Rheumatology & Haematology

Foundations: Defining Inflammatory and Haematological Disorders

A 52-year-old woman presents with bilateral hand pain and morning stiffness lasting 90 minutes. Her metacarpophalangeal joints are swollen and tender. This clinical picture immediately raises suspicion for inflammatory arthritis, specifically , where early recognition transforms outcomes. Meanwhile, in the haematology clinic, a 68-year-old man's routine bloods reveal haemoglobin of 92 g/L with microcytosis-triggering a systematic approach to . These scenarios exemplify the precision required in rheumatological and haematological diagnosis.

Essential Classifications:

• Inflammatory arthropathies:

  • Rheumatoid arthritis (RA): Symmetrical polyarthritis, RF/anti-CCP positive in 70-80%
  • Crystal arthropathies: Monosodium urate (gout) vs calcium pyrophosphate (pseudogout)
  • Prevalence: RA affects 1% UK population; gout affects 2.5%

• Anaemia classification by MCV:

  • Microcytic (MCV <80 fL): iron deficiency, thalassaemia, chronic disease
  • Normocytic (80-100 fL): acute blood loss, chronic disease, haemolysis
  • Macrocytic (>100 fL): B12/folate deficiency, alcohol, hypothyroidism

• Venous thromboembolism (VTE) risk stratification:

  • Provoked vs unprovoked events determine anticoagulation duration
  • Annual recurrence: 3-5% with treatment, 10% without

📌 Mnemonic for RA criteria (ACR/EULAR 2010): JSDAS - Joint involvement, Serology (RF/anti-CCP), Duration (≥6 weeks), Acute phase reactants, Score ≥6/10 confirms diagnosis

2 - Pathophysiology: Understanding Disease Mechanisms

Rheumatoid arthritis exemplifies autoimmune-driven inflammation. Genetic susceptibility (HLA-DR4) combines with environmental triggers (smoking, infection) to breach immune tolerance. Anti-citrullinated protein antibodies (anti-CCP) target synovial proteins, initiating complement activation and cytokine release-particularly TNF-α, IL-6, and IL-1. This inflammatory cascade drives synovial hyperplasia, pannus formation, and cartilage destruction. Understanding this pathway explains why early DMARD therapy in prevents irreversible joint damage within the critical 3-month window.

Mechanistic Insights:

• Crystal arthropathy pathogenesis :

  • Hyperuricaemia (>360 μmol/L) → monosodium urate crystal deposition
  • Crystals activate NLRP3 inflammasome → IL-1β release → neutrophil recruitment
  • Pseudogout: calcium pyrophosphate crystals, associated with hypercalcaemia, hyperparathyroidism

• Anaemia mechanisms require systematic investigation :

  • Iron deficiency: depleted stores → impaired haem synthesis → microcytosis
  • Chronic disease: hepcidin ↑ → iron sequestration → functional deficiency
  • Haemolysis: increased red cell destruction → elevated LDH, bilirubin, low haptoglobin

• VTE pathophysiology (Virchow's triad):

  • Stasis: immobility, surgery, long-haul travel
  • Hypercoagulability: malignancy, thrombophilia, oestrogen
  • Endothelial injury: trauma, surgery, central lines

3 - Clinical Application: Diagnostic Approaches

A 45-year-old presents with sudden-onset first metatarsophalangeal joint pain, erythema, and inability to weight-bear. Serum urate is 520 μmol/L, and joint aspiration reveals negatively birefringent needle-shaped crystals-confirming gout . Meanwhile, a 72-year-old with breathlessness has Wells score 6.5 (PE likely); D-dimer is 850 ng/mL, and CTPA confirms segmental pulmonary embolus . These cases demonstrate guideline-concordant diagnostic pathways.

Evidence-Based Investigation Sequences:

• RA diagnostic workup (NICE NG100):

  • Clinical suspicion: symmetrical small joint arthritis, morning stiffness >30 minutes
  • Bloods: RF, anti-CCP, CRP/ESR, FBC, LFTs, U&Es (baseline for DMARDs)
  • Imaging: X-ray hands/feet (erosions), ultrasound (synovitis, power Doppler)
  • Refer to rheumatology within 3 working days if suspected

• Anaemia investigation pathway :

  • Step 1: FBC → identify MCV pattern
  • Step 2: Microcytic → ferritin, transferrin saturation; if ferritin <30 μg/L → GI investigation
  • Step 3: Macrocytic → B12, folate, TFTs, reticulocyte count
  • Step 4: Normocytic → reticulocytes, blood film, haemolysis screen

• VTE diagnosis (NICE NG158):

  • Wells score: ≤1 (PE unlikely) → D-dimer; >1 (PE likely) → CTPA
  • D-dimer sensitivity 95%, specificity 50% (age-adjusted threshold: age × 10 μg/L if >50 years)

4 - Differential Diagnosis: Distinguishing Similar Conditions

Acute monoarthritis demands rapid differentiation between gout, pseudogout, septic arthritis, and trauma. Septic arthritis is the critical emergency-joint aspiration must occur before antibiotics if feasible. Synovial fluid WCC >50,000/mm³ with neutrophil predominance suggests sepsis, while crystals confirm crystal arthropathy . In anaemia, distinguishing iron deficiency from thalassaemia trait prevents unnecessary iron supplementation: ferritin differentiates, but both cause microcytosis .

