Rheumatoid arthritis (RA)

Rheumatoid arthritis is a chronic inflammatory, destructive and deforming symmetrical polyarthritis associated with systemic involvement. The individuals with HLA-D4 and HLA-DR4 are more prone to RA.

It starts when your immune system, which is supposed to protect you, goes awry and begins to attack your body’s own tissues. It causes inflammation in the lining of your joints (the synovium). As a result, your joints may get red, warm, swollen, and painful.

Symptoms of Rheumatoid Arthritis

Joint pain and swelling
Stiffness, especially in the morning or after you sit for a long time
Fatigue

Who Gets Rheumatoid Arthritis?

Anyone can get RA. It affects about 1% of Americans.

The disease is 2 to 3 times more common in women than in men, but men tend to have more severe symptoms.

It usually starts in middle age. But young children and the elderly also can get it.

Pathogenesis

Synovitis (synovial cell hyperplasia, hypertrophy with CD4 lymphocytic infiltration and synovial effusion)
Pannus formation
Cartilage loss
Fibrosis
Bony erosion, deformity, fibrous and bony ankylosis
Muscle wasting
Periarticular osteoporosis

Triggering Factors

Infection
vaccination
Physical trauma
Psychological stress

Over time, the inflammation wears down the cartilage, a cushy layer of tissue that covers the ends of your bones. As you lose cartilage, the space between your bones narrows. As time goes on, they could rub against each other or move out of place. The cells that cause inflammation also make substances that damage your bones.

The inflammation in RA can spread and affect organs and systems throughout your body, from your eyes to your heart, lungs, kidneys, blood vessels, and even your skin.

Criteria for diagnosis of Rheumatoid Arthritis

There is no single test that shows whether you have RA. Your doctor will give you a checkup, ask you about your symptoms, and possibly perform X-rays and blood tests.

Rheumatoid arthritis is diagnosed from a combination of things, including:

Morning stiffness (more than one hour for more than 6 weeks)
Arthritis involving 3 or more joint areas (with or without soft tissue involvement lasting more than 6 weeks)
Arthritis of hand joints(wrist, MCP or PIP joints more than 6 weeks)
Symmetrical arthritis (at least one area lasting for 6 weeks)
Rheumatoid nodules
Rheumatoid factor
Radiographic changes

Blood Tests

In addition to checking for joint problems, your doctor will also do blood tests to diagnose RA. She’ll be looking for:

Anaemia: People with rheumatoid arthritis may have a low number of red blood cells.

C-reactive protein (CRP): High levels are also signs of inflammation.

Some people with rheumatoid arthritis may also have a positive antinuclear antibody test (ANA), which indicates an autoimmune disease, but the test does not specify which autoimmune disease.

Cyclic citrulline antibody test (anti-CCP): This more specific test checks for anti-CCP antibodies, which suggest you might have a more aggressive form of rheumatoid arthritis.

Erythrocyte sedimentation rate (ESR): How fast your blood clumps up in the bottom of a test tube shows there may be inflammation in your system.

Rheumatoid factor (RF): Most, but not all, people with rheumatoid arthritis have this antibody in their blood. But it can show up in people who don’t have RA.

Rheumatoid Arthritis Treatment

Treatments include medication, rest, exercise, and, in some cases, surgery to correct joint damage.

Your options will depend on several things, including your age, overall health, medical history, and how severe your case is.

Why Are Rest and Exercise Important for RA?

You need to be active, but you also have to pace yourself. During flare-ups, when inflammation gets worse, it’s best to rest your joints. Using a cane or joint splints can help.

When the inflammation eases, it’s a good idea to exercise. It’ll keep your joints flexible and strengthen the muscles that surround them. Low-impact activities, like brisk walking or swimming, and gentle stretching can help. You may want to work with a physical therapist at first.

When Is Surgery Needed?

When joint damage from rheumatoid arthritis has become severe, surgery may help.

Is There a Cure?

Although there isn't a cure for rheumatoid arthritis, early, aggressive treatment will help prevent disability and increase your chances of remission.

Causes and Risk Factors

Doctors don’t know exactly what causes this disease. But they know these things could be risk factors for RA:

Age. RA can affect you at any age, but it’s most common between 40 and 60. It isn’t a normal part of aging.
Family history. If someone in your family has it, you may be more likely to get it.
Environment. A toxic chemical or infection in your environment can up your odds.
Gender. RA is more common in women than men. It’s more likely in women who've never been pregnant and those who've recently given birth.
Obesity. Extra weight, especially if you’re under 55.
Smoking. If your genes already make you more likely to get RA, lighting up can raise your odds even higher. And if you do get the disease, smoking can make it worse.

