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TOPIC: RHEUMATOID ARTHRITIS SUBMITTED BY:

INTRODUCTION Rheumatoid arthritis (RA) is a choric autoimmune disease that primarily affects the joints, causing inflammation, pain, and deformities if left untreated Its characterized by the immune system mistakenly attacking the body own tissues, particularly the synovium- the lining of the members that surround the joints. This relentless assault leads to inflammation, joint damage, and a host of debilitating symptoms

RA mainly attacks the joints, usually many joints at once. RA commonly affects joints in the hands, wrists, and knees. In a joint with RA, the lining of the joint becomes inflamed, causing damage to joint tissue. This tissue damage can cause long-lasting or chronic pain, unsteadiness (lack of balance), and deformity (misshapenness). RA can also affect other parts of the body and cause problems in organs such as the lungs, heart, and eyes.

Additional features of rheumatoid arthritis can include the following: It affects the lining of the joints, which damages the tissue that covers the ends of the bones in a joint. RA often occurs in a symmetrical pattern, meaning that if one knee or hand has the condition, the other hand or knee is often also affected. It can affect the joints in the wrists, hands, elbows, shoulders, feet, spine, knees, and jaw. RA may cause fatigue, occasional fevers, and a loss of appetite.

RA may cause medical problems outside of the joints, in areas such as the heart, lungs, blood, nerves, eyes, and skin. Fortunately, current treatments can help people with the disease to lead productive lives.

Etiology These cells proliferate resulting in thickening & Synovial membrane cells . The new cells layers become an invasive fibroblast- like cell mass called pannus- capable of eroding cartilage & bone. Synovial fluid accumulates & the joint swells distending the capsule pulling on its periosteal attachment & causing pain & potential rupture Ligaments & muscles around the inflamed joint also subject to weakening &potential rupture

Pathophysiology In RA, the immune system malfunctions and attacks healthy joint tissue, specifically the synovium. This triggers an inflammatory response, leading to release of cytokines, enzymes, and other substances that damage cartilage, bone, and surroundings structures.

Overtime chronic inflammation can result in irreversible joint damage, deformities, , and disability. Genetic predisposition environmental factors, hormonal influences and believed to contribute to the development of RA.

Synovitis: Inflammatory cells infiltrate the synovium, leading to synovial hyperplasia and pannus formation. The pannus is an abnormal layer of fibrovascular or granulation tissue that grows over the joint surface and invades cartilage and bone. Cartilage Destruction: Matrix metalloproteinases (MMPs) produced by synovial fibroblasts and chondrocytes degrade the cartilage matrix. Pro-inflammatory cytokines further drive this degradation process.

Bone Erosion: Osteoclasts are activated by cytokines like RANKL (Receptor Activator of Nuclear factor Kappa- Β Ligand), leading to bone resorption and erosions. This results in the characteristic deformities and loss of joint function seen in advanced RA.

Genetic predisposition : HLA-DRB1 Gene: The strongest genetic association with RA is found in the HLA-DRB1 gene, particularly the shared epitope (SE) alleles. These alleles are linked to the presentation of arthritogenic peptides to T cells. Other Genetic Factors: Non-HLA genes such as PTPN22, CTLA4, and STAT4 also contribute to susceptibility to RA.

Enironmental Triggers: Smoking: It is a significant risk factor, especially in genetically predisposed individuals. Infections: Certain infections may trigger RA in susceptible individuals, possibly through molecular mimicry or by inducing an inflammatory response.

Autoantibody Production: Rheumatoid Factor (RF): An autoantibody targeting the Fc portion of IgG. Anti-Citrullinated Protein Antibodies (ACPAs): These target citrullinated proteins, which are modified forms of proteins where arginine residues are converted to citrulline. Immunological Factors

2 . Cell-Mediated Immune Response: T Cells: CD4+ T cells (Th1 and Th17 subsets) play a central role by producing pro-inflammatory cytokines like IFN- γ, IL-17, and TNF- α. B Cells: Besides producing autoantibodies, B cells also act as antigen-presenting cells and secrete cytokines. 3.Cytokine Production: Pro-inflammatory cytokines such as TNF- α, IL-1, IL-6, and IL-17 are key players in the inflammatory cascade. These cytokines promote inflammation, synovial hyperplasia, and joint destruction.

