Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Search in posts
Search in pages
Filter by Categories
15th National Conference of the IAOMFP, Chennai, 2006
Abstracts from current literature
Acne in India: Guidelines for management - IAA Consensus Document
Art & Psychiatry
Association Activities
Association Notes
Award Article
Book Review
Brief Report
Case Analysis
Case Letter
Case Letters
Case Notes
Case Report
Case Reports
Clinical and Laboratory Investigations
Clinical Article
Clinical Studies
Clinical Study
Conference Oration
Conference Summary
Continuing Medical Education
Cosmetic Dermatology
Current Best Evidence
Current Issue
Current View
Derma Quest
Dermato Surgery
Dermatosurgery Specials
Dispensing Pearl
Do you know?
Drug Dialogues
Editor Speaks
Editorial Remarks
Editorial Report
Editorial Report - 2007
Editorial report for 2004-2005
Fourth All India Conference Programme
From Our Book Shelf
From the Desk of Chief Editor
Get Set for Net
Get set for the net
Guest Article
Guest Editorial
How I Manage?
IADVL Announcement
IADVL Announcements
IJDVL Awards
IJDVL Awards 2018
IJDVL Awards 2019
IJDVL Awards 2020
IJDVL International Awards 2018
Images in Clinical Practice
In Memorium
Inaugural Address
Knowledge From World Contemporaries
Leprosy Section
Letter in Response to Previous Publication
Letter to Editor
Letter to the Editor
Letter to the Editor - Case Letter
Letter to the Editor - Letter in Response to Published Article
Letter to the Editor - Observation Letter
Letter to the Editor - Study Letter
Letter to the Editor - Therapy Letter
Letter to the Editor: Articles in Response to Previously Published Articles
Letters in Response to Previous Publication
Letters to the Editor
Letters to the Editor - Letter in Response to Previously Published Articles
Letters to the Editor: Case Letters
Letters to the Editor: Letters in Response to Previously Published Articles
Medicolegal Window
Miscellaneous Letter
Net Case
Net case report
Net Image
Net Letter
Net Quiz
Net Study
New Preparations
News & Views
Observation Letter
Observation Letters
Original Article
Original Contributions
Pattern of Skin Diseases
Pediatric Dermatology
Pediatric Rounds
Presedential Address
Presidential Address
Presidents Remarks
Report of chief editor
Report of Hon : Treasurer IADVL
Report of Hon. General Secretary IADVL
Research Methdology
Research Methodology
Resident page
Resident's Page
Resident’s Page
Residents' Corner
Residents' Corner
Residents' Page
Review Article
Review Articles
Reviewers 2022
Revision Corner
Self Assessment Programme
Seminar: Chronic Arsenicosis in India
Seminar: HIV Infection
Short Communication
Short Communications
Short Report
Special Article
Specialty Interface
Study Letter
Study Letters
Symposium - Contact Dermatitis
Symposium - Lasers
Symposium - Pediatric Dermatoses
Symposium - Psoriasis
Symposium - Vesicobullous Disorders
Symposium Aesthetic Surgery
Symposium Dermatopathology
Symposium-Hair Disorders
Symposium-Nails Part I
Symposium-Nails-Part II
Systematic Review and Meta-Analysis
Systematic Reviews and Meta-analyses
Systematic Reviews and Meta-analysis
Therapeutic Guideline-IADVL
Therapeutic Guidelines
Therapeutic Guidelines - IADVL
Therapy Letter
Therapy Letters
View Point
What’s new in Dermatology
View/Download PDF

Translate this page into:

Case Report
88 (
); 59-61

A case of disseminated subcutaneous phaeohyphomycosis caused by Exserohilum rostratum with CARD9 mutation

Department of Dermatology, Seth GS Medical College and KEM Hospital, Mumbai, India
Dr. Miskeen's Central Clinical Microbiology Laboratory, Thane, India
ICMR-National Institute of Immunohaematology, KEM Hospital, Mumbai, Maharashtra, India
Corresponding author: Dr. Mayuri Kalantri, Department of Dermatology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India.
This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Kalantri M, Khopkar U, Shah A, Bargir UA, Hule G, Madkaikar M. A case of disseminated subcutaneous phaeohyphomycosis caused by Exserohilum rostratum with CARD9 mutation. Indian J Dermatol Venereol Leprol 2022;88:59-61.


Phaeohypomycosis is a rare cutaneous and subcutaneous fungal infection caused by dematiaceous fungi. They have a widespread global distribution occasionally affecting humans. A 26-year-old woman presented with multiple skin lesions over her face and extremities for last 7 years, unresponsive to systemic amphotericin B and itraconazole. Further investigations revealed CARD9 mutation and phaeohyphomycosis caused by the pigmented fungus Exserohilum rosatratum. Lesions subsequently improved with oral flucytosine and itraconazole.


