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Primary cutaneous Aspergillus ustus infection: Second reported case
Primary cutaneous Aspergillus ustus infection: Second reported case Major Rita M. Ricci, USAF, MC, FS,a Major James S. Evans, USAF, MC,a Lt Col Jeffrey J. Meffert, USAF, MC, FS,a Leo Kaufman, PhD,b and Lee C. Sadkowski, MTc Lackland AFB and San Antonio, Texas, and Atlanta, Georgia We describe the second case of primary cutaneous Aspergillus ustus infection in an immunocompromised patient. Cutaneous aspergillosis was confirmed both by culture and positive fluorescent antibody staining. Few species of Aspergillus are pathogenic in human beings, and fewer still cause primary cutaneous disease. The only other reported case of aspergillosis from Aspergillus ustus occurred in an immunosuppressed patient who was temporally and geographically separated from ours. (J Am Acad Dermatol 1998;38:797-8.)
CASE REPORT A 64-year-old white woman had a 2-month history of an eruption on her left arm. She had severe chronic obstructive pulmonary disease and had been taking prednisone 30 mg twice daily for 2 years. The patient reported the eruption on her arm began as an erosion from a plastic identification bracelet. She did not have an intravenous line in her left arm and hospital renovation was not being conducted. The patient was evaluated at another institution 2 weeks before and had been treated with oral itraconazole, 200 mg twice daily for presumed aspergillosis, based on skin biopsy findings. The eruption continued to progress despite treatment. On her left arm, she had a tender 20 × 10 cm erythematous plaque studded with pustules and erosions (Fig. 1). A biopsy specimen revealed a granulomatous dermal reaction with a dense neutrophilic infiltrate. Grocott-Gomori methenamine-silver nitrate stain revealed septate hyphae branching at acute angles (Fig. 2). Aspergillus ustus was identified on culture. Two days after admission, the patient died of cardiac arrest. Postmortem examination failed to reveal disseminated aspergillosis.
This article is made possible through an educational grant from Ortho Dermatological. From the Wilford Hall USAF Medical Center,a Division of Bacterial and Mycotic Diseases, Centers for Disease Control and Prevention,b and the Veterans Administration Mycology Reference Laboratory.c The views expressed are those of the authors and are not to be construed as official or as reflecting those of the US Air Force, Department of Defense, or the federal government. 16/4/85745
Fig. 1. Erythematous plaque on left arm with pustules and erosions. DISCUSSION
Aspergillus spp. are among the most ubiquitous fungi. They are common in soil, water, decaying vegetation, and any substrate that contains organic debris. The respiratory tract is believed to be the most significant primary portal of entry for Aspergillus spp.1 Cutaneous aspergillosis is uncommon and may result from hematogenous dissemination, by extension to skin from a contiguous anatomic site, or from trauma. After Candida albicans, Aspergillus spp. are the second most common cause of human opportunistic fungal infections.2 A. fumigatus is the most common cause of disseminated aspergillosis, whereas A. flavus is most commonly associated with primary cutaneous aspergillosis.3 Primary cutaneous aspergillosis often occurs in immunocompromised hosts. Most cases have 797
798 Ricci et al.
Fig. 2. Skin biopsy specimen showing septate hyphae branching at acute angles. (Grocott-Gomori methenamine-silver stain; original magnification ×240.)
