Rheumatoid arthritis overview

# Overview
Rheumatoid arthritis is a chronic inflammatory systemic disease which is found commonly in women and starts in mid 30's to 40's. Cause of rheumatoid arthritis is idiopathic but there are genetic factors such as  HLA-DR4 cluster, environmental factors like smoking, hormonal factors like hyperprolactinemia, infectious factors like mycoplasma, epstein-Barr virus (EBV), rubella virus, porphyromonas gingivalis, socioeconomic, psychological, and lifestyle factors such as obesity play important role in the development of rheumatoid arthritis. There is no established system for the classification of rheumatoid arthritis. Depending on the presentation of rheumatoid arthritis, it is classified into typical classic rheumatoid arthritis and palindromic rheumatism.  Common symptoms of rheumatoid arthritis are joint pain of small joints of the hands, wrist, and forefoot, joint swelling, morning joint stiffness classically lasting for more than an hour, decreased grip strength, generalized aching, and fatigue, weight loss, depression. Less common symptoms are tingling and numbness in the arm and weakness in the arm. Anti-CCP antibodies testing is the gold standard test for the diagnosis of rheumatoid arthritis.It has the specificity of about 81-100%, with the sensitivity of 3994%. Hallmark of rheumatoid arthritis Xray findings are soft tissue swelling, joint space narrowing, and erosions but it involves small joints with multiple deformities. Findings on an ultrasound suggestive of rheumatoid arthritis are tenosynovitis, bursitis, baker's cyst and inflammation of synovium. Therapeutic use of ultrasound is the guidance of corticosteroid injection in the joint and fluid aspiration from the joint effusion. MRI is helpful in the diagnosis of early and subacute rheumatoid arthritis. Findings on MRI diagnostic of rheumatoid arthritis are synovial hyperemia, synovial hyperplasia, pannus, subchondral cysts, erosions, effusion of joints and bone marrow edema. The mainstay of treatment of rheumatoid arthritis is pharmacotherapy.  There are two types of therapies- non-pharmacological therapy and pharmacological therapy. There are different drug regimen depending upon the stage of the disease. In active stage, combined therapy include disease-modifying antirheumatic drugs (DMARDs) are used along with the anti-inflammatory drugs. Therapy for resistant disease and flares is the addition of oral glucocorticoids. In case of the flare, add another DMARDs with methotrexate or replace with another DMARDs. Surgery is usually reserved for patients with debilitating disease, failure of medical therapy and radiographic findings of end-stage arthritis. Various surgical options used for the treatment of RA are tenosynovectomy, arthroscopic or open synovectomy, joint fusion, small joint implant arthroplasty, total joint replacement of deformed joint. Effective measures for the primary prevention of rheumatoid arthritis are patient education, exercise, physical and occupational therapy and cognitive behavioral therapies. Effective measures for the secondary prevention of rheumatoid arthritis are calcium and vitamin D supplementation to prevent osteoporosis. To prevent cardiovascular complications and recurrent attacks of RA, effective methods are exercise, smoking cessation, and dietary control.

# Historical Perspective
Rheumatoid arthritis signs and symptoms were first noticed by Augustin Jacob Landre-Beauvais, a resident physician at the Saltpetriere asylum in France, in 1800, He named it as  Goutte Asthenique Primitive or Primary Asthenic Gout. The name Rheumatoid arthritis coined by Archibald Garrod in 1890. In 1970, human leukocyte antigen (HLA) was first implicated in the pathogenesis of rheumatoid arthritis.

# Classification
There is no established system for the classification of rheumatoid arthritis. Depending on the presentation of rheumatoid arthritis, it is classified into typical classic rheumatoid arthritis and palindromic rheumatism. The classification criterion for the diagnosis of rheumatoid arthritis according to American College of Rheumatology, uses 4 parameters including joint involvement, serology, duration of symptoms, and acute phase reactants. If the score is more than 6 according to this criteria, the disease is classified as definite rheumatoid arthritis.

