© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
J Cutan Pathol 2014: 41: 409–413 doi: 10.1111/cup.12338 John Wiley & Sons. Printed in Singapore
Journal of Cutaneous Pathology
Cover Quizlet Cesar J. Figueroa, Brendan J. Camp, George I. Varghese, Edwin Miranda, Christiane Querfeld, Hani Hassoun, Mini Kamboj and Melissa P. Pulitzer Figure 1 and 2 are depicted on the journal cover.
Figure 3.
Figure 4.
Figure 5.
Figure 6.
Your diagnosis? Discussion follows on page 410
409
Cover Quizlet
A Case of Protothecosis in a Patient with Multiple Myeloma Cesar J. Figueroa1 , Brendan J. Camp2 , George I. Varghese3 , Edwin Miranda4 , Christiane Querfeld5 , Hani Hassoun6 , Mini Kamboj7 and Melissa P. Pulitzer8 1
Department of Medicine, Infectious Diseases, Memorial Sloan Kettering Cancer Center, New York, 2 Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, 3 Department of Dermatology, Weill Cornell Medical Center, New York, 4 Department of Microbiology, Memorial Sloan Kettering Cancer Center, New York, 5 Department of Medicine, Dermatology Service, Memorial Sloan Kettering Cancer Center, New York, 6 Department of Medicine, Multiple Myeloma Service Memorial Sloan Kettering Cancer Center, New York, 7 Department of Medicine, Infectious Diseases, Memorial Sloan Kettering Cancer Center, New York, and 8 Department of Pathology, Memorial Sloan Kettering Cancer Center, New York email: [email protected]
Keywords: Carfilzomib, Multiple Myeloma, Neutropenia, Protothecosis, Voriconazole Accepted for publication February 8, 2014 CJ Figueroa and BJ Camp contributed equally to the writing of this manuscript.
Protothecosis is an uncommon infection that has recently gained attention due to its potential to cause serious clinical effects in immunocompromised hosts. Herein, we describe a case of protothecosis that occurred during an episode of prolonged neutropenia in an elderly woman undergoing chemotherapy with carfilzomib for refractory multiple myeloma. The patient was treated with amphotericin B followed by a prolonged course of voriconazole, which resulted in a complete resolution of the skin lesions. Early diagnosis and administration of adequate antifungals are necessary to adequately treat immunocompromised patients suffering from this potentially fatal infection. Protothecosis is caused by the achlorophyllic algae Prototheca. Species wickerhamii is the most commonly implicated in human disease.1 The first case of human infection was described in 1964 as a localized skin ulcer on the foot of a rice farmer in Sierra Leone.2 Since then, it has been recognized as an unusual pathogen in immunocompromised hosts. The pathogenesis of protothecosis is largely unknown, although cutaneous inoculation is considered to be the most common route of infection. In the case of immunocompromised hosts, neutrophil abnormalities, opsonin defects, and prolonged corticosteroid use may play a more significant role as risk factors for this type of infection.3
410
A 78-year-old female with a history of relapsed multiple myeloma was evaluated for a nodular skin eruption that presented during hospitalization for fever and neutropenia subsequent to chemotherapy with carfilzomib. Multiple myeloma had been diagnosed eleven years earlier and her initial treatment regimen included dexamethasone followed by autologous hematopoietic stem-cell transplant [HSCT]. The disease relapsed a year after transplantation, and subsequently various chemotherapy regimens were used for treatment including cyclophosphamide, lenalidomide and bortezomib, and adjunct intermittent systemic corticosteroids were also administered. The patient had recently completed three cycles of treatment with carfilzomib [56 mg/m2, subsequently reduced to 45mg/m2, on clinical trial], and dexamethasone [8mg single dose]; the last dose was administered 17 days before admission. The patient was admitted for neutropenic fever and had a prolonged hospital course for a polymicrobial bacteremia (Klebsiella pneumoniae and Vancomycin-resistant Enterococcus faecium) in the setting of treatment-related neutropenia. The bacteremia cleared with broad spectrum antibiotics, but the patient remained neutropenic and intermittently febrile. Thirty days into her hospitalization, she was noted to have numerous non-tender, non-pruritic, erythematous, papular and
Cover Quizlet
Fig. 1. A pauci-cellular dermal infiltrate of histiocytes and lymphocytes is mixed with numerous small and large basophilic spherical bodies (hematoxylin & eosin staining).
