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Medicina Cutánea
Ibero-Latino-Americana

Localizador: 17048
Cutaneous protothecosis in immunosuppressed
patients: a series of 14 cases
Prototecosis cutánea en pacientes inmunodeprimidos: una serie de 14 casos

Víctor Fernando Muñoz-Estrada,* Jorge Arturo Mayorga-Rodríguez,‡ Cipactli Ariel Navarro-Hernández§

Key words:
Protothecosis, ABSTRACT RESUMEN
cutaneous protothecosis,
itraconazole, Introduction: Protothecosis is an infrequent infection in dogs, Introducción: La prototecosis es una infección rara causada por
immunosuppressed cats, cattle, and humans caused by a type of green algae known algas del género Prototheca. Debido a los factores inmunosu-
patients. as Prototheca. Its incidence increases in immunosuppressed presores, los casos han aumentado, siendo considerada como
hosts and it’s considered an emergent disease in such patients. una infección emergente en este grupo de pacientes. Material y
Palabras clave: Material and methods: This is a retrospective review of métodos: Se describe una revisión retrospectiva de casos de pro-
Prototecosis, immunosuppressed patients with protothecosis seen at a totecosis en pacientes inmunosuprimidos, vistos en un hospital
prototecosis cutánea, single academic center in Mexico between 2010-2014. Their de México entre 2010 y 2014. Se discuten datos epidemiológi-
itraconazol, epidemiological, clinical, and therapeutic features are discussed. cos, clínicos y terapéuticos. El diagnóstico se realizó mediante
pacientes The diagnosis of protothecosis was established by mycologic cultivo micológico y/o estudio histopatológico. Resultados: Se
inmunodeprimidos. culture and/or skin biopsy. Results: There were 14 patients. encontraron 14 pacientes, todos inmunosuprimidos. La proto-
All of them were immunosuppressed. The majority (65%) were tecosis predominó en varones (65%), con una edad promedio
male. Average age was 48.8 years. The most frequent cause of de 48.8 años. El principal factor de inmunosupresión asociado
immunosuppression was immunosuppressive drugs associated fue medicación asociada a trasplante renal (35.7%), siendo la
with renal transplantation (35.7%). The most frequent clinical lesión clínica más frecuente los nódulos subcutáneos (64.2%). El
presentation was subcutaneous nodules (64.2%). Diagnosis was diagnóstico fue realizado por cultivo micológico (100%) y estudio
established by mycologic culture (100% of patients) and skin histopatológico (64%). Todos los pacientes fueron tratados con
biopsy (64%). All 14 patients were treated with itraconazole itraconazol (200-400 mg/día) durante 8 y 12 semanas. Ocho
200-400 mg PO QD for 8-12 weeks. Eight patients (57.1%) pacientes presentaron curación completa (57.1%). Conclusio-
were completely cured. Conclusions: Herein, we report nes: Ésta es la mayor serie de casos de prototecosis cutánea en
the largest series of patients with cutaneous protothecosis in pacientes inmunosuprimidos. El pronóstico se relaciona con la
* Dermatologist. Department
of Dermatology and immunosuppressed patients. Prognosis seems to be related to patología subyacente. El itraconazol por vía oral es una alterna-
Micology. Hospital Civil underlying pathology. Oral itraconazole is a relatively effective tiva de tratamiento efectiva y asequible.
Culiacán, Sinaloa. México. and available treatment option.
‡
M.Sc. Mycology Reference
Center (CEREMI) Jalisco,
México.
§
Dermatologist. Research
Department. Instituto
Dermatológico de Jalisco “Dr. INTRODUCTION worldwide. The most common presentation is
José Barba Rubio”. México. cutaneous (58.1%). The most frequent species
Conflict of interests:
None. T he genus Prototheca described by Kruger
in 1894, represents ubiquitous green
algae that lack chlorophyll.1,2 It includes 6
is P. wickerhamii (71.8%), followed by P. zopfii
(6.8%).7 Only five cases have been reported in
Mexico, two with disseminated disease, and
Received: known species.3,4 Prototheca can be found three with onychomycosis.8-10 Protothecosis
15/August/2017. in soil and water. In humans, the infection affects mainly immunosuppressed individuals;

