STEPTRACKERGENERAL PRINCIPLES | IMMUNOLOGY + PATHOLOGY | HIGH-YIELD REVIEW

Autoimmune Disease I — SLE Spectrum

Systemic lupus, drug-induced lupus, antiphospholipid syndrome and neonatal lupus — one antibody family, many organs.

FOCUS ON
ANA is the sensitive screen. Anti-dsDNA and anti-Smith are specific, and dsDNA tracks nephritis activity along with low complement. Antihistone points to drug-induced lupus. A prolonged PTT with clots (not bleeding) means lupus anticoagulant. Kidney disease decides prognosis.
FEATURE
DETAIL
MECHANISM
CLASSIC CLUE
Who
epidemiology
Women of childbearing age (~9:1); more frequent and severe in Black and Hispanic patients.
Genes + hormones + UV light + infections
Flares with sun exposure, pregnancy
Pathogenesis
why antibodies form
Apoptotic debris is cleared poorly → nuclear antigens exposed → autoantibodies.
Early complement deficiency (C1q, C2, C4) impairs clearance · type III > type II injury
↓ C3, C4 in active disease
Skin & joints
Malar rash sparing nasolabial folds, discoid rash, photosensitivity, painless oral ulcers, nonerosive arthritis.
Immune complexes at the dermal–epidermal junction
Butterfly rash after sun
Kidney
lupus nephritis
Diffuse proliferative GN (most common, most severe, nephritic) or membranous (nephrotic).
Subendothelial deposits → wire-loop capillaries
Leading cause of death with infection and cardiovascular disease
Blood
Autoimmune hemolytic anemia, leukopenia, thrombocytopenia; anemia of chronic disease.
Type II antibodies against blood cells
Coombs⁺ hemolysis in a young woman
Serosa, heart, brain
Pleuritis, pericarditis; Libman-Sacks endocarditis; accelerated atherosclerosis; seizures, psychosis.
Sterile vegetations on both sides of the mitral valve
Pleuritic chest pain + rash + arthritis
Drug-induced lupus
reversible
Hydralazine, procainamide, isoniazid, minocycline, quinidine, TNF inhibitors; more likely in slow acetylators.
Antihistone antibodies; kidneys and CNS usually spared
Resolves after stopping the drug
Antiphospholipid syndrome
primary or with SLE
Recurrent arterial or venous thrombosis and recurrent pregnancy loss.
Lupus anticoagulant, anticardiolipin, anti-β₂-glycoprotein I
Prolonged PTT not corrected by mixing; false-positive VDRL; anticoagulate
Neonatal lupus
passive transfer
Maternal IgG anti-Ro/SSA crosses the placenta.
Damages fetal conduction tissue
Congenital complete heart block, neonatal rash
Treatment
Hydroxychloroquine for nearly all; steroids for flares; mycophenolate or cyclophosphamide for nephritis.
Sun protection
Hydroxychloroquine → retinal screening

Mechanism — from debris to disease

TriggersUV, hormones, infection
→
Apoptosis ↑, clearance ↓C1q, C4 deficiency
→
Nuclear antigensAutoantibodies
→
Immune complexesKidney, skin, joints, serosa
→
Complement ↓Inflammation

Cytopenias come from type II antibodies; most organ damage comes from type III complexes.

Antibody guide

ANTIBODY
USE
ANA
Screening — very sensitive, not specific
Anti-dsDNA
Specific; rises with disease and nephritis activity
Anti-Smith
Most specific; does not track activity
Antihistone
Drug-induced lupus
Anti-Ro/SSA
Neonatal lupus, subacute cutaneous lupus, Sjögren
Antiphospholipid
Thrombosis, miscarriage, false-positive VDRL
Anti-U1 RNP
Mixed connective tissue disease (page 2.11)

How it's tested

COMMON CONFUSIONA negative ANA nearly rules out SLE. A positive ANA alone does not rule it in.
THE TRAPA young woman has a DVT and a prolonged PTT that a mixing study does not correct. This is lupus anticoagulant — a clotting disorder despite the "anticoagulant" name.
YOUR APPROACHOrgan pattern → SLE suspected → ANA screen → confirm with dsDNA/Sm → follow activity with dsDNA and C3/C4. Check the drug list for drug-induced lupus.

If you see… think…

Young woman with malar rash, arthritis, proteinuria → SLE
Rising anti-dsDNA with falling C3 → active lupus nephritis
Wire-loop capillaries on renal biopsy → diffuse proliferative lupus nephritis
Sterile vegetations on both sides of the mitral leaflets → Libman-Sacks
On hydralazine or procainamide, joint pain, antihistone ⁺ → drug-induced lupus
Recurrent miscarriage + DVT + prolonged PTT → antiphospholipid syndrome
Newborn with complete heart block, mother anti-Ro ⁺ → neonatal lupus
False-positive VDRL in a woman with arthralgia → antiphospholipid antibodies
C1q or C4 deficiency → lupus-like disease (poor complex clearance)