Case Report: Protothecal Tenosynovitis

Abstract

Protothecosis is a rare infection caused by achlorophyllic algae called Prototheca. Approximately 117 cases have been described in the literature world wide, the majority caused by the species P. wickerhamii. Cutaneous infection is the most common and cases of tenosynovitis are very rare. A local or systemic immunosuppressive factor is seen in half of the cases of protothecosis. We report a case of protothecal tenosynovitis in a middle-aged, immunocompetent woman that developed after she received sclerosing therapy of varicose veins. Administration of itraconazole with surgical débridement produced a good response. We also review the published cases of protothecal tenosynovitis.

Introduction

Protothecosis is a rare infection caused by members of the genus Prototheca, which are considered achlorophyllic algae [1]. These organisms are ubiquitous [5], and the first case of human infection attributed to Prototheca species was reported by Davies et al. in 1964 [3]. Currently, P. zopfii, P. wickerhamii, P. stagnora, P. ulmea, and P. blaschkeae sp nov are assigned to the genus [10]. Of these, P. wickerhamii and P. zopfii have been reported to cause human diseases, with P. wickerhamii being the more common of the two [1, 6, 18]. Clinical cases usually present as cutaneous infection, olecranon bursitis, and disseminated disease [2, 6, 7].

Approximately 117 patients with protothecal infections have been described in the literature [10] with a few involving synovial tendon sheaths [9, 12–14, 17]. Reports of Protothecal tenosynovitis are rare in the orthopaedic literature [17]. We report a case of protothecal tenosynovitis in a middle-aged immunocompetent woman after she underwent sclerosing therapy of varicose veins, and we review the published cases of protothecal tenosynovitis.

Case Report

A 51-year-old woman presented with a circumscribed swollen skin lesion on her right foot dorsum, which enlarged during the course of a year. The lesion originally developed 2 months after injection of a sclerosing agent to treat varicose veins of the right foot 1 year previously. Three of the four injection sites healed without problems whereas the fourth was the site of the swelling. The patient otherwise had been healthy. She was treated with oral antibiotics (amoxicillin/clavulanate) without response. Several months later, intermittent local triamcinolone injections were given; however, they also had no effect. She then was referred to our hospital. Physical examination revealed a 2 x 2-cm circumscribed infiltrated nodule surrounded by diffuse erythema on the right foot dorsum. Routine laboratory evaluations (complete blood count, erythrocyte sedimentation rate, renal and liver function profiles) were within normal limits. MRI showed a well-enhancing mass-like lesion located on the skin and subcutaneous tissue from the first metatarsal bone level to the dorsal aspect of the cuneiform bone. There was no bone marrow signal change or destruction, but fluid collection along the extensor hallucis longus suggested tenosynovitis (Fig. 1). Skin biopsy suggested fungal infection, but tissue culture was not obtained. We were consulted for the possibility of fungal infection and recommended rebiopsy for tissue culture, but she refused and therefore received empiric treatment. She was given itraconazole (400 mg/day) orally for 1 month but was lost to followup. Four months later, a skin nodule developed at the same site and resection of that nodule was performed at a local clinic. An ulcer subsequently developed at the excision site and the patient returned to our clinic with a 2.5 x 2.5-cm ulcer (Fig. 2). Biopsy was performed at the ulcer base and the specimens revealed mild acanthosis and necrosis. Histologic sections revealed multiple morula-like sporangia containing many endospores in periodic acid Schiff staining (Fig. 3). Creamy yeast-like colonies grew on tissue cultures on Sabouraud dextrose agar at room temperature within 48 hours, and microscopic examination showed sporangia with sporangiospores in methenamine blue stain (Fig. 4). Species identification was performed using a Vitek^® II YST card (bioMérieux, Marcy-L’Etoile, France), a ready-to-use commercial kit for identification of yeasts and yeast-like organisms (53 species, 14 genera) based on the biochemical characteristics of isolates, taking 18 hours to get the results. The isolates identified as P. wickerhamii were based on assimilation of galactose, glucose, glycerol, and trehalose. We twice débrided the ulcer (initially and at 8 weeks). After itraconazole (400 mg/day) was administered orally for 5 months, the ulcer was almost completely healed (Fig. 5A). MRI was performed at the 5-month followup and showed disappearance of fluid collection along the extensor hallucis longus and a marked decrease in the extent of the skin and subcutaneous lesion (Fig. 5B). At the patient’s last visit 5 months after discontinuation of itraconazole, she had no evidence of recurrence.

Fig. 1.

A T1-weighted fat-saturated image with gadolinium enhancement shows fluid collection (arrow) along the extensor hallucis longus, suggesting tenosynovitis.

Fig. 2.

A photograph of the right foot dorsum shows erythematous skin change surrounding a round ulcer before definitive therapy with itraconazole.

Fig. 3.

A photomicrograph shows multiple morula-like sporangia containing many endospores (Stain, periodic acid Schiff; original magnification, ×400).

