Management of Persistent Fever and Rash in Immunocompromised Patients

Evaluation and Antifungal Therapy

The European Society for Medical Oncology recommends performing comprehensive imaging of the chest and upper abdomen to exclude fungal or yeast infection and abscesses, especially with rising C-reactive protein 1
The European Society for Medical Oncology suggests considering empiric antifungal therapy immediately, as persistent fever for >4-6 days in an immunocompromised patient strongly suggests fungal infection 1, 2
Initiate empiric amphotericin B after 4-7 days of persistent fever despite broad-spectrum antibiotics, as this has been shown to reduce morbidity and mortality from fungal pathogens 3
The common presentation of fungal infection in granulocytopenic patients is protracted fever despite broad-spectrum antimicrobial therapy and repeatedly negative blood cultures 3
Continue broad-spectrum antibiotics while initiating antifungal therapy, as discontinuation may be associated with fatal bacteremia 3

Monitor EBV DNA levels; levels >10³ copies per milliliter are relevant for the development of EBV-associated hemophagocytic lymphohistiocytosis (HLH) 4
For patients with continuously increasing or sustained high levels of EBV DNA despite rituximab, stem cell transplantation should be considered 4
Although CMV has been cleared, continue monitoring for reactivation, as immunosuppressed patients are at risk for recurrence 5
If CMV reactivation occurs, treat with oral valganciclovir or alternatively with intravenous ganciclovir or foscarnet 5

Consider HLH as a potential diagnosis in patients with persistent fever, cytopenias, and organomegaly, particularly in the setting of EBV infection 4
EBV-triggered HLH may require etoposide treatment without delay if rapid clinical deterioration occurs 4
Monitoring of ferritin, soluble CD25, cell counts, and EBV DNA aids in assessing treatment response 4

Evaluate the need for alternative lymphoma therapy if current regimen is ineffective 6

If clinically stable despite persistent fever, continue with initial antibacterial therapy 1
If clinically unstable, broaden antibacterial coverage and consider adding a glycopeptide 1
Seek expert advice from infectious disease physician or clinical microbiologist for patients with deteriorating condition 1, 2

Assess for tuberculosis reactivation, which can occur in patients receiving immunotherapy 7