GC046 Facial Rash And Painful Fingers: SLE
Systemic lupus erythematosus is a chronic multisystem autoimmune disease characterized by autoantibody production (notably anti-dsDNA and anti-Smith), commonly presenting with a malar butterfly rash, photosensitivity, arthritis, and potential involvement of the kidneys, heart, and other organs.
Systemic Lupus Erythematosus (SLE) — Facial Rash and Painful Fingers
The Big Idea: SLE is the archetypal multisystem autoimmune disease. A genetically predisposed individual (almost always a young woman) loses immune tolerance, produces a vast array of autoantibodies, forms immune complexes, and fails to clear them — leading to tissue damage in virtually any organ. The lecture walks through a unifying case (Helen, F/26) to illustrate how constitutional symptoms, inflammatory polyarthritis, skin rashes, cytopenias, and renal involvement converge into one diagnosis, and then systematically covers immunopathogenesis, classification criteria, organ-by-organ clinical features, serology interpretation, treatment principles, and the changing prognosis of SLE. [1]
Learning Objectives (from slide "Core Knowledge"): [1]
- The immunopathogenesis of SLE
- Evolution of the classification criteria of SLE — based on systemic disease, common disease manifestations, and demonstration of autoimmunity
- Common clinical features of SLE
- Interpretation of serological tests in SLE diagnosis and management
- General management principles
- General use of immunosuppressive drugs
- Changing prognosis of SLE
How it fits into exams: SLE is tested almost every year — in MCQ (serology interpretation, drug side effects, clinical features), SAQ (workup of facial rash + joint pain, pre-pregnancy counselling), and mini-cases (multisystem disease with lab abnormalities). The 2018 Fourth Summative SAQ Q4 is essentially a copy of the lecture case. [3]
Part 1: The Case — Helen F/26 (Systemic Autoimmunity)
This case is the lecture's anchor and has been almost directly reproduced in 2018 Fourth Summative SAQ Q4. [1][3]
| Feature | Detail | Significance |
|---|---|---|
| Age/Sex | 26-year-old female | Peak SLE demographic (F:M = 9:1, reproductive years) |
| Initial complaint (8 months ago) | Painful MCP/PIP arthritis + morning stiffness | Mimicked RA → initially misdiagnosed |
| Treatment | Naproxen 250 mg TDS → improvement | NSAIDs help inflammatory arthritis symptomatically |
| Trigger | Trip to Bangkok 2 months ago → unwell since | UV exposure, infections — known SLE triggers |
| Admission features | Malaise, high fever, facial rash, lower limb purpuric petechiae, arthritis | Constitutional + multi-organ = think systemic autoimmunity |
| Test | Result | Normal Range | Interpretation |
|---|---|---|---|
| WBC | 3.5 × 10⁹/L | 4–11 | Leucopaenia (anti-leucocyte antibodies) |
| Hgb | 9.8 g/dL | 11.5–16 | Anaemia (likely haemolytic — see reticulocyte, LDH, bilirubin) |
| Platelet | 54 × 10⁹/L | 150–400 | Thrombocytopaenia (anti-platelet Ab, APS) |
| Reticulocyte | 6% | ~1% | Elevated → marrow response to peripheral destruction |
| ESR | 58 mm/hr | Elevated → active inflammation | |
| Creatinine | 125 µmol/L | 62–124 | Mildly elevated → early renal involvement |
| Bilirubin | 45 mmol/L | 0–17 | Elevated (unconjugated) → haemolysis |
| Liver enzymes | Normal | Rules out hepatic cause of bilirubin elevation | |
| Albumin | 30 g/L | 36–50 | Low → proteinuria (nephrotic-range), chronic inflammation |
| LDH | 340 U/L | 55–140 | Markedly elevated → haemolysis marker |
| Urine P/Cr ratio | 70 mg/mmol | < 15 | Significant proteinuria → lupus nephritis |
| ANA | 1/1080 | High titre positive | |
| Anti-dsDNA | 230 U/L | < 35 | Markedly elevated → specific for SLE, correlates with activity |
| Anti-ENA | Anti-Sm +ve, Anti-Ro +ve | Anti-Sm = highly specific for SLE | |
| ACA (IgG) | +ve | Antiphospholipid antibody → risk of APS | |
| C3 | 0.56 g/L | 0.9–1.8 | Low → complement consumption by immune complexes |
| C4 | 0.12 g/L | 0.1–0.5 | Low-normal (borderline) |
| Direct Coombs' test | +ve | Autoimmune haemolytic anaemia | |
| Bone marrow | Peripheral consumption | Confirms peripheral destruction, not marrow failure |
High Yield — Connecting the Dots in Helen's Case
The triad of pancytopaenia + elevated reticulocytes/LDH/bilirubin + positive Direct Coombs' test = autoimmune haemolytic anaemia (AIHA) in the context of SLE. The low complement + high anti-dsDNA confirms active immune complex–mediated disease. The proteinuria with borderline creatinine indicates early lupus nephritis. This is a classic exam scenario. [1]
Left column: [1]
- Young female
- Multi-system disease: constitutional symptoms, inflammatory polyarthritis, skin rashes, haemic involvement, renal involvement
- Possible triggering factor: trip to Thailand (UV exposure)
Right column: [1]
- Autoimmunity: positive autoantibody screen, Coombs' test
- Immune complex disease: lowered complement levels
Part 2: What Is SLE and Why Is It Important?
