Case Report
 
A case of subcutaneous phaeohyphomycosis in a cardiac transplant patient
Anil Kumar Jonnalagadda1, Maria Rodrigo2, Farooq Sheikh3, Mark Hofmeyer4, Selma Mohammed5, Samer Najjar6
1Assistant Professor of Medicine, Department of Cardiology, Medstar Washington Hospital Center, Washington, DC, USA
2Assistant Director of Transplant Program, Advanced Heart Failure and Transplant Service, Medstar Washington Hospital Center, Washington, DC, USA
3Director of Infiltrative Cardiomyopathy, Advanced Heart Failure and Transplant Service, Medstar Washington Hospital Center, Washington, DC, USA
4Program Director, Advanced Heart Failure and Transplant Fellowship, Medstar Washington Hospital Center, Washington, DC, USA
5Director of research, Advanced Heart Failure and Transplant Service, Medstar Washington Hospital Center, Washington, DC, USA
6Program Director, Advanced Heart Failure and Transplant Service, Medstar Washington Hospital Center, Washington, DC, USA

Article ID: 100930Z01AJ2018
doi: 10.5348/100930Z01AJ2018CR

Corresponding Author:
Anil Kumar Jonnalagadda
7717 Owen Kellogg Court
Elkridge, MD 21075

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Jonnalagadda AK, Rodrigo M, Sheikh F, Hofmeyer M, Mohammed S, Najjar S. A case of subcutaneous phaeohyphomycosis in a cardiac transplant patient. Int J Case Rep Images 2018;9:100930Z01AJ2018.



ABSTRACT

Introduction: Phaeohyphomycosis is a rare mycotic infection, affecting mainly the immunocompromised patients. It has wide clinical spectrum, ranging from subcutaneous cyst to life threatening cerebral abscess.

Case Report: A 63-year-old female presented with asymptomatic swelling on the left middle finger that evolved one year after the cardiac transplantation. The diagnosis was based on the histopathological examination and culture of the skin lesion. The pathogen was confirmed as Exophiala species. The patient was successfully treated with surgical resection and oral voriconazole.

Conclusion: Asymptomatic swellings in transplant patients should be evaluated carefully to prevent life threatening complications.

Keywords: Pheaeohyphomycosis, Exophiala, Transplant


INTRODUCTION

Phaeohyphomycosis (PHM) is a chronic mycotic infection caused by a group of black-colored fungi called “Dematiaceous Fungi” first described in 1947 [1], [2], [3]. It commonly occurs in immunocompromised patients like transplant recipients or human immunodeficiency virus (HIV) patients, patients with breast cancer, or other chronic illnesses [1], [4], [5]. Severo et al., [6] reported that solid organ transplantation is the most common risk factor for PHM (38.8%). The incidence of such infections is increasing along with the growing number of transplant recipients and widespread use of immunosuppressive medications [7], [8], [9], [10]. Exophiala species are the most common causative organisms of the skin, and subcutaneous PHM in transplant patients [11], [12], [13]. Exophiala species are the most common causative organisms of the skin, and subcutaneous PHM in transplant patients [11], [12], [13]. Herein, we present a case of Exophiala-associated PHM in a cardiac transplant recipient.


CASE REPORT

A 63-year-old female heart transplant recipient presented to the transplant clinic, with swelling of the left middle finger that evolved one year after the transplant. The swelling worsened over the past month, with no associated pain, tenderness, fever, or chills. She denied any history of trauma at the site of the swelling. She was on tacrolimus, mycophenolate and prednisone for immunosuppression. Physical examination revealed a 4 cm mass along the left middle metacarpophalangeal joint, extending to the dorsum of the hand. There were no notable systemic signs of infection.

An X-ray scan showed a soft tissue mass along the left third metacarpophalangeal joint. Computed tomography (CT) showed a multilobulated mass proximal to the third metacarpophalangeal joint (MCP), closely attached to the tendons as shown in Figure 1 (A and B). Giant cell tumor was suspected, and the patient was referred to the orthopedic clinic. Fluid aspiration was performed, revealing a purulent material. She was admitted to hospital for further evaluation. Incision of the swelling revealed a large brown-tan colored cyst attached to the tendon. Debridement was done as much as possible without damaging tendons/nerves. The specimen was sent for culture, and vancomycin (1 gm iv daily) was started emperically. Three days later, preliminary culture results reported yeast infection. Vancomycin was stopped and Amphotericin B (320 mg iv daily) was started. The patient developed acute kidney injury due to Amphotericin B and was switched to voriconazole (loading dose of 300 mgiv twice daily for one week, followed by 200mg oral twice daily). Direct microscopic examination revealed brown-colored hyphae among a multinucleated giant cell infiltration as shown in Figure 2(A–C), and the diagnosis of Phaeohyphomycosis was made. Subsequent fungal cultures grew Exophiala species. Chest CT and brain Magnetic resonance imaging (MRI) showed no evidence of systemic infection. The patient underwent a radical synovectomy and amputation of the left third digit. Subsequent re-exploration of the wound was performed a week later; no abnormality was found, only minor swelling was found along ulnar surface of the left index finger, for which she underwent incision and drainage. Unfortunately, repeat cultures also grew Exophiala species; however, as the site was debrided well, conservative management with oral voriconazole was continued. MRI of hand three months post-debridement did not show any evidence of recurrence. She was closely followed through the Infectious Disease and Orthopedic clinics every three months. The patient successfully completed a one year course with voriconazole. No evidence of recurrence was found, during a follow-up visit 1 month after completion of the voriconazole.


