Multiple Sclerosis (MS) and Systemic Lupus Erythematosus (SLE)

High-Yield Concepts + USMLE Pearls + Pregnancy

PART 1: MULTIPLE SCLEROSIS

Overview & Epidemiology

• Chronic inflammatory demyelinating disease of the CNS - plaques affect white matter at multiple sites separated in time and space
• Prevalence: ~309/100,000 in the U.S. (~730,000 Americans); ~2.8 million worldwide
• Female:Male = 2-2.5:1 (common autoimmune sex predilection)
• Peak onset: 3rd-4th decade of life (post-pubertal teens to 50s)
• Latitude gradient: more common in temperate zones; decreases near the equator
• Risk factors: cigarette smoking, childhood obesity, low vitamin D, Epstein-Barr virus (EBV)

USMLE Pearl: MS is the most common demyelinating disease. A young woman presenting with relapsing neurologic deficits (optic neuritis + spinal cord symptoms) = think MS first.

Pathology

• Plaques: sharply demarcated patches of demyelination and axonal injury - pink-gray color, primarily in white matter
• Periventricular location is classic (especially around the lateral ventricles)
• Lesions spare the root entry zones of cranial/spinal nerves (peripheral myelin is not affected)
• Pathology = T-cell mediated autoimmune attack on myelin (oligodendrocytes)

USMLE Pearl - Dawson's fingers: Periventricular MS plaques oriented perpendicular to ventricles on sagittal MRI FLAIR = pathognomonic appearance.

Clinical Presentations (High-Yield)

USMLE Pearl: The combination of optic neuritis + bilateral INO in a young woman is nearly pathognomonic for MS. Uhthoff phenomenon is unique to MS (worsening with temperature elevation, not true relapse).

Types of MS

USMLE Pearl: PPMS is the only form treated with ocrelizumab (anti-CD20). Natalizumab (anti-VLA-4/anti-α4-integrin) is used for active RRMS. Both are high-yield treatments.

Diagnosis - McDonald Criteria

• Requires lesions disseminated in time AND space
• MRI brain: >95% abnormal in definite MS - T2/FLAIR hyperintense lesions, periventricular, juxtacortical, infratentorial, spinal cord
• Active lesions: gadolinium-enhancing (T1)
• CSF findings: oligoclonal bands (OCBs) in IgG - present in >95%; elevated IgG index; may see mild pleocytosis
• Visual evoked potentials (VEPs): prolonged latency indicates subclinical optic nerve demyelination

USMLE Pearl: OCBs in CSF are present in MS but NOT in serum (if also in serum, think systemic disease, NOT MS). CSF shows <50 WBCs, mildly elevated protein - markedly elevated protein should suggest an alternative diagnosis.

Treatment (USMLE High-Yield)

USMLE Pearl: Natalizumab inhibits lymphocyte migration across the blood-brain barrier. Risk of PML is the major complication - requires JC antibody testing. High antibody index = significant PML risk.

MS in Pregnancy

• During pregnancy: disease activity decreases - relapses reduced by ~2/3 in the 3rd trimester (gestational immunosuppression)
• Postpartum: relapses increase significantly in the first 3-6 months postpartum
• Net effect: overall relapse risk across the full pregnancy/postpartum period is not significantly altered
• Breastfeeding may reduce the postpartum relapse rate
• Pregnancy does NOT change the long-term neurologic disability course
• MS does NOT affect fertility, labor, or delivery significantly (slight increase in C-section and SGA infants reported)

• Most DMTs are NOT recommended during pregnancy
• Teratogens (contraindicated): teriflunomide, mitoxantrone - require washout before conception
• Washout period: 0-6 months depending on drug before conception
• Safer options (low placental transfer): glatiramer acetate, interferon-β, natalizumab, ocrelizumab - minimal transfer to breast milk; likely safe for breastfeeding
• Oral DMTs: avoid during lactation

USMLE Pearl: MS does NOT prevent pregnancy. Remind that the relapse rate falls in the 3rd trimester then rebounds postpartum. The baby's risk of developing MS is low (~3-5% if one parent affected). Counsel optimistically.

PART 2: SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

Overview & Epidemiology

• Chronic multisystem autoimmune disease driven by autoantibodies, complement activation, and immune complex deposition
• Female:Male = 9:1 (classic ratio - highest female predominance of any autoimmune disease)
• Peak onset: women of childbearing age (15-45 years)
• More common and severe in African-American, Hispanic, and Asian women
• Genetic component: concordance 24% in monozygotic twins vs. 2% in dizygotic twins

• 150 susceptibility loci identified (GWAS); strong MHC class II association

USMLE Pearl: ANA is the best screening test (sensitivity ~95%). Specific for SLE: anti-dsDNA and anti-Smith (anti-Sm). Anti-dsDNA correlates with disease activity and lupus nephritis.

