Rheumatoid Arthritis Overview

Rheumatoid Arthritis

• Rheumatoid arthritis (RA) is a common inflammatory arthritis
• It affects people worldwide
• Peak age of onset is 35-50 years, with a female to male ratio of 3:1
• Characterized by exacerbations and remissions
• Involves synovium of joints, leading to cartilage and bone damage
• Has both genetic and environmental components
• Higher concordance in monozygotic twins (12-15%) compared to dizygotic twins (3%)
• Environmental factors, like infection, trigger autoimmunity in susceptible individuals
• Cigarette smoking is a significant environmental risk factor, associated with more severe disease and reduced treatment response
• Remission can occur during pregnancy; sometimes RA first manifests postpartum
• Hormonal changes may play a role in the remission during pregnancy
• The etiology of RA is poorly understood, though environmental factors are suspected to trigger autoimmune response in genetically susceptible individuals
• Smoking is another risk factor
• Genetic predisposition is evident in increased frequency of the disease in patients' first-degree relatives

Pathogenesis

• Characterized by synovial hyperplasia (increased synovial membrane cell number and size)
• Inflammatory cell infiltration (lymphocytes, plasma cells, dendritic cells, and macrophages)
• Joint effusion (fluid accumulation in the joint space)
• Formation of pannus (invasive synovium that erodes cartilage and bone)

Clinical Features

• Typical presentation includes pain, joint swelling and stiffness affecting small joints of hands, feet, and wrists.
• Often symmetrical
• Inflammatory polyarthritis; morning stiffness lasting >1 hour, improving throughout the day
• Common joints involved include hands (PIP, MCP), wrists, knees, ankles, elbows, hips, and shoulders
• Characteristic hand deformities include:
  • Ulnar deviation of the MCP joints
  • Boutonnière deformities of the PIP joints (PIP flexed; DIP hyperextended)
  • Swan-neck contractures of the fingers (MCP flexed; DIP hyperextended)
• Examination typically reveals swelling and tenderness of affected joints, but not necessarily erythema
• Other articular symptoms include triggering of fingers, cock-up toe deformities, and Baker's cyst (in the knee) development

Extra-articular Features

• Most common in patients with long-standing seropositive erosive disease
• Often includes serositis, granuloma and nodule formation, or vasculitis
• Rheumatoid nodules often present; almost exclusively in patients positive for RF or ACPA and typically appear in extensor tendons
• May cause involvement of visceral structures (lungs, pleura, pericardium)
• May be asymptomatic but can be complicated by ulceration and secondary infection
• Can cause systemic symptoms such as fever, weight loss, fatigue, anemia, susceptibility to infection; osteopenia or osteoporosis and musculoskeletal problems

Systemic, Hematological, and Ocular Manifestations

• Includes fever, weight loss, fatigue, susceptibility to infections
• Muscle wasting, tenosynovitis, bursitis, osteoporosis
• Anemia, thrombocytosis, eosinophilia
• Episcleritis, scleritis, scleromalacia
• Keratoconjunctivitis sicca
• Digital arteritis; ulcers; pyoderma gangrenosum; mononeuritis multiplex
• Visceral arteritis.
• Caplan syndrome (a pulmonary complication of RA)

Cardiac and Pulmonary Manifestations

• May involve: pericarditis, myocarditis, endocarditis, conduction defects, coronary vasculitis, granulomatous aortitis, nodules, pleural effusions, fibrosing alveolitis, bronchiolitis

Neurological Manifestations

• Include compression neuropathies, cervical cord compression, peripheral neuropathy, mononeuritis multiplex, and amyloidosis (nephrotic syndrome)

Investigations

• Diagnosis is primarily clinical based on symptoms and physical examination
• Helpful for confirmation and activity assessment
• Rheumatoid factor (RF) positive in about 70% of cases, but less specific than ACPA
• ACPA (Anti-citrullinated protein antibodies); highly specific for RA, often present before clinical symptoms appear
• Investigations of use may include Elevated ESR, CRP and anemia of chronic disease
• Radiographs-not required for diagnosis but helpful. Signs of RA in radiographs can include loss of juxta-articular bone mass; joint space narrowing, marginal erosions; and atlanto-axial disease.