DISCUSSION

PHM is a rare cutaneous disease, caused by dematiaceous fungi [1],[8]. It is more prevalent in tropical and sub-tropical regions, and is classified into four main categories, depending on the distribution of the disease: superficial, cutaneous, subcutaneous, and systemic infection [1],[2],[14]. Clinical symptoms include subcutaneous nodules, cysts, and abscesses [1],[12]. Claudia et al. [2] reported that the skin is the organ most commonly affected by PHM, and 9% of transplant patients experience such infections within few years after the transplant. Schieffelin et al. [14] conducted a retrospective study between 1928 and 2008 of 3441 patients who received transplants, and 27 were proven to have PHM, 9% of them underwent cardiac transplant surgery, the average time between the surgery and PHM was 20 months. Exophiala PHM is mostly seen in immunocompromised patients such as those post-transplant, or with HIV, diabetes, cancer [1],[4]. Exophiala species are saprobes, widely distributed in soil, wood, and plants [1]. Infection with this organism can usually be traced to a traumatic inoculation. The injury may be as simple as a splinter or a prick from a thorn, and it may have occurred months or years before the lesion appears. Our patient doesn’t remember any trauma at site of swelling. Other methods of inoculation include contaminated wounds, inhalation of spores, contagious spread and hematogenous dissemination. Lymph node involvement or dissemination is rare. Cases of PHM involving eyes, paranasal sinuses, joints, lungs, liver and brain were reported. Cerebral PHM is very rare but has poor prognosis with survival rates at two years being less than fifty percent [15]. Most common presentation of exophiala species is slowly enlarging cutaneous and subcutaneous nodules that may be confused with ganglion cysts, epidermal inclusion cysts, or foreign body granulomas [16].

Diagnosis is usually made through the direct microscopy and culture [10],[13]. Microscopic examination shows infiltration of inflammatory cells such as leukocytes, lymphocytes, and multinucleated giant cells [1]. The diagnosis is confirmed in culture specimens by the visualization of dark-walled hyphae or pseudo- hyphae [10]. Arakaki et al. [12] mentioned that CT and non-invasive ultrasonography may also serve as a good diagnostic tool.

At present, there are no clinical trials to guide the management of phaeohyphomycosis due to rarity of this condition. Most data come from isolated case reports and small series. The accepted treatment of choice is surgical excision. In addition, antifungal therapy is recommended for recurrent cases and for immunocompromised patients, but there are no standards in terms of agents or duration of therapy. In vitro, the most effective agents are itraconazole, voriconazole, and amphotericin B. Fluconazole is ineffective, and ketoconazole is associated with side effects. Usual duration of treatment is anywhere between 6 months to 2 years [10],[16].

Reviewing the literature, 12 case reports of PHM in cardiac transplant patients were identified, 11 of which identified Exophiala as the causative species as shown in Table 1 [2],[7],[10],[11],[17], [18], [19], [20], [21], [22]. The symptoms described in those cases included subcutaneous nodules and swellings on the extremities. Most of the cases improved upon surgical removal alone or in combination with antifungal drugs. In a few cases, the symptoms relapsed, requiring long-term antifungal medications or further surgical resection.


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Figure 1(A and B): Coronal (A) and sagittal (B) views of CT of hand showing hypodense deposition around third metacarpophalangeal joint (arrows).


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Figure 2(A–C): (A) Hematoxylin and Eosin (H&E) staining shows infiltration of inflammatory cells such as lymphocytes, and neutrophils. (B) Histopathological examination of Hematoxylin and Eosine (H&E) stain shows granulomas with multinucleated giant cells (white arrow). (C) Showed multinucleated giant cell infiltration (white arrows), Brown spindle-shaped hyphae are seen inside the giant cells (black arrow).


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Table 1: Summary of the findings of published case reports about subcutaneous phaeohyphomycosis in cardiac transplant patients.



CONCLUSION

Although rare, subcutaneous phaeohyphomycosis can spread to brain, especially in immunosuppressed patients and it is a life-threatening condition. Our case signifies that even asymptomatic swellings in transplant patients should be evaluated with great care to prevent life threatening complications.


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Author Contributions
Anil Kumar Jonnalagadda – Substantial contributions to conception and design, Acquisition of data, Analysis and interpretation of data, Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be published
Maria Rodrigo – Substantial contributions to conception and design, Acquisition of data, Analysis and interpretation of data, Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be published
Farooq Sheikh – Substantial contributions to conception and design, Acquisition of data, Analysis and interpretation of data, Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be published
Mark Hofmeyer – Substantial contributions to conception and design, Acquisition of data, Analysis and interpretation of data, Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be published
Selma Mohammed – Substantial contributions to conception and design, Acquisition of data, Analysis and interpretation of data, Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be published
Samer Najjar – Substantial contributions to conception and design, Acquisition of data, Analysis and interpretation of data, Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be published
Guarantor of Submission
The corresponding author is the guarantor of submission.
Source of Support
None
Consent Statement
Written informed consent was obtained from the patient for publication of this case report.
Conflict of Interest
Author declares no conflict of interest.
Copyright
© 2018 Anil Kumar Jonnalagadda et al. This article is distributed under the terms of Creative Commons Attribution License which permits unrestricted use, distribution and reproduction in any medium provided the original author(s) and original publisher are properly credited. Please see the copyright policy on the journal website for more information.