A 46-year-old woman with diffuse cutaneous systemic sclerosis presents with severe headache, blurred vision, dyspnea, and markedly reduced urine output.
During the previous month, she was prescribed prednisone 30 mg daily for inflammatory joint symptoms.
Vital signs:
BP: 218/126 mmHg
HR: 108/min
RR: 24/min
SpO₂: 93% on room air
Physical examination:
Tightened skin over the hands, forearms, chest, and face
Bibasilar crackles
Mild lower-extremity edema
Cotton-wool spots on retinal examination
Laboratory findings:
Creatinine: 286 µmol/L, previously 78 µmol/L
Hemoglobin: 92 g/L
Platelets: 84 × 10⁹/L
LDH: elevated
Haptoglobin: reduced
Blood smear: schistocytes
Urinalysis: mild proteinuria and hematuria
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: B. Scleroderma renal crisis
Abrupt severe hypertension, rapidly progressive acute kidney injury, retinal changes, pulmonary edema, and microangiopathic hemolytic anemia in a patient with diffuse systemic sclerosis are characteristic of scleroderma renal crisis.
Why the Other Options Are Incorrect
A. Lupus nephritis: Usually presents with immune-complex glomerulonephritis, active urinary sediment, low complement, and lupus serology.
C. Chronic essential hypertension: Does not explain the sudden renal failure and microangiopathic hemolysis.
D. Minimal-change disease: Causes nephrotic proteinuria without malignant hypertension or schistocytes.
E. Primary hyperaldosteronism: Usually causes hypertension with hypokalemia rather than acute renal failure and hemolysis.
Q2
What is the most appropriate immediate pharmacologic treatment?
Reveal answer and rationale
✓Correct answer: B. An angiotensin-converting enzyme inhibitor
An ACE inhibitor, commonly a rapidly titratable agent such as captopril, should be started immediately. Treatment should not be withheld merely because creatinine is elevated. EULAR recommendations identify immediate ACE-inhibitor therapy as the central treatment for scleroderma renal crisis.
Why the Other Options Are Incorrect
A. High-dose prednisone: Glucocorticoids can increase the risk of renal crisis.
C. Beta blocker alone: Does not address the disease’s renin-mediated vasoconstrictive process.
D. Spironolactone alone: Is inadequate for this emergency.
E. Cyclophosphamide: Is not a substitute for immediate blood-pressure control.
Q3
The patient requires temporary dialysis. What should generally happen to ACE-inhibitor therapy?
Reveal answer and rationale
✓Correct answer: B. Continue it when clinically tolerated
Dialysis may be required during the acute phase, but ACE-inhibitor treatment is generally continued when blood pressure and potassium permit because renal recovery may occur over time.
Q4
Which exposure in this case is an important recognized risk factor?
Reveal answer and rationale
✓Correct answer: A. Moderate-dose to high-dose systemic glucocorticoids
Systemic glucocorticoid exposure, particularly at higher doses, is associated with increased risk of scleroderma renal crisis. Patients receiving glucocorticoids require careful blood-pressure and renal monitoring.
Diagnosis: Scleroderma renal crisis associated with diffuse systemic sclerosis.
Key differentials
Thrombotic thrombocytopenic purpura
Malignant essential hypertension
ANCA-associated glomerulonephritis
Lupus nephritis
Renal artery disease
Drug-induced thrombotic microangiopathy
Key investigations
Frequent blood-pressure measurements
CBC and peripheral smear
Creatinine and electrolytes
LDH, bilirubin, and haptoglobin
Urinalysis and urine protein measurement
ECG and cardiac biomarkers when indicated
Chest imaging for pulmonary edema
Treatment principles
Immediate ACE-inhibitor therapy
Controlled blood-pressure reduction
Close renal and electrolyte monitoring
Dialysis when indicated
Avoid unnecessary high-dose glucocorticoids
Specialist nephrology and rheumatology care
Botanical safety: Licorice may increase blood pressure and worsen sodium retention. It is contraindicated in this setting.
Clinical Pearl: Creatinine may initially continue to rise after ACE-inhibitor treatment; this alone is not an automatic reason to discontinue lifesaving treatment.
NPLEX Trap: Do not avoid ACE inhibitors simply because the patient already has severe acute kidney injury.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 402
MULTISYSTEM SARCOIDOSIS WITH HYPERCALCEMIAClinical Case 402
What is the principal mechanism of hypercalcemia in sarcoidosis?
Reveal answer and rationale
✓Correct answer: B. Increased extrarenal conversion of 25-hydroxyvitamin D to active 1,25-dihydroxyvitamin D
Activated macrophages within granulomas can express 1-alpha-hydroxylase, increasing active vitamin D production and intestinal calcium absorption.
Q3
Which approach best establishes the diagnosis when tissue confirmation is required?
Reveal answer and rationale
✓Correct answer: A. Biopsy of the safest accessible involved site showing nonnecrotizing granulomas, with exclusion of alternative causes
The diagnosis rests on a compatible clinical presentation, nonnecrotizing granulomatous inflammation when tissue is required, and exclusion of infections, malignancy, occupational disease, and other granulomatous conditions.
Q4
Which counseling is most appropriate while the hypercalcemia is evaluated and treated?
Reveal answer and rationale
✓Correct answer: B. Avoid unnecessary calcium or vitamin D supplements and excessive ultraviolet exposure
Vitamin D supplementation and increased ultraviolet exposure can worsen calcium abnormalities in susceptible patients. Symptomatic hypercalcemia or organ-threatening sarcoidosis may require systemic treatment.
Diagnosis: Sarcoidosis involving the lungs, eyes, skin, parotid glands, and calcium metabolism.
Key differentials
Tuberculosis
Fungal infection
Lymphoma
Berylliosis
Granulomatosis with polyangiitis
Primary hyperparathyroidism
Drug-induced granulomatous disease
Key investigations
Chest imaging
Serum calcium and creatinine
Liver enzymes and alkaline phosphatase
ECG
Ophthalmologic examination
Pulmonary-function testing
Tissue biopsy when required
Microbiologic testing to exclude infection
The ATS recommends baseline calcium assessment even in sarcoidosis patients without overt symptoms of abnormal calcium metabolism.
Treatment principles
Treat organ-threatening or significantly symptomatic disease
Urgent ophthalmologic treatment for uveitis
Hydration and treatment of clinically significant hypercalcemia
Glucocorticoids when appropriate
Steroid-sparing therapy for selected chronic disease
Monitor pulmonary, cardiac, ocular, hepatic, and renal involvement
Nutrition and supplement safety: Avoid indiscriminate vitamin D, calcium, or high-calcium supplementation until calcium metabolism has been assessed.
Clinical Pearl: A low 25-hydroxyvitamin D level does not automatically mean high-dose vitamin D is safe when 1,25-dihydroxyvitamin D and calcium are elevated.
NPLEX Trap: Serum ACE is neither sufficiently sensitive nor sufficiently specific to confirm sarcoidosis by itself.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
A 28-year-old woman with systemic lupus erythematosus presents with facial swelling, leg edema, fatigue, and dark urine.
Medications:
Hydroxychloroquine
Intermittent ibuprofen
Prednisone 5 mg daily
Vital signs:
BP: 158/96 mmHg
HR: 92/min
Laboratory findings:
Creatinine: 168 µmol/L, previously 72 µmol/L
Urine protein: 3.8 g/day
Urinalysis: dysmorphic erythrocytes and red-cell casts
C3 and C4: low
Anti-double-stranded DNA: markedly elevated
Albumin: reduced
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: A. Active lupus nephritis
Proteinuria, hypertension, acute kidney dysfunction, hematuria, red-cell casts, hypocomplementemia, and rising anti-dsDNA antibodies indicate active immune-complex lupus nephritis.
Q2
What is the most important investigation for classifying renal involvement and directing immunosuppressive therapy?
Reveal answer and rationale
✓Correct answer: A. Kidney biopsy
Kidney biopsy identifies the histologic class, activity, chronicity, and additional renal lesions. These findings guide treatment and prognosis.
Q3
Which treatment approach is appropriate for active proliferative lupus nephritis?
Reveal answer and rationale
✓Correct answer: A. Glucocorticoid therapy combined with an appropriate immunosuppressive regimen
Proliferative lupus nephritis generally requires glucocorticoids plus immunosuppressive treatment such as mycophenolate-based or cyclophosphamide-based therapy. Current KDIGO guidance also incorporates selected combination regimens based on disease severity and patient factors.
Q4
The patient wants to become pregnant. Which medication requires particular preconception review because of teratogenicity?
Reveal answer and rationale
✓Correct answer: A. Mycophenolate
Mycophenolate is teratogenic and requires reliable contraception and planned transition to a pregnancy-compatible regimen before conception. Hydroxychloroquine is generally continued in lupus unless contraindicated.
Diagnosis: Active lupus nephritis, with proliferative disease requiring exclusion by biopsy.
Key differentials
ANCA-associated glomerulonephritis
Antiphospholipid-associated nephropathy
Thrombotic microangiopathy
Infection-related glomerulonephritis
Drug-induced interstitial nephritis
Renal vein thrombosis
Key investigations
CBC
Creatinine and electrolytes
Urinalysis and microscopy
Protein-to-creatinine ratio or 24-hour urine protein
Complement levels
Anti-dsDNA
Antiphospholipid antibodies
Kidney biopsy
Pregnancy testing before teratogenic therapy
Treatment principles
Control blood pressure and proteinuria
Hydroxychloroquine unless contraindicated
Immunosuppressive induction according to biopsy class
Maintenance treatment after response
Infection prevention and vaccination review
Pregnancy planning
Monitor renal response and medication toxicity
Pharmacology safety: NSAIDs can worsen renal perfusion and should be avoided during active kidney injury.
Nutrition: Sodium moderation is appropriate for hypertension and edema. Extreme high-protein diets are inappropriate during significant renal disease.
Clinical Pearl: Lupus serology can support disease activity, but kidney biopsy determines the renal lesion and treatment strategy.
NPLEX Trap: Do not diagnose a urinary infection solely because blood and protein are present in the urine when red-cell casts indicate glomerular inflammation.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 404
SPONTANEOUS BACTERIAL PERITONITIS WITH HEPATORENAL SYNDROME–AKIClinical Case 404
A 62-year-old man with alcohol-related cirrhosis and tense ascites presents with fever, diffuse abdominal discomfort, confusion, and reduced urine output.
What is the immediate diagnosis based on the ascitic-fluid result?
Reveal answer and rationale
✓Correct answer: A. Spontaneous bacterial peritonitis
An ascitic-fluid neutrophil count of at least 250 cells/mm³ supports spontaneous bacterial peritonitis and warrants immediate treatment, even when culture results are pending.
Q2
What is the most appropriate initial management?
Reveal answer and rationale
✓Correct answer: A. Begin appropriate intravenous antibiotics and consider intravenous albumin
SBP requires prompt antimicrobial therapy. Albumin is used in selected patients to reduce the risk of worsening renal dysfunction. Treatment must not wait for culture positivity.
Q3
After infection treatment, withdrawal of nephrotoxic medications, and appropriate albumin expansion, kidney function continues to worsen without shock or structural renal disease. What is the most likely renal diagnosis?
Reveal answer and rationale
✓Correct answer: A. Hepatorenal syndrome–acute kidney injury
HRS-AKI is a functional renal failure occurring in advanced cirrhosis after other causes of acute kidney injury, including hypovolemia, shock, nephrotoxicity, and structural renal disease, have been assessed.
Q4
What treatment principle applies to confirmed HRS-AKI?
Reveal answer and rationale
✓Correct answer: A. Vasoconstrictor therapy with albumin and urgent transplant assessment
Appropriate vasoconstrictor therapy combined with albumin is used for HRS-AKI. Liver transplantation is the definitive therapy for eligible patients.
Assessment for gastrointestinal bleeding and other infection
Medication and supplement review
Treatment principles
Immediate antibiotics for SBP
Albumin in appropriate patients
Stop NSAIDs and other nephrotoxins
Temporarily reassess diuretics during hypotension or AKI
Treat HRS-AKI with albumin and appropriate vasoconstrictor therapy
Evaluate for liver transplantation
Secondary SBP prophylaxis after recovery when indicated
Botanical safety: Herbal diuretics can worsen effective circulating-volume depletion, sodium abnormalities, and kidney injury.
Clinical Pearl: SBP may present primarily with confusion, kidney injury, or hypotension rather than marked abdominal guarding.
NPLEX Trap: Do not wait for a positive ascitic culture when the neutrophil count is diagnostic.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 405
CATASTROPHIC ANTIPHOSPHOLIPID SYNDROMEClinical Case 405
A 38-year-old woman with systemic lupus erythematosus is admitted after abdominal surgery. During the next five days, she develops:
Painful swelling of the left leg
Sudden dyspnea
Retiform skin necrosis
Acute kidney injury
Confusion
Thrombocytopenia
Investigations demonstrate:
Proximal deep-vein thrombosis
Multiple pulmonary emboli
Renal cortical infarctions
Positive lupus anticoagulant
Strongly positive anticardiolipin antibodies
Schistocytes on blood smear
Mildly prolonged coagulation testing
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: A. Catastrophic antiphospholipid syndrome
Rapid thrombosis involving several organ systems over a short period in a patient with antiphospholipid antibodies is characteristic of catastrophic antiphospholipid syndrome.
Q2
Which feature most strongly distinguishes catastrophic APS from an isolated venous thromboembolism?
Reveal answer and rationale
✓Correct answer: A. Rapid involvement of multiple organs through widespread thrombosis
CAPS produces rapidly developing small- and large-vessel thrombosis affecting three or more organ systems, commonly involving the kidneys, lungs, brain, skin, heart, or gastrointestinal tract.
Q3
What is the recommended initial treatment strategy?
Reveal answer and rationale
✓Correct answer: A. Therapeutic anticoagulation, high-dose glucocorticoids, and plasma exchange or intravenous immunoglobulin
First-line CAPS treatment uses combination therapy, often described as triple therapy: anticoagulation, glucocorticoids, and plasma exchange and/or IV immunoglobulin. The precipitating infection, surgery-related complication, or lupus flare must also be treated.
Q4
Which supplement history is especially important once therapeutic anticoagulation begins?
Reveal answer and rationale
✓Correct answer: A. High-dose ginkgo or garlic extracts
Products with potential antiplatelet activity may increase bleeding concerns when combined with therapeutic anticoagulation.
Diagnosis: Catastrophic antiphospholipid syndrome triggered by surgery.
Common precipitants
Infection
Surgery
Withdrawal or interruption of anticoagulation
Pregnancy complications
Malignancy
Lupus flare
Certain medications
Key investigations
Vascular imaging based on affected organs
CBC and peripheral smear
Creatinine and urinalysis
Liver enzymes
Cardiac biomarkers and echocardiography
Coagulation studies
Lupus anticoagulant
Anticardiolipin antibodies
Anti-beta-2-glycoprotein I antibodies
Infection assessment
Treatment principles
Immediate therapeutic anticoagulation when not contraindicated
High-dose glucocorticoids
Plasma exchange and/or IV immunoglobulin
Treat the trigger
Intensive organ support
Consider additional immunomodulation in refractory disease
Clinical Pearl: Thrombocytopenia does not protect a patient from thrombosis and does not automatically exclude anticoagulation.
NPLEX Trap: Do not treat CAPS as an isolated DVT when the kidneys, lungs, skin, brain, and hematologic system are becoming involved simultaneously.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 406
GRANULOMATOSIS WITH POLYANGIITIS WITH PULMONARY–RENAL SYNDROMEClinical Case 406
A 47-year-old man presents with chronic sinus pain, recurrent otitis, nasal crusting, hemoptysis, dyspnea, fatigue, and dark urine.
Vital signs:
BP: 154/92 mmHg
HR: 110/min
RR: 28/min
SpO₂: 86% on room air
Investigations:
Hemoglobin: falling
Creatinine: 248 µmol/L
Urinalysis: dysmorphic erythrocytes and red-cell casts
Chest CT: bilateral nodules and diffuse ground-glass opacities
PR3-ANCA: strongly positive
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: A. Granulomatosis with polyangiitis
Destructive upper-airway disease, pulmonary nodules or alveolar hemorrhage, rapidly progressive glomerulonephritis, and PR3-ANCA positivity strongly suggest granulomatosis with polyangiitis.
Q2
What is the most appropriate next management step?
Reveal answer and rationale
✓Correct answer: A. Emergency hospitalization and remission-induction treatment
Pulmonary hemorrhage and rapidly progressive glomerulonephritis are organ-threatening manifestations requiring immediate specialist treatment.
Q3
Which regimen is commonly used to induce remission in severe GPA?
Reveal answer and rationale
✓Correct answer: A. Rituximab plus glucocorticoid therapy
Rituximab or cyclophosphamide is used with glucocorticoids for severe GPA or microscopic polyangiitis. The ACR/Vasculitis Foundation guideline conditionally favors rituximab over cyclophosphamide for remission induction in severe disease.
Q4
Which preventive treatment should be considered during rituximab- or cyclophosphamide-based immunosuppression?
Reveal answer and rationale
✓Correct answer: A. Pneumocystis jirovecii pneumonia prophylaxis
Pneumocystis prophylaxis is generally recommended during cyclophosphamide or rituximab treatment and significant accompanying glucocorticoid exposure, unless contraindicated.
Diagnosis: Severe granulomatosis with polyangiitis causing pulmonary–renal syndrome.
