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Peer Review

Peer Reviewed

Case Q&A

A Case of Upper Extremity Gangrene Likely Secondary to Mucormycosis

October 2024
1937-5719
ePlasty 2024;24:QA23
© 2024 HMP Global. All Rights Reserved.
Any views and opinions expressed are those of the author(s) and/or participants and do not necessarily reflect the views, policy, or position of ePlasty or HMP Global, their employees, and affiliates.

Questions

1. What is the epidemiology and pathology of a mucormycosis infection of the upper extremity?

2. What are some risk factors, signs, and symptoms associated with mucormycosis infections of the upper extremity?

3. What is the surgical management of a mucormycosis infection of the upper extremity?

4. What is the likely outcome of a secondary cutaneous mucormycosis infection?

Case Description

A 77-year-old male with a medical history of benign prostatic hyperplasia, neurogenic bladder with chronic indwelling catheter, hypertension, diabetes type 2 (hemoglobin A1c of 5.9 at 1 month prior to presentation), extensive coronary and arterial disease, and heart failure with reduced ejection fraction presented to our service with a 9-day history of a black, gangrenous left middle finger (Figure 1). Purulence was not encountered upon initial consultation.

Figure 1

Figure 1. Various views of the left middle finger upon presentation to our service.

The patient initially underwent ray amputation and debridement of devitalized tissues (Figure 2). The patient was immediately placed on anidulafungin, linezolid, meropenem, and vancomycin. Wet to dry dressing changes were utilized for the first 2 days post operation. On the second postoperative day, significant progression of necrosis was noted, and the rest of the hand was deemed nonviable (Figure 3). Mucormycosis was suspected as a possible cause, and liposomal amphotericin B was initiated. A distal trans-radial amputation of the left hand was then performed and wet to dry dressing changes were continued.

Figure 2

Figure 2. Left hand surgical site immediately after amputation of the left middle finger.

Figure 3

Figure 3. The surgical site of the left hand showing spreading necrosis and infection.

Over the next few days, the patient subsequently entered multi-organ failure and septic shock. While on hemodialysis, the patient suffered a fatal cardiac arrest on postoperative day 9.

Q1. What is the epidemiology and pathology of a mucormycosis infection of the upper extremity?

Mucormycosis is a life-threatening fungal infection caused by Mucorales species, particularly Rhizopus oryzae. It poses a significant risk to immunocompromised individuals, including those with diabetes, those who receive treatment with corticosteroid use, and those with contaminated traumatic injury. Though it is a rare infection, mucormycosis exhibits a high mortality rate, with mortality rates of 33% to 80% reported in the literature.1

This infection manifests in various types—rhinocerebral, pulmonary, gastrointestinal, cutaneous, and disseminated.2 Cutaneous mucormycosis, particularly in the upper extremity, is generally caused by traumatic inoculation, though it can also present secondary to a disseminated infection.

A key factor contributing to the virulence of mucormycosis is its ability to invade blood vessels, causing endothelial damage, thrombosis, and subsequent tissue ischemia. The spores, prevalent in the environment near decaying organic matter, enter the bloodstream and germinate into hyphae capable of angioinvasion. This angioinvasion sets it apart from other fungal infections, facilitating rapid spread along fascia, leading to tissue necrosis and potentially gangrene. Mucormycosis can release spores into the bloodstream and surrounding tissues, allowing further dissemination, leading to rapid multisystem organ failure.3

Our patient did not have a history of traumatic injury to their left extremity, and it is likely that the infection of his hand disseminated from another source. Moreover, computed tomography scans of our patient's chest demonstrated cavitary lesions consistent with disseminated mucormycosis, further supporting the presence of a disseminated infection. Our patient also suffered acute kidney injury and hematological insufficiencies, eventually entering a state of multisystem organ failure that is characteristic of the later stages of mucormycosis dissemination.

In at-risk individuals, mucormycosis represents a concern that emphasizes a need for heightened awareness, early detection, and targeted interventions. In our patient, more than 48 hours expired before adequate mucormycosis treatment was initiated. Earlier detection might have led to a better prognosis.

Q2. What are some risk factors, signs, and symptoms associated with mucormycosis infections of the upper extremity?

Several risk factors contribute to the development of mucormycosis in the upper extremity: uncontrolled diabetes, which impairs immunity and promotes fungal growth; malignancies, which, with chemotherapeutics, suppress immunity; and high-dose corticosteroids, which offer a favorable state for mucormycosis dissemination.3,4

Our patient was high risk since he had a history of poorly controlled diabetes, malignancy, chemotherapeutic use, and recent high-dose steroid exposure given during multiple past respiratory infections.

Cutaneous mucormycosis manifests with variable signs and symptoms, including red, erythematous skin lesions that may evolve into necrotic eschars, targetoid lesions, tender nodules, ulcers, purpuric lesions, or swollen plaques.5 Monitoring these early cutaneous lesions is crucial for rapid detection and management.

An infection of upper extremity mucormycosis can present as an infection reminiscent of cellulitis or as a gangrenous infection. These can be mistaken for other infections, especially when targetoid lesions appear—which present a wide differential diagnosis including autoimmune, neoplastic, or hypersensitivity disorders.5 In our case, a clear wet gangrene with necrotic eschar was present upon consultation (Figure 1).

