You are in: eMedicine Specialties > Ophthalmology > INFECTIOUS DISEASE CoccidioidomycosisArticle Last Updated: Mar 8, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 10
  Author: Cynthia A Self, MD, Assistant Professor, Department of Ophthalmology, Boston University School of Medicine Cynthia A Self is a member of the following medical societies: American Academy of Ophthalmology and American Society of Cataract and Refractive Surgery Coauthor(s): L Raymond DeBarge, MD, Assistant Professor, Department of Ophthalmology, University of Tennessee College of Medicine at Chattanooga Editors: Andrew A Dahl, MD, Director of Ophthalmology Teaching, Mid-Hudson Family Practice Institute; Assistant Professor of Surgery (Ophthalmology), New York College of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; R Christopher Walton, MD, Professor, Director of Uveitis and Ocular Inflammatory Diseases Service, Assistant Department of Ophthalmology, Assistant Dean for Graduate Medical Education and Continuing Education, University of Tennessee College of Medicine; Consulting Staff, Regional Medical Center, Memphis Veterans Affairs Medical Center, St Jude Children's Research Hospital; Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri; Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences Author and Editor Disclosure Synonyms and related keywords: valley fever, San Joaquin fever, desert fever, desert rheumatism, coccidioidal granuloma, and Posada-Wernicke disease INTRODUCTIONSection 2 of 10
  BackgroundCoccidioidomycosis is a disease caused by Coccidioides immitis, a dimorphic fungus that thrives in the lower Sonoran Desert ecozone of the Western hemisphere, including Arizona, New Mexico, west Texas, parts of central America, Argentina, northwest Mexico, and the San Joaquin Valley in California. The warm dry climate and sandy saline soil are ideal for growth of the mycelial phase of the fungus. The mold forms hyphae of 2-4 mm, which consist of chains of arthroconidia that later germinate under moist conditions. During dry seasons, winds spread the highly infectious arthrospores and infection occurs through inhalation of contaminated dust. No documented cases of animal-to-human or human-to-human transmission have occurred. PathophysiologyIn the pulmonary acinus of the host, the arthroconidia convert to the parasitic phase and form large 20- to 80-mm spherules surrounded by a double-walled capsule. Each spherule contains numerous clear endospores 2-4 mm in diameter. Rupture of a spherule releases the endospores, each of which may form a new spherule. After inhalation of infectious arthrospores, there is a 10- to 14-day incubation period prior to any clinical manifestations. Coccidioidomycosis is asymptomatic in 60% of patients, while others typically have a limited respiratory illness characterized by fever, cough, and malaise. Bronchopneumonia occurs in approximately one fourth of symptomatic patients. Of every 1000 patients with coccidioidomycosis infection, 2-5 develop disseminated coccidioidomycosis from hematogenous spread of endospores. Disseminated coccidioidomycosis has been found in virtually every organ in the body with the exception of the gastrointestinal tract. The most common site of spread is to the skin. Because coccidioidomycosis is a fungal disease, the main line of defense is T-cell–mediated immunity. Patients with HIV or other cell-mediated immune deficiencies can develop severe pulmonary and disseminated disease. Pregnant women are also at higher risk for developing disseminated disease. However, primary and disseminated coccidioidomycosis usually occurs in healthy individuals. Ocular involvement occurs secondary to dissemination and is considered rare. The eyelids and conjunctiva are the most common sites. The skin of the eyelids may contain granulomatous foci of Langerhans giant cells and coccidioidal spherules. Phlyctenular conjunctivitis may be seen and represents a hypersensitivity reaction. True mycotic granulomas of the conjunctiva are less common than hypersensitivity conjunctivitis and usually are seen in the presence of skin lesions. The uvea is the most common site of intraocular disease. A granulomatous iridocyclitis with iris nodules and posterior synechiae may be seen. However, the typical infection is a multifocal choroiditis with many discrete yellow-white lesions less than a disc diameter in size. Vitritis, vasculitis, serous retinal detachment, and retinal haze may occur in the acute phase. Typical coccidioidal granulomas with spherules are seen in the choroid on histopathology. Lesions also have been noted within the optic nerves. There has been one histopathologically documented report of intraretinal granulomas and organisms that occurred in a previously healthy 12-year-old child. FrequencyUnited StatesThe true incidence of ocular coccidioidomycosis is unknown; however, in one series of 10 patients with disseminated coccidioidomycosis, 4 developed evidence of choroidal infection over a 12-month period of observation. Disseminated disease has a higher frequency in women during the second half of pregnancy and the postpartum period and in patients who are immunosuppressed. InternationalIncidence is unknown. Mortality/MorbidityPresenting visual acuity of patients reported in the literature ranges from 20/20 to 20/200. Final visual acuity ranges from 20/20 to no light perception, depending on severity, time to diagnosis, and patient compliance with medical therapy and follow-up care. RaceRacial differences in the development of ocular manifestations of disseminated coccidioidomycosis are unknown. Ethnic origin is a risk factor for disseminated coccidioidomycosis. The following ethnic groups are listed from the highest to lowest risk: Filipino, African American, Native American, Hispanic, Asian, and white. Filipinos are reportedly 180 times as susceptible as whites to developing disseminated disease. SexA slight male preponderance exists. AgeDisease may occur in all ages, but infants and elderly persons have the worst clinical outcomes. CLINICALSection 3 of 10
History
Physical
CausesThe cause of the disease is inhalation of the infectious arthrospores and subsequent dissemination within the body to the eye. A defect in cell-mediated immunity may contribute to the likelihood of dissemination. DIFFERENTIALSSection 4 of 10