Key differentials
Anti-GBM disease
Microscopic polyangiitis
Lupus pulmonary–renal syndrome
Infective endocarditis
Severe pneumonia
Pulmonary embolism
Cocaine-induced midline destructive disease
Key investigations
CBC
Creatinine and electrolytes
Urinalysis and microscopy
Urine protein measurement
PR3-ANCA and MPO-ANCA
Anti-GBM antibodies
Chest CT
Bronchoscopy when indicated
Kidney or other involved-tissue biopsy
Infection screening before immunosuppression
Treatment principles
Stabilize oxygenation and ventilation
Urgent glucocorticoid treatment
Rituximab or cyclophosphamide for severe disease
Pneumocystis prophylaxis
Monitor for treatment-related infection
Maintenance immunosuppression after remission
Botanical safety: Immune-stimulating products should not replace immunosuppression and may be inappropriate in active autoimmune disease.
Clinical Pearl: A positive ANCA supports the diagnosis but does not replace clinical assessment and tissue confirmation when safely obtainable.
NPLEX Trap: Do not interpret hemoptysis, falling hemoglobin, and diffuse opacities as uncomplicated pneumonia when red-cell casts and acute kidney injury indicate a pulmonary–renal syndrome.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 407
DRESS SYNDROME CAUSED BY ALLOPURINOLClinical Case 407
A 52-year-old man presents with fever, facial swelling, diffuse rash, fatigue, and reduced urine output.
Six weeks earlier, allopurinol was started for asymptomatic hyperuricemia.
Physical examination:
Temperature: 39.2°C
Diffuse morbilliform eruption involving more than 50% of body surface area
Facial edema
Cervical lymphadenopathy
No extensive epidermal detachment
Laboratory findings:
Eosinophils: 2.4 × 10⁹/L
Atypical lymphocytes present
ALT: 624 U/L
Bilirubin: elevated
Creatinine: 196 µmol/L
Viral hepatitis testing: negative
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: A. Drug reaction with eosinophilia and systemic symptoms
The delayed onset after a high-risk medication, fever, extensive rash, facial edema, eosinophilia, lymphadenopathy, hepatitis, and kidney injury indicate DRESS syndrome.
Q2
What is the most important immediate action?
Reveal answer and rationale
✓Correct answer: A. Stop allopurinol permanently and arrange urgent hospital assessment
Immediate and permanent withdrawal of the suspected medication is essential. Serious hepatic, renal, pulmonary, cardiac, or hematologic involvement requires urgent specialist management.
Q3
Which finding indicates severe systemic disease rather than a mild cutaneous drug eruption?
Reveal answer and rationale
✓Correct answer: A. Marked hepatitis and acute kidney injury
Internal-organ injury is a defining concern in DRESS. The liver is commonly affected, but renal, pulmonary, cardiac, neurologic, and hematologic complications can occur.
Q4
What treatment may be required when significant internal-organ involvement is present?
Reveal answer and rationale
✓Correct answer: A. Systemic glucocorticoid therapy with specialist-directed supportive care
Management is severity-based. Significant organ involvement commonly leads to systemic glucocorticoid treatment, although treatment must be individualized and infection carefully assessed. Contemporary EAACI work emphasizes clinical diagnosis and severity-based management.
Assessment using a validated diagnostic framework such as RegiSCAR
Evaluation for alternative infectious or autoimmune causes
Treatment principles
Immediate withdrawal of the culprit drug
Hospitalize significant systemic disease
Support affected organs
Consider systemic glucocorticoids for severe organ involvement
Monitor because symptoms may progress after drug withdrawal
Document the drug allergy clearly
Avoid future rechallenge
Botanical safety: “Liver detoxification” supplements can worsen hepatic injury and obscure the clinical course.
Clinical Pearl: DRESS frequently begins several weeks after medication initiation, so the responsible drug may appear unrelated to the current illness.
NPLEX Trap: Do not continue the culprit medication merely because the rash is being treated with antihistamines or topical corticosteroids.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 408
MULTIPLE MYELOMA WITH CAST NEPHROPATHYClinical Case 408
A 68-year-old man presents with fatigue, constipation, progressive back pain, weight loss, and reduced urine output.
Laboratory findings:
Hemoglobin: 82 g/L
Creatinine: 368 µmol/L
Corrected calcium: 3.18 mmol/L
Total protein: elevated
Albumin: reduced
Serum free lambda light chains: markedly elevated
Peripheral smear: rouleaux formation
Imaging demonstrates multiple punched-out lytic lesions and a vertebral compression fracture.
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: A. Multiple myeloma
Anemia, renal impairment, hypercalcemia, lytic bone lesions, a protein gap, rouleaux formation, and markedly elevated monoclonal light chains are characteristic of active multiple myeloma.
Q2
Which investigations are central to confirming and characterizing the plasma-cell disorder?
Reveal answer and rationale
✓Correct answer: A. Serum and urine immunofixation, free-light-chain measurement, and bone-marrow examination
Monoclonal-protein testing and bone-marrow evaluation establish the plasma-cell disorder. Whole-body imaging identifies lytic lesions and other skeletal complications.
Q3
What is the most important treatment principle for suspected myeloma cast nephropathy?
Reveal answer and rationale
✓Correct answer: A. Rapid initiation of effective anti-myeloma therapy with supportive renal care
Rapid reduction of nephrotoxic free light chains is critical. Bortezomib-based therapy and high-dose dexamethasone are central approaches in myeloma-related renal impairment, accompanied by hydration and withdrawal of nephrotoxins. Mechanical light-chain-removal procedures do not replace effective anti-myeloma therapy.
Q4
Which medication should be stopped or avoided because it may worsen the kidney injury?
Reveal answer and rationale
✓Correct answer: A. NSAIDs
NSAIDs can reduce renal perfusion and aggravate acute kidney injury. Contrast exposure and other nephrotoxins should also be minimized when possible.
Diagnosis: Active multiple myeloma with hypercalcemia, anemia, lytic bone disease, and probable cast nephropathy.
Key differentials
Metastatic bone malignancy
Monoclonal gammopathy of undetermined significance
Smoldering myeloma
AL amyloidosis
Primary hyperparathyroidism
Lymphoma
Waldenström macroglobulinemia
Key investigations
CBC
Calcium, albumin, and creatinine
Serum protein electrophoresis with immunofixation
Urine protein electrophoresis with immunofixation
Serum free-light-chain assay
Bone-marrow biopsy
Whole-body low-dose CT, PET-CT, or MRI
Cytogenetic and molecular risk assessment
Treatment principles
Prompt hematology referral
Immediate anti-myeloma treatment when organ damage is present
Appropriate hydration
Treat hypercalcemia
Avoid NSAIDs and unnecessary contrast
Renally adjust supportive medications
Dialysis for standard urgent indications
Manage fractures, infection risk, and thrombosis risk
Nutrition and supplement safety: High-dose calcium or vitamin D is inappropriate during hypercalcemia. Unregulated “bone-building” products may contain calcium or vitamin D.
Clinical Pearl: A urine dipstick may underestimate light-chain protein because it detects albumin more effectively than free light chains.
NPLEX Trap: Do not dismiss severe renal failure because the routine urine dipstick shows only modest protein.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
A 61-year-old man presents with progressive leg edema, exertional dyspnea, dizziness when standing, numbness of the feet, and unintentional weight loss.
Physical examination:
BP: 108/68 mmHg supine and 78/46 mmHg standing
Elevated jugular venous pressure
Bilateral edema
Enlarged tongue
Periorbital purpura
Reduced vibration sensation in both feet
Investigations:
Urine protein: 6.2 g/day
Albumin: markedly reduced
NT-proBNP: markedly elevated
Echocardiogram: thickened ventricular walls with restrictive filling
ECG: low voltage
Serum free-light-chain ratio: abnormal
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: A. Systemic light-chain amyloidosis
Nephrotic proteinuria, restrictive cardiomyopathy, autonomic neuropathy, peripheral neuropathy, macroglossia, periorbital purpura, and a monoclonal light-chain abnormality strongly suggest systemic AL amyloidosis.
Q2
Which screening tests should be performed when AL amyloidosis is suspected?
Reveal answer and rationale
✓Correct answer: A. Serum and urine immunofixation plus serum free-light-chain testing
A combination of serum immunofixation, urine immunofixation, and serum free-light-chain testing improves detection of the underlying monoclonal protein. Serum protein electrophoresis alone is insufficient. The 2026 ASH diagnostic guideline emphasizes comprehensive paraprotein testing in suspected AL amyloidosis.
Q3
How is amyloid deposition confirmed and accurately typed?
Reveal answer and rationale
✓Correct answer: A. Tissue biopsy with Congo-red staining followed by reliable amyloid typing
Congo-red-positive deposits showing characteristic birefringence confirm amyloid. Accurate typing, preferably using a validated method such as mass spectrometry, is essential because treatment differs greatly between AL and transthyretin amyloidosis.
Q4
What is the fundamental treatment strategy for AL amyloidosis?
Reveal answer and rationale
✓Correct answer: A. Rapid clone-directed plasma-cell therapy combined with organ-specific supportive care
Treatment aims to suppress production of the pathogenic light chain while cautiously managing cardiac, renal, neurologic, gastrointestinal, and other organ complications.
Diagnosis: Systemic AL amyloidosis involving the heart, kidneys, autonomic nervous system, peripheral nerves, and soft tissues.
Key differentials
Transthyretin amyloidosis
Multiple myeloma
Hypertrophic cardiomyopathy
Hypertensive cardiac remodeling
Diabetic nephropathy
Constrictive pericarditis
Light-chain deposition disease
Key investigations
Serum immunofixation
Urine immunofixation
Serum free-light-chain assay
Cardiac biomarkers
Echocardiography with strain imaging
Cardiac MRI when appropriate
Tissue biopsy with Congo-red staining
Definitive amyloid typing
Bone-marrow examination
Renal, hepatic, and neurologic assessment
Treatment principles
Urgent hematology referral
Plasma-cell-directed treatment
Careful diuretic therapy for congestion
Avoid excessive reduction in preload
Manage orthostatic hypotension
Renally adjust medication
Evaluate suitability for stem-cell transplantation in selected patients
Pharmacology safety: Standard heart-failure medications may be poorly tolerated because of low blood pressure, restrictive physiology, conduction disease, and autonomic dysfunction.
Botanical safety: Stimulant or vasodilating herbs may worsen arrhythmia or hypotension.
Clinical Pearl: Increased ventricular-wall thickness on echocardiography combined with low ECG voltage is a major clue to cardiac amyloidosis.
NPLEX Trap: Do not assume a positive monoclonal protein proves that all cardiac amyloidosis is AL; tissue typing and an integrated diagnostic assessment remain essential.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 410
SECONDARY HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSISClinical Case 410
A 34-year-old man presents with persistent fever, profound fatigue, abdominal fullness, bruising, and progressive confusion following an Epstein–Barr virus-like illness.
Physical examination:
Temperature: 40.0°C
Marked splenomegaly
Hepatomegaly
Petechiae
Altered mental status
Laboratory findings:
Hemoglobin: 76 g/L
Platelets: 38 × 10⁹/L
Neutrophils: 0.7 × 10⁹/L
Ferritin: 38,000 µg/L
Triglycerides: markedly elevated
Fibrinogen: reduced
AST and ALT: elevated
Soluble interleukin-2 receptor: elevated
Bone-marrow sample: no definite hemophagocytosis on the first specimen
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: A. Secondary hemophagocytic lymphohistiocytosis
Persistent high fever, splenomegaly, pancytopenia, extreme hyperferritinemia, hypertriglyceridemia, hypofibrinogenemia, hepatitis, and neurologic dysfunction strongly suggest HLH.
Q2
How can HLH be diagnosed using the HLH-2004 framework?
Reveal answer and rationale
✓Correct answer: A. A pathogenic molecular diagnosis or fulfillment of at least five of eight clinical and laboratory criteria
The HLH-2004 framework permits diagnosis through a compatible molecular finding or fulfillment of at least five of eight criteria, including fever, splenomegaly, cytopenias, triglyceride or fibrinogen abnormalities, hemophagocytosis, reduced NK-cell activity, elevated ferritin, and elevated soluble CD25.
Q3
Does the absence of hemophagocytosis on the first bone-marrow examination exclude HLH?
Reveal answer and rationale
✓Correct answer: A. No
Hemophagocytosis may be absent early, can be missed during sampling, and is not specific to HLH. Treatment should not be delayed in a critically ill patient whose overall clinical pattern strongly supports the diagnosis.
Q4
What is the most appropriate management principle?
Reveal answer and rationale
✓Correct answer: A. Immediate hematology-directed treatment of hyperinflammation and the underlying trigger
Adult HLH is a medical emergency. Treatment may include dexamethasone, etoposide, or other targeted immunomodulatory therapy depending on severity and the precipitating infection, malignancy, or autoimmune disease. The Histiocyte Society’s adult recommendations stress rapid diagnosis, control of hyperinflammation, and treatment of the trigger.
Diagnosis: Secondary HLH, probably triggered by infection, with neurologic, hepatic, and hematologic involvement.
Common triggers
Epstein–Barr virus
Other severe infections
Lymphoma and leukemia
Autoimmune or autoinflammatory disease
Immunosuppressive treatment
Immune therapies
Post-transplant complications
Key investigations
CBC
Ferritin
Triglycerides
Fibrinogen
Liver enzymes and coagulation profile
Soluble interleukin-2 receptor
NK-cell-function testing when available
Bone-marrow examination
Viral PCR and infection evaluation
Imaging and biopsy to assess occult malignancy
Calculation of an HScore in appropriate adults
Treatment principles
Urgent hematology involvement
Treat the precipitating infection, malignancy, or autoimmune disease
Suppress dangerous hyperinflammation
Provide blood-product and organ support
Monitor for DIC, liver failure, neurologic deterioration, and shock
Consider hematopoietic stem-cell transplantation in selected primary, recurrent, or refractory disease
Nutrition and supplement safety: Extreme ferritin elevation reflects inflammation and iron sequestration; it is not an indication for empiric high-dose iron.
Clinical Pearl: Ferritin values in HLH may be extremely high, but no single ferritin threshold confirms the diagnosis in every adult.
NPLEX Trap: Do not wait for visible hemophagocytosis or fulfillment of every possible criterion before escalating a rapidly deteriorating patient.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 411
ADULT-ONSET STILL DISEASE WITH MACROPHAGE ACTIVATION SYNDROMEClinical Case 411
A 31-year-old woman presents with three weeks of daily high-spiking fever, severe fatigue, sore throat, joint pain, and a faint salmon-coloured rash that appears during febrile episodes.
During the last two days, she has developed confusion, jaundice, and increasing shortness of breath.
Physical examination:
Temperature: 40.1°C
HR: 132/min
BP: 94/58 mmHg
Evanescent salmon-coloured rash over the trunk
Synovitis of both wrists and knees
Hepatosplenomegaly
Laboratory findings:
Ferritin: 28,000 µg/L
Hemoglobin: 86 g/L
Platelets: 54 × 10⁹/L
Neutrophils: 1.1 × 10⁹/L
Triglycerides: elevated
Fibrinogen: reduced
AST and ALT: markedly elevated
ESR: unexpectedly falling
ANA and rheumatoid factor: negative
Blood cultures: negative to date
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: A. Adult-onset Still disease complicated by macrophage activation syndrome
Daily spiking fever, inflammatory arthritis, sore throat, an evanescent salmon-coloured rash, marked hyperferritinemia, and negative ANA and rheumatoid factor suggest Still disease. The subsequent cytopenias, hepatitis, hypofibrinogenemia, hypertriglyceridemia, neurologic deterioration, and extreme ferritin elevation indicate macrophage activation syndrome.
Q2
Which laboratory trend most strongly suggests that macrophage activation syndrome has developed?
Reveal answer and rationale
✓Correct answer: A. Falling platelet count and fibrinogen with rising ferritin and liver enzymes
MAS produces uncontrolled macrophage and T-cell activation. Cytopenias, falling fibrinogen, liver dysfunction, coagulopathy, hypertriglyceridemia, and rapidly rising ferritin are major warning findings.
Q3
Why may the ESR fall despite worsening systemic inflammation?
Reveal answer and rationale
✓Correct answer: A. Reduced fibrinogen can lower the erythrocyte-sedimentation rate
ESR depends partly on fibrinogen. During MAS, fibrinogen may fall because of consumption and liver dysfunction, producing a paradoxically low or falling ESR despite severe inflammation.
Q4
What is the most appropriate management principle?
Reveal answer and rationale
✓Correct answer: A. Urgent specialist treatment of MAS with high-dose anti-inflammatory therapy and consideration of cytokine-directed treatment
MAS is a life-threatening hyperinflammatory emergency. Management commonly includes high-dose glucocorticoids and rapid consideration of cytokine-directed treatment, particularly IL-1 inhibition, while infection and other triggers are investigated and treated.
Diagnosis: Adult-onset Still disease complicated by macrophage activation syndrome.
