|Year : 2014 | Volume
| Issue : 2 | Page : 188-190
Cerebral phaeohyphomycosis by Exophiala dermatitidis
S Sood1, VK Vaid2, M Sharma1, H Bhartiya2
1 Department of Lab Medicine, Fortis Escorts Hospital, Jaipur, Rajasthan, India
2 Department of Neurosurgery, Fortis Escorts Hospital, Jaipur, Rajasthan, India
|Date of Submission||18-Sep-2013|
|Date of Acceptance||20-Dec-2013|
|Date of Web Publication||2-Apr-2014|
Department of Lab Medicine, Fortis Escorts Hospital, Jaipur, Rajasthan
Source of Support: None, Conflict of Interest: None
Cerebral phaeohyphomycosis is a rare and frequently fatal disease. We report a case of cerebral phaeohyphomycosis caused by Exophiala dermatitidis in a young immuno competent male presenting to a tertiary care hospital in Jaipur.
Keywords: Central nervous system, exophiala dermatitidis, phaeohyphomycosis
|How to cite this article:|
Sood S, Vaid V K, Sharma M, Bhartiya H. Cerebral phaeohyphomycosis by Exophiala dermatitidis. Indian J Med Microbiol 2014;32:188-90
|How to cite this URL:|
Sood S, Vaid V K, Sharma M, Bhartiya H. Cerebral phaeohyphomycosis by Exophiala dermatitidis. Indian J Med Microbiol [serial online] 2014 [cited 2020 Aug 9];32:188-90. Available from: http://www.ijmm.org/text.asp?2014/32/2/188/129830
| ~ Introduction|| |
The term 'phaeohyphomycosis' is used to describe cutaneous, subcutaneous and systemic infections caused by hyphomycetous fungi, which develop as dematiaceous, septated hyphae in the host tissue.  Over 100 species and 60 genera of fungi have been implicated in the causation of phaeohyphomycosis. The most severe of phaeohyphomycosis are the infections of central nervous system (CNS). Cladophialophora bantiana and Ramichloridium mackenziei are the most frequent causes of cerebral phaeohyphomycosis; although several other dematiaceous fungi have also been implicated. 
Cerebral phaeohyphomycosis caused by Exophiala dermatitidis is rare and cerebral infections have been limited mostly to humans of East Asian Oriental race. This is the first reported case of cerebral phaeohyphomycosis by Exophiala dermatitidis from India.
| ~ Case Report|| |
A 21-year-old male student, resident of Jaipur city, presented to the Neurosurgery OPD of a tertiary care private hospital in September 2012 with progressive weakness in right hand and slurring of speech for over past one and half months. There was no associated history of fever, vomiting, blurring vision, convulsions and headache. The patient provided a history of two previous surgeries for left ear abscess (details unavailable). A month prior to his visit to our hospital, the patient had been diagnosed as a case of left intra-cranial space occupying lesion at the local Government Medical College Hospital.
At the time of his OPD visit, the patient was conscious, oriented, following verbal commands and afebrile. Systemic examination was normal except for the power in right upper limb which was 4/5 with gripping weakness. The patient was admitted under the Neurosurgery Department for further management and evaluation. Routine blood investigations were reported as normal and the magnetic resonance imaging (MRI) brain was suggestive of multiple, nodular, conglomerated lesions in left fronto-parietal lobes and left capsule-ganglionic region with surrounding mass effect and oedema [Figure 1]. MRI findings were suggestive of a granulomatous lesion (TB/Sarcoid) and or lymphoma. The provisional clinical diagnosis made was of left posterior-frontal perisylvian sub-cortical intra-cranial space occupying lesion and the patient was planned for left temporo-parietal craniotomy and tumour decompression under general anaesthesia.
Intra-operatively, frozen section sent to the Pathology laboratory was suggestive of normal glial tissues with giant cells and necrosis as well as fungal hyphae, and given an impression of infective granuloma. Based on the communication from Pathology laboratory, the excised brain tissue was sent in normal saline to Microbiology laboratory for fungal work up as well. On Periodic acid Schiff (PAS) staining of brain tissue, fungal filaments were reported [Figure 2].
