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Mycetoma caused by Acremonium falciforme: Successful treatment with itraconazole
Journal of the American Academy of Dermatology Volume 32, Number 5, Part 2
Lee et al.
seminated superficial porokeratosisand immunosuppression. Br J Dermatol 1988;119:375-80. 23. TsambaosD, SpiliopoulosT. Disseminatedsuperficialporokeratosis:complete remissionsubsequentto discontinuation of immunosuppression.J AM ACADDERMATOL1993; 28:651-2. 24. Hazen PG, Carney JF, Walker AE, Stewart JJ, Engstrom CW. Disseminated superficial actinic porokeratosis: appearanceassociatedwith photochemotherapy for psoriasis. J Am Acad Dermatol 1985;12:1077-8. 25. Manganoni AM, Facchetti F, GavazzoniR. Involvementof epidermal Langerhans cells in porokeratosisof immuno-
897
suppressed renal transplant recipients. J AM ACAD DERMATOL1989;21:799-801. 26. Kemler BJ, Alpert E. Inflammatory bowel disease:study of cell mediated cytotoxicity for isolated human colonic epithelial cells.Gut 1980;21:353-9. 27. Hodgson HJF, Potter BJ, Jewel1DP. Immune complexes in ulcerativecolitisand Crohn’sdisease.Clin Exp Immunol 1977;29:187-96. 28. FiasseR, Lurhuma AZ, Cambiaso CL. Circulating immune complexesand diseaseactivity in Crohn’s disease. Gut 1978:19:611-7.
Mycetoma caused by Acremonium falciforme: Successful treatment with itraconazole Moo Wong Lee, MD,a Jong Chul Kim, MD: Jong Soo Choi, MD: Ki Hong Kim, MD,a and Donald L. Greer, PhDb Taegu, Korea, and New Orleans, Louisiana Mycetoma has not been previously reported in Korea. A case of mycetoma caused by Acremonium falciforme in a 72-year-old man is described. The patient had a single, large, welldemarcated, erythematous, swollen, black, escharlike lesion and three small satellite lesions on his right temporal area. He was treated with itraconazole, and all lesions healed with residual scars in 70 days. (J AM ACAD DERMATOL 1995;32:897-900.)
Mycetoma is a chronic infectious disease, usually affecting an extremity, that is characterized by induration and draining sinuses involving cutaneous, subcutaneous tissues, fascia, and bone. Usually the causal agents enter the skin as a result of trauma. Weeks or months later, the subcutaneous tissue at the site of inoculation becomes indurated, an abscess develops, and sinuses may drain to the surface. Pus draining from the sinus tract is characteristically granular, with grains that may be visible to the naked eye. Microscopic examination of these grains reveals them to be bacterial microcolonies or aggregates of fungal hyphae embedded within fibrin from From the Departmentof nam University, ogy, Louisiana
Dermatology, College of Medicine,Y eungTaegu. Korea,a and the Department of DermatolState University School of Medicine.b
the host tissues. The color of the grains often assists in the differentiation between bacterial and fungal origins. Special stains, such as periodic acid-Schiff positive and Gomori’s methenamine silver, clearly show hyphae within grains of fungal origin.lm3 The Gram stain demonstrates filamentous bacteria if present. Mycetomas are caused by either actinomycetes (actinomycetoma) or fungi (eumycetoma). Although a variety of organisms are responsible for eumycetoma, the predominant pathogen is Madurella mycetomatis, with Acremonium falciforme a less common agent.4 This case of a man with eumycetoma caused by A. falcijbrme is the first such reported in Korea.
Reprint requests: Donald L. Greer, MD, Department of Dermatology, Louisiana State University Medical Center, 1542 Tulane Ave., New Orleans, LA 70112-2822. Copyright 0190-9622/95
@ 1995 by the American $3.00+0
16/4/60903
Academy
of Dermatology,
Inc.
CASEREPORT A 70-year-old man had chronic ulcerative lesionsof the right temporal area for 3 months. Despite antibiotic treatment, these lesions had increased progressively in
size and number. Examination showed an erythematous, swollen, indurated, black, escharlike sinus, 2.3 cm X 2.3
898
Lee et al.
