To the Editor:
Disseminated candidiasis typically manifests with severe symptoms in
immunocompromised patients and may infrequently present with cutaneous
findings. The mortality rate of candidemia in patients who develop skin
involvement approaches 80%.1 While Candida
albicans is the predominant causative pathogen, Candida kruseiis on the rise and accounts for approximately 1.5-8% of
cases.2 We illustrate an atypical case of C.
krusei fungemia that presented with subtle skin findings in an afebrile
oncology patient, despite amphotericin B prophylaxis.
A 23-year-old female with a one-year history of BCR/ABL-negative B-cell
acute lymphoblastic leukemia with leptomeningeal disease treated with
craniospinal irradiation, refractory to multiple lines of chemotherapy
and CART-cell infusion, was consulted by the dermatology service for an
asymptomatic rash present for two days. The rash started on the face and
spread caudally. On physical examination, she had a diffuse eruption
consisting of multiple pink-to-red macules and papules with surrounding
erythema most prominent on the face and trunk (Fig 1). There were no
vesicles, pustules, erosions, or ulcers with sparing of the oral mucosa
and conjunctiva. Her current medications included venetoclax and
ibrutinib, as well as levofloxacin, valacyclovir, atovaquone, and
micafungin for infection prophylaxis. Blood cultures revealed candidemia
and bacteremia prior to consult, and she was started on amphotericin B,
voriconazole, daptomycin, and meropenem. Given the morphology and
frequent medication changes, a drug reaction was suspected. We also
considered viral exanthem, thrombocytopenic purpura, and fungemia. While
she had previously experienced neutropenic fevers, vital signs at the
time of consult were within normal limits. Significant laboratory
results included pancytopenia with a neutrophil count of 0.0
k/uL. Skin punch biopsy of the right leg demonstrated aggregated
yeast in and around a blood vessel in the papillary dermis, highlighted
with PAS-D stain (Fig 2). The biopsy findings were compatible with
hematogenous yeast dissemination. Blood culture eventually confirmed the
fungal species as Candida krusei and bacterial species asEnterococcus faecium . Despite aggressive therapy, she expired
three days later.
Candida krusei is a rare, often fatal cause of fungemia, most
commonly observed in severely neutropenic patients with hematologic
malignancies.3 Its intrinsic resistance to azole
antifungal agents, specifically fluconazole, and reduced susceptibility
to other azoles and polyenes, including amphotericin B, makes
prophylaxis and treatment challenging.2,4 Furthermore,
azole prophylaxis is reported to increase the risk of C. kruseicandidemia.3 Although reports are limited, cutaneous
lesions may be an initial sign of disseminated C. krusei and vary
from erythematous papules, with or without necrosis and crusting, to
pustulonodular lesions.5 Neutropenic patients are at
risk of severe cutaneous manifestations, including diffuse necrotic
varicelliform papules associated with pain and
pruritis.4 Though our patient was severely
neutropenic, her eruption only consisted of asymptomatic
red-to-violaceous macules and papules predominantly localized to the
face and upper trunk.
While less prevalent, C. krusei infection carries higher
mortality than C. albicans .4 Unlike C.
albicans , which is typically associated with catheter-related
bloodstream infection, the source of C. krusei is frequently
unidentified. However, C. krusei is commonly linked to
gastrointestinal colonization, which is more likely in the setting of
poly-antimicrobial use.5 We theorize that our
patient’s immunosuppression and antimicrobial prophylaxis for
opportunistic infections placed her at risk of gastrointestinal
colonization and dissemination.
This case highlights the diagnostic and treatment challenges surrounding
C. krusei . Since the most susceptible individuals have
pancytopenia on numerous medications, a purpuric eruption may be
attributed to drug reactions or thrombocytopenia. Therefore, new
disseminated cutaneous lesions in an oncology patient, even without
fever, should raise concern for fungemia. There should be a low
threshold for obtaining skin biopsy in these high-risk patients.
Increasing the awareness of the heterogeneous manifestations of C.
krusei is essential given the high mortality rate.
Ethics Statement: Informed patient consent was obtained for
publication of the case details and photographs.