Pathogenesis

• Defective clearance of apoptotic debris → nuclear antigens released → ANA production
• Neutrophil NETosis releases nuclear contents → activates plasmacytoid DCs → type I IFN production
• Complement deficiency (C1q, C1r, C1s, C2, C4) → impaired immune complex clearance → tissue deposition
• Immune complexes deposit in kidneys, skin, joints, vessels → inflammation

USMLE Pearl: C1q deficiency is the strongest single-gene risk factor for lupus. Low C3/C4/CH50 during active disease = complement consumption by immune complexes.

Clinical Features - The SOAP BRAIN MD Mnemonic (2019 EULAR/ACR Criteria)

USMLE Pearl - Libman-Sacks endocarditis: Sterile marantic vegetations on BOTH sides of the valve (usually mitral) - unlike infective endocarditis (irregular, destructive) and rheumatic fever (mitral valve, posterior leaflet only). Associated with antiphospholipid antibodies.

Antibody Panel (Most High-Yield for USMLE)

USMLE Pearl: Anti-Smith is the MOST SPECIFIC antibody for SLE. Anti-dsDNA correlates with DISEASE ACTIVITY (monitor for flares and nephritis). Anti-histone = drug-induced lupus (complement is NORMAL, anti-dsDNA negative).

USMLE Pearl - Drug-induced lupus: Caused by P-HISM - Procainamide (most common), Hydralazine, Isoniazid, Sulfonamides, Minocycline. Spares the kidneys and CNS. Resolves when drug is stopped.

Lupus Nephritis

• Most serious organ manifestation; occurs in 40-60% of SLE patients
• ISN/RPS Classification (Class I-VI):
  • Class III/IV: focal/diffuse proliferative nephritis - worst prognosis, most common to cause ESRD
  • Class V: membranous - nephrotic syndrome presentation
• Markers of activity: rising anti-dsDNA + falling complement (C3/C4) = flare/nephritis
• Treatment: hydroxychloroquine (all patients) + induction with cyclophosphamide or mycophenolate mofetil (MMF) + steroids; maintenance with MMF or azathioprine

USMLE Pearl: Class IV diffuse proliferative LN = "wire-loop" lesions on EM/LM (subendothelial immune complex deposits). Most likely to progress to renal failure. Treat aggressively.

SLE in Pregnancy

• SLE flares are common during pregnancy and the postpartum period
• Pre-eclampsia occurs at higher rates (especially with lupus nephritis)
• Hypercoagulable state - increased VTE risk
• Disease is best controlled when SLE is in remission for 6 months before conception

• Spontaneous abortion, intrauterine fetal demise, preterm birth, IUGR - all increased
• Neonatal lupus: transplacental passage of anti-Ro/SSA and anti-La/SSB antibodies
  • Skin rash, transient thrombocytopenia, liver abnormalities (all transient)
  • Congenital complete heart block (CHB) - the feared complication; permanent; may require pacemaker; risk ~2% if mother is anti-Ro+
• Antiphospholipid Antibody Syndrome (APS) co-existing with SLE:
  • Recurrent first-trimester pregnancy loss, mid/late pregnancy fetal death
  • Thrombosis (arterial and venous)
  • Treatment: aspirin + heparin (LMWH) throughout pregnancy - warfarin is contraindicated in pregnancy

• Active renal disease (lupus nephritis)
• Reduced GFR
• Hypocomplementemia
• Presence of antiphospholipid antibodies

USMLE Pearl: The SLE patient who is anti-Ro+ is at risk for neonatal CHB. Continue hydroxychloroquine throughout pregnancy - it reduces CHB risk, prevents flares, and is safe for the fetus. Screen fetus with fetal echocardiogram between 16-26 weeks.

USMLE Pearl: SLE + recurrent pregnancy loss = think antiphospholipid syndrome. Test for lupus anticoagulant, anticardiolipin, and anti-β2-GPI. Treat with aspirin + heparin (NOT warfarin).