Key Discriminators:

• Monoarthritis differential:

  • Gout: first MTP, rapid onset, urate crystals (negative birefringence)
  • Pseudogout: knee/wrist, elderly, CPPD crystals (weak positive birefringence)
  • Septic arthritis: systemically unwell, fever, WCC >50,000/mm³, Gram stain positive
  • Trauma: clear history, normal inflammatory markers

• Microcytic anaemia differentiation:

  • Iron deficiency: low ferritin (<30 μg/L), high TIBC, low transferrin saturation
  • Thalassaemia trait: normal/high ferritin, raised RBC count, HbA2 elevated
  • Chronic disease: ferritin normal/high, low TIBC, normal HbA2

5 - Management: Evidence-Based Treatment Strategies

Early aggressive DMARD therapy in follows NICE NG100: methotrexate 15-25 mg weekly with folic acid 5 mg weekly (not on methotrexate day) is first-line. Treatment target is remission (DAS28 <2.6) or low disease activity. Failure after 3 months at therapeutic dose warrants escalation to dual/triple DMARD or biologic therapy (anti-TNF, rituximab, tocilizumab). For VTE , NICE NG158 recommends DOACs (apixaban 10 mg BD for 7 days, then 5 mg BD) over warfarin for most patients.

Specific Treatment Protocols:

• Acute gout management (NICE CG177):

  • First-line: NSAIDs (naproxen 750 mg stat, then 250 mg TDS) or colchicine (500 μg BD-QDS)
  • Avoid allopurinol during acute flare (worsens inflammation)
  • Urate-lowering therapy: start 2-4 weeks post-flare, target <300 μmol/L
  • Allopurinol: start 100 mg OD, titrate to 300-900 mg based on response

• Anaemia treatment depends on cause:

  • Iron deficiency: ferrous sulphate 200 mg TDS (65 mg elemental iron per tablet)
  • Recheck Hb after 2-4 weeks; continue 3 months post-normalisation to replete stores
  • IV iron if intolerant/non-adherent/malabsorption/ongoing losses

• VTE anticoagulation duration:

  • Provoked: 3 months
  • Unprovoked: consider extended (assess bleeding risk with HAS-BLED)
  • Active cancer: LMWH preferred (dalteparin 200 units/kg OD for 1 month, then 150 units/kg)

6 - Complex Integration: Managing Multimorbidity

A 78-year-old with RA, CKD stage 3b, and recent PE presents a management challenge. Methotrexate dose requires reduction (10 mg weekly if eGFR 30-50); apixaban needs dose adjustment (2.5 mg BD if ≥2 of: age ≥80, weight ≤60 kg, creatinine ≥133 μmol/L). Concurrent anaemia investigation reveals microcytosis; ferritin is 180 μg/L-suggesting anaemia of chronic disease from RA rather than iron deficiency. This case exemplifies real-world complexity requiring synthesis across rheumatology, haematology, and renal medicine.

Special Population Considerations:

• Pregnancy and VTE :

  • DOACs contraindicated; use LMWH throughout pregnancy and 6 weeks postpartum
  • Prophylactic LMWH if previous unprovoked VTE or thrombophilia

• Elderly with crystal arthropathy :

  • NSAIDs high-risk (GI bleed, AKI, heart failure exacerbation)
  • Colchicine dose-reduce in renal impairment (avoid if eGFR <10)
  • Consider intra-articular steroid if monoarticular

• Complications requiring vigilance:

  • RA: cardiovascular disease (2× risk), interstitial lung disease, cervical myelopathy
  • Long-term anticoagulation: major bleeding 2-3% per year, intracranial haemorrhage 0.5%

High Yield Summary

Key Take-Aways:

• RA requires urgent rheumatology referral within 3 working days if symmetrical small joint swelling with morning stiffness >30 minutes
• Anti-CCP antibody has 98% specificity for RA; methotrexate 15-25 mg weekly is first-line DMARD
• Acute monoarthritis demands joint aspiration before antibiotics to exclude septic arthritis (synovial WCC >50,000/mm³)
• Gout: treat acute flare first, delay allopurinol 2-4 weeks, target urate <300 μmol/L
• Microcytic anaemia: ferritin <30 μg/L confirms iron deficiency and mandates GI investigation in adults
• Wells score >1 for PE: proceed directly to CTPA; D-dimer only if Wells ≤1
• DOACs are first-line for VTE: apixaban 10 mg BD × 7 days, then 5 mg BD; 3 months if provoked

Essential Rheumatology & Haematology Numbers:

Key Principles/Pearls:

• Treat-to-target in RA: Aim for DAS28 <2.6; escalate therapy if not achieved within 3-6 months
• Never start allopurinol during acute gout flare-worsens inflammation by mobilizing crystals
• Ferritin is an acute phase reactant: May be falsely normal/elevated in inflammation; consider transferrin saturation
• DOACs contraindicated in pregnancy, antiphospholipid syndrome, mechanical heart valves-use LMWH or warfarin

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