been reported in patients with hematologic or lymphoreticular malignancies or in organ transplant patients receiving cytotoxic or chemotherapeutic agents, systemic glucocorticoids or broad spectrum antibiotics,2 or in AIDS patients.4 Contributing factors include trauma from arm boards, burns, peripheral and central venous catheters, use of contaminated dressing materials, and aerosolization of fungi during building renovations.2 Primary cutaneous aspergillosis may present with violaceous macules, papules, plaques, or nodules. Hemorrhagic bullae can occur, as can ulcerations with central necrosis or eschar formation. Pustular lesions rarely have been observed.2,3,5,6 Stiller et al.2 described the first case of primary cutaneous A. ustus infection. Their patient was a 62-year-old liver transplant recipient with endstage hepatitis C-induced cirrhosis receiving the immunosuppressive drug FK-506. Trauma to the patient's arm from tape and an arm board, and to the leg from an occlusive brace may have contributed. Their patient responded to a combination of intravenous amphotericin B and topical terbinafine cream. He died shortly thereafter from hepatic failure, but without evidence of systemic aspergillosis.2 A. ustus is one of the less pathogenic species of Aspergillus. It has caused endocarditis and disseminated infection in patients who are undergoing mitral valve replacement or coronary artery bypass surgery, and rarely onychomycosis.2 Risk
Journal of the American Academy of Dermatology May 1998
factors in our patient include long-term prednisone therapy, chronic illness, and possibly trauma to the skin. Histopathologically, the hyphae of Aspergillus are 3 to 4 µm in diameter, septate, and branch at acute angles.3 Granulomatous lesions may form when the disease is subacute or chronic. The hyphae in chronic lesions usually do not show the regular branching pattern seen in acute invasive aspergillosis.1 Consequently, the diagnosis of aspergillosis frequently rests on the identification of an Aspergillus sp. in culture. Use of the structure of the organism in tissue as the sole criterion for diagnosis is not valid except when characteristic anamorphic fruiting heads are present in air sacs.1 Fusarium moniliforme has been reported to look identical to Aspergillus in tissue.7 The drug of choice for invasive aspergillosis is amphotericin B, although nephrotoxicity may be limiting. Our patient was significantly immunosuppressed from drug therapy and chronic illness, as was the only other reported patient with primary cutaneous A. ustus infection. Because the two patients were both temporally and geographically separated, it is more likely that they occurred as opportunistic infections from immunosuppression rather than from the emergence of a more pathogenic strain. REFERENCES 1. Rinaldi MG. Invasive Aspergillosis. Rev Inf Dis 1983;5:1061-77. 2. Stiller MJ, Teperman L, Rosenthal SA, Riordan A, Potter J, Shupack JL, et al. Primary cutaneous infection by Aspergillus ustus in a 62-year-old liver transplant recipient. J Am Acad Dermatol 1994;31:344-7. 3. Radentz WH. Opportunistic fungal infections in immunocompromised hosts. J Am Acad Dermatol 1989;20:989-1003. 4. Hunt SJ, Nagi C, Gross KG, Wong DS, Matthews WC. Primary cutaneous aspergillosis near central venous catheters in patients with the acquired immunodeficiency syndrome. Arch Dermatol 1992;128:1229-32. 5. McCarty JM, Flam MS, Pullen G, Jones R, Kasel SH. Outbreak of primary cutaneous aspergillosis related to intravenous arm boards. J Pediatr 1986;108:721-4. 6. Watsky KL, Eisen RM, Bolognia JL. Unilateral cutaneous emboli of Aspergillus. Arch Dermatol 1990;126:1214-7. 7. Young NA, Kwon-Chung KJ, Kubota TT, Jennings AE, Fisher RI. Disseminated infection by Fusarium moniliforme during treatment for malignant lymphoma. J Clin Microbiol 1978;7:589-94.
CASE REPORT A 64-year-old white woman had a 2-month history of an eruption on her left arm. She had severe chronic obstructive pulmonary disease and had been taking prednisone 30 mg twice daily for 2 years. The patient reported the eruption on her arm began as an erosion from a plastic identification bracelet. She did not have an intravenous line in her left arm and hospital renovation was not being conducted. The patient was evaluated at another institution 2 weeks before and had been treated with oral itraconazole, 200 mg twice daily for presumed aspergillosis, based on skin biopsy findings. The eruption continued to progress despite treatment. On her left arm, she had a tender 20 × 10 cm erythematous plaque studded with pustules and erosions (Fig. 1). A biopsy specimen revealed a granulomatous dermal reaction with a dense neutrophilic infiltrate. Grocott-Gomori methenamine-silver nitrate stain revealed septate hyphae branching at acute angles (Fig. 2). Aspergillus ustus was identified on culture. Two days after admission, the patient died of cardiac arrest. Postmortem examination failed to reveal disseminated aspergillosis.
This article is made possible through an educational grant from Ortho Dermatological. From the Wilford Hall USAF Medical Center,a Division of Bacterial and Mycotic Diseases, Centers for Disease Control and Prevention,b and the Veterans Administration Mycology Reference Laboratory.c The views expressed are those of the authors and are not to be construed as official or as reflecting those of the US Air Force, Department of Defense, or the federal government. 16/4/85745
Fig. 1. Erythematous plaque on left arm with pustules and erosions. DISCUSSION
Aspergillus spp. are among the most ubiquitous fungi. They are common in soil, water, decaying vegetation, and any substrate that contains organic debris. The respiratory tract is believed to be the most significant primary portal of entry for Aspergillus spp.1 Cutaneous aspergillosis is uncommon and may result from hematogenous dissemination, by extension to skin from a contiguous anatomic site, or from trauma. After Candida albicans, Aspergillus spp. are the second most common cause of human opportunistic fungal infections.2 A. fumigatus is the most common cause of disseminated aspergillosis, whereas A. flavus is most commonly associated with primary cutaneous aspergillosis.3 Primary cutaneous aspergillosis often occurs in immunocompromised hosts. Most cases have 797
798 Ricci et al.
Fig. 2. Skin biopsy specimen showing septate hyphae branching at acute angles. (Grocott-Gomori methenamine-silver stain; original magnification ×240.)