Exserohilum rosatratum


The term phaeohyphomycosis, coined by Ajello et al. in 1974,1 refers to infections caused dematiaceous fungi belonging to a diverse group of organisms found in the soil, plants and organic debri.2 The major etiologic agents include Bipolaris, Exophiala, Curvularia, Exserohilum and Wangiella species. These fungi can infect the skin and subcutaneous tissue along with paranasal sinuses, eyes, bones or central nervous systemThese infections usually result from inconspicuous penetrating injuries. The common presentations include a solitary cutaneous nodule, plaque or deep-seated subcutaneous cyst or abscess localized to the exposed areas of body, especially the extremities.2

Susceptibility to fungal infections in otherwise healthy individuals with Mendelian disorders is being increasingly recognized due to widespread genome sequencing. Primary immunodeficiencies, characterized by various genetic defects hinder the proper development of innate and adaptive immunity. Caspase recruitment domain-containing protein 9 (CARD9) is an important regulator of innate immunity, present in neutrophils, macrophages and dendritic cells. Thus, mutations involving the CARD9 gene can lead to severe immunosuppression resulting in severe disseminated infections.3

We report this case of Amphotericin B non-responsive disseminated subcutaneous phaeohyphomycosis caused by Exserohilum rostratum, in a patient with novel CARD9 mutation.

Case Report

A 26-year-old married woman, agriculturist by profession, presented with several skin lesions affecting her face and extremeties for the last seven years; gradually increasing in size. There was no past history of known trauma. She was afebrile without any history of significant medical illness. Four years back she was prescribed anti-tubercular drugs (ATD) for nine months without any improvement of her skin lesions. Surgical excision was followed by recurrence of lesions at the same sites and distant places within six months. She also received two cycles of intravenous amphotericin B for 26 days each five months apart along with oral itraconazole, 200 mg twice daily for eight months with minimal improvement.

Cutaneous examination revealed multiple grouped, skin-colored to hyperpigmented, verrucous papules, nodules and plaques, diameters ranging from few mm to 6 cm, affecting the bilateral forearm, right knee, left leg and right cheek [Figures 1 and 2]. They were non-tender and soft to firm on palpation. No lymphadenopathy was noted.

Figure 1:: Well-defined, erythematous plaque on the right cheek extending to nose and chin
Figure 2:: Multiple grouped. verrucous, papules, nodules and plaques on bilateral forearm, right knee and left leg

Clinically, chromoblastomycosis, phaeohyphomycosis, tuberculosis verrucous cutis and atypical mycobacterial infections were considered as the differentials.

Routine biochemistry including blood sugar and serum electrolytes was within normal limits. Serum was negative for HBV, HCV and HIV viral markers.

Histological examination of a representative papule (right arm) demonstrated pseudo-epitheliomatous hyperplasia with nodular granulomatous infiltrate in the dermis and multiple pigmented septate hyphae [Figure 3].

Figure 3:: Pigmented, septate hyphae in the stratum corneum (Gomori methenamine-silver nitrate stain GMS stain, x100)

Tissue for fungal culture yielded growth within seven days on Sabouraud’s dextrose agar. Colonies were grey to olive-brown with cottony texture and black reverse pigmentation. Slide culture showed septate hyphae. The conidiophores were long with multiple septae demonstrating sympodial geniculate growth with knobby, zigzag appearance.The conidia were elliptical with transverse septations and distinct protruding hilum at their base [Figure 4]. All these features were suggestive of the pigmented fungus Exserohilum rostratum.

Figure 4:: Conidia with protruding hilum (arrow) (Lactophenol cotton blue stain LCB,×100)

The lymphocyte sub-population analysis and nitro blue tetrazolium test were normal. Her serum IgE was raised (9350 IU/L). Primary immunedeficiency gene panel by next-generation sequencing detected a homozygous non-sense variation in exon 8 of the CARD9 gene HMZ p.Q370X (c.1108C>T). A whole-body CT scan (brain, chest, abdomen and pelvis) failed to show any systemic involvement.

She was administered a combination therapy of oral itraconazole 200 mg twice daily with oral flucytosine 500 mg four times daily resulting in significant improvement of her lesions within one month. [Figure 5]. Notably she failed to respond to intravenous Amphotericin B previously. We advised regular follow-up to assess the long-term therapeutic response.

