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Systemic Lupus Erythematosus (SLE) - Complete Clinical Notes

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1. Definition

• Goldman-Cecil Medicine, p. 2808

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2. Epidemiology

• Female predominance: F:M ratio ~9:1 in adults (ages 15-44 years); closer to 2:1 in children and those >55 years
• Prevalence: ~72.8 per 100,000 in the USA; incidence ~5.1 per 100,000/year
• Ethnic disparities: 3-4x more prevalent in Black, American Indian, and Native Alaskan women than White women; Asians also have higher incidence
• Socioeconomic factors are major contributors to increased prevalence and severity in Black and Hispanic Americans

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3. Clinical Features

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3.1 Mucocutaneous

• Malar (butterfly) rash - erythematous rash over both cheeks and the bridge of the nose, sparing the nasolabial folds (pathognomonic)
• Discoid lupus - chronic scarring plaques, may cause permanent hair loss
• Photosensitivity - rash triggered or worsened by UV exposure
• Subacute cutaneous lupus erythematosus (SCLE) - annular or papulosquamous lesions
• Oral ulcers (usually painless)
• Non-scarring alopecia / "lupus hair" (frontal hair thinning)

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3.2 Musculoskeletal

• Arthritis / arthralgias in 76% - typically symmetric, non-erosive, non-deforming polyarthritis affecting small joints of the hands, wrists, and knees
• Jaccoud arthropathy - reducible hand deformities from ligamentous laxity (without erosion)
• Myalgias and myositis (5%)
• Avascular necrosis (especially femoral head) - often steroid-related

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3.3 Renal (Lupus Nephritis)

• Occurs in ~50% of SLE patients; clinically apparent nephritis in ~31%
• WHO/ISN-RPS Classes I-VI:
  • Class I: Minimal mesangial
  • Class II: Mesangial proliferative (mild, good prognosis)
  • Class III: Focal proliferative
  • Class IV: Diffuse proliferative (most common; worst prognosis)
  • Class V: Membranous
  • Class VI: Advanced sclerosing
• Presents with: proteinuria, haematuria, hypertension, rising creatinine, nephrotic syndrome

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3.4 Neuropsychiatric (NPSLE)

• Headache, cognitive dysfunction, mood disorders
• Seizures, strokes (including from antiphospholipid antibodies)
• Psychosis
• Transverse myelitis
• Peripheral and cranial neuropathies
• Chorea

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3.5 Cardiovascular

• Pleuritis (~30%) and pericarditis - most common serosal manifestations
• Libman-Sacks endocarditis - non-bacterial verrucous endocarditis, typically mitral and aortic valves; associated with antiphospholipid antibodies
• Premature atherosclerosis (up to 10x increased mortality from atherosclerotic disease vs. age/sex-matched controls)
• Myocarditis (5%)
• Raynaud phenomenon (up to 60%) - episodic digital vasospasm triggered by cold/stress; pallor → cyanosis → rubor

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3.6 Pulmonary

• Pleuritis with exudative effusions (~30%)
• Alveolar haemorrhage (up to 12%)
• Pulmonary hypertension
• Pulmonary embolism (secondary to DVT, especially with antiphospholipid antibodies)
• Shrinking lung syndrome (diaphragm dysfunction)

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3.7 Haematological

• Haemolytic anaemia (Coombs-positive)
• Leucopaenia / lymphopaenia
• Thrombocytopaenia (~30%)
• These may be isolated presentations of SLE

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3.8 Antiphospholipid Syndrome (APS)

• Present in ~1/3 of SLE patients
• Associated with venous and arterial thromboses, cardiac valve lesions, livedo reticularis, thrombocytopaenia, haemolytic anaemia, CNS disease, and recurrent fetal loss
• Catastrophic APS: multi-organ thrombosis, fatal in up to 30%

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4. Investigations

4.1 Autoantibody / Serological Tests

4.2 Complement

• Decreased C3 and C4 - indicate complement consumption; useful markers of disease activity (especially nephritis)
• CH50 (total haemolytic complement) may also be reduced

4.3 Full Blood Count

• Haemolytic anaemia, leucopaenia, lymphopaenia, thrombocytopaenia
• Direct Coombs test (positive in haemolytic anaemia)

