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This covers **Systemic Lupus Erythematosus (SLE)** and **Antiphospholipid Syndrome (APS)** from all 7 pages you provided. --- ## 🧠 SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) ### Overview * **SLE** is an example of a **Type III hypersensitivity reaction**. * **Characteristic features:** * Butterfly rash / Malar rash that spares nasolabial folds * Worsens on sunlight exposure * Malar flush seen in mitral stenosis --- ### 🔬 Pathology * **Increased Netosis** (Neutrophil Extracellular Trap formation) and **autophagy abnormalities** --- ### 👩‍⚕️ Incidence * Female : Male ratio = **5.5–6.5 : 1** --- ### 🧬 Genes Involved * **TREX1** gene on X chromosome * Number of X chromosomes correlates with SLE severity --- ### ⚙️ Most Affected Organ System * **Musculoskeletal system** * Common: Myalgia and joint pain --- ### ☠️ Causes of Death * **Renal involvement and infections** — leading causes of early mortality (within first decade of disease) --- ## 🧾 2019 EULAR/ACR Classification Criteria * **Renal biopsy findings** of **Class III/IV lupus nephritis** → maximum diagnostic weight * **Entry criterion:** Antinuclear antibody (ANA) positivity * Criteria are spread over **7 clinical** and **3 immunologic** domains * **≥10 points** = Classified as SLE --- ## 🧩 SLICC Criteria * ≥4 clinical + immunological features required * Must have at least **1 clinical + 1 immunological** criterion ### Weighted Domains | Domain | Example Criteria | Weight | | ---------------- | -------------------------------------------------------- | ------ | | Constitutional | Fever | 2 | | Hematologic | Leukopenia / Thrombocytopenia / AI hemolysis | 3–4 | | Neuropsychiatric | Delirium / Psychosis / Seizure | 2–5 | | Mucocutaneous | Alopecia / Oral ulcers / Discoid lupus / Cutaneous lupus | 2–6 | | Renal | Proteinuria >0.5 g/24h; Class III–IV biopsy | 4–10 | **Classify as SLE if score ≥10** --- ## 🧪 AUTOANTIBODIES IN SLE | Antibody | Key Point | | ------------------------------ | ------------------------------------------------------------------------------- | | **Antinuclear antibody (ANA)** | Most sensitive; detected >1:80 titer by immunofluorescence | | **Anti-dsDNA** | Highly specific; correlates with severity & renal involvement | | **Anti-Smith (Sm)** | Most specific for SLE | | **Anti-Ro (SSA)** | Causes photosensitivity; neonatal lupus with congenital heart block | | **Anti-La (SSB)** | Often with Anti-Ro | | **Anti-histone** | Drug-induced lupus (SHIP mnemonic: Sulfa, Hydralazine, Isoniazid, Procainamide) | | **Antiphospholipid antibody** | Causes recurrent fetal loss & thrombosis | | **Anti-erythrocyte** | Autoimmune hemolytic anemia | | **Anti-platelet** | Thrombocytopenia → petechiae | | **Antineuronal** | CNS lupus | | **Antiribosomal-P** | Neuropsychiatric lupus (psychosis, depression) | --- ## 🧫 RENAL INVOLVEMENT * **Secondary nephrotic-range proteinuria** * **Urinary protein/creatinine ratio (UPCR) > 0.5** * **RBC casts** on urine microscopy * **Biopsy findings:** Wire-loop lesions * **↓ GFR** → ↑ Renin * May progress to **end-stage renal disease (eGFR <15 ml/min/1.73 m²)** ### 🔹 Major Classes * **Class III (Focal)** lupus nephritis * **Class IV (Diffuse)** lupus nephritis * **Class V (Membranous)** lupus nephritis **Leading cause of mortality:** Nephritis (III/IV) + Infections > **Treatment:** Mycophenolate, Cyclophosphamide, or Calcineurin inhibitors (e.g., Tacrolimus) --- ## ⚗️ IMMUNOLOGICAL FEATURES * **ANA >1:80** * **Anti-dsDNA** → Monitors disease activity * **Anti-Smith** → Diagnostic specificity * **Antiphospholipid antibody** → Thrombosis/fetal loss * **Low complement (C3, C4)** * **Positive Coombs test** --- ## 🧠 CLINICAL CRITERIA (Mnemonic: SONAR) ### 1. Synovitis * ≥2 joint involvement * Soft tissue swelling + tenderness * Often small joints or knee ### 2. Serositis * **Lungs:** Pleuritis * **Heart:** Pericarditis * Libman-Sacks endocarditis *(FMGE 2021)* * Myocarditis, Arrhythmia * Shrinking lung syndrome (least common) ### 3. Skin involvement * **Subacute cutaneous lupus (SCLE):** Photosensitivity, malar rash * **Chronic cutaneous lupus:** Discoid lesions * **Panniculitis** (deep dermal lupus) ### 4. Oral/Nasal Ulcers * Painless aphthous ulcers * Seen in Crohn’s, UC, Behçet’s (genital) — but **SLE has no genital ulcers** ### 5. Non-scarring alopecia * Diffuse hair loss ### 6. Neurological Manifestations * Headache, Seizures, Myelopathy (rare) * Depression, Peripheral nerve involvement * **Psychosis (Anti-ribosomal P antibody)** * Steroids not used as they can worsen psychosis ### 7. Autoimmune Hemolytic Anemia * **Coombs-positive hemolysis** * **Features:** Leukopenia, lymphopenia, thrombocytopenia, petechiae --- ## 🩸 ANTIPHOSPHOLIPID SYNDROME (APS) ### Definition * Autoantibody-mediated **thrombophilia** * Can be **primary** or **secondary** (with SLE) --- ### When to Suspect * <55 years old with cerebrovascular accident * Pregnancy morbidity * Recurrent miscarriage * Fetal death / preeclampsia / preterm birth * Livedo reticularis * Thrombocytopenia * Multiple clot formation --- ### 🧪 Laboratory Criteria (Repeat tests ≥12 weeks apart) * **Lupus anticoagulant** → *Dilute Russell viper venom time test* * **Anti-cardiolipin antibody** → *ELISA* * **Anti-β2 glycoprotein I antibody** → *ELISA* > Need ≥1 clinical + ≥1 lab criterion --- ### 🧬 Mechanism * Antibodies enhance endothelial apoptosis → clot activation * Platelet consumption → thrombocytopenia * Delayed prothrombin time --- ### 🩹 Specialized Test **Dilute Russell viper venom time test:** * Activates Factor X → clotting * Lupus anticoagulant **inhibits** this activation → **prolonged clotting time** --- ### 🧫 Findings * ↑ Kaolin clotting time * ↑ aPTT * **Rabbit brain phospholipid** shortens clotting time * May cause **false-positive VDRL/RPR** --- ### ⚕️ Treatment | Scenario | Treatment | | -------------------------- | ------------------------------------------------------- | | **1st thrombotic event** | Warfarin (VKA); INR 2–3 for venous, 3–4 for arterial | | **Obstetric APS** | Low-dose aspirin + LMWH; immunomodulators if refractory | | **Asymptomatic/high-risk** | Low-dose aspirin prophylaxis | --- ### 🧬 With SLE (Secondary APS) * **Treated with:** Low-dose aspirin + LMWH * **Severe cases:** May use glucocorticoids, mycophenolate, or cyclophosphamide * **Catastrophic APS (CAPS):** ≥3 organ involvement, life-threatening --- ### 🩹 Livedo Reticularis * **Fishnet appearance** from dilated cutaneous veins * **Causes:** SLE, APS, Polyarteritis nodosa, Cryoglobulinemia --- ### 🧴 Treatment of SLE | Type | Regimen | | ------------------------ | ------------------------------------------------------------- | | **Non–life-threatening** | Low-dose glucocorticoids ± Belimumab | | **Life-threatening** | High-dose glucocorticoids + Mycophenolate or Cyclophosphamide | --- ### ⚠️ Pregnancy & Lupus * **Active SLE in pregnancy:** Hydroxychloroquine + Prednisolone * **Steroids not 1st line** due to: 1. Deactivation by placental 11β-dehydrogenase 2. Fetal malformation risk --- ## 🧷 Additional Notes * **Antiphospholipid antibody → Recurrent fetal loss** * **Antiribosomal-P antibody → Depression / Psychosis** * **Anti-erythrocyte antibody → AIHA** * **Antiplatelet antibody → Thrombocytopenia** * **Antineuronal antibody → CNS lupus** * **Anti-C1q antibody → Indicates lupus nephritis severity** --- ### 🩺 Clinical Criteria Summary **Vascular thrombosis:** * Arterial/venous/small-vessel clots * Budd–Chiari syndrome, DVT → PE * MI, Stroke, Gangrene, Retinal thrombosis, AIHA, Thrombocytopenia **Pregnancy morbidity:** * Unexplained death of morphologically normal fetus * Preterm baby <34 weeks due to preeclampsia or eclampsia * ≥3 consecutive unexplained spontaneous abortions --- ✅ **Classification as SLE:** * **ANA ≥1:80**, at least **one clinical + one immunological** criterion, total score ≥10 --- Would you like me to now: * 🧩 Generate **15 case-based MCQs** from this topic (SLE + APS), * Or 🎨 Convert this cleaned text into a **stylish scrollable webpage (HTML/CSS/JS)** format (with collapsible theory sections)?