Journal of the American Academy of Dermatology May 1995
Fig. 1. Single, well-demarcated, 2.3 X 2.3 cm, erythematous, swollen, indurated, black, escharlike sinus and three small satellite lesions on right temporal area.
Fig. 2. Histopathologic examination shows infiltration of eosinophils and mononuclear cells in middle and lower layers of dermis. (Hematoxylin-eosin stain; X 100).
cm in size. The sinus was round, indurated, and surrounded by three small, satellite lesions (Fig. 1). Examination of a biopsy specimen revealed necrosis of the epidermis and upper dermis, with a moderately dense infiltration of eosinophils and lymphocytes in the middle and lower layers of the dermis (Fig. 2). Periodic acid-Schitf positive stain showed aggregates of numerous septate hy-
phae within a fibrous matrix in the upper necrotic area (Fig. 3). At the initial visit, tissue was cultured on Sabouraud dextrose agar tubes. The results were negative. Two weeks after the first visit, other tissue samples were examined in a potassium hydroxide preparation. Abundant, granular clumps of hyaline hyphae were observed.
Journal of the American Academy of Dermatology Volume 32, Number 5, Part 2
Lee et al.
899
Fig. 3. Histopathologic examination shows aggregates of numerous septate hyphae on ne-
crotic area (Periodic acid-Schiff positive stain; x200).
Results of cultures at this time were positive, and the same fungus was recovered from three different lesions by culture on Sabouraud dextrose agar tubes but not on Sabouraud dextrose agar with cycloheximide. The colonies, which grew rapidly, were downy and grayish-white, with a moist area. The backs of the colonies were flat, with no folds. A nondiffusible purple pigment was noticeable. Growth rate was slower at 37” C than at room temperature. Morphologic characteristics of the colony were identical at both temperatures. The microscopic findings by slide culture revealed narrow, septate hyphae and erect, simple conidiophores. The crescent-shaped conidia were formed in clusters around thin, tapering ends of the conidiophores. The conidia were either one or two celled. Scanning electron microscopy revealed that conidia were produced from inner wall of hyphae (enteroblastic). The surface tip of the conidiophore, after separation of the conidium, showed a cuplike appearance (phialide) . Itraconazole was given orally at a dose of 200 mg/day, and lesions progressively healed. Thirty days after therapy, the smaller, satellite lesions showed almost complete healing and the large, primary lesion revealed a significant reduction in oozing and swelling. All lesions cleared after 70 days of treatment. DISCUSSION
Since Gill first reported mycetoma in 1842, it has been reported in tropical countries such as Sudan and Mexico.’ This is the first reported case in Korea of mycetoma caused by A. falcijbrme.
The first case of eumycetoma caused by A. j&ifirme was reported in Puerto Rico by Carrion5 in 195 I as eumycetoma caused by Cephalosporium falciforme. In 197 1, Gams6 reclassified these organisms, choosing Acremonium as the name for the new genus. He recognized three species: A. falciforme (C. falciforme), Acremonium kiliense (Cephalosporium granulomatis), and Acremonium recifei (Cephalosporium recifei). A. falciforme accounts for most infections in human beings. Although Acremonium species can be found throughout the world, eumycetoma caused by Acremonium species is reported infrequently. Either these fungi have a low virulence or they rarely contaminate wounds.7 Because of the long incubation period, patients often do not recall any injury at the site of mycetoma development. This suggests that the fungus may be implanted superficially. Many factors are necessary for a mycetoma to develop. The patient’s overall health, immune system, personal hygiene, and nutritional status need to be considered in evaluation.8 The treatment of mycetoma consists of medical therapy, surgical therapy, or both.9 Most eumycetomas eventually necessitate amputation. Linda et a1.8 tried a regimen of amphotericin B and ketoconazole in a patient with a eumycetoma caused by A. falciforme. The patient’s condition did not respond. Mahgoub et al.‘O reported improvement in a patient
900
Lee et al.
