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Australasian Journal of Dermatology (2015) 56, e71–e73
doi: 10.1111/ajd.12153
BRIEF REPORT
Cutaneous protothecosis in a patient with previously undiagnosed HIV infection Kenneth Fong,1 Shang-Ian Tee,2 Madeline S L Ho2 and Jiun Yit Pan2 1
St John’s Institute of Dermatology, King’s College London, (Guy’s Campus), London, UK; and 2National Skin Centre, Singapore
described to date. Here, we report a case of cutaneous protothecosis in a patient, which uncovered an underlying HIV infection.
ABSTRACT Protothecosis is an uncommon condition resulting from infection by achlorophyllous algae of the Prototheca species. Immunocompromised individuals are generally most susceptible to protothecal infection and tend to develop severe and disseminated disease. However, the association between protothecosis and HIV-induced immunosuppression is not clear, with only a handful of cases having been described to date. Here we report a case of cutaneous protothecosis in a Chinese man with previously undiagnosed HIV infection that responded well to oral itraconazole. Key words: prototheca, immunosuppression.
protothecosis,
HIV,
INTRODUCTION Protothecosis is an uncommon condition resulting from infection by achlorophyllous algae of the Prototheca species. To date, approximately 160 cases have been reported worldwide.1 P. wickerhamii and P. zopfii are responsible for infection in humans, which can result in any of three distinct clinical presentations: cutaneous lesions, olecranon bursitis or disseminated infection.2 Immunocompromised individuals are generally the most susceptible, particularly to disseminated disease.3 However, despite HIV being a major cause of immunodeficiency, relatively few cases of HIV patients with protothecosis have been
Correspondence: Dr Jiun Yit Pan, National Skin Centre, 1 Mandalay Road, Singapore 308205. Email: [email protected] Kenneth Fong, BSc. Shang-Ian Tee, MRCP. Madeline S. L. Ho, MRCP. Jiun Yit Pan, FRCP. Conflicts of interest: none. Submitted 26 October 2013; accepted 16 January 2014. © 2014 The Australasian College of Dermatologists
CASE REPORT A 58-year old Chinese man was being treated at a tertiary dermatological centre in Singapore for a chronic psoriasiform rash with prurigo nodularis affecting mainly his arms and legs. These were fairly well controlled with topical steroids. During a routine visit he complained of an asymptomatic but gradually enlarging lesion on his left cheek of 6 weeks duration. The patient worked on a construction site and recalled cutting himself while shaving 3 weeks prior to onset of the rash. His travel history was significant for multiple trips overseas in the previous 5 years for paid sex. A physical examination revealed a non-tender, mildly scaly, erythematous plaque over his left cheek measuring 3 × 2 cm (Fig. 1). A 4-mm punch biopsy was performed. A histopathological examination revealed neutrophilic microabscesses in the papillary dermis in association with a granulomatous infiltrate of histiocytes, plasma cells and Langhans-type multinucleated giant cells. The latter were seen to engulf lightly bluish sporangia measuring 5–10 μm in diameter, which contained spores arranged circumferentially to resemble morula (Fig. 2). These stained intensely with periodic acid–Schiff and Gomori methenamine silver stains, but not with Fontana–Masson or mucicarmine stains. The overall features were consistent with cutaneous protothecosis. A subsequent tissue fungal culture (slide culture on nutrient agar plate) confirmed the growth of prototheca. Because of the uncommon nature of protothecal infection, he was evaluated for HIV infection. Laboratory investigations revealed positive HIV serology, which was confirmed on Western blot. He had a viral load of 24 734 copies and a CD4+ lymphocyte count of 38 cells/μL. The patient was treated with oral itraconazole 200 mg daily and commenced on anti-retroviral therapy comprising tenofovir, lamivudine and lopinavir/ ritonavir. A clinical review at 2 weeks revealed significant improvement (Fig. 1b).