QUICK COMPARISON TABLE: MS vs. SLE in Pregnancy

Key References

• Adams and Victor's Principles of Neurology, 12th Edition - MS pathology and classification
• Goldman-Cecil Medicine, 2025 - MS diagnosis, treatment, and pregnancy
• Harrison's Principles of Internal Medicine 22E (2025) - SLE pathogenesis and lupus nephritis
• Creasy & Resnik's Maternal-Fetal Medicine - MS and SLE in pregnancy
• Wind M et al., Pregnancy outcome predictors in SLE - Lancet Rheumatol 2024 (PMID 39153486) - active renal disease, hypocomplementemia, and APS predict poor pregnancy outcomes
• Singh M et al. - Autoimmune diseases and adverse pregnancy outcomes - BMC Med 2024 (PMID 38438886) - umbrella review confirming elevated risks across autoimmune conditions

USMLE-Standard High-Yield Questions: Multiple Sclerosis

QUESTION 1 - Classic Presentation / Diagnosis

• A) Hyperintense lesion in the right optic nerve on T1 with gadolinium enhancement
• B) Multiple periventricular T2/FLAIR hyperintense lesions oriented perpendicular to the lateral ventricles
• C) Diffuse cortical atrophy with sulcal widening
• D) Bilateral basal ganglia T2 hyperintensities
• E) A single enhancing ring lesion with surrounding edema

Adams and Victor's Principles of Neurology, 12th Ed.

QUESTION 2 - MRI Imaging (Image-Based)

• A) Oligoclonal bands in CSF are 100% specific for MS
• B) Oligoclonal bands present in both CSF and serum support a diagnosis of MS
• C) Oligoclonal bands present in CSF but not in serum indicate intrathecal IgG synthesis
• D) The CSF IgG index is expected to be low in MS
• E) A CSF protein > 100 mg/dL is characteristic of MS

Henry's Clinical Diagnosis and Management by Laboratory Methods; Neuroanatomy through Clinical Cases, 3rd Ed.

QUESTION 3 - Eye Movement / Localization

• A) Right abducens nucleus (CN VI)
• B) Left oculomotor nucleus (CN III)
• C) Left medial longitudinal fasciculus (MLF)
• D) Right medial longitudinal fasciculus (MLF)
• E) Cerebellar vermis

Goldman-Cecil Medicine; K.J. Lee's Essential Otolaryngology

QUESTION 4 - Uhthoff and Lhermitte Phenomena

• A) A new demyelinating plaque in the optic nerve
• B) Thermoregulatory autonomic dysfunction causing vasospasm
• C) Conduction block in previously demyelinated axons due to elevated temperature
• D) Increased intracranial pressure from cerebral edema
• E) Psychogenic exacerbation of symptoms

• Uhthoff phenomenon: temporary worsening of symptoms with heat or exercise due to conduction block in demyelinated axons when temperature rises even slightly. This is NOT a new relapse - it reverses on cooling.
• Lhermitte sign: electrical sensation down the spine on neck flexion, caused by a demyelinating lesion in the cervical spinal cord (dorsal columns).

Kanski's Clinical Ophthalmology, 10th Ed.; Goldman-Cecil Medicine

QUESTION 5 - Types of MS

• A) Interferon beta-1a
• B) Glatiramer acetate
• C) Natalizumab
• D) Ocrelizumab
• E) Fingolimod

Goldman-Cecil Medicine; Bradley and Daroff's Neurology

QUESTION 6 - Pharmacology / Drug Mechanism

• A) Natalizumab - blocks α4-integrin, preventing lymphocyte CNS migration
• B) Fingolimod - sphingosine-1-phosphate receptor modulator, sequesters lymphocytes in lymph nodes
• C) Dimethyl fumarate - activates Nrf2 pathway, reduces oxidative stress
• D) Teriflunomide - inhibits dihydroorotate dehydrogenase, blocks pyrimidine synthesis
• E) Alemtuzumab - anti-CD52, depletes T and B lymphocytes

• First-dose bradycardia and AV block → requires 6-hour cardiac monitoring after first dose
• Macular edema → baseline ophthalmologic exam required
• Pulmonary function changes (FEV1 reduction)
• Increased risk of herpes infections

Goldman-Cecil Medicine; Katzung's Basic and Clinical Pharmacology, 16th Ed.

QUESTION 7 - Pharmacology / Dangerous Complication

• A) MS relapse; number of prior relapses
• B) CNS lymphoma; prior use of corticosteroids
• C) Progressive multifocal leukoencephalopathy (PML); JC virus antibody index
• D) Glioblastoma multiforme; duration of natalizumab therapy
• E) Acute disseminated encephalomyelitis; recent vaccination

1. JC antibody seropositivity (and index level - higher index = higher risk)
2. Duration of natalizumab (>2 years significantly increases risk)
3. Prior immunosuppressive therapy

Goldman-Cecil Medicine; Yamada's Textbook of Gastroenterology, 7th Ed.

QUESTION 8 - CSF Analysis / Diagnosis

• Opening pressure: normal
• WBC: 18 (80% lymphocytes)
• Protein: 62 mg/dL
• Glucose: normal
• IgG index: 0.78 (elevated)
• Oligoclonal bands: present in CSF, absent in serum

• A) Oligoclonal bands in CSF; ~60%
• B) MRI brain (T2/FLAIR lesions); >95%
• C) Visual evoked potentials; ~80%
• D) Anti-aquaporin-4 antibody; ~70%
• E) CSF IgG index elevation; ~50%

Goldman-Cecil Medicine; Grainger & Allison's Diagnostic Radiology

QUESTION 9 - Treatment of Acute Relapse

• A) Oral prednisone 1 mg/kg/day × 4 weeks; permanently reduces disability
• B) IV methylprednisolone 1 g/day × 3-5 days; shortens duration of relapse but does not alter long-term disability
• C) Plasma exchange; first-line for all MS relapses
• D) Start interferon beta-1a immediately; treats both the relapse and prevents future relapses
• E) Watchful waiting; most relapses resolve spontaneously without treatment

Goldman-Cecil Medicine, 2025

QUESTION 10 - MS and Pregnancy

• A) Relapse rate increases significantly throughout all trimesters of pregnancy
• B) Relapse rate decreases during pregnancy (especially 3rd trimester) but increases in the first 3-6 months postpartum
• C) Glatiramer acetate should be stopped immediately as it is a known teratogen
• D) Pregnancy increases the long-term risk of disability from MS
• E) Breastfeeding is absolutely contraindicated in all MS patients

Creasy & Resnik's Maternal-Fetal Medicine; Goldman-Cecil Medicine

QUESTION 11 - MS Mimics / Differential Diagnosis

• A) Anti-Ro/SSA; Sjögren syndrome-associated myelopathy
• B) Anti-AQP4 (aquaporin-4 / NMO-IgG); neuromyelitis optica spectrum disorder (NMOSD)
• C) Anti-MOG (myelin oligodendrocyte glycoprotein); MS
• D) Anti-dsDNA; SLE-associated CNS disease
• E) Anti-GQ1b; Miller Fisher syndrome

• Bilateral or rapidly alternating optic neuritis (MS typically unilateral)
• Longitudinally extensive transverse myelitis (LETM) - >3 vertebral segments (MS lesions span <2 segments)
• Area postrema involvement - intractable hiccups/nausea
• Normal brain MRI (or non-MS pattern lesions)
• OCBs absent in ~80% of NMOSD (present in >95% MS)
• Anti-AQP4 antibody positive in ~70-80% of NMOSD

Adams and Victor's Principles of Neurology, 12th Ed.

QUESTION 12 - Pharmacology / Teratogenicity

• A) Teriflunomide is safe in pregnancy; no washout is needed
• B) Teriflunomide requires a washout with cholestyramine or activated charcoal to eliminate the drug rapidly before conception
• C) Teriflunomide can be continued in the first trimester only
• D) Teriflunomide is safe but must be switched after pregnancy is confirmed
• E) Teriflunomide causes cardiac defects specifically in the 3rd trimester

Creasy & Resnik's Maternal-Fetal Medicine

QUESTION 13 - Secondary Progressive MS / Disease Course

• A) Primary progressive MS
• B) Clinically isolated syndrome
• C) Secondary progressive MS (active)
• D) Acute Marburg MS
• E) Secondary progressive MS (inactive)

Goldman-Cecil Medicine, 2025

QUESTION 14 - Symptom Management

• A) Fatigue → baclofen; Spasticity → oxybutynin; Bladder → amantadine
• B) Fatigue → amantadine; Spasticity → baclofen; Bladder → oxybutynin
• C) Fatigue → fingolimod; Spasticity → methylprednisolone; Bladder → tamsulosin
• D) Fatigue → modafinil; Spasticity → tizanidine; Bladder → bethanechol
• E) Fatigue → amantadine; Spasticity → diazepam; Bladder → oxybutynin

