1. Primary Cutaneous Mold Infections in Hematologic Malignancy
with a Review of the Literature
Jane Mai, MD, MPH*1; Abraham T. Yacoub, MD2; Kiran Soni, JD1; Lysenia Mojica, MD1; Ramon L. Sandin MD, MS2
Jamie Morano MD, MPH1; Aliyah Baluch, MD, MSc2; John N. Greene, MD2
1University of South Florida Morsani College of Medicine, Tampa, FL 2Moffitt Cancer Center, Tampa, FL
1466
PURPOSE
METHODS
The literature was reviewed for all cases of primary cutaneous fungal infections in immunosuppressed patients reported in the English literature utilizing the PUBMED database from with the search terms “primary,” “cutaneous,” “fungal,” “infection” and “cancer.”
The review yielded 50 cases of primary cutaneous fungal infections in patients with hematologic malignancies with few cases excluded if there was lack of significant comparable data.
The data was then organized onto a spreadsheet which included basic demographics such as age, sex, patient’s neutropenic status and type of underlying hematologic malignancy (Table 1)
Fungal pathogens were identified to the genus and species level when possible (Figure 4)
Information regarding the treatment modalities (surgical vs non-surgical intervention) and the outcomes of treatment (survival vs death) were also analyzed (Figure 5)
To present a case of primary cutaneous gangrenous mucormycosis in a neutropenic 72 year-old female with aplastic anemia after cat bite exposure
To discuss a review of the literature of all cases of primary cutaneous fungal infections in immunosuppressed patients with hematologic malignancies
Correlate clinical risk factors/ treatment modalities in terms of survival outcomes
INTRODUCTION
Mucorales are comprised of abundant, ubiquitous, saprobic, and rapidly growing mycelia, which are typically unseptate or irregularly septate [1].
Opportunistic fungal infections are often lethal in patients with hematologic malignancies [3] .
Mucormycosis is a broad term for a multitude of diseases caused by infection with different fungi in the order of Mucorales and the most common causative organisms are from the Rhizopus species [5].
There are six clinical forms of mucormycosis: rhinocerebral, cutaneous, pulmonary, disseminated, gastrointestinal and miscellaneous [7].
Two main types of cutaneous fungal infections in the immunocompromised and neutropenic patient are 1) primary cutaneous fungal infections and 2) cutaneous manifestations of fungemia from hematogenous spread [4].
Primary cutaneous mucormysosis infections are extremely rare, and the incidence, survival outcomes, and factors associated with survival within hematologic malignancies are not clear.
Figure 1: Right forearm eschar
Figure 2: Right forearm after debridement
RESULTS
We identified a total of 51 cases of primary cutaneous mold infections in patients with hematologic malignancies between 1980 and 2013
In the 51 cases identified, 28 (54.9%) of these patients were male and 23 were female
The median age of these patients was 26 years and mean age was 32 years
87.2% of the patients were neutropenic upon presentation
Aspergillus species (17, 33.3%) was the most cited followed by Rhizopus species (10, 19.6%) (Figure 4) as the causative organism
15 patients (29.4% of all patients) did not survive
The majority of the patients that did not survive were neutropenic (60%) and did not receive any surgical intervention (80%)
22 patients (43.1%) underwent surgical intervention. Of the 22 patients that received surgical debridement, 19 patients survived (86.4%) versus 3 patients died (13.6%) (Figure 5)
29 patients (56.9%) did NOT receive any surgical intervention and of those patients, 17 patients survived (58.6%) and 12 patients died (41.4%) (Figure 5)
Figure 3: Haematoxylin + eosin stains of punch biopsy showing multiple, broad ribbon-like hyposeptated hyphae with abundant vascular invasion. This is characteristic of Zygomycetes.
