Manifestations and treatment of extrapulmonary coccidioidomycosis
- Carol A Kauffman, MD
Carol A Kauffman, MD
- Section Editor — Fungal Infections
- Professor of Internal Medicine
- University of Michigan Medical School
- Veterans Affairs Ann Arbor Healthcare System
Coccidioidomycosis is caused by the dimorphic fungi, Coccidioides immitis, or Coccidioides posadasii. These organisms are endemic to certain arid regions of the western hemisphere. Infection is virtually always acquired by inhalation, and primary infection frequently goes unrecognized [1,2]. Dissemination of infection beyond the lungs can occur, but it is difficult to estimate the incidence of overt disseminated disease. (See "Primary coccidioidal infection", section on 'Epidemiology' and "Primary coccidioidal infection", section on 'Microbiology'.)
The manifestations and treatment of extrapulmonary coccidioidomycosis other than involvement of the central nervous system will be reviewed here. Primary infection, laboratory diagnosis, pulmonary sequelae, coccidioidal meningitis, and infection in immunocompromised hosts are discussed separately. (See "Primary coccidioidal infection" and "Coccidioidomycosis: Laboratory diagnosis and screening" and "Management of pulmonary sequelae and complications of coccidioidomycosis" and "Coccidioidal meningitis" and "Coccidioidomycosis in compromised hosts".)
INCIDENCE OF DISSEMINATED INFECTIONS
Coccidioidomycosis occasionally spreads from the initial pulmonary lesion to other parts of the body. Past estimates of this risk vary from approximately 4.7 percent of recognized infections  to 0.2 percent of all respiratory exposures to Coccidioides spp . This substantial range in estimates is probably due to the under-recognition of mild infections . Patient groups at risk for extrapulmonary infection include those who are of African or Filipino ancestry and those who are immunosuppressed.
The Arizona Department of Health Services sought to review medical charts of every 10th person newly reported with coccidioidomycosis from January 2007 to February 2008 and were 65.7 percent successful for a total of 324 cases . Of these, 26 (8.0 percent) had clinical or laboratory evidence of infection beyond the lungs. If this sample was representative of all reported infections that year (approximately 5000), then, by extrapolation, there were a total of 400 newly diagnosed disseminated infections in Arizona.
When disseminated infection occurs, it usually becomes evident within weeks after the initial exposure. Thus, it is common for dissemination to be clinically apparent at the time infection is first diagnosed. In patients who do not receive treatment for early coccidioidal infections, new onset of disseminated disease after two years is very uncommon in the absence of immunosuppression. However, in studies of patients who have received early antifungal treatment, there are reports of delayed recognition of dissemination until up to two years after treatment is stopped . In the author's practice, a patient's vertebral coccidioidal osteomyelitis first became evident seven years after a brief course of fluconazole was given for early coccidioidal pneumonia.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- SMITH CE, BEARD RR. Varieties of coccidioidal infection in relation to the epidemiology and control of the diseases. Am J Public Health Nations Health 1946; 36:1394.
- Smith CE. Epidemiology of Acute Coccidioidomycosis with Erythema Nodosum ("San Joaquin" or "Valley Fever"). Am J Public Health Nations Health 1940; 30:600.
- Johnson RH, Caldwell JW, Welch G, et al. The great coccidioidomycosis epidemic: Clinical features. In: Einstein HE, Catanzaro A, eds. Coccidioidomycosis. Proceedings of the 5th International Conference. Washington: National Foundation for Infectious Diseases; 1996:77.
- Barnato AE, Sanders GD, Owens DK. Cost-effectiveness of a potential vaccine for Coccidioides immitis. Emerg Infect Dis 2001; 7:797.
- Chang DC, Anderson S, Wannemuehler K, et al. Testing for coccidioidomycosis among patients with community-acquired pneumonia. Emerg Infect Dis 2008; 14:1053.
- Foley CG, Tsang CA, Christ C, Anderson SM. Impact of Disseminated Coccidioidomycosis in Arizona, 2007-2008. Proceedings of the 55th Annual Coccidioidomycosis Study Group, April 2, 2011. University of California Davis, Davis, CA. https://www.vfce.arizona.edu/resources/pdf/csg/55Proceedings.pdf (Accessed on May 08, 2015).
