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 Table of Contents  
CASE REPORT
Year : 2019  |  Volume : 21  |  Issue : 1  |  Page : 40-43

Phaeoacremonium parasiticum hand infection in renal transplant patient


1 Department of Plastic Surgery, Government Medical College, Kozhikode, Kerala, India
2 Department of Pathology, Government Medical College, Kozhikode, Kerala, India
3 Department of Dermatology, Government Medical College, Kozhikode, Kerala, India
4 Department of Microbiology, Government Medical College, Kozhikode, Kerala, India

Date of Web Publication12-Aug-2019

Correspondence Address:
Dr. Sheeja T M Rajan
Department of Plastic Surgery, Government Medical College, Kozhikode, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jacm.jacm_24_18

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  Abstract 


Phaeohyphomycosis is a group of rare opportunistic infections caused by dematiaceous fungi. Their significance in the newly emerging and rare fungal infections of solid organ transplant recipients is being increasingly recognised. We present a case of fungal infection of both hands in a post-renal transplant patient on immunosuppressive drugs, by Phaeoacremonium parasiticum. Diagnostic confirmation by fungal cultures, histopathologic examination with special stains and confirmation by polymerase chain reaction technique was done. Remission was achieved by a combination of surgical debulking followed by systemic azoles, intralesional amphotericin B and saturated solution of potassium iodide. Significance of such infections in transplant tourism is implicated since the fungus is frequently found in tropical and subtropical regions.

Keywords: Immunosuppression, opportunistic infection, phaeoacremonium, phaeohyphomycosis, renal transplantation


How to cite this article:
M Rajan ST, Bhaskaran S, George M, George SH. Phaeoacremonium parasiticum hand infection in renal transplant patient. J Acad Clin Microbiol 2019;21:40-3

How to cite this URL:
M Rajan ST, Bhaskaran S, George M, George SH. Phaeoacremonium parasiticum hand infection in renal transplant patient. J Acad Clin Microbiol [serial online] 2019 [cited 2019 Aug 20];21:40-3. Available from: http://www.jacmjournal.org/text.asp?2019/21/1/40/264249




  Introduction Top


Phaeohyphomycosis is a rare sporadic infection caused by dematiaceous fungi commonly found in tropic and sub-tropic environments as saprophytes in soil and vegetation or causing Petri or esca diseases in plants. Human infection was first reported in 1974 by Ajello et al.,[1] as subcutaneous infection in a renal transplant recipient. Infections follow invasive trauma in immunocompromised patients and may present variedly from subcutaneous infections to disseminated fungal septicaemia.[2] In many cases, there may not be a preceding traumatic event. Most often, the diagnosis is delayed due to the rarity and variable nature of the presentation. Hence, a clinician must keep a high index of suspicion of phaeohyphomycosis in all atypical lesions of immunocompromised patients, especially with a history of travel to tropics, to institute early treatment measures.


  Case Report Top


A 26-year-old male electrician presented with painful cystic swelling over right palm [Figure 1] of 3 months' duration. He was post-renal transplant for 1 year and on immunosuppression with tacrolimus, prednisolone and mycophenolate mofetil. He was not on prophylactic antifungal agents during his period. No preceding trauma or contact with soil or vegetation was recollected. He was afebrile on presentation and was treated with a course of amoxicillin. Complete blood count revealed haemoglobin level of 9.1 gm% and a total WBC count of 9600 with P55, L33, E2. Biochemical investigations revealed borderline renal impairment (blood urea 52 mg/dL and serum creatinine 1.8 mg/dL); high blood glucose levels (fasting blood sugar 280 mg/dL) suggestive of post-transplant diabetes and non-reactive results for HIV, hepatitis B surface antigen and hepatitis C virus screening. Plain X-ray of the hand showed no bone erosion.
Figure 1: Cystic swelling over the right palm

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Incision and drainage of the lesion were done, and copious necrotic debris was let out from the lesion. Bacterial cultures were negative. He developed a recurrence of the lesion in 2 months with extension of swelling to the right middle finger. Representative biopsy from the lesion was sent for bacterial and fungal cultures and histopathologic examination.