# Pathophysiology
Rheumatoid arthritis is mediated by the combination of a predisposing genotype upon which genetic factors, environmental and microorganism also contribute resulting in the inflammation and destruction of the synovial membrane. All the factors lead to citrullination or post-translational modifications, the altered peptides bind to MHC protein with shared epitopes which further lead to antigen presentation to T-cells.
T-cells further stimulate B-cells and cytokines which leads to cartilage damage. Mutation of human leukocyte antigen (HLA) genes on chromosome 6 is involved in pathogenesis of rheumatoid arthritis. Conditions associated with RA are vasculitis, uveitis, scleritis, peripheral ulcerative keratitis, 
interstitial fibrosis, pulmonary nodules, bronchiolitis obliterans, organizing pneumonia, venous thromboembolism, pericarditis, myocarditis, congestive heart failure, atrial fibrillation, sjogren's syndrome, felty's syndrome.

# Causes
Rheumatoid arthritis occurs when your immune system attacks the synovium  the lining of the membranes that surround your joints.The resulting inflammation thickens the synovium, which can eventually destroy the cartilage and bone within the joint.The tendons and ligaments that hold the joint together weaken and stretch. Gradually, the joint loses its shape and alignment.Cause of rheumatoid arthritis is idiopathic but genetic like HLA-DR4 cluster, environmental like smoking, hormonal like hyperprolactinemia, immunologic, infectious factors like mycoplasma, epstein-Barr virus (EBV), rubella virus, porphyromonas gingivalis, socioeconomic, psychological, and lifestyle factors such as obesity play important role in the development of rheumatoid arthritis.

# Differentiating Rheumatoid Arthritis from other Diseases
Rheumatoid arthritis must be differentiated from  osteoarthritis , septic arthritis, reactive arthritis, behcet's disease and psoriatic arthritis.

# Epidemiology and Demographics
The incidence of rheumatoid arthritis is approximately  40 per 100,000 individuals worldwide. The prevalence of  rheumatoid arthritis is approximately 1 percent in Caucasians per 100,000 individuals worldwide.The peak onset of the disease is between the age of  50 and 75 years. Women are three times more commonly affected by rheumatoid arthritis than men. The mortality rate of rheumatoid arthritis is approximately 10%.

# Risk Factors
Common risk factors in the development of rheumatoid arthritis are the family history of RA, cigarette smoking, race like more prevalent in Native Americans, strongly associated with  major histocompatibility complex (MHC) class II antigen HLA-DR4 and patient with silica and asbestos exposure.
Less common risk factors are obesity and high consumption of red meat.

# Screening
According to the American College of Rheumatology Guideline, screening for rheumatoid arthritis is not recommended.

# Natural History, Complications and Prognosis
The symptoms of rheumatoid arthritis  usually develop in the third to fourth decade of life and start with symptoms such as fatigue, small joints pain and morning stiffness which lasts more than 1 hour. Complication of rheumatoid arthritis involve all the systems. Cardiac complications are pericarditis, congestive heart failure, endocarditis and myocardial infarction. Pulmonary complications are pleurisy, alveolitis, pleural effusion and pulmonary fibrosis. Rheumatological complications are joint deformities, felty's syndrome, sjogren's syndrome, osteoporosis  and atlantoaxial subluxation. Eye complications such as scleritis and keratitis. Renal complications are chronic renal failure from amyloidosis. Nervous system complications like peripheral neuropathy and mononeuritis multiplex. Prognosis is generally good with early diagnosis and treatment, and 10-year disability rate of patients with rheumatoid arthritis is approximately 40%.

# Diagnostic study of choice
Anti-CCP antibodies testing is the gold standard test for the diagnosis of rheumatoid arthritis.It has the specificity of about 81-100%, with the sensitivity of 3994%.

# History and Symptoms
Patients with rheumatoid arthritis may have a positive history of the family history of RA, history of smoking and other autoimmune disease. Common symptoms of rheumatoid arthritis are joint pain of small joints of the hands, wrist, and forefoot, joint swelling, morning joint stiffness classically lasting for more than an hour, decreased grip strength, generalized aching, and fatigue, weight loss, depression. Less common symptoms are tingling and numbness in the arm and weakness in the arm.

# Physical Examination
Patients with rheumatoid arthritis usually appear fatigued. On skin examination, rheumatoid nodules, erythema nodosum, atrophy of the digital skin, palmar erythema and diffuse thinning of the skin are found. If there is involvement of eyes, Scleritis and Scleromalacia are seen. On auscultation of lungs, there are decreased breath sounds on both sides and crackles may be present. On palpation of the abdomen, hepatomegaly and splenomegaly is usually found when it is associated with Felty's syndrome. On examination of extremities, redness, and swelling of the affected joints, tenderness, pain on movement and decreased the range of movement is usually found.