4.4 Inflammatory Markers

• ESR - elevated (nonspecific, used to monitor activity)
• CRP - often paradoxically low in SLE despite elevated ESR (exception: serositis or concurrent infection where CRP rises)
• Prolonged aPTT - suggests antiphospholipid antibodies (lupus anticoagulant)

4.5 Urine

• Urinalysis: proteinuria, haematuria, red cell casts (nephritic picture)
• 24-hour urine protein or spot protein:creatinine ratio
• Urine microscopy - RBC casts highly suggestive of glomerulonephritis

4.6 Renal Biopsy

• Mandatory for classification of lupus nephritis (WHO/ISN Class I-VI) to guide treatment

4.7 Other Tests

• Serum creatinine and eGFR
• LFTs
• Coagulation screen (especially if antiphospholipid antibodies suspected)
• Chest X-ray (pleural effusions, cardiomegaly, alveolar infiltrates)
• ECG / echocardiogram (pericarditis, Libman-Sacks, pulmonary hypertension)
• CT head / MRI brain (neuropsychiatric SLE)
• DEXA scan (baseline before long-term steroids)

4.8 Classification Criteria (2019 EULAR/ACR)

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5. Treatment

5.1 General Principles

• Sun protection (SPF 50+ sunscreen, protective clothing) - reduces photosensitive flares
• Lifestyle: smoking cessation, cardiovascular risk factor management, regular exercise
• Vaccinations - avoid live vaccines in immunosuppressed patients; annual influenza, pneumococcal
• Monitor and treat hypertension (ACE inhibitors or ARBs preferred, especially with nephritis)
• Vitamin D and calcium supplementation (if on long-term corticosteroids)

5.2 Hydroxychloroquine (HCQ)

• Backbone of SLE therapy - should be prescribed to virtually all SLE patients unless contraindicated
• Reduces flare frequency, protects against organ damage, decreases thrombotic risk, improves survival
• Dose: typically 200-400 mg/day (max 5 mg/kg/day to reduce retinal toxicity risk)
• Annual ophthalmology review required (baseline + every 12 months)

5.3 Corticosteroids

• Low-dose prednisone (<10 mg/day) for mild-to-moderate disease (arthritis, rash, serositis)
• High-dose prednisone (0.5-1 mg/kg/day or 60 mg/day) for serious organ involvement
• IV methylprednisolone pulse (1 g/day x 3 days) for life-threatening flares (severe nephritis, CNS lupus, vasculitis)
• Long-term use carries significant side effects - aim to taper to lowest effective dose

5.4 Immunosuppressants

5.5 Biologic Agents

5.6 Antiphospholipid Syndrome (in SLE)

• Long-term warfarin (target INR 2-3, or 3-4 for arterial thrombosis) for patients with thrombosis and antiphospholipid antibodies
• Hydroxychloroquine reduces thrombotic risk

5.7 Intravenous Immunoglobulin (IVIG)

• Used for refractory disease or life-threatening complications (e.g., TTP-like picture, severe cytopaenias)
• Typical dose: 2 g/kg over 3-5 days

5.8 Plasmapheresis

• Reserved for life-threatening complications clearly attributable to pathogenic autoantibodies (e.g., catastrophic APS, TTP)

5.9 Pregnancy in SLE

• Plan pregnancy during disease remission
• Azathioprine and hydroxychloroquine are safe in pregnancy
• HCQ reduces risk of congenital heart block (from anti-Ro antibodies)
• Progestin-only contraception or IUD advised in active disease (avoid combined OCP in moderate-to-severe disease)

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6. Differential Diagnosis

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Key Points Summary

• ANA positive in ~99% of SLE patients - a negative ANA makes SLE very unlikely
• Anti-dsDNA is the most disease-specific antibody and tracks disease activity
• Anti-Sm is highly specific but not sensitive
• Low C3/C4 + rising anti-dsDNA = impending flare/nephritis
• CRP is paradoxically low in SLE (unlike most inflammatory conditions); a high CRP should prompt investigation for infection
• Class IV lupus nephritis is the most common and most severe renal class
• Hydroxychloroquine is the cornerstone of SLE therapy for all patients
• The malar rash spares the nasolabial folds (unlike rosacea, which affects them)
• Premature atherosclerosis is a major cause of late mortality

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