Fungal culture on Sabouraud's dextrose agar at 37°C showed growth in 48 h. The culture was slow growing, greyish white initially, subsequently progressing to olivaceous grey to typically black colour colonies by 3 weeks, without diffusion of pigment into the culture medium [Figure 2]. Subculture on potato dextrose agar with incubation at room temperature showed slender phialides after 1 week. On microscopy, the phialides were long, slender, thick-walled, brown cylinders and slightly tapering towards the tips with distinct proliferating tubular collarettes [Figure 3]. The small conidia were thin-walled, hyalinised and grouped. Macroscopy and microscopy of isolate was suggestive of Phaeoacremonium parasiticum. Sequence-based confirmation with 5' end of the beta-tubulin gene analysis using polymerase chain reaction (PCR) technique was done, confirming P. parasiticum.
Figure 2: Growth in Sabouraud dextrose agar at room temperature beginning as beige colored colony later on becoming greenish grey and finally turning into brown

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Figure 3: Potassium hydroxide examination: Thick walled phialides slightly tapering towards tip and cylindrical to sausage-shaped conidia in slimy heads at apices of phialides

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Histopathologic examination with haematoxylin and eosin stains showed granulomatous lesions with fungal hyphae in fibrocollagenous tissue with minimal inflammatory tissue consisting of lymphocytes, eosinophils and multinucleated giant cells. Special staining with periodic acid–Schiff stain [Figure 4], Gomori methenamine silver stain [Figure 5] and Masson-Fontana stain [Figure 6] was also done subsequently confirming the diagnosis of phaeohyphomycosis.
Figure 4: Periodic acid–Schiff staining of tissue biopsy specimen

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Figure 5: Gomori methenamine silver staining of tissue biopsy specimen

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Figure 6: Masson-Fontana staining of tissue biopsy specimen

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After diagnostic confirmation, antifungal therapy was started with oral itraconazole 400 mg daily. Following an initial remission, the patient developed a relapse within 3 months with fresh lesions appearing on the index finger of right hand and dorsum of the left hand, which was confirmed by histopathology. Surgical debulking was undertaken, including ray amputation of the right middle finger. Extensive deeper tissue involvement up to the periosteum was evident in histopathological regression. Postoperatively, he was administered oral voriconazole 400 mg daily for 3 months along with weekly intralesional amphotericin B as 50% solution in distilled water for 4 weeks. Since the remission was initially unsatisfactory, saturated solution of potassium iodide, 1 g total dissolved solids by oral route for 12 weeks was also supplemented. The lesion healed, and the patient has complete remission of the disease over a 2-year follow-up period.


  Discussion Top


Phaeohyphomycosis refers to mycotic opportunistic infections caused by a heterogeneous group of phaeoid fungi widely disseminated in nature. These are dematiaceous fungi characterised by septate hyphae and pseudohyphae, sometimes coexisting with yeast forms. Ajello et al.[1] listed 71 species from 39 genera as causative agents of phaeohyphomycosis. Phaeoacremonium genus is morphologically intermediate between Acremonium and Phialophora genus, all of which are pathogens implicated in opportunistic infections. In 1996, Crous et al.[2] proposed a new type species called Phaeoacremonium parasiticum with distinctive microscopic features. Their significance in the newly emerging and rare fungal infections of solid organ transplant recipients is being increasingly recognised. This species is reported to cause subcutaneous infection of extremities, eumycetomas, osteomyelitis, arthritis, fungaemia and endocarditis in susceptible hosts.

In many cases, patients fail to give a definitive history of exposure. Since the fungus is widely disseminated in the environment in the soil, vegetation, food, water, sewage and air, acquisition of infection through contamination of minor wounds or intravascular access sites are to be considered. Although the tropics and subtropics offer an ideal environment for thriving fungal presence, the incidence of such infections is often under-reported. Eighteen cases of phaeohyphomycosis have so far been reported in India[3],[4],[5],[6] involving diseases in orbit, extremities and disseminated fungaemia. Kubak and Huprikar.[7] state that with popularisation of transplant tourism, organ transplant recipient returning from South East Asian countries should be investigated for opportunistic infections due to geographically restricted mycosis including phaeohyphomycosis and chromoblastomycosis.

In general, itraconazole, voriconazole and posaconazole are reported to have excellent activity against dematiaceous fungi.[8],[9] Since the clinical syndromes associated with phaeohyphomycosis have a spectrum of clinical presentations and show variable susceptibility to the routine antifungal therapy, there are no interpretative European Committee on Antibiotic Susceptibility Testing breakpoints for any drugs. Furthermore, the treatment for these rare fungal infections is not standardised.[8],[9],[10]

Surgical excision along with systemic itraconazole therapy is the usual treatment protocol in most centres globally.[11] Amphotericin fluconazole, ketoconazole, terbinafine and 5-fluorocytosine (5FC) have been proposed for the treatment of phaeohyphomycosis, as an alternative therapy for those patients with severe disease, poor response or hepatic toxicity to itraconazole.[11],[12] Isavuconazole demonstrates broad-spectrum activity in vitro against a global collection of opportunistic fungi, but no clinical data is available on its use in phaeohyphomycosis.[13]

Despite being used in medicine for over a century, potassium iodine remains a good therapeutic option for the treatment of several dermatoses.[14],[15] Gugnani et al.[16] reported complete remission of phaeohyphomycosis caused by Cladosporium oxysporum with potassium iodide therapy.

Multicentre controlled trials for prevention or treatment of P. parasiticum infections are unavailable, but there is an overall consensus for surgical debulking followed by systemic antifungal drugs as appropriate management.[11] Marques et al.[17] and Mahajan et al.[18] reported significant improvement with itraconazole and intra-lesional amphotericin B. Since our patient developed recurrence with itraconazole and was not showing satisfactory remission with voriconazole and intralesional amphotericin B, we used potassium iodide also in the initial phase of the antifungal regimen with complete subsidence of the lesions.

In summary, P. parasiticum is a newly emerging opportunistic fungal infection in solid organ transplant patients. Since the clinical presentations are variable, a high index of suspicion and confirmation of diagnosis with fungal culture, histopathology and phenotypic identification with PCR technique will help in institution of early appropriate treatment.[10] Although the Triazoles, amphotericin B, terbinafine and 5FC are the most frequently employed antifungal agents, potassium iodide still has a role in combination therapy. Surgical debulking of the lesion should be instituted early to increase the efficacy of antifungal therapy.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Acknowledgements

We would like to express our gratitude to Dr Sreelatha M, Professor and Head, Department of Nephrology, Government Medical College, Kozhikode, Kerala, Dr Kalpana George, Associate Professor, Department of Microbiology Government Medical College, Kottayam, Kerala and Dr Anitha Moorkoth, Professor, Department of Microbiology Government Medical College, Manjeri, Kerala for their immense help in preparation of this article.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Ajello L, Georg LK, Steigbigel RT, Wang CJ. A case of phaeohyphomycosis caused by a new species of Phialophora. Mycologia 1974;66:490-8.  Back to cited text no. 1
    
2.
Mostert L, Halleen F, Fourie P, Crous PW. A review of Phaeoacremonium species involved in Petri disease and esca of grapevines. Phytopathol Mediterr 2006;45:12-29.  Back to cited text no. 2
    
3.
Crous P, Gams W, Wingfield M, Van Wyk PS. Phaeoacremonium gen. Nov. Associated with wilt and decline diseases of woody hosts and human infections. Mycologia 1996;88:786-96.  Back to cited text no. 3
    
4.
Kumar KK, Hallikeri K. Phaeohyphomycosis. Indian J Pathol Microbiol 2008;51:556-8.  Back to cited text no. 4
[PUBMED]  [Full text]  
5.
Sharma NL, Mahajan V, Sharma RC, Sharma A. Subcutaneous pheohyphomycosis in India – A case report and review. Int J Dermatol 2002;41:16-20.  Back to cited text no. 5
    
6.
Mishra D, Singal M, Rodha MS, Subramanian A. Subcutaneous phaeohyphomycosis of foot in an immunocompetent host. J Lab Physicians 2011;3:122-4.  Back to cited text no. 6
[PUBMED]  [Full text]  
7.
Kubak BM, Huprikar SS; AST Infectious Diseases Community of Practice. Emerging & rare fungal infections in solid organ transplant recipients. Am J Transplant 2009;9 Suppl 4:S208-26.  Back to cited text no. 7
    
8.
Revankar SG. Phaeohyphomycosis in transplant patients. J Fungi (Basel) 2015;2. pii: E2.  Back to cited text no. 8
    
9.
Guégan S, Garcia-Hermoso D, Sitbon K, Ahmed S, Moguelet P, Dromer F, et al. Ten-year experience of cutaneous and/or subcutaneous infections due to coelomycetes in France. Open Forum Infect Dis 2016;3:ofw106.  Back to cited text no. 9
    
10.
Cornely OA, Cuenca-Estrella M, Meis JF, Ullmann AJ. European Society of Clinical Microbiology and infectious Diseases (ESCMID) Fungal Infection Study Group (EFISG) and European Confederation of Medical Mycology (ECMM) 2013 joint guidelines on diagnosis and management of rare and emerging fungal diseases. Clin Microbiol Infect 2014;20 Suppl 3:1-4.  Back to cited text no. 10
    
11.
Ogawa MM, Galante NZ, Godoy P, Fischman-Gompertz O, Martelli F, Colombo AL, et al. Treatment of subcutaneous phaeohyphomycosis and prospective follow-up of 17 kidney transplant recipients. J Am Acad Dermatol 2009;61:977-85.  Back to cited text no. 11
    
12.
Larsen CG, Arendrup MC, Krarup E, Pedersen M, Thybo S, Larsen FG. Subcutaneous phaeohyphomycosis in a renal transplant recipient successfully treated with voriconazole. Acta Derm Venereol 2009;89:657-8.  Back to cited text no. 12
    
13.
Pfaller MA, Messer SA, Rhomberg PR, Jones RN, Castanheira M.In vitro activities of isavuconazole and comparator antifungal agents tested against a global collection of opportunistic yeasts and molds. J Clin Microbiol 2013;51:2608-16.  Back to cited text no. 13
    
14.
Costa RO, Macedo PM, Carvalhal A, Bernardes-Engemann AR. Use of potassium iodide in dermatology: Updates on an old drug. An Bras Dermatol 2013;88:396-402.  Back to cited text no. 14
    
15.
Narendranath S, Sudhakar GK, Pai MR, Kini H, Pinto J, Pai MR, et al. Safety and efficacy of oral potassium iodide in chromoblastomycosis. Int J Dermatol 2010;49:341-3.  Back to cited text no. 15
    
16.
Gugnani HC, Ramesh V, Sood N, Guarro J, Moin-Ul-Haq, Paliwal-Joshi A, et al. Cutaneous phaeohyphomycosis caused by Caldosporium oxysporum and its treatment with potassium iodide. Med Mycol 2006;44:285-8.  Back to cited text no. 16
    
17.
Marques SA, Camargo RM, Summerbell RC, De Hoog GS, Ishioka P, Chambô-Cordaro LM, et al. Subcutaneous phaeohyphomycosis caused by Phaeoacremonium parasiticum in a renal transplant patient. Med Mycol 2006;44:671-6.  Back to cited text no. 17
    
18.
Mahajan VK, Sharma V, Prabha N, Thakur K, Sharma NL, Rudramurthy SM, et al. Arare case of subcutaneous phaeohyphomycosis caused by a Rhytidhysteron species: A clinico-therapeutic experience. Int J Dermatol 2014;53:1485-9.  Back to cited text no. 18
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]



 

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