Fig. 4.

A wet mount preparation shows many characteristic sporangia containing endospores (Stain, methenamine blue; original magnification, ×400).

Fig. 5A–B.

After 5 months of treatment with itraconazole, (A) a photograph of the right foot dorsum shows healed ulcer lesions. (B) The MR image, also obtained after 5 months of treatment with itraconazole, shows disappearance of the fluid collection and a minimally enhancing skin and subcutaneous lesion.

Discussion

Prototheca species are spherical, unicellular, achlorophyllous algae ranging from 3 to 30 μm in diameter that propagate by means of asexual reproduction and exist as saprophytes [1]. Although the genetic diagnosis indicates these organisms are fungi, it generally is believed the genus developed from Chlorella at some point in its evolution [15] and evolved differences in cell wall composition and physiology and the ability to survive environmental stress [3, 4]. Typical sources of Prototheca species are trees, fresh and salt water, sewage treatment plants, garbage dumps, and household garbage [16]. They can be isolated from skin, feces, or sputum of humans or animals in the absence of clinical manifestations [19]. The pathogenesis of protothecosis is largely unknown, but it is believed Prototheca species infect humans by contact with potential sources or by traumatic inoculation of the algae [8]. At least half of protothecosis cases are simple cutaneous infections and presentations of cutaneous protothecosis can take various forms, including erythematous plaque, pustules, papules, nodules, verrucous lesions, pyodermic and herpetiform lesions, vesicles, ulcers, and hypopigmented or atrophic lesions [10].

The literature contains reports of only six patients with tenosynovitis caused by Prototheca species (Table 1). Three (including the infection in our patient) developed after a surgical procedure or open wound and were treated with antibiotics or antifungal agents plus surgery. One patient with AIDS had tenosynovitis develop in association with Prototheca septicemia and he died despite intensive intravenous antifungal therapy [13]. Most of the treated patients underwent surgical intervention with long-term antifungal therapy.

Table 1.

Published cases of protothecal tenosynovitis

Authors	Age (years)/gender	Site of infection	Diagnosis	Medical history	Possible sources	Treatment	Outcome
Laeng et al. [9]	Not reported	Extensor tendon of thumb	Histopathology (Prototheca spp)	AIDS	Not reported	Excision	Cure
Moyer et al. [12]	62/female	Tenosynovium of hand	Histopathology and culture (P. wickerhamii)		Postsurgical infection	Synovectomy, amphotericin B	Cure
Pascual et al. [13]	49/male	Extensor tendon of ankle	Histopathology and culture (P. wickerhamii)	AIDS	Disseminated protothecosis	Itraconazole, amphotericin B	Death
Pegram et al. [14]	46/female	Wrist tendons	Histopathology and culture (P. wickerhamii)	Steroids: topical and systemic, moderate alcoholism	Postsurgical infection (wrist tenolysis)	Ketoconazole	Cure
Sirikulchayanonta et al. [17]	24/female	Extensor tendon of hand	Histopathology (Prototheca spp)		Hand trauma from broken glass	Excision, amphotericin B, tetracycline	Cure
Current authors	51/female	Extensor tendon of foot	Histopathology and culture (P. wickerhamii)		Sclerosing therapy of varicose vein	Incision and débridement, itraconazole	Cure

A local or systemic immunosuppressive factor (eg, AIDS, corticosteroid use, hematologic or solid organ malignancy, or diabetes mellitus) occurs in half of the cases of protothecosis [11]. Ten patients with cutaneous protothecosis have been reported in Korea. Among those 10 patients, most were middle-aged or elderly with predisposing factors such as use of corticosteroids or diabetes mellitus [2, 7]. Although our patient also had a history of local steroid injection, it is likely protothecosis had developed before local steroid injection because steroids were used several months after the skin lesion had appeared. Hospital-acquired cases of protothecosis have been reported in association with surgery and orthopaedic procedures [6]. In our patient, protothecosis developed after sclerosing therapy of varicose veins and this is the first reported case of protothecal tenosynovitis associated with sclerosing therapy.

Treatment of protothecal infections remains controversial, and there has been no consistency in the clinical responses [11]. Antifungals such as ketoconazole, itraconazole, fluconazole, and amphotericin B are the most commonly used drugs to date [10, 11]. Usually treatment involves medical and surgical approaches. Treatment failure is not uncommon [10]. In our patient, surgical resection of a skin nodule was performed shortly before her second presentation to our hospital and wound débridement with oral itraconazole for 5 months produced a good response.

We report a case of protothecal tenosynovitis in a middle-aged, immunocompetent woman that developed after the patient had sclerosing therapy for varicose veins. Protothecosis should be included in the differential diagnosis for chronic tenosynovitis resistant to usual treatment. Tissue biopsy with culture (including fungal culture) is needed when deep fungal infection is suspected or when infected lesions do not respond to conventional antibacterial treatment.