- Ampel NM, Giblin A, Mourani JP, Galgiani JN. Factors and outcomes associated with the decision to treat primary pulmonary coccidioidomycosis. Clin Infect Dis 2009; 48:172.
- Crum NF, Lederman ER, Stafford CM, et al. Coccidioidomycosis: a descriptive survey of a reemerging disease. Clinical characteristics and current controversies. Medicine (Baltimore) 2004; 83:149.
- Johnson RH, Caldwell D. State of the art lecture. Extra-pulmonary nonmeningeal coccidioidomycosis. In: Coccidioidomycosis. Proceedings of the Fifth International Conference, edited by H. Einstein and A. Catanzaro, Bethesda MD:National Foundation for Infectious Diseases, 1996, p. 347-358.
- Adam RD, Elliott SP, Taljanovic MS. The spectrum and presentation of disseminated coccidioidomycosis. Am J Med 2009; 122:770.
- Campbell M, Kusne S, Renfree KJ, et al. Coccidioidal Tenosynovitis of the Hand and Wrist: Report of 9 Cases and Review of the Literature. Clin Infect Dis 2015; 61:1514.
- Stadalnik RC, Goldstein E, Hoeprich PD, et al. Diagnostic value of gallium and bone scans in evaluation of extrapulmonary coccidioidal lesions. Am Rev Respir Dis 1980; 121:673.
- Erly WK, Carmody RF, Seeger JF, Lund PJ. Magnetic resonance imaging of coccidioidal spondylitis. Int J Neuroradiol 1997; 3:385.
- Papadopoulos KI, Castor B, Klingspor L, et al. Bilateral isolated adrenal coccidioidomycosis. J Intern Med 1996; 239:275.
- Smilack JD, Argueta R. Coccidioidal infection of the thyroid. Arch Intern Med 1998; 158:89.
- Rodenbiker HT, Ganley JP. Ocular coccidioidomycosis. Surv Ophthalmol 1980; 24:263.
- Cunningham ET Jr, Seiff SR, Berger TG, et al. Intraocular coccidioidomycosis diagnosed by skin biopsy. Arch Ophthalmol 1998; 116:674.
- Stone JL, Kalina RE. Ocular coccidioidomycosis. Am J Ophthalmol 1993; 116:249.
- Goldberg B, Loeffler AM. Respiratory distress and a liver mass. Pediatr Infect Dis J 1999; 18:1105.
- Huntington RW. Pathology of coccidioidomycosis. In: Coccidioidomycosis: A text, Stevens DA (Ed), Plenum Medical Book Co, New York City 1980. p.113.
- Baden LR, Digumarthy SR, Guimaraes AS, Branda JA. Case records of the Massachusetts General Hospital. Case 35-2009. A 60-year-old male renal-transplant recipient with renal insufficiency, diabetic ketoacidosis, and mental-status changes. N Engl J Med 2009; 361:1980.
- Kuntze JR, Herman MH, Evans SG. Genitourinary coccidioidomycosis. J Urol 1988; 140:370.
- Liao JC, Reiter RE. Coccidioidomycosis presenting as testicular mass. J Urol 2001; 166:1396.
- Dykes TM, Stone AB, Canby-Hagino ED. Coccidioidomycosis of the epididymis and testis. AJR Am J Roentgenol 2005; 184:552.
- Halsey ES, Rasnake MS, Hospenthal DR. Coccidioidomycosis of the male reproductive tract. Mycopathologia 2005; 159:199.
- Sohail MR, Andrews PE, Blair JE. Coccidioidomycosis of the male genital tract. J Urol 2005; 173:1978.
- Lawrence MA, Ginsberg D, Stein JP, et al. Coccidioidomycosis prostatitis associated with prostate cancer. BJU Int 1999; 84:372.
- Niku SD, Dalgleish G, Devendra G. Coccidioidomycosis of the prostate gland. Urology 1998; 52:127.
- Phillips P, Ford B. Peritoneal coccidioidomycosis: case report and review. Clin Infect Dis 2000; 30:971.