"SLE is a chronic multisystem autoimmune disorder characterised by profound immunological disturbances resulting in an excessive production of autoantibodies, some of which may cause direct tissue damage while others take part in immune complex (IC) formation. Failure to remove these ICs is the most important pathological mechanism of tissue damage in SLE." [1]
Why this definition matters for exams: It tells you the TWO mechanisms of tissue damage:
- Direct autoantibody-mediated damage (e.g., anti-RBC antibodies → AIHA, anti-platelet → thrombocytopaenia)
- Immune complex deposition (e.g., glomerulonephritis, vasculitis, skin) — this is the MORE IMPORTANT mechanism overall
SLE sits at the centre of a spectrum that includes: [1]
- uCTD (undifferentiated connective tissue disorder)
- SSc (systemic sclerosis)
- APS (antiphospholipid syndrome)
- RA (rheumatoid arthritis)
- PM/DM (polymyositis/dermatomyositis)
- PBC (primary biliary cirrhosis)
- Sjögren's syndrome
Clinical implication: These conditions overlap. A patient initially labelled as "uCTD" may evolve into SLE. Similarly, SLE can coexist with secondary APS or secondary Sjögren's. This concept of overlap/spectrum is frequently tested. [2]
| Feature | Detail |
|---|---|
| F:M ratio | 9:1 |
| Caucasians | ~10–20/100,000; best disease outcomes |
| Orientals | ~50–70/100,000 |
| Caribbean blacks | ~1/250 women in Jamaica; worst disease outcomes |
| Peak onset | Reproductive years (15–45) |
Exam Pearl
Wide racial differences exist in incidence, prevalence, clinical presentation, and course of SLE. Orientals have higher prevalence than Caucasians. Caribbean blacks have the worst outcomes. This is a frequently examined factoid. [1]
Part 3: Immunopathogenesis of SLE
Key genetic factors: [1]
- High concordance rate in identical twins (24–70%)
- 10% of relatives have abnormal serology
- HLA association: B8, DR2, DR3
- Other HLA class III or non-HLA genes
- Genes influencing sex hormone status
- Complement deficiency (e.g., C4 deficiency) — ~5% of SLE patients
Why complement deficiency causes SLE: Complement is essential for clearing immune complexes and apoptotic debris. If you lack C4 (or C1q, C2), apoptotic material accumulates → acts as auto-antigen → loss of tolerance → autoimmunity. This is a beautiful example of how understanding the pathogenesis explains the disease.
| Pathway | Genes |
|---|---|
| T cell activation | PTPN22, TNFSF4, HLA class II |
| B cell signalling | BANK1, BLK, PRDM1 |
| Immune complex/antigen clearance | ITGAM, TREX1, FcγR genes, complement genes |
| TLR–IFN pathways | IRF5, STAT4, IRAK1 |
Exam takeaway: SLE is NOT a single-gene disease. It involves multiple pathways — T cell activation, B cell hyperactivity, defective IC clearance, and aberrant innate immunity (type I interferon). You don't need to memorize every gene, but understanding the four categories is important.
