Blog
About

4
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Clinical spectrum of phaeohyphomycosis in solid organ transplant recipients

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Introduction Phaeohyphomycosis is a rare, opportunistic infection caused by melanized fungi that predominates in tropical climates.1, 2 The increase in the number of organ transplant recipients (OTRs), in conjunction with improvement in their long-term treatment, has led to an increase in the incidence of phaeohyphomycosis.1, 3, 4, 5, 6, 7 Phaeohyphomycosis has a wide range of clinical presentations, which are associated with the immune status of the host.1, 2, 3, 4, 5, 6, 7, 8, 9, 10 We describe 7 cases of phaeohyphomycosis in OTRs, which clearly demonstrate that the clinical presentations can have profound variations and that treating this infection in this specific patient population can be challenging. Materials and methods We present a case series of 7 OTRs with phaeohyphomycosis that have been followed up with our specialized dermatologic clinic for more than 4 years. Their clinical presentations and treatment approaches are discussed. Table I summarizes the findings. Results Case 1 A 57-year-old male farmer presented with multiples nodules with a sporotrichoid pattern on his lower right limb that developed 2 years after kidney transplantation (Fig 1). There were no signs of systemic symptoms. His immunosuppressive medications included azathioprine, tacrolimus, and prednisone. A direct examination found dematiaceous filamentous fungi, and culture yielded Exophiala sp. Histopathologic analysis found granulomatous dermatitis, and fungal melanized structures were seen through Fontana-Masson stain. Imaging studies ruled out internal foci of infection. He was initially treated with 200 mg twice a day of voriconazole, which was discontinued very soon because of severe hyponatremia. Itraconazole, 200 mg twice a day was started afterwards, which was accompanied by severe headache, anorexia, and weight loss. After reducing the tacrolimus dose, the symptoms gradually resolved. The lesions were surgically removed. Itraconazole was continued for 6 months, and no relapse has occurred so far. Case 2 A 59-year-old male gardener presented with an erythematous violaceous plaque on his right thigh that developed 18 months after kidney transplantation (Fig 2). His immunosuppressive medications included mycophenolate mofetil, tacrolimus, and prednisone. Direct examination of the biopsy specimen found several melanized septate hyphae. Microscopic examination of the fungal colony identified Exophiala sp. The biopsy specimen underwent Fontana-Masson and Gridley stains, which also confirmed the diagnosis of phaeohyphomycosis. Treatment included surgical removal of the lesion along with 200 mg twice a day of itraconazole for 4 months. There was no recurrence 2 years after completion of the treatment. Case 3 A 43-year-old male rural worker presented with a nodule over his left knee that evolved 2 years after cardiac transplantation. His immunosuppressive medications included mycophenolate mofetil, cyclosporine, and prednisone. Direct microscopy examination of the biopsy specimen found dematiaceous hyphae, and microscopic examination of fungal colony found Exophiala sp (Fig 3, A and B). The histopathology findings showed neutrophilic infiltrate and giant cells with dematiaceous hyphae. The patient was treated with surgical excision followed by itraconazole, 200 mg/d orally for 2 months. He has been undergoing follow-up for more than 2 years without recurrence. Case 4 A 64-year-old female maid presented an asymptomatic nodule on her right elbow that had grown 9 months after cardiac transplantation. There was no history of local trauma. Her immunosuppressive medications included cyclosporine, mycophenolate mofetil, and prednisone. The lesion was surgically removed. Direct microscopy examination of the biopsy specimen found dematiaceous hyphae, and microscopic analysis of fungal culture showed Exophiala sp. The histopathologic examination found granulomatous inflammatory infiltrate with multinucleated giant cells (Fig 4). Filamentous fungi were seen through Grocott stain (Fig 5). She has undergone follow-up for more than 2 years without recurrence. Case 5 A 42-year-old male retired policeman presented with an asymptomatic hyperkeratotic tumor on his right leg that evolved 11 months after cardiac transplantation. His immunosuppressive medications included mycophenolate mofetil, tacrolimus, and prednisone. Direct microscopy of the biopsy specimen found dematiaceous filamentous fungi (Fig 6), and fungal culture yielded Exophiala sp. Histopathology found a cystic structure with multinucleate giant cells, and dematiaceous filamentous fungi were seen on Fontana-Masson stain. Surgical excision was performed. Itraconazole, 200 mg twice a day, was started before surgery and maintained for 4 months. He has undergone follow-up for more than 2 years without recurrence. Case 6 A 34-year-old female hair stylist presented with a verrucous plaque between her first and second right toes that had grown 10 months after kidney transplantation (Fig 7). Her immunosuppressive medications included tacrolimus, mycophenolate mofetil, and