nodular skin lesions. The lesions preferentially involved the medial aspect of both thighs, and upper extremities in a peri-articular distribution around the elbows and wrists (Figures 3, 4 and 6). She also had scattered lesions over the face and trunk. The patient was clinically non-toxic appearing and hemodynamically stable. The most remarkable laboratory finding was profound and sustained neutropenia. A computed tomography of the chest, abdomen and pelvis showed no evidence of visceral involvement. A biopsy of one of the skin nodules was performed. Histopathologic findings in hematoxylin and eosin-stained sections demonstrated a paucicellular dermal and subcutaneous infiltrate of histiocytes and lymphocytes amidst numerous interstitially localized small and large basophilic spherical bodies, some with septation, and many within foreign body macrophages (Figure 1). Internal septations of spherical bodies and the wreath-like arrangement of the organisms were highlighted by Gomori methenamine silver (GMS) and periodic acid-Schiff (PAS) stains (Figures 2 and 5). A pathologic diagnosis favoring Protothecosis was rendered. Bacterial and fungal tissue cultures from the skin, bone marrow and peripheral blood were negative. The patient was started on liposomal amphotericin B three days after the lesions first appeared. Signs of marrow recovery were noted five days after the initiation of treatment. During this time, the fever defervesced and skin lesions showed progressive inflammatory changes, eventually ulcerated, and drained a tan malodorous fluid. This fluid was inoculated on blood and Sabouraud agar medium and was incubated at 30◦ C for 24 hours, after which multiple white-colored, smooth colonies were noted.
Fig. 2. Periodic acid-Schiff positive morulae exhibit internal septations (PAS staining)
A direct wet-mount examination of the colonies showed many non-motile, spherical organisms, 10 μm in diameter, with typical endospores. The microorganism was identified as Prototheca wickerhamii based on sugar assimilation tests. The patient received liposomal amphotericin B for twelve days, during which the skin lesions showed signs of resolution and blood counts recovered. She was then treated with oral voriconazole (200 mg twice daily), and after five months of treatment all lesions healed completely. Protothecosis represents a rarely reported opportunistic infection.4,5 In a recent review, the majority of patients described were immunocompromised, mostly secondary to the use of systemic steroids.6 The incubation period is not known but is thought to be long, ranging from weeks to months.5 The organism is known for its pervasiveness and worldwide distribution, as well as its ubiquitous presence in sewage, slime flux and animal waste.7 It can also colonize human skin, fingernails, and the respiratory and digestive tracts.3 Protothecosis typically occurs in one of three forms: 1) cutaneous or subcutaneous infection, 2) bursitis (typically involving the olecranon bursa), and 3) systemic infection. Skin disease may present as vesiculobullous and ulcerative lesions, sometimes associated with purulent discharge and crusting, but can also manifest as papules and nodules; as well as eczematous, herpetiform, granulomatous, and verrucous lesions.4,8 Exposed areas, especially the extremities, are predominantly affected. In a literature review of 13 protothecosis cases that developed during the treatment of cancer, half of the patients suffered from hematologic malignancies. Six patients received corticosteroids or chemotherapy within four weeks of disease onset, but neutropenia was uncommon. Isolation
411
Cover Quizlet of Prototheca mainly occurred from skin and blood, and most patients received amphotericin B as initial therapy for a median length of 24 days (range, 6-60 days).9 The nature of immune-defects that predispose to Protothecosis is not clearly defined. However, the relatively small number of cases described in patients with acquired immunodeficiency syndrome (AIDS) suggests that neutrophilic dysfunction and impaired humoral immunity play a more important role in development compared to defects in cell-mediated immunity.10 Cases of protothecosis have also been described in patients with functional neutrophil defects,11,12 following the administration of infliximab for treatment of graft-versus-host disease in hematopoietic stemcell transplant recipients,13 and in patients with abnormal immunoglobulin levels.4,14 We believe that therapy-related prolonged neutropenia and hypogammaglobulinemia were the predisposing risk factors in this patient. The diagnosis of protothecosis is often provided histopathologically because the disease is infrequently suspected on clinical grounds. Microscopic reaction patterns vary and can include granulomatous inflammation, lymphoid hyperplasia, or a mixed infiltrate with variable numbers of neutrophils, eosinophils, plasma cells and/or giant cells. Necrosis and/or pseudocarcinomatous hyperplasia may be prominent. Prototheca is best visualized with periodic acid-Schiff (PAS) and Gomori methenamine-silver (GMS) stains, which highlight structures with typical soccer-ball-like or berry-like appearance. Wet-mount preparations usually reveal organisms that appear as spherical morulae with multiple endospores that appear polyhedral or wedge-shaped in a radial arrangement.3,15,16 Culture of the organism in routine media is required for definitive diagnosis,4 and noticeable growth occurs best between 25◦ C to 37◦ C.16 Infections caused by fungi such as Blastomyces, Coccidioides, Cryptococcus, Paracoccidioides, and Rhinosporidium,15 – 17 can have a similar presentation and should be considered in the differential diagnosis.