Key differentials
Secondary HLH
Severe bacterial infection
Viral infection
Hematologic malignancy
Systemic lupus erythematosus
Drug hypersensitivity
Catastrophic antiphospholipid syndrome
Key investigations
Serial CBC
Ferritin
Fibrinogen and triglycerides
Liver enzymes and coagulation profile
Soluble IL-2 receptor when available
Bone-marrow assessment when appropriate
Cultures and infection testing
Imaging and malignancy assessment when indicated
Treatment principles
Emergency rheumatology and hematology involvement
High-dose glucocorticoid therapy
Consider IL-1-directed therapy
Treat identified infections or other precipitants
Manage coagulopathy and organ failure
Do not delay treatment solely for bone-marrow confirmation
Botanical safety: Immune-stimulating supplements are inappropriate during uncontrolled systemic hyperinflammation.
Clinical Pearl: A falling ESR can be an ominous sign when fibrinogen is being consumed.
NPLEX Trap: Extreme ferritin elevation does not mean the patient needs iron supplementation.
Current EULAR/PReS recommendations emphasize early recognition of MAS and rapid cytokine-directed and glucocorticoid-based treatment for severe Still disease.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 412
EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITISClinical Case 412
A 48-year-old woman with adult-onset asthma and chronic sinusitis presents with worsening dyspnea, painful numbness of the right foot, weakness of the left hand, and a purpuric rash.
✓Correct answer: A. Eosinophilic granulomatosis with polyangiitis
Adult-onset asthma, sinus disease, marked eosinophilia, transient pulmonary infiltrates, palpable purpura, mononeuritis multiplex, renal abnormalities, and myocarditis are characteristic of EGPA.
Q2
Which finding makes this organ-threatening disease?
Reveal answer and rationale
✓Correct answer: A. Myocarditis and mononeuritis multiplex
Cardiac involvement can cause arrhythmia, heart failure, and death. Progressive vasculitic neuropathy also represents significant organ damage requiring urgent treatment.
Q3
What is an appropriate induction strategy for severe EGPA?
Reveal answer and rationale
✓Correct answer: A. High-dose glucocorticoid therapy combined with an appropriate immunosuppressive agent
Severe EGPA generally requires systemic glucocorticoids plus an induction agent such as cyclophosphamide or rituximab. Mepolizumab is particularly useful in selected nonsevere, relapsing, or eosinophilic disease but is not a substitute for intensive induction treatment in life-threatening vasculitis.
Q4
Which statement about ANCA testing is correct?
Reveal answer and rationale
✓Correct answer: A. A negative ANCA test would not exclude EGPA
Only a subset of patients with EGPA are ANCA-positive. Diagnosis depends on the complete clinical pattern rather than ANCA testing alone.
Diagnosis: Severe EGPA involving the lungs, peripheral nerves, skin, kidneys, and heart.
Key differentials
Hypereosinophilic syndrome
Parasitic infection
Drug-induced eosinophilia
Allergic bronchopulmonary aspergillosis
GPA
Eosinophilic pneumonia
Hematologic malignancy
Key investigations
CBC with eosinophil count
ANCA testing
Creatinine and urinalysis
Troponin, ECG, echocardiography, or cardiac MRI
Chest CT
Nerve-conduction testing
Tissue biopsy when appropriate
Parasite and medication assessment
Treatment principles
Treat severe disease urgently
Systemic glucocorticoids
Cyclophosphamide or rituximab for organ-threatening disease
Mepolizumab in selected nonsevere or relapsing disease
Treat asthma and sinus disease
Monitor cardiac and neurologic recovery
Botanical safety: Ephedra and other stimulants may worsen tachycardia and cardiac stress.
Clinical Pearl: Cardiac EGPA may occur even when ANCA is negative.
NPLEX Trap: Do not classify marked eosinophilia with neuropathy, purpura, and myocarditis as uncomplicated allergic asthma.
The ACR/Vasculitis Foundation guideline distinguishes severe EGPA requiring glucocorticoid-based immunosuppressive induction from nonsevere disease in which mepolizumab may be used.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 413
POLYARTERITIS NODOSA ASSOCIATED WITH HEPATITIS BClinical Case 413
A 44-year-old man presents with severe postprandial abdominal pain, weight loss, muscle pain, painful skin nodules, and progressive right-foot weakness.
Vital signs:
BP: 192/112 mmHg
HR: 106/min
Physical examination:
Livedo reticularis
Tender subcutaneous nodules
Right foot drop
Diffuse abdominal tenderness without guarding
Laboratory findings:
Creatinine: elevated
Urinalysis: mild proteinuria but no red-cell casts
Hepatitis B surface antigen: positive
Hepatitis B viral load: elevated
ANCA: negative
Mesenteric and renal angiography demonstrates multiple microaneurysms and irregular narrowing of medium-sized arteries.
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: A. Hepatitis B-associated polyarteritis nodosa
Medium-vessel disease causing mesenteric ischemia, renovascular hypertension, skin nodules, livedo reticularis, mononeuritis multiplex, and angiographic microaneurysms is characteristic of PAN.
Q2
Which finding supports PAN rather than microscopic polyangiitis?
Reveal answer and rationale
✓Correct answer: A. Medium-vessel microaneurysms without glomerulonephritis
PAN affects medium and small muscular arteries but typically spares glomerular capillaries. Hematuria may occur from renal ischemia, but an active glomerulonephritic sediment is not typical.
Q3
Which test can establish the diagnosis when an involved accessible tissue is present?
Reveal answer and rationale
✓Correct answer: A. Biopsy of symptomatic skin, nerve, or muscle
Biopsy may show necrotizing inflammation of medium or small muscular arteries. Angiography is particularly useful when abdominal or renal arterial involvement is suspected.
Q4
What additional management is essential in hepatitis B-associated PAN?
Reveal answer and rationale
✓Correct answer: A. Specialist-directed antiviral treatment for hepatitis B
Treatment must address both the vasculitis and active hepatitis B. Antiviral therapy is central, with carefully selected short-term immunosuppression and plasma exchange in some severe presentations.
Glucocorticoids and immunosuppression when indicated
Antiviral treatment for hepatitis B
Plasma exchange in selected severe HBV-associated cases
Blood-pressure control
Management of ischemic complications
Physical medicine safety: Deep massage over painful nodules or ischemic limbs is inappropriate.
Clinical Pearl: Severe hypertension in PAN is often caused by renal arterial ischemia rather than glomerulonephritis.
NPLEX Trap: Pulmonary capillaritis and glomerulonephritis suggest another vasculitis, not classic PAN.
The ACR/Vasculitis Foundation PAN guideline supports tissue biopsy or vascular imaging and severity-based immunosuppressive treatment.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 414
ANTI-MDA5 DERMATOMYOSITIS WITH RAPIDLY PROGRESSIVE INTERSTITIAL LUNG DISEASEClinical Case 414
A 42-year-old woman presents with painful hand lesions, fatigue, dry cough, and rapidly worsening shortness of breath.
Physical examination:
Violaceous papules over the knuckles
Painful palmar papules
Ulceration near the fingernails
Faint heliotrope discoloration around the eyelids
Minimal objective muscle weakness
Bilateral fine inspiratory crackles
Investigations:
Creatine kinase: normal
Ferritin: markedly elevated
Anti-MDA5 antibody: positive
HRCT: bilateral ground-glass and organizing-pneumonia-like opacities
Oxygen saturation: 86% on room air
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: A. Anti-MDA5-positive clinically amyopathic dermatomyositis with rapidly progressive ILD
Characteristic dermatomyositis skin findings, little muscle weakness, normal CK, anti-MDA5 positivity, hyperferritinemia, and rapidly progressive ILD indicate this high-risk phenotype.
Q2
Which feature does not exclude dermatomyositis?
Reveal answer and rationale
✓Correct answer: A. A normal creatine kinase level
Anti-MDA5 disease may be clinically amyopathic, meaning classic skin and systemic manifestations occur without substantial muscle weakness or CK elevation.
Q3
What is the most appropriate management principle?
Reveal answer and rationale
✓Correct answer: A. Urgent combined immunosuppressive treatment rather than slow sequential monotherapy
Rapidly progressive anti-MDA5 ILD carries substantial mortality. Current guidance supports early combination immunosuppression, often involving glucocorticoids plus additional agents, rather than waiting for failure of prolonged monotherapy.
Q4
Which investigation is most useful for defining the pulmonary pattern and extent?
Reveal answer and rationale
✓Correct answer: A. High-resolution CT of the chest
HRCT identifies ground-glass opacity, consolidation, organizing-pneumonia patterns, and fibrotic change. Pulmonary-function testing and oxygen assessment provide additional severity information.
Diagnosis: Anti-MDA5 dermatomyositis with rapidly progressive ILD.
Key differentials
Antisynthetase syndrome
Viral pneumonia
Pneumocystis pneumonia
Hypersensitivity pneumonitis
Systemic sclerosis-associated ILD
Idiopathic organizing pneumonia
Drug-induced pneumonitis
Key investigations
HRCT
Oxygen saturation and blood gases
Pulmonary-function testing
Myositis-antibody panel
CK, aldolase, AST, and LDH
Ferritin
Infection evaluation
Malignancy assessment based on phenotype and age
Treatment principles
Emergency respiratory and rheumatology assessment
Early combination immunosuppression
Infection prophylaxis when indicated
Screen for treatment-associated infection
Consider transplant-centre involvement in refractory respiratory failure
Avoid delaying treatment because CK is normal
Nutrition and rehabilitation: Exercise may be useful after stabilization but is not appropriate during severe hypoxemic respiratory deterioration.
Clinical Pearl: Skin ulceration and painful palmar papules are important clues to anti-MDA5 disease.
NPLEX Trap: Normal muscle enzymes do not exclude life-threatening dermatomyositis-associated lung disease.
The ACR/CHEST ILD guideline conditionally recommends upfront combination treatment for rapidly progressive autoimmune ILD, with triple therapy considered when anti-MDA5 disease is suspected.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 415
BEHÇET SYNDROME WITH CEREBRAL VENOUS SINUS THROMBOSISClinical Case 415
A 29-year-old man presents with severe progressive headache, vomiting, and transient double vision.
History:
Recurrent painful oral ulcers
Recurrent genital ulcers
Previous episode of anterior uveitis
Painful nodules over the legs
Physical examination:
Papilledema
Right sixth-nerve palsy
Healing oral and genital ulcers
Erythema-nodosum-like lesions
MRI venography demonstrates superior sagittal sinus thrombosis.
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: A. Neuro-Behçet syndrome with cerebral venous sinus thrombosis
Recurrent oral and genital ulcers, uveitis, inflammatory skin lesions, and cerebral venous thrombosis form a characteristic Behçet pattern.
Q2
What mechanism principally causes the thrombosis?
Reveal answer and rationale
✓Correct answer: A. Inflammation of the vessel wall
Thrombosis in Behçet syndrome is strongly associated with vascular inflammation. Management therefore focuses on controlling inflammation rather than viewing the event as an ordinary unprovoked clot.
Q3
What is the primary acute treatment approach?
Reveal answer and rationale
✓Correct answer: A. High-dose glucocorticoid treatment with specialist-directed immunosuppression
Acute cerebral venous involvement generally requires rapid control of vascular inflammation. Additional immunosuppressive treatment is individualized according to severity, recurrence, and other organ involvement.
Q4
What should be considered before anticoagulation is used?
Reveal answer and rationale
✓Correct answer: A. Evaluation for pulmonary-artery aneurysm or another major bleeding risk
Anticoagulation is individualized in Behçet thrombosis. Pulmonary-artery aneurysms can cause catastrophic hemorrhage, so vascular imaging and specialist assessment may be required before anticoagulation.
Diagnosis: Behçet syndrome with nonparenchymal neurologic involvement caused by cerebral venous sinus thrombosis.
Key differentials
Antiphospholipid syndrome
Infection-related cerebral thrombosis
Inflammatory bowel disease
Multiple sclerosis
Sarcoidosis
Malignancy
Inherited thrombophilia
Key investigations
MRI with venography
Ophthalmologic examination
Assessment for pulmonary-artery aneurysm
Inflammatory markers
Thrombosis and bleeding-risk evaluation
Lumbar puncture only when safe and clinically needed
Assessment for other systemic vascular involvement
Treatment principles
High-dose glucocorticoids
Immunosuppression based on disease severity
Manage raised intracranial pressure
Individualize anticoagulation
Treat ocular and other organ involvement
Long-term rheumatology and neurology follow-up
Botanical safety: Products with antiplatelet effects may complicate anticoagulation and bleeding-risk assessment.
Clinical Pearl: Behçet thrombosis is closely linked to inflamed vessel walls.
NPLEX Trap: Do not treat the clot while ignoring the underlying systemic vasculitis.
EULAR recommendations prioritize immunosuppressive control of vascular inflammation and individualized decisions regarding anticoagulation.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 416
WILSON DISEASE PRESENTING WITH ACUTE LIVER FAILUREClinical Case 416
✓Correct answer: A. Wilson disease causing acute liver failure and Coombs-negative hemolysis
Acute liver failure in a young patient, disproportionately low alkaline phosphatase, Coombs-negative hemolytic anemia, renal dysfunction, low ceruloplasmin, and Kayser–Fleischer rings strongly suggest Wilson disease.
Q2
What is the most important immediate management step?
Reveal answer and rationale
✓Correct answer: A. Urgent transfer to a liver-transplant centre
Wilson-related acute liver failure can progress rapidly and carries a poor prognosis without transplantation. Transplant evaluation must not be delayed for completion of every confirmatory test.
Q3
Which additional tests support the diagnosis?
Reveal answer and rationale
✓Correct answer: A. Twenty-four-hour urinary copper and quantitative hepatic copper assessment when appropriate
Diagnosis integrates clinical findings, ceruloplasmin, urinary copper, eye examination, hepatic copper when safe, and ATP7B genetic testing. No single test is sufficient in every patient.
Q4
Which intervention may be used as a bridge while transplantation is arranged?
Reveal answer and rationale
✓Correct answer: A. Specialist-directed extracorporeal copper-removal or plasma-exchange therapy
Plasma exchange and other extracorporeal support may reduce circulating copper and stabilize selected patients while urgent transplantation is arranged. They do not replace transplant assessment.
Diagnosis: Wilson disease presenting as acute liver failure with intravascular hemolysis.
Key differentials
Autoimmune hepatitis
Viral hepatitis
Acetaminophen toxicity
Acute fatty liver of pregnancy
Budd–Chiari syndrome
Hemolytic-uremic syndrome
Drug-induced liver injury
Key investigations
Ceruloplasmin
Serum and urinary copper
Slit-lamp examination
CBC and hemolysis studies
Liver enzymes, bilirubin, glucose, INR
Renal function
ATP7B testing
Hepatic copper when safe and appropriate
Treatment principles
Immediate intensive-care management
Urgent transplant-centre referral
Correct hypoglycemia and coagulopathy as clinically indicated
Manage cerebral edema and renal failure
Consider plasma exchange as a bridge
Screen siblings after diagnosis
Nutrition: Dietary copper restriction is supportive in chronic management but cannot treat acute liver failure.
Clinical Pearl: Coombs-negative hemolysis can result from sudden copper release from damaged hepatocytes.
NPLEX Trap: Do not manage Wilson-related acute liver failure with outpatient chelation or zinc alone.
AASLD and EASL guidance emphasize multidisciplinary diagnosis and immediate transplant-centre evaluation for Wilson-related acute liver failure.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
A 27-year-old woman presents with severe diffuse abdominal pain, vomiting, constipation, anxiety, and progressive weakness.
She recently began a very-low-carbohydrate weight-loss diet and was prescribed a new antiseizure medication.
Vital signs:
BP: 176/104 mmHg
HR: 124/min
Examination:
Abdomen is mildly tender without guarding
Proximal muscle weakness
Reduced reflexes
No skin blistering
Laboratory findings:
Sodium: 118 mmol/L
Urinalysis: initially normal
Urine becomes dark reddish-brown after standing
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: A. Acute intermittent porphyria
Severe neurovisceral abdominal pain, autonomic instability, psychiatric symptoms, motor neuropathy, hyponatremia, medication exposure, fasting, and darkening urine suggest an acute hepatic porphyria.
Q2
What is the best initial biochemical test during the attack?
Reveal answer and rationale
✓Correct answer: A. Random urine porphobilinogen normalized to creatinine
Urinary porphobilinogen is markedly elevated during most acute attacks and is the key initial diagnostic test. Samples should be protected from light.
Q3
What is the appropriate treatment for a severe attack with neurologic manifestations?
Reveal answer and rationale
✓Correct answer: A. Intravenous hemin with supportive treatment
Severe attacks require intravenous hemin, withdrawal of precipitating medications, carbohydrate support, careful correction of hyponatremia, pain control, and respiratory monitoring.
Q4
Which advice is most appropriate for prevention?
Reveal answer and rationale
✓Correct answer: A. Avoid prolonged fasting and verify medication safety before starting new drugs
Fasting, severe carbohydrate restriction, alcohol, hormonal changes, illness, and porphyrinogenic medications can precipitate attacks. Medication safety should be checked using a reliable porphyria-drug resource.
Diagnosis: Acute intermittent porphyria causing a severe neurovisceral attack.
Key differentials
Bowel obstruction
Appendicitis
Guillain–Barré syndrome
Lead toxicity
Hyponatremic encephalopathy
Psychiatric illness
Opioid withdrawal
Key investigations
Urinary porphobilinogen and aminolevulinic acid
Electrolytes
Renal and liver function
ECG
Respiratory-force monitoring
Genetic testing after biochemical confirmation
Medication and supplement review
Treatment principles
Discontinue triggering drugs
Intravenous hemin for severe attacks
Glucose or carbohydrate support in selected mild disease
Correct fluid and sodium disturbances carefully
Treat pain, nausea, hypertension, and tachycardia safely
Monitor for bulbar or respiratory weakness
Botanical safety: Herbal products may contain unrecognized porphyrinogenic compounds or induce hepatic enzymes.
