Index: WOUNDS. 2013;25(5):136–140.

  Abstract: Primary cutaneous mucormycosis is a rare disease in the immunocompetent, and research on this condition is limited to case reports. Clinical presentation is not sufficiently distinctive to allow a diagnosis and the immunocompetent state precludes even the suspicion of the condition. There is agreement in literature regarding the absence of guidelines for its treatment. Most reports have used a combination of aggressive and repeated surgical debridement and systemic antifungals, usually amphotericin B. The authors propose the use of vacuum-assisted closure technology in managing these wounds with a possible role in decreasing the number and extent of debridement and limiting deeper tissue damage.

Introduction

  Primary cutaneous mucormycosis is a rare disease, unexpected in the immunocompetent, because fungal infections usually affect immunocompromised patients. There are only case reports in the literature.1,2 The wound is not sufficiently distinctive morphologically to allow a clinical diagnosis and the immunocompetent state precludes even the suspicion.3 There is agreement in the literature regarding the absence of guidelines for its treatment.2,4 Most reports have used a combination of aggressive surgical debridement and systemic antifungals, usually amphotericin B. The authors report an experience with managing a case of primary cutaneous mucormycosis in an immunocompetent adult with the use of vacuum-assisted closure (VAC) technology. To the best of the authors’ knowledge, this is the first report of the use of VAC for managing such wounds.

Case

  A 36-year-old male, previously in good health, fell onto masonry rubble, sustaining a minor abrasion on the right flank. The abrasion began to enlarge and produce a discharge 2 days after the injury. The patient visited a local health center where he was prescribed oral amoxicillin/clavulanate. Given the rapid enlargement of the lesion, and no response to the prescribed antibiotic, he was referred to the Jai Prakash Narayan Apex Trauma Center (New Delhi, India), a tertiary care level I trauma center, 4 days after the injury.   At presentation, the patient had a 33 cm x 24 cm oval-shaped necrotic wound in the right flank (Figure 1A) with irregular surface, mottled areas of hemorrhage, necrosis, and black, cottony exudate. The wound was odorless and the surrounding area was warm, erythematous, and indurated. His pulse rate was 92/minute; blood pressure was 130/78 mm Hg; and body temperature was 99.1º F (37.3º C).   Other systems were unremarkable. The patient was not a known diabetic, nor was he on any long-term drug therapy. Initial laboratory parameters were: hemoglobin - 13.1 g/dL; total leukocyte count - 19,000; serum Na+ - 140 mEq/L; K+ - 4.1 mEq/L; urea - 23 mg/dL; creatinine - 0.8 mg/dL; and fasting blood sugar - 76 mg%. Gram stain of wound swabs did not reveal bacteria.   The black, cottony appearance caused the authors to suspect a fungal etiology, and potassium hydroxide (KOH) preparations showed branched, nonseptate hyphae. Fungal cultures and a tissue biopsy were also taken. Serology for HIV type 1, HIV type 2, and hepatitis B were negative. The patient was started on antifungal therapy (amphotericin B) and broad spectrum antibiotics, and underwent a wide surgical debridement.   Necrosis and exudate reappeared within 24 hours. The dose of amphotericin B was gradually increased with daily monitoring of renal functions and electrolytes, and maintenance of hydration. A total of 1.5 g of amphotericin B was administered to the patient over the next 21 days. A fungal wound culture grew Rhizopus, which was confirmed on histopathology (Figure 2A). Fungal invasion of tissues and blood vessels was also demonstrated (Figure 2B). The bacterial wound cultures were sterile. A second surgical debridement was undertaken. Gross tissue necrosis and exudates were again visible the next day; a third extensive debridement was undertaken and clean muscle bed was obtained. Minimal loss of muscle tissue was noted and a decision was made to use the VAC (KCI, San Antonio, TX) device. The device was set in continuous mode at a negative suction pressure of 100 mm Hg (Figure 1B). The VAC was removed after 3 days with a total output of 1830 ml. There was minimal exudate and the wound was largely clean. The VAC was reapplied, and removed after another 3 days; total output was 950 ml. A healthy, red granulating wound was obtained (Figure 1C) but the KOH preparation was still positive for fungi. Wet gauze dressings were continued twice a day. After 1 week, a KOH mount from multiple areas of the wound was negative. Split-thickness skin grafting was undertaken and the patient was discharged after a hospital stay of 30 days.   The wound was considered healed at 1 month. At 3-month and 6-month follow-up, the patient was doing well and the wound was still healed (Figure 1D). The hospital course is described graphically in Figure 3.