Wet gangrene is frequently attributed to bacterial necrotizing fasciitis, which should receive staphylococcal and streptococcal empiric treatment. A similar assumption was made with our patient, and empiric treatment lacked aggressive coverage of Mucorales species. However, mucormycosis was considered quickly thereafter, and empiric coverage was added to their regiment. Fungal infection was further supported by the lack of purulence on presentation.

In order to confirm this infection and tailor antibiotic specificity, cultures were taken. Since cultures have a non-ideal timeline, biopsies are used.5 We took several biopsies of the hand in our first operation that, along with the amputated digit, displayed pathological fungal elements consistent with zygomycetes, likely originating from Mucorales. While not a definitive diagnosis, this confirmed the need to continue aggressive antifungal treatment.

Q3. What is the surgical management for a mucormycosis infection of the upper extremity?

Management of a cutaneous infection with mucormycosis follows the principles used in all cutaneous infections—source control and antibiotics. In the case of mucormycosis, source control must be rapidly identified in order to avoid dissemination. Additionally, rapid administration of antifungals is critical, with amphotericin B being considered the first-line antibiotic for empiric management. As sensitivities return from the lab, this can be tailored down to other options that have a less harmful adverse effect profile. However, fungal cultures may take several weeks, so empiric management will likely need to proceed during that time.6

For source control, surgery should follow on an emergent basis. Wide debridement of tissues with collection of biopsy and cultures should be done. In our patient, surgery was performed immediately, and wide debridement was achieved down to bleeding, healthy tissues (Figure 2). However, given the likely disseminated state prior to this operation, the infection likely recurred in the hand, leading to the rapid necrosis seen just 2 days later (Figure 3). Moreover, the patient's extensive arterial disease likely contributed to an accelerated state of devitalization. This necessitated further debridement down to the forearm by way of a transradial amputation. For the 9 postoperative days that our patient lived, the stump appeared healthy, without signs of furthering necrosis, fungal infection recurrence, or bacterial coinfection.

Q4. What is the likely outcome of a secondary cutaneous mucormycosis infection?

As mentioned earlier, mucormycosis is a frequently fatal infection. In this case, a disseminated infection was already likely present before the initial surgery, suggesting that our efforts in eradicating the cutaneous infection were likely ineffective in addressing the primary source of the infection. At this disseminated stage, aggressive treatment with antifungals, targeted at the susceptibility of cultured fungus, is the most important step in management.7 Proceeding along this route is challenging—fungal cultures frequently return false negatives and typically take several weeks for final results.

Since many patients who develop an infection with mucormycosis have profound comorbidities, the successful treatment of the fungal infection may be limited by one of those comorbidities. This was the case with our patient, who suffered cardiac arrest during an episode of hemodialysis. The multisystem organ failure secondary to disseminated mucormycosis is fulminant, with mortality rates approaching 95%.6

Acknowledgments

Authors: Ricardo Cortes, BS1; Shaarav Ghose, BS2; John Chao, MD1; Ashley Ignatiuk, MD1

Affiliations: 1Rutgers New Jersey Medical School, Department of Surgery, Division of Plastic Surgery, Rutgers, New Jersey; 2Northeast Ohio Medical University, College of Medicine, Rootstown, Ohio

Correspondence: Ricardo Cortes; RC75790@gmail.com

Ethics: This case report is not considered research under the IRB requirements of what is research, therefore IRB review is not required. Written informed consent was obtained for the use of this patient's case information and images.

Disclosures: All authors declare that they have no known competing financial nor personal interests/relationships that could have appeared to influence the work reported in this paper.

References

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2. Prakash H, Chakrabarti A. Global epidemiology of mucormycosis. J Fungi (Basel). 2019 Mar 21;5(1):26. doi:10.3390/jof5010026

3. Ibrahim AS, Spellberg B, Walsh TJ, Kontoyiannis DP. Pathogenesis of mucormycosis. Clin Infect Dis. 2012 Feb;54(Suppl 1):S16-S22. doi:10.1093/cid/cir865

4. Petrikkos G, Skiada A, Lortholary O, Roilides E, Walsh TJ, Kontoyiannis DP. Epidemiology and clinical manifestations of mucormycosis. Clin Infect Dis. 2012 Feb;54(Suppl 1):S23-S34. doi:10.1093/cid/cir866

5. Pagano L, Offidani M, Fianchi L, et al. Mucormycosis in hematologic patients. Haematologica. 2004 Feb;89(2):207-214.

6. Castrejón-Pérez AD, Welsh EC, Miranda I, Ocampo-Candiani J, Welsh O. Cutaneous mucormycosis. An Bras Dermatol. 2017 May-Jun;92(3):304-311. doi:10.1590/abd1806-4841.20176614

7. Guymer C, Khurana S, Suppiah R, Hennessey I, Cooper C. Successful treatment of disseminated mucormycosis in a neutropenic patient with T-cell acute lymphoblastic leukaemia. BMJ Case Rep. 2013 Jul 31;2013:bcr2013009577. doi:10.1136/bcr-2013-009577