A 29-year-old woman, gravida 1, para 0, at 33 weeks' gestation comes to her doctor for a routine visit. Her pregnancy has been uncomplicated. She has systemic lupus erythematosus and has had no flares during her pregnancy. She does not smoke cigarettes, drink alcohol, or use illicit drugs. Current medications include iron, vitamin supplements, and hydroxychloroquine. Her temperature is 37.2°C (98.9°F), pulse is 70/min, respirations are 17/min, and blood pressure is 134/70 mm Hg. She appears well. Physical examination shows no abnormalities. Ultrasound demonstrates fetal rhythmic breathing for > 30 seconds, amniotic fluid with deepest vertical pocket of 1 cm, one distinct fetal body movement over 30 minutes, and no episodes of extremity extension over 30 minutes. Nonstress test is reactive and reassuring. Which of the following is the next best step in management?

Administer corticosteroids and continue close monitoring

Discontinue hydroxychloroquine and continue close monitoring

Reassurance with expectant management

A 40-year-old man presents to a clinic in Michigan in December complaining of painful blue fingers and toes. He also complains of numbness and tingling. The patient’s vital signs are within normal limits, and his symptoms typically disappear when he comes back into a warm room. The patient also notes that he recently moved to the area from Arizona and had recently recovered from a viral infection in which he had a low-grade fever and severe lymphadenopathy. Which of the following tests would most likely be positive in this patient?

Direct Coomb’s test with anti-C3 reagent

Direct Coomb’s test with anti-IgG reagent

A 27-year-old Asian woman presents to her primary care physician with joint pain and a headache. She has had intermittent joint and muscle pain for the past several months in the setting of a chronic headache. She states that the pain seems to migrate from joint to joint, and her muscles typically ache making it hard for her to sleep. The patient's past medical history is non-contributory, and she is currently taking ibuprofen for joint pain. Physical exam is notable for an asymmetrical pulse in the upper extremities. The patient has lost 10 pounds since her previous visit 2 months ago. Laboratory values are notable for an elevated C-reactive protein and erythrocyte sedimentation rate. Which of the following is the best next step in management?

Recommend exercise and optimize the patient's sleep regimen

A previously healthy 13-year-old girl is brought to the physician for evaluation of a 2-month history of fatigue. She reports recurrent episodes of pain in her right wrist and left knee. During this period, she has had a 4-kg (8.8-lb) weight loss. Her mother has rheumatoid arthritis. Her temperature is 38°C (100.4°F). Examination shows diffuse lymphadenopathy. Oral examination shows several painless oral ulcers. The right wrist and the left knee are swollen and tender. Laboratory studies show a hemoglobin concentration of 9.8 g/dL, a leukocyte count of 2,000/mm3, and a platelet count of 75,000/mm3. Urinalysis shows excessive protein. This patient's condition is associated with which of the following laboratory findings?

Anti-citrullinated peptide antibodies

Leukocytoclastic vasculitis with IgA and C3 immune complex deposition

A 31-year-old woman presents to her primary care provider to discuss the results from a previous urine analysis. She has no new complaints and feels well. Past medical history is significant for systemic lupus erythematosus. She was diagnosed 5 years ago and takes hydroxychloroquine every day and prednisone when her condition flares. Her previous urine analysis shows elevated protein levels (4+) and blood (3+). The urine sediment contained red blood cells (6 RBCs/high-power field). The treating physician would like to perform a renal biopsy to rule out lupus nephritis. What type of hypersensitivity is suggestive of lupus nephritis?

Type III, mediated by IgG antibodies

Type IV, mediated by IgG and IgM antibodies

Type IV, mediated by CD4+ T cells

Type I, mediated by IgE antibodies

Type II, mediated by IgG and IgM antibodies

A 26-year-old woman presents with episodes of intermittent fever, arthralgias, constant fatigue, weight loss, and plaque-like rash on sun-exposed areas, which have been gradually increasing over the last 6 months. On presentation, her vital signs include: blood pressure is 110/80 mm Hg, heart rate is 87/min, respiratory rate is 14/min, and temperature is 37.5°C (99.5°F). Physical examination reveals an erythematous scaling rash on the patient’s face distributed in a ‘butterfly-like’ fashion, erythematous keratinized patches on the sun-exposed areas, and mild lower leg edema. During the workup, the patient is found to be positive for anti-Sm (anti-Smith) antibodies. Which process is altered in this patient?