prednisone. Direct examination of the biopsy specimen found dematiaceous filamentous fungi, and microscopic study of culture found Exophiala sp. Histopathologic analysis found inflammatory infiltrate with multinucleated giant cells. Dematiaceous hyphae were seen through Fontana-Masson stain. The patient refused treatment and became lost to follow-up. Case 7 A 43-year-old male mason presented with asymptomatic erythematous plaques on his right leg and on the index finger of his left hand that had grown 16 months after cardiac transplantation (Fig 8). His immunosuppressive medications included mycophenolate mofetil, tacrolimus, and prednisone. Direct examination of the biopsy specimens found dematiaceous fungi, and microscopic analysis of culture found Exophiala sp. Histology confirmed the presence of fungal structures along with a granulomatous reaction. All lesions were surgically removed. In addition, the patient was treated with 200 mg twice a day itraconazole for 6 months, which had started just before surgery. The tacrolimus dose was adjusted accordingly. He has undergone follow-up for more than 2 years without recurrence. Conclusions Phaeohyphomycosis is a group of rare opportunistic fungal infections predominantly affecting the skin, although systemic disease can occur.1, 2, 3, 4 The incidence of phaeohyphomycosis in OTR is approximately 9%, and disease usually occurs in the first few years after transplant.1, 2, 8 Phaeohyphomycosis developed in all of our patients within the first 2 years after transplant. The incidence of phaeohyphomycosis seems to be increasing as a result of increasing numbers of OTRs and scientific advances made in immunosuppressant medications.4, 5, 6, 8 Regarding the specific immunosuppressant drug, it seems that calcineurin inhibitors such as tacrolimus are more associated with greater susceptibility to fungal infections, which later can become recurrent.1, 4, 5, 7 All of our patients were taking this medication. Although it has been published that phaeohyphomycosis is more frequent in kidney transplant recipients,1, 4, 6, 7, 8, 10 we did not find a statistical difference between kidney and heart transplants in our series. This finding may be owing to the limited number of patients. However, we stress that all patients, regardless of the type of organ received, were under heavy immunosuppressive therapy. Diagnosis of phaeohyphomycosis is complicated by its highly variable clinical presentation.1, 2, 3, 4, 5, 6, 7 In our patients, the diagnosis was based on clinical, microbiologic, and histopathologic studies. We observed a wide spectrum of clinical lesions including nodules, cysts, tumors, and verrucous plaques, mostly with subcutaneous involvement. The diversity of lesions presented in this series may reflect the differences in disease progression, variable host response, and degree of the immunosuppression. Despite that there are more than 100 species of fungi associated with this disease, there is still no correlation between the etiologic agent and morphology of lesions.3, 7, 8 Exophiala sp was the only agent identified in this group of OTRs. This species is ubiquitous in nature and typically causes infections via traumatic implantation.9, 10 All of our patients had lesions on the limbs, which can be attributed to direct inoculation of the fungus into damaged skin after contact with a contaminated fomite or plant. The treatment of phaeohyphomycosis is a challenging issue, as there is no standardized treatment and a high possibility of dangerous drug-drug interactions.1, 4, 6, 7 Surgery is likely the best treatment for well-circumscribed lesions, but additional medical treatment is recommended to avoid local sporotrichoid dissemination and to treat concomitant subclinical lesions.4, 7, 10 In the selected patients, a cure can be achieved by surgery alone as could be seen in case 4. However, we do believe that surgery can be an important adjuvant therapeutic method that should be associated whenever possible with antifungal medications. Itraconazole was the antifungal medication used in most of our patients and was associated with high cure rate. Itraconazole, which is fungistatic and inhibits ergosterol synthesis, seems to be the most effective agent, especially against Exophiala sp.9, 10 One of the most important points to consider in the use of broad-spectrum azoles in OTRs is that these drugs are strong cytochrome CYP3A4/5 inhibitors and may cause major drug-drug interactions with calcineurin and mammalian target of rapamycin (mTOR) inhibitors.1, 4, 6 Because these immunosuppressive drugs are characterized by a narrow therapeutic window, these drug-drug interactions could lead to clinical complications as also clearly seen in the first case. It is important to closely monitor tacrolimus concentrations and be on the look out for signs of drug-related toxicity. Because of the increased incidence of phaeohyphomycosis in OTRs, it is important that all clinicians involved in solid organ transplants always consider the possibility of this disease in allograft recipients with skin lesions. The high degree of clinical suspicion is essential to establish the correct diagnosis and to start treatment promptly to avoid serious complications and organ rejection.