Precautions to Prevent RA

There’s no way to prevent RA, but you can lower your chances if you:

Quit smoking. It’s the one sure thing besides your genes that boosts your odds of getting RA. Some studies show it also can make the disease get worse faster and lead to more joint damage, especially if you’re ages 55 or younger. If you’re overweight and a smoker, your chances of developing RA go up.
Take care of your gums: New research shows a link between RA and periodontal (gum) disease. Brush, floss, and see your dentist for regular checkups.

RA Symptoms in Joints

RA almost always affects your joints. It may take a few weeks or months for the first signs to show. The inflammation it causes results in classic symptoms like:

Stiffness. The joint is harder to use and doesn't move as well as it should. It’s especially common in the morning. While many people with other forms of arthritis have stiff joints in the morning, it takes people with RA more than an hour (sometimes several hours) before their joints feel loose.
Swelling. Fluid in the joint makes it puffy and tender.
Pain. Inflammation inside a joint makes it hurt whether you’re moving it or not. Over time, it causes damage and pain.
Redness and warmth. The joints may be warmer and show color changes related to the inflammation.

What Joints Does RA Affect?

RA usually starts in the hands, but it can affect any joint, including your:

Elbows
Feet
Hips
Jaw
Knees
Neck
Shoulders
Wrists

If you have RA, you’ll notice a symmetrical pattern. It shows up in the same joints on both sides of your body, like both wrists or both hips.

It doesn’t happen often, but RA can also affect a joint in your voice box. It can make your voice hoarse.

Whole-Body Symptoms

RA symptoms can go beyond your joints. You could also feel:

Fatigue
Muscle aches
Poor appetite
Malaise
Depression

Extreme fatigue could be a sign of anemia, or a lack of healthy red blood cells. Your doctor will test for this as part of your RA diagnosis.

Depression could also cause some of these symptoms. A chronic disease like RA can be hard to live with. Talk to your doctor if you think RA has you down.

Extra- articular manifestations

Skin

Dermal atrophy
Leg ulcers
Nail dystrophy
Nodules
Pyoderma gangrenosum

Cardiovascular system

pericarditis
endocarditis
cardiac arrhythmias
cardiomyopathy
conduction defects
infiltration of valves
myocardial infarction

Ocular

The most common problems are:

Cataracts: A clouding of the lens in your eye that affects your vision

Dry eye syndrome: Whether it’s medications or damage to your tear glands, your eyes can’t make a healthy tear film.

Scleritis: Inflammation and redness in the white part of your eye

Other Body Parts RA Can Affect

Bones: The chemicals that cause inflammation can also take a bite out of your bones. It often affects your hips and spine. Sometimes it’s a byproduct of years of treating RA with steroids.

Liver and kidneys: It’s rare for RA to affect these organs. But the drugs that treat it can. Nonsteroidal anti-inflammatory drugs (NSAIDs) and are bad for both. Cyclosporine can cause kidney disease. Methotrexate can damage your liver.

Immune system: The medications you take can slow it down. This makes you more likely to get infections.

Mucous membranes: You might be more likely to get a condition called Sjogren’s syndrome that dries out moist places in your body like your eyes, mouth, and inside your nose.

Muscles: When inflammation stops you from moving your joints, the attached muscles can get weak. Or you could get a condition called myositis that weakens them. The medications you take for RA can also be to blame.

Nerves: RA causes symptoms that range from numbness and tingling to paralysis. It can result from joint damage that RA causes, the disease process itself, or medications that treat it.

Blood vessels: RA can cause inflammation of your blood vessels. It can show up as spots on the skin or can cause ulcers in more severe cases.

Lab and Blood Tests for RA

Here are some of the things you can expect to happen at your appointment if the doctor thinks you have RA.

Personal and family medical history: Your doctor will ask about your past and your relatives’. If someone in your family tree has RA, you may be more likely to have the disease.

Physical examination: The doctor will check your joints for swelling, tenderness, and range of motion. RA tends to strike several joints.

Antibody bloo tests: Doctors look for certain proteins that show up in your blood when you have RA. These proteins mistakenly target healthy cells and kick off the inflammation process. So a high or positive test result means inflammation is in your body.