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Figure 1 Clinical appearance of cutaneous protothecosis. (a) Irregular erythematous plaque with mild overlying scale. (b) Follow up at 2-weeks post-treatment showing significant improvement.
Figure 2 Histopathology of the lesion. (a) The upper dermis contains aggregates of neutrophils, histiocytes, lymphocytes and Langhans-type giant cells, some engulfing light bluish organisms (haematoxylin and eosin, original magnification 200×). (b) These organisms also lie freely in the dermal papillae (haematoxylin and eosin, original magnification 400×). (c) Periodic acid–Schiff stain highlights the presence of a thick cell wall (original magnification 400×). (d) Gomori methenamine silver stain at high power shows sporangia, each containing numerous spores and resembling early embryos (i.e. morula). Some spores also possess internal septations (original magnification 1000×).
DISCUSSION Prototheca are ubiquitous in nature and can be isolated from the skin, nails, respiratory and digestive tracts of healthy individuals.4 However, infection in humans may occur following traumatic inoculation after exposure to protothecal reservoirs such as contaminated water and vegetation. Although prototheca are typically indolent, immunocompromising factors, including diabetes mellitus, malignancy and potent corticosteroid use have been shown to increase its virulence in humans.1 Cutaneous protothecosis is the most common presentation, accounting for nearly 60% of all cases.1 Lesions typically appear as solitary ill-defined erythematous plaques, although nodular, pustular, verrucous and ulcerated variants have also been described. In our patient, possible routes of inoculation include the shaving cut he sustained as well as occupational exposure to prototheca at the construction site he worked at. Differential diagnoses for the facial plaque included eczema, deep fungal infection, granuloma faciale and sarcoidosis. However, the histology of the lesion demonstrated the © 2014 The Australasian College of Dermatologists
presence of infective organisms consistent with protothecosis, and the diagnosis was further supported with positive isolates on tissue culture. Although facilities for sub-speciation were not available, the diameter of the spores was suggestive of a P. wickerhamii (3–10 μm) rather than a P. zopfii (7–30 μm) infection.2 Topical steroid use (for dermatitis) was an additional predisposing factor for protothecal infection in our patient. The finding of cutaneous protothecosis led us to consider an immunocompromised state, investigations into which subsequently revealed an underlying HIV infection. Compromised host immunity is generally considered to be a predisposing factor for protothecal infection, with a recent review demonstrating the existence of host immunosuppression (from either underlying disease or steroid use) in up to two-thirds of reported cases to date.1 However, the relevance of HIV infection specifically to the pathogenesis of cutaneous protothecosis, is unclear. The incidence of cutaneous protothecosis in HIV patients is relatively low, with only a small number of cases having been described to date.5–7 This is supported by a study involving 5034 HIV-positive blood cultures, which reported a positive
Cutaneous protothecosis in a HIV patient protothecal culture rate of only 0.07%.8 Additionally, the degree of HIV-mediated CD4+ cytopaenia does not appear to correlate directly with the severity of protothecal infection. In contrast to a previous report of disseminated protothecosis, our patient developed only localised cutaneous infection despite a similar CD4+ lymphocyte count of 38 cells/μL.9 The reasons accounting for this paradoxically low pathogenicity among HIV patients remains to be elucidated. There is currently no defined treatment regimen for protothecal infection. Amphotericin B has shown to have the most efficacy, particularly in cases of disseminated infection.1 However, its systemic toxicity and the lack of oral preparations limit its routine usage. Azole antifungal agents are also used, although their effectiveness is variable and cases of treatment failure have been reported. Our patient responded well to treatment with oral itraconazole, even prior to the initiation of anti-retroviral therapy, demonstrating a significant improvement at 2-weeks follow up. Itraconazole appears to be a reasonable first-line approach for mild localised protothecal infections, with amphotericin B reserved as second-line treatment for disseminated infection or infection refractory to other antifungal agents. Surgical excision is also a curative option for localised lesions. In conclusion, we report a case of cutaneous protothecosis which revealed an underlying HIV infection in a patient. This highlights the need to consider potential causes of host immunocompromise in all cases of protothecal infections.
