By the end of this note you will be able to describe the clinical approach to rheumatoid arthritis, recognise its key features, order and interpret relevant investigations, and outline immediate and definitive management – remembering to verify drug doses and local protocols against the Kenya MoH guideline and your hospital formulary.
Definition
Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune inflammatory arthritis characterised by symmetric synovial joint involvement that leads to progressive joint destruction, functional disability, and extra‑articular manifestations.
Anatomy and physiology you need
| Structure | Relevance to RA |
|---|---|
| Synovial membrane (intima) | Site of inflammatory cell infiltration and pannus formation |
| Joint capsule & ligaments | Targeted by pannus → erosion of cartilage & bone |
| Subchondral bone | Resorption by osteoclasts driven by cytokines |
| Periarticular muscles | Atrophy from disuse and inflammatory cytokines |
| Lymphoid tissue (e.g., spleen, lymph nodes) | Source of auto‑reactive B‑ and T‑cells |
| Systemic organs (lung, heart, vessels) | Sites of extra‑articular disease (e.g., interstitial lung disease) |
Causes and risk factors
- Genetic predisposition – HLA‑DRB1 shared epitope alleles common in African populations.
- Sex – Female predominance (≈3:1).
- Age – Peak onset 40–60 years, but can present earlier.
- Environmental triggers – Smoking (including shisha), silica dust, periodontal disease.
- Infections relevant to Kenya –
- HIV – Immune dysregulation may precipitate seronegative arthritis mimicking RA.
- Tuberculosis – Chronic immune activation; TB‑associated arthritis can coexist.
- Malaria & other endemic infections – Repeated immune stimulation may unmask autoimmunity.
- Co‑morbid tropical conditions –
- Sickle cell disease – Vaso‑occlusive crises and chronic inflammation increase auto‑immune risk.
- Rheumatic fever – Though primarily a post‑streptococcal disease, overlapping joint symptoms can confuse early RA.
- Obesity – Adipokines amplify systemic inflammation.
- Hormonal factors – Post‑menopausal estrogen decline may influence disease activity.
Pathophysiology
- Genetic & environmental hit →
- Loss of tolerance to citrullinated self‑proteins →
- Auto‑antibody production (RF, anti‑CCP) →
- Immune complex formation & complement activation →
- Synovial infiltration by CD4⁺ T‑cells, B‑cells, macrophages →
- Cytokine storm (TNF‑α, IL‑1, IL‑6, IL‑17) →
- Synovial hyperplasia → pannus formation →
- Cartilage degradation (MMPs) & bone erosion (RANKL‑mediated osteoclasts) →
- Joint deformity, functional loss & systemic inflammation.
Clinical features
| Aspect | Key questions / findings | Why it occurs |
|---|---|---|
| Onset & duration | “When did the joint pain start? Has it been gradual or sudden?” | RA usually begins insidiously over weeks‑months; chronicity distinguishes it from post‑infective or crystal arthropathies. |
| Pattern of joint involvement | “Which joints are painful or swollen? Are they the same on both sides?” “Do you have morning stiffness? How long does it last?” | Symmetrical polyarthritis of small joints (MCP, PIP, wrists) is classic; stiffness >30 min reflects inflammatory synovitis. |
| Systemic symptoms | “Do you feel feverish, fatigued, lose weight or have night sweats?” | Cytokine‑driven inflammation produces constitutional features; helps separate from purely mechanical pain. |
| Functional impact | “Can you dress, write or open jars?” “Any difficulty climbing stairs?” | Joint damage and pain limit daily activities; early functional loss signals aggressive disease. |
| Extra‑articular manifestations | “Do you have dry eyes or mouth, nodules on elbows, rash, shortness of breath, chest pain, or leg swelling?” | Rheumatoid nodules, sicca symptoms (secondary Sjögren), interstitial lung disease, pleuritis, pericarditis, vasculitis are immune‑mediated extensions of the disease. |
| Past medical & infection history | “Have you been diagnosed with HIV, TB, malaria, or sickle‑cell disease? Any recent infections or vaccinations?” | In our setting, HIV, TB and chronic malaria can trigger or mimic RA; sickle‑cell disease may cause joint pain that confounds the picture. |
| Family & ethnic background | “Any relatives with rheumatoid arthritis or other autoimmune disease?” “What is your tribe/ethnicity?” | Genetic predisposition (HLA‑DRB1 shared epitope) and certain ethnic groups have higher prevalence. |