been reported in patients with hematologic or lymphoreticular malignancies or in organ transplant patients receiving cytotoxic or chemotherapeutic agents, systemic glucocorticoids or broad spectrum antibiotics,2 or in AIDS patients.4 Contributing factors include trauma from arm boards, burns, peripheral and central venous catheters, use of contaminated dressing materials, and aerosolization of fungi during building renovations.2 Primary cutaneous aspergillosis may present with violaceous macules, papules, plaques, or nodules. Hemorrhagic bullae can occur, as can ulcerations with central necrosis or eschar formation. Pustular lesions rarely have been observed.2,3,5,6 Stiller et al.2 described the first case of primary cutaneous A. ustus infection. Their patient was a 62-year-old liver transplant recipient with endstage hepatitis C-induced cirrhosis receiving the immunosuppressive drug FK-506. Trauma to the patient's arm from tape and an arm board, and to the leg from an occlusive brace may have contributed. Their patient responded to a combination of intravenous amphotericin B and topical terbinafine cream. He died shortly thereafter from hepatic failure, but without evidence of systemic aspergillosis.2 A. ustus is one of the less pathogenic species of Aspergillus. It has caused endocarditis and disseminated infection in patients who are undergoing mitral valve replacement or coronary artery bypass surgery, and rarely onychomycosis.2 Risk
Journal of the American Academy of Dermatology May 1998
factors in our patient include long-term prednisone therapy, chronic illness, and possibly trauma to the skin. Histopathologically, the hyphae of Aspergillus are 3 to 4 µm in diameter, septate, and branch at acute angles.3 Granulomatous lesions may form when the disease is subacute or chronic. The hyphae in chronic lesions usually do not show the regular branching pattern seen in acute invasive aspergillosis.1 Consequently, the diagnosis of aspergillosis frequently rests on the identification of an Aspergillus sp. in culture. Use of the structure of the organism in tissue as the sole criterion for diagnosis is not valid except when characteristic anamorphic fruiting heads are present in air sacs.1 Fusarium moniliforme has been reported to look identical to Aspergillus in tissue.7 The drug of choice for invasive aspergillosis is amphotericin B, although nephrotoxicity may be limiting. Our patient was significantly immunosuppressed from drug therapy and chronic illness, as was the only other reported patient with primary cutaneous A. ustus infection. Because the two patients were both temporally and geographically separated, it is more likely that they occurred as opportunistic infections from immunosuppression rather than from the emergence of a more pathogenic strain. REFERENCES 1. Rinaldi MG. Invasive Aspergillosis. Rev Inf Dis 1983;5:1061-77. 2. Stiller MJ, Teperman L, Rosenthal SA, Riordan A, Potter J, Shupack JL, et al. Primary cutaneous infection by Aspergillus ustus in a 62-year-old liver transplant recipient. J Am Acad Dermatol 1994;31:344-7. 3. Radentz WH. Opportunistic fungal infections in immunocompromised hosts. J Am Acad Dermatol 1989;20:989-1003. 4. Hunt SJ, Nagi C, Gross KG, Wong DS, Matthews WC. Primary cutaneous aspergillosis near central venous catheters in patients with the acquired immunodeficiency syndrome. Arch Dermatol 1992;128:1229-32. 5. McCarty JM, Flam MS, Pullen G, Jones R, Kasel SH. Outbreak of primary cutaneous aspergillosis related to intravenous arm boards. J Pediatr 1986;108:721-4. 6. Watsky KL, Eisen RM, Bolognia JL. Unilateral cutaneous emboli of Aspergillus. Arch Dermatol 1990;126:1214-7. 7. Young NA, Kwon-Chung KJ, Kubota TT, Jennings AE, Fisher RI. Disseminated infection by Fusarium moniliforme during treatment for malignant lymphoma. J Clin Microbiol 1978;7:589-94.