Prototheca wickerhamii hand infection successfully treated by itraconazole and voriconazole


  • Muhammad Sheikh-Ahmad MD,

    1. *Infectious Diseases and Travel Clinic and Department of Orthopedic Surgery, Bnai Zion Medical Centre, Rappaport Faculty of Medicine, Technion, Haifa, Israel
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  • Shaul Goldstein MD,

    1. *Infectious Diseases and Travel Clinic and Department of Orthopedic Surgery, Bnai Zion Medical Centre, Rappaport Faculty of Medicine, Technion, Haifa, Israel
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  • Israel Potasman MD

    Corresponding author
    1. *Infectious Diseases and Travel Clinic and Department of Orthopedic Surgery, Bnai Zion Medical Centre, Rappaport Faculty of Medicine, Technion, Haifa, Israel
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Israel Potasman, MD, Infectious Diseases and Travel Clinic, Bnai Zion Medical Ctr, 47 Golomb Street, Haifa 31048, Israel. E-mail:

Infections in human beings are usually caused by bacteria, viruses, protozoa, or fungi. It is extremely uncommon for clinicians to encounter infections caused by other pathogens. Prototheca is an alga that reproduces by endosporulation and rarely causes infections in humans; most cases are reported among immunocompromised patients.1 Protothecosis usually involves the skin but may also cause systemic infection.2 During the past two decades, infections caused by Prototheca have been increasingly recognized, and about 100 cases have been reported worldwide.3 Herein, we present the case of a hand infection caused by Prototheca wickerhamii, possibly acquired in the Red sea.

Case report

A 60-year-old diabetic, amateur gardener (orchid grower) presented with a 3-month history of painful swelling of his right hand. Two months before the swelling began, he underwent a release of “trigger finger” of the third finger. The incision had almost healed completely but was reopened by trauma, while the patient was diving in the Red sea (Sharm-El-Sheik). The patient noted that a considerable amount of sea water had entered his wound during each dive.

Upon examination, his hand looked edematous, with a red-purplish hue. Discrete, somewhat tender, nodules were noted over the involved finger (Figure 1). Temperature at presentation was 36°C. The white cell count was 8,240/μL, with a normal differential. C-reactive protein was 25.3 mg/dL (normal <5 mg/dL). Gallium scan focusing on the hand revealed no pathological uptake. Surgical exploration of the hand revealed pus and nodular material, which were debrided. Histology (Hematoxylin and Eosin, Figure 2) revealed necrotizing granulomata, while Periodic Acid Schiff and Grocott’s stains demonstrated yeast forms with endospores (Figure 3). Within a few days, whitish colonies grew on Sabrouraud’s agar; microscopy was consistent with P wickerhamii. The patient was initially treated with itraconazole 200 mg/day for 1 month with only moderate improvement. Based on sensitivity tests, the treatment was switched to voriconazole at 400 mg loading dose, followed by a maintenance of 200 mg twice daily for an additional month. At follow-up after 6 and 12 months, the infection had completely resolved. In an attempt to uncover the source of the patient’s uncommon infection, cultures were taken from a fishpond and tree barks in his garden, but all were negative.

Figure 1.

Nodules and edema of the third finger.

Figure 2.

Hematoxylin and eosin stain demonstrating necrotizing granulomata.

Figure 3.

Periodic Acid Schiff stain (magnified ×25) demonstrating yeast forms with endospores.


Prototheca is an ubiquitous, achlorophyllic aerobic algae.3Prototheca can be isolated from slime flux of trees, fresh and salt water, sewage, soil, potato skins, grass, cow’s milk, cattle, deer, dogs, cats, and fruit bats. It has been found to colonize humans in the fingernails, skin, respiratory tract, and digestive systems.4 Only two of the known five species of Prototheca cause infections in humans: P wickerhamii and P zopfii, with the former being more common.4

Davies and colleagues described the first case of human infection with Prototheca back in 1964.3 The case presented as a localized skin lesion in a rice farmer from Western Africa. Since then, an additional 100 cases have been reported in the literature.3

About half of the reported patients with protothecosis had some degree of immune deficiency,2 which included diabetes mellitus, peritoneal dialysis, renal transplantation, steroid treatment, or immunologic defects involving lymphocytes and neutrophils.4 It is unclear why this infection is not more common in cancer patients.4

Trauma and inoculation with contaminated water is the most common mechanism of transmission to humans.5 Infection develops after an incubation period of several weeks. The infection usually spreads indolently locally but may be more widespread in immunocompromised patients, causing aggressive and fatal infections.6,7 The skin is the organ most frequently involved6 and presents as erythematous nodules, plaques, or superficial ulcers. Distal lesions of the hand may spread proximally to cause olecranon bursitis. One report described protothecal arthritis and tenosynovitis resulting from hematogenous dissemination.8 Protothecosis may present rarely as urinary tract infection,4 meningitis,9 or endocarditis.10 Interestingly, protothecosis can also be a nosocomial pathogen, complicating endotracheal intubation, peritoneal dialysis, IV catheters, corticosteroid injection, hand or wrist surgery, and orthopedic procedures.5

Prototheca seems to be a cosmopolitan organism. Cases of Prototheca were reported from all continents except Antarctica.1 In the United States, protothecosis has been reported most often in the southeast.4

Diagnosis of Prototheca requires a high index of suspicion. Most cases present as indolent hand infections and are diagnosed by skin biopsy or fungal culture. The differential diagnosis of indolent hand infections includes sporotrichosis,11Mycobacterium marinum infection,12 and primary cutaneous nocardiosis (most commonly caused by Nocardia brasiliensis).13

Histologically, cutaneous protothecosis is characterized by a suppurative or granulomatous infiltration of the dermis and the presence of many solitary spherical spores that measure 6 to 10 μm in diameter, which can be found both within giant cells and extracellularly.3 The organism grows well on Sabouraud’s dextrose agar and is identified under wet mount.2

The exact source of Prototheca in our patient is unclear. The possibility that this rare infection was acquired during the release of the trigger finger in the operating room is highly unlikely. Fungal cultures were not taken at the operating room, and we were unaware of additional cases of protothecosis in our hospital. On the other hand, he had dived in the Red Sea a few weeks before noticing the lesions. A history of recurrent “contamination” with sea water may cause unusual infections,14 but likewise he could have contracted his illness as a gardener in his own yard. The latter option is less likely as we were unsuccessful in culturing the organism from his yard.

To date, there is no standard treatment regimen for Prototheca. Widespread and deeper lesions can be treated by systemic amphotericin B.2 Voriconazole15 and Itraconazole16 may offer an option for the treatment. The Prototheca in our patient was susceptible to amphotericin B (Minimal Inhibitory Concentration [MIC] = 0.5 mg/L), fluconazole (MIC = 0.25 mg/L), and voriconazole (MIC = 0.75 mg/L). To the best of our knowledge, this is the first report of a clinical case successfully treated with voriconazole. Some patients with protothecosis may require surgical intervention, as happened in our case. Olecranon bursitis can be treated by bursectomy.2

In conclusion, indolent hand infections, especially those exhibiting granulomata should be suspected to be caused by Prototheca. Optimal treatment includes one of the newer azoles, or amphotericin B, and occasionally surgery.

Declaration of interests

The authors state that they have no conflicts of interest.