Figure 5:: Significant improvement after 1 month of treatment


Phaeoid fungi can cause a diverse group of infections including chromoblastomycosis (characteristic sclerotic bodies in tissue), eumycetoma (secretion of black coloured grains from the lesions) and hence, phaeohyphomycosis is a term used for other clinical presentations caused by dematiaceous fungi which form yeast-like cells, pseudohyphae, hyphae or a combination of these in the infected tissues.4

CARD9 deficiency is an autosomal-recessive disorder. Mutations in CARD9 (a key regulator of innate immunity) lead to impaired synthesis of pro-inflammatory cytokines resulting in depressed Th17- and Th22-associated anti-fungal response.5 Till now, 24 different genetic alterations in CARD9 have been described in 60 patients with fungal infections like candidiasis, dermatophytosis, phaeohyphomycosis and invasive aspergillosis resulting in CARD9 deficiency.3 This is the first Indian case of phaeohyphomycosis with a novel genetic alteration in the CARD9 gene.

The treatment of phaeohyphomycosis varies depending on their clinical presentation. Localized lesions respond to surgical excision and cryotherapy. Itraconazole and voriconazole demonstrate the most consistent in vitro activity against dematiaceous fungi while fluconazole has no role. Amphotericin B has good in vitro activity against most clinically important dematiaceous fungi. However, in vitro resistance and therapeutic failures have been reported with this drug. Flucytosine has an unique mechanism of action, inhibiting DNA and RNA synthesis. Combination therapy is often useful for refractory cases.6

Therapeutic success depends on the time of diagnosis, extent of lesions, comorbidities, the choice of anti-fungal drug and host immune status. Patients with CARD9 deficiency are often recalcitrant to conventional antifungal ltherapy.5 The use of sub-cutaneous granulocyte colony-stimulating factor as adjunctive immunomodulator in CARD9-deficient patients with CNS infection by Candida species has been described.7

In a review of 48 cases of phaeohyphomycosis caused by Exserohilum, immunosuppression (27.2%) was the commonest underlying condition followed by trauma (16.6%) and atopy (12.5%). Systemic involvement was reported in 73% patients while cutaneous (25%), corneal (16.7%) and subcutaneous (10.4%) infection were also recorded.8 There are two prior reports of subcutaneous phaeohyphomycosis due to Exserohilum rostratum from India.9,10

The underlying immunological mechanisms, particularly CARD9 mutation needs to be investigated in such apparently healthy patients with atypical, disseminated and refractory fungal infections. A multidisciplinary approach involving immunologists, microbiologists and dermatologists is necessary to gain newer insights into host immune response against fungi which may facilitate the development of newer and effective therapeutic strategies.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


  1. , , , . A case of phaeohyphomycosis caused by a new species of Phialophora. Mycologia. 1974;66:490-8.
    [CrossRef] [PubMed] [Google Scholar]
  2. , , , . Subcutaneous phaeohyphomycosis in an immunocompetent Individual: A case report. Indian Dermatol Online J. 2017;8:29-31.
    [CrossRef] [PubMed] [Google Scholar]
  3. , , , , , , et al. Frequency and geographic distribution of CARD9 mutations in patients with severe fungal infections. Front Microbiol. 2018;9:2434.
    [CrossRef] [PubMed] [Google Scholar]
  4. , , , , , . Disseminated cutaneous phaeohyphomycosis due to Cladophialophora bantiana. Indian J Dermatol Venereol Leprol. 2015;81:491-4.
    [CrossRef] [PubMed] [Google Scholar]
  5. , , , , , . Phaeohyphomycosis caused by Phialophora americana with CARD9 mutation and 20 year literature review in China. Mycoses. 2019;62:908-19.
    [CrossRef] [PubMed] [Google Scholar]
  6. . Dematiaceous fungi. Mycoses. 2007;50:91-101.
    [CrossRef] [PubMed] [Google Scholar]
  7. , , , , , , et al. Successful Granulocyte colony stimulating factor treatment of relapsing Candida albicans meningoencephalitis Caused by CARD9 Deficiency. Pediatr Infect Dis J. 2016;35:428-31.
    [CrossRef] [PubMed] [Google Scholar]
  8. , , , , , . Exserohilum infections: Review of 48 cases before the 2012 United States outbreak. Med Mycol. 2014;52:376-86.
    [CrossRef] [PubMed] [Google Scholar]
  9. , , , , . A case of subcutaneous phaeohyphomycosis caused by Exserohilum species in an immunocompromised patient. Our Dermatol Online. 2013;4:498-500.
    [CrossRef] [Google Scholar]
  10. , . A case of cutaneous phaeohyphomycosis caused by Exserohilum rostratum, its in vitro sensitivity and review of literature. Mycopathologia. 1995;131:9-12.
    [CrossRef] [PubMed] [Google Scholar]

Fulltext Views

PDF downloads
View/Download PDF
Download Citations
Show Sections