Clinical Pearl: Severe abdominal pain can occur with a relatively benign abdominal examination.
NPLEX Trap: AIP does not characteristically cause photosensitive blistering skin lesions.
AGA guidance identifies urinary porphobilinogen testing during symptoms, removal of triggers, carbohydrate support, and intravenous hemin as central management principles.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
A 58-year-old man with high-grade lymphoma develops nausea, muscle cramps, weakness, reduced urine output, and palpitations 24 hours after beginning chemotherapy.
Which medication rapidly lowers existing uric acid?
Reveal answer and rationale
✓Correct answer: A. Rasburicase
Rasburicase enzymatically converts existing uric acid into a more soluble metabolite. Allopurinol prevents formation of additional uric acid but does not rapidly remove uric acid already present.
Q3
In which patient is rasburicase contraindicated?
Reveal answer and rationale
✓Correct answer: A. A patient with glucose-6-phosphate dehydrogenase deficiency
Rasburicase can cause severe oxidative hemolysis and methemoglobinemia in G6PD deficiency.
Q4
How should asymptomatic hypocalcemia generally be approached?
Reveal answer and rationale
✓Correct answer: A. Avoid routine calcium unless clinically necessary because calcium-phosphate precipitation may worsen
Calcium is administered when significant symptoms such as tetany, seizure, or dangerous arrhythmia are present. Unnecessary calcium can increase tissue and renal calcium-phosphate deposition.
Diagnosis: Acute tumour lysis syndrome with cardiac and renal complications.
Key risk factors
High-grade lymphoma or leukemia
Large tumour burden
High LDH
Highly treatment-sensitive malignancy
Pre-existing kidney disease
Dehydration
Elevated baseline uric acid
Key investigations
Potassium
Phosphate
Calcium
Uric acid
Creatinine
LDH
ECG
Continuous cardiac monitoring in severe disease
Frequent repeat metabolic testing
Treatment principles
Aggressive but individualized intravenous hydration
Immediate hyperkalemia treatment
Rasburicase when appropriate
Allopurinol for selected prophylaxis
Manage phosphate and symptomatic hypocalcemia
Nephrology consultation
Dialysis for refractory electrolyte abnormalities, volume overload, severe acidosis, or uremia
Nutrition and supplement safety: Potassium, phosphate, calcium, and vitamin D supplements should not be given without reviewing current laboratory abnormalities.
Clinical Pearl: Hyperphosphatemia may become a major driver of ongoing kidney injury.
NPLEX Trap: Allopurinol prevents new uric-acid formation but does not remove existing uric acid.
Current TLS guidance emphasizes risk-based prevention, hydration, frequent biochemical monitoring, and rapid treatment with uric-acid-lowering therapy.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
Acute hypermetabolism after exposure to succinylcholine or a volatile anesthetic, with rapidly increasing CO₂, rigidity, tachycardia, acidosis, hyperkalemia, rhabdomyolysis, and hyperthermia, is characteristic of malignant hyperthermia.
Q2
What is the first specific medication?
Reveal answer and rationale
✓Correct answer: A. Intravenous dantrolene
Dantrolene reduces abnormal skeletal-muscle calcium release. It should be administered immediately while triggering agents are discontinued and resuscitative care begins.
Q3
Which finding is often an early clue?
Reveal answer and rationale
✓Correct answer: A. Unexpected rapid increase in end-tidal CO₂
Hypercapnia despite increased minute ventilation is often an early manifestation. Marked hyperthermia may develop later.
Q4
Which long-term advice is essential after recovery?
Reveal answer and rationale
✓Correct answer: A. Refer for malignant-hyperthermia susceptibility assessment and avoid triggering anesthetics
The patient and close relatives may require genetic or contracture testing. The event must be documented clearly, and future anesthesia should use nontriggering techniques.
Diagnosis: Malignant hyperthermia triggered by succinylcholine and volatile anesthetic exposure.
Key triggers
Succinylcholine
Volatile inhalational anesthetics
Key manifestations
Rapidly increasing end-tidal CO₂
Muscle rigidity
Tachycardia
Metabolic and respiratory acidosis
Hyperkalemia
Rhabdomyolysis
Hyperthermia
Arrhythmia
Acute kidney injury
DIC
Treatment principles
Stop triggering agents
Give 100% oxygen and hyperventilate
Administer dantrolene promptly
Active cooling when hyperthermia is present
Treat hyperkalemia and acidosis
Monitor CK, electrolytes, coagulation, urine output, and recurrence
Continue post-crisis monitoring
Naturopathic safety: No supplement or antipyretic substitutes for dantrolene and anesthetic-crisis management.
Clinical Pearl: Hyperthermia is not always the first abnormality.
NPLEX Trap: Acetaminophen does not correct malignant-hyperthermia physiology.
MHAUS identifies immediate trigger discontinuation, hyperventilation, cooling when indicated, and rapid dantrolene administration as the core emergency response.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
A 22-year-old woman develops insomnia, paranoia, agitation, and bizarre behaviour over ten days. She subsequently develops seizures, mutism, repetitive lip-smacking movements, limb dyskinesias, and episodes of severe tachycardia and blood-pressure fluctuation.
Investigations:
Toxicology testing: negative
Brain MRI: mild nonspecific changes
EEG: diffuse slowing
CSF: lymphocytic pleocytosis
Pelvic ultrasound: ovarian mass
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: A. Anti-NMDA receptor encephalitis associated with ovarian teratoma
Rapid psychiatric change followed by seizures, speech dysfunction, dyskinesias, reduced consciousness, and autonomic instability strongly suggests anti-NMDA receptor encephalitis.
Q2
Which test best confirms the diagnosis?
Reveal answer and rationale
✓Correct answer: A. CSF anti-NMDA receptor antibody testing
CSF antibody testing is central to confirmation. Serum testing alone can produce misleading results and should be interpreted cautiously.
Q3
What is the appropriate initial treatment?
Reveal answer and rationale
✓Correct answer: A. Tumour removal when present plus corticosteroids, IV immunoglobulin, or plasma exchange
Early immunotherapy and removal of an associated ovarian teratoma improve the likelihood of recovery. Second-line immunotherapy is considered when first-line treatment is inadequate.
Q4
Which complication requires intensive monitoring?
Reveal answer and rationale
✓Correct answer: A. Autonomic instability and central hypoventilation
Patients may develop arrhythmia, severe blood-pressure fluctuations, fever, respiratory failure, aspiration, and prolonged seizures.
Diagnosis: Anti-NMDA receptor autoimmune encephalitis associated with an ovarian teratoma.
Key differentials
Viral encephalitis
Toxic ingestion
Primary psychotic illness
Neuroleptic malignant syndrome
Serotonin syndrome
Status epilepticus
Lupus cerebritis
Key investigations
CSF cell count, protein, oligoclonal bands, and antibody testing
EEG
Brain MRI
Infectious encephalitis testing
Pelvic imaging
Age- and sex-appropriate tumour assessment
Continuous cardiac and respiratory monitoring in severe disease
Treatment principles
Stabilize airway and seizures
Treat autonomic instability
Remove associated tumour
First-line immunotherapy
Escalate to second-line treatment when necessary
Begin rehabilitation early
Avoid assuming the illness is purely psychiatric
Pharmacology safety: Antipsychotic medications may worsen rigidity, autonomic instability, or movement disorders and require cautious use.
Clinical Pearl: Brain MRI can be normal despite severe disease.
NPLEX Trap: New psychosis accompanied by seizures and dyskinesias requires neurologic investigation.
Canadian and international guidance supports early immunotherapy, CSF antibody testing, tumour screening, and tumour removal when applicable.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 421
CARCINOID SYNDROME WITH CARCINOID HEART DISEASEClinical Case 421
A 59-year-old woman presents with episodic facial flushing, watery diarrhea, wheezing, weight loss, and progressive leg swelling.
Examination:
Facial telangiectasia
Elevated jugular venous pressure
Systolic murmur increasing with inspiration
Hepatomegaly
Peripheral edema
Imaging identifies an ileal neuroendocrine tumour with multiple liver metastases.
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: A. Carcinoid syndrome with right-sided carcinoid heart disease
Flushing, secretory diarrhea, bronchospasm, metastatic neuroendocrine tumour, tricuspid or pulmonary valve disease, and right-sided heart failure indicate carcinoid syndrome with cardiac involvement.
Q2
Which biochemical test supports the diagnosis?
Reveal answer and rationale
✓Correct answer: A. Twenty-four-hour urinary or plasma 5-hydroxyindoleacetic acid
5-HIAA is the principal serotonin metabolite and is commonly elevated in serotonin-secreting neuroendocrine tumours. Medication and dietary interference must be considered.
Q3
What is the principal medication for controlling flushing and diarrhea?
Reveal answer and rationale
✓Correct answer: A. A somatostatin analogue
Octreotide or lanreotide reduces mediator release and improves carcinoid-syndrome symptoms. Additional tumour-directed treatment depends on tumour location, extent, and progression.
Q4
Which nutritional deficiency can occur because tryptophan is diverted into serotonin production?
Reveal answer and rationale
✓Correct answer: A. Niacin deficiency
Substantial tryptophan diversion may reduce niacin synthesis and produce pellagra-like dermatitis, diarrhea, and neurocognitive symptoms.
Tumour-directed surgery or systemic therapy when appropriate
Manage right-sided heart failure
Evaluate for valve surgery in advanced cardiac disease
Prevent perioperative carcinoid crisis
Monitor nutrition and fat-soluble vitamin status
Botanical safety: Serotonergic supplements such as 5-HTP may complicate symptoms and biochemical interpretation.
Clinical Pearl: Carcinoid heart disease predominantly damages right-sided valves because vasoactive substances are normally inactivated in the lungs.
NPLEX Trap: Antidiarrheal medication alone does not treat serotonin secretion or the underlying tumour.
ENETS guidance recommends biochemical assessment, somatostatin-analogue treatment, cardiac surveillance, and multidisciplinary management of carcinoid heart disease.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 422
IgG4-RELATED DISEASE WITH AUTOIMMUNE PANCREATITIS AND RETROPERITONEAL FIBROSISClinical Case 422
A 63-year-old man presents with painless jaundice, weight loss, dry mouth, bilateral salivary-gland enlargement, and dull flank pain.
Investigations:
Pancreas: diffusely enlarged with a capsule-like rim
Common bile duct: narrowed
CT abdomen: soft-tissue encasement of the abdominal aorta and ureters
Bilateral hydronephrosis
Serum IgG4: elevated
Creatinine: increasing
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: A. IgG4-related disease involving the pancreas, salivary glands, biliary tract, and retroperitoneum
Autoimmune pancreatitis, salivary-gland enlargement, biliary involvement, and retroperitoneal fibrosis causing ureteral obstruction are classic manifestations of systemic IgG4-related disease.
Q2
Which finding is characteristic on tissue biopsy?
Reveal answer and rationale
✓Correct answer: A. Lymphoplasmacytic inflammation with storiform fibrosis and obliterative phlebitis
Characteristic histology and IgG4-positive plasma-cell infiltration support the diagnosis. Histology varies by organ and must be interpreted in the full clinical context.
Q3
Why is tissue diagnosis important before treatment when feasible?
Reveal answer and rationale
✓Correct answer: A. Malignancy and other inflammatory diseases can closely mimic IgG4-related disease
Pancreatic, biliary, lymph-node, and retroperitoneal malignancies can resemble IgG4-related disease. Elevated serum IgG4 is neither completely sensitive nor specific.
Q4
What is the appropriate management?
Reveal answer and rationale
✓Correct answer: A. Relieve obstructive complications and begin specialist-directed glucocorticoid treatment
Active organ-threatening disease generally requires glucocorticoid induction. Ureteral or biliary obstruction may require immediate drainage or stenting. Rituximab or other strategies may be used for selected relapsing or refractory disease.
Clinical Pearl: Serum IgG4 can be normal in some affected patients and elevated in unrelated conditions.
NPLEX Trap: Do not label a pancreatic mass as autoimmune disease without adequately excluding malignancy.
Revised diagnostic criteria combine clinical or radiologic disease, serologic findings, and characteristic pathology rather than relying on serum IgG4 alone.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 423
D-LACTIC ACIDOSIS IN SHORT-BOWEL SYNDROMEClinical Case 423
A 37-year-old man with extensive small-bowel resection and an intact colon presents with episodic confusion, slurred speech, irritability, and unsteady gait.
His symptoms commonly begin several hours after consuming large amounts of sweetened beverages and refined carbohydrates.
Laboratory findings during an episode:
Bicarbonate: 12 mmol/L
Anion gap: elevated
Standard serum L-lactate: normal
Glucose: normal
Renal function: stable
Toxicology testing: negative
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: A. D-lactic acidosis
Short-bowel syndrome with colonic continuity, carbohydrate-triggered neurologic symptoms, and unexplained high-anion-gap acidosis with a normal routine lactate level strongly suggest D-lactic acidosis.
Q2
Why may the standard lactate result be normal?
Reveal answer and rationale
✓Correct answer: A. Routine assays primarily measure L-lactate rather than D-lactate
D-lactate requires a specialized assay. Failure to recognize this limitation can delay diagnosis.
Q3
What is the most appropriate acute management?
Reveal answer and rationale
✓Correct answer: A. Reduce carbohydrate substrate, provide fluid and acid-base support, and consider targeted antibiotic therapy
Treatment reduces fermentable carbohydrate reaching colonic bacteria, corrects dehydration and acidosis, and may use antibiotics to reduce D-lactate-producing organisms.
Q4
Which dietary strategy helps reduce recurrence?
Reveal answer and rationale
✓Correct answer: A. Individualized restriction of rapidly absorbed simple carbohydrates
Large carbohydrate loads provide substrate for colonic bacterial production of D-lactate. Nutrition must still provide adequate calories and micronutrients under specialist supervision.
Probiotic safety: Probiotic use should be individualized because some organisms may contribute to D-lactate production.
Clinical Pearl: Neurologic findings can resemble alcohol intoxication.
NPLEX Trap: A normal routine lactate does not exclude D-lactic acidosis.
Reviews of D-lactic acidosis emphasize carbohydrate restriction, correction of acidosis and dehydration, and selective alteration of intestinal bacteria.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 424
HEPATITIS C-ASSOCIATED MIXED CRYOGLOBULINEMIC VASCULITISClinical Case 424
A 56-year-old woman with untreated chronic hepatitis C presents with fatigue, joint pain, painful numbness of the feet, and a purpuric rash over both legs.
Physical examination:
Palpable purpura
Mild leg edema
Reduced distal sensation
Hypertension
Laboratory findings:
Creatinine: increasing
Urinalysis: hematuria, proteinuria, and red-cell casts
C4: markedly reduced
Rheumatoid factor: positive
Hepatitis C RNA: positive
Serum cryoglobulin: initially reported negative
Kidney biopsy shows membranoproliferative glomerulonephritis with immune-complex deposition.
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: A. Hepatitis C-associated mixed cryoglobulinemic vasculitis
The combination of chronic hepatitis C, palpable purpura, arthralgia, neuropathy, low C4, positive rheumatoid factor, and immune-complex glomerulonephritis is characteristic of mixed cryoglobulinemic vasculitis.
Q2
Why might the cryoglobulin result be falsely negative?
Reveal answer and rationale
✓Correct answer: A. The blood sample was not kept warm before serum separation
Cryoglobulins may precipitate before laboratory processing if the sample is not maintained at an appropriate warm temperature, producing a falsely negative result.
Q3
What is the central treatment for clinically significant hepatitis C-associated disease?
Reveal answer and rationale
✓Correct answer: A. Direct-acting antiviral therapy
Eradication of hepatitis C treats the underlying antigenic driver. Mild-to-moderate disease may improve substantially after effective antiviral treatment.
Q4
What additional treatment may be required for rapidly progressive glomerulonephritis or another life-threatening manifestation?
Reveal answer and rationale
✓Correct answer: A. Rituximab-based immunosuppression with possible plasma exchange
Severe renal, neurologic, pulmonary, gastrointestinal, or hyperviscosity manifestations may require urgent immunosuppression and plasma exchange in addition to antiviral therapy.
Diagnosis: HCV-associated mixed cryoglobulinemic vasculitis with membranoproliferative glomerulonephritis and neuropathy.
Key manifestations
Palpable purpura
Arthralgia
Weakness
Peripheral neuropathy
Glomerulonephritis
Skin ulceration
Mesenteric ischemia
Pulmonary hemorrhage in severe disease
Key investigations
Hepatitis C antibody and RNA
Cryoglobulin testing with correct handling
C3 and C4
Rheumatoid factor
Urinalysis and protein quantification
Kidney function
Kidney biopsy when indicated
Assessment for B-cell lymphoproliferative disease
Treatment principles
Direct-acting antiviral treatment
Rituximab for severe vasculitis
Plasma exchange for selected life-threatening disease
Glucocorticoid use individualized to severity
Control blood pressure and renal complications
Monitor after viral eradication because vasculitis may persist or relapse
Botanical safety: Supplements marketed for “immune stimulation” or liver cleansing can interact with antiviral and immunosuppressive treatment.
Clinical Pearl: Low C4 is a strong laboratory clue in mixed cryoglobulinemia.