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Accepted: by these algae is known as protothecosis. it can occur at any age, although, it’s more
07/March/2018.
The first case was described in 1964 by frequent in the elderly.11 The cutaneous form
Davies et al. 5 Cutaneous infection is very is clinically and histologically similar to many
rare. Usually, it occurs through inadvertent deep mycoses. Diagnosis depends on accurate
trauma with an unknown incubation period. morphologic identification of the etiologic
Clinically, there are 3 presentations: cutaneous, agent through biopsy, culture, biochemical
bursitis of olecranon, and disseminated.6 Up tests, and/or molecular biology.6,11,12 Herein,
until 2012, there were 160 cases reported we describe the clinical, epidemiological, and

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 Muñoz-Estrada VF et al. Cutaneous protothecosis in immunosuppressed patients ORIGINAL

therapeutic characteristics of a large series of patients with As regards the clinical presentation of protothecosis,
protothecosis from a single tertiary center. Lass-Flörl described a spectrum of lesions including
erythematous, verrucous, and atrophic hypopigmented
MATERIAL AND METHODS plaques; papules, nodules, pustules, vesicles, and
purulent and crusted ulcers.14 In our series, we found 3
This is a retrospective review of patients with types of skin lesions: subcutaneous nodules, infiltrated
protothecosis seen at a single Department of plaques, and ulcers. This is in striking contrast with
Dermatology in Culiacan, Sinaloa. Mexico, between previous reports from Mexico showing predominantly
2010 and 2014. Epidemiological data included onychomycosis.8-10
age, gender, type of immunosuppression, clinical
presentation, and time of evolution before diagnosis.
Diagnosis was established via skin biopsy with periodic
acid-Schiff stain and mycologic culture in Sabouraud
media. Treatment was done with itraconazole 200-400
mg/ day for 8-12 weeks.
Results are presented with descriptive statistics using
measures of central tendency.

RESULTS

There were 14 patients. Their characteristics are

summarized in table 1. The majority were male (65%),
with a male-to-female ratio of 1.8:1. The median age was
48.8 years (range 34-65) with 35.7% of cases in patients
between 51-60 years old. Most patients (35.7%) had
history of renal transplantation. All patients developed
limited disease to skin.
The most common location of lesions was the
lower extremities (78.5%). Only one patient (7.1%)
had trunkal lesions. Four patients (28.4%) had lesions
in 2 locations. Clinical lesions included subcutaneous
nodules (64.2%), infiltrated plaques (35.7%), and ulcers Figure 1. Cutaneous protothecosis.
(14.2%) (Figure 1).
Thirteen patients (92.8%) had lesions for 3-6 months.
Diagnosis was established via mycologic culture in all
patients (100%), and skin biopsy in 9 patients (64%) (Figure
2). Eight patients (57.1%) were treated with itraconazole 400
mg/day. Treatment resulted in cure in 8 patients (57.1%).
There were 6 deaths (42.9%): two patients (14.3%) died
from sepsis and 4 (28.6%) from their underlying disease.

DISCUSSION
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Protothecosis in humans is infrequent. There are
approximately 160 cases described worldwide but only
a few in the dermatological literature. Torres et al.13
described the largest series of 13 patients with underlying
cancer. In their report, only 5 patients (38%) had cutaneous
disease exclusively: 2 with non-Hodgkin lymphoma, 2 with
breast cancer, and 1 with cervical cancer.13 Figure 2. Histopathologic analysis shows Prototheca spp. (PAS, 100x).