"More than just genes" — the lecture emphasises that SLE is common among Afro-Americans but rare in Afro-Africans, suggesting environmental factors are crucial. [1]
| Trigger | Examples |
|---|---|
| Infections | EBV, Parvovirus B19, Rhabdovirus, HIV-1, Adenovirus, Salmonella |
| Chemical agents | Hydrazine, tartrazine, hair dyes, eosin, heavy metals (mercuric chloride, gold, cadmium) |
| Foods | L-Canavanine (alfalfa seeds and sprouts) |
| Ultraviolet light | UVA and UVB |
Why UV light triggers SLE: UV radiation induces keratinocyte apoptosis → nuclear antigens are exposed on the cell surface → in a genetically predisposed individual, these auto-antigens trigger an immune response → flare. This is why photosensitivity is both a clinical feature and a trigger.
Genetic background + triggers (UV, drugs, infection) → APC presents auto-Ag via MHC/B7 to T cells → T cell help to B cells → Excessive autoantibody production → Immune complex formation → Failure to remove auto-Abs/ICs = tissue damage [1]
Additional mechanisms from the slide:
- Increased adhesion molecule expression / endothelial damage
- Defective apoptosis clearance
- Cytokine dysregulation
EULAR/ACR 2019 Classification Criteria
Entry criterion: ANA ≥ 1/80 [1] SLE classified if ≥ 10 points Must have at least one clinical domain Must exclude other more likely disease No double counting within each domain — only highest point in each domain counts Criteria can be serial or in parallel (i.e., they don't all have to be present at the same time)
High Yield — Why Classification Criteria Matter
Classification criteria are designed for research (to ensure homogeneous study populations), NOT for clinical diagnosis. A clinician may diagnose SLE even if the patient doesn't fully meet criteria. Conversely, meeting criteria doesn't automatically mean the patient has clinical SLE if another diagnosis is more likely. This distinction is a common exam trap. [1]
Domains and Points (for reference — the lecture doesn't enumerate every criterion but highlights the framework):
| Domain | Examples | Points |
|---|---|---|
| Constitutional | Fever | 2 |
| Haematological | Leucopaenia, thrombocytopaenia, autoimmune haemolysis | 2–4 |
| Neuropsychiatric | Delirium, psychosis, seizure | 2–5 |
| Mucocutaneous | Oral ulcers, non-scarring alopecia, SCLE, ACLE, DLE | 2–6 |
| Serosal | Pleural/pericardial effusion | 5–6 |
| Musculoskeletal | Joint involvement | 6 |
| Renal | Proteinuria, Class III/IV/V nephritis on biopsy | 4–10 |
| Immunological | Anti-dsDNA, anti-Sm, antiphospholipid, complement, direct Coombs' | 2–6 |
Part 5: Clinical Features of SLE — System by System
- Fever
- Malaise
- Poor appetite
- Weight loss
These are non-specific but important because they indicate active systemic disease.
Mucocutaneous Features
| Lesion | Key Features | Exam Points |
|---|---|---|
| Malar (butterfly) rash | Erythema over cheeks and nose; nasolabial folds often spared; may or may not be associated with sun exposure | Most iconic SLE sign; sparing of nasolabial folds differentiates from rosacea, seborrheic dermatitis |
| Photosensitivity | Rash appearing after sun exposure | Both a trigger and a manifestation |
| Discoid lupus erythematosus (DLE) | Chronic, palpable, indurated plaques; follicular plugging; scarring alopecia; hyper/hypopigmented | Only ~10% of DLE patients have systemic SLE |
| Subacute cutaneous lupus (SCLE) | Annular or psoriasiform; resolves without scarring; strongly associated with anti-Ro antibodies | ~50–60% have systemic involvement |
| Cutaneous vasculitis | Nail edge/fold, splinter haemorrhages, palms, elbows, lower limbs | Small vessel vasculitis |
| Livedo reticularis | Reticular (net-like) purplish discolouration | Associated with antiphospholipid antibodies |
| Non-scarring alopecia | Diffuse thinning or hair fragility with visible broken hairs | Scarring alopecia = think DLE |
Lupus band test: Immunofluorescence showing deposition of immune complexes (IgG, IgM, IgA, C3) at the dermoepidermal junction. Positive at lesional skin in DLE and at uninvolved, sun-protected skin in systemic SLE. [1]
- Purpuric skin rash — due to thrombocytopaenia OR leucocytoclastic vasculitis
