In a patient with myelodysplastic syndrome who develops neutropenic fever (absolute neutrophil count <500/µL), what is the most common end‑organ lesion?

End-Organ Lesions in MDS with Neutropenic Fever

Skin and soft tissue infections are the most common end-organ lesions in MDS patients with neutropenic fever, occurring in more than 20% of cases, often from hematogenous dissemination. 1

Primary Sites of Infection

The most frequent end-organ sites affected in neutropenic MDS patients include:

• Skin and soft tissues represent the most clinically documented end-organ manifestation, with >20% of neutropenic patients developing these lesions, many due to bloodstream dissemination 1
• Lungs are the most common primary infection site overall, with pneumonia being the predominant infection type in MDS 2, 3
• Alimentary tract (mouth, pharynx, esophagus, large/small bowel, rectum) serves as both a primary site and portal of entry 1
• Sinuses can harbor silent infections that disseminate to other organs 1

Critical Characteristics of Skin Lesions

No matter how small or innocuous in appearance, skin lesions in neutropenic MDS patients should be aggressively evaluated, as signs and symptoms of inflammation are often diminished or absent. 1

• Skin lesions frequently result from hematogenous spread rather than primary cutaneous infection 1
• These lesions may be the only visible manifestation of disseminated infection 1
• Early biopsy or aspiration is essential for histological, cytological, and microbiological diagnosis 1

Diagnostic Approach to End-Organ Involvement

When evaluating suspected end-organ lesions:

• Obtain at least 2 sets of blood cultures immediately before antibiotics if possible, but never delay treatment 1
• Perform chest radiography (or CT if indicated) to identify silent pulmonary sources that may have disseminated 1
• Biopsy or aspirate skin/soft tissue lesions for definitive pathogen identification, combining this with blood cultures, serial antigen detection, and nucleic acid amplification 1
• Consider sinus imaging to detect occult sources of dissemination 1

Risk Stratification for Severe End-Organ Disease

High-risk patients (MASCC score <21 or ANC <100 cells/µL for >7 days) are significantly more likely to develop disseminated or complex skin and soft tissue infections compared to low-risk patients 1

Immediate Management

Hospitalization with empiric vancomycin plus antipseudomonal antibiotics (cefepime, carbapenem, or piperacillin-tazobactam) is mandatory for all neutropenic MDS patients with fever and suspected end-organ involvement. 1

• Gram-negative bacteria must be primarily targeted initially due to high mortality rates, despite gram-positive organisms being more common 1
• Early involvement of infectious disease specialists, surgeons, and dermatologists improves outcomes when skin lesions are present 1
• Surgical debridement may be necessary if the initial antimicrobial regimen fails 1

Common Pitfall

The most dangerous error is underestimating seemingly minor skin lesions in neutropenic patients—these require the same aggressive evaluation as more dramatic presentations, as inflammatory responses are blunted and disseminated infection may be present despite minimal local findings. 1