MYCOSES 35,
ACCEPTED: JANUARY 28, 1992
243-246 (1992)
CASEREPORT
Cutaneous phaeohyphomycosis due to CZadosporiurn
cladosporioides Cladosporium cladosporioides als Erreger einer ku tanen Phaeohyphomykose G. Annessil, A. Cimitanl, G. Zambruno' and A. Di Silverio' Key words. Cladosporium cladosporioides, phaeohyphomycosis, cutaneous infection, steroid-induced diabetes, fluconazole. Schliisselworter. Cladosporium cladosporioides, Phaeohyphomykose, Hau tinfektion, steroidinduzierter Diabetes, Fluconazol.
Summary. A 54-year-old man, affected by pemphigus vulgaris and severe steroid-induced diabetes, developed seven red-brown, firm, slightly raised 0.1- 1 cm papular lesions on the anterior aspect of both knees and thighs. A cutaneous biopsy showed a granulomatous infiltrate with numerous fungal elements scattered in the dermis and also within giant cells. Cultures of cutaneous biopsy fragments on Sabouraud glucose agar in presence of chloramphenicol resulted in the growth of dark-green colonies at 25 "C. They were identified as typical Cladosporium cladosporioides. As far as we know, this species was previously isolated only in an HIV-seropositive patient as opportunistic pathogen in the site of skin testing. Zusammenfassung. Ein 54 Jahre alter Patient, der wegen Pemphigus vulgaris vier Wochen lang mit Methylprednisolon-Natriumsuccinat in der Dosierung von 1.5 mg kg-' pro Tag behandelt wurde, entwickelte einen schweren Diabetes; er wies auf der ventralen Seite beider Knie und Oberschenkel sieben rotbraune, feste, leicht erhabene Hautlasionen mit einem Durchmesser von 0.1 - 1 cm auf. Eine Exzisionsbiopsie zeigte in der Dermis ein granulomatoses Infiltrat, durch-
' Clinica Dermatologica, Universitl di Modena and 'Clinica Dermatologica, Universitl di Pavia, Italy. Correspondence: Dr Adriano Di Silverio, Clinica Dermatologica, Universita di Pavia, Piazzale Golgi 25, 1-27100 Pavia, Italy.
setzt mit zahlreichen Pilzelementen und Riesenzellen. I n der Kultur wuchsen aus dem Biopsiematerial nach einer Woche Bebrutung bei 25 "C auf Sabouraud-Glucose-Agar mi t Chloramphenicol dunkelgrune Kolonien, die als Cladosporium cladosporioides identifiziert wurden. Nach unserer Kenntnis ist diese Pilzart bisher nur einma1 als opportunistischer Krankheitserreger aus dem Situs eines Hauttests bei einem HIV-positiven Patienten isoliert worden.
Introduction Phaeohyphomycoses are a heterogeneous group of fungal diseases due to darkly pigmented dematiaceous fungi whose hyphae, yeast-like cells and pseudohyphae are found in affected tissues in various combinations [l, 21. Phaeohyphomycosis may' present as superficial, cutaneous, subcutaneous and systemic infections occurring in immunocompromised hosts, but also in healthy subjects. In subcutaneous infections the causative organisms are introduced into the skin by traumatic inoculation [2]. Although many organisms may cause subcutaneous phaeohyphomycosis, the isolated agents are represented mostly by Exophiala janselmei, Wangiella dermatiditis, Bipolaris spp., Phialophora spp., Alternuria spp., etc. [3]. Herein we report a case of localized cutaneous and subcutaneous phaeohyphomycosis due to Cladosporium cladosporioides in an immunocompromised
244
G. ANNEWET
AL.
patient. To our knowledge this is the second case in medical literature [4].