Although, complete surgical excision may be considered for localized superficial infections in nonimmunocompromised patients, intravenous amphotericin B has been the most commonly used drug for treatment of Prototheca infection.16 The optimal dose and duration of therapy is unclear, as no clinical trials exist.3 Other medications used to treat Protothecosis include ketoconazole, itraconazole, fluconazole, and tetracyclines; however, these have been mostly used for localized infections.3 Despite previous reports that describe the successful use of voriconazole as salvage therapy in immunocompetent hosts,18,19 experience with the use of voriconazole and posaconazole in treating immunosuppressed patients is limited. Voriconazole seems an effective option for the treatment of infections caused by Prototheca, mainly due to its activity in vitro against species wickerhamii.20 In summary, we report a case of disseminated protothecosis highlighting the clinical presentation of this rare opportunistic infection with predilection for skin involvement. Our patient suffered from multiple myeloma and was immunosuppressed due to chronic neutropenia, hypogammaglobulinemia and multiple chemotherapy regimens; and we posit that all of these factors played a role in the development of this infection. Additionally, we report cure of the disease with voriconazole, underlining the potential role of this agent for the treatment of infections caused by Prototheca. Fig. 3. Erythematous nodular skin lesions involved the left antecubital fold. Fig. 4. Papular, non-pruritic, erythematous lesions were present on the thigh. Fig. 5. Soccer ball-like structures and wreath-like arrangement of the organisms (GMS staining). Fig. 6. Fluctuant nodular skin lesions were present in a periarticular distribution around the right wrist.
References 1. Wirth FA, Passalacqua JA, Kao G. Disseminated cutaneous protothecosis in an immunocompromised host: a case report and literature review. Cutis; cutaneous medicine for the practitioner 1999; 63: 185. 2. Davies RR, Spencer H, Wakelin PO. A Case of Human Protothecosis. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1964; 58: 448. 3. Lass-Florl C, Mayr A. Human protothecosis. Clin Microbiol Rev 2007; 20: 230.
412
4. Boyd AS, Langley M, King LE Jr. Cutaneous manifestations of Prototheca infections. J Am Acad Dermatol 1995; 32(5 Pt 1): 758. 5. Woolrich A, Koestenblatt E, Don P, Szaniawski W. Cutaneous protothecosis and AIDS. J Am Acad Dermatol 1994; 31(5 Pt 2): 920. 6. Todd JR, King JW, Oberle A, et al. Protothecosis: report of a case with 20-year follow-up, and review of previously published cases. Medical mycology : official publication
of the International Society for Human and Animal Mycology 2012; 50: 673. 7. Huerre M, Ravisse P, Solomon H, et al. Human protothecosis and environment. Bull Soc Pathol Exot 1993; 86(5 Pt 2): 484. 8. Zhang QQ, Li L, Zhu LP, et al. Cutaneous Protothecosis in Patient with Diabetes Mellitus and Review of Published Case Reports. Mycopathologia. 2011. 9. Torres HA, Bodey GP, Tarrand JJ, Kontoyiannis DP. Protothecosis in patients with
Cover Quizlet cancer: case series and literature review. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 2003; 9: 786. 10. Carey WP, Kaykova Y, Bandres JC, Sidhu GS, Brau N. Cutaneous protothecosis in a patient with AIDS and a severe functional neutrophil defect: successful therapy with amphotericin B. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 1997; 25: 1265. 11. Phair JP, Williams JE, Bassaris HP, Zeiss CR, Morlock BA. Phagocytosis and algicidal activity of human polymorphonuclear neutrophils against Prototheca wickerhamii. The Journal of infectious diseases 1981; 144: 72.
