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

USMLE High-Yield Vignettes: Multiple Sclerosis & SLE

MULTIPLE SCLEROSIS — 13 Vignettes

MS Vignette 1 — Classic First Presentation

A 27-year-old woman presents with 4 days of painful blurring of vision in her right eye, worse when looking to the right. She notes colors appear washed out. On exam, a swinging flashlight test reveals the right pupil dilates when light is swung from the left eye. Fundoscopy is normal. The patient had an episode of left leg numbness 18 months ago that lasted 2 weeks and fully resolved.

MS Vignette 2 — Internuclear Ophthalmoplegia

A 25-year-old woman reports intermittent horizontal double vision for 3 weeks. On exam, when asked to look to the right, her LEFT eye fails to adduct. Her right eye abducts and shows nystagmus. When asked to converge, both eyes adduct normally. A similar milder finding is noted on left gaze as well.

MS Vignette 3 — Uhthoff vs. True Relapse

A 30-year-old woman with known RRMS calls her neurologist. Every afternoon when she exercises at the gym, her vision in her right eye blurs dramatically and her right leg becomes weak, lasting 30-45 minutes each time. Symptoms completely resolve when she cools down. She also reports an electric shock sensation that runs from her neck down her spine when she looks down at her phone.

MS Vignette 4 — CSF Findings

A 29-year-old man undergoes lumbar puncture after MRI shows multiple periventricular white matter lesions. CSF results: opening pressure normal, WBC 14 (lymphocytes), protein 60 mg/dL, glucose normal, IgG index elevated (0.82). Electrophoresis shows multiple discrete bands in the CSF gamma region NOT present in a simultaneously run serum sample.

MS Vignette 5 — Primary Progressive MS

A 51-year-old man presents with a 16-month history of slowly progressive bilateral leg stiffness, difficulty walking, and urinary urgency. He denies any discrete episodes of worsening or improvement. Exam reveals spastic paraparesis and hyperreflexia. MRI shows spinal cord T2 lesions with relatively few brain lesions. No gadolinium-enhancing lesions. CSF: oligoclonal bands positive.

MS Vignette 6 — Natalizumab Complication

A 36-year-old man with RRMS has been on natalizumab for 3 years. His JC virus antibody index has risen to 3.2. He now presents with 5 weeks of progressive cognitive slowing, right arm weakness, and aphasia. MRI reveals a large, non-enhancing, asymmetric white matter lesion in the left frontal and parietal lobes that crosses gyral boundaries and does not respect vascular territory.

MS Vignette 7 — Fingolimod First Dose

A 28-year-old woman with RRMS is started on fingolimod (Gilenya). Six hours after her first dose, her ECG shows a heart rate of 46 bpm and a PR interval of 240 ms. She is asymptomatic.

MS Vignette 8 — Acute Relapse Management

A 33-year-old woman with known RRMS presents with acute onset left-sided weakness and left hemibody numbness for 6 days. MRI confirms a new gadolinium-enhancing lesion. Her neurologist starts high-dose IV methylprednisolone 1g/day × 5 days.

MS Vignette 9 — MS and Pregnancy Counseling

A 28-year-old woman with RRMS on interferon beta-1a informs her neurologist she is trying to conceive. She is worried her MS will worsen during pregnancy and asks whether she needs to stop her medication.

MS Vignette 10 — Marburg Variant

A 22-year-old woman with no prior neurologic history presents with rapidly progressive quadriparesis, obtundation, and respiratory distress developing over 3 weeks. MRI shows large, tumefactive demyelinating lesions with mass effect bilaterally. She had been in perfect health 1 month ago. No prior relapses. CSF positive for oligoclonal bands.

MS Vignette 11 — McDonald Criteria / Clinically Isolated Syndrome

A 24-year-old woman presents after a single episode of right leg weakness and urinary retention lasting 8 days that resolved. MRI brain shows 3 periventricular lesions and 1 infratentorial lesion. CSF shows oligoclonal bands in CSF only (not serum). There are no gadolinium-enhancing lesions.

MS Vignette 12 — MS Mimic (NMOSD)

A 30-year-old woman presents with acute bilateral visual loss and severe weakness with a sensory level at T6. MRI spine shows T2 hyperintensity spanning 6 vertebral segments. Brain MRI shows no periventricular lesions. CSF: oligoclonal bands absent. Serum NMO-IgG (anti-aquaporin-4 antibody) is positive.

MS Vignette 13 — Symptomatic Management

A 40-year-old man with long-standing RRMS has developed severe fatigue ("the most disabling thing in my life"), leg spasms and stiffness that limit walking, and urinary urgency with incontinence. He is asking about medication options for each of these issues.

• Fatigue: Amantadine (first-line) or modafinil
• Spasticity: Baclofen (oral; 5-160 mg/day in divided doses) or tizanidine; intrathecal baclofen pump for severe cases
• Urinary urgency/incontinence (overactive bladder/detrusor hyperreflexia): Oxybutynin or tolterodine (anticholinergics)
• Neuropathic pain: gabapentin, carbamazepine, tricyclics (amitriptyline)

SYSTEMIC LUPUS ERYTHEMATOSUS — 12 Vignettes

SLE Vignette 1 — Classic Presentation / Serology

A 22-year-old African-American woman presents with 3 months of joint pain in her hands and wrists, facial rash across her cheeks sparing the nasolabial folds, painful mouth sores, and profound fatigue. CBC shows hemoglobin 9.0 g/dL (Coombs-positive), WBC 2,400, platelets 85,000. ANA 1:1280, anti-dsDNA positive, anti-Smith positive, C3 and C4 both low.

SLE Vignette 2 — Lupus Nephritis Flare Recognition

A 28-year-old woman with SLE returns for follow-up feeling well with no complaints. Her labs show: anti-dsDNA risen from 1:80 to 1:640; C3 fallen from 92 to 44 mg/dL; C4 from 18 to 6 mg/dL; creatinine risen from 0.7 to 1.3 mg/dL; urinalysis: 2+ protein, 15 RBCs/hpf, occasional granular casts.

SLE Vignette 3 — Wire-Loop Nephritis (Pathology)

A 24-year-old woman with SLE undergoes renal biopsy for nephrotic-range proteinuria and rising creatinine. Light microscopy shows global endocapillary proliferation in >60% of glomeruli with thickened capillary walls (wire-loop appearance). Immunofluorescence shows "full house" pattern (IgG, IgM, IgA, C3, C1q). Electron microscopy shows massive subendothelial deposits.

SLE Vignette 4 — Drug-Induced Lupus

A 65-year-old man with hypertension has been on hydralazine for 5 years. He presents with bilateral arthralgia, pleuritis, and a mild rash. Labs: ANA positive, anti-histone antibodies positive, anti-dsDNA NEGATIVE, C3 and C4 NORMAL, creatinine normal, no CNS symptoms.

SLE Vignette 5 — APS Paradox

A 32-year-old woman with SLE presents with a DVT in her left leg. Her aPTT is prolonged at 65 seconds; PT is normal. Platelets are 90,000. She has had two first-trimester miscarriages. Tests for lupus anticoagulant, anticardiolipin IgG, and anti-β2-GP1 are positive on two occasions 12 weeks apart.

SLE Vignette 6 — Libman-Sacks Endocarditis

A 27-year-old woman with SLE and antiphospholipid antibodies has a routine echocardiogram. It shows small, irregular, flat vegetations on both the atrial and ventricular surfaces of the mitral valve. She is afebrile; three blood cultures are negative; no leukocytosis.

SLE Vignette 7 — Neonatal Lupus

A 26-year-old anti-Ro/SSA-positive woman delivers a healthy-appearing baby. At 3 weeks of age, the infant develops a photosensitive circular rash on the face and scalp. Neonatology notes that a fetal echocardiogram performed at 24 weeks had detected complete AV block.

SLE Vignette 8 — Neuropsychiatric SLE

A 20-year-old woman with known SLE presents to the ER with new-onset auditory hallucinations and disorganized thinking over 48 hours. She is on prednisone 60 mg/day for a recent lupus flare. Workup including cultures, LP, and brain MRI are unremarkable. Anti-dsDNA is unchanged; complement levels are stable.

SLE Vignette 9 — False-Positive VDRL in SLE

A 23-year-old woman with SLE is found to have a positive VDRL during routine screening. She denies sexual risk factors. The FTA-ABS (fluorescent treponemal antibody) confirmatory test is NEGATIVE.

SLE Vignette 10 — SLE Medications in Pregnancy

A 30-year-old woman with SLE and biopsy-proven Class IV lupus nephritis in remission is taking mycophenolate mofetil (MMF) 2g/day and hydroxychloroquine. She is now 7 weeks pregnant.

SLE Vignette 11 — Discoid Lupus vs. SLE

A 45-year-old woman presents with a 3-year history of scarring plaques on her face, ears, and scalp with central hypopigmentation and alopecia. She denies arthralgia, fever, or fatigue. ANA is weakly positive (1:80); anti-dsDNA negative; complement normal; urinalysis normal; CBC normal.

SLE Vignette 12 — Shrinking Lung Syndrome

A 35-year-old woman with long-standing SLE develops progressive dyspnea on exertion. CXR shows small lung volumes bilaterally and elevated hemidiaphragms. PFTs show a restrictive pattern with reduced FVC and TLC but normal DLCO and no obstructive pattern. CT chest shows no parenchymal infiltrates or fibrosis. Pleural surfaces are clear.

Complete Vignette Index at a Glance

MS Vignettes (13)

SLE Vignettes (12)

• 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