NPLEX Trap: One negative cryoglobulin test does not exclude disease when collection and processing were inadequate.
HCV-associated cryoglobulinemic vasculitis requires treatment of the infection, with rituximab and plasma exchange considered for severe organ-threatening disease.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
A 52-year-old man presents with progressive numbness, burning pain, and weakness of both legs. He has difficulty climbing stairs and has recently begun using a cane.
Additional findings:
Hepatosplenomegaly
Gynecomastia
Hypothyroidism
Hyperpigmentation
Hemangioma-like skin lesions
Peripheral edema
Papilledema
Thrombocytosis
Investigations:
Nerve conduction: demyelinating polyneuropathy
Serum immunofixation: small monoclonal lambda protein
VEGF: markedly elevated
CT: several sclerotic bone lesions
Bone marrow: clonal plasma-cell disorder
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: A. POEMS syndrome
Polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma-cell disease, skin changes, elevated VEGF, edema, thrombocytosis, papilledema, and sclerotic bone lesions form the classic POEMS syndrome pattern.
Q2
Which two findings are mandatory major criteria?
Reveal answer and rationale
✓Correct answer: A. Polyneuropathy and a monoclonal plasma-cell proliferative disorder
The diagnostic framework requires both polyneuropathy and a monoclonal plasma-cell disorder, plus additional major and minor criteria.
Q3
Which biomarker is particularly useful for supporting diagnosis and monitoring response?
Reveal answer and rationale
✓Correct answer: A. Vascular endothelial growth factor
VEGF is frequently markedly elevated and reflects disease activity. It is interpreted alongside the clinical and hematologic findings.
Q4
What is the fundamental treatment principle?
Reveal answer and rationale
✓Correct answer: A. Eradicate or suppress the underlying plasma-cell clone
Localized disease driven by an isolated sclerotic plasmacytoma may be treated with radiation. Diffuse or marrow-based disease generally requires systemic plasma-cell-directed therapy, with autologous stem-cell transplantation considered in eligible patients.
Diagnosis: POEMS syndrome caused by an underlying lambda-restricted plasma-cell neoplasm.
Mandatory major criteria
Polyneuropathy
Monoclonal plasma-cell proliferative disorder
Additional major criteria
Sclerotic bone lesion
Castleman disease
Elevated VEGF
Minor criteria include
Organomegaly
Extravascular volume overload
Endocrinopathy
Skin changes
Papilledema
Thrombocytosis or polycythemia
Key investigations
Nerve-conduction testing
Serum and urine immunofixation
Free-light-chain assessment
VEGF
Bone-marrow examination
Whole-body imaging for sclerotic lesions
Endocrine evaluation
Pulmonary and cardiac assessment
Treatment principles
Local radiation for appropriately selected isolated disease
Systemic plasma-cell-directed therapy for disseminated disease
Consider autologous stem-cell transplantation
Manage thrombosis risk, edema, endocrine abnormalities, pain, and rehabilitation
Monitor VEGF, neurologic status, and hematologic response
Supplement safety: High-dose pyridoxine can itself cause sensory neuropathy and should not be used indiscriminately.
Clinical Pearl: POEMS usually causes sclerotic rather than classic punched-out lytic bone lesions.
NPLEX Trap: Do not diagnose CIDP alone when neuropathy is accompanied by monoclonal lambda protein, endocrinopathy, organomegaly, skin changes, and elevated VEGF.
Contemporary diagnostic frameworks require polyneuropathy and a monoclonal plasma-cell disorder, with therapy directed at the underlying plasma-cell clone.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 426
SYSTEMIC MASTOCYTOSIS WITH RECURRENT ANAPHYLAXISClinical Case 426
A 46-year-old man presents after developing flushing, generalized pruritus, abdominal cramping, wheezing, and syncope following a wasp sting.
He reports several previous unexplained episodes of flushing and lightheadedness. Examination after stabilization reveals multiple brown macules that become raised and pruritic when rubbed.
Investigations:
Baseline serum tryptase: persistently elevated
Acute tryptase: significantly increased from baseline
Bone-marrow biopsy: dense mast-cell aggregates
KIT D816V mutation: detected
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: A. Systemic mastocytosis with mast-cell-mediated anaphylaxis
Recurrent systemic mast-cell symptoms, persistently elevated baseline tryptase, characteristic skin lesions, clonal mast-cell aggregates, and a KIT mutation support systemic mastocytosis.
Q2
What is the first-line treatment during the acute hypotensive reaction?
Reveal answer and rationale
✓Correct answer: A. Intramuscular epinephrine
Anaphylaxis requires immediate intramuscular epinephrine. Antihistamines and other mediator-directed treatments are adjuncts and must not delay epinephrine.
Q3
Which change in serum tryptase supports acute systemic mast-cell activation?
Reveal answer and rationale
✓Correct answer: A. An increase exceeding the patient’s baseline by approximately 20% plus 2 ng/mL
Comparison with the individual baseline is more informative than applying one universal acute tryptase threshold.
Q4
Which long-term safety measure is essential?
Reveal answer and rationale
✓Correct answer: A. Carry epinephrine auto-injectors and receive trigger-specific emergency education
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 427
HEREDITARY ANGIOEDEMA WITH LARYNGEAL ATTACKClinical Case 427
A 23-year-old woman presents with progressive tongue swelling, throat tightness, hoarseness, and difficulty swallowing.
She has no urticaria or pruritus. Previous episodes involved severe abdominal pain and swelling of the hands. Her father died unexpectedly during an episode of throat swelling.
Laboratory findings from a previous assessment:
C4: reduced
C1 inhibitor functional activity: reduced
C1 inhibitor level: reduced
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: A. Hereditary angioedema caused by C1-inhibitor deficiency
Recurrent nonpruritic angioedema, abdominal attacks, absent urticaria, a family history, low C4, and reduced C1-inhibitor quantity and function indicate type 1 hereditary angioedema.
Q2
What is the immediate priority?
Reveal answer and rationale
✓Correct answer: A. Protect the airway and administer specific on-demand HAE treatment
Laryngeal HAE can rapidly become fatal. Airway planning and immediate bradykinin-directed treatment are essential.
Q3
Which therapy is appropriate for an acute attack?
Reveal answer and rationale
✓Correct answer: A. C1-inhibitor concentrate or an approved bradykinin/kallikrein-directed treatment
Q4
Which medication can worsen bradykinin-mediated angioedema?
Diagnosis: Type 1 hereditary angioedema with an acute upper-airway attack.
Key investigations
C4
C1-inhibitor antigen level
C1-inhibitor functional activity
C1q when acquired angioedema is suspected
Genetic testing in selected cases
Treatment principles
Treat attacks as early as possible
Secure the airway when progression threatens ventilation
Ensure access to more than one on-demand treatment dose
Consider long-term prophylaxis based on attack burden
Provide procedure-related prophylaxis when indicated
Pharmacology safety: Antihistamines, corticosteroids, and epinephrine generally do not reverse the core bradykinin-mediated process, although epinephrine may be given when the diagnosis is uncertain and anaphylaxis remains possible.
Clinical Pearl: The absence of urticaria strongly supports a bradykinin-mediated process.
NPLEX Trap: Do not wait for visible respiratory distress before treating progressive laryngeal swelling.
Reference basis: WAO/EAACI guidance recommends early on-demand treatment with C1 inhibitor, icatibant, or ecallantide where available.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 428
STRONGYLOIDES HYPERINFECTION AFTER CORTICOSTEROID THERAPYClinical Case 428
Continue until stool and sputum remain negative for an appropriate period
Treat associated bacterial sepsis
Screen at-risk patients before immunosuppression when feasible
Botanical safety: No antiparasitic botanical preparation should replace ivermectin in hyperinfection.
Clinical Pearl: Eosinophilia may disappear during severe disseminated disease.
NPLEX Trap: Do not give repeated corticosteroids to an at-risk patient without considering latent Strongyloides infection.
Reference basis: CDC guidance identifies ivermectin as first-line therapy and recommends daily treatment in hyperinfection until parasitologic clearance.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 429
DISSEMINATED HISTOPLASMOSIS DURING TNF-INHIBITOR THERAPYClinical Case 429
Liposomal amphotericin B for severe disseminated disease
Step down to prolonged itraconazole after stabilization
Monitor itraconazole concentrations and interactions
Withhold significant immunosuppression when appropriate
Monitor antigen levels for response and recurrence
Pharmacology safety: Itraconazole has substantial CYP-mediated interactions and can worsen heart failure in susceptible patients.
Clinical Pearl: TNF is important for granuloma maintenance, making TNF inhibitors a major risk factor for disseminated fungal disease.
NPLEX Trap: Do not intensify immunosuppression for a presumed inflammatory-disease flare before excluding invasive fungal infection.
Reference basis: IDSA guidance and updated reviews identify TNF inhibitors as a major risk factor and amphotericin-to-itraconazole therapy as standard for severe disseminated disease.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
Echocardiography and blood-culture-negative endocarditis evaluation
Treatment principles
Use therapy effective in the CNS
Continue prolonged eradication treatment
Monitor for relapse
Recognize immune-reconstitution inflammatory syndrome after treatment begins
Nutrition: Correct malnutrition and micronutrient deficits, but nutritional therapy does not eradicate infection.
Clinical Pearl: Arthritis may precede intestinal manifestations by years.
NPLEX Trap: Do not begin immunosuppression for presumed seronegative arthritis before reconsidering chronic infection in a patient with weight loss and malabsorption.
Reference basis: Clinical trials and contemporary reviews support an initial ceftriaxone- or meropenem-based phase followed by prolonged oral treatment.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 431
NEUROMYELITIS OPTICA SPECTRUM DISORDERClinical Case 431
Serum aquaporin-4 IgG using an appropriate cell-based assay
MOG-IgG when indicated
MRI brain, optic nerves, and entire spinal cord
CSF testing
Autoimmune-disease assessment
Treatment principles
Treat acute relapse immediately
Use plasma exchange early in severe attacks
Begin relapse-prevention immunotherapy
Avoid assuming that every demyelinating disorder should receive conventional MS therapy
Clinical Pearl: Longitudinally extensive transverse myelitis spans at least three vertebral segments.
NPLEX Trap: Do not delay plasma exchange until all glucocorticoid doses are completed when a severe attack is rapidly progressing.
Reference basis: Current NMOSD recommendations support high-dose glucocorticoids and early apheresis for acute attacks.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 432
LAMBERT–EATON MYASTHENIC SYNDROMEClinical Case 432
A 63-year-old man with a 45-pack-year smoking history presents with proximal leg weakness, dry mouth, erectile dysfunction, and difficulty rising from a chair.
Examination:
Reduced reflexes
Leg strength briefly improves after repeated contraction
Minimal ocular involvement
Testing demonstrates P/Q-type voltage-gated calcium-channel antibodies and an incremental response on high-frequency repetitive nerve stimulation.
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: A. Lambert–Eaton myasthenic syndrome
Q2
Which associated malignancy must be investigated?
Reveal answer and rationale
✓Correct answer: A. Small-cell lung carcinoma
Q3
Which finding helps distinguish LEMS from myasthenia gravis?
Reveal answer and rationale
✓Correct answer: A. Reduced reflexes with temporary facilitation after exercise
Q4
Which medication is used for symptomatic improvement?
Continued malignancy surveillance when initial evaluation is negative
Treatment principles
Treat the underlying cancer
Amifampridine for symptomatic weakness
Consider immunotherapy for significant autoimmune disease
Monitor swallowing and respiratory function in severe presentations
Pharmacology safety: Amifampridine can increase seizure risk and requires individualized dosing.
Clinical Pearl: Strength and reflexes may transiently improve after brief exercise.
NPLEX Trap: Do not diagnose myasthenia gravis automatically when autonomic symptoms and absent reflexes are prominent.
Reference basis: Amifampridine is an approved symptomatic treatment, and contemporary criteria emphasize electrophysiology, calcium-channel antibodies, and SCLC investigation.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 433
NATALIZUMAB-ASSOCIATED PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHYClinical Case 433
A 42-year-old woman with multiple sclerosis treated with natalizumab develops progressive right-arm clumsiness, expressive-language difficulty, visual-field loss, and personality change over three weeks.
MRI shows asymmetric subcortical white-matter lesions without substantial mass effect. CSF JC-virus PCR is positive.
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: A. Progressive multifocal leukoencephalopathy
Q2
What causes PML?
Reveal answer and rationale
✓Correct answer: A. Reactivation of JC polyomavirus during impaired cellular immunity
Q3
What is the central management principle?
Reveal answer and rationale
✓Correct answer: A. Stop the responsible immunosuppressive therapy and restore immune function
Q4
What complication can occur during immune recovery?
Reveal answer and rationale
✓Correct answer: A. Immune-reconstitution inflammatory syndrome
Repeat ultrasensitive PCR when suspicion remains high
Brain biopsy in selected unresolved cases
HIV and immune-status assessment
Treatment principles
Discontinue natalizumab or other implicated therapy
Accelerate drug removal in selected cases
Monitor and treat PML-IRIS
Provide seizure, swallowing, and rehabilitation care
Clinical Pearl: CSF PCR can initially be negative when viral burden is low.
NPLEX Trap: A slowly progressive, atypical neurologic syndrome during natalizumab treatment should not automatically be labelled an MS relapse.
Reference basis: Diagnostic guidance emphasizes MRI plus CSF JC-virus PCR and restoration of immune surveillance.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 434
PAROXYSMAL NOCTURNAL HEMOGLOBINURIA WITH BUDD–CHIARI SYNDROMEClinical Case 434
Consider stem-cell transplantation in selected severe marrow failure
Clinical Pearl: Unexplained hepatic, portal, cerebral, or abdominal venous thrombosis should prompt consideration of PNH.
NPLEX Trap: A negative direct antiglobulin test does not mean hemolysis is absent.
Reference basis: Contemporary hematology reviews identify unusual-site thrombosis as a major PNH manifestation and complement inhibition plus anticoagulation as central treatment.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 435
WALDENSTRÖM MACROGLOBULINEMIA WITH HYPERVISCOSITYClinical Case 435
Delay viscosity-increasing transfusion when clinically possible
Monitor IgM flare with selected therapy
Clinical Pearl: Symptoms, funduscopic findings, and clinical urgency are more important than one universal viscosity threshold.
NPLEX Trap: Plasma exchange provides rapid stabilization but does not eradicate the underlying clone.
Reference basis: Hematology and emergency guidance identifies plasmapheresis as the acute treatment of symptomatic IgM hyperviscosity.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
Clinical Pearl: Acute chest syndrome may develop after admission for an uncomplicated pain crisis.
NPLEX Trap: Do not attribute new hypoxemia to opioid use alone without obtaining chest imaging.
Reference basis: Sickle-cell guidance recommends incentive spirometry, antimicrobial therapy, oxygen support, and early transfusion for hypoxic or progressive disease.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 437
G6PD DEFICIENCY WITH OXIDATIVE HEMOLYSIS AND METHEMOGLOBINEMIAClinical Case 437
G6PD activity, repeated after recovery if initially normal
Treatment principles
Stop the trigger
Treat infection
Oxygen and supportive care
Transfuse severe symptomatic anemia
Use expert-guided alternatives for significant methemoglobinemia
Clinical Pearl: G6PD testing during an acute hemolytic episode may be falsely normal because older, enzyme-deficient cells have already been destroyed.
NPLEX Trap: Do not reflexively give methylene blue to a patient with suspected G6PD deficiency.
Reference basis: Current reviews emphasize trigger withdrawal, supportive care, and avoidance of oxidant exposures.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 438
STATIN-ASSOCIATED IMMUNE-MEDIATED NECROTIZING MYOPATHYClinical Case 438
Consider IV immunoglobulin early in anti-HMGCR disease
Use rehabilitation after inflammation is controlled
Monitor swallowing and respiratory involvement
Clinical Pearl: Persistent progression after statin discontinuation is the critical diagnostic clue.
NPLEX Trap: Do not tell a patient to “exercise through” severe active necrotizing myopathy.
Reference basis: Contemporary reviews support immunotherapy, with anti-HMGCR disease often responding to IV immunoglobulin.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 439
ANTISYNTHETASE SYNDROME WITH INTERSTITIAL LUNG DISEASEClinical Case 439
Clinical Pearl: ILD can dominate the presentation even when muscle weakness is modest.
NPLEX Trap: Do not exclude inflammatory myositis because pulmonary symptoms appeared first.
Reference basis: ACR/CHEST guidance and contemporary reviews support immunosuppressive treatment and close monitoring for myositis-associated ILD.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 440
RELAPSING POLYCHONDRITIS WITH AIRWAY COLLAPSEClinical Case 440
Evaluation for associated autoimmune or hematologic disease
Treatment principles
Stabilize threatened airway
Systemic glucocorticoids
Steroid-sparing or biologic treatment for significant disease
Airway dilation, stenting, or surgery when required
Physical medicine safety: Cervical manipulation and forceful airway techniques are inappropriate during active airway compromise.
Clinical Pearl: Wheezing in relapsing polychondritis may reflect dynamic central-airway collapse rather than asthma.
NPLEX Trap: Do not perform routine spirometry or bronchoscopy without considering the risk of critical airway deterioration.