12. Venezio FR, Lavoo E, Williams JE, et al. Progressive cutaneous protothecosis. American journal of clinical pathology 1982; 77: 485. 13. Khoury JA, Dubberke ER, Devine SM. Fatal case of protothecosis in a hematopoietic stem cell transplant recipient after infliximab treatment for graft-versus-host disease. Blood 2004; 104: 3414. 14. Cox GE, Wilson JD, Brown P. Protothecosis: a case of disseminated algal infection. Lancet 1974; 2: 379. 15. Hillesheim PB, Bahrami S. Cutaneous protothecosis. Archives of pathology & laboratory medicine 2011; 135: 941. 16. Kantrow SM, Boyd AS. Protothecosis. Dermatol Clin 2003; 21: 249. 17. Hightower KD, Messina JL. Cutaneous protothecosis: a case report and review of the
literature. Cutis; cutaneous medicine for the practitioner 2007; 80: 129. 18. Dalmau J, Pimentel CL, Alegre M, et al. Treatment of protothecosis with voriconazole. Journal of the American Academy of Dermatology 2006; 55(5 Suppl): S122. 19. Sheikh-Ahmad M, Goldstein S, Potasman I. Prototheca wickerhamii hand infection successfully treated by itraconazole and voriconazole. Journal of travel medicine 2006; 13: 321. 20. Linares MJ, Solis F, Casal M. In vitro activity of voriconazole against Prototheca wickerhamii: comparative evaluation of sensititre and NCCLS M27-A2 methods of detection. Journal of clinical microbiology 2005; 43: 2520.
413
J Cutan Pathol 2014: 41: 409–413 doi: 10.1111/cup.12338 John Wiley & Sons. Printed in Singapore
Journal of Cutaneous Pathology
Cover Quizlet Cesar J. Figueroa, Brendan J. Camp, George I. Varghese, Edwin Miranda, Christiane Querfeld, Hani Hassoun, Mini Kamboj and Melissa P. Pulitzer Figure 1 and 2 are depicted on the journal cover.
Figure 3.
Figure 4.
Figure 5.
Figure 6.
Your diagnosis? Discussion follows on page 410
409
Cover Quizlet
A Case of Protothecosis in a Patient with Multiple Myeloma Cesar J. Figueroa1 , Brendan J. Camp2 , George I. Varghese3 , Edwin Miranda4 , Christiane Querfeld5 , Hani Hassoun6 , Mini Kamboj7 and Melissa P. Pulitzer8 1
Department of Medicine, Infectious Diseases, Memorial Sloan Kettering Cancer Center, New York, 2 Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, 3 Department of Dermatology, Weill Cornell Medical Center, New York, 4 Department of Microbiology, Memorial Sloan Kettering Cancer Center, New York, 5 Department of Medicine, Dermatology Service, Memorial Sloan Kettering Cancer Center, New York, 6 Department of Medicine, Multiple Myeloma Service Memorial Sloan Kettering Cancer Center, New York, 7 Department of Medicine, Infectious Diseases, Memorial Sloan Kettering Cancer Center, New York, and 8 Department of Pathology, Memorial Sloan Kettering Cancer Center, New York email: [email protected]
Keywords: Carfilzomib, Multiple Myeloma, Neutropenia, Protothecosis, Voriconazole Accepted for publication February 8, 2014 CJ Figueroa and BJ Camp contributed equally to the writing of this manuscript.
