Allograft of Primary Cutaneous Mucormycosis in a Preterm Neonate: A Case Report

Mucormycosis is a fungal infection caused by organisms of the order Mucorales. Preterm neonates are at an increased risk for primary cutaneous mucormycosis (PCM), as they are often in critical condition with poorly developed immune functions. A preterm neonate’s skin has a thinner epidermis and dermis with smaller collagen fibrils and fewer connecting points between the 2 layers.¹ 

Primary cutaneous mucormycosis can develop when organisms from the environment are inoculated via cutaneous trauma, including invasive device entry sites.² Fungal hyphae invade vessels, causing thrombosis and surrounding tissue necrosis. During early stages, the skin may appear normal but then quickly become erythematous and edematous before turning necrotic.

There is little information regarding treatment for PCM in preterm neonates. Aggressive antifungal therapy and debridement with grafting previously have been reported to be effective.² Reports of grafts used include tumescent skin autografting, allograft overlying autograft, and bilayered cellular matrices, also known as Transcyte (Shire Regenerative Medicine, San Diego, CA), from donor neonatal foreskins.^2-4 In this case report, the authors discuss the use of wound excision and allografting as a therapeutic option for neonatal PCM in addition to systemic antifungal therapy. 

A female preterm triplet was born to a 35-year-old G1P0211 mother at 23⁴⁺ weeks gestation due to preterm premature rupture of the membranes and maternal chorioamnionitis. Birth weight was 605 g. She was delivered vaginally in breech position. The Apgar scores were 1 and 8 at 1 and 5 minutes, respectively. She developed respiratory distress syndrome and required ventilatory support and surfactant replacement therapy. Umbilical lines were placed at birth. She was pancytopenic on delivery (white blood cell: 2800, platelet: 109).

On day of life (DOL) 4, a papular rash was noted on her chest wall and back. Fluconazole and liposomal amphotericin B (LAmB; AmBisome [Gilead Sciences, Inc., Foster City, CA]; 3 mg/kg intravenously) were initiated. Fungal cultures and potassium hydroxide smears were sent. On DOL 6, the lesion progressed to a necrotic plaque with eschar located on the right chest with satellite lesions on her back. The thoracic lesion continued to progress into a large, firm eschar involving 5 cm x 5 cm of the right thoracoabdominal wall (Figure 1). 

On DOL 11, the burn surgery service was consulted. In addition to the eschar, a new, crusting white lesion was noted on the back (Figure 2). The LAmB dose was increased to 5 mg/kg. Betadine and bacitracin were applied to the right thoracoabdominal lesion twice daily and nystatin powder to the white lesion on her back while systemic LAmB was continued. The initial decision to not excise the eschar was made due to concerns that the lesion may have extended deep into the chest wall, with resection potentially leading to further respiratory compromise. 

The right thoracoabdominal cultures revealed an organism morphologically consistent with the Rhizopus genus and also Aspergillus niger of the back; Rhizopus isolates were not further speciated. The lesion involved the full thickness of the skin. It was at operation that the authors identified the tissue damage extended through the chest wall. 

Intraoperatively, tissue necrosis involved skin, subcutaneous fat, muscle, and portions of 3 ribs, and extended to the deepest layer of intercostal muscle with sparing of some fibers and preservation of the parietal pleura. There was a small but noticeable air leak with positive pressure respirations, which disappeared after application of the allograft. The surgical team covered the defect (measuring, 5 cm x 5 cm) with a freshly thawed human cadaver allograft, held in place with absorbable sutures (Figure 3). There was about 3 mL of blood loss. The grafted wound and back lesion were dressed in a long-acting, silver-containing dressing (ACTICOAT Antimicrobial Silver Dressing; Smith & Nephew, Fort Worth, TX). The patient remained hemodynamically stable throughout the procedure. The skin biopsies sent at excision confirmed culture findings of Rhizopus and A niger. The graft was monitored for several weeks and showed no sign of rejection (Figure 4). There was excellent graft take, albeit with some degree of epidermolysis. 

The patient’s overall course remained unstable. She showed no evidence of persistent fungal infection, but had recurrent episodes of group B streptococcal sepsis, requiring systemic antimicrobials, enteral nutrition, and progressive weaning from positive pressure ventilation. She ultimately succumbed to a third recurrence of sepsis on DOL 101. There was no postmortem exam. The allograft had remained in place for about 11 weeks.

The authors report treatment of PCM in a preterm neonate with systemic antifungal therapy and allografting as an alternative method that may reduce bleeding and infection risk for infants in critical states.

Research^4,5 has described debridement and graft placement for treatment of PCM. Kumar et al⁴ described tumescent skin grafting in a preterm neonate with PCM. While autografting in a preterm neonate eliminates graft rejection risks, allografting in this case was effective with minimal blood loss and anticipated lower infection risk, given the absence of a donor site. Assali⁵ previously noted that infants reject allografts from sources other than parents or siblings, but the authors found no primary data on allograft outcomes in preterm neonates. 

Considering neonatal immunologic immaturity, one might expect the allograft to initially take but need future replacement with an autograft as the infant matures; however, it is also possible the allograft would persist long enough for native tissue to grow into it, eliminating the need for later autografting. Research in transplant recipients have shown it is possible for allografts to survive indefinitely in immunosuppressed patients.⁶ In patients whose immunosuppressants were discontinued, skin allograft cells were destroyed and replaced with autogenous cells.⁶ Even though long-term graft outcomes are uncertain, allografting serves as a temporizing option to either allow native skin to grow in or to provide time for the neonate to stabilize clinically and clear the infection prior to autografting.

Early identification and treatment are critical to managing patients with PCM. In this case, starting antifungal therapy on DOL 8 and operating on DOL 17 demonstrated good outcomes with respect to the lesion. Earlier intervention may have been warranted to avoid deep chest wall extension, which can compromise respiratory mechanics and complicate the surgical approach. In this case, operative intervention was delayed due to the patient’s critical status and initial uncertainty about the diagnosis.

In conclusion, PCM is a condition with life-threatening outcomes in preterm neonates. Allografting can serve as a valuable option for immunologically and physiologically immature preterm infants, with lower risk for blood loss and infection, and, as demonstrated in this case report, prolonged graft survival. 

Authors: Tania Benjamin, MD¹; Rachel L. Wattier, MD²; and William Dominic, MD³

Affiliations: ¹Resident Physician, Department of Otolaryngology – Head and Neck Surgery, University of California San Francisco (UCSF), San Francisco, CA; ²Division of Infectious Diseases and Global Health, Department of Pediatrics, UCSF; and ³Department of Surgery, UCSF Fresno, Fresno, CA

Correspondence: Tania Benjamin, MD, Resident Physician, 2233 Post St, San Francisco, CA 94115; tania.benjamin@ucsf.edu 

Disclosure: The authors disclose no financial or other conflicts of interest.