Endogenous Stromal Keratitis Due to Coccidioidomycosis
PEDIATRIC INFECTIOUS DISEASE JOURNAL(2023)
Abstract
To the Editors: Coccidioidomycosis is an infectious disease caused by a dimorphic fungus, Coccidioides immitis, which is endemic to the southwestern USA and areas of Mexico, Central and South America. The infection is acquired through the inhalation of arthroconidia that transform into endospore-filled spherules in the lungs. Extrapulmonary dissemination and uncommon coccidioidomycosis presentations are 4–7 times more common in males and 10–15 times more likely in patients of African ancestry than Caucasians.1,2 Hematogenous spread to the skin, bones, lymph nodes, and central nervous system has been well-documented,1 but intraocular involvement is rare and usually consists of iridocyclitis, endophthalmitis or chorioretinitis.3 This case report describes a pediatric patient with endogenous seeding of coccidioidomycosis to the cornea. An 11-year-old Somali male presented to a tertiary care center in the southwestern USA with blurred vision (20/50 in the right eye and 20/20 in the left), anterior chamber cellular reaction and corneal scarring. He was being treated for presumed anterior uveitis with prednisolone acetate 1% eye drops. Coccidioides IgM and IgG were positive by enzyme immunoassay, and serum complement fixation titer was elevated at 1:16 (normal: negative). To evaluate for disseminated disease, a nuclear medicine whole-body bone scan and lumbar puncture with cerebrospinal fluid analysis were performed and showed no central nervous system or musculoskeletal involvement. At follow-up, progressive corneal endothelial precipitates and stromal opacities with satellite lesions were noted (Fig. 1A). Fluorescein staining for an epithelial defect was negative. Fungal infiltrates were presumed due to the satellite lesions and indolent course. Multiple attempts to culture the aqueous fluid, as well as a 6-0 vicryl suture passing through the corneal stroma in the area of the infiltrates, were negative. Despite treatment with topical voriconazole 1%, 6 intracameral and intrastromal voriconazole 100 mcg/0.1 mL injections and oral fluconazole (10 mg/kg = 600 mg) daily, the corneal lesions persisted. Therefore, he underwent 7 weekly injections of amphotericin B 10 mcg/0.1 mL. Seven months later, the corneal infiltrates had cleared (Fig. 1B), right eye visual acuity was 20/25, and the Coccidioides complement fixation titers returned to normal (negative).FIGURE 1.: A: Initial presentation of the right eye showing corneal endothelial precipitates (red arrows) and stromal infiltrates with satellite lesions (green arrows). No epithelial defect was present on fluorescein staining. B: Resolution of endothelial precipitates and stromal infiltrates, with mild residual stromal scarring, after completion of 7 weeks of amphotericin B injections.Fungal keratitis is a refractory infection due to delayed presentation, difficulty in microbiologic culturing and varying sensitivity to antifungal agents.3 Before arriving at the diagnosis, the patient was treated for anterior uveitis. Though a positive culture could not be obtained, several factors implicated fungal keratitis: patient’s area of residence and ancestry; insidious onset of symptoms; progressive, nummular corneal opacities with satellite lesions; lack of clinical improvement with steroid eye drops and positive Coccidioides serology with an appropriate response to treatment. Topical voriconazole was unsuccessful due to poor penetration through an intact overlying corneal epithelium. Intracameral and intrastromal injections promote higher therapeutic drug loads into deeper corneal layers. Although intrastromal injections of voriconazole have previously been used effectively,4 refractory infection necessitated switching to amphotericin B. Exact duration of antifungal therapy is currently individualized, taking into consideration host factors, symptoms and examination findings. A larger study using Coccidioides complement fixation titers to track response to ocular therapy may provide a more standardized treatment regimen.
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