| Medication & exposure history | “Do you take any herbal remedies, antibiotics, or anti‑malarial drugs?” | Some drugs (e.g., minocycline) can cause drug‑induced arthritis; herbal products may mask symptoms. |
Examination findings
| Finding | What it indicates | Pathophysiologic basis |
|---|---|---|
| Symmetrical swelling of MCP/PIP/wrist joints | Active synovitis | Synovial membrane hypertrophy and effusion from cytokine‑driven inflammation. |
| Tenderness over the same joints | Pain generator | Inflamed pannus irritates nociceptors. |
| Joint warmth & erythema | Inflammatory nature | Increased blood flow and capillary leak in inflamed synovium. |
| Reduced range of motion (active > passive) | Pain‑limited movement | Pain inhibits active motion; passive may be preserved early. |
| Ulnar deviation of fingers, boutonnière or swan‑neck deformities | Chronic damage | Tendon imbalance and ligamentous laxity from prolonged synovitis. |
| Rheumatoid nodules (subcutaneous, over extensor surfaces) | Extra‑articular disease | Granulomatous inflammation in subcutaneous tissue. |
| Sicca signs (dry eyes, dry mouth) | Secondary Sjögren’s | Autoimmune exocrine gland involvement. |
| Pleural rub, reduced breath sounds, crackles | Pulmonary involvement | Rheumatoid pleuritis or interstitial lung disease. |
| Peripheral edema, skin ulcerations | Vasculitis | Small‑vessel immune complex deposition. |
| Positive rheumatoid factor or anti‑CCP in serum (lab) | Serologic confirmation | Autoantibodies formed against Fc portion of IgG (RF) or citrullinated peptides (anti‑CCP). |
Differential diagnosis
| Condition | Points toward it | How it differs from RA |
|---|---|---|
| Osteoarthritis | Age >50, mechanical pain, worsens with use, no morning stiffness | Asymmetric, non‑inflammatory, no systemic features, normal inflammatory markers |
| Psoriatic arthritis | Skin psoriasis, nail pitting, dactylitis, asymmetric oligo/polyarthritis | Presence of skin lesions, distal interphalangeal joint involvement, negative RF/anti‑CCP |
| Reactive arthritis | Recent GI or GU infection, enthesitis, sacroiliac pain | Usually asymmetric, HLA‑B27 positive, no rheumatoid nodules, seronegative |
| Systemic lupus erythematosus | Malar rash, photosensitivity, renal involvement, ANA positive | Non‑erosive arthritis, often migratory, serology distinct (ANA, anti‑dsDNA) |
| Infective (septic) arthritis | Acute mono‑articular pain, fever, rapid progression | Purulent joint fluid, positive cultures, usually single joint |
| Tuberculous arthritis | History of TB, mono‑articular involvement of weight‑bearing joints, chronic | Synovial biopsy shows granulomas, positive TB PCR/AFB |
| HIV‑associated arthritis | HIV positive, may be asymmetric, may coexist with opportunistic infections | Often self‑limiting, may improve with antiretroviral therapy, serology for RF often negative |
| Sickle‑cell vaso‑occlusive pain | Known sickle‑cell disease, pain crises, no true synovitis | No joint swelling, pain episodic, triggered by hypoxia |
| Gout / calcium pyrophosphate deposition disease | Acute mono‑articular pain, tophi (gout), chondrocalcinosis (CPPD) | Crystal identification in joint fluid, usually non‑symmetrical, no systemic rheumatoid features |
Investigations
| Test | What it answers | Interpretation |
|---|---|---|
| CBC & ESR/CRP | Inflammation level, anemia of chronic disease | Elevated ESR/CRP supports active inflammation; anemia common in chronic RA |
| RF (IgM) | Presence of rheumatoid factor | Positive in many RA patients but also in other diseases; high titres suggest severe disease |
| Anti‑CCP antibodies | Specificity for RA | Positive strongly supports RA; predicts erosive disease |
| X‑ray of hands/feet | Joint erosions, space narrowing, osteopenia | Marginal erosions, juxta‑articular osteopenia typical of RA; helps stage disease |
| Ultrasound or Power Doppler | Synovial hypertrophy, active vascularity | Detects early synovitis, guides joint aspiration, monitors response |
| Joint aspiration & fluid analysis | Rule out infection or crystal disease | Sterile, inflammatory fluid (high WBC, neutrophils) without crystals favors RA |
| Chest X‑ray | Pulmonary involvement (interstitial changes, pleural effusion) | Interstitial infiltrates or pleural plaques suggest extra‑articular RA |
| HIV, TB screening (ELISA, GeneXpert) | Co‑infection status | Positive results modify immunosuppressive therapy choices |
Diagnosis and severity
Diagnostic criteria (adapted for our setting)
- Clinical – Symmetrical polyarthritis of ≥2 small joints lasting ≥6 weeks.