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 Muñoz-Estrada VF et al. Cutaneous protothecosis in immunosuppressed patients
ORIGINAL

Table 1. Patients’ characteristics (n=14). liver toxicity and hepatitis; amphotericin B carries the risk
of renal failure, electrolyte imbalances, liver toxicity and
No. of cases %
blood dyscrasias. Less kidney toxicity has been reported
Gender with liposomal formulations of amphotericin B. The use
Males 9 65
of topical amphotericin B would avoid both the toxicity
Females 5 35
Age group (years) of systemic therapy and adverse effects of intravenous
31 - 40 4 28.6 administration, but requires further research.7
41 - 50 3 21.4 Unlike the vast majority of cases of protothecosis, in
51 - 60 5 35.7
61 - 70 2 14.3
the setting of immunosuppressed patients with exclusive
Cause of immunosuppression cutaneous disease, it is recommended to start with the
Renal transplant 5 35.7 combination of itraconazole plus amphotericin B when
Chronic lymphocytic leukemia 4 28.6 possible. As a second line of treatment amphotericin B
Hodgkin’s disease 4 28.6
Multiple myeloma 1 7.1
or azoles in topical preparation would be the choice.
Este documento
Duration of lesionses elaborado por Medigraphic Finally, the systemic administration of either itraconazole,
< 3 months 5 35.7 voriconazole or amphotericin B is indicated.
3 - 6 months 8 57.1 Unless toxicity appears in a short time, the trend is to
> 6 months 1 7.1
Oral itraconazole dose
treat for at least 1 month. The optimal dose and duration
200 mg/day 4 28.6 of therapy are uncertain.14
300 mg/day 2 14.3 Immunocompromising underlying disease is associated
400 mg/day 8 57.1 with lower treatment success rates, nevertheless, its
Therapeutic result
Cure 8 57.1 only significant when a therapy with corticosteroids is
Death due to prototecosis 2 14.3 associated.7 The prognosis depends on both the underlying
Death due to underlying disease disease and the efficacy of the treatment in avoiding the
• Renal transplant medication 2 14.3 spread of the infection; when this happens, the forecast
• Hodgkin’s disease 2 14.3
is ominous in the short term.

In our patients, the diagnosis was established via mycologic CONCLUSION

culture in 100% of cases and with skin biopsy in 64%.
Previously, Todd et al.7 reported that culture was positive in This is one of the largest series of cutaneous protothecosis
80.62% of cases and skin biopsy in 83.7%. In contrast to our in immunosuppressed patients. Protothecosis is clinically
study, this author identified the etiologic species. nonspecific. It may present with a varied morphology.
There is not enough evidence to make a recommendation The definitive diagnosis will depend on the morphological
about standard treatment regimen and treatment may identification of the organism; therefore, both microbiological
vary case by case.11 In a review by Todd et al, from 167 and histopathological tests are recommended. Therapy
evaluable treatments, there was an overall treatment with itraconazole is an acceptable alternative for patients
success rate of 71%.7 Cure rates for protothecosis include in whom amphotericin B is contraindicated, moreover, it
intravenous amphotericin B (56-91%), itraconazole (49- seems to be more effective in immunosuppressed and in
82%), fluconazole (38-88%), caspofungin and voriconazole cutaneous disease. The limitations of this study were its
(19-99%).6,7 Based on this, it is reasonable to use a retrospective nature and the scarcity of cases.
combination of treatment. This leads to an success rate
Acknowledgment
of 57-98%.7 In our series, we treated our patients with
itraconazole achieving a cure rate of 57.1%. We elected To Dr. Carlos García for his invaluable support in the
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not to treat with amphotericin B because 35.7% of our
patients were renal transplant recipients, and the rest had
writing of this work.

various other contraindications for its use. In addition

Correspondence:
to this, amphotericin B seems to be less effective in Cipactli Ariel Navarro-Hernández
immunocompromised than itraconazole alone.7 Another Av. Federalismo Norte Núm. 3102,
reason for choosing itraconazole, is its superiority in Atemajac, Zapopan, Jalisco, 45190, México.
effectiveness than other antifungals in the treatment of Tel: (33) 3030 4536, (33) 1799 8468
localized infections.11 The treatment with azoles can cause E-mail: [email protected]

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 Muñoz-Estrada VF et al. Cutaneous protothecosis in immunosuppressed patients ORIGINAL

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