# Laboratory findings
Laboratory tests used to diagnose rheumatoid arthritis are complete blood count with differentials, erythrocyte sedimentation rate, CRP, Renal function test, LFT and antibodies such as rheumatoid factor, anti-CCP and anti MCV.

# X-ray
Hallmark of rheumatoid arthritis are soft tissue swelling, joint space narrowing and erosions. Hand and wrist findings on xray are subchondral cysts, ulnar deviation of the MCP joints, boutonniere and swan neck deformities, hitchhikers thumb deformity, scapholunate dissociation, ulnar translocation and ankylosis. Feet findings on xray are Subtalar joint involvement, posterior calcaneal tubercle erosion, hammer toe deformity and hallux valgus. Findings of shoulder such as distal clavicle erosions, erosions of the superolateral aspect of the head of the humerus, high riding shoulder due to subacromial-subdeltoid bursitis. Knee findigs are joint effusions, loss of joint space and prepatellar bursitis. Hip findings are concentric loss of joint space and acetabular protrusio. Spine findings are atlantoaxial subluxation, atlantoaxial impaction: cephalad migration of C2,osteoporosis and osteoporotic fractures and erosion of spinous processes.

# ECG
There are no ECG findings associated with rheumatoid arthritis. An ECG may be helpful in the diagnosis of pericarditis associated with rheumatoid arthritis. Findings of pericarditis are diffuse ST-segment elevation and PR segment depression.

# Ultrasound
Ultrasound is helpful in the diagnosis of rheumatoid arthritis. Findings on an ultrasound suggestive of rheumatoid arthritis are tenosynovitis, bursitis, baker's cyst and inflammation of synovium. Therapeutic use of ultrasound are  guidance of corticosteroid injection in the joint and fluid aspiration from the joint effusion.

# CT
CT scan is a useful non-invasive test used to diagnose the complications of rheumatoid arthritis such as subluxation of the alanto-axial joint. It is also used in the presurgical assessment of neurological symptoms.

# MRI
MRI is helpful in the diagnosis of early and subacute rheumatoid arthritis. Findings on MRI diagnostic of rheumatoid arthritis are synovial hyperemia, synovial hyperplasia, pannus, subchondral cysts, erosions, effusion of joints and bone marrow edema.

# Other imaging studies
DEXA Scan is helpful in the diagnosis of the complication of rheumatoid arthritis such as osteoporosis and osteopenia.

# Other diagnostic studies
There are no other diagnostic studies associated with rheumatoid arthritis.

# Treatment

# Medical Therapy
The mainstay of treatment of rheumatoid arthritis is pharmacotherapy. Early diagnosis of rheumatoid arthritis is helpful in treatment. Choice of treatment depends on various factors such as stage of disease, comorbid conditions, stage of therapy and presence of severe prognostic signs. There are two types of therapies- non-pharmacological therapy and pharmacological therapy. There are different drug regimen depending upon the stage of the disease. In active stage, combined therapy include disease-modifying antirheumatic drugs (DMARDs) are used along with the anti-inflammatory drugs. Therapy for resistant disease and flares is the addition of oral glucocorticoids. In case of the flare, add another DMARDs with methotrexate or replace with another DMARDs.

# Surgical Therapy
The mainstay of treatment for rheumatoid arthritis is medical therapy. Surgery is usually reserved for patients with debilitating disease, failure of medical therapy and radiographic findings of end-stage arthritis. Various surgical options used for the treatment of RA are tenosynovectomy, arthroscopic or open synovectomy, joint fusion, small joint implant arthroplasty, total joint replacement of deformed joint.

# Primary prevention
Effective measures for the primary prevention of rheumatoid arthritis are patient education, exercise, physical and occupational therapy and cognitive behavioral therapies.

# Secondary prevention
Effective measures for the secondary prevention of rheumatoid arthritis are calcium and vitamin D supplementation to prevent osteoporosis. To prevent cardiovascular complications and recurrent attacks of RA, effective methods are exercise, smoking cessation, and dietary control.

# Reference