AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

The skin is most commonly involved, resulting from primary inoculation through a wound or abrasion. The infection is usually localized to the site of inoculation; however, in immunocompromised individuals, it can become widespread.

Pathophysiology

Prototheca is an achlorophyllic mutant of the green alga Chlorella. The organism is ubiquitous in the environment, particularly in aqueous locales. Infection usually occurs as a result of inoculation into or beneath the skin with subsequent exposure to contaminated water. Person-to-person transmission does not occur. However, Prototheca has been cultured from under the fingernails and other cutaneous sites in healthy individuals.

While healthy individuals can become infected, the organism has low virulence. Protothecosis infections are more commonly described in patients who are immunosuppressed. In healthy individuals, the infection is localized and curable, but cases of disseminated disease in individuals who are severely immunocompromised can be fatal. Cases of disseminated disease have involved the blood, the peritoneum, the GI tract, the liver, and the meninges. A neutrophilic response appears to be critical in eradicating the infection; however, recent reports in the literature dispute this.

Frequency

United States

Protothecosis is a rare infection, with fewer than 100 cases reported since the initial report in 1964. Most cases in the United States are from the Southeast, though cases from virtually all geographic regions have been reported.

International

Protothecosis is a rare infection, but it is seen worldwide, with cases reported in Europe, Asia, Africa, and Central and South America.

Mortality/Morbidity

Patients who are severely immunocompromised can develop disseminated disease, which is often fatal.

• Localized infection: In immunocompetent individuals, the infection usually remains confined to the skin at the site of inoculation. Olecranon bursitis can develop from protothecosis.
• Systemic infection: Rare cases of systemic infection occur almost exclusively in patients who are severely immunocompromised, as in patients receiving chemotherapy, or immunosuppressed patients, such as those on infliximab. Involvement of the meninges has been reported in a few cases of patients with AIDS.

Race

No racial predilection is noted.

Sex

No sexual predilection is evident.

Age

Protothecosis may occur in persons of any age; however, it is exceedingly rare in the pediatric population.

CLINICAL

Section 3 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

The classic history is that of trauma (eg, abrasion, cut) to the skin and subsequent exposure to contaminated water. In severely immunocompromised individuals, cutaneous lesions can be widespread and the algae can be present in the blood.

• Patients typically present with an isolated plaque or nodule, with or without ulceration and/or pustules. However, large eczematous plaques or ulcers have also been reported. Erythema and pain may occur.
• Patients with protothecosis bursitis present with painful swelling of the elbow; mild erythema; and, occasionally, drainage.

Physical

The skin is the most common site of infection, followed by the periarticular bursae (typically causing olecranon bursitis).

• Patients typically have an ill-defined plaque or nodule that may have a verrucous surface. Large eczematous plaques, pustular lesions, and cutaneous ulceration have also been reported.
• Bullous lesions may occur with subsequent rupture, drainage, and crusting.
• Lesions with the appearance of apple jelly have been reported.
• The extremities are the most common sites of involvement.
• In patients who are immunocompetent, the lesions may be more subtle, with papules or plaques with mild erythema that have been stable for long periods.
• Patients with olecranon bursitis have swelling; mild erythema; and, occasionally, drainage in the vicinity of the elbow.
• In cases of meningeal involvement, patients may have meningeal signs of headache, nuchal rigidity, and photophobia.

Causes

Infection is usually caused by Prototheca wickerhamii. Less commonly, infection occurs with Prototheca zopfii.

• Prototheca is ubiquitous in the environment. It has been cultured from a wide variety of aqueous sources, including lakes, streams, ponds, and even tap water. Prototheca species have also been cultured from animal feces, soil, and a variety of other sources.
• This organism is widely encountered in the environment, but it does not produce infection in most individuals. Most reported cases have occurred in patients who are severely immunosuppressed (eg, long-term immunosuppression for organ transplantation; autoimmune disease; graft versus host disease; as a result of chemotherapy or radiation therapy, AIDS, diabetes mellitus, chronic renal failure, or Cushing disease).