          Related collections

          Most cited references 10

          • Record: found
          • Abstract: found
          • Article: not found

          Subcutaneous phaeohyphomycosis (mycotic cyst).

          Phaeohyphomycosis designates fungal infections caused by pheoid or melanized fungi and characterized histopathologically by the presence of septate hyphae, pseudohyphae, and yeasts. Etiologic agents include Exophiala, Phoma, Bipolaris, Phialophora, Colletotrichum, Curvularia, Alternaria, Exserohilum, and Phialemonium sp. The most common are Exophiala jeanselmei and Wangiella dermatitidis. The clinical presentation depends on the immune status of the host: superficial (tinea nigra and black piedra); cutaneous (scytalidiosis) and corneal; subcutaneous (mycotic cyst); and systemic phaeohyphomycosis in the immunocompromised host. The mycotic cyst is a localized form, characterized by subcutaneous asymptomatic nodular lesions that develop after traumatic implantation of fungi, especially on the extremities. The average size of the cysts is 2.5 cm. KOH examination reveals pigmented yeasts, pseudohyphae, and hyphae. A cutaneous biopsy specimen usually shows an abscess or a suppurative granuloma with pigmented yeasts and pseudohyphae. The treatment of choice is surgical excision, but additional anti-fungal therapy is recommended for recurrent cases and immunocompromised patients.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Cutaneous phaeohyphomycosis in renal allograft recipients: report of 2 cases and review of the literature.

            Dematiaceous molds are increasingly recognized as important human pathogens. We report 2 cases of cutaneous phaeohyphomycosis in renal allograft recipients, caused by Alternaria alternata and Curvularia spp., respectively, which demonstrate the diversity in clinical presentation, the different therapeutic strategies, and the clinical importance of azole antifungal-induced drug-drug interactions with immunosuppressive therapy. Copyright © 2010 Elsevier Inc. All rights reserved.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Phaeohyphomycosis due to Exophiala species: clinical spectrum of disease in humans.

              Phaeohyphomycosis caused by Exophiala species is an unusual infection, but it has been reported with increasing frequency as immunosuppressive therapy has become more widespread and laboratory methods for diagnosis have improved. To our knowledge, the first case of subcutaneous phaeohyphomycosis due to Exophiala jeanselmei in a cardiac transplant patient is presented, and previously reported cases of exophiala infection are reviewed. This patient was successfully managed with surgical excision of the lesion and combination therapy with amphotericin B and 5-fluorocytosine.
                Bookmark

                Author and article information

                Contributors
                Journal
                JAAD Case Rep
                JAAD Case Rep
                JAAD Case Reports
                Elsevier
                2352-5126
                05 December 2016
                November 2016
                05 December 2016
                : 2
                : 6
                : 465-469
                Affiliations
                [a ]Department of Dermatology, University of São Paulo, São Paulo, Brazil
                [b ]Medical School, University of Piauí, Piauí, Brazil
                Author notes
                []Correspondence to: Maria Claudia Carvas Passarelli Tirico, MD, Rua Bastos Pereira 116, CEP 04507-010, Vila Nova Conceição, São Paulo, SP, Brasil.Rua Bastos Pereira 116CEP 04507-010Vila Nova ConceiçãoSão PauloSPBrasil mariaclaudiaptirico@ 123456gmail.com
                Article
                S2352-5126(16)30109-6
                10.1016/j.jdcr.2016.09.009
                5148774
                © 2016 by the American Academy of Dermatology, Inc. Published by Elsevier, Inc.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                Categories
                Case Series

                Comments

                Comment on this article