FS

Autoimmune Rheumatic Diseases – Principles of Medical Management

Lecture Context and Structure

  • Two afternoon lectures (today) focus on relatively uncommon, specialist-managed autoimmune rheumatic diseases.
  • Two morning lectures (tomorrow) will address common conditions (gout, osteoarthritis, soft-tissue disease) and contain more examinable core knowledge.
  • Emphasis today: understanding principles and overall approach rather than exhaustive drug minutiae.

Holistic Management Principles

  • Management of autoimmune rheumatic disease is “the tip of an iceberg”—pharmacology is only one visible piece.
  • Requires interdisciplinary teamwork:
    • Physicians (rheumatology, internal medicine & subspecialists)
    • Allied health: physiotherapy, occupational therapy, dietetics, psychology, podiatry, social work
    • Patient-support organisations & families
  • Always consider: symptom relief, disease modification, prevention/management of complications, comorbidity surveillance, and quality of life.

Non-Pharmacological Management

  • Simple modalities: heat/cold packs, splints, braces, ultrasound, TENS.
  • Occupational therapy: energy conservation ("plan washing/ironing to avoid flares"), joint-protection techniques, assistive devices.
  • Physiotherapy: mobility, range-of-motion exercises, posture correction, strengthening.
  • Lifestyle & psychosocial factors: stress management, sleep hygiene, smoking cessation, weight optimisation, counselling, support-group participation.

Chronic Disease Framework

  1. Identify the disease accurately and early.
  2. Control current symptoms (most patients present with \text{pain}).
  3. Suppress underlying pathogenesis to prevent irreversible damage & disability.
  4. Screen continually for:
    • Disease complications (e.g., extra-articular manifestations)
    • Therapy toxicities (drug side-effects, iatrogenic damage)
    • Independent comorbidities (CV risk, infection, osteoporosis, malignancy).

Symptom Control vs Disease Modification

  • Symptom-only approach = “plaster over a wound”: pain improves but inflammatory damage continues covertly.
  • True success requires disease modification—halt the immunological cascade causing ongoing synovitis / enthesitis / bone erosion / ankylosis.

Pharmacologic Symptom Relief

  • Non-steroidal anti-inflammatory drugs (NSAIDs): analgesic + anti-inflammatory but carry GI, renal, CV, bleeding risks.
  • Paracetamol ± codeine ± central co-analgesics: pain relief without strong anti-inflammatory effect.
  • Combination therapy common; always assess adverse-effect profile & contraindications.

Disease Modification in Rheumatoid Arthritis (RA)

Early Aggressive Treatment & Window of Opportunity

  • Radiographic damage can begin within \le 2\,\text{years} of onset—often irreversible.
  • Initiate DMARDs as soon as accurate diagnosis made (ideally inside 3–6 months of symptom onset).

Treat-to-Target Strategy

  • Define a target (remission or low disease activity):
    • Ideally \text{swollen joints} \le 1 AND \text{tender joints} \le 1; pragmatically < 2.
  • Re-assess every 1–3 months; if target unmet, escalate or switch therapy.
  • Principle similar to hypertension, diabetes, hyperlipidaemia control.

Classes of DMARDs in RA

  1. Conventional synthetic (csDMARDs)
    • Methotrexate (cornerstone; cheap; intricated titration; folic acid supplementation mandatory).
    • Leflunomide, Sulfasalazine, (Hydroxy)chloroquine.
  2. Targeted synthetic (tsDMARDs)
    • Janus-kinase (JAK) inhibitors – interfere with intracellular cytokine signalling. Two agents currently registered locally.
  3. Biologic (bDMARDs)
    • Injectable (IV or SC); exquisitely specific.
    • Broad categories with examples:
      • Anti-TNF-α (oldest; still widely used)
      • Anti-IL-6 (tocilizumab, etc.)
      • Anti-CD20 (rituximab: B-cell depletion)
      • CTLA-4-Ig (abatacept: blocks T–B co-stimulation)

Corticosteroids in RA

  • Potent anti-inflammatory & disease-modifying; retard erosions.
  • Side-effect constellation: metabolic (diabetes, dyslipidaemia), musculoskeletal (osteoporosis, myopathy, avascular necrosis), ocular (cataract, glaucoma), GI, CV, dermatological, neuropsychiatric, endocrine, infectious.
  • Practical use: short-term “bridging” while DMARDs take effect; lowest effective dose; taper ASAP.

Monitoring Disease Activity & Damage

  • Quantitative indices (DAS-28, CDAI, SDAI) combine tender/swollen joint counts, CRP/ESR, patient & physician VAS.
  • Damage accrual monitored radiographically; once erosions appear, changes generally permanent.

Comorbidities & Complications in RA

  • Osteoporosis: disease + glucocorticoids; give Ca/Vit D routinely, screen with DEXA.
  • CV disease: accelerated atherosclerosis; aggressive risk factor modification (BP, lipids, smoking).
  • Infections: immunosuppression; vaccinate (influenza annually, pneumococcal, varicella/zoster per agent), screen for TB before anti-TNF.
  • Malignancy: lymphoma risk (disease activity) vs skin cancer (phototoxic DMARDs).
  • Functional impact: \approx 30\% unemployed within 5 years; average life expectancy ↓ \approx 10\;\text{years} (mainly CV & infection-related).

Key RA Takeaways

  1. Early diagnosis → initiate DMARDs quickly.
  2. Treat-to-target with objective indices; change therapy if \text{DAS-28} > 2.6 persists.
  3. Multidisciplinary & comorbidity-centric approach essential.