RF: high levels (over 20 u/ml)
Anti-CCP (anti-cyclic citrullinated peptide): high levels (over 20 u/ml)
ANA, or antinuclear antibodies: the results are positive or negative.

Not all people with RA have these proteins.

Other blood tests: Besides RF and anti-CCP, other blood tests could include:

Complete blood count: It helps your doctor find anaemia (low red blood cells), which is common in RA. It looks for four things:

White blood cells 4.8-10.8
Red blood cells 4.7-6.1
Hemoglobin 14.0-18.0
Hematocrit 42-52
Platelets 150-450

Erythrocyte sedimentation rate: This measures how fast your red blood cells clump and fall to the bottom of a glass tube within an hour. Your doctor might call it a sed rate.

Normal ranges are:

Men younger than 50: 0-15 mm/h
Men older than 50: 0-20 mm/h
Women younger than 50: 0-20 mm/h
Women older than 50: 0-30 mm/h

C-reactive protein : This test measures levels of a protein your liver makes when inflammation is present. Results vary from person to person and lab to lab, but most of the time a normal result is less than 1.0.

Imaging tests: These can help your doctor judge how severe your disease is and track its progress over time.

X-rays can show whether (and how much) joint damage you have, though damage may not show up early on.
MRI and ultrasound give a more detailed picture of your joints. These scans aren’t normally used to diagnose RA, but they can help doctors find it early.

MANAGEMENT

Drug therapy

Group 1: Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

Aspirin
Indomethacin
Fenamides
Propionic acid compounds (Ibuprofen, Ketoprofen, Fenoprofen, Flubiprofen, Naproxen)
Sulindac (clinoryl)
Tolmetin
Piroxicam
Diclofenac
COX-2 inhibitor

Choice of NSAIDs

Salicylates (aspirin) is the initial treatment of choice of RA

Dose: 3 to 4 grams per day

Group 2: Disease modifying agents (DMARDs)

Methotexate

Methotrexate is the first choice in the management of moderate and severe RA.It is non-oncogenic and it acts rapidly in 4 to 6 weeks and is comparatively less toxic. It can be used along with NSAIDs. It is given in a dose of 7.5 mg PO weekly once along with breakfast. The dose can be increased to 15 mg once a week.

Folic acid supplementation at a dosage of 1 to 2 mg saily may reduce its toxicity without impeding its efficacy.

Sulphasalazine

It is metabolized by the colonic bacteria into 5 amino salicylic acid and sulpha pyridine of which sulpha pyridine has more important anti-inflammatory role in RA.

DOSE: started at 500 mg/day and slowly increased to 1 gm BD over a period of 4 weeks.

Toxicity: Rash, Depression, Megaloblastic anaemia, Leukopenia.

Hydroxychloroquine

Indications: Failure to respond to conservative regimen of rest, salicylates, other NSAIDs.

Contraindication: patient with significant visual, hepatic, renal impairement or with porphyria, in pregnancy and in children.

Dose: 200 mg OD

Toxicity: Keratopathy, Retinopathy, Neuropathy, Myopathy.

Penicillamine

It is particularly of value in the therapy of extraarticular manifestation of RA.

Dose: 600 to 1200 mg per day

Toxicity: Taste impairement, anorexia, nausea and dyspepsia, Bone marrow aplasia, polyarteritis, nephrotic syndrome, ocular and lingual ulceration, skin rashes

Gold therapy

Indications: reserved for patients who continued to have active synovitis or who develop erosions on a conservative regimen of NSAIDs, rest and physiotherapy.

Dose: start with 10 mg per week and increase up to 50 mg per week.

Group 3 (Highly Toxic)

Corticosteroids, ACTH
Leflunomide
Azathioprine
Cyclophosphamide
Cyclosporine
Levamisole

Corticosteroids

Indications:

Along with DNARDs in the initial phase.
Failure to control the disabling symptoms.
Elderly patients in acute conditions.
Life-threatening conditions (severe pericarditis, polyarteritis or scleritis).

Dose: Prednisolone 10 to 15 mg per day

Leflunomide

It inhibits autoimmune T cell proliferation and production of antibodies by T cells. It also block TNF dependent nuclear factor kappa B activation.

Dose: Initiate with 1.5mg/kg/day PO in two divided doses and to be increased to 2.5 to 3mg/kg/day PO after 8 weeks.