infectedwith M. mycetomatis after treatmentwith 400 mg/day oral ketoconazole.Josephet al.11also reportedclinical improvementin a caseof eumycetoma causedby A. falciforme that wastreatedwith oral ketoconazoleat a doseof 400 mg/day. In the casedescribedhere, the lesionsclearedin 70 days after treatment with oral itraconazoleat 200 mg/ day. REFERENCES
1. Rippon JW. Medical mycology. 3rd ed. Philadelphia:WB Saunders, 1988;80-117. 2. Arnold HL, Odom RB, Fames WD. Andrews’ diseasesof the skin. 8th ed. Philadelphia: WB Saunders, 1990:371-3. 3. Wiedman FD, Kligman AM. A new speciesof Cephalosporium in Madura foot. J Bacterial 1945;50:491-5. 4. Taralakshmi VV, PankajalakshmiVV, ParamasivanCN, et al. Mycetoma in Madras. Sabouraudia 1977;15:17-22.
Journal of the American Academy of Dermatology May 1995
5. Carrion AL. Cephalosporium falciforme sp. nov., a new etiologic agent of maduromycosis. Mycologia 1951;43: 522-3. 6. Gams W. Cephalosporium-artige
Schimmelpilze (Hyphomycetes).Stuttgart: Gustav Fischer Verlag, 1971. 7. Halde C, Padhye AA, Haley LD, et al. Acremonium falczjbrme as a causeof mycetoma in California. Sabouraudia 1976;14:319-26. 8. Linda VE, Lance RP, Dale NG. Acremonium falciforme (Cephalosporium falciforme) mycetoma in a renal transplant patient. Arch Dermatol 1983;119:707-8. 9. John PU, Shadomy HJ. Deep fungal infections. In: Fitzpatrick TB, EisenAZ, Wolff K, et al, cds.Dermatology in general medicine.3rd ed. New York: McGraw-Hill Book, 1987:2252-4. 10. Mahgoub ES, Gumaa SA. Ketoconazolein the treatment of eumycetomadue to Madurella mycetomii. Trans R Sot Trop Med Hyg 1984;78:376-9. 11. JosephGM, Peter BM, Martin HT, et al. Mycetoma associated with Acremonium falciforme infection. Med J Aust 1987;147:187-8.
Lee et al.
seminated superficial porokeratosisand immunosuppression. Br J Dermatol 1988;119:375-80. 23. TsambaosD, SpiliopoulosT. Disseminatedsuperficialporokeratosis:complete remissionsubsequentto discontinuation of immunosuppression.J AM ACADDERMATOL1993; 28:651-2. 24. Hazen PG, Carney JF, Walker AE, Stewart JJ, Engstrom CW. Disseminated superficial actinic porokeratosis: appearanceassociatedwith photochemotherapy for psoriasis. J Am Acad Dermatol 1985;12:1077-8. 25. Manganoni AM, Facchetti F, GavazzoniR. Involvementof epidermal Langerhans cells in porokeratosisof immuno-
897
suppressed renal transplant recipients. J AM ACAD DERMATOL1989;21:799-801. 26. Kemler BJ, Alpert E. Inflammatory bowel disease:study of cell mediated cytotoxicity for isolated human colonic epithelial cells.Gut 1980;21:353-9. 27. Hodgson HJF, Potter BJ, Jewel1DP. Immune complexes in ulcerativecolitisand Crohn’sdisease.Clin Exp Immunol 1977;29:187-96. 28. FiasseR, Lurhuma AZ, Cambiaso CL. Circulating immune complexesand diseaseactivity in Crohn’s disease. Gut 1978:19:611-7.
Mycetoma caused by Acremonium falciforme: Successful treatment with itraconazole Moo Wong Lee, MD,a Jong Chul Kim, MD: Jong Soo Choi, MD: Ki Hong Kim, MD,a and Donald L. Greer, PhDb Taegu, Korea, and New Orleans, Louisiana Mycetoma has not been previously reported in Korea. A case of mycetoma caused by Acremonium falciforme in a 72-year-old man is described. The patient had a single, large, welldemarcated, erythematous, swollen, black, escharlike lesion and three small satellite lesions on his right temporal area. He was treated with itraconazole, and all lesions healed with residual scars in 70 days. (J AM ACAD DERMATOL 1995;32:897-900.)