Discussion

  The organisms of class Zygomyetes, order Mucorales are ubiquitous in nature and are primarily soil saprophytes.2 They have even been isolated from 22% air samples from 2 different hospitals.5 Cutaneous mucormycosis may be primary or secondary, the latter occurs by hematogenous spread as a part of disseminated disease.6-8   Mucormycosis can be nasopharyngeal, rhinocerebral, pulmonary, intestinal, and disseminated. The cutaneous form accounts for fewer than 10% of reports.7,9,10 Rhinocerebral mucormycosis in individuals with diabetes is the most common pattern.   The most common factors that predispose patients to mucormycosis are diabetes mellitus, hematological malignancies, chemotherapy, neutropenia, chronic steroid therapy, burns, renal failure, and long and complicated post-operative courses. In addition, immunosuppression puts patients at risk for developing the condition, which puts transplant recipients as a group at heightened risk for developing mucormycosis.11   Originally described in elastic adhesive tape use,12 trauma is a well-documented, though rare, modality of affliction with mucormycosis.10 An exhaustive review reports various scenarios like falls, farm accidents, traffic accidents, being kicked by a horse, abdominal impalement with a steel rod, Tsunami survivors, and volcanic eruption survivors.4 Although even trivial trauma may be implicated in the diagnosis, contamination of the wound with soil is a recurring commonality among individuals with mucormycosis.   Prognosis for patients with posttraumatic mucormycosis is poor. Limb cases have relatively better prognosis.13 Two issues present challenges to the clinician in regard to management of mucormycosis.   First, diagnosis is elusive. Because the disease is so rare in the immunocompetent, the index of clinical suspicion is low. Clinical manifestations lack specificity and are greatly variable. At one end of the spectrum are relatively superficial vesicles and pustules which may ulcerate and form eschars, and on the other is a hemorrhagic-necrotic and rapidly progressive gangrenous lesion akin to necrotizing fasciitis.14 Exudate may have a cottony appearance similar to bread mold. Although KOH mounts and special staining can rapidly identify fungi in the wound, it may not necessarily establish the diagnosis, because Mucorales may occur as skin saprophytes as well.6,7,15   The hallmark of mucormycosis is vascular invasion.15,16 Histopathological demonstration of irregular, broad, nonseptate hyphae (10µ – 20µ) with right angled branching, and characteristic hyphal invasion of blood vessels with occlusion, thrombosis, infarction, necrosis, and hemorrhage, is essential for diagnosis. The problem with diagnosing mucormycosis therefore remains that the condition has poor clinical indicators, lacks rapid laboratory methods for diagnosis, and requires a reliance on histopathology, which takes time.   Second, guidelines are lacking for managing mucormycosis. The cornerstone of treatment is repeated surgical debridement and systemic fungicidals. Most reports recommend a 1 cm - 2 cm surgical margin around the wound. While the drug of choice for the organisms of class Zygomycetes is amphotericin B, the drug is well-known for its severe side effects. Very often, a serious acute reaction after the infusion (1 hour to 3 hours later) is noted, consisting of high fever, shaking chills, hypotension, anorexia, nausea, vomiting, headache, dyspnea and tachypnea, drowsiness, and generalized weakness. Nephrotoxicity is a frequently reported side effect, and can be severe and/or irreversible. It is much milder when liposomal form of amphotericin B is used. Two liters of normal saline should be transfused in 24 hours to decrease nephrotoxicity associated with conventional amphotericin B.16   Though, historically, amphotericin B has been the most effective drug for treatment of the condition, newer alternatives like voriconazole and posaconazole may prove to be less toxic alternatives.17   In a review of upper extremity cutaneous mucormycosis in the immunocompetent, the authors have mentioned the average number of debridement procedures to be 9.14, with a range from 4 to 20.18 Many authors have reported the advantages of VAC application, especially in managing large infected wounds.19-21 But VAC therapy is not a replacement for surgical debridement. Perhaps fewer major debridement procedures may suffice if coupled with VAC therapy, as in the authors’ experience, of a very large wound. In literature there are few case reports advocating the use of VAC therapy in case of fungal cutaneous wounds.22-24 More data is needed before concluding that VAC is helpful in reducing the number of surgical debridement procedures and changing the standard of care in the case of fungal cutaneous wounds.