Patient and method A 54-year-old man developed in a few days seven red-brown, firm, slightly raised, 0.1- 1 cm papular lesions distributed on the anterior aspect of both knees and thighs (Fig. 1). The lesions were completely asymptomatic. There was no regional lymphadenopathy. The patient was not able to recall injury to those areas. The patient had been admitted to our department about two months before for a pemphigus vulgaris and had been treated with methylprednisolone sodium succinate, 1.5 mg kg- day- i.v. for 4 weeks, followed by gradual tapering. In the meantime he developed severe steroid-induced diabetes. Laboratory evaluation revealed a white blood cell count of 6990/mm3 with a differential of 77 polymorphonuclear leukocytes, 17 lymphocytes and 2 monocytes, glucose 142 mg dl-', serum alanine aminotransferase 109 U 1- ', y-glu tamyl transpeptidase 131 U 1-', serum protein 5.4g dl-' and urinary glucose 820 mg dl-'. Chest X-ray and hepatobiliary ul trasonography were normal. An
Figure 1. Papules of the anterior aspect of the knee.
excisional biopsy of two papules was taken for routine histology and cultural examination. Histologic examination revealed a dense inflammatory infiltrate distributed within the dermis and extending into the subcutaneous tissue (Fig. 2). It was composed of numerous polymorphonuclear leukocytes and cellular debris admixed with histiocytes, epithelioid cells, scattered foreign body giant cells and a few lymphocytes. Numerous fungal cells were observed spread in the granulomatous infiltrate and also within giant cells (Fig. 3). Fungal elements consisted of light chestnut-brown yeast-like cells either solitary or connected in short chains. Short septate and usually unbranched hyphae were better visualized with special stains (Fig. 4a,b). No sclerotic bodies were observed. Moreover a foreign body was present in the reticular dermis and it appeared surrounded by a granulomatous reaction. Owing to the characteristics of its internal. structures, it was identified as a vegetal fragment with sclerenchyma fibres and pits (Fig. 5). I t seems likely that the vegetal fragment could have been the carrier of the inoculum. A microscopic examination of a cutaneous specimen with 20% KOH showed hyphal elements; moreover, cultures of biopsy fragments from the same tissue, on Sabouraud glucose agar in presence of chloramphenicol, resulted in the growth of olivaceous black colonies after 1 week at 25°C. By contrast, cultures previously stored at 37 "C showed no colony growth at 25°C. Slide cultures showed chains of onecelled blastoconidia arising from erect terminal and' lateral conidiophores. The isolate was referred to Professor C. de Vroey, Mycology Laboratory, Institute of Tropical Medicine, Antwerp, who identified it as Cladosporium cladosporioides. The patient was treated with fluconazole 50 mg daily 'per 0s'. After 4 weeks of treatment, 3 of 4 residual lesions had completely flattened, appearing as pigmented macules and
Figure 2. Diffuse dense infiltrate extending into the subcutaneous tissue. x 40.
mycoses 35, 243-246 (1992)
CUTANEOUS CLADOSPORIUM PHAEOHYPHOMYCOSIS
245
Figure 4. Fungal elements: chestnut brown yeast-like cells scatFigure 3. High magnification of the granulomatous infiltrate: note polymorphonucleargranulocytes, histiocytes, lymphocytes, and a giant cell containing a spherical body referred to as fungus. x 600.
tered in the granulomatous infiltrate particularly evident in the right side (a: PAS staining; b: silver-methenamine staining). x 300.
the fourth one, although flattened, was still palpable. An excisional biopsy of the last lesion was performed. Histologic examination showed dermal fibrosis and a foreign body granulomatous reaction surrounding a vegetal fragment similar to that found in the first biopsy, but no fungal elements. One year later the patient remains clinically healed. Pemphigus is well controlled with prednisone 10 mg every other day.
