A male patient, aged 48, presents to an ambulatory care facility reporting a 6-week histor… — USMLE Step 2 CK

A male patient, aged $48$ , presents to an ambulatory care facility reporting a $6$ -week history of a persistent cough and episodes of blood-tinged sputum. Over this same period, he has experienced recurrent nosebleeds, intermittent low-grade fevers, and profound fatigue. His medical history includes major depressive disorder, for which he has been taking citalopram for the last $3$ years. He does not smoke or use illicit drugs.

Vital signs show a temperature of $37.7^\circ\text{C}$ ( $99.9^\circ\text{F}$ ), blood pressure of $152/96\text{ mm Hg}$ , heart rate of $88/\text{min}$ , and respiratory rate of $16/\text{min}$ .

Examination of the nasal cavity reveals mucosal ulcerations and adherent crusts. Auscultation of the lungs demonstrates scattered crackles in the right middle lung field.

Laboratory studies reveal:
Hemoglobin: $10.2\text{ g/dL}$
Leukocyte count: $11,500/\text{mm}^3$
Blood urea nitrogen: $34\text{ mg/dL}$
Serum creatinine: $2.2\text{ mg/dL}$ (was $0.8\text{ mg/dL}$ during a routine checkup $8$ months ago)
Urinalysis: $2+$ protein, large blood, $>50\text{ red blood cells/hpf}$ , and several red blood cell casts.

A radiograph of the chest demonstrates a $3.5\text{-cm}$ cavitary lesion in the right middle lobe with thick walls.

Based on the most likely diagnosis, which of the following is the most appropriate next step in evaluation or management?

Measurement of serum autoantibodies against proteinase-3 and myeloperoxidaseAnswer
B
Empiric treatment with intravenous clindamycin and ceftriaxone
C
Administration of intravenous furosemide and noninvasive positive pressure ventilation
D
Immediate cessation of the patient's selective serotonin reuptake inhibitor
E
Assessment of serum thyrotropin and free thyroxine levels

Answer

Measurement of serum autoantibodies against proteinase-3 and myeloperoxidase

The correct answer is the measurement of serum autoantibodies against proteinase-3 and myeloperoxidase. This patient presents with the classic triad of Granulomatosis with Polyangiitis (GPA): upper respiratory tract disease (recurrent epistaxis, nasal ulcerations/crusting), lower respiratory tract disease (cough, hemoptysis, cavitary lung lesion), and glomerulonephritis (hypertension, elevated creatinine, hematuria, and red blood cell casts). GPA is an ANCA-associated small-vessel vasculitis. The most appropriate initial non-invasive step in the diagnostic workup is testing for anti-neutrophil cytoplasmic antibodies (ANCA). Approximately 90% of patients with active systemic GPA will test positive for c-ANCA (which targets proteinase-3, or PR3). Once seropositivity is confirmed, a tissue biopsy (typically from the kidney or upper airway) is obtained for definitive diagnosis.

Step-by-Step Solution

Analyze the clinical triad of symptoms

The patient exhibits upper respiratory tract involvement (epistaxis, nasal mucosal ulcerations), lower respiratory tract involvement (hemoptysis, cavitary lung lesion), and renal involvement (acute kidney injury with red blood cell casts indicating glomerulonephritis).

Identifying the pattern of organ involvement is crucial for recognizing specific systemic vasculitides.

Formulate the most likely diagnosis

The combination of this triad is highly characteristic of Granulomatosis with Polyangiitis (GPA, formerly Wegener's granulomatosis).

GPA uniquely causes necrotizing granulomatous inflammation affecting these three distinct vascular beds.

Determine the best initial diagnostic step

Serologic testing for anti-neutrophil cytoplasmic antibodies (ANCA), specifically PR3-ANCA and MPO-ANCA.

While a tissue biopsy (often nasal or renal) is required for definitive confirmation, ANCA testing is the most appropriate, rapid, and non-invasive initial step to support the diagnosis and guide urgent immunosuppressive therapy.

Key Concept

The classic presentation and initial diagnosis of Granulomatosis with Polyangiitis (GPA)

Estimated Time:1m 15s

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