What causes RA ? RA occurs when the body’s immune system attacks its own healthy cells.  The specific causes of RA are unknown, but some factors can increase the risk of developing the disease.

Causes Researchers do not know what causes the immune system to turn against the body’s joints and other tissues. Studies show that a combination of the following factors may lead to the disease: Genes. Certain genes that affect how the immune system works may lead to rheumatoid arthritis. However, some people who have these genes never develop the disease. This suggests that genes are not the only factor in the development of RA. In addition, more than one gene may determine who gets the disease and how severe it will become.

Environment. Researchers continue to study how environmental factors such as cigarette smoke may trigger rheumatoid arthritis in people who have specific genes that also increase their risk. In addition, some factors such as inhalants, bacteria, viruses, gum disease, and lung disease may play a role in the development of RA.

Sex hormones. Researchers think that sex hormones may play a role in the development of rheumatoid arthritis when genetic and environmental factors also are involved. Studies show: Women are more likely than men to develop rheumatoid arthritis. The disease may improve during pregnancy and flare after pregnancy.

Clinical Manifestations Pain: Patient will experience pain at rest which may intensify with activity, but which may also lessen after a period of activity. Exaggerated nervous responses may result from normally non- noxious simulation such as movement or pressure Sensitisation of pain fibres is a major component of inflammatory joint Pain & is induced by inflammatory mediators such as prostaglandins & bradykinins

Symptoms of Rheumatois Arthritis C ommon symptoms of rheumatoid arthritis include: RA affects people differently. In some people, RA starts with mild or moderate inflammation affecting just a few joints. However, if it is not treated or the treatments are not working, RA can worsen and affect more joints. This can lead to more damage and disability. At times, RA symptoms worsen in “flares” due to a trigger such as stress, environmental factors (such as cigarette smoke or viral infections), too much activity, or suddenly stopping medications.

In some cases, there may be no clear cause. The goal of treatment is to control the disease so it is in remission or near remission, with no signs or symptoms of the disease.

Rheumatoid arthritis can cause other medical problems, such as: Joint pain at rest and when moving, along with tenderness, swelling, and warmth of the joint. Joint stiffness that lasts longer than 30 minutes, typically after waking in the morning or after resting for a long period of time. Joint swelling that may interfere with daily activities, such as difficulty making a fist, combing hair, buttoning clothes, or bending knees.

Fatigue – feeling unusually tired or having low energy. Occasional low-grade fever. Loss of appetite.

Rheumatoid nodules that are firm lumps just below the skin, typically on the hands and elbows. Anemia due to low red blood cell counts. Neck pain. Dry eyes and mouth. Inflammation of the blood vessels, the lung tissue, airways, the lining of the lungs, or the sac enclosing the heart. Lung disease, characterized by scarring and inflammation of the lungs that can be severe in some people with RA

Rheumatoid arthritis can happen in any joint; however, it is more common in the wrists, hands, and feet. The symptoms often happen on both sides of the body, in a symmetrical pattern. For example, if you have RA in the right hand, you may also have it in the left hand. RA affects people differently. In some people, RA starts with mild or moderate inflammation affecting just a few joints. However, if it is not treated or the treatments are not working, RA can worsen and affect more joints. This can lead to more damage and disability.

At times, RA symptoms worsen in “flares” due to a trigger such as stress, environmental factors (such as cigarette smoke or viral infections), too much activity, or suddenly stopping medications. In some cases, there may be no clear cause. The goal of treatment is to control the disease so it is in remission or near remission, with no signs or symptoms of the disease.