In the Microbiology laboratory, the brain tissue was minced and vortexed in normal saline. The Potassium hydroxide(KOH) preparation showed septate fungal hyphae [Figure 3]. The brain tissue was further inoculated onto two Sabraud's dextrose agar (SDA) slants and incubated at 25°C and 37°C. Within 48-72 hours, black coloured colonies, with reverse black, appeared on SDA [Figure 4]. The colonies were slimy and yeast like and could be easily picked up as a string of material with an inoculating loop. The Gram's staining of the black colony showed yeast cells. On slide culture on Corn meal agar [Figure 5], cylindrical conidiogenous cells with rounded apices producing one-celled conidia were observed. Round to ovoid, conidia accumulated in balls or down the side of conidiophores were also seen. Based on the morphology on slide culture, the organism was presumptively identified as Exophiala species. The organism was then forwarded to a Reference laboratory where its identity was confirmed as Exophiala dermatitidis by sequencing of ribosomal DNA internal transcribed spacer (ITS) region. The media and stains used for identification of the organism at our laboratory were procured from HiMedia, India. Post-operatively the patient was shifted to the intensive care unit (ICU) where he was put on Amphotericin B 3-5 mg/kg/day. Due to the issue of renal derangement (high serum creatinine), the anti-fungal therapy was changed to Voriconazole 200 mg BD. The patient recovered well, was shifted to ward with stable vitals and finally discharged. Now, after a year post-surgery, the patient is constantly visiting the OPD for follow up and is still continued on Voriconazole. The post-surgery MRI film is not available, but it revealed the lesion to be of similar in size compared with pre-surgery lesion on MRI but additionally has a cavity visible reflecting the site from where the brain biopsy was excised. This case is being reported after due approval from Institutional review board.
|Figure 4: Growth of black mucoid colony on Sabraudæs Dextrose Agar at 37 degree C after 48 hours of incubation|
Click here to view
| ~ Discussion|| |
Exophiala dermatitidis was previously known as Wangiella dermatitidis and is a member of Ascomycete order Chaetothyriales. The species has been reported from the environment but is not a commonly found saprobe. It is absent from dead plant material or soil and also from the outdoor air. However, it has been isolated abundantly from public steam baths and water reservoirs. The natural ecological niche of E. dermatitidis still needs to be determined but it appears to be probably characterised by high temperature and humidity and a low concentration of organic compounds. 
Exophiala species resemble microscopically and species can be differentiated based upon the following: temperature tolerance, nitrate assimilation and also by molecular characterisation.  In a recent study of 188 clinical Exophiala isolates in USA, re-identification by ITS sequencing found E. dermatitidis to be the most common species followed by E. xenobiotica and E. oligosperma.  E. dermatitidis is a constitutive producer of melanin, is consistently able to grow at temperatures >37°C and produces extracellular polysaccharide capsules.  These three factors have been associated with the virulence of this fungus.
In a recent review, Suzukia et al., identified the following pre-disposing factors for E. dermatitidis infections-peritoneal dialysis, leukaemia, steroid use, human immunodeficiency virus infection, cancer, bronchiectasis, diabetes mellitus and multiple myeloma.  However, no such underlying factor could be identified in our patient.
E. dermatitidis cause mycoses ranging from neurotropic infections, cutaneous and sub-cutaneous infections to systemic lymphadenitis, airways colonisation in cystic fibrosis patients and mycoses related to continuous ambulatory peritoneal dialysis.  Our patient was a healthy adolescent male, who presented to the hospital with neurological findings. Primary cerebral infection caused by E. dermatitidis appears to occur mostly in patients of Asian origin. ,, The possibility of the involvement of race-dependent virulence has been suggested as an explanation of this observation. 
The portal of entry for the fungus in brain remains unclear for our patient; however, the possibility of direct extension into the brain cannot be ruled out in lieu of the history of previous ear surgeries on the same side. It has been postulated that Chaetothyriales can reach the brain through blood or lymphatic vessels, by directly spreading from adjacent lesions, or by accidental inoculation. 
The mortality associated with E. dermatitidis infection is extremely high, reaching up to almost 100% in cases of CNS involvement.  Because of the rarity of such cases, there is no consensus regarding appropriate treatment of cerebral phaeohyphomycosis. A combination of medical and surgical treatment is generally recommended.  Polyene drugs demonstrate modest anti-fungal activity in vitro against dematiaceous fungi and these have been used for treating some disseminated infections. The azoles are commonly used for treatment of phaeohyphomycosis because of their safety in administration over long duration and as these drugs exhibit moderate to excellent activity against dematiaceous fungi. Among the available azoles, itraconazole and voriconazole have been reported to have the most consistent and potent activity. Itraconazole has poor cerebrospinal fluid penetration but is able to attain high levels in the brain tissue. In contrast, voriconazole is able to attain good penetration in both cerebrospinal fluid and brain tissue. 
In this patient, surgical excision followed by an anti-fungal therapy with Amphotericin B and then Voriconazole was employed and this has led to a relatively uneventful clinical recovery.
| ~ Conclusion|| |
Fungal infection of the CNS is a life-threatening disease. Complete surgical removal of the brain lesion combined with anti-fungal drug therapy is the best management for this rare fungal disease.
| ~ Acknowledgement|| |
Authors thank Dr Arunaloke Chakrabarti, Professor and In-Charge, Center of Advance Research in Medical Mycology, WHO Collaborating Center for Reference and Research of Fungi of Medical Importance, National Culture Collection of Pathogenic Fungi and Head, Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, for his kind help in the final identification of the organism.
| ~ References|| |
|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. |
|2.||Revankar SG, Sutton DA, Rinaldi MG. Primary central nervous system phaeohyphomycosis: A review of 101 cases. Clin Infect Dis 2004;38:206-16. |
|3.||Matos T, de Hoog GS, de Boer AG, de Crom I, Haase G. High prevalence of the neurotrope Exophiala dermatitidis and related oligotrophic black yeasts in sauna facilities. Mycoses 2002;45:373-7. |
|4.||Revankar SG, Sutton DA. Melanized fungi in human disease. Clin Microbiol Rev 2010;23:884-928. |
|5.||Zeng JS, Sutton DA, Fothergill AW, Rinaldi MG, Harrak MJ, de Hoog GS. Spectrum of clinically relevant Exophiala species in the United States. J Clin Microbiol 2007;45:3713-20. |
|6.||Suzukia K, Nakamurab A, Fujiedaa A, Nakasea K, Katayamaa N. Pulmonary infection caused by Exophiala dermatitidis in a patient with multiple myeloma: A case report and a review of the literature. Med Mycol Case Rep 2012;1:95-8. |
|7.||Ajanee N, Alam M, Holmberg K, Khan J. Brain abscess caused by Wangiella dermatitidis: Case report. Clin Infect Dis 1996;23:197-8. |
|8.||Chang CL, Kim DS, Park DJ, Kim HJ, Lee CH, Shin JH. Acute cerebral phaeohyphomycosis due to Wangiella dermatitidis accompanied by cerebrospinal fluid eosinophilia. J Clin Microbiol 2000;38:1965-6. |
|9.||Chang X, Li R, Yu J, Bao X, Qin J. Phaeohyphomycosis of the central nervous system caused by Exophiala dermatitidis in a 3-year-old immunocompetent host. J Child Neurol 2008;24:342-5. |
|10.||Li DM, de Hoog GS. Cerebral phaeohyphomycosis-a cure at what lengths? Lancet Infect Dis 2009;9:376-83. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
|This article has been cited by|
||Cerebral Phaeohyphomycosis : A Rare Cause of Brain Abscess
| ||Na-Young Jung,Ealmaan Kim |
| ||Journal of Korean Neurosurgical Society. 2014; 56(5): 444 |
|[Pubmed] | [DOI]|