|Year : 2010 | Volume
| Issue : 4 | Page : 396-399
Subcutaneous phaeohyphomycosis due to Exophiala spinifera in an immunocompromised host
Deepa Radhakrishnan, G Jayalakshmi, A Madhumathy, S Thasneem Banu, S Geethalakshmi, G Sumathi
Institute of Microbiology, Madras Medical College and Government General Hospital, Chennai - 600 003, India
|Date of Submission||14-Dec-2009|
|Date of Acceptance||14-Jul-2010|
|Date of Web Publication||20-Oct-2010|
Institute of Microbiology, Madras Medical College and Government General Hospital, Chennai - 600 003
Source of Support: None, Conflict of Interest: None
A case of phaeohyphomycosis presenting as multiple subcutaneous abscesses in a young lady with deteriorating liver function was reported here. The lesion started as a solitary abscess in the neck, mimicking tuberculous cold abscess and rapidly involved the face, chest, arms, and legs within six months with ulceration and discharge of thick brownish foul smelling pus. Potassium hydroxide mount of pus from various sites revealed septate dematiaceous hyphae and pseudohyphae. Culture yielded pure growth of Exophiala spinifera. Tissue debridement was done along with initiation of antifungal therapy with ketoconazole. As liver function deteriorated, antifungal therapy was withdrawn after seven days. Patient expired three weeks after admission due to hepatic failure.
Keywords: Exophiala spinifera, immunocompromised host, subcutaneous phaeohyphomycosis
|How to cite this article:|
Radhakrishnan D, Jayalakshmi G, Madhumathy A, Banu S T, Geethalakshmi S, Sumathi G. Subcutaneous phaeohyphomycosis due to Exophiala spinifera in an immunocompromised host. Indian J Med Microbiol 2010;28:396-9
|How to cite this URL:|
Radhakrishnan D, Jayalakshmi G, Madhumathy A, Banu S T, Geethalakshmi S, Sumathi G. Subcutaneous phaeohyphomycosis due to Exophiala spinifera in an immunocompromised host. Indian J Med Microbiol [serial online] 2010 [cited 2019 Nov 13];28:396-9. Available from: http://www.ijmm.org/text.asp?2010/28/4/396/71838
| ~ Introduction|| |
Exophiala spinifera is an emerging dematiaceous fungus reported from various parts of the world as the causative agent of phaeohyphomycosis and chromoblastomycosis. It is classified within the family Herpotrichiellaceae of the class Euascomycetes and order Chaetothyriales.  These organisms are widespread in the environment, being found in soil, wood, and decomposing plant debris. The severity of infections ranges from solitary cutaneous nodules to deep subcutaneous abscesses with lymph node and bony involvement.  Systemic dissemination has been observed in patients with or without proven immune disorder and are often fatal. 
We report a case of subcutaneous phaeohyphomycosis caused by E. spinifera in a young lady with deteriorating liver function. This case is being reported for the rarity of its presentation.
| ~ Case Report|| |
A 20 year-old-lady, resident of rural Tamil Nadu, presented with multiple non-healing skin ulcers for six months. She was in apparent good health before the illness. Six months ago, she developed a painless solitary soft nodule in the left side of the neck. She was given antituberculous treatment empirically. She developed jaundice after three weeks and therefore discontinued treatment. There was no history of fever. She developed abscesses in other parts of her body, which suppurated with foul smelling discharge. She continued to have jaundice.
She was not diabetic nor on oral steroids. Though she did not give a history of trauma, her daily chores included carrying fire wood.
On examination, she was sick, malnourished, with pallor, anasarca, jaundice, and generalized lymphadenopathy. She had non-healing ulcers over her face, body, arms, and legs .The ulcer base was covered with unhealthy black granulation tissue and foul-smelling pus [Figure 1]. She had oral thrush as well. Abdominal examination revealed ascites and mild hepatomegaly. Other systems were normal.
|Figure 1: Ulcerated lesions on face and neck with thick brownish purulent discharge|
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Blood counts revealed anaemia. Peripheral smear examination showed microcytic hypochromic anaemia with anisopoikilocytosis with relative neutrophilia with shift to left. ESR was raised and prothrombin time was increased. No blood parasites were seen. She had hypoalbuminaemia, elevated serum bilirubin levels, and elevated liver enzymes. Ultrasonogram of abdomen showed ascites and mild hepatomegaly with altered echo texture. Chest X-ray was normal. VDRL and ELISA for HIV-1 and HIV-2 were non-reactive. Hepatitis-B surface antigen was positive; IgM antibodies to hepatitis-A virus and antibody to hepatitis-C virus were negative. Fasting gastric juice was negative for acid-fast bacilli.
Wedge biopsy of ulcer of right forearm and leg revealed sheets of neutrophils, plump histiocytes, few epithelioid cells and black-pigmented hyphal elements in a necrotic background suggestive of a non-caseating granulomatous lesion. No sclerotic cells were found. Cervical lymph node biopsy revealed reactive hyperplasia. X-ray of leg ruled out bony involvement. Tissue debridement of the lesions was done. The biopsy sample was inoculated on Lowenstein-Jensen medium.
Gram stain of pus and debrided tissues from various sites revealed gram-negative bacilli, pus cells and gram-variable hyphal elements. Ziehl-Neelsen-stained smear of pus did not reveal acid-fast bacilli. Potassium hydroxide mount revealed a mixture of septate dematiaceous hyphal elements and pseudohyphae [Figure 2]. Giemsa stain was negative for Leishmania tropica bodies.
|Figure 2: Potassium hydroxide mount showing phaeoid hyphae and pseudohyphae (×400)|
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A clinical diagnosis of cirrhosis with subcutaneous phaeohyphomycosis was made. In view of the impaired liver function, she was started on oral ketoconazole 200 mg/day with monitoring of liver function tests along with supportive therapy for liver that included bed rest, salt- and protein-restricted diet, oral lactulose and neomycin, parenteral vitamin K, potassium-sparing diuretic, infusion of albumin and fresh-frozen plasma.
Pus from various sites was inoculated onto Sabouraud's dextrose agar (SDA) with gentamicin and incubated at 25 o C and 37 o C. Blood agar, MacConkey agar, and thioglycollate medium were inoculated and incubated under standard conditions. Culture of blood and ascitic fluid was done according to standard procedures.
Growth on blood agar and MacConkey was identified as Acinetobacter baumannii, sensitive to Amikacin and Ciprofloxacin. The patient was started on antibiotics and supportive treatment continued. No anaerobic organisms were isolated from thioglycollate medium. Blood and ascitic-fluid culture did not reveal any growth. No growth was observed in LJ medium as well. Culture of tongue scrapings yielded growth of Candida albicans.
All pus samples inoculated onto SDA grew moist, mucoid olive black colonies with olivaceous black reverse on the seventh day of incubation at both temperatures. Lactophenol cotton blue mount showed numerous dematiaceous septate hyphae with conidiophores bearing ellipsoidal annelloconidia suggestive of E. species [Figure 3]. The culture isolate was speciated as E. spinifera by the Mycology Division, PGIMER, Chandigarh.
On follow-up of the status of hepatitis, Hepatitis-B e-antigen was negative. Liver biopsy was not performed in view of the prolonged prothrombin time. As there was a further elevation of liver enzymes and serum bilirubin levels, antifungal treatment was withdrawn after seven days of therapy. The patient developed clinical signs of confusion, disorientation, gastrointestinal bleeding, and deterioration in the clinical condition. Patient expired three weeks after admission due to hepatic failure.
|Figure 3: Lactophenol cotton blue mount of isolate showing dematiaceous spine-like annellophores and annelloconidia (×400)|
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| ~ Discussion|| |
Phaeohyphomycosis is a term for any fungus present in tissue with brownish yeast-like cells, pseudohyphae or hyphae or a combination of these forms. The term black yeast may be used to refer to Exophiala species as they produce budding cells at some stage in their life cycle. E. spinifera is one of the most aggressive species of black yeasts. It produces a capsule-like extracellular polysaccharide around yeast cells which is associated with high virulence to humans. 
Phaeohyphomycosis caused by E. spinifera is a disease of rare occurrence. Clinical presentations of cutaneous lesions caused by E. spinifera vary widely, including erythaematous papules, verrucous plaques and deep subcutaneous abscesses. , Only 11 human cases have been reported in the English literature so far from different geographic regions of the world.
The first case of human infection was described in a seven-year-old boy from northern India, who had disseminated infection with bone involvement.  The second case of phaeohyphomycosis due to Exophiala spinifera in India was reported in a 12-year-old female patient with no immunocompromising condition, who presented with similar disseminated infection with lymph node involvement.  The third case in India was reported in a 10-year-old immunocompetent boy with disseminated phaeohyphomycotic lesions.  Exophiala spinifera infection presenting as a single painless soft tissue nodule in the dorsal aspect of the ring finger in an immunocompromised host has also been described.  Thus it is noteworthy that the clinical presentation may be single or a few lesions in immunocompromised adults or disseminated lesions in the immunocompetent. ,,,
Infection occurs due to traumatic implantation of fungal material from contaminated plants and soil. Many cases of phaeohyphomycosis may have no evident exposure history. As collecting and chopping firewood was part of her daily house-hold work, the probable mode of transmission of the disease in our case was traumatic inoculation, though a definite history of trauma was not recalled by her.
Impaired liver function is associated with impaired leukocyte function. In our patient, altered host defence due to hepatic dysfunction is a predisposing factor.  The presence of oral thrush due to C. albicans also points towards an immunocompromised state. 
The presence of fungal elements in direct microscopic examination of clinical specimens is of immense importance in determining the significance of a fungal isolate. A pyogenic inflammatory response with granuloma is a common histopathological feature of phaeohyphomycosis. In our case, the presence of phaeoid polymorphous septate hyphae in the potassium hydroxide mount and black-pigmented hyphal elements with granulomatous inflammatory reaction in histopathology of skin along with pure growth of E. spinifera from all sites proves the clinical significance of our isolate.
The various agents of subcutaneous or systemic phaeohyphomycosis in tissues are so similar in appearance that they cannot be differentiated solely on the basis of morphology. The pleomorphic nature of the Exophiala species can make their identification a challenge. Exophiala spinifera differs from E. jeanselmei by having longer, multicellular stiff spine-like annellophores that are darker at their bases and terminate in annelides with long tapering tips. 
The optimal therapy for black-yeast infections is controversial. Surgical excision, antifungal drug monotherapy or drug combinations have been used, but prolonged treatment is needed because of relapse.  Padhye et al. described a case of multiple subcutaneous phaeohyphomycosis who responded to amphotericin-B, ketoconazole and flucytosine. Archana et al. reported a case of disseminated phaeohyphomycosis, who showed minimal response to combination antifungal treatment with itraconazole and fluconazole for initial three months, followed by itraconazole, terbinafine, and cryotherapy. As these drugs may cause hepatotoxicity to a variable extent, dose reduction in chronic liver disease with monitoring of liver function tests is warranted.  In the present case, antifungal therapy was initiated with ketoconazole but was withdrawn due to poor hepatic function.
To conclude, E. spinifera infections are increasingly reported globally. This rare fungal condition can masquerade as a tuberculous lesion leading to delay in initiation of antifungal therapy. Management of the disease is difficult when poor hepatic function complicates the course of disease. This case highlights the need of awareness of this condition among family physicians at the primary healthcare level to which patients in the rural area make their visit.
| ~ Acknowledgement|| |
We thank Dr. Arunaloke Chakraborthy, Professor & Head, Mycology Division, Department of Microbiology, Postgraduate Institute of Medical Education & Research, Chandigarh for confirmation and speciation of Exophiala spinifera.
| ~ References|| |
|1.||Sybren DE Hoog G, Roxana G. Vitale. Bipolaris, Exophiala, Scedosporium, Sporothrix and Other Dematiaceous fungi. Chapter 125. In: Murray PR, Baron EJ, Jorgensen JH, Landry ML, Pfaller MA, editors. Manual of Clinical Microbiology. 9 th ed, Vol. 2. Washington DC: ASM Press; 2007. p. 1898-917. |
|2.||Rajendran C, Khaitan BK, Mittal R, Ramam M, Bhardwaj M, Datta KK. Phaeohyphomycosis caused by Exophiala spinifera in India. Med Mycol 2003;41:437-41. |
|3.||Rajam RV, Kandhari KC, Thirumalachar MJ. Chromomycosis caused by a rare yeast like dematiaceous fungus. Mycopathol Mycol Appl 1958;9:5-19. |
|4.||Singal A, Pandhi D, Bhattacharya SN, Das S, Aggarwal S, Mishra K. Pheohyphomycosis caused by Exophiala spinifera: A rare occurrence. Int J Dermatol 2008;47:44-7. |
|5.||Kotylo PK, Israel KS, Cohen JS, Bartlett MS. Subcutaneous phaeohyphomycosis of the finger caused by Exophiala spinifera. Am J Clin Pathol 1989;91:624-7. |
|6.||Cooper CR Jr. Deep phaeohyphomycosis, Chapter 35. In: Merz WG, Hay RJ, editors. Medical Mycology, Topley and Wilson's Microbiology and Microbial Infections. 10 th ed. Washington DC: ASM Press; 2005. p. 739-45. |
|7.||Clΰria J, Titos E, Jimιnez W, Ros J, Ginθs P, Arroyo V, et al. Altered biosynthesis of leukotrienes and lipoxins and host defense disorders in patients with cirrhosis and ascites.Gastroenterology1998;115:147-56. |
|8.||Edwards JE Jr. Candidiasis,Chapter 196. In: Fauci AS, Kasper DL, Longo DL, Braunwald E, Hauser SL, Jameson JL, Loscalzo J, editors. Harrison's Principles of Internal Medicine. 17 th ed, Vol. 1. USA: McGraw-Hill Medical publisher; 2008. p. 1254-6. |
|9.||Padhye AA, Ajello L, Chandler FW, Banos JE, Hernandez-Perez E, Llerena J, et al. Phaeohyphomycosis in El Salvador caused by Exophiala spinifera. Am J Trop Med Hyg 1983;32:799-803. |
|10.||Chen SC, Sorrell TC. Antifungal agents. Med J Aust 2007;187:404-9. |
[Figure 1], [Figure 2], [Figure 3]
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