World Journal of Pharmacy and Pharmaceutical Sciences Vol 3, Issue 9, 2014. 1074

2. Gary S Firestein. Evolving concepts of rheumatoid arthritis, Nature 423 (6937), 356, 2003

3. Iain B Mclnnes, georgSchett. Nature Reviews Immunology 7 (6), 429, 2007

4. Wolfe AM, Kellegren JH, Masi AT. The epidemiology of rheumatoid arthritis: areview. II. Incidence and diagnostic criteria. Bull Rheum Dis. 1968; 19:524-529.

5. Pincus T. Long-term outcomes in rheumatoid arthritis. Br J Rheumatol, 1995; 34(S2): 59– 73

6. Ramachandran et al. World Journal of Pharmacy and Pharmaceutical Sciences Vol 3, Issue 9, 2014. 1074

7. Rheumatoid arthritis support network. 1-877-284-0235

8. Alamanos Y, Drosos AA (2005) Epidemiology of adult rheumatoid arthritis. Autoimmun Rev 4: 130-136.

9. Di Giuseppe D, Orsini N, Alfredsson L, Askling J, Wolk A (2013) Cigarette smoking and smoking cessation in relation to risk of rheumatoid arthritis in women. Arthritis Res Нer 15: R56.

10. Karlson EW, Mandl LA, Hankinson SE, Grodstein F (2004) Do breastfeeding and other reproductive factors influence future risk of rheumatoid arthritis? Results from the Nurses' Health Study. Arthritis Rheum 50: 3458-3467

11. Iain B. McInnes and Georg Schett Nature Reviews Immunology volume7, pages429-442 (2007).Cytokines in pathogenesis of rheumatoid arthritis

12. Moldofsky H , Lue FA , Smythe HA, The Journal of Rheumatology [01 Jun 1983, 10(3):373-379]

13. Nicassio PM, Ormseth SR, Kay M, Custodio M , Irwin MR , Olmstead R, Weisman MH, Affiliations, Pain [01 Nov 2011, 153(1):107-112]

14. Lineker S , Badley E , Charles C, Hart L, Streiner D, The Journal of Rheumatology [01 May 1999, 26(5):1052-1057

15. Early Symptoms To Watch For To Detect Arthritis, By Jonathan Cluett, MD, a board-certified physician

16. N Engl J Med 1996; 334:1287-1291 DOI: 10.1056/NEJM199605163342002

17. Richard Conway, Candice Low, Robert J. Coughlan, Martin J. O’Donnell, John J. Carey. (2015) Risk of liver injury among methotrexate users: A meta-analysis of randomised controlled trials. Seminars in Arthritis and Rheumatism45:2, 156-162

18. Treatment of Rheumatoid Arthritis by Selective Inhibition of T-Cell Activation with Fusion Protein CTLA4Ig.N Engl J Med 2003; 349:1907-1915 DOI: 10.1056/NEJMoa035075

Received on 20.02.2019 Modified on 18.03.2019

Res. J. Pharma. Dosage Forms and Tech.2019; 11(2):131-133.

DOI: 10.5958/0975-4377.2019.00021.1