- Differentiating feature: Vasculitic purpura is raised, palpable, and sometimes tender (vs. thrombocytopaenic purpura which is flat/non-palpable)
- Erythema nodosum
- Oral ulcers — usually painless (exam pearl!) on palate, buccal mucosa, tongue, or nasal
- Raynaud's phenomenon — triphasic colour change (white → blue → red) [5]
| Feature | Key Points |
|---|---|
| Non-deforming polyarthritis/polyarthralgia | RA distribution but NO radiological erosions — this is the classic distinction from RA |
| Jaccoud's arthritis | Deforming but non-erosive — reducible deformities (ulnar deviation, swan neck) due to ligament laxity, not bone erosion |
| Avascular necrosis (AVN) | Often secondary to corticosteroid use; affects femoral head most commonly |
| Erosive arthritis | Rare in SLE |
| Myopathy | Weakness, myalgia, myositis — may be drug-induced (steroids, statins) or SLE-related |
| Myasthenia gravis | Can coexist with SLE (autoimmune overlap) |
Exam Pearl — SLE Arthritis vs. RA
SLE arthritis has an RA-like distribution (MCPs, PIPs, wrists) but is classically non-erosive on X-ray. If you see a young woman with bilateral hand synovitis but normal X-rays → think SLE before RA. The presence of Jaccoud's arthropathy (deforming but passively correctable) is also a giveaway. [1][6]
- Pleurisy — most common pulmonary manifestation; may cause pleural effusion
- Infections — immunocompromised state
- Recurrent atelectasis / "shrinking lung syndrome" — diaphragmatic myopathy
- Diffuse lung infiltration and fibrosis
- Pulmonary hypertension
- Pulmonary infarct (often related to APS)
- Pericarditis — most common cardiac manifestation
- Cardiomyopathy
- Pulmonary hypertension
- Libman-Sacks endocarditis — aseptic, sterile vegetations on valve leaflets (typically mitral); NOT infective endocarditis
Why Libman-Sacks matters: These sterile vegetations can be a source of emboli → stroke. They are also associated with antiphospholipid antibodies. Differentiate from infective endocarditis (no fever, negative blood cultures).
Renal Features — Lupus Nephritis [1]
Lupus nephritis is one of the most important determinants of morbidity and mortality in SLE.
- Proteinuria
- Urine sediments (RBCs, casts)
- Hypertension
- Acute renal failure
- Chronic renal failure
| Class | Name | Key Features | Prognosis |
|---|---|---|---|
| I | Normal | Normal by light microscopy | Excellent |
| II | Mesangial | Mesangial hypercellularity, IC deposition | Good |
| III | Focal proliferative | < 50% glomeruli affected | Moderate; needs treatment |
| IV | Diffuse proliferative | ≥ 50% glomeruli affected; most severe and common form | Worst prognosis; needs aggressive Rx |
| V | Membranous | Subepithelial IC deposits; presents as nephrotic syndrome | Variable |
| VI | Sclerotic | > 90% globally sclerosed glomeruli | End-stage; irreversible |
The role of renal biopsy: Immuno-staining showing Ig deposition confirms immune complex–mediated glomerulonephritis and guides classification → which determines treatment intensity. [1]
High Yield — Class IV Lupus Nephritis
Class IV (diffuse proliferative) is the most common and most severe form of lupus nephritis. It requires aggressive immunosuppression (induction with cyclophosphamide or MMF + steroids, then maintenance with MMF or azathioprine). Always think of this when an SLE patient presents with active urinary sediment + proteinuria + rising creatinine + low C3/C4. [1][7]
Two categories by patho-aetiology:
Unknown aetiology:
- Depression/psychosis — not always related to disease activity; considerable variability; usually reversible; somatic treatment may help
- Migrainous headache — peri-menstrual; may be associated with disease activity; poor response to treatment
Known pathological mechanisms (vasculitis/thrombosis/auto-Ab/infection):
- Cerebral ischaemia (TIAs or stroke) — often related to APS
- Retinopathy — cytoid bodies (cotton-wool spots) = microinfarcts
- Cranial or peripheral neuropathy
- Myelitis (especially transverse myelitis — think APS)
- Chorea
- Cerebellar ataxia
- Meningitis and cerebral abscesses (infectious)
| Feature | Mechanism |
|---|---|
| Lymphadenopathy | ~25% of patients; reactive |
| Leucopaenia | Anti-leucocyte antibodies |
