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Disseminated zygomycosis heralded by a subtle cutaneous finding

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Disseminated zygomycosis heralded by a subtle cutaneous finding
Thomas Lewis Hocker MD, David Akio Wada MD, Alina Bridges DO, Rokea el-Azhary MD PhD
Dermatology Online Journal 16 (9): 3

Mayo Clinic


BACKGROUND: Zygomycosis is the preferred name for the angiotropic infection produced by the Zygomycete class of fungi. Although healthy individuals may be affected, the majority of patients diagnosed with zygomycosis have diabetes, malignancy, or have had solid organ or bone marrow transplantation. Unlike other filamentous fungi that tend to disseminate hematogenously to skin, cutaneous zygomycosis most commonly arises via direct inoculation. Cutaneous lesions of zygomycosis are characteristically hemorrhagic, ulcerated or necrotic plaques. Histology typically demonstrates angioinvasion with associated necrosis. CASE: We present a case of a neutropenic patient who presented with disseminated zygomycosis heralded by a clinically non-specific erythematous macule that showed non-specific, mild, inflammatory changes on histological examination. Tissue culture was performed at the time of initial evaluation and was consistent with zygomycosis. Rhizomucor was subsequently confirmed by PCR. The patient was diagnosed with disseminated zygomycosis, treatment was promptly initiated, and the patient recovered completely. Our case represents an atypical clinical and histological presentation of disseminated zygomycosis and highlights the value of performing tissue culture of non-distinctive cutaneous lesions, especially in the setting of severely immunocompromised states.

Case report

Figure 1Figure 2
Figure 1. Photograph of the right abdomen showing a faintly erythematous macule.

Figure 2. Biopsy demonstrated dermal edema and nonspecific dermal inflammation.

A 45-year-old male with AML who recently underwent induction chemotherapy with 7+3 cytarabine and idarubicin was admitted to the hematology service for neutropenic fever. He was found to have S. epidermidis bacteremia and was discharged home on levofloxacin, daptomycin, and rifampin. He was continued on prophylactic acyclovir and voriconazole, which he had been taking prior to admission. One week later, he was re-admitted for neutropenic fever. CT scan showed a new consolidation in the lingula along with a pleural effusion. On exam, the patient was afebrile and appeared quite comfortable. He was noted to have a mildly tender erythematous macule on the right abdomen (Figure 1) that had been present for 2-3 days. He denied any recent trauma or instrumentation in that area.

Figure 3Figure 4
Figure 3. Tissue culture obtained from 4 mm punch biopsy. Rhizomucor classically grows rapidly, maturing within 4 days. The texture has been likened to “cotton-candy.”

Figure 4. Tissue culture from 4 mm punch biopsy demonstrates sparsely septate broad hyphae, irregularly branched sporangiophores, brown-colored round sporangia, and rhizoids that are located on stolons between the sporangiophores. Morphology was consistent with Rhizomucor.

Two adjacent 4 mm punch biopsies were obtained: one for histologic examination and one for tissue culture. The H&E demonstrated dermal edema and nonspecific dermal inflammation (Figure 2). Gram, GMS, and AFB stains were all negative. Despite the non-specific histological findings, tissue culture yielded growth of zygomycosis within 3 days (Figures 3 and 4). Rhizomucor sp., was confirmed via PCR.

Notably, cultures obtained from all other body sites during the hospitalization were negative, including: blood, bone marrow, bronchoalveolar lavage, and pleural fluid. The patient was treated with liposomal amphotericin B and G-CSF. Serial CT scans showed progression of his abdominal skin lesion with involvement of the abdominal wall musculature. New pulmonary nodules were also noted. Posaconazole was added and the surgery department was consulted. The infection stabilized with medical therapy while the patient was awaiting surgery. Ultimately, a wedge excision of the lingula and wide excision of the intramuscular abscess on the right abdominal wall were performed. Fungal smears from the surgical specimens confirmed the diagnosis of disseminated zygomycosis. The patient recovered and is currently awaiting bone marrow transplantation for his AML.


Zygomycosis is the preferred name for the angiotropic infection produced by the zygomycete class of fungi, which includes three orders: Mucorales, Entomophthorales, and Mortierellales. An older alternative name, Mucormycosis, has fallen out of favor because it fails to reflect the wide diversity of human pathogens within the class zygomycetes.

The incidence of zygomycosis has steadily increased since the 1940s. Unfortunately, the mortality rate has remained between 47-57 percent since the 1960s when amphotericin B began to be widely utilized. Although healthy individuals may be affected, the majority of patients diagnosed with zygomycosis have diabetes or malignancy, or have undergone solid organ or bone marrow transplantation [1]. Zygomycosis most commonly affects the sinuses and pulmonary system.

Unlike other filamentous fungi that tend to hematogenously disseminate to the skin, cutaneous zygomycosis is rarely (3%) caused by disseminated infection but instead arises via direct inoculation [2]. Primary cutaneous infection can involve the muscle or bone, and can become disseminated in up to 25 percent of cases. Cutaneous lesions characteristically present as hemorrhagic or necrotic plaques and ulcers. In contrast, our patient had relatively subtle skin findings and no history of trauma to suggest direct inoculation.

Disseminated zygomycosis may occur in severely immuno-compromised patients and is associated with an exceedingly high mortality rate [3]. Therefore, early recognition of cutaneous zygomycosis is essential. Histological examination of cutaneous lesions usually demonstrates angioinvasion and necrosis, but this was not present in our patient’s biopsy. Tissue culture can be used to aid in diagnosis. DNA sequencing helps with speciation but is not widely available.

Primary treatment consists of surgical excision plus antifungal therapy with amphotericin B or a second-generation azole such as posaconazole [4]. In addition to surgical treatment and antifungal agents, G-CSF has been reported to be of some benefit [5]. First generation azoles and voriconazole – which this patient was taking for prophylaxis – have minimal to no activity against zygomycetes. In fact, several reports have documented an increase in zygomycosis among stem cell transplant recipients receiving voriconazole for treatment or prophylaxis [6, 7].

In our patient, tissue culture of a subtle skin lesion allowed for early recognition of disseminated zygomycosis. Rapid initiation of liposomal amphotericin B and posaconazole seemed to help hold the infection at bay while the patient was awaiting definitive surgical excision. This case represents a subtle presentation of disseminated zygomycosis and highlights the value of performing tissue culture in immunocompromized patients who present with non-specific skin findings.


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