Mycetoma is a chronic infectious disease, usually affecting an extremity, that is characterized by induration and draining sinuses involving cutaneous, subcutaneous tissues, fascia, and bone. Usually the causal agents enter the skin as a result of trauma. Weeks or months later, the subcutaneous tissue at the site of inoculation becomes indurated, an abscess develops, and sinuses may drain to the surface. Pus draining from the sinus tract is characteristically granular, with grains that may be visible to the naked eye. Microscopic examination of these grains reveals them to be bacterial microcolonies or aggregates of fungal hyphae embedded within fibrin from From the Departmentof nam University, ogy, Louisiana
Dermatology, College of Medicine,Y eungTaegu. Korea,a and the Department of DermatolState University School of Medicine.b
the host tissues. The color of the grains often assists in the differentiation between bacterial and fungal origins. Special stains, such as periodic acid-Schiff positive and Gomori’s methenamine silver, clearly show hyphae within grains of fungal origin.lm3 The Gram stain demonstrates filamentous bacteria if present. Mycetomas are caused by either actinomycetes (actinomycetoma) or fungi (eumycetoma). Although a variety of organisms are responsible for eumycetoma, the predominant pathogen is Madurella mycetomatis, with Acremonium falciforme a less common agent.4 This case of a man with eumycetoma caused by A. falcijbrme is the first such reported in Korea.
Reprint requests: Donald L. Greer, MD, Department of Dermatology, Louisiana State University Medical Center, 1542 Tulane Ave., New Orleans, LA 70112-2822. Copyright 0190-9622/95
@ 1995 by the American $3.00+0
16/4/60903
Academy
of Dermatology,
Inc.
CASEREPORT A 70-year-old man had chronic ulcerative lesionsof the right temporal area for 3 months. Despite antibiotic treatment, these lesions had increased progressively in
size and number. Examination showed an erythematous, swollen, indurated, black, escharlike sinus, 2.3 cm X 2.3
898
Lee et al.
Journal of the American Academy of Dermatology May 1995
Fig. 1. Single, well-demarcated, 2.3 X 2.3 cm, erythematous, swollen, indurated, black, escharlike sinus and three small satellite lesions on right temporal area.
Fig. 2. Histopathologic examination shows infiltration of eosinophils and mononuclear cells in middle and lower layers of dermis. (Hematoxylin-eosin stain; X 100).
cm in size. The sinus was round, indurated, and surrounded by three small, satellite lesions (Fig. 1). Examination of a biopsy specimen revealed necrosis of the epidermis and upper dermis, with a moderately dense infiltration of eosinophils and lymphocytes in the middle and lower layers of the dermis (Fig. 2). Periodic acid-Schitf positive stain showed aggregates of numerous septate hy-
phae within a fibrous matrix in the upper necrotic area (Fig. 3). At the initial visit, tissue was cultured on Sabouraud dextrose agar tubes. The results were negative. Two weeks after the first visit, other tissue samples were examined in a potassium hydroxide preparation. Abundant, granular clumps of hyaline hyphae were observed.
Journal of the American Academy of Dermatology Volume 32, Number 5, Part 2
Lee et al.
899
Fig. 3. Histopathologic examination shows aggregates of numerous septate hyphae on ne-
crotic area (Periodic acid-Schiff positive stain; x200).
Results of cultures at this time were positive, and the same fungus was recovered from three different lesions by culture on Sabouraud dextrose agar tubes but not on Sabouraud dextrose agar with cycloheximide. The colonies, which grew rapidly, were downy and grayish-white, with a moist area. The backs of the colonies were flat, with no folds. A nondiffusible purple pigment was noticeable. Growth rate was slower at 37” C than at room temperature. Morphologic characteristics of the colony were identical at both temperatures. The microscopic findings by slide culture revealed narrow, septate hyphae and erect, simple conidiophores. The crescent-shaped conidia were formed in clusters around thin, tapering ends of the conidiophores. The conidia were either one or two celled. Scanning electron microscopy revealed that conidia were produced from inner wall of hyphae (enteroblastic). The surface tip of the conidiophore, after separation of the conidium, showed a cuplike appearance (phialide) . Itraconazole was given orally at a dose of 200 mg/day, and lesions progressively healed. Thirty days after therapy, the smaller, satellite lesions showed almost complete healing and the large, primary lesion revealed a significant reduction in oozing and swelling. All lesions cleared after 70 days of treatment. DISCUSSION
Since Gill first reported mycetoma in 1842, it has been reported in tropical countries such as Sudan and Mexico.’ This is the first reported case in Korea of mycetoma caused by A. falcijbrme.