Actinomycosis Conjunctivitis, Allergic Endophthalmitis, Fungal Episcleritis Glaucoma, Uveitic Herpes Simplex Ocular Manifestations of Syphilis Presumed Ocular Histoplasmosis Syndrome Retinal Detachment, Exudative Sarcoidosis Scleritis Tuberculosis Uveitis, Anterior, Granulomatous Uveitis, Intermediate
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| Drug Name | Amphotericin B (Amphocin, Fungizone) |
|---|---|
| Description | For fungal infections. Polyene antibiotic produced by a strain of Streptomyces nodosus; can be fungistatic or fungicidal. Binds to sterols, such as ergosterol, in the fungal cell membrane, causing intracellular components to leak with subsequent fungal cell death. Note that liposomal amphotericin B has the advantage of decreased toxicity over conventional amphotericin B, making administration of larger doses possible. |
| Adult Dose | 1-5 mg/kg/d IV in 50-mg increments daily or 3 weekly infusions over 21-24 h Alternatively: 3-5 mg/kg/d IV of liposomal amphotericin B over approximately 120 min Intravitreal injection: 5-10 mcg of amphotericin B |
| Pediatric Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Antineoplastic agents may enhance the potential of amphotericin B for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; the risk of renal toxicity is increased with cyclosporine |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Monitor renal function, serum electrolytes, such as magnesium and potassium, liver function, CBC, and hemoglobin concentrations; resume therapy at the lowest level (eg, 0.25 mg/kg) when therapy is interrupted for more than 7 d; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in neutropenic patients receiving leukocyte transfusions (separate time of amphotericin infusion from time of leukocyte transfusion); fever and chills are not uncommon after first few administrations of drug; rare acute reactions may include hypotension, bronchospasm, arrhythmias, and shock |
| Drug Name | Ketoconazole (Nizoral) |
|---|---|
| Description | For fungal infections. Fungistatic activity. Imidazole broad-spectrum antifungal agent; inhibits synthesis of ergosterol, causing cellular components to leak, resulting in fungal cell death. Use for mild-to-moderate stable coccidioidomycosis. |
| Adult Dose | 200 mg PO qd; increase to 400 mg PO qd, if clinically indicated |
| Pediatric Dose | <2 years: Not established >2 years: 3.3-6.6 mg/kg/d PO single dose |
| Contraindications | Documented hypersensitivity; fungal meningitis |
| Interactions | Isoniazid may decrease bioavailability of ketoconazole; coadministration decreases effects of either rifampin or ketoconazole; may increase effect of anticoagulants; may increase toxicity of corticosteroids and cyclosporine (cyclosporine dosage can be adjusted); may decrease theophylline levels |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Hepatotoxicity may occur; may reversibly decrease corticosteroid serum levels (adverse effects avoided with dose of 200-400 mg/d); administer antacid, anticholinergics, or H2 blockers at least 2 h after taking ketoconazole |
| Drug Name | Fluconazole (Diflucan) |
|---|---|
| Description | For fungal infections. Fungistatic activity. Synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P-450 and sterol C-14 alpha-demethylation, which prevents conversion of lanosterol to ergosterol, thereby disrupting cellular membranes. Use for mild-to-moderate stable coccidioidomycosis. |
| Adult Dose | 150 mg PO single dose or 400 mg qd depending on severity of infection |
| Pediatric Dose | 3-6 mg/kg PO qd for 14-28 d or 6-12 mg/kg qd depending on severity of infection |
| Contraindications | Documented hypersensitivity |
| Interactions | Levels may increase with hydrochlorothiazides; fluconazole levels may decrease with long-term coadministration of rifampin; coadministration of fluconazole may decrease phenytoin concentrations; may increase concentrations of theophylline, tolbutamide, glyburide, and glipizide; effects of anticoagulants may increase with fluconazole coadministration; increases in cyclosporine concentrations may occur when administered concurrently |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Adjust dose for renal insufficiency; monitor closely if rashes develop, and discontinue drug if lesions progress; may cause clinical hepatitis, cholestasis, and fulminant hepatic failure (including death), with underlying medical conditions, such as AIDS or a malignancy, and while taking multiple concomitant medications; not recommended for mothers who are breastfeeding; convenience and efficacy of single dose regimen for treatment of vaginal yeast infections should be weighed against difficulties resulting from higher incidence of adverse reactions reported with oral fluconazole vs intravaginal agents |
| Drug Name | Itraconazole (Sporanox) |
|---|---|
| Description | For fungal infections. Fungistatic activity. Synthetic triazole antifungal agent that slows fungal cell growth by inhibiting cytochrome P-450–dependent synthesis of ergosterol, a vital component of fungal cell membranes. Use not defined for coccidioidomycosis. |
| Adult Dose | 200 mg PO qd; not to exceed 400 mg/d; increase in 100-mg increments if no improvement (administer >200 mg/d in divided doses) |
| Pediatric Dose | Not established; suggested dose of 100 mg/d for systemic fungal infections |
| Contraindications | Documented hypersensitivity |
| Interactions | Antacids may reduce absorption of itraconazole; edema may occur with coadministration of calcium channel blockers (eg, amlodipine, nifedipine); hypoglycemia may occur with sulfonylureas; may increase tacrolimus and cyclosporine plasma concentrations when high doses are used; rhabdomyolysis may occur with coadministration of HMG-CoA reductase inhibitors (lovastatin or simvastatin); may increase digoxin levels; coadministration may increase plasma levels of midazolam or triazolam; phenytoin and rifampin may reduce itraconazole levels (phenytoin metabolism may be altered) |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Caution in hepatic insufficiencies |
Article Last Updated: Mar 8, 2007
