أسئلة الثانية روماتولوجي حورس

Rheumatoid Arthritis (RA) Definition

• RA is a chronic, systemic autoimmune disease
• RA primarily targets the synovium (the lining of the joints)

RA Epidemiology

• Incidence: Affects approximately 1% of the adult population
• Age: Can occur at any age, but commonly affects women in their late childbearing years
• Sex: More common in females, with a female-to-male ratio of 3:1

Rheumatoid Arthritis Pathogenesis

• Genetic predisposition (HLA/Non-HLA) and environmental factors (e.g., smoking, infection) contribute to the development of RA
• Pre-RA phase involves: ACPA, RF, impaired T/B-cell tolerance and deregulated TLR/cytokine signalling
• Trigger events lead to synovial inflammation like: minor trauma, vascular factors or innate immune mechanisms
• RA phenotype can manifest as: bone erosion, disability, atheroma, and extra-articular features

RA Pathology

• Primary pathology is inflammation of the synovial membrane
• Inflammation leads to synovitis and proliferation
• This progress to loss of articular cartilage and erosion of juxtaarticular bone

RA Clinical Features

• Onset of disease
• Systemic symptoms
• Distribution of involved joints
• Morning stiffness
• Articular manifestations
• Extra-articular manifestations

Onset

• Insidious: Weeks to months, patient may hardly notice disease onset
• Fulminant: Abrupt onset of pain and stiffness
• Palindromic rheumatism: Episodic or self-limited attacks of polyarthritis

Number of Joints

• Monoarthritis: Atypical presentation
• Oligoarthritis
• Polyarticular: Typical presentation

Systemic Symptoms

• Fatigue
• Low-grade fevers (≤38°C)
• Weight loss

Distribution of Involved Joints

• Joints involved: PIP, MCP, MTP joints, and large joints occurring later
• Joints spared: DIP joints
• Joints that may be affected: Temporomandibular, cricoarytenoid, sternoclavicular joints, and upper cervical spine (C1-2 articulation)
• Significance: Involvement is a hallmark of inflammatory arthritis

Morning Stiffness

• Is a hallmark of inflammatory arthritis
• Worst upon arising in the morning and after prolonged periods of rest
• Stiffness is located in and around joints
• Duration can last for hours
• Symptoms improve with activity, running, or warm water

Articular Manifestations

• Pain, swelling, and stiffness
• Affects the hands:
  • Synovial proliferation and swelling of MCP, PIP joints
  • Late-stage deformities include ulnar deviation, swan neck, and boutonnière deformities
• Wrists:
  • Early indication is Synovial proliferation
  • Late sign is carpal tunnel syndrome
• Affects the feet:
  • MTP joints with subluxation of the toes
  • Skin ulceration
• Large Joints: Involvement is common at the late stage, and occurs Symmetrically
• Cervical Spine: Can involve Atlantoaxial subluxation

Extra-Articular Manifestations

• Dermatologic:
  • Rheumatoid nodules (with/without ulceration)
  • Periungual vasculitic infarcts
  • Vasculitic leg ulcers
  • Pyoderma gangrenosum
• Mucosal:
  • Sicca symptoms (ocular, oral, vaginal mucosa)
  • Sjögren syndrome
• Ocular:
  • Keratoconjunctivitis sicca
  • Episcleritis
  • Scleritis
  • Scleromalacia perforans
  • Peripheral ulcerative keratitis
• Pulmonary:
  • Nonspecific interstitial pneumonitis
  • Cryptogenic organizing pneumonitis
  • Bronchiectasis
  • Bronchiolitis obliterans
  • Pleuritis and pleural effusion
  • Rheumatoid nodulosis in the lungs
  • Caplan syndrome
• Cardiac:
  • Pericarditis and pericardial effusion
  • Constrictive pericarditis
  • Valvular thickening and nodulosis
  • Conduction abnormalities
  • Coronary vasculitis
  • Myocarditis
• Hematologic and Lymphatic System:
  • Anemia of chronic disease
  • Felty syndrome
  • Large granular lymphocyte leukemia
  • Extremity lymphedema (unilateral or bilateral)
• Neurologic:
  • Compression neuropathies
  • Atlantoaxial subluxation
  • Peripheral neuropathy
  • Mononeuritis multiplex
  • Rheumatoid pachymeningitis
• Renal:
  • AA amyloidosis
  • Necrotizing crescentic glomerulonephritis (rare)

Felty Syndrome Components

• Splenomegaly
• Anemia
• Neutropenia
• Thrombocytopenia
• Rheumatoid Arthritis

Felty Syndrome Physical Examination

• Swollen spleen
• Joints that show signs of rheumatoid arthritis
• Possibly swollen liver and lymph nodes

Rheumatoid Arthritis Investigations, Lab Findings

• CBC:
  • Anemia of chronic disease
  • Increased white blood cell count, decreased (Felty syndrome) or normal levels
  • Thrombocytosis during active disease
• Acute phase reactants: Elevated ESR and CRP
• Autoantibodies:
  • RF: Against IgG
  • Anti-CCP antibodies
  • ANA (30%)
  • ANCA (30%)
• Synovial fluid: WBCs 5000-50,000/mcL

Differential Diagnosis of a Positive Rheumatoid Factor

• Rheumatic diseases like rheumatoid arthritis, Sjögren syndrome, and systemic lupus erythematosus
• Infections, especially viral infections like Hepatitis C or bacterial infections like endocarditis
• Inflammation from chronic inflammatory conditions and others
• Others that can cause include liver disease, inflammatory bowel disease, and aging

Rheumatoid Arthritis Imaging Studies

• X-ray findings:
  • Juxta articular demineralization
  • Joint-space narrowing
  • Late-stage bony erosions, deformities, subluxation
• Musculoskeletal Ultrasound:
  • Synovitis
  • Erosions
  • Tenosynovitis
• MRI of cervical spine: Used to detect Atlantoaxial subluxation

Making a Diagnosis of Rheumatoid Arthritis

• A single finding on physical exam or lab tests is not diagnostic of RA
• The American College of Rheumatology (ACR) classification criteria is used for diagnosis

1987 American College of Rheumatology Criteria

• Morning stiffness
• Arthritis of three joint areas
• Arthritis of the hands
• Symmetric arthritis
• Rheumatoid nodules
• Serum rheumatoid factor
• Radiographic changes
• These criteria must be present for more than 6 weeks

2010 Classification Criteria for Rheumatoid Arthritis

• Uses a scoring system based on joint involvement, serology, acute-phase reactants, and duration of symptoms
• Criteria apply only to patients who have objective signs of synovitis in at least one joint and who do not have a better alternative explanation for synovitis
• A patient is classified as having rheumatoid arthritis if the sum of the scores in categories A-D is >6

Rheumatoid Arthritis Differential Diagnosis

• Viral syndromes (Hepatitis B and C, Epstein-Barr virus)
• Psoriatic arthritis
• Reactive arthritis
• Tophaceous gout
• Systemic lupus erythematosus
• Calcium pyrophosphate disease
• Polymyalgia rheumatica
• Paraneoplastic syndromes
• Osteoarthritis
• Sarcoidosis

Rheumatoid Arthritis Treatment

• Aggressive treatment using disease-modifying antirheumatic drugs (DMARDs) can lead to better long-term outcomes
• Glucocorticoids
• Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Synthetic DMARDs
• Biologic DMARDs
• Janus Kinase (JAK) Inhibitors

Glucocorticoids for RA Treatment

• Use: Low-dose glucocorticoids (e.g., prednisone 5–10 mg daily) and intra-articular injections in large joints
• Caution: Not appropriate as monotherapy for RA

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) for RA Treatment

• Used to provide symptomatic relief
• Caution: Should not be used as the sole therapy for RA

Disease-Modifying Antirheumatic Drugs (DMARDs)

• Optimal control of Rheumatoid Arthritis often requires combinations of different synthetic DMARDs or combinations of synthetic DMARDs and a biologic DMARD
• Common Synthetic DMARD's:
  • Methotrexate
  • Hydroxychloroquine
  • Sulfasalazine
  • Leflunomide
  • Minocycline

Methotrexate

• Dose: Single dose once a week,(maximum of 25 mg), never on a daily basis
• Supplementation: Oral folate should be taken
• Monitoring: Blood cell counts, liver transaminase levels, and serum creatinine checked every 3 months
• Contraindications: Liver disease and renal impairment
• Toxicities: Oral ulcers, nausea, hepatotoxicity, bone marrow suppression, and pneumonitis

Hydroxychloroquine

• Mechanism of action: Antimalarial
• Dose: 200–400 mg daily
• Side effects: Retinal toxicity

Sulfasalazine

• Dose: 1-3 g daily
• Side effects: Hypersensitivity

Leflunomide

• Dose: 10-20 mg
• Side effects: Diarrhea, hepatotoxicity, hypertension, and teratogenic effects

Biologic DMARDs

• Targets/Agents:
  • TNF-α: Infliximab, Adalimumab, Golimumab, Certolizumab pegol
  • TNF-α Lymphotoxin: Etanercept
  • CD80, CD86: Abatacept
  • CD20: Rituximab
  • Interleukin-6 receptor: Tocilizumab
• Side effects: Increase risk of infection

Janus Kinase (JAK) Inhibitors

• Mechanism of action: Small-molecule inhibitors
• Drugs: Tofacitinib, Baricitinib, Upadacitinib
• Administration: Oral
• Side effects: Increase the risk of herpes zoster reactivation

Adult-Onset Still Disease

• Characterized by quotidian fever over 39°C, rash, and pharyngitis
• Rash:
  • Evanescent
  • Salmon-colored macular rash
  • Often coincident with fever spikes
• Includes: Polyarthralgia, Lymphadenopathy, Splenomegaly, Serositis
• Common laboratory abnormalities: Leukocytosis, elevated acute phase reactants (ESR, CRP) and dramatic increases in the serum ferritin level