Radiographs

• X-rays and other images are valuable but not required for diagnosis
• Juxta-articular osteoporosis, and joint space narrowing are common findings; these features are typically seen late in disease progression
• Marginal joint erosions
• X-rays of atlanto-axial joints are important to check

Classification Criteria

• 1987 and 2010 ACR/EULAR criteria for classification of rheumatoid arthritis.
• Presence of synovitis in at least one joint.
• Absence of another better diagnosis explaining the synovitis
• Score greater than 6/10 on:
  • Number and site of involved joints (range 0-5)
  • Serological abnormality (range 0-3)
  • Elevated acute phase response (range 0-1)
  • Symptom duration (two levels, range 0-1)

Disease Activity Measures

• DAS28 index is commonly used for assessing RA activity, treatment response, and biological therapy requirement
• Combination of swollen and tender joint count, ESR, and patient-reported disease activity on a visual analog scale
• Data input into calculator to provide numerical score
• Higher score indicates more active disease

Principles of Management

• Aims to educate patients about their disease
• Control pain, minimize symptoms, and optimize function
• Modify the course of the disease
• Identify and treat comorbidities
• Combination of pharmacological and non-pharmacological therapies, considering factors like age (especially pregnancy)
• Education on diet and lifestyle is crucial

Education and Exercise

• Crucial components
• Improves quality of life and treatment outcomes
• Includes aerobic fitness training, local strengthening exercises, and physical and occupational therapy
• Local heat, ice packs, splints, and orthoses
• Weight control; obesity increases mechanical strain and is a progression risk factor for joint damage

Symptomatic Treatment

• NSAIDs for pain control
• Short-term corticosteroid use for flares; avoid long-term use

Disease-Modifying Antirheumatic Drugs (DMARDs)

• Methotrexate is best initial DMARD, with improvement evident within 4-6 weeks
• Side effects include gastrointestinal upset, mild alopecia, bone marrow suppression and potential liver/interstitial pulmonary issues
• Supplemental folic acid is often necessary
• Other DMARDs given if primary fails or toxicity occurs, often in combination
• Dose-limiting toxicity or lack of response prompts addition or switching of DMARDs
• Low-dose glucocorticoids might be needed during the transition period, if symptoms persist.

Biologic Therapies (for high disease activity)

• Used if disease activity persists despite other treatment modalities.
• Include monoclonal antibodies, fusion proteins and decoy receptors for cytokines, receptors.
• Target specific cytokines, receptors, and other immune molecules
• Target specific cells or molecules in the immune system to reduce inflammatory processes
• Examples include TNF inhibitors (etanercept, infliximab), abatacept, and rituximab
• JAK inhibitors (tofacitinib and baricitinib) are alternative treatment choices

Surgery

• Synovectomy (surgical removal of synovium): beneficial for joints that haven't responsive to other treatments, especially in intra-articular injections.
• Joint replacement may be necessary/required for severe joint damage but has become less common due to early aggressive management
• Other possible procedures include excision of metatarsal heads, neurosurgery, and fusion of joints to correct subluxation or other damage

Long-term Prognosis

• Factors correlating with an unfavorable prognosis include HLA-DRB1*04/04 genotype
• High serum titers of autoantibodies (eg, RF, ACPA)
• Extra-articular manifestations
• Large number of involved joints
• Age younger than 30 years
• Female sex
• Insidious onset

Rheumatoid Arthritis and Pregnancy

• Immunological changes influence RA during pregnancy.
• Conception planning—certain medications such as methotrexate and leflunomide should be stopped before pregnancy
• Paracetamol is the analgesic of choice during pregnancy
• Oral NSAIDs and COX-2 inhibitors are generally considered safe from implantation to 20 weeks
• Glucocorticoids can be used in flare-ups but come with risks like hypertension, glucose disorders, and osteoporosis

Pregnancy and Medications

• DMARD choices during pregnancy are limited due to potential risks to the fetus.
• Avoid methotrexate, leflunomide, cyclophosphamide, and gold
• Some biologics, like certolizumab, cross the placenta to some extent but may be relatively safe
• Breastfeeding is contraindicated with these medications.