The physical examination should address the following: Upper extremities (metacarpophalangeal joints, wrists, elbows, shoulders) Lower extremities (ankles, feet, knees, hips) Cervical spine

During the physical examination, it is important to assess the following: Stiffness Tenderness Pain on motion Swelling Deformity Limitation of motion Extra-articular manifestations

Who gets Rheumatoid Arthritis ? You are more likely to get rheumatoid arthritis if you have certain risk factors. These include: Age. The disease can happen at any age; however, the risk for developing rheumatoid arthritis increases with older age. Children and younger teenagers may be diagnosed with juvenile idiopathic arthritis, a condition related to rheumatoid arthritis.

Sex. Rheumatoid arthritis is more common among women than men. About two to three times as many women as men have the disease. Researchers think that reproductive and hormonal factors may play a role in the development of the disease for some women.

Family history and genetics. If a family member has RA, you may be more likely to develop the disease. There are several genetic factors that slightly increase the risk of getting RA. Smoking. Research shows that people who smoke over a long period of time are at an increased risk of getting rheumatoid arthritis. For people who continue to smoke, the disease may be more severe. Obesity. Some research shows that being obese may increase your risk for the disease as well as limit how much the disease can be improved.

Periodontitis. Gum disease may be associated with developing RA. Lung diseases. Diseases of the lungs and airways may also be associated with developing RA.

Causes of Joint Deformities In RA, certain immune system cells — mostly T cells and B cells — migrate to the joint lining (the synovium), where they cause inflammation. This can lead to the formation of abnormally thick tissue called pannus, which can damage cartilage and surrounding ligaments and tendons. As a result, joints lose their shape and alignment.

Types of deformities In the early stages of RA, the feet may be affected slightly more than the hands, partly because they have the added stress of bearing the body’s weight. Extra pounds may make the problem worse. One small study of 82 people with RA found that ankle pain occurred more often with higher body weight, more severe symptoms and longer disease duration. Another study involving 230 people with RA found that those with a higher body mass index (BMI) had more foot pain and more limited mobility but not more deformities.

Common foot deformities Bunion (hallux valgus) . A bony lump at the base of the big toe joint, this is one of the most common foot problems in the general population, usually due to an injury or inherited problem with foot anatomy. Whether tight shoes or high heels cause bunions is controversial. Bunions are also common in people with RA — the result of erosion in the joint that causes the toe to shift or dislocate, crowding the other toes and pushing the big toe joint out. Finding shoes to fit a foot with a bunion can be challenging, but roomy, wide, comfortable shoes are key. Over-the-counter shoe inserts or prescription orthotics that help distribute pressure evenly may also help.

Flat feet (pes planus) . The medial longitudinal arch runs the length of the foot. It’s braced by thick bands of ligaments and tendons and acts as a support for the rest of the body. It’s normally the highest of the foot’s three arches, but in people with flat feet, this arch virtually disappears so that the entire bottom of the foot touches or nearly touches the ground. Hammertoe. This is an unusual bend in the middle joint of one or more toes, usually the second, third or fourth. Mallet toe, a similar condition, affects the joint(s) nearest the toenail.

In the later stages, muscles and tendons can become more rigid so it’s harder to uncurl the toes. As with many foot problems, shoes that have a wide, deep toe box are essential to keep pressure off of the raised joint. Toe-stretching exercises and off-the-shelf or custom orthotics that help hold toes in the right position may also help. It’s possible to straighten hammertoes and mallet toes; it just takes some time and patience.

Claw toe . This is another condition like hammer and mallet toe, except both the toe’s middle and top joints are bent, so they look something like a claw. The same advice as for hammertoe and mallet toe applies: Choose shoes with an extra-deep toe box and good arch support Use pads or inserts to support the toe Stretch and strengthen toes with specific exercises Use a splint or tape to hold the toe in the right position

Common Hand Deformities Arthritic fingers may be more disabling and affect your life more than bent toes, although these problems are much rarer these days, especially when RA is well controlled. Finger deformities can include: Boutonniere deformity. In this condition, the middle joint of the finger won’t straighten while the upper joint bends upward. It happens when RA or an injury damages the tendon on the top of the finger that helps straighten the middle joint. This can be reversed with a splint that keeps the middle joint straight. It must be worn continuously for up to eight weeks.