Toxicity: nausea and vomiting, hepatotoxicity, increased incidence of infections

Cyclophosphamide

It is effective for the treatment of rheumatoid vasculitis.

Dose: Low-dose PO 1 to 3 mg/kg/day or high-dose IV bolus 0.5 to 1.0 g/m2 every 1 to 3 months. The goal is to obtain a WBC count 4500 cells/microlitre.

Levamisole

It is an immunomodulator and can be given in a dose of 150 mg single weekly dose.

Cyclosporine

It is occasionally used to treat refractory synovitis.

Dose: 2 to 3 mg/kg/day PO

Group 4 (Cytokine Antagonist)

TNF alpha Antagonist

Infliximab: It is a chimeric monoclonal antibody that binds with high affinity and specificity to human TNF alpha.
Etanercept: It is a recombinant fusion protein capable of binding to 2 TNF alpha molecules given 25 mg subcutaneously twice weekly.
Adalimumab: It is a fully human monoclonal antibody against TNF alpha given 20 to 80 mg SC every 2 weeks.
Golimumab: It is humanized monoclonal antibody given 50 mg SC monthly.
Certolizumab pegol: It is a pegylated Fc free fragment of a humanised monoclonal antibody with binding specificity for TNF alpha.

IL 1 Receptor Antagonist

Anakinra: It ia a recombinant form of naturally occuring IL-1 receptor antagonist Dose: 100 mg SC daily
Abatacept: It is a soluble fusion protein consisting of extracellular domain of human cytotoxic T lymphocyte associated with antigen 4 (CTLA-4) linked to the modified portion of human IgG. It inhibits co-stimulation of T cells by blocking CD 28 to CD 80/86 interactions and inhibit the function of antigen presenting cells.
Rituximab: It is a chimeric monoclonal antibody against CD 20. Dose: 1000 mg IV 2 doses at 0 and 14 days and then repeated every 24 weeks.
Tocilizumab: It is a humanized monoclonal antibody against IL-6 receptor, given 4 to 8 mg/kg IV monthly.
Plasmapheresis

Surgery

Synovectomy
Arthroplasty
Osteotomy
Arthrodesis.

Surgical fusion of joints usually results in freedom from pain but also in total loss of motion and this procedure is well tolerated in the wrist and thumb.

Physical and Occupational Therapy

Physical and occupational therapy make a big difference to your daily life. They are a key part of any RA treatment plan.

Physical therapists can give you an exercise plan, teach you how to use heat and ice, do therapeutic massage, and encourage and motivate you.

Occupational therapists help you handle daily tasks -- like cooking or using your computer -- and show you easier ways to do those things. They can also check on whether any gadgets would help you.

Cognitive Therapy

Because one of the most trying aspects of rheumatoid arthritis is learning to live with pain, many doctors recommend pain management training. They may call it “cognitive therapy.”

The goal is to improve your emotional and psychological well-being as you develop ways to relax, handle stress, and pace yourself. For instance, it may include activity scheduling, guided imagery, relaxation, distraction, and creative problem-solving.

Exercise, Joint Pain, and Rheumatoid Arthritis

When your joints are stiff and painful, exercise might be the last thing on your mind. Yet with RA, exercising regularly is one of the best things you can do.

People who work out live longer, with or without rheumatoid arthritis.
Regular exercise can cut down on RA pain.
Your bones will be stronger. Thinning of the bones can be a problem with rheumatoid arthritis, especially if you need to take steroids.
Stronger muscles help you move better.
Your mood and energy level will benefit.

Natural Treatments for Rheumatoid Arthritis

There are some complementary medicine treatments that might help your RA. It’s a good idea to talk it over with your doctor. You’ll still need to take your medicine and keep up with the other parts of your treatment plan.

Heat and cold: Ice packs can reduce joint swelling and inflammation. Heat compresses relax muscles and stimulate blood flow.

Acupuncture: Studies show that acupuncture curbs pain, may lower the need for painkillers, and is good for flexibility in affected joints.

Mind/body therapy: Mind/body therapies can help with stress management, plus improve sleep and how you react to pain. Strategies include deep belly breathing, relaxing your muscles one by one from head to toe, visualization (such as picturing a calming scene), meditation, and tai chi.

Nutritional supplements:

Research shows that omega-3 fatty acids in fish oil have an anti-inflammatory effect in the body. Several studies have shown that fish oil supplements may help reduce morning stiffness with RA.

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