The first case of eumycetoma caused by A. j&ifirme was reported in Puerto Rico by Carrion5 in 195 I as eumycetoma caused by Cephalosporium falciforme. In 197 1, Gams6 reclassified these organisms, choosing Acremonium as the name for the new genus. He recognized three species: A. falciforme (C. falciforme), Acremonium kiliense (Cephalosporium granulomatis), and Acremonium recifei (Cephalosporium recifei). A. falciforme accounts for most infections in human beings. Although Acremonium species can be found throughout the world, eumycetoma caused by Acremonium species is reported infrequently. Either these fungi have a low virulence or they rarely contaminate wounds.7 Because of the long incubation period, patients often do not recall any injury at the site of mycetoma development. This suggests that the fungus may be implanted superficially. Many factors are necessary for a mycetoma to develop. The patient’s overall health, immune system, personal hygiene, and nutritional status need to be considered in evaluation.8 The treatment of mycetoma consists of medical therapy, surgical therapy, or both.9 Most eumycetomas eventually necessitate amputation. Linda et a1.8 tried a regimen of amphotericin B and ketoconazole in a patient with a eumycetoma caused by A. falciforme. The patient’s condition did not respond. Mahgoub et al.‘O reported improvement in a patient
900
Lee et al.
infectedwith M. mycetomatis after treatmentwith 400 mg/day oral ketoconazole.Josephet al.11also reportedclinical improvementin a caseof eumycetoma causedby A. falciforme that wastreatedwith oral ketoconazoleat a doseof 400 mg/day. In the casedescribedhere, the lesionsclearedin 70 days after treatment with oral itraconazoleat 200 mg/ day. REFERENCES
1. Rippon JW. Medical mycology. 3rd ed. Philadelphia:WB Saunders, 1988;80-117. 2. Arnold HL, Odom RB, Fames WD. Andrews’ diseasesof the skin. 8th ed. Philadelphia: WB Saunders, 1990:371-3. 3. Wiedman FD, Kligman AM. A new speciesof Cephalosporium in Madura foot. J Bacterial 1945;50:491-5. 4. Taralakshmi VV, PankajalakshmiVV, ParamasivanCN, et al. Mycetoma in Madras. Sabouraudia 1977;15:17-22.
Journal of the American Academy of Dermatology May 1995
5. Carrion AL. Cephalosporium falciforme sp. nov., a new etiologic agent of maduromycosis. Mycologia 1951;43: 522-3. 6. Gams W. Cephalosporium-artige
Schimmelpilze (Hyphomycetes).Stuttgart: Gustav Fischer Verlag, 1971. 7. Halde C, Padhye AA, Haley LD, et al. Acremonium falczjbrme as a causeof mycetoma in California. Sabouraudia 1976;14:319-26. 8. Linda VE, Lance RP, Dale NG. Acremonium falciforme (Cephalosporium falciforme) mycetoma in a renal transplant patient. Arch Dermatol 1983;119:707-8. 9. John PU, Shadomy HJ. Deep fungal infections. In: Fitzpatrick TB, EisenAZ, Wolff K, et al, cds.Dermatology in general medicine.3rd ed. New York: McGraw-Hill Book, 1987:2252-4. 10. Mahgoub ES, Gumaa SA. Ketoconazolein the treatment of eumycetomadue to Madurella mycetomii. Trans R Sot Trop Med Hyg 1984;78:376-9. 11. JosephGM, Peter BM, Martin HT, et al. Mycetoma associated with Acremonium falciforme infection. Med J Aust 1987;147:187-8.