DIFFERENTIALS

Section 4 of 11  

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Other Problems to be Considered

Blastomycosislike pyoderma
Deep fungal infection

WORKUP

Section 5 of 11  

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• Follow-up
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Lab Studies

• A diagnosis of protothecosis can be made based on findings from either biopsy or culture.
• • Prototheca species readily grow on Sabouraud glucose agar. Smooth, white-to-beige colonies typically demonstrate growth within 48 hours at room temperature.
  • Prototheca species may also be cultured on blood agar, heart-brain infusion agar, or beef infusion broth.
  • Commercial assays that rely on the unique components of the cell wall are also available for identification of Prototheca species.

Other Tests

• No other tests are necessary; however, electron microscopy reveals a double-layered cell wall without chloroplasts. These features differentiate Prototheca organisms from other types of algae.

Histologic Findings

Protothecosis demonstrates rounded endospores, typically 6-10 µm in diameter either outside of the macrophages or within the macrophages. They are best visualized with special stains (eg, periodic acid-Schiff, Gomori methenamine-silver) that are used to highlight fungi. The diagnostic feature of P wickerhamii is the presence of sporangia with a central rounded endospore surrounded by a corona of molded endospores. The appearance of the sporangia is diagnostic, and it is described as moruloid, daisylike, spokelike, and frambesiform.

The principal histopathologic differential diagnosis is coccidioidomycosis, which often shows larger sporangia and always shows smaller endospores (2-4 µm).

TREATMENT

Section 6 of 11  

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Medical Care

Protothecosis is difficult to eradicate once infection takes hold. Given that the infection is rare, no defined pharmacologic protocol is available. All reported patients with disseminated disease have been treated with intravenous amphotericin B. Isolated reports describe successful treatment of localized disease with ketoconazole, itraconazole, and fluconazole. Sensitivity in vitro has not been shown to be correlated with in vivo efficacy. Surgical removal of isolated lesions in combination with antifungal therapy (eg, with azoles) is effective in immunocompetent individuals.

Surgical Care

Surgical excision is the treatment of choice in all cases amenable to excision.

MEDICATION

Section 7 of 11  

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The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Antifungal agents

These agents exert a fungicidal effect by altering the permeability of the fungal cell membrane. The mechanism of action may also involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell.

Drug Name	Fluconazole (Diflucan)
Description	Synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby disrupting cellular membranes. Has little affinity for mammalian cytochromes, which is believed to explain its low toxicity. Available as tabs for oral administration, as a powder for oral suspension, and as a sterile solution for IV use. Has fewer adverse effects and better tissue distribution than older systemic imidazoles. Can be used in severe or life-threatening infections in patients intolerant of amphotericin B and may be used for maintenance after a course of amphotericin B in coccidioidal meningitis. Penetrates well into CSF. Metabolic clearance is prolonged in patients with renal dysfunction.
Adult Dose	400 mg/d PO/IV; in certain circumstances dosages of 800 mg/d or higher have been administered
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Levels may increase with hydrochlorothiazides; levels may decrease with chronic coadministration of rifampin; may increase concentrations of theophylline, phenytoin, tolbutamide, cyclosporine, glyburide, and glipizide; effects of anticoagulants may increase with coadministration
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Adjust dose for renal insufficiency; closely monitor if rashes develop, and discontinue drug if lesions progress; may cause clinical hepatitis, cholestasis, and fulminant hepatic failure (including death) when taken with underlying medical conditions (eg, AIDS, malignancy) or while taking multiple concomitant medications; not recommended for breastfeeding mothers Convenience and efficacy of single-dose regimen for treatment of vaginal yeast infections should be weighed against difficulties resulting from higher incidence of adverse reactions reported with oral fluconazole versus intravaginal agents