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ACKNOWLEDGEMENTS We are grateful to Dr Lee Cheng Chuan, Department of Infectious Diseases, Communicable Disease Centre, for co-managing this patient with us.
REFERENCES 1.
2. 3. 4. 5.
6.
7. 8.
9.
Todd JR, King JW, Oberle A et al. Protothecosis: report of a case with 20-year follow-up, and review of previously published cases. Med. Mycol. 2012; 50: 673–89. Lass-Florl C, Mayr A. Human protothecosis. Clin. Microbiol. Rev. 2007; 20: 230–42. Leimann BC, Monteiro PC, Lazera M et al. Protothecosis. Med. Mycol. 2004; 42: 95–106. Huerre M, Ravisse P, Solomon H et al. [Human protothecosis and environment]. Bull. Soc. Pathol. Exot. 1993; 86: 484–8. Piyophirapong S, Linpiyawan R, Mahaisavariya P et al. Cutaneous protothecosis in an AIDS patient. Br. J. Dermatol. 2002; 146: 713–5. Carey WP, Kaykova Y, Bandres JC et al. Cutaneous protothecosis in a patient with AIDS and a severe functional neutrophil defect: successful therapy with amphotericin B. Clin. Infect. Dis. 1997; 25: 1265–6. Woolrich A, Koestenblatt E, Don P et al. Cutaneous protothecosis and AIDS. J. Am. Acad. Dermatol. 1994; 31: 920–4. Bianchi M, Robles AM, Vitale R et al. The usefulness of blood culture in diagnosing HIV-related systemic mycoses: evaluation of a manual lysis centrifugation method. Med. Mycol. 2000; 38: 77–80. Kaminski ZC, Kapila R, Sharer LR et al. Meningitis due to Prototheca wickerhamii in a patient with AIDS. Clin. Infect. Dis. 1992; 15: 704–6.
© 2014 The Australasian College of Dermatologists
Australasian Journal of Dermatology (2015) 56, e71–e73
doi: 10.1111/ajd.12153
BRIEF REPORT
Cutaneous protothecosis in a patient with previously undiagnosed HIV infection Kenneth Fong,1 Shang-Ian Tee,2 Madeline S L Ho2 and Jiun Yit Pan2 1
St John’s Institute of Dermatology, King’s College London, (Guy’s Campus), London, UK; and 2National Skin Centre, Singapore
described to date. Here, we report a case of cutaneous protothecosis in a patient, which uncovered an underlying HIV infection.
ABSTRACT Protothecosis is an uncommon condition resulting from infection by achlorophyllous algae of the Prototheca species. Immunocompromised individuals are generally most susceptible to protothecal infection and tend to develop severe and disseminated disease. However, the association between protothecosis and HIV-induced immunosuppression is not clear, with only a handful of cases having been described to date. Here we report a case of cutaneous protothecosis in a Chinese man with previously undiagnosed HIV infection that responded well to oral itraconazole. Key words: prototheca, immunosuppression.
