A 65-year-old man visits the clinic reporting a 3-week history of profound fatigue, subjec… — USMLE Step 2 CK

A $65$ -year-old man visits the clinic reporting a $3$ -week history of profound fatigue, subjective fevers, and widespread joint pain. He notes that his wrists, knees, and ankles feel stiff and swollen. His past medical history is significant for ischemic cardiomyopathy with a reduced ejection fraction and chronic obstructive pulmonary disease. His daily medications include carvedilol, lisinopril, furosemide, hydralazine, and a tiotropium inhaler. Vital signs show a temperature of $37.9^\circ\text{C}$ ( $100.2^\circ\text{F}$ ), blood pressure of $128/78\text{ mmHg}$ , and heart rate of $76/\text{min}$ . Physical examination reveals mild symmetric effusions in the knees and wrists without overlying erythema. Cardiopulmonary examination reveals normal heart sounds without murmurs, and clear lung fields bilaterally.

Laboratory investigations reveal the following:

Laboratory Test	Result	Reference Range
Antinuclear antibodies (ANA)	Positive ( $1:640$ )	Negative
Anti-double-stranded DNA	Negative	Negative
Anti-histone antibodies	Positive	Negative
Rheumatoid factor (RF)	Negative	Negative
Thyroid-stimulating hormone (TSH)	$2.1\text{ \mu U/mL}$	$0.4-4.0\text{ \mu U/mL}$

Based on the patient's clinical presentation and laboratory findings, which of the following is the most appropriate next step in management?

Discontinuation of hydralazineAnswer
B
Administration of oral azithromycin and prednisone
C
Empiric intravenous vancomycin and ceftriaxone
D
Initiation of levothyroxine therapy
E
Initiation of methotrexate therapy

Answer

Discontinuation of hydralazine

The correct answer involves discontinuing hydralazine because the patient's clinical picture is highly characteristic of drug-induced lupus erythematosus (DILE). DILE presents with systemic symptoms such as fever, fatigue, and polyarthritis. The serological hallmark is a positive ANA and the presence of anti-histone antibodies, with a notable absence of anti-dsDNA antibodies (which are more specific to idiopathic systemic lupus erythematosus). Hydralazine is one of the most common medications known to cause DILE. The cornerstone of management is simply stopping the offending medication, which typically results in complete resolution of symptoms over several weeks.

Step-by-Step Solution

Analyze the clinical presentation and laboratory findings.

The patient has new-onset polyarthralgia, fatigue, and fever. Labs show positive ANA and positive anti-histone antibodies, but negative anti-dsDNA and negative RF.

Synthesizing symptoms with targeted serology is required to narrow the rheumatologic differential diagnosis.

Correlate the serologic profile with the patient's medication list.

The combination of positive ANA and anti-histone antibodies is the classic serologic signature for drug-induced lupus erythematosus (DILE). Hydralazine is a well-known high-risk medication for DILE.

Identifying the causative agent is the critical step in diagnosing a drug-induced autoimmune phenomenon.

Determine the appropriate therapeutic intervention.

The primary and most effective treatment for DILE is the removal of the offending drug.

Discontinuing hydralazine leads to the resolution of clinical symptoms, making it the most appropriate next step in management.

Key Concept

Drug-induced lupus erythematosus (DILE) classically presents with constitutional symptoms, arthralgias, positive ANA, and positive anti-histone antibodies, often triggered by medications like hydralazine or procainamide. The primary treatment is discontinuing the offending drug.

Estimated Time:1m 15s

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