| Anaemia | Haemolytic (AIHA — Coombs' +ve) or anaemia of chronic disease (normochromic normocytic) |
| Thrombocytopaenia | Anti-platelet antibody; antiphospholipid syndrome |
| Thrombosis | APS; vasculitis; corticosteroid use |
| Splenomegaly | Part of disease or related to haemolysis |
"Infections: the most important cause of death in SLE" [1]
| Intrinsic Factors | Extrinsic Factors |
|---|---|
| Low complements | Steroids |
| Anti-WBC antibodies | Other immunosuppressive drugs |
| Impaired cell-mediated immunity | Nephrotic syndrome |
| Defective phagocytosis | Uraemia |
| Poor antibody response to certain antigens | |
| Hyposplenism |
Part 6: Serological Tests in SLE
- ANA — usually suffices as screening
- Anti-dsDNA, anti-ENA, APA → only if ANA is positive or SLE is strongly suspected
- Rheumatoid factor → to exclude possible RA/Sjögren's
- Complement levels (C3, C4)
- Ig pattern
- CBC + differential
- Renal function tests + urinalysis
- Serum albumin and globulin
ANA: Highly sensitive but non-specific and NOT diagnostic
Key exam points:
- Staining pattern (homogeneous, speckled, nucleolar) has NO prognostic value
- Serum titre does NOT correlate with disease severity/activity
- May become negative if there is severe proteinuria (antibodies lost in urine)
- ANA can be positive in many conditions: SLE, SSc, Sjögren's, drug-induced lupus, RA, even healthy individuals (especially elderly)
| ANA Sub-type | Target Antigen |
|---|---|
| Anti-ssDNA | Single-stranded DNA |
| Anti-histone | Histone proteins (think drug-induced lupus) |
| Anti-dsDNA | Double-stranded DNA |
| Anti-Sm | Smith antigen |
| Anti-RNP | Ribonucleoprotein |
| Anti-Ro (SSA) | Ro antigen |
| Anti-La (SSB) | La antigen |
| Anti-P | Ribosomal P protein |
Occurs in ~60% of patients with SLE Highly specific for SLE Is one of the classification criteria for SLE Titre correlates with overall disease activity May be associated with lupus nephritis
Why this matters: Anti-dsDNA is the ONLY autoantibody where titre is useful for monitoring. If anti-dsDNA rises and complement falls → flare is likely.
| Antibody | Frequency in SLE | Clinical Association |
|---|---|---|
| Anti-Ro (SSA) | 40–50% | SCLE, neonatal lupus, congenital heart block, Sjögren's overlap |
| Anti-La (SSB) | 30–40% | Usually with anti-Ro; Sjögren's overlap; may be protective against nephritis |
| Anti-Sm | 10–20% | Highly specific for SLE (most specific antibody); NOT sensitive |
| Anti-RNP | 30–40% | High titres → MCTD; lower titres in SLE |
Most anti-ENA antibodies (except anti-Sm) are NOT diagnostic of SLE. They probably don't correlate with disease activity. They are found in many connective tissue disorders. They may predict clinical manifestations and have prognostic value. [1]
Three types:
- Anti-cardiolipin antibodies (IgG and IgM)
- Anti-β2 glycoprotein I antibodies
- Lupus anticoagulant (a coagulation assay — paradoxically causes thrombosis, not bleeding)
Clinical features:
- Arterial/venous thrombosis
- Superficial thrombophlebitis and livedo reticularis
- Transverse myelitis
- Recurrent abortions
- Mild/moderate thrombocytopaenia
1° vs 2° APS: [1]
| 1° APS | 2° APS |
|---|---|
| All APS features present | All APS features present |
| NO underlying condition | An underlying condition exists (e.g., SLE, other CTD) |
Exam Trap — Positive Anti-PL ≠ APS
Patients with other conditions may have antiphospholipid antibodies but not thrombosis or pregnancy morbidity. They do NOT have APS. APS requires BOTH the antibody AND the clinical event. [1]
| Test | Role in Monitoring |
|---|---|
| Clinical assessment + BP | Essential every visit |
| ANA and anti-ENA | Have NO role in monitoring activity |
| Anti-dsDNA | Level positively correlates with activity (↑ = flare) |
| C3/C4 | Levels negatively correlate with activity (↓ = flare) |
| Urinalysis | Protein, cells, casts → detect nephritis flare |
| CBC | Detect cytopenias |
| Blood biochemistry | Renal function, albumin |
In most cases, active SLE disease does NOT evoke a CRP response. High CRP levels in patients with SLE should lead to suspicion of INFECTION. Patients with active arthritis, serositis, or vasculitis may have moderately elevated CRP.