- Serology – Positive RF or anti‑CCP (or both).
- Acute‑phase reactants – Elevated ESR or CRP.
- Imaging – Radiographic erosions or ultrasound evidence of synovitis.
Definite RA requires ≥4 points (clinical + serology + acute‑phase + imaging). Probable if 3 points, possible if 2 points with strong clinical suspicion.
Severity grading (used to guide therapy)
| Category | Clinical / lab features | Management implication |
|---|---|---|
| Mild | ≤3 swollen joints, low ESR/CRP, no erosions, functional score low | Start conventional DMARD (e.g., methotrexate) ± short course NSAID; monitor every 3 months |
| Moderate | 4–10 swollen joints, moderate ESR/CRP, early erosions, some functional limitation | Conventional DMARD + consider combination DMARD or biologic if inadequate response at 3–6 months |
| Severe | >10 swollen joints, high ESR/CRP, progressive erosions, extra‑articular disease (nodules, lung) | Early combination DMARD + biologic (TNF‑α inhibitor, IL‑6 blocker, or B‑cell depletor) plus glucocorticoid bridge; close monitoring for toxicity |
Severity is reassessed using disease activity scores (e.g., DAS28) and functional indices (HAQ). Prompt escalation is essential to prevent irreversible joint damage and systemic complications.
Management
| Phase | Goal | Key Interventions | Monitoring / Safety |
|---|---|---|---|
| Immediate stabilisation | Relieve severe pain, protect joints, prevent functional loss | • High‑dose oral or parenteral glucocorticoid bridge (short‑term) <br>• NSAID for analgesia (avoid if active TB, peptic ulcer, renal impairment) <br>• Splinting of inflamed joints, physiotherapy to maintain range | • Vital signs, blood pressure, blood glucose (steroids) <br>• GI protection if NSAID used (PPI) <br>• Screen for latent TB and hepatitis before steroids |
| Definitive disease‑modifying therapy | Suppress immune‑mediated synovitis, halt radiographic progression | • Conventional synthetic DMARDs (methotrexate, leflunomide, sulfasalazine) – start early, preferably within 3 months of symptom onset <br>• If rapid erosive disease or poor prognostic factors → add a biologic (TNF‑α inhibitor, IL‑6 receptor antagonist, abatacept, rituximab) or targeted synthetic DMARD (JAK inhibitor) <br>• Hydroxychloroquine for milder disease or as part of triple therapy | • Baseline CBC, LFT, renal function; repeat every 4–8 weeks initially <br>• Hepatitis B/C screening before biologics/JAK inhibitors <br>• TB screening (IGRA or Mantoux) and chest X‑ray before biologics <br>• Vaccination status – give inactivated vaccines before immunosuppression |
| Adjunctive care | Preserve function, reduce comorbidity impact | • Regular physiotherapy & occupational therapy <br>• Patient education on joint protection, smoking cessation <br>• Osteoporosis prophylaxis (calcium, vitamin D, bisphosphonate if steroid‑dependent) <br>• Cardiovascular risk assessment (lipids, BP) | • Bone mineral density every 1–2 years if on long‑term steroids <br>• Lipid profile annually |
| Follow‑up | Assess disease activity, drug toxicity, adjust therapy | • DAS28 or SDAI every 3 months <br>• Review for infections, skin lesions, cytopenias <br>• Adjust DMARDs based on response and side‑effects | • Prompt evaluation of new fever, cough, skin rash (possible infection or drug reaction) |
Contra‑indications / safety notes
- NSAIDs: avoid in active peptic ulcer disease, severe renal insufficiency, uncontrolled heart failure.
- Glucocorticoids: avoid high‑dose long‑term use in uncontrolled diabetes, active TB, severe osteoporosis without prophylaxis.
- Methotrexate: contraindicated in pregnancy, severe hepatic disease, uncontrolled infection.
- Biologics / JAK inhibitors: avoid in active TB, untreated hepatitis B, recent serious infection, demyelinating disease, or uncontrolled malignancy.
Complications and prognosis
- Joint damage: erosive arthritis → deformities (swan‑neck, boutonnière, ulnar deviation) → functional disability. Early DMARDs markedly improve long‑term joint preservation.
- Extra‑articular disease: rheumatoid nodules, interstitial lung disease, pleuritis, pericarditis, vasculitis, ocular sicca, amyloidosis.
- Infection risk: immunosuppression + disease activity ↑ bacterial, viral (especially TB, herpes zoster) and opportunistic infections.
- Cardiovascular disease: accelerated atherosclerosis; leading cause of mortality. Control inflammation and traditional risk factors.
- Osteoporosis & fractures: chronic steroids + inflammation.
