Saksenaea vasiformis Orbital Cellulitis in an Immunocompetent Child Treated With Posaconazole

Abstract

An 11-year-old immunocompetent girl presented with two and a half months of progressive right orbital cellulitis, which did not respond to multiple courses of antibiotics or prednisone. A panfungal polymerase chain reaction primer was positive for Saksenaea vasiformis, and she completed 5 months of oral posaconazole therapy after debridement. Saksenaea vasiformis is a rare cause of zygomycosis, and it typically causes skin and soft tissue infection in immunocompetent hosts, particularly after a traumatic injury. The diagnosis should be considered in cases with a protracted course that fail to respond to typical antibiotic therapy. Treatment includes surgical debridement, in additional to antifungal therapy with amphotericin B or posaconazole.

CASE REPORT

An 11-year-old previously healthy girl presented with two and a half months of progressive right infraorbital redness and swelling, which she developed after swimming in brackish water. She recalled no specific traumatic injury, and she had no associated fever, eye pain, vision changes, or other symptoms. There was no improvement after courses of amoxicillin, amoxicillin-clavulanic acid, clindamycin, trimethoprim-sulfamethoxazole, topical antibiotic ointments, or prednisone and only slight improvement after a 5-day course of azithromycin. Physical examination revealed a well appearing child with marked right infraorbital erythema, induration, and swelling, which was nontender and nonfluctuant (Figure 1A). A complete blood count (CBC) and basic metabolic panel were normal. A magnetic resonance image showed a 2.5 by 1.5 centimeter infiltrative right naso-orbital mass extending to the right medial orbit and right medial rectus muscles.

Figure 1.

Clinical response as seen preoperatively (A) and 8 months postoperatively (B).

She was taken for debridement by oculoplastic surgery, with the following intraoperative findings: semipurulent liquid white material, several adjacent loculated fluid collections, and robust surrounding soft tissue fibrosis. Frozen section analysis of tissue samples collected at the time of debridement showed nonnecrotizing granulomatous inflammation. Clarithromycin, rifampin, and ethambutol were initiated due to suspicion for possible Mycobacterium marinum infection given the aquatic exposure and transient response to azithromycin. Oral posaconazole (delayed release tablets, 300 mg once daily based on adolescent dosing recommendations) was added after hyphal forms were visualized on hematoxylin and eosin stain (Figure 2A) and Grocott-Gomori’s methenamine silver stain (Figure 2B). Final pathology showed nonnecrotizing granulomas centered on pauciseptate, branching fungal hyphae on a background of mixed inflammation, and fibrosis. Image consultation was obtained through the Centers for Disease Control and Prevention (CDC) ePathology service and subsequently tissue samples were sent to the CDC Infectious Diseases Pathology Branch where the fungal elements were strongly reactive with mucormycete fungus immunohistochemistry (IHC) stain (Figure 2C), which detects zygomycetes of the Mucorales and Entomophthorales orders. A CDC panfungal polymerase chain reaction (PCR) primer, which amplifies the ITS2 region of the ribosomal deoxyribonucleic acid, was positive for Saksenaea vasiformis. Mycobacterium species IHC and PCR testing was negative. Routine bacterial and fungal cultures were negative, and acid-fast bacterial cultures grew Mycobacterium gordonae at 6 weeks, which was considered a contaminant.

Figure 2.

Nonnecrotizing granulomatous inflammation with hyphal forms on hematoxylin and eosin (A), Grocott-Gomori’s methenamine silver (B), and mucormycete fungus immunohistochemistry (C) stains.

She completed 5 months of posaconazole after debridement with near complete resolution of the right infraorbital redness and swelling (Figure 1B) and no resultant visual deficits. Posaconazole levels were therapeutic, ranging from 2170 to 3490 ng/mL. Multiple CBCs with differential and dihydrorhodamine flow testing for chronic granulomatous disease were normal.

DISCUSSION

Saksenaea vasiformis is a zygomycete with a worldwide distribution, which causes human and veterinary infections primarily in tropical and subtropical climates, including the United States [1, 2]. In contrast to most infections caused by other zygomycetes such as Rhizopus or Mucor species, more than 80% of S. vasiformis infections occur in immunocompetent patients [1, 2]. Localized cutaneous or subcutaneous infections are the most common manifestation, but rare cases of rhino-orbital, renal, or disseminated disease have been reported [1, 3, 4]. Skin and soft tissue manifestations can include rapidly progressive cellulitis or necrotizing fasciitis, abscess formation, ulceration, or chronic lesions that progress over several months, and 50% of cases are associated with prior trauma [1]. The diagnosis should be considered in patients with a protracted course, negative routine bacterial cultures, and failure to respond to antibiotic therapy. Inoculation most commonly occurs due to soil contamination at the site of trauma, but it may also occur after water contamination (presumably secondary to a laceration while swimming), direct inhalation of spores into the sinuses, after needle stick trauma, or after insect bites [1, 4]. Infections have also been described in patients with underlying immunocompromising conditions such as hematologic malignancies, solid neoplasms, prior splenectomy, uncontrolled diabetes mellitus, and corticosteroid use [1, 4].

Mixed purulent and granulomatous masses with central necrosis containing hyphal elements are visualized on histopathology, with growth of fluffy, white colonies on fungal media [1, 4]. However, final identification can be difficult because Saksenaea species rarely sporulate well in routine fungal media, and thus the classic flask-shaped sporangia may not be identified [1, 2, 4]. In such cases, panfungal PCR testing should be considered. Amphotericin B, posaconazole, and itraconazole demonstrate in vitro activity, and aggressive surgical debridement is a mainstay of treatment [1]. Amphotericin B is the conventional antifungal agent used, but posaconazole has previously been used successfully as maintenance therapy after induction with amphotericin B [3] or salvage therapy in patients with acute kidney injury from amphotericin B [5]. Mortality rates of 20%–30% are seen in immunocompetent individuals with S vasiformis infection, but these are as high as 70%–100% in immunocompromised patients and those with disseminated disease [1, 2].

CONCLUSIONS

Saksenaea vasiformis is a rare cause of zygomycosis, and it most commonly causes skin and soft tissue infection in immunocompetent hosts, particularly after a traumatic injury. This diagnosis should be considered in cases with a protracted course, negative routine bacterial cultures, or failure to respond to typical antibiotic therapy. In suspected cases, a fungal stain and culture should be obtained and panfungal PCR testing should be considered. Treatment includes surgical debridement, in additional to antifungal therapy with amphotericin B or posaconazole.