- McCarty JM, Demetral LC, Dabrowski L, et al. Pediatric coccidioidomycosis in central California: a retrospective case series. Clin Infect Dis 2013; 56:1579.
- Galgiani JN, Ampel NM, Blair JE, et al. 2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Treatment of Coccidioidomycosis. Clin Infect Dis 2016; 63:e112.
- Blair JE. State-of-the-art treatment of coccidioidomycosis skeletal infections. Ann N Y Acad Sci 2007; 1111:422.
- Blair JE. State-of-the-art treatment of coccidioidomycosis: skin and soft-tissue infections. Ann N Y Acad Sci 2007; 1111:411.
- Catanzaro A, Galgiani JN, Levine BE, et al. Fluconazole in the treatment of chronic pulmonary and nonmeningeal disseminated coccidioidomycosis. NIAID Mycoses Study Group. Am J Med 1995; 98:249.
- Graybill JR, Stevens DA, Galgiani JN, et al. Itraconazole treatment of coccidioidomycosis. NAIAD Mycoses Study Group. Am J Med 1990; 89:282.
- Galgiani JN, Catanzaro A, Cloud GA, et al. Comparison of oral fluconazole and itraconazole for progressive, nonmeningeal coccidioidomycosis. A randomized, double-blind trial. Mycoses Study Group. Ann Intern Med 2000; 133:676.
- Stevens DA, Rendon A, Gaona-Flores V, et al. Posaconazole therapy for chronic refractory coccidioidomycosis. Chest 2007; 132:952.
- Catanzaro A, Cloud GA, Stevens DA, et al. Safety, tolerance, and efficacy of posaconazole therapy in patients with nonmeningeal disseminated or chronic pulmonary coccidioidomycosis. Clin Infect Dis 2007; 45:562.
- Kim MM, Vikram HR, Kusne S, et al. Treatment of refractory coccidioidomycosis with voriconazole or posaconazole. Clin Infect Dis 2011; 53:1060.
- Prabhu RM, Bonnell M, Currier BL, Orenstein R. Successful treatment of disseminated nonmeningeal coccidioidomycosis with voriconazole. Clin Infect Dis 2004; 39:e74.
- Proia LA, Tenorio AR. Successful use of voriconazole for treatment of Coccidioides meningitis. Antimicrob Agents Chemother 2004; 48:2341.
- Cortez KJ, Walsh TJ, Bennett JE. Successful treatment of coccidioidal meningitis with voriconazole. Clin Infect Dis 2003; 36:1619.
- Levy ER, McCarty JM, Shane AL, Weintrub PS. Treatment of pediatric refractory coccidioidomycosis with combination voriconazole and caspofungin: a retrospective case series. Clin Infect Dis 2013; 56:1573.
- Homans JD, Spencer L. Itraconazole treatment of nonmeningeal coccidioidomycosis in children: two case reports and review of the literature. Pediatr Infect Dis J 2010; 29:65.
- Yurkanin JP, Ahmann F, Dalkin BL. Coccidioidomycosis of the prostate: a determination of incidence, report of 4 cases, and treatment recommendations. J Infect 2006; 52:e19.
- Kuberski TT, Servi RJ, Rubin PJ. Successful treatment of a critically ill patient with disseminated coccidioidomycosis, using adjunctive interferon-gamma. Clin Infect Dis 2004; 38:910.
- Vinh DC, Masannat F, Dzioba RB, et al. Refractory disseminated coccidioidomycosis and mycobacteriosis in interferon-gamma receptor 1 deficiency. Clin Infect Dis 2009; 49:e62.
- Dorman SE, Holland SM. Interferon-gamma and interleukin-12 pathway defects and human disease. Cytokine Growth Factor Rev 2000; 11:321.
- INCIDENCE OF DISSEMINATED INFECTIONS
- CLINICAL MANIFESTATIONS
- General principles
- Soft tissue infection without bone involvement
- Bone and joint infection
- - Antifungal therapy
- - Surgical management
- Meningeal involvement
- Special considerations
- - Supraclavicular adenopathy
- - Retropharyngeal abscess
- - Solitary cutaneous lesions in children
- - Prostatic infection
- Risk of relapse after treatment
- ADJUNCTIVE INTERFERON-GAMMA
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS