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Rheumatoid arthritis is a systemic autoimmune disorder characterized by chronic destructive inflammation of joints.
Risk factors:
Female gender.
Genetic predisposition:
- HLA-DR4 association: This gene is located within Major Histocompatibility complex (MHC) and encodes the MHC II beta chain molecule.
- Non-MHC genes:
- Gene encoding protein tyrosine phosphatase non receptor 22 (PTPN22).
- Peptidyl arginine deiminase type IV (PADI4) gene.
Clinical features:
Symptoms:
Insidious onset painful multiple symmetric joints (MCP joints, PIP joints of hand, wrist, ankle, knee, shoulder, hips, elbow). Initial pattern of joint involvement could be polyarticular (>5 joints), Oligoarticular (<4) or monoarticular (1).
Morning stiffness.
Pain and stiffness decrease on activity.
Ligament and tendon deformity:
- Swan neck deformity: Hyperextension at PIP and flexion at DIP.
- Boutonniere deformity: flexion at PIP and hyperextension at DIP.
- Z line deformity: subluxation of first MCP and distal radio ulnar joint.
Extra articular manifestations of Rheumatoid Arthritis:
- Rheumatoid nodules: Non tender nodules at bony prominence and near joints affected by disease at extensor surface of hand.
- Lungs: Pleuritis, exudative pleural effusion.
- Mononeuritis multiplex: multiple neuropathy occurring concomitantly. Eg. Carpel tunnel syndrome, Tarsal tunnel syndrome.
- Livido retucularis: fine blood vessels giving fish net appearance at skin.
Fish net appearance on immune fluorescence study of skin biopsy is seen in pemphigus vulgaris.
- Purpura.
- Ulcers at tip of fingers.
Spine: C axial spine: Cervical axial spine is highly vulnerable to atlanto axial dislocation thus producing compression myelopathy.
- Eyes: Keratocunjuctive sicca, scleritis, episcleritis, scleromalacia perforans.
- Salivary glands: Xerostomia.
- Heart: Pericarditis, Myocarditis, Mitral regurgitation, Tachyarrhythmias.
- Kidney: Membranous glomerulopathy, Secondary amyloidosis.
- Bone: osteoporosis.
- Hematology: anemia of chronic disease (Normocytic Normochromic).
Work up and diagnosis:
- Complete blood count: Anemia, Normocytic normochromic anemia.
- RA factor: IgM, and can be biologically false positive in 5% of population and used for screening.
- Anti-Cyclic citrulline peptide: Increased.
- Joint aspiration: Turbid fluid and increased WBC count (5000-50000 cells/microliter).
- X-rays:
- Early: soft tissue swelling and peri-articular osteoporosis/ demineralization.
- Late: Symmetric joint space narrowing and erosions.
- MRI hands: Synovitis, Joint involvement.
Rheumatoid Arthritis can coexist with multiple autoimmune disorders like: Rhupus (Systemic Lupus Erythematosus + Rheumatoid Arthritis), 20 Sjögren’s syndrome (Sicca + Rheumatoid Arthritis).
Synovial fluid analysis:
| Disorders | Color | Clarity | Viscosity | WBC | Neutrophils | Gram stain | Crystals |
| Normal | Colorless | Translucent | Increased | <200 | <25 % | Negative | Negative |
| Non-inflammatory | Straw | Translucent | Increased | 200-2000 | < 25% | Negative | Negative |
| Inflammatory | Yellow | Cloudy | Decreased | 2000-50000 | >50% | Negative | Positive |
| Septic | Yellow/ Green | Cloudy / Opaque | Decreased | >50000 | >75% | Positive | Negative |
| Hemarthrosis | Red/ Xanthochromic | Bloody | Variable | 200-2000 | 50-75% | Negative | Negative |
Diagnostic Criteria:
1. 2010 ACR/EULAR criteria for Diagnosis of Rheumatoid arthritis:
| Joint involvement: 1 large joint 2-10 large joints 1-3 small joints 4-10 small joints >10 joints | Score 0 1 2 3 5 |
| Serology: Negative RF and Negative Anti cyclic citrulline peptide Low positive RF or Low positive Anti cyclic citrulline peptide High positive RF or High positive Anti cyclic citrulline peptide | 0 2 3 |
| Acute phase Reactants Normal C-reactive protein and Normal Erythrocyte sedimentation rate High C-reactive protein and High Erythrocyte sedimentation rate | 0 1 |
| Duration of symptoms <6 weeks ≥6 weeks | 0 1 |
Need ≥6 for diagnosis.
2. ACR criteria 1987:
- Morning stiffness >or= 1 hour.
- Arthritis of >or= 3 joints observed by physician simultaneously: Right/left PIP, MCP, Wrist, Elbow, knee, ankle, MTP.
- Arthritis of hand joints: PIP, MXP, Wrist.
- Symmetric arthritis.
- Rheumatoid nodules.
- Positive Rheumatoid Factor
- Radiographic erosions or peri-articular osteopenia in hand or wrist joints.
Criteria 1-4 must be present for ≥ 6 weeks. Must have ≥ 4 criteria to meet diagnosis of Rheumatoid arthritis.
Treatment and Management:
NSAIDs: for pain management but no other role in Rheumatoid Arthritis. Intra-articular steroids injection has no effect on disease progression.
Disease modifying anti-Rheumatoid drugs (DMARDs): Methotrexate on once a week basis.
Triple therapy: Methotrexate (higher dose) + Sulfasalazine + Hydroxychloroquine.
Methotrexate + Biologics (Certolizumab, Rituximab, Abatacept, Tocilizumab).
Methotrexate + Tofacitinib (JAK 3 inhibitor).
References:
- Apley & Solomon’s System of Orthopaedics and Trauma, 10th edition.
- Harrison’s Principles of Internal Medicine, 21st edition.
- Robbins Basic Pathology: 10th Edition
