วันเสาร์ที่ 23 สิงหาคม พ.ศ. 2568

Rheumatoid Arthritis (RA): Systemic และ Extraarticular Manifestations

Rheumatoid Arthritis (RA): Systemic และ Extraarticular Manifestations


ภาพรวม

  • RA มีพยาธิสรีรวิทยาหลักที่ synovium แต่ ~40% ของผู้ป่วยจะมี extraarticular involvement
  • มักสัมพันธ์กับ seropositive RA, severe disease, long disease duration, smoking, HLA-DRB1 shared epitope
  • Extraarticular disease = marker ของ disease severity, morbidity, premature mortality
  • กลไก: cytokines เดียวกันกับที่ทำลายข้อ ก่อพยาธิสภาพในอวัยวะอื่น
  • การรักษาหลักคือ ควบคุม joint disease (DMARDs, biologics, glucocorticoids)

Manifestations ที่สำคัญ

1. Constitutional/Systemic

  • Fatigue (multifactorial: pain, sleep, mood, social)
  • Chronic widespread pain / Fibromyalgia (~20% ของ RA, โดยเฉพาะ seronegative)
  • Psychiatric: depression พบบ่อย (prevalence ~17–39%, independent mortality risk)
  • Weight loss (สัมพันธ์กับ inflammatory activity, erosive disease, BMI สูงตอนเริ่มต้น)

2. Bone and Muscle

  • Osteopenia/Osteoporosis
    • Systemic: chronic inflammation + immobility + GC therapy
    • Periarticular: bone edema/osteitis (MRI), predictor of erosions
    • Focal: erosions จาก pannus + osteoclast activation
    • Risk fracture 50–100% (vertebral compression, stress fracture fibula, metatarsals)
    • GC-induced osteoporosis additive risk
    • Risk factors: postmenopause, age, low BMI, smoking, disability, high disease activity
    • Dx: DXA; Rx: FRAX-based, Ca/VitD, bisphosphonate, lifestyle
  • Muscle Weakness
    • Synovitis disuse atrophy (eg. quadriceps)
    • Drug-induced myopathy: GC, antimalarials (HCQ, CQ), statins
    • Myositis (rare true polymyositis in RA) manage as polymyositis (prednisolone + MTX/AZA)
    • RA vasculitis skeletal muscle ischemia, neuropathic weakness
  • Altered body composition (RA cachexia/sarcopenia + fat mass)
    • Risk factors: age, long disease duration, high inflammatory activity, RF+, sedentary lifestyle
    • Consequences: disability, CV/metabolic risk
    • Exercise (aerobic + resistance) improves body composition & reduces disease activity

3. Skin

  • Rheumatoid nodules (seropositive RA, pressure points, lungs, heart)
  • Skin ulcers: multifactorial, vasculitis-related risk amputation, mortality
  • Neutrophilic dermatoses: Sweet’s, pyoderma gangrenosum, RA neutrophilic dermatitis
  • Medication-induced: GC (atrophy, ecchymosis), cytopenia-related petechiae
  • Others: erythema elevatum diutinum, Raynaud phenomenon (~25%)

4. Eye

  • Sjögren’s disease (secondary, dry eye/mouth)
  • Episcleritis (benign, self-limited)
  • Scleritis (severe, risk scleromalacia perforans, vision-threatening)
  • Rare: uveitis, peripheral ulcerative keratitis corneal melt
  • Urgent referral: vision, ocular pain, progressive redness

5. Lung

  • Parenchymal disease: interstitial fibrosis, nodules, bronchiolitis obliterans, organizing pneumonia
  • Pleural disease: pleuritis, effusion
  • Drug-induced: MTX, LEF, biologics
  • Infectious complications: from immunosuppression
  • VTE risk pulmonary embolism

6. Cardiac

  • Pericarditis (symptomatic uncommon; more in seropositive active RA)
  • Myocarditis (rare; granulomatous > interstitial)
  • CAD: RA = independent risk factor MI, sudden death
  • Heart failure: risk 2x, often HFpEF
  • Arrhythmia (AF): risk , stroke risk
  • Rheumatoid nodules: pericardium, myocardium, valves AV block, embolic stroke
  • Subclinical myocardial disease detectable by MRI (fibrosis, inflammation)

7. Vascular Disease

  • Rheumatoid vasculitis: digital infarcts systemic PAN-like arteritis; neuropathy, ulcers, gangrene
  • Atherosclerotic PAD: prevalence; risk from inflammation + glucocorticoid
  • VTE: risk 1.4–2x (esp. with JAK inhibitors, some biologics, uncontrolled disease)
  • Stroke: risk mildly
  • Lymphedema: rare, due to lymphatic obstruction

8. Kidney

  • Rare direct: mesangioproliferative/membranous GN, vasculitis
  • More common: drug toxicity (NSAIDs, cyclosporine, TNFi)
  • Risk CKD (eGFR <60) associated with high ESR, CVD, NSAID use
  • AA (secondary) amyloidosis: rare now, but still possible in longstanding uncontrolled RA

9. Neurologic & Psychiatric

  • Neurologic
    • Peripheral: carpal tunnel (most common), neuropathy from vasculitis, mononeuritis multiplex
    • Central: cervical spine subluxation (C1–C2) myelopathy
  • Psychiatric
    • Depression: common (17–39% prevalence), worsens disability & mortality

10. Hematologic

  • Anemia of chronic disease (normocytic, Hb rarely <10 g/dL)
  • Felty’s syndrome: RA + neutropenia + splenomegaly ± anemia/thrombocytopenia
  • LGL leukemia (pseudo-Felty): neutropenia, splenomegaly, recurrent infection
  • Reactive thrombocytosis/eosinophilia: parallels disease activity
  • Lymphoma risk : longstanding active RA = major risk factor (even w/o MTX)
  • Drug-induced cytopenia: TNFi, IL-6 inhibitors, JAK inhibitors, immunosuppressants

Key Clinical Pearls

  • Extraarticular RA = marker of severe disease ต้อง aggressive treatment
  • Risk factors: seropositive, RF/ACPA high titer, smoking, long-standing disease
  • ต้อง screen & monitor organ involvement (CV, lung, kidney, eye, bone)
  • การควบคุม systemic inflammation คือการป้องกัน extraarticular complications ที่ดีที่สุด

 

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