Ineffective clearance of cellular debris

A 39-year-old woman comes to the physician because of a 5-day history of pain and stiffness in her hands and wrists and a nonpruritic generalized rash. The stiffness is worst in the morning and improves after 15–20 minutes of activity. She had fever and a runny nose 10 days ago that resolved without treatment. She is sexually active with a male partner and uses condoms inconsistently. She works as an elementary school teacher. Her temperature is 37.3°C (99.1°F), pulse is 78/min, and blood pressure is 120/70 mm Hg. Examination shows swelling, tenderness, and decreased range of motion of the wrists as well as the metacarpophalangeal and proximal interphalangeal joints. There is a lacy macular rash over the trunk and extremities. Laboratory studies, including erythrocyte sedimentation rate and anti-nuclear antibody and anti-dsDNA serology, show no abnormalities. Which of the following is the most likely cause of this patient's symptoms?

Disseminated gonococcal disease

Systemic lupus erythematosus — USMLE Lesson

Pathophysiology - The Great Imitator

Core Defect: Failure of self-tolerance, leading to autoantibody production against nuclear antigens (e.g., DNA, histones).
Primary Mechanism: Type III hypersensitivity. Immune complexes (Ag-Ab) deposit in tissues (kidneys, skin, joints), activating complement (↓C3/C4) and causing inflammation.
- Also involves Type II hypersensitivity (cytotoxic antibodies against blood cells).
Key Triggers: Genetic predisposition (HLA-DR2, HLA-DR3), UV light (induces keratinocyte apoptosis), infections, and drugs (hydralazine, procainamide).

Lupus Nephritis: Glomerular Immune Complex Deposition

⭐ Anti-dsDNA antibodies are highly specific for SLE, and their titers often correlate with disease activity, especially lupus nephritis.

Clinical Presentation - Butterfly & Betrayal

Malar rash in systemic lupus erythematosus

SLE is a quintessential multi-system autoimmune disease, presenting with a constellation of symptoms. The presentation is notoriously variable, ranging from indolent to fulminant.

📌 Mnemonic: SOAP BRAIN MD

Serositis: Pleuritis or pericarditis.
Oral ulcers: Typically painless.
Arthritis: Non-erosive, involving ≥2 peripheral joints.
Photosensitivity: Skin rash as an unusual reaction to sunlight.
Blood disorders: Hemolytic anemia, leukopenia, lymphopenia, or thrombocytopenia.
Renal disease: Proteinuria or cellular casts.
ANA positive: The most sensitive test (>95%).
Immunologic disorder: Anti-dsDNA, Anti-Sm, or antiphospholipid antibodies.
Neurologic disorder: Seizures or psychosis.
Malar rash: "Butterfly rash" over cheeks, sparing nasolabial folds.
Discoid rash: Raised, scaly patches.

⭐ Drug-induced lupus (hydralazine, procainamide, isoniazid) is associated with anti-histone antibodies; renal and CNS involvement is rare.

Diagnosis & Labs - Cracking the Code

Screening: Best initial test is Antinuclear Antibody (ANA); highly sensitive (>98%) but not specific. An ANA-negative result virtually excludes SLE.
Confirmatory Antibodies:
- Anti-dsDNA: Highly specific, fluctuates with disease activity, strongly linked to lupus nephritis.
- Anti-Smith (Sm): The most specific antibody for SLE; part of diagnostic criteria.
Other Key Labs:
- ↓ Low complement (C3, C4) indicates immune complex deposition and active disease.
- Pancytopenia (anemia of chronic disease, leukopenia, thrombocytopenia).
- Antiphospholipid antibodies (e.g., lupus anticoagulant, anti-cardiolipin).

⭐ High titers of anti-dsDNA antibodies and low complement levels are strong indicators of active lupus nephritis, a major cause of morbidity.

Anti-DNA and Anti-RBP Antibody Pathogenesis in SLE

Management - Taming the Wolf

Goal: Control flares, prevent organ damage, improve quality of life.
Sun protection: Essential for all patients to prevent photosensitivity-induced flares.
NSAIDs: For arthritis and serositis.

⭐ Hydroxychloroquine (HCQ) is foundational for ALL patients, regardless of severity. It reduces flares, organ damage, and mortality.

High‑Yield Points - ⚡ Biggest Takeaways

SLE is a chronic, multi-system autoimmune disease primarily affecting young women.

Key autoantibodies include ANA (highly sensitive) and the more specific anti-dsDNA and anti-Sm.

Drug-induced lupus is linked to anti-histone antibodies (e.g., hydralazine, procainamide).

Classic features include malar rash, discoid rash, photosensitivity, and non-erosive arthritis.

Lupus nephritis is a severe complication requiring renal biopsy for staging and management.

Hydroxychloroquine is foundational therapy for all SLE patients.

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