Reference basis: Airway involvement is a major cause of morbidity and may require early immunosuppression and interventional management.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 441
AUTOIMMUNE HEPATITIS–PRIMARY BILIARY CHOLANGITIS OVERLAPClinical Case 441
ANA, smooth-muscle antibody, and antimitochondrial antibody
Liver biopsy
Imaging to exclude mechanical biliary obstruction
Bone and fat-soluble-vitamin assessment
Treatment principles
Ursodeoxycholic acid for cholestatic disease
Glucocorticoid-based immunosuppression for active interface hepatitis
Monitor biochemical response
Screen for cirrhosis-related complications
Botanical safety: Kava, concentrated green-tea extract, and other hepatotoxic supplements should be discontinued during active liver injury.
Clinical Pearl: Overlap is a clinical phenotype requiring evidence of both parent diseases, not merely one positive antibody.
NPLEX Trap: Do not treat severe interface hepatitis with ursodeoxycholic acid alone.
Reference basis: Hepatology guidance supports combined UDCA and immunosuppressive treatment when both cholestatic and hepatitis features are present.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
Consider transplant-centre assessment for persistent failure
Clinical Pearl: Aminotransferase levels may be only moderately elevated despite severe liver failure.
NPLEX Trap: Do not delay delivery while waiting for liver biopsy.
Reference basis: Obstetric and hepatology literature identifies prompt delivery and intensive supportive care as the key interventions.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 443
HELLP SYNDROME WITH SUBCAPSULAR HEPATIC HEMATOMAClinical Case 443
Activate obstetric, anesthesia, surgery, interventional-radiology, and transfusion teams
Control severe hypertension
Administer magnesium when indicated
Correct coagulopathy
Deliver after maternal stabilization
Manage rupture with surgery or embolization when required
Physical examination safety: Avoid repeated forceful palpation over a suspected hepatic hematoma.
Clinical Pearl: Severe epigastric or right-upper-quadrant pain in HELLP may precede catastrophic rupture.
NPLEX Trap: Do not attribute severe upper-abdominal pain to reflux without checking blood pressure, platelets, and liver enzymes.
Reference basis: ACOG-associated evidence emphasizes hemodynamic monitoring, transfusion support, delivery planning, and intervention for rupture.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 444
ECLAMPSIA WITH POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROMEClinical Case 444
Brain imaging for atypical or persistent neurologic findings
Treatment principles
Protect airway and prevent injury
Magnesium sulfate
Treat severe hypertension
Evaluate HELLP and other complications
Deliver after stabilization
Continue postpartum monitoring
Clinical Pearl: PRES reflects vasogenic edema and is often reversible when the precipitating disorder is treated promptly.
NPLEX Trap: Do not delay magnesium and blood-pressure treatment while waiting for MRI.
Reference basis: ACOG guidance supports magnesium sulfate, urgent severe-hypertension treatment, and delivery after maternal stabilization.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 445
AMNIOTIC-FLUID EMBOLISM WITH DISSEMINATED INTRAVASCULAR COAGULATIONClinical Case 445
A 37-year-old woman develops sudden respiratory distress, cyanosis, hypotension, and loss of consciousness during labour immediately after membrane rupture.
Minutes later, she develops severe uterine and venipuncture-site bleeding.
Laboratory findings:
Platelets: rapidly falling
Fibrinogen: markedly reduced
PT and aPTT: prolonged
D-dimer: markedly elevated
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: A. Amniotic-fluid embolism
Q2
Which clinical triad is characteristic?
Reveal answer and rationale
✓Correct answer: A. Sudden hypoxemia, cardiovascular collapse, and coagulopathy
Q3
What is the appropriate management?
Reveal answer and rationale
✓Correct answer: A. Immediate advanced resuscitation with oxygenation, circulatory support, and massive-hemorrhage management
Q4
How is the diagnosis established?
Reveal answer and rationale
✓Correct answer: A. Clinically, after considering and excluding other causes of sudden obstetric collapse
Consider urgent delivery during maternal arrest when appropriate
Clinical Pearl: AFE is an anaphylactoid obstetric syndrome rather than a simple mechanical blockage by amniotic material.
NPLEX Trap: Do not wait for pathologic confirmation before resuscitation.
Reference basis: Obstetric emergency literature emphasizes immediate cardiopulmonary resuscitation and aggressive treatment of DIC and hemorrhage.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 446
FAMILIAL CHYLOMICRONEMIA SYNDROME WITH RECURRENT PANCREATITISClinical Case 446
Avoid triglyceride-raising medications when possible
Ensure adequate essential fatty acids and fat-soluble vitamins
Treat pancreatitis conventionally
Consider specialist-directed targeted therapy
Supplement safety: Fish oil and medium-chain triglycerides should not be prescribed casually; use must be individualized within the patient’s total-fat plan.
Clinical Pearl: Eruptive xanthomas and lipemia retinalis indicate extreme chylomicronemia.
NPLEX Trap: Do not recommend a ketogenic diet to a patient with familial chylomicronemia.
Reference basis: National Lipid Association guidance identifies lifelong severe fat restriction as the foundation of FCS management.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 447
MELAS WITH AN ACUTE STROKE-LIKE EPISODEClinical Case 447
A 19-year-old woman with short stature, sensorineural hearing loss, migraines, and exercise intolerance presents with seizures, vomiting, confusion, and right-sided visual loss.
NPLEX Trap: Do not assume every acute focal deficit in MELAS is a thromboembolic stroke.
Reference basis: A 2026 international consensus provides updated diagnostic and management recommendations for MELAS and stroke-like episodes.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
Carbohydrate feeding increases insulin, driving phosphate, potassium, and magnesium into cells while increasing thiamine demand and sodium-water retention.
Potential complications
Respiratory-muscle failure
Arrhythmia
Heart failure
Seizures
Rhabdomyolysis
Wernicke encephalopathy
Treatment principles
Slow or temporarily reduce feeding
Replace phosphate, potassium, and magnesium
Administer thiamine
Manage fluid balance
Monitor glucose and cardiac status
Advance nutrition gradually
Clinical Pearl: Total-body electrolyte stores can be profoundly depleted despite initially normal serum levels.
NPLEX Trap: Do not “catch up” calories rapidly in a severely malnourished patient.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 449
ZINC-INDUCED COPPER-DEFICIENCY MYELONEUROPATHYClinical Case 449
Clinical Pearl: Hematologic recovery is often faster and more complete than neurologic recovery.
NPLEX Trap: Do not assume every posterior-column syndrome is caused by vitamin B12 deficiency.
Reference basis: NIH nutritional resources recognize copper’s hematologic and neurologic roles and excessive zinc as a clinically important cause of deficiency.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 450
CHRONIC VITAMIN A TOXICITY WITH INTRACRANIAL HYPERTENSION AND LIVER INJURYClinical Case 450
Neuroimaging and lumbar-puncture assessment when appropriate
Treatment principles
Stop excess preformed vitamin A and interacting retinoids
Protect vision
Manage intracranial hypertension
Monitor liver recovery
Avoid pregnancy during and after teratogenic retinoid exposure according to medication guidance
Supplement safety: Multiple products may contain overlapping vitamin A doses. Cod-liver oil must be included in the total intake calculation.
Clinical Pearl: Serum retinol may not reliably reflect total tissue toxicity.
NPLEX Trap: Do not assume all “natural” vitamin products are safe when several retinol-containing products are combined.
Reference basis: Established nutrition guidance sets an adult tolerable upper intake level for preformed vitamin A and recognizes liver injury and teratogenicity as principal toxicity concerns.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 451
STEVENS–JOHNSON SYNDROME/TOXIC EPIDERMAL NECROLYSISClinical Case 451
A 32-year-old woman presents with fever, malaise, painful skin, mouth ulceration, red eyes, and difficulty swallowing.
Three weeks earlier, lamotrigine was started and rapidly increased for bipolar disorder.
Examination reveals:
Dusky atypical target lesions
Epidermal blistering and detachment over approximately 18% of body surface area
Positive Nikolsky sign
Hemorrhagic crusting of the lips
Conjunctival inflammation
Vulvovaginal erosions
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: B. Stevens–Johnson syndrome/TEN overlap
Painful epidermal necrosis, prominent mucosal involvement, medication exposure, and skin detachment involving 10–30% of body surface area indicate SJS/TEN overlap. SJS involves less than 10%, while TEN involves more than 30%.
Q2
What is the most important immediate action?
Reveal answer and rationale
✓Correct answer: C. Stop the suspected medication and arrange emergency specialist admission
Prompt withdrawal of the causative medication may improve survival. The patient requires multidisciplinary care in an intensive-care, burn, or specialized dermatology environment.
Q3
Which consultation is urgent even when visual acuity is initially preserved?
Reveal answer and rationale
✓Correct answer: A. Ophthalmology
Early ocular inflammation may progress to corneal ulceration, scarring, symblepharon, dry-eye disease, and permanent visual impairment.
Q4
Which future action is inappropriate?
Reveal answer and rationale
✓Correct answer: D. Rechallenging with lamotrigine to confirm causation
Intentional rechallenge after SJS/TEN is dangerous and generally contraindicated.
Botanical safety: Newly introduced herbs and supplements must also be reviewed as possible triggers. No “detoxification” therapy should delay hospital care.
Clinical Pearl: Skin pain may precede obvious blistering or detachment.
NPLEX Trap: Antihistamines do not treat epidermal necrosis.
Prompt withdrawal and intensive supportive care are central to SJS/TEN management.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
A 39-year-old man taking sertraline begins linezolid for pneumonia. He also uses dextromethorphan and St. John’s wort.
Within 12 hours, he develops agitation, diarrhea, sweating, tremor, and fever.
Examination:
Temperature: 39.3°C
HR: 138/min
BP: 174/98 mmHg
Dilated pupils
Ocular clonus
Inducible ankle clonus
Marked lower-limb hyperreflexia
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: C. Serotonin syndrome
Rapid onset following serotonergic medication interaction, together with agitation, autonomic hyperactivity, diarrhea, clonus, and hyperreflexia, indicates serotonin toxicity.
Q2
Which finding most strongly favours serotonin syndrome over neuroleptic malignant syndrome?
Reveal answer and rationale
✓Correct answer: B. Clonus and hyperreflexia
Neuromuscular excitation, particularly clonus and hyperreflexia, is characteristic of serotonin syndrome. NMS more commonly produces generalized lead-pipe rigidity and reduced or normal reflexes.
Q3
What is the first management step?
Reveal answer and rationale
✓Correct answer: A. Discontinue serotonergic agents and begin supportive care
All serotonergic contributors must be stopped. Benzodiazepine sedation, intravenous fluids, oxygenation, active cooling, and management of complications are central.
Q4
Which botanical product contributed to this patient’s risk?
Reveal answer and rationale
✓Correct answer: D. St. John’s wort
St. John’s wort has serotonergic activity and can interact with antidepressants and other serotonergic medications.
Intubation and nondepolarizing paralysis for extreme hyperthermia
Consider cyproheptadine in selected cases, recognizing that evidence is limited
Pharmacology safety: Physical restraints without adequate sedation can increase muscle activity, acidosis, and hyperthermia.
Clinical Pearl: Serotonin syndrome often begins within hours of a dose increase, overdose, or drug interaction.
NPLEX Trap: Antipyretics do not correct medication-induced muscular hyperactivity.
Hunter-type neuromuscular findings and rapid supportive management are central to diagnosis and treatment.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
Immediate poison-centre or toxicology consultation
Fomepizole
Sodium bicarbonate for significant acidosis
Thiamine and pyridoxine as metabolic cofactors
Hemodialysis for severe toxicity
Monitor calcium and renal function
Clinical Pearl: The osmolar gap may fall as the toxic alcohol is metabolized while the anion gap and organ injury worsen.
NPLEX Trap: Calcium-oxalate crystals support the diagnosis but may be absent.
CDC toxicology guidance supports early fomepizole and hemodialysis for severe acidosis or renal failure.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 454
CYANIDE POISONING AFTER SMOKE INHALATIONClinical Case 454
A 36-year-old man is rescued from an enclosed-space industrial fire.
He is confused and hypotensive and develops cardiovascular collapse despite high-concentration oxygen.
Findings:
Soot around the mouth
Severe lactic acidosis
Lactate: 14 mmol/L
Normal methemoglobin
Carboxyhemoglobin: moderately elevated
Q1
What is the most likely additional toxic exposure?
Reveal answer and rationale
✓Correct answer: D. Cyanide
Enclosed-space combustion of synthetic materials can release cyanide. Profound lactic acidosis, altered consciousness, hypotension, and cardiovascular collapse are important clues.
Q2
What is cyanide’s principal toxic mechanism?
Reveal answer and rationale
✓Correct answer: A. Inhibition of mitochondrial cytochrome oxidase
Cyanide prevents cells from using oxygen for oxidative phosphorylation, producing histotoxic hypoxia and severe lactic acidosis.
Q3
Which antidote is generally preferred in a smoke-inhalation patient?
Reveal answer and rationale
✓Correct answer: B. Hydroxocobalamin
Hydroxocobalamin binds cyanide to form cyanocobalamin. It does not induce methemoglobinemia and is therefore useful when concurrent carbon-monoxide exposure is possible.
Q4
Should treatment wait for a cyanide level?
Reveal answer and rationale
✓Correct answer: C. No; treatment is clinical when severe poisoning is strongly suspected
Cyanide assays are generally not available rapidly enough to direct emergency treatment.
Treat concurrent carbon-monoxide and burn injuries
Clinical Pearl: A normal arterial oxygen tension does not exclude cyanide toxicity because oxygen delivery may be intact while cellular use is blocked.
NPLEX Trap: Do not use nitrite-based antidotes casually when concurrent carbon-monoxide poisoning may already impair oxygen carriage.
Hydroxocobalamin is a recommended antidote for acute cyanide poisoning.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
A family eats wild mushrooms collected in a forest. Twelve hours later, a 41-year-old woman develops severe vomiting and profuse watery diarrhea.
Her symptoms briefly improve, but 36 hours after ingestion she develops jaundice, hypoglycemia, confusion, and coagulopathy.
Laboratory findings:
AST and ALT: rapidly rising
INR: 3.8
Glucose: 2.6 mmol/L
Creatinine: increasing
Lactate: elevated
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: B. Amatoxin poisoning
Delayed gastrointestinal symptoms followed by a deceptive improvement and subsequent acute hepatic failure are characteristic of amatoxin-containing mushrooms such as Amanita phalloides.
Q2
What cellular process is inhibited by amatoxin?
Reveal answer and rationale
✓Correct answer: A. RNA polymerase II-dependent protein synthesis
Q3
What is the most appropriate management?
Reveal answer and rationale
✓Correct answer: C. Immediate toxicology care, aggressive support, and early transplant-centre involvement
Patients can deteriorate after an apparent recovery. Serial liver tests, INR, glucose, lactate, renal function, and mental status are essential.
Q4
What is the definitive treatment for progressive irreversible acute liver failure?
Botanical safety: Commercial milk-thistle supplements are not equivalent to intravenous silibinin protocols studied in amatoxin poisoning.
Clinical Pearl: Delayed onset of diarrhea after mushroom ingestion is more concerning than immediate gastrointestinal upset.
NPLEX Trap: Symptomatic improvement does not mean hepatic toxicity has resolved.
Severe amatoxin poisoning requires aggressive supportive treatment and early transplant assessment.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
A 57-year-old woman develops blurred vision, diplopia, dry mouth, dysphagia, and generalized weakness after eating home-canned vegetables.
Examination:
Bilateral ptosis
Fixed or poorly reactive pupils
Dysarthria
Symmetric descending weakness
Reduced reflexes
Normal sensation
Clear mental status
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: C. Foodborne botulism
Acute bilateral cranial-nerve palsies followed by symmetric descending flaccid paralysis, autonomic symptoms, normal sensation, and preserved consciousness indicate botulism.
Q2
What is the immediate management priority?
Reveal answer and rationale
✓Correct answer: A. Respiratory monitoring and early airway support
Respiratory-muscle failure can develop rapidly. Serial vital capacity and inspiratory-force assessment are important.
Q3
When should botulinum antitoxin be administered?
Reveal answer and rationale
✓Correct answer: B. As early as possible on clinical suspicion
Antitoxin neutralizes circulating toxin but cannot reverse toxin already bound to nerve terminals. Laboratory confirmation must not delay treatment.
Q4
Which finding argues against organophosphate poisoning?
Reveal answer and rationale
✓Correct answer: D. Dry mouth without bronchorrhea or diaphoresis
Serum, stool, or food toxin testing through public health
EMG when diagnosis is uncertain
Evaluation of exposed meal companions
Treatment principles
Notify public health immediately
Administer antitoxin early
Support ventilation and swallowing
Prevent aspiration and pressure injury
Debride and treat infected wounds in wound botulism
Clinical Pearl: Patients generally remain alert and afebrile unless a secondary complication occurs.
NPLEX Trap: Do not delay antitoxin while awaiting toxin-assay results.
CDC guidelines identify early antitoxin and respiratory support as the principal treatments.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
CDC clinical guidance supports TIG, wound care, airway management, spasm control, and vaccination.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
Clindamycin when toxin-producing streptococcal or clostridial disease is suspected
Sepsis resuscitation
Intensive-care support
Clinical Pearl: Skin findings may appear modest early because the infection spreads along deeper fascial planes.
NPLEX Trap: A low-risk laboratory score cannot safely rule out necrotizing fasciitis.
