Coccidioidomycosis Uveitis and Retinitis
Definition: Fungal systemic infection caused by inhalation of airborne spores from Coccidioides immitis.
Etiology: Coccidioidomycosis is a fungus found in the soil. It is related to dust storms. The ocular disease was described in 1948.
Incidence/Prevalence: Cocci is prevalent in regions considered Sonoran desert zones including the southwestern United States, parts of Mexico as well as Central and South America. In the U.S. it is most notable in the San Joaquin valley of California and Arizona. In Arizona in 2001 the incidence was reported as 43/100,000 population, a marked rise from 1995.
Systemic Clinical Findings: The disease has 4 different presentations, asymptomatic, primary pulmonary illness, persistent pulmonary disease, and disseminated disease. Clinical manifestations occur in only about 40% of infected persons. The most common presentation is a influenza-like illness. However it can progress to severe pneumonia and, rarely, extrapulmonary disseminated disease. Only a few arthroconidia, the mycelial form, can infect people. Persons at highest risk for disseminated disease include blacks, Filipinos, pregnant women in their third trimester, and immunocompromised persons.
Ocular Clinical Findings: Ocular Coccidioidomycosis generally segregates into 4 groups.
1. External eye disease including the eyelids and conjunctiva as the most common sites.
2. Anterior uveitis- presenting with hypopyon, iridocyclitis and a red eye. Pulmonary findings may be difficult to find in this subgroup and therefore must be suspected in cases of anterior uveitis of unknown origin in the proper clinical setting.
3. Posterior retinitis and uveitis- usually as part of the presentation of severe disseminated disease and often discovered late in the disease course. Many presumed cases have been described. Most cases documented pathologically originated from enucleation or autopsy. The posterior disease shows focal small white lesions that may be superficial and deep to retinal blood vessels.
4. Anterior and posterior disease- all cases that have been documented had initial involvement of the anterior segment and underwent vitrectomy. All eyes were lost.
Gross: The retina features single superficial discrete white lesions, which are granulomata surrounding the organisms (arrow 1). The choroid shows slightly less discrete white lesions with blurred margins (arrow 2).
Microscopic: In every tissue the key findings are granulomata that contain both spherules and endospores. In the figure, one sees a discrete granuloma in the inner nuclear layer. There is a spherule which contains endospores that are even visible on hematoxylin and eosin stains. Note that the endospores (inside the spherule at arrow 3) do not have nuclei (different from tachyzoites and bradyzoites of toxoplasmosis that are so often confused by ophthalmology residents). The spherule (arrow 3) is surrounded by a multinucleated giant cell (arrow 4). PAS and GMS highlight the organism.
Here the choroidal granuloma, really a single multinucleated giant cell in the figure (arrow 5) surrounds the PAS positive spherule. Multiple endospores are seen within the spherule, which also stain with PAS. This spherule is intact.
The GMS stain captures a ruptured spherule (arrow 6) that is releasing endospores (arrow 7).
Treatment: Amphotericin B is the drug of choice for pulmonary Coccidioidomycosis that is persistent or in which there is evidence of dissemination. The drug penetrates poorly into tissue and so it is administered intracamerally (intraocularly). Immunotherapy has been given for the disease with some success. Liposomes are sometimes used as a vehicle for slow release.
Prognosis: In the patients most at risk the disease may be fatal. Patients with anterior uveitis have a uniformly poor prognosis for useful vision. The lesions of the posterior segment have a better prognosis provided the patient survives the systemic illness.