Spondyloarthritis (SpA) Spectrum

Core Members

  1. Reactive arthritis (post-infectious)
  2. Axial SpA (formerly ankylosing spondylitis)
  3. Psoriatic arthritis (PsA)
  4. SpA associated with inflammatory bowel disease (IBD-SpA)
  • Shared clinical/immune features: HLA-B27 association, enthesitis, dactylitis, uveitis, axial involvement; yet each subtype stresses different “domains.”

Pathogenesis Snapshot

  • Genetic predisposition: \text{HLA-B27}^{+} markedly raises risk.
  • Environmental triggers: mechanical stress (Achilles, patella), GI/GU infections (Salmonella, Shigella, Campylobacter, Chlamydia).
  • Distinctive lesions: synovitis and enthesitis → bone erosion and new-bone formation/ankylosis (bamboo spine).

DMARD Strategy in SpA

  • csDMARDs: sulfasalazine, methotrexate, leflunomide, chloroquine.
    • Methotrexate NOT particularly effective for pure axial disease; sulfasalazine emphasized for peripheral/reactive forms.
  • tsDMARDs (JAK inhibitors): oral; increasing evidence for use in PsA and axial SpA (registration pending locally).
  • bDMARDs:
    • Anti-TNF-α: effective across most domains (joints, entheses, skin, bowel, eye).
    • Anti-IL-17 (secukinumab, ixekizumab): excellent for skin & axial disease, less so for bowel.
    • Anti-IL-12/23 (ustekinumab): strong for skin/bowel, modest for axial skeleton.
    • B-cell & CTLA-4 biologics (rituximab, abatacept) NOT useful – underlying pathogenesis different.

Domain-Specific Therapeutic Considerations

Peripheral Arthritis
  1. NSAIDs.
  2. If persistent > 3\,\text{months} → csDMARD (sulfasalazine > methotrexate for reactive/I BD-SpA).
  3. Escalate to anti-TNF or other biologic if failure.
Enthesitis
  • Local measures (ice, physio, ultrasound) + NSAIDs ± cautious steroid injection (avoid Achilles/patellar tendon rupture).
  • csDMARDs ineffective → jump directly to bDMARD or tsDMARD when necessary.
Axial Disease
  • At least 2 different NSAID trials (full dose, \ge 2 weeks each).
  • Refractory → biologic (anti-TNF or anti-IL-17). JAK inhibitors emerging.
Skin & Mucocutaneous Disease (Psoriasis, Keratoderma, Circinate Balanitis)
  • Topical corticosteroids ± vitamin D analogues.
  • Moderate–severe: methotrexate, leflunomide, biologic (anti-IL-17/23, anti-TNF, JAK inhibitor).
Eye Manifestations (Uveitis)
  • Co-management with ophthalmology obligatory.
  • Local steroid drops → systemic immunosuppression (methotrexate, anti-TNF) for recurrent cases.

Role of Corticosteroids in SpA

  • Systemic steroids discouraged (exacerbate osteopenia; minimal axial efficacy).
  • Use short oral tapers or local/epidural/CT-guided injections sparingly and precisely.

Allied Health & Rehabilitation in SpA

  • Daily posture & spinal-extension exercises maintain mobility.
  • Physiotherapy prevents fixed kyphosis; occupational therapy adapts workstations, driving aids.
  • Podiatry/orthotics for heel lift ± insoles in enthesitis.

Surgical Interventions

  • Pedicle subtraction osteotomy for severe fixed kyphosis (restores horizontal gaze).
  • Total hip replacement common in early-onset axial SpA with hip joint destruction.

Vaccination Guidance (All Autoimmune Rheumatic Diseases)

  • Inactivated vaccines safe; administer BEFORE initiating intense immunosuppression when possible.
    • Influenza annually.
    • Pneumococcal conjugate + polysaccharide.
    • Hepatitis B for B-cell depletion (rituximab) or baseline risk.
  • Live vaccines (MMR, varicella, yellow fever) contraindicated during active immunosuppression.
  • TNF inhibitors: mandatory TB screening (T-spot/Quantiferon and chest X-ray) ± isoniazid prophylaxis.
  • JAK inhibitors: varicella-zoster reactivation risk ⇒ zoster vaccination (not yet SA-available) ideally pre-treatment.

Quality of Life & Disability Prevention

  • Severe disease can shorten life expectancy \approx 10\,\text{years} primarily via CV events and infection.
  • Aggressive control of inflammation + risk-factor modification can shrink this gap.
  • Employment impact: 1 in 3 RA patients cease work within \le 5\,\text{years}; similar trends in PsA/AS if untreated.

Monitoring Tools & Apps

  • Free smartphone applications calculate disease indices:
    • EULAR/ACR DAS-28, CDAI, ASDAS (axial SpA), PsAID.
  • Facilitate treat-to-target and shared decision-making.

Summary of Core Principles

  1. Early, accurate diagnosis unlocks a therapeutic “golden window.”
  2. Treat-to-target: measure, respond, and re-measure until remission/low activity.
  3. Layered management: symptom relief + disease modification + comorbidity control + psychosocial support.
  4. Multidisciplinary approach mandatory; rheumatologist, allied health, patient, & family form a single team.
  5. Vaccination and infection screening integral before and during immunosuppression.
  6. Balance efficacy vs toxicity: “First, do no harm”—use corticosteroids judiciously, monitor DMARD safety labs.
  7. Remember unique domain-based therapy in SpA (joints, entheses, skin, bowel, eye) and the variable performance of each drug class in those domains.
  8. Ongoing patient education—empower self-management, stress reduction, adherence, and early reporting of side-effects or flare.