SPEX Exam Internal Medicine 5

Question 1

A 58-year-old woman with known primary biliary cholangitis presents with worsening fatigue and a new pruritus unresponsive to cholestyramine. Labs show ALP 420 U/L, total bilirubin 3.1 mg/dL, and IgM 890 mg/dL. She has been on ursodeoxycholic acid for 3 years. Which finding would MOST strongly suggest overlap syndrome with autoimmune hepatitis rather than pure PBC progression?

Accepted Answer

Serum ALT > 5× upper limit of normal with interface hepatitis on biopsy

Answer

PBC-AIH overlap syndrome (Paris criteria) requires AIH features including ALT ≥ 5× ULN and/or IgG ≥ 2× ULN plus interface hepatitis on biopsy. Elevated ALP and anti-mitochondrial antibodies are expected in PBC alone. Anti-gp210 is associated with poor prognosis in PBC but not overlap. The disproportionate transaminase elevation with histologic interface hepatitis is the key discriminating feature warranting addition of corticosteroids.

Question 2

A 72-year-old man with heart failure (EF 35%) is started on sacubitril/valsartan. Three days later he develops angioedema of the lips and tongue requiring epinephrine. He had previously tolerated lisinopril for 4 years without incident. What is the most appropriate long-term strategy for managing his heart failure after the acute episode resolves?

Accepted Answer

Initiate hydralazine-isosorbide dinitrate combination therapy

Answer

Sacubitril inhibits neprilysin, which degrades bradykinin; this markedly increases bradykinin levels and angioedema risk — independent of the ACE inhibitor mechanism. Patients who develop angioedema on ARNI (sacubitril/valsartan) have a contraindication to all neprilysin inhibitors. ARBs alone do not inhibit bradykinin degradation and are generally safer, but the angioedema here occurred on sacubitril/valsartan after prior ACE inhibitor tolerance, meaning the neprilysin component is implicated. Hydralazine-isosorbide dinitrate is the evidence-based alternative (especially in self-identified Black patients) when RAAS agents are contraindicated. An ARB alone could be considered, but given the severity of the reaction involving sacubitril, the safest well-evidenced alternative for HFrEF is hydralazine-isosorbide dinitrate.

Question 3

A 44-year-old woman with relapsing-remitting multiple sclerosis develops acute encephalopathy, seizures, and multifocal demyelinating lesions on MRI after 18 months of natalizumab therapy. CSF JC virus PCR returns at 45 copies/mL. She is started on plasma exchange. As immune reconstitution begins, the MOST feared complication and its defining characteristic is:

Accepted Answer

Immune reconstitution inflammatory syndrome (IRIS) causing paradoxical neurological worsening despite decreasing viral load

Answer

In natalizumab-associated PML, plasma exchange removes natalizumab and allows lymphocyte re-entry into the CNS. As immune function restores, an exaggerated inflammatory response against JC virus-infected cells — IRIS — can paradoxically worsen neurological status even as viral load falls. IRIS in this setting carries 30–50% mortality and is characterized by new or worsening contrast enhancement, mass effect, and clinical deterioration despite declining CSF JC virus copies. This paradoxical worsening distinguishes IRIS from treatment failure. Corticosteroids are used to modulate (not prevent) IRIS.

Question 4

A 61-year-old man with type 2 diabetes, stage 3b CKD (eGFR 38 mL/min/1.73m²), and a recent hospitalization for acute decompensated heart failure is being optimized for outpatient management. Which of the following medication adjustments is MOST evidence-based given his combined comorbidities?

Accepted Answer

Add an SGLT-2 inhibitor (empagliflozin or dapagliflozin) despite reduced glucose-lowering efficacy at this eGFR level

Answer

SGLT-2 inhibitors (empagliflozin, dapagliflozin) have robust evidence for reducing heart failure hospitalizations and slowing CKD progression independent of their glucose-lowering effect, which diminishes at eGFR < 45. Current guidelines (ADA, ESC) support SGLT-2 inhibitor use down to eGFR 20–25 mL/min for cardiorenal protection — not glucose control. In a patient with recent HF hospitalization and CKD 3b, the cardiorenal benefit justifies use. Metformin can be continued cautiously down to eGFR 30 in many guidelines. GLP-1 agonists have cardiac benefit but less direct HF impact. SGLT-2 inhibitors represent the strongest evidence-based choice here.

Question 5

A 39-year-old woman presents with episodic hypertension (BP 210/115 during episodes), diaphoresis, and palpitations. 24-hour urine metanephrines are 3× upper limit of normal. CT abdomen shows a 4.2 cm right adrenal mass. Genetic testing reveals a SDHB mutation. Which statement about her management and prognosis is MOST accurate?

Accepted Answer

SDHB mutations are associated with paraganglioma syndrome type 4 and carry up to 40% risk of malignant disease, requiring lifetime surveillance

Answer

SDHB mutations (succinate dehydrogenase subunit B) confer the highest malignancy risk among all pheochromocytoma/paraganglioma genetic syndromes — approximately 30–40% risk of metastatic disease compared to ~10% for sporadic tumors. SDHB is associated with hereditary paraganglioma-pheochromocytoma syndrome type 4 (PGL4). Even after biochemically successful resection, lifelong annual biochemical testing and periodic imaging are mandatory due to high recurrence and late metastasis rates. Pre-operative alpha-blockade before beta-blockade is correct (to avoid hypertensive crisis from unopposed alpha stimulation), but the critical prognostic point here is the malignant potential of SDHB mutations.

SPEX Exam Practice Test

SPEX Exam Practice Test

SPEX Exam Internal Medicine 5