Why this is crucial: This is a discriminator question in exams. A lupus patient with fever + high CRP → think INFECTION first, not lupus flare. A lupus patient with fever + high ESR but normal CRP → more likely lupus flare.
High Yield — ESR vs CRP in SLE
ESR is elevated in active SLE (due to hypergammaglobulinaemia). CRP is usually normal in SLE flares. If CRP is high → think infection, NOT flare (unless arthritis/serositis/vasculitis). This is tested almost every year. [1]
Part 7: Treatment of SLE
- SLE is a multisystem disease. Diagnosis is based on clinical grounds + serologic abnormalities.
- SLE care is multidisciplinary, based on a shared patient-physician decision.
- Organ-/life-threatening complications require initial high-intensity and subsequent maintenance immunosuppressive therapy.
- Treatment goals: long-term patient survival, prevention of organ damage, and optimisation of health-related quality of life.
- Counselling — patients, spouse, and relatives
- Poor compliance is a major risk factor of poor prognosis
- Regular monitoring
- Avoid excessive sun exposure
- Avoid potential antigenic stimuli
- ? Avoid oral contraceptives (controversial — oestrogen may trigger flares)
- Infection control (most important cause of death)
- Pregnancy issues (pre-pregnancy counselling is a common exam topic)
- Supportive treatment (e.g., dialysis)
Drug Treatment — 4 Recommendation Areas [1]
- Aim at remission or low disease activity and prevention of flares in all organs
- Lowest possible dose of glucocorticoids
- Flares treated according to severity by adjusting ongoing therapies
2. General Drug Treatment
Hydroxychloroquine is recommended for ALL patients with SLE
Benefits:
- Useful for arthritis, cutaneous manifestations, constitutional symptoms
- May reduce systemic complications
- May improve pregnancy outcomes
- May reduce secondary infectious disease complications
Side effects (commonly tested — 2018 SAQ Q4b, 2021 MCQ Q13):
- Retinal toxicity (bull's eye maculopathy) — > 10% after 20 years of use
- Major risk factors:
- Duration of treatment (OR 4.71 for every 5 years)
- Dose (OR 3.34 for every 100 mg daily dose increase)
- Risk is very low for doses < 5 mg/kg/day
- Chronic kidney disease (adjusted OR 8.56)
- Pre-existing retinal/macular disease
- Major risk factors:
- Drug blood levels can be used to assess compliance
| Drug | Specific Side Effect | Universal Side Effects |
|---|---|---|
| Azathioprine | Hepatotoxicity | All: bone marrow suppression |
| Cyclophosphamide | Infertility; haemorrhagic cystitis | All: increased susceptibility to infection |
| Cyclosporin A | Renal toxicity | All: potentially carcinogenic |
| Methotrexate | Hepatotoxicity | All: potentially teratogenic |
| Leflunomide | Hepatotoxicity | |
| Mycophenolate mofetil (MMF) | GI side effects | |
| Tacrolimus | Nephrotoxicity, diabetes |
Exam Pearl — Cyclophosphamide Side Effects
Cyclophosphamide causes haemorrhagic cystitis (due to the metabolite acrolein — prevented by co-administration of MESNA and aggressive hydration) and infertility (gonadotoxic — counsel patients about fertility preservation before starting). [1]
- Belimumab — anti-BAFF (B-lymphocyte stimulator); reduces B cell survival; approved add-on for active SLE
- Rituximab — anti-CD20; depletes B cells; used off-label for refractory SLE (especially nephritis, cytopenias)
- Anifrolumab — anti-type I interferon receptor; newer agent; showed rapid BICLA response in TULIP trials
- Skin
- Neuropsychiatric disease
- Haematological disease
- Renal disease (lupus nephritis — often requires the most aggressive therapy)
- Antiphospholipid syndrome — anticoagulation
- Infectious diseases — prophylaxis, vaccination (avoid live vaccines), early treatment
- Cardiovascular disease — accelerated atherosclerosis; manage traditional risk factors
Part 8: Prognosis of SLE
| Era | 5-Year Survival | 10-Year Survival |
|---|---|---|
| 1950s | ~50% | Very low |
| 1980s | ~80% | ~65% |
| 1990s–present | ~95% | ~90% |
The case of Helen: At age 26, her 5-year and 10-year survival chances are now excellent (~95% and ~90%), but she still faces a higher mortality risk than age-matched healthy women.
