EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Mucormycosis is an uncommon opportunistic infec-tion that is caused by Mucorales from the Zygomycetes class. Patients with severe immuno-deficiency admitted to the hospital are at greatest risk for developing this infection. Mucormycosis usually is transmitted in humans by inhalation or inoculation of spores in the skin or mucous membranes.

A 66-year-old man developed a surgical wound infection at 1 week after kidney transplant that did not improve despite broad-spectrum antibiotics and debridement. He was transferred to our hospital 45 days after transplant and had fever and a large purulent wound that was surrounded by a black necrotizing margin. Immunosuppressive drugs were discontinued and the dosage of prednisolone was decreased. Massive debridement was performed but was incomplete because he had full-thickness abdominal wall necrosis. Histopathology showed broad fungal hyphae without septation, consistent with the diagnosis of mucormycosis. Despite antifungal therapy with amphotericin B and additional debridement, the patient died of septic shock at 52 days after kidney transplant.

Cutaneous fungal infections should be considered in the differential diagnosis of any nonhealing infected wound that does not respond to broad-spectrum antibiotics, especially in patients with predisposing risk factors such as transplant.

Key words : Complications, Fungus, Immunosuppression, Infection, Skin

Mucormycosis is an uncommon opportunistic infection that is caused by Mucorales fungi from the Zygomycetes class.^1-5 These grow rapidly and produce airborne spores.6 These spores are ubiquitous and commonly grow in the soil, animal waste, vegetables, fruits, and breads. Mucorales also may be found in the air of hospitals and laboratories, on tongue blades and dressings, in hospital water, and in the nose and mouth of a healthy person.^1,5,7-9

The risk factors for developing mucormycosis include poorly controlled diabetes mellitus, immuno-suppressive drugs, chemotherapy, hematologic malignancies (eg, leukemia and lymphoma), neutro-penia, contaminated traumatic ulcers, burn wounds, malnutrition, stem cell and solid-organ transplant recipients, kidney and liver failure, corticosteroid therapy, broad-spectrum antibiotic therapy, defer-oxamine therapy, intravenous drug use, and low birth weight.^1,4,5,10,11 Patients who have severe immunodeficiency and who are admitted to the hospital are at greatest risk for developing this infection.⁵

Mucormycosis usually is transmitted in humans by inhalation or inoculation of spores in the skin or mucous membranes.¹¹ Cutaneous mucormycosis arises from inoculation of spores at skin wounds caused by trauma, laceration, surgery, injection, burn, abrasion, insect bite, or tattoo. Contaminated dressings and hematogenous spread rarely may cause mucormycosis.^4,5,7,11

Mucormycosis has many clinical manifestations.⁶ The 5 main types of involvement include rhinocerebral (frequency, 39%), pulmonary (24%), cutaneous (19%), gastrointestinal, and disseminated.^5,12 The cutaneous type is rare but has the best survival when diagnosed early because cutaneous disease frequently may be resected completely.⁴ Cutaneous mucormycosis may vary from a mild chronic infection to rapidly progressive disease.^4,11 There is no pathognomonic sign for mucormycosis, and symptoms may vary with patient condition and immunosuppressive state.⁴ Common signs of cutaneous mucormycosis include black necrotic tissue that is caused by vascular invasion, thrombosis, and infarction. In addition, patients may have fever, severe pain, cutaneous erythema, cellulitis, vesicles, pustules, nodules, and lesions that appear similar to ecthyma gangreno-sum.^4,11,12 Infection usually progresses rapidly because of fungal invasion and destruction of deep cellular layers.⁷ The differential diagnosis of cutaneous mucormycosis includes ecthyma gangrenosum, pyoderma gangrenosum, vasculitis, and other fungal infections such as aspergillosis, histoplasmosis, and cryptococcosis.²

We treated a patient who died because of cutaneous mucormycosis after kidney transplant. The purpose of this report is to describe the clinical course of this patient and increase awareness about the possibility of this infection in patients after kidney transplant.

A 66-year-old man was evaluated for fever and wound necrosis after a kidney transplant. He had end-stage renal disease for 10 years and received hemodialysis for 10 months. Past medical history included diabetes mellitus and hypertension. He received a kidney transplant in another hospital, and the immunosuppressive regimen after transplant included prednisolone (60 mg/d), mycophenolate mofetil (1 g twice daily), and tacrolimus (3 mg twice daily). At 1 week after transplant, a surgical wound infection was observed. The sutures were opened and pus was evacuated. Despite broad-spectrum antibiotics (imipenem, vancomycin, and ciprofloxacin) and 3 débridements, the soft tissue infection worsened.