elements. I n contrast, chromoblastomycosis is characterized by the presence in the examined tissues of thick-walled, fungal cells with septation in two planes, referred to as sclerotic bodies or Medlar bodies or muriform cells. I n mycetoma the fungi occur as granules in colliquative lesions of destroyed tissues. Etiologic agents of phaeohyphomycosis include more than 70 species of opportunistic fungi that are ubiquitous saprophytes of soil, wood and decaying vegetable matter. The histopathologic features as well as clinical presentation of phaeohyphomycosis are highly variable, depending on interactions between the dematiaceous fungus and the host. Four basic forms have been categorized by McGinnis et al.: superficial, cutaneous, subcutaneous and systemic (Table 1). The subcutaneous form typically results from traumatic implantation of the fungus into the subcutaneous tissue. Lesions develop slowly a t the site of inoculation, in most cases appearing as solitary, asymptomatic, subcutaneous nodules. The histopathologic changes consist of cystic granulomata or of dispersed granulomatous reactions in the deep dermis and subcutaneous tissue, the epidermis being not involved. The principal fungi isolated are Exophiala jeanselmei,
Discussion
Dematiaceous fungi are now more frequently recognized as causative agents for mycosis in immunocompromised as well as apparently healthy persons. Phaeohyphomycosis represents one of the three diseases caused by dematiaceous fungi, the other two being chromoblastomycosis and mycetoma. The term phaeohyphomycosis was created by Ajello et al. in 1974 and more recently redefined by McGinnis [ l ] and colleagues; it describes a heterogeneous group of mycotic infections whose morphology in tissue includes dematiaceous yeast-like cells, pseudohyphae, hyphae, or any combination of these mycoses 35, 243-246 (1992)
246
G . ANNESSI ET
AL.
and in’ the air representing a well-known source of allergies to mould. Other Cladosporium spp. are well-recognized human fungal pathogens. The more thermophilic species Cl. bantianum and Cl. carrionii [3] are the most common agents of visceral and cerebral phaeohyphomycosis and chromoblastomycosis respectively. In contrast, infections due to C1. cladosporioides have been rarely reported. As far as we know, only one case of cutaneous infection caused by C1. cladosporioides has been described. I t developed as a complication of skin testing in a Human Immunodeficiency Virus (H1V)-seropositive patient [4]. In our case infection occurred in a patient receiving a high dose of methylprednisolone (1.5 mg kg- day- i.v.) who developed severe diabetes, which is a dismetabolic condition often associated with opportunistic infections. The improvement of pemphigus and tapering of steroid were followed by diabetes control. Simultaneously, systemic treatment with fluconazole 50 mg daily for 4 weeks induced the complete healing of lesions. Acknowledgement Figure 5. Foreign body referred as vegetal fragment likely carrier of the fungus. x 300.
Table 1. Classification of phaeohyphomycoses (McGinnis) [ I ]
References
1 Superficial phaeohyphomycoses 1.1 Black piedra
1.2 Tinea nigra 2 Cutaneous and corneal phaeohyphomycoses 2.1 Dermatomycoses 2.2 Mycotic keratitis 2.3 Onychomycoses 3 Subcutaneous phaeohyphomycoses 4 Systemic or visceral phaeohyphomycoses
We want to thank Professor Charles de Vroey for his kind help in the identification of C1. cladosporioides.
I
Wangiella dermatiditis, B$olaris spp. and Phialophora spp. In our case the isolated fungus was C1. cladosporioides. It is one of the most common species of fungi found on dead organic substances
1 McGinnis, M. (1983) Chromoblastomycosis and phaeohyphomycosis: New concepts, diagnosis, and mycology. 3. Am. Acad. Dermatol. 8, 1-16. 2 Dixon, D. M. & Polak-Wyss, A. (1991) The medically important dernatiaceous fungi and their identification. Mycoses, 34, 1-18. 3 Banerjee, U., Mohapatra, A. K., Sarkar, C. & Chaudhery, R. (1989) Cladosporiosis (cerebral phaeohyphomycosis) of brain-a case report. Mycopathologia 105, 163- 166. 4 Drabick, J. J., Gomatos, J. P. & Solis, J. B. (1990) Cutaneous cladosporiosis as a complication of skin testing in a man positive for human immunodeficiency virus. 3. Am. Acad. Dermatol. 22, 135-136. 5 de B i k e C. (1991) Les Alternuria pathogines pour l’homme: mycologie ipidimiologique. j.Mycol. Mkd. 1, 50-7 1.