Protothecosis is an uncommon infection that has recently gained attention due to its potential to cause serious clinical effects in immunocompromised hosts. Herein, we describe a case of protothecosis that occurred during an episode of prolonged neutropenia in an elderly woman undergoing chemotherapy with carfilzomib for refractory multiple myeloma. The patient was treated with amphotericin B followed by a prolonged course of voriconazole, which resulted in a complete resolution of the skin lesions. Early diagnosis and administration of adequate antifungals are necessary to adequately treat immunocompromised patients suffering from this potentially fatal infection. Protothecosis is caused by the achlorophyllic algae Prototheca. Species wickerhamii is the most commonly implicated in human disease.1 The first case of human infection was described in 1964 as a localized skin ulcer on the foot of a rice farmer in Sierra Leone.2 Since then, it has been recognized as an unusual pathogen in immunocompromised hosts. The pathogenesis of protothecosis is largely unknown, although cutaneous inoculation is considered to be the most common route of infection. In the case of immunocompromised hosts, neutrophil abnormalities, opsonin defects, and prolonged corticosteroid use may play a more significant role as risk factors for this type of infection.3
410
A 78-year-old female with a history of relapsed multiple myeloma was evaluated for a nodular skin eruption that presented during hospitalization for fever and neutropenia subsequent to chemotherapy with carfilzomib. Multiple myeloma had been diagnosed eleven years earlier and her initial treatment regimen included dexamethasone followed by autologous hematopoietic stem-cell transplant [HSCT]. The disease relapsed a year after transplantation, and subsequently various chemotherapy regimens were used for treatment including cyclophosphamide, lenalidomide and bortezomib, and adjunct intermittent systemic corticosteroids were also administered. The patient had recently completed three cycles of treatment with carfilzomib [56 mg/m2, subsequently reduced to 45mg/m2, on clinical trial], and dexamethasone [8mg single dose]; the last dose was administered 17 days before admission. The patient was admitted for neutropenic fever and had a prolonged hospital course for a polymicrobial bacteremia (Klebsiella pneumoniae and Vancomycin-resistant Enterococcus faecium) in the setting of treatment-related neutropenia. The bacteremia cleared with broad spectrum antibiotics, but the patient remained neutropenic and intermittently febrile. Thirty days into her hospitalization, she was noted to have numerous non-tender, non-pruritic, erythematous, papular and
Cover Quizlet
Fig. 1. A pauci-cellular dermal infiltrate of histiocytes and lymphocytes is mixed with numerous small and large basophilic spherical bodies (hematoxylin & eosin staining).
nodular skin lesions. The lesions preferentially involved the medial aspect of both thighs, and upper extremities in a peri-articular distribution around the elbows and wrists (Figures 3, 4 and 6). She also had scattered lesions over the face and trunk. The patient was clinically non-toxic appearing and hemodynamically stable. The most remarkable laboratory finding was profound and sustained neutropenia. A computed tomography of the chest, abdomen and pelvis showed no evidence of visceral involvement. A biopsy of one of the skin nodules was performed. Histopathologic findings in hematoxylin and eosin-stained sections demonstrated a paucicellular dermal and subcutaneous infiltrate of histiocytes and lymphocytes amidst numerous interstitially localized small and large basophilic spherical bodies, some with septation, and many within foreign body macrophages (Figure 1). Internal septations of spherical bodies and the wreath-like arrangement of the organisms were highlighted by Gomori methenamine silver (GMS) and periodic acid-Schiff (PAS) stains (Figures 2 and 5). A pathologic diagnosis favoring Protothecosis was rendered. Bacterial and fungal tissue cultures from the skin, bone marrow and peripheral blood were negative. The patient was started on liposomal amphotericin B three days after the lesions first appeared. Signs of marrow recovery were noted five days after the initiation of treatment. During this time, the fever defervesced and skin lesions showed progressive inflammatory changes, eventually ulcerated, and drained a tan malodorous fluid. This fluid was inoculated on blood and Sabouraud agar medium and was incubated at 30◦ C for 24 hours, after which multiple white-colored, smooth colonies were noted.