• Fatigue (most common disabling symptom in MS): amantadine (first-line) or modafinil
• Spasticity: baclofen (oral or intrathecal); tizanidine is an alternative
• Urinary urgency/incontinence (detrusor hyperreflexia/overactive bladder): oxybutynin (anticholinergic) or tolterodine; contrast with urinary retention (detrusor areflexia) which would be treated with bethanechol or self-catheterization
• Neuropathic pain: gabapentin, carbamazepine
• Depression: SSRIs

Goldman-Cecil Medicine

QUESTION 15 - Integrated/Most Challenging

• A) She cannot be diagnosed with MS because she has had only one clinical episode
• B) She can be diagnosed with MS because CSF oligoclonal bands fulfill dissemination in time criteria
• C) She has a clinically isolated syndrome; MS cannot be diagnosed without a second clinical episode
• D) She requires a repeat MRI in 3-6 months before any diagnosis can be made
• E) She needs a visual evoked potential before any diagnosis can be made

• Dissemination in space (DIS): lesions in ≥2 of the 4 typical MS locations (periventricular, cortical/juxtacortical, infratentorial, spinal cord) - this patient has periventricular + juxtacortical = DIS satisfied
• Dissemination in time (DIT): In the 2017 revision, CSF-specific oligoclonal bands can substitute for DIT when DIS is already demonstrated clinically or on MRI

Goldman-Cecil Medicine, 2025; Grainger & Allison's Diagnostic Radiology

Summary Answer Key

USMLE-Style High-Yield Questions: Systemic Lupus Erythematosus (SLE)

10 Questions

QUESTION 1 - Antibody Interpretation / Diagnosis

• A) ANA and anti-histone; ANA titer
• B) Anti-dsDNA and anti-Smith; anti-dsDNA
• C) Anti-Ro/SSA and anti-La/SSB; anti-Ro titer
• D) Anti-dsDNA and anti-Ro; complement levels only
• E) ANA and antiphospholipid antibodies; anticardiolipin titer

• ANA: most sensitive (~95%) but NOT specific - positive in many conditions and normal individuals
• Anti-dsDNA: highly specific (~97%) for SLE; titer correlates with disease activity - rising anti-dsDNA + falling complement = imminent flare (especially lupus nephritis)
• Anti-Smith (anti-Sm): MOST specific (55-100%) for SLE but low sensitivity (~25-30%); does NOT correlate with disease activity
• Anti-histone: drug-induced lupus
• Anti-Ro/SSA: SCLE and neonatal lupus

Harrison's Principles of Internal Medicine 22E; Harriet Lane Handbook, 23rd Ed.

QUESTION 2 - Renal Pathology (Image-Based)

• A) Class II (mesangial proliferative); hydroxychloroquine alone
• B) Class III (focal proliferative); oral prednisone alone
• C) Class IV (diffuse proliferative); mycophenolate mofetil OR cyclophosphamide + high-dose steroids
• D) Class V (membranous); ACE inhibitor monotherapy
• E) Class VI (advanced sclerosis); renal transplant listing

Henry's Clinical Diagnosis; Brenner & Rector's The Kidney; Comprehensive Clinical Nephrology, 7th Ed.

QUESTION 3 - Drug-Induced Lupus

• A) He has true SLE triggered by hydralazine; anti-dsDNA confirms the diagnosis
• B) He has drug-induced lupus (DIL); anti-histone is the hallmark; kidneys and CNS are spared; it resolves on drug discontinuation
• C) He has drug-induced lupus; complement consumption confirms active disease
• D) He requires indefinite hydroxychloroquine treatment
• E) Antinuclear antibodies are negative in drug-induced lupus

Quick Compendium of Clinical Pathology, 5th Ed.

QUESTION 4 - Antiphospholipid Syndrome (APS) Paradox

• A) Prolonged aPTT indicates a bleeding disorder, making DVT unlikely
• B) Lupus anticoagulant prolongs aPTT in vitro but is PRO-thrombotic in vivo
• C) Anticardiolipin antibodies are responsible for thrombocytopenia and not thrombosis
• D) The prolonged aPTT is due to heparin contamination of the blood sample
• E) Lupus anticoagulant inhibits the extrinsic coagulation pathway

• In vitro: lupus anticoagulant interferes with phospholipid-dependent coagulation assays → prolonged aPTT (NOT corrected by mixing study with normal plasma)
• In vivo: lupus anticoagulant is strongly PRO-thrombotic → DVT, PE, arterial strokes, recurrent pregnancy loss

• Acute DVT: heparin bridge → warfarin (target INR 2-3, or 3-4 for arterial events)
• Pregnancy (APS): aspirin + LMWH throughout pregnancy - warfarin is teratogenic
• Note: DOACs (rivaroxaban) are inferior to warfarin in APS - avoid

Tintinalli's Emergency Medicine; Goldman-Cecil Medicine; Adams and Victor's Principles of Neurology, 12th Ed.

QUESTION 5 - Cardiac Manifestation / Libman-Sacks Endocarditis

• A) Infective endocarditis - treat with IV antibiotics for 6 weeks
• B) Rheumatic heart disease - involves the posterior mitral valve leaflet only with commissural fusion
• C) Libman-Sacks endocarditis - sterile verrucous vegetations on both surfaces of valves; risk of systemic embolism
• D) Nonbacterial thrombotic endocarditis (marantic) - associated with malignancy
• E) Carcinoid heart disease - fibrous plaques on right-sided valves only

Robbins Basic Pathology; Dermatology 2-Volume Set 5e

QUESTION 6 - Serositis and Constitutional Manifestations

• A) IV antibiotics for presumed bacterial pleuropericarditis
• B) Emergency pericardiocentesis
• C) High-dose NSAIDs (indomethacin) + colchicine
• D) Oral prednisone for lupus serositis
• E) Anticoagulation with heparin for presumed APS

• Mild: NSAIDs or colchicine (used for idiopathic pericarditis)
• Lupus-related serositis: corticosteroids are preferred, especially when there is laboratory evidence of active SLE flare (rising anti-dsDNA, low complement)
• Colchicine (C) is used for idiopathic pericarditis but corticosteroids are first-line when SLE is the underlying cause

Goldman-Cecil Medicine, 2025; Harrison's Principles of Internal Medicine 22E

QUESTION 7 - Neonatal Lupus / SLE in Pregnancy

• A) The rash and heart block are both permanent and require lifelong treatment
• B) The rash will resolve spontaneously by 6-8 months; the heart block is permanent and may require a pacemaker
• C) Both the rash and heart block will resolve within 6 months as maternal antibodies clear
• D) The rash indicates the infant has developed true SLE; immune suppression is required
• E) Anti-Ro antibodies do not cross the placenta; maternal testing is not relevant

Goldman-Cecil Medicine; Creasy & Resnik's Maternal-Fetal Medicine; Janeway's Immunobiology, 10th Ed.

QUESTION 8 - Lab Monitoring / Flare Recognition

• A) Reassure the patient and repeat labs in 6 months since she feels well
• B) Increase hydroxychloroquine dose
• C) Obtain a renal biopsy to classify lupus nephritis and initiate induction immunosuppression
• D) Start anticoagulation with warfarin
• E) Order antiphospholipid antibodies and defer treatment

• Rising anti-dsDNA (1:40 → 1:320): most reliable marker of flare activity
• Falling C3 and C4: complement consumption by immune complex deposition
• Rising creatinine + hematuria + proteinuria: glomerulonephritis

Tietz Textbook of Laboratory Medicine, 7th Ed.; Comprehensive Clinical Nephrology, 7th Ed.

QUESTION 9 - Treatment / Medications in SLE Pregnancy

• A) Continue MMF and hydroxychloroquine throughout pregnancy
• B) Stop hydroxychloroquine immediately due to teratogenicity
• C) Switch MMF to azathioprine; continue hydroxychloroquine
• D) Switch MMF to cyclophosphamide; add low-dose aspirin
• E) Discontinue all immunosuppression during the first trimester only

Brenner & Rector's The Kidney; Goldman-Cecil Medicine; Comprehensive Clinical Nephrology, 7th Ed.

QUESTION 10 - Integrated / Most Challenging

• A) Positive ANA (entry criterion); ≥5 points total
• B) Lupus nephritis (renal domain); ≥10 points total
• C) Hemolytic anemia (hematology domain); ≥8 points total
• D) Anti-dsDNA positive (immunology domain); ≥10 points total
• E) Malar rash (mucocutaneous domain); ≥8 points total

• Entry criterion: ANA ≥1:80 (must be present; if negative, criteria NOT applicable)
• Minimum score for classification: ≥10 points
• Highest-weighted domains (selected):

Tietz Textbook of Laboratory Medicine, 7th Ed.; Harrison's Principles of Internal Medicine 22E

Quick Answer Key

• A 2-4 sentence clinical scenario (age, sex, symptoms, labs/findings)
• A focused question (diagnosis, mechanism, next step, treatment decision)
• A concise answer
• A "Teaching Point" summarizing exactly what USMLE expects you to know