ACCEPTED: JANUARY 28, 1992
243-246 (1992)
CASEREPORT
Cutaneous phaeohyphomycosis due to CZadosporiurn
cladosporioides Cladosporium cladosporioides als Erreger einer ku tanen Phaeohyphomykose G. Annessil, A. Cimitanl, G. Zambruno' and A. Di Silverio' Key words. Cladosporium cladosporioides, phaeohyphomycosis, cutaneous infection, steroid-induced diabetes, fluconazole. Schliisselworter. Cladosporium cladosporioides, Phaeohyphomykose, Hau tinfektion, steroidinduzierter Diabetes, Fluconazol.
Summary. A 54-year-old man, affected by pemphigus vulgaris and severe steroid-induced diabetes, developed seven red-brown, firm, slightly raised 0.1- 1 cm papular lesions on the anterior aspect of both knees and thighs. A cutaneous biopsy showed a granulomatous infiltrate with numerous fungal elements scattered in the dermis and also within giant cells. Cultures of cutaneous biopsy fragments on Sabouraud glucose agar in presence of chloramphenicol resulted in the growth of dark-green colonies at 25 "C. They were identified as typical Cladosporium cladosporioides. As far as we know, this species was previously isolated only in an HIV-seropositive patient as opportunistic pathogen in the site of skin testing. Zusammenfassung. Ein 54 Jahre alter Patient, der wegen Pemphigus vulgaris vier Wochen lang mit Methylprednisolon-Natriumsuccinat in der Dosierung von 1.5 mg kg-' pro Tag behandelt wurde, entwickelte einen schweren Diabetes; er wies auf der ventralen Seite beider Knie und Oberschenkel sieben rotbraune, feste, leicht erhabene Hautlasionen mit einem Durchmesser von 0.1 - 1 cm auf. Eine Exzisionsbiopsie zeigte in der Dermis ein granulomatoses Infiltrat, durch-
' Clinica Dermatologica, Universitl di Modena and 'Clinica Dermatologica, Universitl di Pavia, Italy. Correspondence: Dr Adriano Di Silverio, Clinica Dermatologica, Universita di Pavia, Piazzale Golgi 25, 1-27100 Pavia, Italy.
setzt mit zahlreichen Pilzelementen und Riesenzellen. I n der Kultur wuchsen aus dem Biopsiematerial nach einer Woche Bebrutung bei 25 "C auf Sabouraud-Glucose-Agar mi t Chloramphenicol dunkelgrune Kolonien, die als Cladosporium cladosporioides identifiziert wurden. Nach unserer Kenntnis ist diese Pilzart bisher nur einma1 als opportunistischer Krankheitserreger aus dem Situs eines Hauttests bei einem HIV-positiven Patienten isoliert worden.
Introduction Phaeohyphomycoses are a heterogeneous group of fungal diseases due to darkly pigmented dematiaceous fungi whose hyphae, yeast-like cells and pseudohyphae are found in affected tissues in various combinations [l, 21. Phaeohyphomycosis may' present as superficial, cutaneous, subcutaneous and systemic infections occurring in immunocompromised hosts, but also in healthy subjects. In subcutaneous infections the causative organisms are introduced into the skin by traumatic inoculation [2]. Although many organisms may cause subcutaneous phaeohyphomycosis, the isolated agents are represented mostly by Exophiala janselmei, Wangiella dermatiditis, Bipolaris spp., Phialophora spp., Alternuria spp., etc. [3]. Herein we report a case of localized cutaneous and subcutaneous phaeohyphomycosis due to Cladosporium cladosporioides in an immunocompromised
244
G. ANNEWET
AL.
patient. To our knowledge this is the second case in medical literature [4].
