Rheumatoid Arthritis & Inflammatory Arthritis
Anti-CCP, the early-methotrexate window, and the HLA-B27 PAIR
Rheumatoid arthritis: presentation and diagnosis
Joint pattern. Rheumatoid arthritis (RA) is a chronic, symmetric inflammatory polyarthritis of the MCP, PIP and wrist joints (often the MTPs too) that SPARES the DIP. Morning stiffness lasts over 1 hour and improves with use. Women are affected about 3:1, onset peaks at 30–50, and HLA-DR4 (and smoking) confer risk.
RA spares the DIP; osteoarthritis targets it (Heberden nodes), with brief stiffness and pain that worsens with use, a fast bedside discriminator.
Serology. Anti-CCP antibody is about 95% specific for RA and predicts erosive disease. Rheumatoid factor (IgM against the Fc portion of IgG) is sensitive but nonspecific: it is also positive in hepatitis C, Sjögren syndrome and endocarditis. ESR and CRP rise. The 2010 ACR/EULAR classification criteria combine the number and size of joints involved, serology, acute-phase reactants and symptom duration (6 weeks or more).
Erosions and deformities. Untreated synovial pannus erodes the joint: juxta-articular osteopenia first, then marginal erosions and joint-space narrowing. Chronic hand deformities include ulnar deviation at the MCPs, swan-neck (PIP hyperextension, DIP flexion), boutonnière (PIP flexion, DIP hyperextension) and Z-thumb.
| Feature | Rheumatoid arthritis | Seronegative spondyloarthropathy |
|---|---|---|
| Joints | Symmetric small joints; spares the DIP | Asymmetric, axial (sacroiliitis), large lower-limb joints; DIP in psoriatic disease |
| Serology | RF and anti-CCP positive | RF negative |
| Genetics | HLA-DR4 | HLA-B27 |
| Distinctive features | Nodules, marginal erosions, extra-articular organ disease | Enthesitis, dactylitis, anterior uveitis |
RA as a systemic disease
- Skin: rheumatoid nodules over extensor surfaces, usually with high-titer RF.
- Lung: interstitial lung disease, pleural effusions with very low glucose, and lung nodules (Caplan syndrome with pneumoconiosis).
- Blood: anemia of chronic disease; Felty syndrome (RA + splenomegaly + neutropenia).
- Eyes and glands: secondary Sjögren syndrome, episcleritis and scleritis.
- Heart and vessels: pericarditis and accelerated atherosclerosis; cardiovascular disease is the leading cause of death in RA.
- Kidney: AA amyloidosis from chronic inflammation.
- Cervical spine: atlantoaxial (C1–C2) subluxation, which endangers intubation; check the neck before anesthesia.
Treating RA
Principles. Start disease-modifying therapy EARLY, as soon as RA is diagnosed and ideally within 3 months of symptom onset, to prevent irreversible erosions, and treat to target (remission or low disease activity), escalating until the target is reached. Methotrexate is the anchor DMARD. NSAIDs and glucocorticoids only relieve symptoms; they do not halt joint destruction. Glucocorticoid bridging is optional and should be brief (under 3 months) and low dose: the 2021 ACR guideline conditionally favors starting methotrexate without it and recommends against long-term use. Prolonged steroid use calls for bone protection.
Before starting. Obtain baseline hand and foot radiographs, CBC, liver and renal tests, and hepatitis B and C serologies; screen for latent TB before any biologic. Update vaccines, giving live vaccines before biologic therapy begins.
- Diagnose earlyanti-CCP, RF, ESR/CRP
- Start methotrexate nowideally within 3 months of onset to prevent erosions
- Treat to targetescalate to remission or low activity
- Add a biologic if inadequateTNF inhibitor or another targeted agent
| Drug | Mechanism | Key toxicity and monitoring |
|---|---|---|
| Methotrexate | Dihydrofolate reductase inhibitor | Myelosuppression, hepatotoxicity, pneumonitis; give folic acid; monitor CBC, LFTs and creatinine; teratogen and abortifacient |
| Hydroxychloroquine | Antimalarial immunomodulator | Irreversible retinopathy: baseline retinal exam, then annual screening after 5 years (sooner if high risk) |
| Sulfasalazine | Sulfapyridine + 5-ASA | GI upset, rash, reversible oligospermia |
| Leflunomide | Pyrimidine synthesis inhibitor | Teratogen with a very long half-life (cholestyramine washout); hepatotoxicity |
| TNF inhibitors | Etanercept, infliximab, adalimumab | Reactivate latent TB and hepatitis B, so screen first; avoid in heart failure and demyelinating disease |
| Other targeted agents | Rituximab (anti-CD20), abatacept (CTLA4-Ig), tocilizumab (anti-IL-6 receptor), tofacitinib (JAK inhibitor) | Serious infections; JAK inhibitors carry thrombosis and cardiovascular warnings |
Methotrexate and leflunomide are contraindicated in pregnancy (stop methotrexate 1 to 3 months before conception; leflunomide needs a cholestyramine washout, 8 g three times daily for 11 days, until teriflunomide is below 0.02 mg/L on two tests 14 days apart). Hydroxychloroquine, sulfasalazine, TNF inhibitors (certolizumab can be continued throughout) and low-dose prednisone are pregnancy compatible. RA activity often eases during pregnancy and flares postpartum.
Seronegative spondyloarthropathies
Shared features. These disorders are RF-NEGATIVE and HLA-B27-linked and share sacroiliitis with inflammatory back pain, enthesitis (e.g., Achilles), dactylitis and anterior uveitis. Mnemonic PAIR: Psoriatic arthritis, Ankylosing spondylitis, IBD-associated arthritis, Reactive arthritis.
| Disease | Typical patient | Hallmarks | Treatment |
|---|---|---|---|
| Ankylosing spondylitis | Young men | Back pain worse at rest and in the morning, BETTER with exercise; sacroiliitis progressing to bamboo spine; reduced chest expansion; anterior uveitis, aortic regurgitation | NSAIDs and physical therapy; TNF inhibitors if refractory |
| Psoriatic arthritis | Up to a third of psoriasis patients | Asymmetric DIP disease, dactylitis (sausage digit), nail pitting and onycholysis, pencil-in-cup deformity, rarely arthritis mutilans | NSAIDs; methotrexate or biologics for progressive disease |
| IBD-associated | Crohn disease, ulcerative colitis | Peripheral arthritis tracks bowel activity; axial disease does not | Treat the bowel disease; TNF inhibitors |
| Reactive arthritis | Weeks after Shigella, Salmonella, Campylobacter, Yersinia or genitourinary Chlamydia infection | Conjunctivitis, urethritis, asymmetric arthritis ("can't see, pee or climb a tree"); keratoderma blennorrhagicum, circinate balanitis | NSAIDs; treat active chlamydia |
Ankylosing spondylitis. Sacroiliac x-rays confirm established disease; MRI detects early sacroiliitis when films are normal. Methotrexate does not treat axial disease. The fused, osteoporotic spine can fracture after minor trauma.