| Timing | Main Cause |
|---|---|
| Early/medium stage | Infection — the most important cause of death overall |
| Late stage | Cardiovascular thrombosis (accelerated atherosclerosis) |
Risk factors for worse prognosis: [1]
- Late disease onset
- Male SLE (worse than female)
- Lower socioeconomic class
- Poor compliance (emphasised in the lecture)
High Yield — Bimodal Mortality in SLE
Early deaths in SLE are from infections (due to immunosuppression + intrinsic immune defects). Late deaths are from cardiovascular disease (due to accelerated atherosclerosis from chronic inflammation, steroid use, and metabolic derangements). This bimodal pattern is a classic exam point. [1]
Part 9: Pre-Pregnancy Counselling in SLE (Exam Favourite)
This is directly tested in 2018 SAQ Q4c-d. [3]
| Test | Reason |
|---|---|
| Anti-Ro (SSA) and Anti-La (SSB) | Associated with neonatal lupus and congenital heart block in the baby |
| Antiphospholipid antibodies (ACA, LA, anti-β2GPI) | Associated with recurrent miscarriage, pre-eclampsia, IUGR, placental insufficiency |
| Anti-dsDNA + C3/C4 | Assess current disease activity — pregnancy should be planned during remission |
| Renal function + urinalysis | Active nephritis = higher risk pregnancy |
| Drug | Advice | Reason |
|---|---|---|
| Methotrexate | Must STOP at least 3 months before conception | Teratogenic |
| Cyclophosphamide | Must STOP; counsel about fertility | Teratogenic + gonadotoxic |
| Hydroxychloroquine | CONTINUE | Safe in pregnancy; stopping may cause flare |
| Azathioprine | Generally safe to continue (low dose) | Less teratogenic than MTX/CYC |
| Prednisolone | Can continue at lowest effective dose | Mostly metabolised by placental 11β-HSD |
| MMF | Must STOP; switch to azathioprine | Teratogenic |
Part 10: Integration with Related Material
Raynaud's occurs in SLE as part of vasospastic/vasculitic phenomena. The triphasic colour change (white → blue → red) can also be seen in SSc, MCTD, and primary Raynaud's. When Raynaud's occurs in a young woman with other systemic symptoms → screen for CTD (ANA, anti-dsDNA, etc.). [5]
SLE (and Sjögren's) can cause distal (Type 1) RTA — presenting with normal anion gap metabolic acidosis, hypokalaemia, and nephrocalcinosis. This is a commonly tested crossover point. [7]
Lupus anticoagulant/APS is the classical acquired cause of BOTH arterial and venous thrombosis — unlike inherited thrombophilias which cause mainly VTE. [10]
Bull's eye maculopathy from HCQ — tested in 2021 MCQ Q13. Baseline eye exam, then annual screening after 5 years (or earlier if risk factors). [9]
Likely Exam Questions
-
A 28-year-old woman with SLE presents with fever. ESR is 85 mm/hr, CRP is 2 mg/L (normal). What is the most likely explanation?
- Answer: Active SLE flare — CRP is typically normal in SLE flares (ESR is elevated due to hypergammaglobulinaemia). If CRP were high → suspect infection.
-
Which antibody is most specific for SLE?
- Answer: Anti-Sm (though anti-dsDNA is also highly specific and more commonly present)
-
A patient on HCQ for 10 years develops bilateral progressive visual loss. What is the diagnosis?
- Answer: Bull's eye maculopathy (HCQ retinal toxicity)
-
Which class of lupus nephritis is the most severe and common?
- Answer: Class IV — diffuse proliferative
Q: A 26-year-old lady with facial rash, oral ulcers, and hair loss for 3 months. Examination shows diffuse malar rash sparing the nasolabial fold and synovitis of PIP joints.
