Patient presents with painless erythematous macules on the palms and soles (Janeway lesions) and skin bullae—what is the most likely diagnosis and what diagnostic work‑up and initial management should be undertaken?

Infective Endocarditis with Cutaneous Manifestations

The combination of painless erythematous macules on palms/soles (Janeway lesions) and bullae strongly suggests infective endocarditis (IE) with septic emboli and immune complex vasculitis; immediately obtain three sets of blood cultures before initiating empiric antibiotics, perform urgent echocardiography (transesophageal preferred), and consult cardiology and infectious disease. 1, 2, 3

Pathophysiology and Clinical Significance

Janeway lesions result from septic microemboli causing localized microabscesses in the dermis, while Osler nodes (painful nodules) arise from immune complex deposition causing vasculitis 1. The presence of these cutaneous manifestations indicates:

• Higher risk of embolic complications, particularly cerebral emboli (32.8% vs 18.4% in patients without skin findings) 3
• More severe disease with larger cardiac vegetations (mean 18.1 mm vs 13.7 mm) 3
• Increased extracardiac complications, though not necessarily higher mortality 3

Bullae formation suggests particularly aggressive infection with extensive vascular involvement and tissue destruction 1.

Immediate Diagnostic Work-Up

Blood Cultures (Priority #1)

• Obtain three sets from separate venipuncture sites before any antibiotics 1, 4
• Draw over 1-2 hours if patient is hemodynamically stable 4
• Staphylococcus aureus and Streptococcus species are most common, but expect variable organisms including MRSA in healthcare-associated cases 1, 5

Echocardiography (Priority #2)

• Transesophageal echocardiography (TEE) is superior to transthoracic (TTE) for detecting vegetations, particularly in prosthetic valves or intracardiac devices 4
• Perform urgently within 24 hours of presentation 4
• If initial TEE is negative but clinical suspicion remains high, repeat in 7-10 days 1

Additional Imaging

• Obtain brain MRI or CT given the 32.8% risk of cerebral emboli in patients with skin manifestations 3
• Consider cardiac CT or PET/CT if prosthetic material present and echocardiography is inconclusive 4

Skin Biopsy of Bullae

• Perform biopsy with tissue culture and histopathology to differentiate infectious from immune-mediated bullae 1
• Send for bacterial, fungal, and mycobacterial cultures 1
• Histology may reveal septic emboli with bacterial invasion of vessel walls (similar to ecthyma gangrenosum pattern) 1

Initial Management

Empiric Antibiotic Therapy

Start immediately after blood cultures are drawn:

• Vancomycin 15-20 mg/kg IV every 8-12 hours (target trough 15-20 mcg/mL) PLUS
• Gentamicin 1 mg/kg IV every 8 hours (or ceftriaxone 2g IV daily if gentamicin contraindicated) 1

This covers MRSA, streptococci, and enterococci pending culture results 1.

Adjust Based on Culture Results

• Methicillin-sensitive S. aureus: Switch to nafcillin or oxacillin 2g IV every 4 hours 5
• Streptococcus viridans: Penicillin G or ceftriaxone with or without gentamicin 1
• Duration typically 4-6 weeks depending on organism and valve involvement 1

Risk Stratification and Surgical Consultation

Obtain urgent cardiothoracic surgery consultation if any of the following are present 4:

• Heart failure from severe valvular regurgitation
• Persistent bacteremia despite appropriate antibiotics (>5-7 days)
• Perivalvular abscess or fistula formation
• Large vegetations (>10 mm) with embolic events
• Prosthetic valve involvement
• Fungal endocarditis

Early surgical intervention reduces mortality even in high-risk patients because antibiotic eradication alone is often insufficient 4.

High-Risk Features in This Patient

The presence of both Janeway lesions AND bullae suggests:

• Aggressive bacterial infection with high embolic burden 6, 3
• Possible S. aureus etiology, which has worse prognosis and higher complication rates 5
• Need for close monitoring for development of heart failure, stroke, or septic shock 6

Critical Pitfalls to Avoid

• Never delay blood cultures waiting for fever spike—draw immediately on presentation 4
• Do not start antibiotics before blood cultures unless patient is in septic shock 1
• Do not rely on TTE alone—TEE has significantly higher sensitivity for vegetations and complications 4
• Do not dismiss negative initial echocardiography—repeat if clinical suspicion remains high, as vegetations may take time to develop 1
• Recognize that skin manifestations predict complicated course—these patients require aggressive monitoring and often prolonged hospitalization 6, 3

Monitoring During Hospitalization

• Daily cardiovascular examination for new murmurs or signs of heart failure 1
• Serial blood cultures every 48-72 hours until clearance documented 1
• Neurologic checks every 4-6 hours for embolic stroke 3
• Monitor for development of new embolic phenomena (splenic infarct, renal infarct, mycotic aneurysm) 1