protothecosis,
HIV,
INTRODUCTION Protothecosis is an uncommon condition resulting from infection by achlorophyllous algae of the Prototheca species. To date, approximately 160 cases have been reported worldwide.1 P. wickerhamii and P. zopfii are responsible for infection in humans, which can result in any of three distinct clinical presentations: cutaneous lesions, olecranon bursitis or disseminated infection.2 Immunocompromised individuals are generally the most susceptible, particularly to disseminated disease.3 However, despite HIV being a major cause of immunodeficiency, relatively few cases of HIV patients with protothecosis have been
Correspondence: Dr Jiun Yit Pan, National Skin Centre, 1 Mandalay Road, Singapore 308205. Email: [email protected] Kenneth Fong, BSc. Shang-Ian Tee, MRCP. Madeline S. L. Ho, MRCP. Jiun Yit Pan, FRCP. Conflicts of interest: none. Submitted 26 October 2013; accepted 16 January 2014. © 2014 The Australasian College of Dermatologists
CASE REPORT A 58-year old Chinese man was being treated at a tertiary dermatological centre in Singapore for a chronic psoriasiform rash with prurigo nodularis affecting mainly his arms and legs. These were fairly well controlled with topical steroids. During a routine visit he complained of an asymptomatic but gradually enlarging lesion on his left cheek of 6 weeks duration. The patient worked on a construction site and recalled cutting himself while shaving 3 weeks prior to onset of the rash. His travel history was significant for multiple trips overseas in the previous 5 years for paid sex. A physical examination revealed a non-tender, mildly scaly, erythematous plaque over his left cheek measuring 3 × 2 cm (Fig. 1). A 4-mm punch biopsy was performed. A histopathological examination revealed neutrophilic microabscesses in the papillary dermis in association with a granulomatous infiltrate of histiocytes, plasma cells and Langhans-type multinucleated giant cells. The latter were seen to engulf lightly bluish sporangia measuring 5–10 μm in diameter, which contained spores arranged circumferentially to resemble morula (Fig. 2). These stained intensely with periodic acid–Schiff and Gomori methenamine silver stains, but not with Fontana–Masson or mucicarmine stains. The overall features were consistent with cutaneous protothecosis. A subsequent tissue fungal culture (slide culture on nutrient agar plate) confirmed the growth of prototheca. Because of the uncommon nature of protothecal infection, he was evaluated for HIV infection. Laboratory investigations revealed positive HIV serology, which was confirmed on Western blot. He had a viral load of 24 734 copies and a CD4+ lymphocyte count of 38 cells/μL. The patient was treated with oral itraconazole 200 mg daily and commenced on anti-retroviral therapy comprising tenofovir, lamivudine and lopinavir/ ritonavir. A clinical review at 2 weeks revealed significant improvement (Fig. 1b).
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K Fong et al.
Figure 1 Clinical appearance of cutaneous protothecosis. (a) Irregular erythematous plaque with mild overlying scale. (b) Follow up at 2-weeks post-treatment showing significant improvement.
Figure 2 Histopathology of the lesion. (a) The upper dermis contains aggregates of neutrophils, histiocytes, lymphocytes and Langhans-type giant cells, some engulfing light bluish organisms (haematoxylin and eosin, original magnification 200×). (b) These organisms also lie freely in the dermal papillae (haematoxylin and eosin, original magnification 400×). (c) Periodic acid–Schiff stain highlights the presence of a thick cell wall (original magnification 400×). (d) Gomori methenamine silver stain at high power shows sporangia, each containing numerous spores and resembling early embryos (i.e. morula). Some spores also possess internal septations (original magnification 1000×).
DISCUSSION Prototheca are ubiquitous in nature and can be isolated from the skin, nails, respiratory and digestive tracts of healthy individuals.4 However, infection in humans may occur following traumatic inoculation after exposure to protothecal reservoirs such as contaminated water and vegetation. Although prototheca are typically indolent, immunocompromising factors, including diabetes mellitus, malignancy and potent corticosteroid use have been shown to increase its virulence in humans.1 Cutaneous protothecosis is the most common presentation, accounting for nearly 60% of all cases.1 Lesions typically appear as solitary ill-defined erythematous plaques, although nodular, pustular, verrucous and ulcerated variants have also been described. In our patient, possible routes of inoculation include the shaving cut he sustained as well as occupational exposure to prototheca at the construction site he worked at. Differential diagnoses for the facial plaque included eczema, deep fungal infection, granuloma faciale and sarcoidosis. However, the histology of the lesion demonstrated the © 2014 The Australasian College of Dermatologists