Drug Name	Itraconazole (Sporanox)
Description	Fungistatic activity. Synthetic triazole antifungal agent that slows fungal cell growth by inhibiting cytochrome P-450?dependent synthesis of ergosterol, a vital component of fungal cell membranes.
Adult Dose	200 mg PO qd; not to exceed 400 mg/d; increase in 100-mg increments if no improvement (administer >200 mg/d in divided doses) 200 mg IV bid for 4 doses, followed by 200 mg/d Nail infections: 200 mg/d PO for 3-4 mo or pulse dosing of 400 mg/d for 1 wk each mo for 3-4 mo
Pediatric Dose	Not established; 100 mg/d PO suggested for systemic fungal infections
Contraindications	Documented hypersensitivity
Interactions	Antacids may reduce absorption; edema may occur with coadministration of calcium channel blockers (eg, amlodipine, nifedipine); hypoglycemia may occur with sulfonylureas; may increase tacrolimus and cyclosporine plasma concentrations when high doses are used; rhabdomyolysis may occur with coadministration of HMG-CoA reductase inhibitors (lovastatin or simvastatin); coadministration with cisapride can cause cardiac rhythm abnormalities and death May increase digoxin levels; coadministration may increase plasma levels of midazolam or triazolam; phenytoin and rifampin may reduce levels (phenytoin metabolism may be altered)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in hepatic insufficiencies

FOLLOW-UP

Section 8 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Complications

• Failure to eradicate protothecosis may result in an expanded area of skin infection. Rare cases have progressed to disseminated infection, typically in patients who are severely immunocompromised.

Prognosis

• Patients with localized disease have an excellent prognosis and can expect cure.
• The prognosis of patients with severe disease and immunosuppression is poor.

Patient Education

• Patients who have contracted protothecosis on one occasion should avoid bathing or swimming in lakes, streams, and ponds.

MISCELLANEOUS

Section 9 of 11  

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• Introduction
• Clinical
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• Follow-up
• Miscellaneous
• Multimedia
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Special Concerns

• Protothecosis is a rare infection, often involving individuals who are immunocompromised. An immune status evaluation may be judicious in patients presenting with this disorder.

MULTIMEDIA

Section 10 of 11  

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• Differentials
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• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  This subtle lesion of cutaneous protothecosis on the shoulder shows an ill-defined, slightly erythematous, thin plaque.
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Media file 2:  Periodic acid-Schiff–stained sections of protothecosis reveal rounded endospores that form characteristic moruloid structures in the dermis.
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Media type:  Photo

Media file 3:  Electron photomicrograph of Prototheca wickerhamii shows a central rounded endospore surrounded by a corona of molded endospores.
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Media type:  Photo

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
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• Follow-up
• Miscellaneous
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• References

• Boyd AS, Langley M, King LE Jr. Cutaneous manifestations of Prototheca infections. J Am Acad Dermatol. May 1995;32(5 Pt 1):758-64. [Medline].
• 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. Nov 1997;25(5):1265-6. [Medline].
• Kantrow SM, Boyd AS. Protothecosis. Dermatol Clin. Apr 2003;21(2):249-55. [Medline].
• 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 (10):3414-5. [Medline].
• Polk P, Sanders DY. Cutaneous protothecosis in association with the acquired immunodeficiency syndrome. South Med J. Aug 1997;90(8):831-2. [Medline].
• Torres HA, Bodey GP, Tarrand JJ, Kontoyiannis DP. Protothecosis in patients with cancer: case series and literature review. Clin Microbiol Infect. Aug 2003;9(8):786-92. [Medline].
• Walsh SV, Johnson RA, Tahan SR. Protothecosis: an unusual cause of chronic subcutaneous and soft tissue infection. Am J Dermatopathol. Aug 1998;20(4):379-82. [Medline].
• Zaitz C, Godoy AM, Colucci FM, et al. Cutaneous protothecosis: report of a third Brazilian case. Int J Dermatol. Feb 2006;45(2):124-6. [Medline].

Article Last Updated: Sep 15, 2006