Patient and method A 54-year-old man developed in a few days seven red-brown, firm, slightly raised, 0.1- 1 cm papular lesions distributed on the anterior aspect of both knees and thighs (Fig. 1). The lesions were completely asymptomatic. There was no regional lymphadenopathy. The patient was not able to recall injury to those areas. The patient had been admitted to our department about two months before for a pemphigus vulgaris and had been treated with methylprednisolone sodium succinate, 1.5 mg kg- day- i.v. for 4 weeks, followed by gradual tapering. In the meantime he developed severe steroid-induced diabetes. Laboratory evaluation revealed a white blood cell count of 6990/mm3 with a differential of 77 polymorphonuclear leukocytes, 17 lymphocytes and 2 monocytes, glucose 142 mg dl-', serum alanine aminotransferase 109 U 1- ', y-glu tamyl transpeptidase 131 U 1-', serum protein 5.4g dl-' and urinary glucose 820 mg dl-'. Chest X-ray and hepatobiliary ul trasonography were normal. An
Figure 1. Papules of the anterior aspect of the knee.
excisional biopsy of two papules was taken for routine histology and cultural examination. Histologic examination revealed a dense inflammatory infiltrate distributed within the dermis and extending into the subcutaneous tissue (Fig. 2). It was composed of numerous polymorphonuclear leukocytes and cellular debris admixed with histiocytes, epithelioid cells, scattered foreign body giant cells and a few lymphocytes. Numerous fungal cells were observed spread in the granulomatous infiltrate and also within giant cells (Fig. 3). Fungal elements consisted of light chestnut-brown yeast-like cells either solitary or connected in short chains. Short septate and usually unbranched hyphae were better visualized with special stains (Fig. 4a,b). No sclerotic bodies were observed. Moreover a foreign body was present in the reticular dermis and it appeared surrounded by a granulomatous reaction. Owing to the characteristics of its internal. structures, it was identified as a vegetal fragment with sclerenchyma fibres and pits (Fig. 5). I t seems likely that the vegetal fragment could have been the carrier of the inoculum. A microscopic examination of a cutaneous specimen with 20% KOH showed hyphal elements; moreover, cultures of biopsy fragments from the same tissue, on Sabouraud glucose agar in presence of chloramphenicol, resulted in the growth of olivaceous black colonies after 1 week at 25°C. By contrast, cultures previously stored at 37 "C showed no colony growth at 25°C. Slide cultures showed chains of onecelled blastoconidia arising from erect terminal and' lateral conidiophores. The isolate was referred to Professor C. de Vroey, Mycology Laboratory, Institute of Tropical Medicine, Antwerp, who identified it as Cladosporium cladosporioides. The patient was treated with fluconazole 50 mg daily 'per 0s'. After 4 weeks of treatment, 3 of 4 residual lesions had completely flattened, appearing as pigmented macules and
Figure 2. Diffuse dense infiltrate extending into the subcutaneous tissue. x 40.
mycoses 35, 243-246 (1992)
CUTANEOUS CLADOSPORIUM PHAEOHYPHOMYCOSIS
245
Figure 4. Fungal elements: chestnut brown yeast-like cells scatFigure 3. High magnification of the granulomatous infiltrate: note polymorphonucleargranulocytes, histiocytes, lymphocytes, and a giant cell containing a spherical body referred to as fungus. x 600.
tered in the granulomatous infiltrate particularly evident in the right side (a: PAS staining; b: silver-methenamine staining). x 300.
the fourth one, although flattened, was still palpable. An excisional biopsy of the last lesion was performed. Histologic examination showed dermal fibrosis and a foreign body granulomatous reaction surrounding a vegetal fragment similar to that found in the first biopsy, but no fungal elements. One year later the patient remains clinically healed. Pemphigus is well controlled with prednisone 10 mg every other day.