(a) What immunological tests will you arrange to confirm diagnosis? (3 marks)
- ANA (screening — highly sensitive)
- Anti-dsDNA antibodies (highly specific, correlates with activity)
- Complement levels (C3, C4 — low in active disease)
- Anti-ENA (anti-Sm for specificity; anti-Ro for cutaneous/pregnancy implications)
- CBC (look for cytopenias)
- Urinalysis (proteinuria, haematuria for nephritis)
(b) State two potential side effects of hydroxychloroquine. (1 mark)
- Retinal toxicity (bull's eye maculopathy)
- GI upset (nausea, diarrhoea)
- [Also accept: skin pigmentation, cardiomyopathy (rare)]
(c) What immunological tests before pregnancy and their prognostic values? (4 marks)
- Anti-Ro/Anti-La → risk of neonatal lupus + congenital heart block
- Antiphospholipid antibodies (ACA, LA, anti-β2GPI) → risk of recurrent miscarriage, thrombosis, pre-eclampsia
(d) What advice regarding current drug regimen? (2 marks)
- Continue hydroxychloroquine (safe in pregnancy, stopping may cause flare)
- Stop methotrexate at least 3 months before conception (teratogenic)
High Yield Summary
SLE in a nutshell for exams:
- Who: Young woman (F:M = 9:1), Orientals > Caucasians in prevalence
- What: Chronic multisystem autoimmune disease; excessive autoantibody production + immune complex deposition → tissue damage
- Triggers: UV light, infections, drugs in genetically predisposed individuals
- Diagnosis: ANA ≥ 1/80 (screening) → anti-dsDNA (specific, correlates with activity) → anti-Sm (most specific); EULAR/ACR 2019 criteria ≥ 10 points
- Key clinical features: Malar rash (spares nasolabial folds), non-erosive polyarthritis, lupus nephritis (Class IV worst), cytopenias, serositis, neuropsychiatric manifestations
- Monitoring: Anti-dsDNA (↑ = flare), C3/C4 (↓ = flare); ANA/anti-ENA NOT useful for monitoring; CRP usually normal in flares (high CRP → think infection)
- Treatment: HCQ for all; steroids (lowest dose); immunosuppressants (AZA, MMF, CYC) for organ-threatening disease; biologics (belimumab, rituximab, anifrolumab)
- Prognosis: 5-year survival ~95%; early deaths from infection, late deaths from CVD
- Pregnancy: Check anti-Ro/La (congenital heart block) and APA (miscarriage); stop MTX/MMF; continue HCQ
Active Recall - SLE Lecture Notes
[1] Lecture slides: GC 046. Facial rash and painful fingers_SLE.pdf (all sections) [2] Senior notes: Block A - Fingers turn white and blue_ Scleroderma and MCTD, Raynaud's disease, other rheumatic diseases.pdf [3] Past papers: 2018 Fourth Summative SAQ.pdf (Question 4) [4] Lecture slides: GC 022. Visual Spot Diagnoses - Survival Guide for Primary Care [Updated 20250425].pdf [5] Lecture slides: GC 053. Fingers turn white and blue.pdf [6] Senior notes: Block A - Multiple joint pain_ Rheumatoid arthritis and the concept of inflammatory arthritis.pdf [7] Senior notes: Block A - Electrolyte and Acid-Base Disorders.pdf (Distal RTA section) [8] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (SLE clinical manifestation section) [9] Past papers: 2021 Fourth Summative Assessment MCQ.pdf (Question 13) [10] Senior notes: Block A - Leg swelling and chest pain_ deep vein thrombosis; pulmonary embolism; Thrombophilia.pdf [11] Senior notes: Maksim Medicine Notes.pdf (Rheumatology section) [12] Senior notes: Ryan Ho Fundamentals.pdf (Examination of hands section) [13] Senior notes: Block A - Facial rash and painful fingers_ SLE.pdf [14] Senior notes: Ryan Ho Opthalmology.pdf (Rheumatological disease and the eye section)
GC045 End-of-life Care For Hospitalised Older Adults
End-of-life care for hospitalized older adults is a comprehensive, patient-centered approach focused on symptom management, comfort, dignity, and shared decision-making for elderly patients nearing death during an inpatient admission.
GC047 Family History Of Anaemia
A documented record of anemia occurring in one or more blood relatives, suggesting a possible hereditary predisposition to conditions such as sickle cell disease, thalassemia, or other inherited anemias.