References

1. Li H, Hwang SK, Zhou C, Du J, Zhang J. Gangrenous cutaneous mucormycosis caused by Rhizopus oryzae: a case report and review of primary cutaneous mucormycosis in China over past 20 years. Mycopathologia. 2013 Apr 25. [Epub ahead of print] 2. Losee JE, Selber J, Vega S, Hall C, Scott G, Serletti JM. Primary cutaneous mucormycosis: guide to surgical management. Ann Plast Surg. 2002;49(4):385-390. 3. Bentur Y, Shupak A, Ramon Y, et al. Hyperbaric oxygen therapy for cutaneous/soft-tissue zygomycosis complicating diabetes mellitus. Plast Reconstr Surg. 1998;102(3):822-824. 4. Vitrat-Hincky V, Lebeau B, Bozonnet E, et al. Severe filamentous fungal infections after widespread tissue damage due to traumatic injury: six cases and review of the literature. Scand J Infect Dis. 2009;41(6-7):491-500. 5. Wirth F, Perry R, Eskenazi A, Schwalbe R, Kao G. Cutaneous mucormycosis with subsequent visceral dissemination in a child with neutropenia: a case report and review of the pediatric literature. J Am Acad Dermatol. 1997;36(2, pt 2):336-341. 6. Mizutari K, Nishimoto K, Ono T. Cutaneous mucormycosis. J Dermatol. 1999;26(3):174-177. 7. Umbert IJ, Su WP. Cutaneous mucormycosis. J Am Acad Dermatol. 1989;21(6):1232-1234. 8. Ingram CW, Sennesh J, Cooper JN, Perfect JR. Disseminated zygomycosis: report of four cases and review. Rev Infect Dis. 1989;11(5):741-754. 9. Roberts HJ. Cutaneous mucormycosis. Report of a case with survival. Arch Intern Med. 1962;110:108-112. 10. Prevoo RL, Starink TM, de Haan P. Primary cutaneous mucormycosis in a healthy young girl. Report of a case caused by Mucor hiemalis Wehmer. J Am Acad Dermatol. 1991;24(5, pt 2):882-885. 11. Walsh TJ, Groll A, Hiemenz J, Fleming R, Roilides E, Anaissie E. Infections due to emerging and uncommon medically important fungal pathogens. Clin Microbiol Infect. 2004;10(suppl 1):48-66. 12. Everett ED, Pearson S, Rogers W. Rhizopus surgical wound infection with elasticized adhesive tape dressings. Arch Surg. 1979;114(6):738-739. 13. Cocanour CS, Miller-Crotchett P, Reed RL 2nd, Johnson PC, Fischer RP. Mucormycosis in trauma patients. J Trauma. 1992;32(1):12-15. 14. Ryan ME, Ochs D, Ochs J. Primary cutaneous mucormycosis: superficial and gangrenous infections. Pediatr Infect Dis. 1982;1(2):110-114. 15. Sugar AM. Mucormycosis. Clin Infect Dis. 1992;14(suppl 1):S126-S129. 16. Kumar A, Khilnani GC, Aggarwal S, Kumar S, Banerjee U, Xess I. Primary cutaneous mucormycosis in an immunocompetent host: report of a case. Surg Today. 2003;33(4):319-322. 17. Tobón AM, Arango M, Fernández D, Restrepo A. Mucormycosis (zygomycosis) in a heart-kidney transplant recipient: recovery after posaconazole therapy. Clin Infect Dis. 2003;36(11):1488-1491. 18. Moran SL, Strickland J, Shin AY. Upper-extremity mucormycosis infections in immunocompetent patients. J Hand Surg Am. 2006;31(7):1201-1205. 19. Negosanti L, Sgarzani R, Nejad P, et al. VAC therapy for wound management in patients with contraindications to surgical treatment. Dermatol Ther. 2012;25(3):277-280. 20. Ogawa R. Treatment of surgical site infection and hypertrophic scars [in Japanese]. Kyobu Geka. 2012;65(5):409-417. 21. Webster J, Scuffham P, Sherriff KL, Stankiewicz M, Chaboyer WP. Negative pressure wound therapy for skin grafts and surgical wounds healing by primary intention. Cochrane Database Syst Rev. 2012;4:CD009261. 22. Tehmeena W, Hussain W, Zargar HR, Sheikh AR, Iqbal S. Primary cutaneous mucormycosis in an immunocompetent host. Mycopathologia. 2007;164(4):197-199. 23. Pyle JW, Holladay J, Molnar JA, Martin JS, Defranzo AJ. Multiple modality treatment regimen in an aggressive resistant fungal hand infection: a case report. Hand (N Y). 2010;5(3):318-321. 24. Blazquez D, Ruiz-Contreras J, Fernández-Cooke E, et al. Lichtheimia corymbifera subcutaneous infection successfully treated with amphotericin B, early debridement, and vacuum-assisted closure. J Pediatr Surg. 2010;45(12):e13-e15. The authors are from the Jai Prakash Narayan Apex Trauma Center, All India Institute of Medical Sciences, New Delhi, India. Address correspondence to: Subodh Kumar, MD, FACS Room No. 306 Jai Prakash Narayan Apex Trauma Center All India Institute of Medical Sciences New Delhi – 110029 subodh6@gmail.com