Left column: ^[1]

• Young female
• Multi-system disease: constitutional symptoms, inflammatory polyarthritis, skin rashes, haemic involvement, renal involvement
• Possible triggering exposure: travel-related UV or infection, not proven by chronology alone

Right column: ^[1]

• Autoimmunity: positive autoantibody screen, Coombs' test
• Immune complex disease: lowered complement levels

"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:

1. Direct autoantibody-mediated damage (e.g., anti-RBC antibodies → AIHA, anti-platelet → thrombocytopaenia)
2. Immune complex deposition (e.g., glomerulonephritis, vasculitis, skin) — this is the MORE IMPORTANT mechanism overall

The slide's flower diagram places SLE at the centre of overlapping autoimmune phenotypes. The useful message is overlap, not that every surrounding disorder is a subtype of SLE: ^[1]

• uCTD (undifferentiated connective tissue disorder)
• SSc (systemic sclerosis)
• APS (antiphospholipid syndrome)
• RA (rheumatoid arthritis)
• PM/DM (polymyositis/dermatomyositis)
• PBC (now termed primary biliary cholangitis)
• 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]

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
• Rare inherited early classical-pathway deficiencies (especially C1q, C2, or C4) carry a strong SLE association; this is distinct from acquired low C3/C4 through consumption during active disease

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.

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.

The slide's long list mixes established flare-promoting exposures, epidemiologic associations, rare case reports, and speculative older claims. Keep the evidence tiers separate: ^[1][18]

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

• Fever
• Malaise
• Poor appetite
• Weight loss

These are non-specific but important because they indicate active systemic disease.

AVN image reading (slide 34): the hip radiograph shows femoral-head sclerosis/subchondral collapse, while the coronal MRI demonstrates bilateral osteonecrosis more clearly. MRI is more sensitive in early disease. New groin pain or reduced hip rotation in a steroid-exposed patient should prompt imaging rather than being attributed to “lupus arthralgia.”

• 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 embolise and are associated with antiphospholipid antibodies. The serial chest radiographs on slide 37 show progressive enlargement of the cardiac silhouette compatible with a growing pericardial effusion, but echocardiography is required to confirm the effusion and assess tamponade physiology. Slide 38 shows bulky sterile fibrin/platelet vegetations on a valve surface. Fever can occur in active SLE, so blood cultures and the full infectious assessment matter more than the simplistic “no fever” distinction.

Attribution is the key step: depression, cognitive symptoms, psychosis, and headache may reflect active inflammatory SLE, APS/thrombosis, infection, metabolic disease, medication (especially glucocorticoids), or an unrelated primary disorder. “Lupus headache” is not a safe shortcut; new severe, focal, febrile, seizure-associated, or thunderclap headache needs standard urgent neurologic/infectious/vascular assessment.

Important syndromes and mechanisms (inflammation, thrombosis/APS, autoantibodies, or infection):

• Cerebral ischaemia (TIAs or stroke) — often related to APS
• Retinopathy — the fundus image shows cytoid/cotton-wool bodies, reflecting retinal nerve-fibre-layer ischaemia; severe visual symptoms require urgent ophthalmology
• Cranial or peripheral neuropathy
• Myelitis (especially transverse myelitis — think APS)
• Chorea
• Cerebellar ataxia
• Meningitis and cerebral abscesses (infectious mimics/complications rather than inflammatory NPSLE)

MRI caveat: the paired MRI images labelled “microinfarcts” show white-matter lesions, but this appearance is non-specific. Attribution to SLE requires the clinical syndrome and exclusion of vascular risk, APS, infection, demyelination, and other causes. Current ACR guidance treats severe, confidently attributed inflammatory syndromes with glucocorticoids plus organ-appropriate immunosuppression, while seizures and psychosis also receive standard symptomatic treatment. ^[16]

Infection is a major preventable cause of morbidity and mortality in SLE. The slide's absolute “most important cause” wording is cohort- and era-dependent. Always distinguish flare from infection before escalating immunosuppression. ^[1][15][16]

• ANA — usually suffices as screening
• Anti-dsDNA, anti-ENA, APA → only if ANA is positive or SLE is strongly suspected
• Rheumatoid factor is not an exclusion test for RA or Sjögren disease and can be positive in SLE; order it only when the differential makes it useful (often with anti-CCP for suspected RA)
• 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:

