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Primary and Disseminated Cutaneous Coccidioidomycosis: Clinical Aspects and Diagnosis

  • Fungal Infections of Skin and Subcutaneous Tissue (A Bonifaz, Section Editor)
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Abstract

Coccidioidomycosis is an endemic systemic mycosis of the western hemisphere that has acquired mayor relevance after a raise in cases in the recent years. Two species, Coccidioides immitis and C. posadasii are recognized as the causative agents of this disease that, in principle, primarily affects the lungs. Extra pulmonary cutaneous forms have been more frequently reported and its manifestations present a vast clinical spectrum that resembles subcutaneous mycosis, cutaneous tuberculosis or even skin cancer. The interaction of the host and its immune response against the fungus and its pathogenic mechanism play a major role in the evolution, clinical and histopathological aspects and finally in the resolution of the disease.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Colombo AL, Tobón A, Restrepo A, et al. Epidemiology of endemic systemic fungal infections in Latin America. Med Mycol. 2011;49(8):785–98.

    PubMed  Google Scholar 

  2. Benedict K, Thompson III GR, Deresinski S, Chiller T. Mycotic infections acquired outside areas of known endemicity. United States Emerg Infect Dis. 2015;21(11):1935–41. doi:10.3201/eid2111.141950.

    Article  PubMed  Google Scholar 

  3. Blair J, Chang YH, Cheng MR, et al. Characteristics of patients with mild to moderate primary pulmonary coccidioidomycosis. Emerg Infect Dis. 2014;20(6):983–90. doi:10.3201/eid2006.131842. Prospective study and detail description of patients with pulmonary coccidioidomycosis.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Chang A, Tung RC, McGillis TS, et al. Primary cutaneous coccidioidomycosis. J Am Acad Dermatol. 2003;49(5):944–9.

    Article  PubMed  Google Scholar 

  5. Blair JE. State-of-the-art treatment of coccidioidomycosis skin and soft-tissue infections. Ann NY Acad Sci. 2007;1111:411–21.

    Article  PubMed  Google Scholar 

  6. Sondermeyer G, Lee L, Gilliss D, et al. Associated-associated hospitalizations, California, USA, 2000–2011. Emerg Infect Dis. 2013;19(10):1590–7. doi:10.3201/eid1910.130427.

    Article  PubMed  PubMed Central  Google Scholar 

  7. CDC. Increase in reported coccidioidomycosis—United States, 1998–2011. MMWR. 2013;62(12):217–21. Epidemiology report of coccidiodomycosis cases have increased dramatically in endemic areas.

    Google Scholar 

  8. Seitz AE, Prevots DR, Holland SM. Hospitalizations associated with disseminated coccidioidomycosis, Arizona and California, USA. Emerg Infect Dis. 2012;18(9):1476–9. doi:10.3201/eid1809.120151.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Crum NF, Ballon-Landa G. Coccidioidomycosis in pregnancy: case report and review of the literature. Am J Med. 2006;119(11):993. e11-7.

    Article  PubMed  Google Scholar 

  10. Marsden-Haug N, Goldoft M, Ralston C, et al. Coccidioidomycosis acquired in Washington State. Clin Infect Dis. 2013;56(6):847–50. doi:10.1093/cid/cis1028.

    Article  PubMed  Google Scholar 

  11. Litvintseva AP, Marsden-Haug N, Hurst S, et al. Valley fever: Finding new places for an old disease: Coccidioides immitis found in Washington state soil associated with recent human infection. Clin Infect Dis. 2015;60(1):e1–3. doi:10.1093/cid/ciu681. This study demonstrates colonization of soils by C. immitis linked to human infections and located outside the endemic range.

    Article  PubMed  Google Scholar 

  12. Wilson JW. The importance of portal of entry in certain microbial infections. The primary cutaneous “chancriform syndrome”. Dis Chest; 54(S1): 299–304. http://journal.publications.chestnet.org.

  13. Deus Filho A, Deus ACB, Meneses AO, et al. Skin and mucous membrane manifestations of coccidioidomycosis: a study of thirty cases in the Brazilian states of Piauí and Maranhão. An Bras Dermatol. 2010;85(1):45–51. doi:10.1590/S0365-05962010000100006.

    Article  PubMed  Google Scholar 

  14. Simental-Lara F, Bonifaz A. Coccidioidomicosis en la región lagunera de Coahuila, México. Dermatol Rev Mex. 2011;55(3):140–51.

    Google Scholar 

  15. Moreno-Coutiño G, Arce-Ramírez M, Medina A, et al. Coccidioidomicosis cutánea. Comunicación de seis casos mexicanos. Rev Chilena Infectol. 2015;32(3):339–43. This article is one of first reports of Coccidioides posadasii infection in cutaneous coccidioidomycosis.

    Article  PubMed  Google Scholar 

  16. Salas-Alanis JC, Ocampo-Candiani J, Cepeda-Valdes R, et al. