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Granulomatous skin infection caused by Scopulariopsis brevicaulis
Granulomatous skin infection caused by Scopulariopsis brevicaulis Ineke Bruynzeel, MD, PhD,a and Theo M. Starink, MD, PhDb Amsterdam, The Netherlands A 14-year-old girl with a granulomatous infection of the cheek caused by Scopulariopsis brevicaulis is described. Treatment successively consisted of itraconazole and/or terbinafine for 19 months, after which clinical and mycologic cure seemed to be obtained. However, a relapse occurred 10 months later. (J Am Acad Dermatol 1998;39:365-7.)
Scopulariopsis is a genus of nondermatophytic filamentous fungi. These common saprophytic fungi are found in soil, on vegetable and other organic wastes, and have a wide geographic distribution. Scopulariopsis brevicaulis is not generally considered to be a skin pathogen, although it is the cause of 1.6% to 2.3% of onychomycoses.1-3 Since 1987, several case reports described S brevicaulis infections of deep tissue or skin in immunocompromised hosts4-6 and sporadic cases of ocular infection have been recorded.7 Recently, S brevicaulis skin infections were also found in otherwise healthy persons.8-10 We describe a patient with a slowly progressive granulomatous skin infection of 9-years duration caused by S brevicaulis. CASE REPORT A 14-year-old girl had a slightly itchy plaque on her left cheek. When she was 5 years old, a small red papule had appeared that had gradually extended. At the age of 7, examination revealed an annular 3 cm plaque (Fig. 1). A biopsy specimen was interpreted as granuloma annulare. A cortico-steroid cream was prescribed and used for some weeks, but the patient was not seen again for 7 years. Examination showed an annular, erythematous, slightly scaling 7-cm plaque, with nodules at the proximal border (Fig. 2). She was otherwise in good health and did not take any medication. There were no pets at home. A KOH preparation of skin scrapings This article is made possible through an educational grant from Ortho Dermatological. From the Departments of Dermatology, Groene Hart Hospital, Gouda,a and Free University Hospital, Amsterdam,b The Netherlands Reprint requests: Prof. Dr Th. M. Starink, Department of Dermatology, Free University Hospital, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. Copyright © 1998 by the American Academy of Dermatology, Inc. 0190-9622/98/$5.00 + 0 16/4/90287
showed no hyphae. A biopsy specimen showed a nodular granulomatous dermatitis with foreign-body giant cells and a mild folliculitis, with conidia and hyphae in the giant cells (Fig. 3) and in some of the hair follicles. Reexamination of the initial specimen showed the same features with fragments of hyphae within giant cells. Skin scrapings and tissue culture on Sabouraud medium yielded S brevicaulis. Treatment was started with itraconazole, 100 mg daily, but after 4 and 8 weeks, cultures of skin scrapings again grew S brevicaulis. Therapy was changed to terbinafine, 250 mg daily, which was increased to 500 mg when, after 4 weeks of treatment, skin scrapings were still positive for S brevicaulis. The next 5 months she received a combination of terbinafine (250 mg daily) and itraconazole (100 mg daily), during which the lesion improved clinically, but cultures of scrapings taken every 4 to 6 weeks remained positive for S brevicaulis. Therapy was changed to terbinafine, 500 mg daily, in combination with topical terbinafine twice daily for the next 6 months. After 1, 3, and 5 months of treatment, the cultures were negative and treatment was stopped. The patient remained clear for the next 10 months, after which a red and scaling plaque reappeared. Cultures again grew S brevicaulis. Treatment with terbinafine, 500 mg daily, itraconazole, 100 mg daily, and terbinafine cream twice daily for a proposed period of 1 year was begun. DISCUSSION
In 1936, Markley et al.11 reported one of the first and best documented cases of a skin infection caused by S brevicaulis in a healthy woman. Since then, sporadic cases of eye (keratitis, endophthalmitis, corneal ulcer) or ear (otitis, mastoiditis) infections with S brevicaulis and several cases of systemic infections in immunocompromised patients (AIDS, during chemotherapy for leukemia and aplastic anemia) have been described. In recent years, 3 reports of S brevicaulis infections 365
366 Bruynzeel and Starink
Fig. 1. Cutaneous S brevicaulis infection of cheek, patient at age of 5.
Fig. 2. Same patient at age of 14, before antimycotic treatment.
in otherwise healthy persons have been published: a 14-year-old girl with cutaneous “ringworm” on her legs,8 a 43-year-old man with ulcerous granulomatous cheilitis and submaxillary lymph node invasion,9 and a 42-year old woman with a plantar erythematosquamous plaque and onychomycosis caused by S brevicaulis.10 Treatment of S brevicaulis infections has proven to be difficult. In vitro studies of the susceptibility of S brevicaulis show that the minimum inhibitory concentration for terbinafine is 0.5 to 2.0 µg/mL and for itraconazole >64 µg/mL.12 Of equal importance is the concentration of the drug in the stratum corneum after oral intake. Terbinafine (250 mg for 12 days) and itraconazole (200 mg for 7 days) produce a level of 9.1 µg/mL and 0.79 µg/mL, respectively.13 However, it is questioned whether the in vitro and in vivo results for azoles always coincide.14,15 The patient with cheilitis9 was treated with itraconazole, 200 mg/day, and this resulted in complete healing after 2 months. The patient with
Journal of the American Academy of Dermatology August 1998
Fig. 3. Biopsy specimen showing granulomatous dermatitis with foreign body giant cells, some of which contain hyphae (arrow). (Hematoxylin-eosin; original magnification, ×20.)
the “ringworm” lesions8 was successfully treated with terbinafine, 250 mg/day, for about 3 months. However, treatment with both itraconazole (400 mg/day for 1 week every month during 9 months) and terbinafine (250 mg/day for 6 months) did not cure the patient with the plantar infection.10 The treatment of onychomycosis caused by S brevicaulis has also been proven difficult. In one study, only 1 of 6 patients with S brevicaulis infection of the toenails was cured after treatment with itraconazole (400 mg daily 1 week/mo for 4 months). The others did not have a mycologic cure but had marked clinical improvement with itraconazole pulse therapy or with terbinafine, 250 mg daily for 4 months.16 However, in another study, 8 of 10 patients with pedal onychomycosis caused by S brevicaulis were clinically and mycologically cured with itraconazole (200 mg twice daily 1 week/mo for 2 to 4 months).17 S brevicaulis is usually thought of as a nonpathogenic fungus when cultured from human skin, although it has been increasingly recognized as a serious pathogen.18 REFERENCES 1. Meinhof W, Schropl F. Die Haufigkeit von hautpathogenen Pilzen bei Patienten einer uberregionalen Diagnoseklinik. Hautarzt 1974;25:139-42. 2. Summerbell RC, Kane J, Krajden S. Onychomycosis, tinea pedis and tinea manuum caused by non-dermatophytic filamentous fungi. Mycoses 1989;32:609-19. 3. Greer DL. Evolving role of nondermatophytes in onychomycosis. Int J Dermatol 1995;34:521-4. 4. Neglia JP, Hurd DD, Ferrieri P, Snover DC. Invasive Scopulariopsis in the immunocompromised host. Am J Med 1987;83:1163-6. 5. Phillips P, Wood WS, Phillips G, Rinaldi MG. Invasive
Journal of the American Academy of Dermatology Volume 39, Number 2, Part 2
6. 7.
8. 9.
10. 11.
12.
Hyalohyphomycosis caused by Scopulariopsis brevicaulis in a patient undergoing allogeneic bone marrow transplant. Diagn Microbiol Infect Dis 1989;12:429-32. Dhar I, Carey PB. Scopulariopsis brevicaulis skin lesions in an AIDS patient. AIDS 1993;7:1283-4. Ragge NK, Hart JCD, Eastly DL, Tyers AG. A case of fungal keratitis caused by Scopulariopsis brevicaulis: treatment with antifungal agents and penetrating keratoplasty. Br J Ophtalmol 1990;74:561-2. Cox NH, Irving B. Cutaneous ‘ringworm’ lesions of Scopulariopsis brevicaulis. Br J Dermatol 1993;129: 726-8. Creus L, Umbert P, Torres-Rodriguez JM, Lopez-Gil F. Ulcerous granulomatous cheilitis with lymphatic invasion caused by Scopulariopsis brevicaulis infection. J Am Acad Dermatol 1994;31:881-3. Ginarte M, Pereiro M, Fernandez-Redondo V, Toribio J. Plantar infection by Scopulariopsis brevicaulis. Dermatology 1996;193:149-51. Markley AJ, Philpott OS, Weidman FD. Deep scopulariopsosis of ulcerating granuloma type confirmed by culture and animal inoculation. Arch Dermatol Syph 1936;33:627-41. Clayton YM. Relevance of broad-spectrum and fungicidal activity of antifungals in the treatment of dermatomycoses. Br J Dermatol 1994;130(suppl 43):7-8.
Bruynzeel and Starink 367 13. Faergemann J, Zehender H, Jones T, Maibach I. Terbinafine levels in serum, stratum corneum, dermisepidermis (without stratum corneum), hair, sebum and eccrine sweat. Acta Derm Venereol 1990;71:322-6. 14. Kobayashi GS, Spitzer ED. Testing of organisms for susceptibility to triazoles: Is it justified? Eur J Clin Microbiol Infect Dis 1989;8:387-9. 15. Gupta AK, Saunder DN, Shear NH. Antifungal agents: an overview. Part II. J Am Acad Dermatol 1994;30:91133. 16. Tosti A, Piraccini BM, Stinchi C, Lorenzi S. Onychomycosis due to Scopulariopsis brevicaulis: clinical features and response to systemic antifungals. Br J Dermatol 1996;135:799-802. 17. De Doncker PRG, Scher RK, Baran RL, Baran RL, Decroix J, Degreef HJ, et al. Itraconazole therapy is effective for pedal onychomycosis caused by some nondermatophyte molds and in mixed infection with dermatophytes and molds: a multicenter study with 36 patients. J Am Acad Dermatol 1997;36:173-7. 18. Anaissie EJ, Bodey GP, Rinaldi MG. Emerging fungal pathogens. Eur J Clin Microbiol Infect Dis 1989;8:32330.
Scopulariopsis is a genus of nondermatophytic filamentous fungi. These common saprophytic fungi are found in soil, on vegetable and other organic wastes, and have a wide geographic distribution. Scopulariopsis brevicaulis is not generally considered to be a skin pathogen, although it is the cause of 1.6% to 2.3% of onychomycoses.1-3 Since 1987, several case reports described S brevicaulis infections of deep tissue or skin in immunocompromised hosts4-6 and sporadic cases of ocular infection have been recorded.7 Recently, S brevicaulis skin infections were also found in otherwise healthy persons.8-10 We describe a patient with a slowly progressive granulomatous skin infection of 9-years duration caused by S brevicaulis. CASE REPORT A 14-year-old girl had a slightly itchy plaque on her left cheek. When she was 5 years old, a small red papule had appeared that had gradually extended. At the age of 7, examination revealed an annular 3 cm plaque (Fig. 1). A biopsy specimen was interpreted as granuloma annulare. A cortico-steroid cream was prescribed and used for some weeks, but the patient was not seen again for 7 years. Examination showed an annular, erythematous, slightly scaling 7-cm plaque, with nodules at the proximal border (Fig. 2). She was otherwise in good health and did not take any medication. There were no pets at home. A KOH preparation of skin scrapings This article is made possible through an educational grant from Ortho Dermatological. From the Departments of Dermatology, Groene Hart Hospital, Gouda,a and Free University Hospital, Amsterdam,b The Netherlands Reprint requests: Prof. Dr Th. M. Starink, Department of Dermatology, Free University Hospital, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands. Copyright © 1998 by the American Academy of Dermatology, Inc. 0190-9622/98/$5.00 + 0 16/4/90287
showed no hyphae. A biopsy specimen showed a nodular granulomatous dermatitis with foreign-body giant cells and a mild folliculitis, with conidia and hyphae in the giant cells (Fig. 3) and in some of the hair follicles. Reexamination of the initial specimen showed the same features with fragments of hyphae within giant cells. Skin scrapings and tissue culture on Sabouraud medium yielded S brevicaulis. Treatment was started with itraconazole, 100 mg daily, but after 4 and 8 weeks, cultures of skin scrapings again grew S brevicaulis. Therapy was changed to terbinafine, 250 mg daily, which was increased to 500 mg when, after 4 weeks of treatment, skin scrapings were still positive for S brevicaulis. The next 5 months she received a combination of terbinafine (250 mg daily) and itraconazole (100 mg daily), during which the lesion improved clinically, but cultures of scrapings taken every 4 to 6 weeks remained positive for S brevicaulis. Therapy was changed to terbinafine, 500 mg daily, in combination with topical terbinafine twice daily for the next 6 months. After 1, 3, and 5 months of treatment, the cultures were negative and treatment was stopped. The patient remained clear for the next 10 months, after which a red and scaling plaque reappeared. Cultures again grew S brevicaulis. Treatment with terbinafine, 500 mg daily, itraconazole, 100 mg daily, and terbinafine cream twice daily for a proposed period of 1 year was begun. DISCUSSION
In 1936, Markley et al.11 reported one of the first and best documented cases of a skin infection caused by S brevicaulis in a healthy woman. Since then, sporadic cases of eye (keratitis, endophthalmitis, corneal ulcer) or ear (otitis, mastoiditis) infections with S brevicaulis and several cases of systemic infections in immunocompromised patients (AIDS, during chemotherapy for leukemia and aplastic anemia) have been described. In recent years, 3 reports of S brevicaulis infections 365
366 Bruynzeel and Starink
Fig. 1. Cutaneous S brevicaulis infection of cheek, patient at age of 5.
Fig. 2. Same patient at age of 14, before antimycotic treatment.
in otherwise healthy persons have been published: a 14-year-old girl with cutaneous “ringworm” on her legs,8 a 43-year-old man with ulcerous granulomatous cheilitis and submaxillary lymph node invasion,9 and a 42-year old woman with a plantar erythematosquamous plaque and onychomycosis caused by S brevicaulis.10 Treatment of S brevicaulis infections has proven to be difficult. In vitro studies of the susceptibility of S brevicaulis show that the minimum inhibitory concentration for terbinafine is 0.5 to 2.0 µg/mL and for itraconazole >64 µg/mL.12 Of equal importance is the concentration of the drug in the stratum corneum after oral intake. Terbinafine (250 mg for 12 days) and itraconazole (200 mg for 7 days) produce a level of 9.1 µg/mL and 0.79 µg/mL, respectively.13 However, it is questioned whether the in vitro and in vivo results for azoles always coincide.14,15 The patient with cheilitis9 was treated with itraconazole, 200 mg/day, and this resulted in complete healing after 2 months. The patient with
Journal of the American Academy of Dermatology August 1998
Fig. 3. Biopsy specimen showing granulomatous dermatitis with foreign body giant cells, some of which contain hyphae (arrow). (Hematoxylin-eosin; original magnification, ×20.)
the “ringworm” lesions8 was successfully treated with terbinafine, 250 mg/day, for about 3 months. However, treatment with both itraconazole (400 mg/day for 1 week every month during 9 months) and terbinafine (250 mg/day for 6 months) did not cure the patient with the plantar infection.10 The treatment of onychomycosis caused by S brevicaulis has also been proven difficult. In one study, only 1 of 6 patients with S brevicaulis infection of the toenails was cured after treatment with itraconazole (400 mg daily 1 week/mo for 4 months). The others did not have a mycologic cure but had marked clinical improvement with itraconazole pulse therapy or with terbinafine, 250 mg daily for 4 months.16 However, in another study, 8 of 10 patients with pedal onychomycosis caused by S brevicaulis were clinically and mycologically cured with itraconazole (200 mg twice daily 1 week/mo for 2 to 4 months).17 S brevicaulis is usually thought of as a nonpathogenic fungus when cultured from human skin, although it has been increasingly recognized as a serious pathogen.18 REFERENCES 1. Meinhof W, Schropl F. Die Haufigkeit von hautpathogenen Pilzen bei Patienten einer uberregionalen Diagnoseklinik. Hautarzt 1974;25:139-42. 2. Summerbell RC, Kane J, Krajden S. Onychomycosis, tinea pedis and tinea manuum caused by non-dermatophytic filamentous fungi. Mycoses 1989;32:609-19. 3. Greer DL. Evolving role of nondermatophytes in onychomycosis. Int J Dermatol 1995;34:521-4. 4. Neglia JP, Hurd DD, Ferrieri P, Snover DC. Invasive Scopulariopsis in the immunocompromised host. Am J Med 1987;83:1163-6. 5. Phillips P, Wood WS, Phillips G, Rinaldi MG. Invasive
Journal of the American Academy of Dermatology Volume 39, Number 2, Part 2
6. 7.
8. 9.
10. 11.
12.
Hyalohyphomycosis caused by Scopulariopsis brevicaulis in a patient undergoing allogeneic bone marrow transplant. Diagn Microbiol Infect Dis 1989;12:429-32. Dhar I, Carey PB. Scopulariopsis brevicaulis skin lesions in an AIDS patient. AIDS 1993;7:1283-4. Ragge NK, Hart JCD, Eastly DL, Tyers AG. A case of fungal keratitis caused by Scopulariopsis brevicaulis: treatment with antifungal agents and penetrating keratoplasty. Br J Ophtalmol 1990;74:561-2. Cox NH, Irving B. Cutaneous ‘ringworm’ lesions of Scopulariopsis brevicaulis. Br J Dermatol 1993;129: 726-8. Creus L, Umbert P, Torres-Rodriguez JM, Lopez-Gil F. Ulcerous granulomatous cheilitis with lymphatic invasion caused by Scopulariopsis brevicaulis infection. J Am Acad Dermatol 1994;31:881-3. Ginarte M, Pereiro M, Fernandez-Redondo V, Toribio J. Plantar infection by Scopulariopsis brevicaulis. Dermatology 1996;193:149-51. Markley AJ, Philpott OS, Weidman FD. Deep scopulariopsosis of ulcerating granuloma type confirmed by culture and animal inoculation. Arch Dermatol Syph 1936;33:627-41. Clayton YM. Relevance of broad-spectrum and fungicidal activity of antifungals in the treatment of dermatomycoses. Br J Dermatol 1994;130(suppl 43):7-8.
Bruynzeel and Starink 367 13. Faergemann J, Zehender H, Jones T, Maibach I. Terbinafine levels in serum, stratum corneum, dermisepidermis (without stratum corneum), hair, sebum and eccrine sweat. Acta Derm Venereol 1990;71:322-6. 14. Kobayashi GS, Spitzer ED. Testing of organisms for susceptibility to triazoles: Is it justified? Eur J Clin Microbiol Infect Dis 1989;8:387-9. 15. Gupta AK, Saunder DN, Shear NH. Antifungal agents: an overview. Part II. J Am Acad Dermatol 1994;30:91133. 16. Tosti A, Piraccini BM, Stinchi C, Lorenzi S. Onychomycosis due to Scopulariopsis brevicaulis: clinical features and response to systemic antifungals. Br J Dermatol 1996;135:799-802. 17. De Doncker PRG, Scher RK, Baran RL, Baran RL, Decroix J, Degreef HJ, et al. Itraconazole therapy is effective for pedal onychomycosis caused by some nondermatophyte molds and in mixed infection with dermatophytes and molds: a multicenter study with 36 patients. J Am Acad Dermatol 1997;36:173-7. 18. Anaissie EJ, Bodey GP, Rinaldi MG. Emerging fungal pathogens. Eur J Clin Microbiol Infect Dis 1989;8:32330.