elements. I n contrast, chromoblastomycosis is characterized by the presence in the examined tissues of thick-walled, fungal cells with septation in two planes, referred to as sclerotic bodies or Medlar bodies or muriform cells. I n mycetoma the fungi occur as granules in colliquative lesions of destroyed tissues. Etiologic agents of phaeohyphomycosis include more than 70 species of opportunistic fungi that are ubiquitous saprophytes of soil, wood and decaying vegetable matter. The histopathologic features as well as clinical presentation of phaeohyphomycosis are highly variable, depending on interactions between the dematiaceous fungus and the host. Four basic forms have been categorized by McGinnis et al.: superficial, cutaneous, subcutaneous and systemic (Table 1). The subcutaneous form typically results from traumatic implantation of the fungus into the subcutaneous tissue. Lesions develop slowly a t the site of inoculation, in most cases appearing as solitary, asymptomatic, subcutaneous nodules. The histopathologic changes consist of cystic granulomata or of dispersed granulomatous reactions in the deep dermis and subcutaneous tissue, the epidermis being not involved. The principal fungi isolated are Exophiala jeanselmei,
Discussion
Dematiaceous fungi are now more frequently recognized as causative agents for mycosis in immunocompromised as well as apparently healthy persons. Phaeohyphomycosis represents one of the three diseases caused by dematiaceous fungi, the other two being chromoblastomycosis and mycetoma. The term phaeohyphomycosis was created by Ajello et al. in 1974 and more recently redefined by McGinnis [ l ] and colleagues; it describes a heterogeneous group of mycotic infections whose morphology in tissue includes dematiaceous yeast-like cells, pseudohyphae, hyphae, or any combination of these mycoses 35, 243-246 (1992)
246
G . ANNESSI ET
AL.
and in’ the air representing a well-known source of allergies to mould. Other Cladosporium spp. are well-recognized human fungal pathogens. The more thermophilic species Cl. bantianum and Cl. carrionii [3] are the most common agents of visceral and cerebral phaeohyphomycosis and chromoblastomycosis respectively. In contrast, infections due to C1. cladosporioides have been rarely reported. As far as we know, only one case of cutaneous infection caused by C1. cladosporioides has been described. I t developed as a complication of skin testing in a Human Immunodeficiency Virus (H1V)-seropositive patient [4]. In our case infection occurred in a patient receiving a high dose of methylprednisolone (1.5 mg kg- day- i.v.) who developed severe diabetes, which is a dismetabolic condition often associated with opportunistic infections. The improvement of pemphigus and tapering of steroid were followed by diabetes control. Simultaneously, systemic treatment with fluconazole 50 mg daily for 4 weeks induced the complete healing of lesions. Acknowledgement Figure 5. Foreign body referred as vegetal fragment likely carrier of the fungus. x 300.
Table 1. Classification of phaeohyphomycoses (McGinnis) [ I ]
References
1 Superficial phaeohyphomycoses 1.1 Black piedra
1.2 Tinea nigra 2 Cutaneous and corneal phaeohyphomycoses 2.1 Dermatomycoses 2.2 Mycotic keratitis 2.3 Onychomycoses 3 Subcutaneous phaeohyphomycoses 4 Systemic or visceral phaeohyphomycoses
We want to thank Professor Charles de Vroey for his kind help in the identification of C1. cladosporioides.
I
Wangiella dermatiditis, B$olaris spp. and Phialophora spp. In our case the isolated fungus was C1. cladosporioides. It is one of the most common species of fungi found on dead organic substances
1 McGinnis, M. (1983) Chromoblastomycosis and phaeohyphomycosis: New concepts, diagnosis, and mycology. 3. Am. Acad. Dermatol. 8, 1-16. 2 Dixon, D. M. & Polak-Wyss, A. (1991) The medically important dernatiaceous fungi and their identification. Mycoses, 34, 1-18. 3 Banerjee, U., Mohapatra, A. K., Sarkar, C. & Chaudhery, R. (1989) Cladosporiosis (cerebral phaeohyphomycosis) of brain-a case report. Mycopathologia 105, 163- 166. 4 Drabick, J. J., Gomatos, J. P. & Solis, J. B. (1990) Cutaneous cladosporiosis as a complication of skin testing in a man positive for human immunodeficiency virus. 3. Am. Acad. Dermatol. 22, 135-136. 5 de B i k e C. (1991) Les Alternuria pathogines pour l’homme: mycologie ipidimiologique. j.Mycol. Mkd. 1, 50-7 1.