Swan neck deformity. This condition also affects a finger’s middle joint, which bends backward while the tip bends down, mimicking the curve of a swan’s neck. It’s the mirror image of a boutonniere deformity. In RA, it can result when inflammation weakens the joint at the tip of the finger and the extensor tendon slips out of place. The most common treatment is using a ring splint to hold the finger in the right position, or extension block splints, which can help correct excessive movement of the middle joint.

Ulnar deviation (ulnar drift). This occurs when chronic inflammation of the knuckle joints causes the fingers to bend toward the outer side of the forearm. Splints can help realign the joints and relieve pain.

Complications of RA Rheumatoid arthritis (RA) has many physical and social consequences and can lower quality of life. It can cause pain, disability, and premature death. Premature heart disease. People with RA can have a higher risk for developing other chronic diseases such as heart disease and diabetes. To prevent people with RA from developing heart disease, treatment of RA also focuses on reducing heart disease risk factors.  For example, doctors will recommend that patients with RA stop smoking and lose weight.

Employment. RA can make work difficult.  Adults with RA are less likely to be employed than those who do not have RA. As the disease gets worse, many people with RA find they do less work than they used to. Work loss among people with RA is highest among people whose jobs are physically demanding. Work loss is lower among those in jobs with few physical demands, or in jobs where they have influence over the job pace and activities.

Diagnosis 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, also known as sed rate) or C-reactive protein (CRP) level, 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 May recommend X-rays to help track the progression of rheumatoid arthritis in your joints over time. MRI and ultrasound tests can help the doctor to judge the severity of the disease in your body.

Treatment There is no cure for rheumatoid arthritis. But clinical studies indicate that remission of symptoms is more likely when treatment begins early with medications known as disease-modifying antirheumatic drugs (DMARDs). The types of medications recommended by your doctor will depend on the severity of your symptoms and how long you've had rheumatoid arthritis. Medications

NSAIDs. Nonsteroidal anti-inflammatory drugs (NSAIDs) can relieve pain and reduce inflammation. Over-the-counter NSAIDs include ibuprofen (Advil, Motrin IB, others) and naproxen sodium (Aleve). Stronger NSAIDs are available by prescription. Side effects may include stomach irritation, heart problems 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 symptoms quickly, with the goal of gradually tapering off the medication.

Conventional 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 , others), leflunomide (Arava), hydroxychloroquine (Plaquenil) and sulfasalazine (Azulfidine). Side effects vary but may include liver damage and severe lung infections. 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), sarilumab (Kevzara) and tocilizumab (Actemra) Biologic DMARDs are usually most effective when paired with a conventional DMARD, such as methotrexate. This type of drug also increases the risk of infections. Targeted synthetic DMARDs . Baricitinib (Olumiant), tofacitinib (Xeljanz) and upadacitinib ( Rinvoq ) may be used if conventional DMARDs and biologics haven't been effective. Higher doses of tofacitinib can increase the risk of blood clots in the lungs, serious heart-related events and cancer.

Therapy Your doctor may refer 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 that will be easier on your joints. For example, you may want to pick up an object using your forearms.

Conservative Treatment Ice packs applied to the affected joint cool the skin temp. which is possibly elevated from the inflammation Ice uses the physiological process of the hunting response of alternating vasodilation & constrictions, which assist with swelling Cooling will diminish the rate of swelling & production of irritants & alleviate the pain Contraindication: Vasculitis & Raynauds

Heat It can be applied during disease remissions & chronic rather than acutely inflamed joint It reduces pain attributed to muscle spasm, has a sedative effect on sensory nerve endings & may activate the pain gate Mild superficial heat may facilitate stretching of rheumatoid joints as increased collagen extensibility

Conservative Treatment

Assistive devices can make it easier to avoid stressing your painful joints. For instance, a kitchen knife equipped with a hand grip 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.

Surgery 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 improve function. Rheumatoid arthritis surgery may involve one or more of the following procedures: Synovectomy. Surgery to remove the inflamed lining of the joint (synovium) can help reduce pain and improve the joint's flexibility.

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.

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