At 45 days after transplant, the patient was referred to Imam Khomeini Hospital. He had fever and a large purulent wound that was surrounded by a black necrotizing margin. There was yellow discharge noted across the abdominal wall distant from the surgical incision (Figure 1). The bacterial culture from the wound showed no growth. Broad spectrum antibiotics were continued. Mycophenolate mofetil and tacrolimus were discontinued and the dosage of prednisolone was decreased to 30 mg/day. The patient had a biopsy of the skin and soft tissue at the wound margin and underwent massive debridement, which showed full-thickness abdominal wall necrosis. Debridement was incomplete because of the potential risk of exposed abdominal viscera. Empiric antifungal therapy with amphotericin B (70 mg/d) was started. Histopathology showed broad fungal hyphae without septation, consistent with the diagnosis of mucormycosis that invaded the subcutaneous tissue (Figure 2). Additional wound debridement was performed, but the patient died of septic shock at 52 days after kidney transplant.

This kidney transplant recipient died because of cutaneous mucormycosis at the surgical wound. Mucormycosis comprises a small proportion of invasive fungal infections in organ transplant recipients but is associated with high mortality in these patients.¹¹ Most cases of mucormycosis in organ transplant recipients have been reported after kidney transplant.⁹ Kidney transplant recipients may be susceptible to this infection because of long-term immunosuppression associated with renal failure, frequent use of various antibiotics, malnutrition, uremia, old age, and posttransplant diabetes mellitus.⁶ In a study of 16 kidney transplant recipients with mucormycosis, the most common types were rhinocerebral (56%), pulmonary, and disseminated mucormycosis, but no patients had cutaneous mucormycosis.⁶ In organ transplant recipients, the prevalence of cutaneous mucor-mycosis is 5% to 7%, and disseminated disease may occur with cutaneous involvement.^8,11

The average time from transplant to occurrence of mucormycosis is 60 days (range, 1 d to 8 y).⁹ Risk factors for mucormycosis in organ transplant recipients include kidney transplant, posttransplant diabetes mellitus, and previous use of voriconazole and caspofungin; whereas tacrolimus may be associated with a decreased risk of developing mucormycosis.^6,11 The present patient developed signs of infection at 1 week after transplant, and he had several risk factors for mucormycosis including chronic kidney disease, long-term diabetes mellitus, kidney transplant, and immunosuppressive therapy.

The diagnosis of mucormycosis may be difficult to make, and clinician must have awareness and high clinical suspicion about this problem.^1,4 In the present patient, the diagnosis of fungal infection was considered late and only after prolonged antibiotic therapy with no response. Early diagnosis and treatment of mucormycosis is important for preventing morbidity and mortality.² The best diagnostic methods include tissue biopsy for direct smear and fungal culture.¹ Histopathologic examination may show ribbonlike, wide, thick hyphae with right angle branches and no septation. Other histopathologic findings include vascular invasion, thrombosis, infarction, and hemorrhage.^1,2,4,5

Treatment of mucormycosis includes minimizing immunosuppressive drugs, correcting metabolic disorders, performing radical surgical debridement, and giving systemic antifungal drugs. Amphotericin B is the best antifungal drug, but some azoles such as posaconazole may have efficacy against Mucorales.^1,3,4 Surgical debridement of all gangrenous tissue must be performed until healthy tissue is observed, and this may require several operations; however, complete surgical debridement sometimes may not be feasible because of the anatomic structures involved.^2,12 Despite treatment, the frequency of mortality from mucormycosis may be 60%.^1,4,6 In 1 study of 16 transplant patients who had mucor-mycosis, 10 patients (63%) survived after treatment.⁶

In summary, the present case confirms that cutaneous mucormycosis after kidney transplant may be fatal. Rapid progression of infection occurred, and complete debridement was impossible because of extensive cutaneous involve-ment. Delay in diagnosis and treatment may have contributed to the poor outcome. Therefore, cutaneous fungal infections should be considered in the differential diagnosis of any nonhealing infected wound that does not respond to broad-spectrum antibiotics, especially in patients who have predisposing risk factors such as transplant.¹²

Volume: 13 Issue: 1 February 2015

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