Fig. 2. Periodic acid-Schiff positive morulae exhibit internal septations (PAS staining)
A direct wet-mount examination of the colonies showed many non-motile, spherical organisms, 10 μm in diameter, with typical endospores. The microorganism was identified as Prototheca wickerhamii based on sugar assimilation tests. The patient received liposomal amphotericin B for twelve days, during which the skin lesions showed signs of resolution and blood counts recovered. She was then treated with oral voriconazole (200 mg twice daily), and after five months of treatment all lesions healed completely. Protothecosis represents a rarely reported opportunistic infection.4,5 In a recent review, the majority of patients described were immunocompromised, mostly secondary to the use of systemic steroids.6 The incubation period is not known but is thought to be long, ranging from weeks to months.5 The organism is known for its pervasiveness and worldwide distribution, as well as its ubiquitous presence in sewage, slime flux and animal waste.7 It can also colonize human skin, fingernails, and the respiratory and digestive tracts.3 Protothecosis typically occurs in one of three forms: 1) cutaneous or subcutaneous infection, 2) bursitis (typically involving the olecranon bursa), and 3) systemic infection. Skin disease may present as vesiculobullous and ulcerative lesions, sometimes associated with purulent discharge and crusting, but can also manifest as papules and nodules; as well as eczematous, herpetiform, granulomatous, and verrucous lesions.4,8 Exposed areas, especially the extremities, are predominantly affected. In a literature review of 13 protothecosis cases that developed during the treatment of cancer, half of the patients suffered from hematologic malignancies. Six patients received corticosteroids or chemotherapy within four weeks of disease onset, but neutropenia was uncommon. Isolation
411
Cover Quizlet of Prototheca mainly occurred from skin and blood, and most patients received amphotericin B as initial therapy for a median length of 24 days (range, 6-60 days).9 The nature of immune-defects that predispose to Protothecosis is not clearly defined. However, the relatively small number of cases described in patients with acquired immunodeficiency syndrome (AIDS) suggests that neutrophilic dysfunction and impaired humoral immunity play a more important role in development compared to defects in cell-mediated immunity.10 Cases of protothecosis have also been described in patients with functional neutrophil defects,11,12 following the administration of infliximab for treatment of graft-versus-host disease in hematopoietic stemcell transplant recipients,13 and in patients with abnormal immunoglobulin levels.4,14 We believe that therapy-related prolonged neutropenia and hypogammaglobulinemia were the predisposing risk factors in this patient. The diagnosis of protothecosis is often provided histopathologically because the disease is infrequently suspected on clinical grounds. Microscopic reaction patterns vary and can include granulomatous inflammation, lymphoid hyperplasia, or a mixed infiltrate with variable numbers of neutrophils, eosinophils, plasma cells and/or giant cells. Necrosis and/or pseudocarcinomatous hyperplasia may be prominent. Prototheca is best visualized with periodic acid-Schiff (PAS) and Gomori methenamine-silver (GMS) stains, which highlight structures with typical soccer-ball-like or berry-like appearance. Wet-mount preparations usually reveal organisms that appear as spherical morulae with multiple endospores that appear polyhedral or wedge-shaped in a radial arrangement.3,15,16 Culture of the organism in routine media is required for definitive diagnosis,4 and noticeable growth occurs best between 25◦ C to 37◦ C.16 Infections caused by fungi such as Blastomyces, Coccidioides, Cryptococcus, Paracoccidioides, and Rhinosporidium,15 – 17 can have a similar presentation and should be considered in the differential diagnosis.
Although, complete surgical excision may be considered for localized superficial infections in nonimmunocompromised patients, intravenous amphotericin B has been the most commonly used drug for treatment of Prototheca infection.16 The optimal dose and duration of therapy is unclear, as no clinical trials exist.3 Other medications used to treat Protothecosis include ketoconazole, itraconazole, fluconazole, and tetracyclines; however, these have been mostly used for localized infections.3 Despite previous reports that describe the successful use of voriconazole as salvage therapy in immunocompetent hosts,18,19 experience with the use of voriconazole and posaconazole in treating immunosuppressed patients is limited. Voriconazole seems an effective option for the treatment of infections caused by Prototheca, mainly due to its activity in vitro against species wickerhamii.20 In summary, we report a case of disseminated protothecosis highlighting the clinical presentation of this rare opportunistic infection with predilection for skin involvement. Our patient suffered from multiple myeloma and was immunosuppressed due to chronic neutropenia, hypogammaglobulinemia and multiple chemotherapy regimens; and we posit that all of these factors played a role in the development of this infection. Additionally, we report cure of the disease with voriconazole, underlining the potential role of this agent for the treatment of infections caused by Prototheca. Fig. 3. Erythematous nodular skin lesions involved the left antecubital fold. Fig. 4. Papular, non-pruritic, erythematous lesions were present on the thigh. Fig. 5. Soccer ball-like structures and wreath-like arrangement of the organisms (GMS staining). Fig. 6. Fluctuant nodular skin lesions were present in a periarticular distribution around the right wrist.