- Pregnancy considerations: disease control before conception; safe DMARDs (hydroxychloroquine, sulfasalazine) vs teratogenic (methotrexate, leflunomide).
Prognosis is now favorable for most patients who receive early DMARDs; 70 % achieve low disease activity or remission within 2 years. Delayed treatment, seropositivity (RF, anti‑CCP), high baseline DAS28, and smoking predict poorer outcomes.
High‑yield exam points
- Look‑alike conditions:
- Psoriatic arthritis – asymmetric oligo‑/polyarthritis, skin plaques, nail pitting.
- Systemic lupus erythematosus – malar rash, renal involvement, anti‑dsDNA.
- Infective arthritis (TB, gonococcal) – mono‑articular, systemic signs, positive cultures.
- Common wrong first step: prescribing NSAID alone without DMARD initiation; examiners expect early DMARDs.
- Bedside questioning:
- “What is the significance of a positive anti‑CCP?” (high specificity, predicts erosive disease).
- “How would you assess disease activity at the bedside?” (tender/swollen joint count, patient global VAS).
- “Which extra‑articular manifestation would make you screen for interstitial lung disease?” (dry cough, dyspnoea, crackles).
Clinical case
Case: A 42‑year‑old Kenyan woman presents with a 4‑month history of symmetrical morning stiffness lasting >1 hour, affecting both wrists, MCPs and PIPs. She reports swelling, fatigue and recent weight loss. Examination shows bilateral ulnar deviation, swan‑neck deformities, and tender, warm synovitis of wrists and MCPs. ESR and CRP are markedly elevated; RF and anti‑CCP are positive. Chest X‑ray is normal.
Questions
- What is the next best step in management?
Answer: Initiate a conventional synthetic DMARD (methotrexate) together with a short course of oral glucocorticoid bridge while arranging baseline investigations (CBC, LFT, renal, hepatitis and TB screening).
- Which extra‑articular feature would prompt urgent referral to a pulmonologist?
Answer: New onset dry cough with inspiratory crackles suggesting interstitial lung disease.
- If the patient becomes pregnant in the next year, which medication should be stopped and which can be continued?
Answer: Stop methotrexate (teratogenic); continue hydroxychloroquine or sulfasalazine if disease control permits, and switch to a safe biologic (e.g., certolizumab) if needed.
Practice questions
Question 1
A 55‑year‑old man with known RA on methotrexate presents with fever, productive cough and pleuritic chest pain. Chest X‑ray shows a new infiltrate. What is the most appropriate immediate action?
A. Increase methotrexate dose
B. Start empirical broad‑spectrum antibiotics and hold methotrexate
C. Add a TNF‑α inhibitor
D. Give high‑dose oral steroids
Answer: B. start empirical broad‑spectrum antibiotics and hold methotrexate
Explanation: Infection is the leading cause of acute deterioration; immunosuppressants should be paused until infection is controlled.
Question 2
A 30‑year‑old woman with seronegative symmetric polyarthritis has negative RF and anti‑CCP but positive HLA‑B27. Which diagnosis is most likely?
A. Rheumatoid arthritis
B. Psoriatic arthritis
C. Ankylosing spondylitis
D. Reactive arthritis
Answer: C. ankylosing spondylitis
Explanation: HLA‑B27 positivity with seronegative symmetric arthritis points toward axial spondyloarthropathy rather than RA.
Question 3
A patient on long‑term steroids for RA develops new lumbar vertebral fracture. Which adjunct is indicated to reduce further bone loss?
A. Calcium alone
B. Vitamin D alone
C. Bisphosphonate therapy
D. NSAID therapy
Answer: C. bisphosphonate therapy
Explanation: Bisphosphonates are the cornerstone for steroid‑induced osteoporosis prevention.
Question 4
Which of the following is a contraindication to starting a TNF‑α inhibitor in a Kenyan RA patient?
A. Controlled hypertension
B. Positive IGRA for latent TB
C. Prior hepatitis B vaccination
D. Mild anemia
Answer: B. positive IGRA for latent TB
Explanation: TNF blockade reactivates latent TB; screening and treatment are required before initiation.
Question 5
A 68‑year‑old man with established RA presents with new onset dyspnoea and fine bibasal crackles. Which investigation best evaluates suspected RA‑associated interstitial lung disease?
A. High‑resolution CT of the chest
B. Spirometry only
C. Echocardiogram
D. Sputum culture
Answer: A. high‑resolution CT of the chest
Explanation: HRCT is the gold standard for detecting early interstitial changes in RA‑ILD.
Drafted with AI assistance from standard references and reviewed for structure. Check details against your lecture notes and the Kenya MoH guideline.