CDC guidance identifies early aggressive surgery plus broad parenteral antibiotic treatment as essential.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 459
STREPTOCOCCAL TOXIC SHOCK SYNDROMEClinical Case 459
A 43-year-old woman presents with severe arm pain two days after a small skin injury.
Vital signs:
BP: 72/38 mmHg
HR: 142/min
Temperature: 39.5°C
Laboratory findings:
Creatinine: elevated
Platelets: reduced
AST and ALT: elevated
Lactate: 6.2 mmol/L
CK: elevated
Surgical exploration reveals necrotic fascia. Blood and tissue cultures grow group A Streptococcus.
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: B. Streptococcal toxic shock syndrome
Q2
Which antimicrobial combination is preferred once group A streptococcal infection is confirmed?
Reveal answer and rationale
✓Correct answer: A. Penicillin plus clindamycin
Penicillin is active against GAS, while clindamycin suppresses bacterial protein and toxin production and remains active during stationary-phase growth.
Q3
What additional treatment is frequently essential?
Reveal answer and rationale
✓Correct answer: A. Surgical source control
Q4
Which intervention may be considered in selected severe cases but does not replace surgery or antibiotics?
CDC guidance recommends penicillin, clindamycin, organ support, and surgery when a removable source is present.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 460
MENINGOCOCCEMIA WITH PURPURA FULMINANSClinical Case 460
A previously healthy 19-year-old university resident presents with fever, severe myalgia, vomiting, confusion, and rapidly spreading purple skin lesions.
Findings:
BP: 68/34 mmHg
HR: 148/min
Nonblanching petechiae and ecchymoses
Cool extremities
No marked neck stiffness
Laboratory findings:
Platelets: 32 × 10⁹/L
INR and aPTT: prolonged
Fibrinogen: reduced
Lactate: 7.1 mmol/L
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: C. Meningococcemia with purpura fulminans
Q2
What is the appropriate immediate antibiotic?
Reveal answer and rationale
✓Correct answer: B. Intravenous ceftriaxone or cefotaxime
Suspected invasive meningococcal disease requires immediate parenteral treatment. Antibiotics must not be delayed for imaging, lumbar puncture, or culture results.
Q3
What causes the rapidly progressive skin necrosis?
Reveal answer and rationale
✓Correct answer: A. Disseminated intravascular coagulation and microvascular thrombosis
Q4
What is required for close contacts?
Reveal answer and rationale
✓Correct answer: C. Prompt public-health-directed antimicrobial chemoprophylaxis
Clinical Pearl: Meningococcemia may cause fatal shock without prominent meningitis.
NPLEX Trap: Do not perform lumbar puncture before stabilizing an unstable patient.
CDC guidance emphasizes immediate third-generation cephalosporin therapy and public-health management of contacts.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 461
SEVERE BABESIOSIS IN AN ASPLENIC PATIENTClinical Case 461
A 66-year-old asplenic man from Ontario presents with high fever, drenching sweats, jaundice, dark urine, dyspnea, and confusion after hiking in a wooded area.
Laboratory findings:
Hemoglobin: 67 g/L
Platelets: 46 × 10⁹/L
Bilirubin and LDH: elevated
Haptoglobin: undetectable
Creatinine: elevated
Parasitemia: 14%
Blood smear: intraerythrocytic ring forms and Maltese-cross formations
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: A. Severe babesiosis
Q2
Which feature most strongly supports Babesia rather than malaria?
Reveal answer and rationale
✓Correct answer: C. Maltese-cross tetrads without malarial pigment
Q3
What treatment should be considered because of the high parasitemia and organ dysfunction?
Reveal answer and rationale
✓Correct answer: B. Red-cell exchange transfusion
Q4
Which patients are at increased risk of severe or relapsing babesiosis?
Reveal answer and rationale
✓Correct answer: C. Asplenic, older, or significantly immunocompromised patients
Evaluation for Lyme disease and anaplasmosis coinfection
Treatment principles
Hospitalize severe disease
Use specialist-directed combination antimicrobial therapy
Monitor smears frequently
Consider red-cell exchange when parasitemia exceeds approximately 10% or severe hemolysis or organ dysfunction is present
Use prolonged treatment in selected immunocompromised patients
Clinical Pearl: Babesiosis may be acquired through transfusion as well as tick exposure.
NPLEX Trap: A single negative smear does not exclude low-level infection; repeat microscopy or PCR may be required.
CDC guidance supports exchange transfusion for high-grade parasitemia or serious organ compromise.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
Significant jaundice with another organ complication
Treatment principles
Start intravenous artesunate immediately
Do not delay for transfer or complete species confirmation
Monitor glucose, parasitemia, renal function, hemoglobin, and lactate
Follow with a complete oral regimen
Monitor for delayed hemolysis
Clinical Pearl: Nonimmune travellers can deteriorate rapidly even with a relatively short symptom history.
NPLEX Trap: Exchange transfusion is not routine treatment when effective intravenous artesunate is available.
Current CDC guidance identifies intravenous artesunate as the treatment for severe malaria.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
Consider early ECMO at an experienced centre for refractory cardiopulmonary failure
Provide empiric antibiotics until alternative bacterial causes are excluded
Clinical Pearl: Thrombocytopenia and hemoconcentration can precede severe pulmonary edema.
NPLEX Trap: Large empiric fluid boluses can worsen respiratory failure in the capillary-leak phase.
CDC states that no specific antiviral treatment exists and early ICU supportive care is critical.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 464
SEVERE LEPTOSPIROSIS: WEIL DISEASEClinical Case 464
A 42-year-old sanitation worker develops fever, severe calf pain, headache, red eyes, jaundice, reduced urine output, and hemoptysis after working in floodwater.
Laboratory findings:
Bilirubin: markedly elevated
AST and ALT: moderately elevated
Creatinine: elevated
Platelets: reduced
Urinalysis: protein and blood
Chest imaging: diffuse alveolar infiltrates
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: C. Severe leptospirosis
Q2
Which physical finding is a classic clue?
Reveal answer and rationale
✓Correct answer: A. Conjunctival suffusion
Q3
What is appropriate treatment for severe disease?
Reveal answer and rationale
✓Correct answer: B. Intravenous penicillin or an appropriate third-generation cephalosporin
Q4
Does a negative antibody test during the first week exclude the diagnosis?
Reveal answer and rationale
✓Correct answer: C. No; early serology can be negative
Provide dialysis, ventilation, and hemodynamic support when needed
Monitor for a Jarisch–Herxheimer reaction
Clinical Pearl: Bilirubin may be markedly elevated despite only moderate aminotransferase elevation.
NPLEX Trap: Do not dismiss conjunctival redness as ordinary conjunctivitis when fever, calf pain, renal failure, and floodwater exposure coexist.
CDC guidance recommends immediate treatment, using intravenous penicillin or ceftriaxone for severe disease.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
Transfuse blood for clinically important hemorrhage
Avoid NSAIDs and aspirin
Clinical Pearl: A narrow pulse pressure may identify compensated shock before systolic hypotension develops.
NPLEX Trap: Falling fever does not necessarily indicate recovery.
Current CDC guidance emphasizes careful fluid titration and advises against prophylactic platelet transfusion.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
Delayed treatment substantially increases severe complications and death
Treatment principles
Start doxycycline immediately
Treat adults and children
Continue until clinically improved and afebrile for an appropriate period
Provide organ support for severe disease
Clinical Pearl: Palms-and-soles involvement is helpful but is often a later finding.
NPLEX Trap: Do not wait for the classic rash or a positive antibody result.
CDC recommends immediate doxycycline for suspected RMSF in patients of every age.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 467
FULMINANT CLOSTRIDIOIDES DIFFICILE COLITISClinical Case 467
Clinical Pearl: Diarrhea may decrease after ileus develops even as the disease becomes more severe.
NPLEX Trap: Reduced stool output does not prove improvement in a distended, systemically toxic patient.
IDSA/SHEA guidance recommends oral vancomycin, intravenous metronidazole, rectal vancomycin with ileus, and surgical management when required.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 468
SEVERE HUMAN GRANULOCYTIC ANAPLASMOSISClinical Case 468
Clinical Pearl: Many patients do not recall a tick bite.
NPLEX Trap: Beta-lactam antibiotics used for Lyme disease do not adequately treat anaplasmosis.
CDC recommends doxycycline for suspected anaplasmosis in adults and children.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 469
SEVERE EHRLICHIOSIS WITH MENINGOENCEPHALITISClinical Case 469
A 56-year-old man receiving immunosuppressive therapy presents with fever, severe headache, confusion, vomiting, and a maculopapular rash after a lone-star tick exposure.
Laboratory findings:
Leukopenia
Thrombocytopenia
Elevated liver enzymes
Hyponatremia
CSF: lymphocytic pleocytosis
PCR: Ehrlichia chaffeensis
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: A. Severe ehrlichiosis
Q2
Which cells may contain characteristic morulae?
Reveal answer and rationale
✓Correct answer: B. Monocytes
Q3
What is the first-line treatment?
Reveal answer and rationale
✓Correct answer: B. Doxycycline
Q4
Which statement is correct?
Reveal answer and rationale
✓Correct answer: C. Early treatment reduces progression to severe disease
Continue until the patient has improved and remained afebrile for the recommended period
Provide organ support
Clinical Pearl: Rash is more common in children and may be absent in adults.
NPLEX Trap: Ceftriaxone for presumed meningitis does not reliably treat ehrlichiosis.
CDC identifies doxycycline as first-line treatment for all ages and advises immediate empiric therapy.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
Begin appropriate antimicrobial treatment promptly
Notify public health and the laboratory
Provide respiratory and hemodynamic support
Consider exposure route and disease severity when selecting therapy
Clinical Pearl: Pneumonic tularemia may occur without a skin ulcer after aerosol exposure.
NPLEX Trap: Routine beta-lactams are unreliable because F. tularensis is intrinsically resistant to many commonly used agents.
CDC’s 2025 recommendations include aminoglycosides, fluoroquinolones, and tetracyclines, selected according to severity and clinical form.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
A 38-year-old wildlife biologist presents with abrupt fever, chest pain, cough, and bloody sputum after handling a sick prairie dog in an endemic region.
Assess close contacts for postexposure prophylaxis
Provide septic-shock and respiratory support
Clinical Pearl: Pneumonic plague can spread person-to-person through respiratory droplets.
NPLEX Trap: Do not delay therapy while awaiting definitive laboratory identification.
CDC recommends prompt treatment—commonly with gentamicin or a fluoroquinolone—and immediate public-health notification.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 472
VIBRIO VULNIFICUS SEPSIS AND NECROTIZING WOUND INFECTIONClinical Case 472
Nutrition and prevention: Patients with chronic liver disease should avoid raw oysters and protect wounds from coastal water exposure.
Clinical Pearl: Hemorrhagic bullae in a cirrhotic patient after shellfish or seawater exposure are a major diagnostic clue.
NPLEX Trap: Do not wait for culture confirmation before antibiotics and surgery.
CDC recommends doxycycline plus a third-generation cephalosporin and prompt surgical treatment.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 473
CAPNOCYTOPHAGA SEPSIS AFTER A DOG BITEClinical Case 473
Broad intravenous beta-lactam/beta-lactamase-inhibitor or other appropriate therapy
Wound management
Prolonged culture incubation or molecular identification when needed
Evaluate tetanus and rabies risk separately
Clinical Pearl: Severe infection can follow a seemingly trivial bite, scratch, or saliva exposure.
NPLEX Trap: A mild-looking bite wound does not predict the severity of systemic disease in an asplenic patient.
CDC warns that Capnocytophaga infection can progress rapidly after dog or cat exposure, particularly in high-risk patients.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 474
RESPIRATORY DIPHTHERIA WITH MYOCARDITISClinical Case 474
Provide vaccination after recovery because illness may not confer reliable immunity
Clinical Pearl: Antitoxin neutralizes circulating toxin but cannot reverse toxin already bound to tissue.
NPLEX Trap: Antibiotics eradicate the organism and reduce transmission but do not replace antitoxin.
CDC recommends immediate antitoxin for respiratory diphtheria, plus erythromycin or penicillin and close cardiac and neurologic monitoring.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
A 45-year-old postal worker develops fever, profound fatigue, dry cough, chest discomfort, and nausea several days after handling a suspicious powder-containing package.
He briefly improves and then develops severe dyspnea, confusion, and shock.
Imaging demonstrates:
Widened mediastinum
Large bilateral pleural effusions
Mediastinal lymphadenopathy
Blood cultures grow large gram-positive rods.
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: B. Inhalation anthrax
Q2
Which imaging finding is particularly suggestive?
Reveal answer and rationale
✓Correct answer: B. Widened mediastinum with pleural effusions
Q3
What is the appropriate treatment principle for systemic anthrax?
Reveal answer and rationale
✓Correct answer: B. Combination intravenous antimicrobial therapy with toxin-suppressing coverage
Q4
What additional therapy should be considered in severe systemic disease?
PCR and toxin testing through public-health laboratories
Immediate assessment for meningitis
Lumbar puncture when safe and indicated
Treatment principles
Do not delay treatment for confirmation
Use multidrug intravenous therapy for systemic disease
Include a protein-synthesis inhibitor to reduce toxin production
Add antitoxin in severe systemic disease when indicated
Drain clinically significant pleural effusions
Notify public health and law enforcement when intentional exposure is possible
Provide postexposure prophylaxis to appropriately exposed asymptomatic persons
Clinical Pearl: Early symptoms may resemble influenza before abrupt systemic deterioration.
NPLEX Trap: Inhalation anthrax typically causes hemorrhagic mediastinitis rather than a classic focal lobar pneumonia.
CDC guidelines recommend combination antimicrobial treatment and consideration of adjunctive antitoxin for systemic anthrax.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
A 68-year-old man presents with recurrent high fever, fatigue, painful ear swelling, inflammatory arthritis, tender skin nodules, and shortness of breath.
During the previous year, he has required repeated courses of prednisone. Symptoms recur whenever the dosage is reduced.
Laboratory findings:
Hemoglobin: 82 g/L
MCV: 111 fL
Platelets: 76 × 10⁹/L
CRP: markedly elevated
Vitamin B12 and folate: normal
Bone-marrow examination: cytoplasmic vacuoles in myeloid and erythroid precursors
Somatic UBA1 mutation: detected
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: C. VEXAS syndrome
Late-onset severe systemic inflammation, chondritis, skin disease, macrocytic anemia, thrombocytopenia, marrow vacuoles, and a somatic UBA1 mutation indicate VEXAS syndrome.
Q2
What does the genetic abnormality represent?
Reveal answer and rationale
✓Correct answer: B. A somatic mutation affecting hematopoietic cells
VEXAS is caused by an acquired UBA1 mutation within hematopoietic stem or progenitor cells. It is not usually an inherited childhood inflammatory syndrome.
Q3
Which laboratory abnormality is especially characteristic?
Reveal answer and rationale
✓Correct answer: B. Macrocytic anemia despite adequate vitamin B12 and folate
Q4
What is the appropriate management principle?
Reveal answer and rationale
✓Correct answer: B. Hematology–rheumatology assessment with steroid-sparing or clone-directed therapy
Consider targeted cytokine therapy or JAK inhibition
Consider hypomethylating therapy when associated myeloid disease is present
Assess selected patients for allogeneic stem-cell transplantation
Botanical safety: Immune-stimulating supplements are not appropriate substitutes for hematologic evaluation.
Clinical Pearl: New severe inflammatory disease in an older man with otherwise unexplained macrocytic anemia should prompt consideration of VEXAS.
NPLEX Trap: Do not attribute macrocytosis automatically to vitamin deficiency when B12 and folate are adequate.
Current reviews identify somatic UBA1 testing as confirmatory and emphasize combined hematologic and inflammatory management.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
Evaluation for infection, lymphoma, autoimmune disease, and POEMS
Treatment principles
Urgent hematology involvement
IL-6-directed treatment in appropriate patients
Glucocorticoids
Rituximab, calcineurin inhibition, or other immune-directed treatment in selected disease
Renal, respiratory, and fluid-balance support
Clinical Pearl: Lymph nodes may be relatively small despite severe systemic illness.
NPLEX Trap: Do not diagnose ordinary nephrotic syndrome when thrombocytopenia, intense inflammation, organomegaly, and Castleman-like pathology coexist.
Recent consensus work provides diagnostic and severity-based treatment frameworks for TAFRO syndrome.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
Consider MEK inhibition for other MAPK-pathway alterations
Relieve ureteral or cardiovascular obstruction
Replace deficient pituitary hormones
Monitor multiple organ systems longitudinally
Clinical Pearl: The combination of hairy-kidney infiltration and coated-aorta appearance is highly suggestive.
NPLEX Trap: Do not treat bone pain alone without assessing renal, cardiovascular, orbital, and neurologic involvement.
International consensus recommendations support molecular testing and MAPK-pathway-directed therapy.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 479
AUTOIMMUNE AUTONOMIC GANGLIONOPATHYClinical Case 479
A 39-year-old woman develops severe lightheadedness, dry mouth, blurred vision, constipation, urinary retention, and markedly reduced sweating over three weeks.
Findings:
Supine BP: 128/76 mmHg
Standing BP: 72/40 mmHg
Minimal compensatory heart-rate increase
Dilated, poorly reactive pupils
Normal limb strength and sensation
Ganglionic acetylcholine-receptor antibodies are strongly positive.
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: B. Autoimmune autonomic ganglionopathy
Q2
Which pattern supports neurogenic orthostatic hypotension?