• ANA by HEp-2 immunofluorescence is sensitive but not specific; titre and pattern modify the differential rather than diagnosing SLE.
• Repeating ANA titres is not useful for routine disease-activity monitoring.
• The slide's claim that severe proteinuria makes ANA negative through urinary antibody loss is not a reliable clinical rule.
• ANA can be positive in many conditions: SLE, SSc, Sjögren's, drug-induced lupus, RA, even healthy individuals (especially elderly)

Occurs in ~60% of patients with SLE Highly specific for SLE Is one of the classification criteria for SLE A rising titre may accompany activity, especially nephritis, but performance is patient- and assay-dependent Association is not proof of active nephritis

Why this matters: serial anti-dsDNA and C3/C4 can support monitoring, especially when their pattern has tracked that individual's renal disease. Their sensitivity and specificity are only modest: a change should trigger clinical, urine, and kidney-function reassessment, not pre-emptive treatment in isolation. ^[17]

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:

1. Anti-cardiolipin antibodies (IgG and IgM)
2. Anti-β2 glycoprotein I antibodies
3. Lupus anticoagulant (a coagulation assay — paradoxically causes thrombosis, not bleeding)

Clinical spectrum:

• Objectively confirmed arterial, venous, or small-vessel thrombosis
• Defined obstetric morbidity (use precise gestation-specific criteria rather than the vague phrase “recurrent abortions”)
• Valve disease, livedo, thrombocytopaenia, nephropathy, and selected neurologic manifestations may be associated, but are not all equivalent to a qualifying thrombosis

APS with or without an associated systemic autoimmune disease: ^[1]

Many SLE flares produce less CRP than expected for the ESR. High CRP should increase suspicion of infection, but does not prove infection or exclude a flare. 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.

1. SLE is a multisystem disease. Diagnosis is based on clinical grounds + serologic abnormalities.
2. SLE care is multidisciplinary, based on a shared patient-physician decision.
3. Organ-/life-threatening complications require initial high-intensity and subsequent maintenance immunosuppressive therapy.
4. 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
• Review smoking, UV exposure, vaccinations, exercise, bone and cardiovascular health; do not chase the slide's speculative “antigenic stimuli” list
• Do not advise blanket avoidance of contraception. Choose method by disease activity, thrombosis/aPL profile, teratogenic medication, and preference; oestrogen-containing contraception is inappropriate in selected high-thrombotic-risk patients, while effective contraception is essential with teratogens. ^[22]
• Infection prevention and early recognition (a major preventable cause of morbidity and mortality)
• Pregnancy issues (pre-pregnancy counselling is a common exam topic)
• Supportive treatment (e.g., dialysis)

The lecture’s treatment chart groups non-renal SLE into mild, moderate, and severe disease. Read it as an older conceptual map, not a prescribing algorithm: BSA, platelet, SLEDAI, and BILAG cut-offs do not replace identifying the organ at risk. Adjunctive measures include sun protection, vaccination, exercise, smoking cessation, and management of body weight, blood pressure, lipids, glucose, and bone health. Antiplatelet/anticoagulant therapy is risk- and event-based—not automatic for every positive aPL result. ^{[1][15][16][18]}

Treatment targets: the slide depicts remission or low disease activity. Current EULAR/ACR strategy is to achieve sustained remission/low activity, introduce steroid-sparing therapy early, and taper maintenance prednisone to ≤5 mg/day and ideally zero, rather than accepting the slide's older 7.5 mg/day ceiling. ^[15][16]

How to read the charts: slide 82 documents historical population-level improvement across eras. Slide 83 simply subtracts those old survival percentages from 100 and labels the bars as Helen's “chance of dying.” That is not a valid personalised prognostic calculation: Helen's risk depends on organ damage, infection, thrombosis/APS, kidney response, treatment toxicity, adherence, access to care, and other individual factors.

Risk factors for worse prognosis: ^[1]

• Late disease onset
• Male SLE (worse than female)
• Lower socioeconomic class
• Poor compliance (emphasised in the lecture)

Plan conception during stable, preferably quiescent disease on pregnancy-compatible medication, with rheumatology and maternal-fetal-medicine input. In anti-Ro/SSA or anti-La/SSB positivity, guideline-based fetal surveillance is considered during weeks 16–26; a positive antibody does not mean congenital heart block is inevitable. ^[22]

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]

HCQ retinal toxicity — tested in 2021 MCQ Q13. The bull's-eye appearance is late disease; use baseline and risk-adjusted screening according to the 2025 AAO revision rather than memorising one universal interval. ^[9][23]