References 1. Wirth FA, Passalacqua JA, Kao G. Disseminated cutaneous protothecosis in an immunocompromised host: a case report and literature review. Cutis; cutaneous medicine for the practitioner 1999; 63: 185. 2. Davies RR, Spencer H, Wakelin PO. A Case of Human Protothecosis. Transactions of the Royal Society of Tropical Medicine and Hygiene. 1964; 58: 448. 3. Lass-Florl C, Mayr A. Human protothecosis. Clin Microbiol Rev 2007; 20: 230.
412
4. Boyd AS, Langley M, King LE Jr. Cutaneous manifestations of Prototheca infections. J Am Acad Dermatol 1995; 32(5 Pt 1): 758. 5. Woolrich A, Koestenblatt E, Don P, Szaniawski W. Cutaneous protothecosis and AIDS. J Am Acad Dermatol 1994; 31(5 Pt 2): 920. 6. Todd JR, King JW, Oberle A, et al. Protothecosis: report of a case with 20-year follow-up, and review of previously published cases. Medical mycology : official publication
of the International Society for Human and Animal Mycology 2012; 50: 673. 7. Huerre M, Ravisse P, Solomon H, et al. Human protothecosis and environment. Bull Soc Pathol Exot 1993; 86(5 Pt 2): 484. 8. Zhang QQ, Li L, Zhu LP, et al. Cutaneous Protothecosis in Patient with Diabetes Mellitus and Review of Published Case Reports. Mycopathologia. 2011. 9. Torres HA, Bodey GP, Tarrand JJ, Kontoyiannis DP. Protothecosis in patients with
Cover Quizlet cancer: case series and literature review. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 2003; 9: 786. 10. Carey WP, Kaykova Y, Bandres JC, Sidhu GS, Brau N. Cutaneous protothecosis in a patient with AIDS and a severe functional neutrophil defect: successful therapy with amphotericin B. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 1997; 25: 1265. 11. Phair JP, Williams JE, Bassaris HP, Zeiss CR, Morlock BA. Phagocytosis and algicidal activity of human polymorphonuclear neutrophils against Prototheca wickerhamii. The Journal of infectious diseases 1981; 144: 72.
12. Venezio FR, Lavoo E, Williams JE, et al. Progressive cutaneous protothecosis. American journal of clinical pathology 1982; 77: 485. 13. Khoury JA, Dubberke ER, Devine SM. Fatal case of protothecosis in a hematopoietic stem cell transplant recipient after infliximab treatment for graft-versus-host disease. Blood 2004; 104: 3414. 14. Cox GE, Wilson JD, Brown P. Protothecosis: a case of disseminated algal infection. Lancet 1974; 2: 379. 15. Hillesheim PB, Bahrami S. Cutaneous protothecosis. Archives of pathology & laboratory medicine 2011; 135: 941. 16. Kantrow SM, Boyd AS. Protothecosis. Dermatol Clin 2003; 21: 249. 17. Hightower KD, Messina JL. Cutaneous protothecosis: a case report and review of the
literature. Cutis; cutaneous medicine for the practitioner 2007; 80: 129. 18. Dalmau J, Pimentel CL, Alegre M, et al. Treatment of protothecosis with voriconazole. Journal of the American Academy of Dermatology 2006; 55(5 Suppl): S122. 19. Sheikh-Ahmad M, Goldstein S, Potasman I. Prototheca wickerhamii hand infection successfully treated by itraconazole and voriconazole. Journal of travel medicine 2006; 13: 321. 20. Linares MJ, Solis F, Casal M. In vitro activity of voriconazole against Prototheca wickerhamii: comparative evaluation of sensititre and NCCLS M27-A2 methods of detection. Journal of clinical microbiology 2005; 43: 2520.
413