Reveal answer and rationale
✓Correct answer: A. Large blood-pressure fall with little compensatory tachycardia
Q3
Which additional assessment is important?
Reveal answer and rationale
✓Correct answer: A. Evaluation for an associated malignancy or autoimmune disorder
Q4
What treatment may be used for significant autoimmune disease?
Reveal answer and rationale
✓Correct answer: A. IV immunoglobulin or plasma exchange
Medications such as midodrine or droxidopa when appropriate
Immunotherapy in autoimmune disease
Manage gastrointestinal, bladder, ocular, and sweating dysfunction
Clinical Pearl: Diffuse autonomic failure can occur without major motor or sensory abnormalities.
NPLEX Trap: Do not diagnose POTS when the dominant abnormality is profound hypotension without adequate tachycardia.
Autoimmune autonomic ganglionopathy is associated with ganglionic AChR antibodies and may respond to IVIG, plasma exchange, or other immunotherapy.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
Screening for autoimmune diabetes and thyroid disease
Cancer assessment when amphiphysin or other paraneoplastic antibodies are suspected
Treatment principles
GABA-enhancing symptomatic medication
IVIG for clinically important autoimmune disease
Consider plasma exchange, rituximab, or other therapy in selected refractory cases
Fall prevention and cautious rehabilitation
Physical medicine safety: Forceful manipulation can provoke severe spasms and injury.
Clinical Pearl: Anxiety may develop because patients fear unpredictable stimulus-triggered spasms; this does not make the disorder psychogenic.
NPLEX Trap: Do not attribute objective rigidity and continuous motor-unit activity to anxiety alone.
Stiff-person spectrum disorders are characterized by rigidity and stimulus-sensitive spasms and are treated with symptomatic GABAergic therapy plus immunotherapy when indicated.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
Use plasma exchange or IVIG for inadequate response
Taper glucocorticoids carefully because rapid withdrawal may be followed by relapse
Consider maintenance immunotherapy for recurrent disease
Clinical Pearl: MOG-associated optic neuritis frequently causes optic-disc edema and may involve both eyes.
NPLEX Trap: A positive low-titre result without a compatible clinical syndrome should not automatically establish MOGAD.
International criteria require a compatible demyelinating event, appropriate MOG-IgG testing, and exclusion of better diagnoses.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
A 36-year-old man presents with burning pain in his hands and feet, reduced sweating, heat intolerance, abdominal cramping, and early kidney dysfunction.
Examination:
Angiokeratomas around the groin and umbilicus
Corneal verticillata
Mild left-ventricular hypertrophy
His maternal uncle died from kidney failure at age 47.
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: A. Fabry disease
Q2
Which enzyme is deficient?
Reveal answer and rationale
✓Correct answer: A. Alpha-galactosidase A
Q3
Which inheritance pattern is typical?
Reveal answer and rationale
✓Correct answer: A. X-linked
Q4
What is the appropriate disease-specific treatment principle?
Reveal answer and rationale
✓Correct answer: A. Enzyme-replacement or appropriate chaperone therapy
Monitor kidney, cardiac, neurologic, auditory, and ocular disease
Clinical Pearl: Heterozygous women may have substantial disease because of variable X-chromosome inactivation.
NPLEX Trap: Normal enzyme activity in a woman does not reliably exclude Fabry disease; genetic testing may be required.
GeneReviews describes enzymatic and genetic diagnosis, family screening, and disease-specific treatment.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
Reassess warfarin, calcium-containing binders, and activated vitamin D
Intensive wound care and pain control
Treat infection promptly
Consider sodium thiosulfate
Consider parathyroid-directed treatment in selected disease
Clinical Pearl: Normal serum calcium does not exclude calciphylaxis.
NPLEX Trap: Skin biopsy may worsen ulceration or infection and should be individualized when the clinical pattern is highly characteristic.
Recent nephrology guidance emphasizes early recognition, wound and infection management, modification of risk factors, and multidisciplinary care.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 484
ENTERIC HYPEROXALURIA WITH OXALATE NEPHROPATHYClinical Case 484
Clinical Pearl: Calcium restriction can paradoxically increase intestinal oxalate absorption.
NPLEX Trap: Recurrent stones after bariatric surgery should not automatically be managed with a low-calcium diet.
Kidney Health Initiative reviews support dietary oxalate and fat reduction, calcium with meals, hydration, and treatment of malabsorption.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
Stop contributing vitamin D or thiazide when appropriate
Restore intravascular volume
Treat severe hypercalcemia
Dialyze selected patients with refractory toxicity or severe renal failure
Clinical Pearl: Patients may count their osteoporosis supplement but forget calcium-containing antacid use.
NPLEX Trap: Suppressed PTH in hypercalcemia should trigger a search for supplements, medications, malignancy, and vitamin D-related disease.
Calcium-alkali syndrome is defined by hypercalcemia, metabolic alkalosis, and renal impairment from excessive calcium with absorbable alkali.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 486
VITAMIN D TOXICITY WITH HYPERCALCEMIC KIDNEY INJURYClinical Case 486
Recognize that toxicity may persist because vitamin D is fat soluble
Clinical Pearl: Sunlight exposure does not ordinarily cause vitamin D intoxication; supplement dosing errors are the usual exogenous cause.
NPLEX Trap: Do not use 1,25-dihydroxyvitamin D as the principal screening test for supplement-induced toxicity.
Vitamin D toxicity management focuses on stopping exposure, hydration, and treatment of hypercalcemia.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
Early loss of deciduous teeth in childhood disease
Key investigations
Repeat alkaline phosphatase using age-appropriate reference ranges
Pyridoxal-5′-phosphate
Urinary phosphoethanolamine
ALPL genetic testing
Skeletal imaging
Dental history
Clinical Pearl: Low alkaline phosphatase is often overlooked because clinicians focus primarily on elevated results.
NPLEX Trap: Do not label low-ALP fracture disease as routine osteoporosis and prescribe bisphosphonates without further assessment.
GeneReviews describes low alkaline phosphatase, elevated enzyme substrates, ALPL testing, and avoidance of bisphosphonates.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
Urinary phosphate and tubular reabsorption calculations
FGF23
1,25-dihydroxyvitamin D
Functional somatostatin-receptor imaging
Targeted anatomical imaging
Selective venous sampling in difficult cases
Clinical Pearl: Serum phosphate is not always included in routine chemistry panels and may remain unchecked for years.
NPLEX Trap: Recurrent fractures with normal calcium do not automatically represent osteoporosis.
Global guidance emphasizes confirmation of renal phosphate wasting, tumour localization, surgical removal, and medical therapy when unresectable.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
A 59-year-old man with a known thymoma presents with recurrent bacterial sinus infections, chronic diarrhea, oral candidiasis, and cytomegalovirus retinitis.
Laboratory findings:
IgG: markedly reduced
IgA and IgM: reduced
Peripheral B cells: nearly absent
CD4 T cells: reduced
Poor vaccine-antibody responses
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: B. Good syndrome
Q2
What combination defines this syndrome?
Reveal answer and rationale
✓Correct answer: A. Thymoma with adult-onset immunodeficiency
Q3
Which immunologic finding is characteristic?
Reveal answer and rationale
✓Correct answer: A. Low immunoglobulins with markedly reduced or absent B cells
Q4
What long-term treatment is generally required?
Reveal answer and rationale
✓Correct answer: A. Immunoglobulin-replacement therapy
Clinical Pearl: Removing the thymoma does not usually reverse the immunodeficiency.
NPLEX Trap: Opportunistic infection in a patient with thymoma should not be attributed solely to chemotherapy or age.
Good syndrome is an adult immunodeficiency associated with thymoma, hypogammaglobulinemia, and profound B-cell reduction.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
Evaluation for protein loss, medication effects, malignancy, and HIV
Chest imaging and pulmonary function
Gastrointestinal assessment
Treatment principles
Immunoglobulin replacement
Prompt antimicrobial treatment
Bronchiectasis management
Monitor autoimmune cytopenias, enteropathy, liver disease, lymphoproliferation, and malignancy
Clinical Pearl: B cells are usually present, but effective antibody production is impaired.
NPLEX Trap: Recurrent sinus infection plus low IgG should not automatically be called selective IgA deficiency.
The ICON consensus defines CVID through low immunoglobulins, impaired antibody responses, appropriate age, and exclusion of secondary causes.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
Clinical Pearl: Recurrent meningococcal infection is a classic clue even when other infection history is limited.
NPLEX Trap: Vaccination reduces risk but does not eliminate meningococcal disease in patients with complement defects.
CDC reports emphasize complement testing after recurrent meningococcal disease and continued vaccination and prevention planning.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
Clinical Pearl: Autosomal-recessive forms may present later than classic X-linked disease.
NPLEX Trap: A normal neutrophil count does not mean neutrophil function is normal.
GeneReviews and current diagnostic reviews support DHR testing, antimicrobial prophylaxis, and transplantation assessment.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 493
CLOSTRIDIUM PERFRINGENS SEPSIS WITH MASSIVE HEMOLYSISClinical Case 493
A 65-year-old woman with diabetes and a recently diagnosed hepatic mass presents with fever, severe abdominal pain, jaundice, and rapidly progressive shock.
Laboratory findings:
Hemoglobin falls from 112 to 54 g/L within hours
LDH: extremely elevated
Haptoglobin: undetectable
Potassium: 7.0 mmol/L
Blood smear: spherocytes, ghost cells, and marked hemolysis
Blood specimens appear grossly hemolyzed
CT demonstrates a gas-forming liver abscess.
Q1
What is the most likely diagnosis?
Reveal answer and rationale
✓Correct answer: B. Clostridium perfringens sepsis with massive intravascular hemolysis
Q2
Which bacterial toxin drives the hemolysis?
Reveal answer and rationale
✓Correct answer: A. Alpha toxin with phospholipase activity
Q3
What is the appropriate treatment?
Reveal answer and rationale
✓Correct answer: A. Immediate broad anaerobic antimicrobial therapy and urgent source control
Q4
Which complication requires immediate treatment in addition to infection control?
Reveal answer and rationale
✓Correct answer: A. Hyperkalemia from massive hemolysis
Consider penicillin plus a toxin-suppressing agent such as clindamycin
Drain or surgically remove the infectious focus
Treat hyperkalemia, DIC, kidney failure, and severe anemia
Provide massive-transfusion support when required
Clinical Pearl: Laboratory analyzers may repeatedly reject specimens because of extreme in-vivo hemolysis.
NPLEX Trap: Do not assume every grossly hemolyzed sample represents collection error when the patient is jaundiced and rapidly deteriorating.
Published reviews describe C. perfringens septicemia as a rare, rapidly fatal cause of massive intravascular hemolysis requiring immediate antimicrobial and source-control treatment.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
Assessment for peritonsillar or deep-neck infection
Evaluation for pleural infection
Treatment principles
Beta-lactamase-stable therapy with anaerobic coverage
Drain abscesses or empyema
Support sepsis and respiratory failure
Individualize anticoagulation for extensive or progressive thrombosis
Clinical Pearl: A patient may appear to recover from pharyngitis before developing septic thrombophlebitis.
NPLEX Trap: Do not diagnose uncomplicated pneumonia without investigating the neck when pulmonary septic emboli follow a recent throat infection.
Reviews identify internal-jugular septic thrombophlebitis, F. necrophorum, and prolonged anaerobic antimicrobial therapy as defining features.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
Clinical Pearl: Vegetations may be very small or absent on routine echocardiography.
NPLEX Trap: Culture-negative endocarditis does not mean noninfectious endocarditis.
CDC recommends doxycycline plus hydroxychloroquine for at least 18 months for adult Q fever endocarditis or vascular infection.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
Extend treatment for neurologic, vertebral, or cardiac disease
Assess for surgery in endocarditis
Notify public-health and laboratory personnel
Evaluate potentially exposed laboratory workers
Clinical Pearl: Endocarditis is uncommon but accounts for a large proportion of brucellosis-related deaths.
NPLEX Trap: Temporary improvement does not justify early treatment discontinuation.
Brucellosis is a zoonotic infection associated with unpasteurized dairy and animal exposure and requires combination antibiotics, with longer therapy for focal disease.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
Begin appropriate treatment immediately when suspected
Intensive intravenous phase
Drain accessible abscesses
Follow with prolonged eradication therapy
Optimize diabetes and other risk factors
Ensure laboratory awareness because of biosafety concerns
Clinical Pearl: Multiple liver and splenic abscesses may produce a characteristic clustered appearance.
NPLEX Trap: Clinical improvement after intravenous therapy does not remove the need for prolonged eradication treatment.
CDC guidance recommends an intravenous intensive phase followed by several months of oral eradication therapy.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 498
DISSEMINATED NOCARDIOSIS WITH BRAIN ABSCESSClinical Case 498
Use combination treatment for severe, disseminated, or CNS disease
Drain large or poorly responsive brain abscesses
Treat for an extended duration
Reduce immunosuppression when feasible
Clinical Pearl: Nocardia has a particular tendency to spread from the lungs to the brain.
NPLEX Trap: Routine culture disposal after a few days may miss the organism; the laboratory must be alerted.
CDC notes that nocardiosis commonly presents as invasive pulmonary disease, dissemination, or brain abscess and requires extended culture incubation.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
Addition of RAAS-blocking or potassium-retaining medication
Treatment principles
Stop AV-nodal-blocking and potassium-raising medications
Stabilize the myocardium with intravenous calcium
Shift and remove potassium
Restore perfusion with appropriate fluids and vasopressor or chronotropic support
Treat renal failure
Consider dialysis when indicated
Clinical Pearl: The bradycardia is often more severe than expected from either the potassium level or AV-blocker dose alone.
NPLEX Trap: Atropine may be ineffective because the syndrome is not primarily caused by excessive vagal tone.
Canadian emergency guidance stresses simultaneous treatment of every component of BRASH rather than focusing on bradycardia alone.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
NPLEX Part II • Phase 5 • Clinical Case 500
NITROUS-OXIDE–INDUCED FUNCTIONAL VITAMIN B12 DEFICIENCYClinical Case 500
Correct coexisting folate deficiency after B12 treatment begins
Provide neurologic rehabilitation
Address substance-use risk and relapse prevention
Monitor for incomplete recovery
Clinical Pearl: Neurologic disease may be severe even without macrocytic anemia or a frankly low serum B12 result.
NPLEX Trap: Do not delay treatment while waiting for serum B12 to fall below the laboratory reference range.
Repeated nitrous-oxide exposure can inactivate vitamin B12 and produce myelopathy, neuropathy, and megaloblastic changes.
Educational exam-preparation content. Emergency findings in these cases require urgent medical assessment and should not be managed solely with complementary care.
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Common Adult Laboratory Reference Values
Exam reference: Approximate adult intervals in SI units. Ranges vary by laboratory, assay, age, sex, pregnancy and clinical setting; use values supplied in the question when provided.
Hematology and Coagulation
Hemoglobin
Female 120–160 g/L; Male 135–175 g/L
Hematocrit
Female 0.36–0.46; Male 0.40–0.52
WBC count
4.0–11.0 × 10⁹/L
Platelets
150–400 × 10⁹/L
MCV
80–100 fL
Reticulocytes
0.5–2.5%
PT / INR
INR 0.8–1.2 when not anticoagulated
aPTT
Approximately 25–35 seconds
Electrolytes and Renal
Sodium
135–145 mmol/L
Potassium
3.5–5.0 mmol/L
Chloride
98–106 mmol/L
Bicarbonate
22–29 mmol/L
Urea / BUN
Urea 2.5–7.1 mmol/L
Creatinine
Female ~45–90 µmol/L; Male ~60–110 µmol/L
Serum osmolality
275–295 mOsm/kg
Urine specific gravity
1.005–1.030
Glucose, Minerals and Endocrine
Fasting glucose
3.9–5.5 mmol/L
Calcium, total
2.15–2.55 mmol/L
Magnesium
0.70–1.00 mmol/L
Phosphate
0.80–1.50 mmol/L
TSH
Approximately 0.4–4.0 mIU/L
Free T4
Approximately 10–23 pmol/L
Morning cortisol
Assay- and time-dependent; interpret with local range
HbA1c
Normal <5.7% (<39 mmol/mol)
Liver and Pancreas
AST
Approximately 10–40 U/L
ALT
Approximately 7–56 U/L
Alkaline phosphatase
Approximately 40–130 U/L
Total bilirubin
3–21 µmol/L
Albumin
35–50 g/L
GGT
Assay- and sex-dependent
Lipase
Assay-dependent; pancreatitis often ≥3× upper limit
Ammonia
Assay- and specimen-handling dependent
Arterial Blood Gas
pH
7.35–7.45
PaCO₂
35–45 mm Hg
PaO₂
80–100 mm Hg at sea level
HCO₃⁻
22–26 mmol/L
Base excess
−2 to +2 mmol/L
Lactate
Approximately 0.5–2.0 mmol/L
Oxygen saturation
Usually 95–100%
CSF and Useful Conversions
CSF opening pressure
Approximately 10–20 cm H₂O
CSF WBC
0–5 cells/µL
CSF protein
0.15–0.45 g/L
CSF glucose
~60–70% of simultaneous serum glucose
Glucose conversion
mg/dL ÷ 18 = mmol/L
Creatinine conversion
mg/dL × 88.4 = µmol/L
Bilirubin conversion
mg/dL × 17.1 = µmol/L
Calcium conversion
mg/dL × 0.25 = mmol/L
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