presence of infective organisms consistent with protothecosis, and the diagnosis was further supported with positive isolates on tissue culture. Although facilities for sub-speciation were not available, the diameter of the spores was suggestive of a P. wickerhamii (3–10 μm) rather than a P. zopfii (7–30 μm) infection.2 Topical steroid use (for dermatitis) was an additional predisposing factor for protothecal infection in our patient. The finding of cutaneous protothecosis led us to consider an immunocompromised state, investigations into which subsequently revealed an underlying HIV infection. Compromised host immunity is generally considered to be a predisposing factor for protothecal infection, with a recent review demonstrating the existence of host immunosuppression (from either underlying disease or steroid use) in up to two-thirds of reported cases to date.1 However, the relevance of HIV infection specifically to the pathogenesis of cutaneous protothecosis, is unclear. The incidence of cutaneous protothecosis in HIV patients is relatively low, with only a small number of cases having been described to date.5–7 This is supported by a study involving 5034 HIV-positive blood cultures, which reported a positive
Cutaneous protothecosis in a HIV patient protothecal culture rate of only 0.07%.8 Additionally, the degree of HIV-mediated CD4+ cytopaenia does not appear to correlate directly with the severity of protothecal infection. In contrast to a previous report of disseminated protothecosis, our patient developed only localised cutaneous infection despite a similar CD4+ lymphocyte count of 38 cells/μL.9 The reasons accounting for this paradoxically low pathogenicity among HIV patients remains to be elucidated. There is currently no defined treatment regimen for protothecal infection. Amphotericin B has shown to have the most efficacy, particularly in cases of disseminated infection.1 However, its systemic toxicity and the lack of oral preparations limit its routine usage. Azole antifungal agents are also used, although their effectiveness is variable and cases of treatment failure have been reported. Our patient responded well to treatment with oral itraconazole, even prior to the initiation of anti-retroviral therapy, demonstrating a significant improvement at 2-weeks follow up. Itraconazole appears to be a reasonable first-line approach for mild localised protothecal infections, with amphotericin B reserved as second-line treatment for disseminated infection or infection refractory to other antifungal agents. Surgical excision is also a curative option for localised lesions. In conclusion, we report a case of cutaneous protothecosis which revealed an underlying HIV infection in a patient. This highlights the need to consider potential causes of host immunocompromise in all cases of protothecal infections.
e73
ACKNOWLEDGEMENTS We are grateful to Dr Lee Cheng Chuan, Department of Infectious Diseases, Communicable Disease Centre, for co-managing this patient with us.
REFERENCES 1.
2. 3. 4. 5.
6.
7. 8.
9.
Todd JR, King JW, Oberle A et al. Protothecosis: report of a case with 20-year follow-up, and review of previously published cases. Med. Mycol. 2012; 50: 673–89. Lass-Florl C, Mayr A. Human protothecosis. Clin. Microbiol. Rev. 2007; 20: 230–42. Leimann BC, Monteiro PC, Lazera M et al. Protothecosis. Med. Mycol. 2004; 42: 95–106. Huerre M, Ravisse P, Solomon H et al. [Human protothecosis and environment]. Bull. Soc. Pathol. Exot. 1993; 86: 484–8. Piyophirapong S, Linpiyawan R, Mahaisavariya P et al. Cutaneous protothecosis in an AIDS patient. Br. J. Dermatol. 2002; 146: 713–5. Carey WP, Kaykova Y, Bandres JC et al. Cutaneous protothecosis in a patient with AIDS and a severe functional neutrophil defect: successful therapy with amphotericin B. Clin. Infect. Dis. 1997; 25: 1265–6. Woolrich A, Koestenblatt E, Don P et al. Cutaneous protothecosis and AIDS. J. Am. Acad. Dermatol. 1994; 31: 920–4. Bianchi M, Robles AM, Vitale R et al. The usefulness of blood culture in diagnosing HIV-related systemic mycoses: evaluation of a manual lysis centrifugation method. Med. Mycol. 2000; 38: 77–80. Kaminski ZC, Kapila R, Sharer LR et al. Meningitis due to Prototheca wickerhamii in a patient with AIDS. Clin. Infect. Dis. 1992; 15: 704–6.
© 2014 The Australasian College of Dermatologists