CASE REPORT
VARIABLE
Total
(n = 51)
Survival
(n = 36)
Death
(n = 15)
AGE (years)
Mean 32
Median 26
GENDER
Male 28 21 7
Female 23 15 8
NEUTROPENIA
ANC < 500 34 25 9
ANC > 500 5 3 2
Not Stated 12 4
MALIGNANCY
AML/MDS/AMML 18
ALL 6
CML 1
CLL
Hodgkin’s lymphoma
Non Hodgkin/Mixed cutaneous Lymphoma
Aplastic Anemia
Multiple Myeloma
History of Present Illness:
72 year-old female with history of aplastic anemia and prolonged neutropenia was transferred from an outside hospital for a lesion on her right forearm
She sustained a traumatic cat bite to the area approximately 13 days prior to her initial hospitalization
The patient denied fevers, chills, sweats or other penetrating trauma
Labs at the outside hospital revealed that she had 2/2 positive blood cultures growing Pseudomonas aeruginosa
On hospital day 4, the patient developed a right forearm lesion (approximately neutropenia day 30+)
On hospital day 16, she was transferred to the referral cancer facility on vancomycin, cefepime, metronidazole, fluconazole and acyclovir. There was immediate suspicion that the right forearm lesion was fungal in origin during the initial Infectious Disease evaluation.
Physical Exam:
Vital signs were within normal limits
On the dorsal aspect of her right forearm there was a prominent 12x14 cm flat, homogenous, circular eschar with surrounding erythema (Figure 1)
Laboratory analysis:
Significant for absolute neutrophil count (ANC) of 70/mm3 and platelet count of 65/mm3 (neutropenia day 40+)
Hospital Course:
Bedside punch biopsy of the forearm lesion’s histological sections revealed multiple broad-hyposeptated hyphae in cross sectional and longitudinal views with abundant vascular invasion, consistent with Zygomycetes fungi (Rhizopus spp.) (Figures 3)
Treatment was adjusted to amphotericin B liposomal 5mg/kg IV daily and posaconazole 300mg delayed release tablets PO BID on day 1 then 300mg PO daily. This anti-fungal regimen was started immediately and the patient underwent prompt surgical evaluation.
The wound was extensively debrided however the fungal infection had invaded the entire forearm extensor compartment including the skin, fat, fascia and underlying musculature demonstrating significant necrosis (Figure 2). It was determined that the wound would best be resolved with amputation of the extremity which the patient and daughter both declined.
The area was closed and a temporary skin allograft was applied.
The patient and family subsequently declined any further surgical intervention or treatment and she was discharged home with hospice.
DISCUSSION
Primary cutaneous mucormycosis is an increasingly prevalent form of mucormycosis which has been described predominantly in immunocompromised patients after minor trauma [11, 12].
Neutropenia within hematologic malignancies demonstrates a risk for developing severe cutaneous fungal infections of which cutaneous mucormycosis can carry significant mortality.
Patients with hematological malignancies are at risk of developing opportunistic fungal infections in areas of minor or major skin trauma (i.e. intravenous catheters with dressings or animal bites).
Early biopsy of non-healing skin lesions, especially at known sites of penetrating trauma in immunosuppressed patients is essential for initiating appropriate anti-fungal therapy and early surgical evaluation [38].
Patients with surgical therapy are 4.5 times more likely to survive than patients without surgical intervention (p= 0.031, OR =4.5, CI ).
Early surgical evaluation in combination with aggressive anti-fungal therapy must be considered for neutropenic patients with hematologic malignancies and cutaneous mold infections.
From this case series, clinicians should be aware that combination antifungal therapy/ surgical debridement appears be associated with higher survival outcomes in patients with primary cutaneous mold infections in hematologic malignancies and warrants further investigation.
Table 1: Clinical characteristics of case series
Figure 4: Distribution of reported primary cutaneous molds infections
Number of cases
(n = 51)
Non-surgical
(n = 29, 56.9%)
Surgical
(n = 22, 43.1%)
Survived
(n = 17, 58.6%)
Deceased
(n = 12, 41.4%)
Survived
(n = 19, 86.4%)
Deceased
(n = 3, 13.6%)
REFERENCES
Figure 5: Number of patients who underwent non-surgical vs surgical intervention and survival outcomes
Please see supplemental handout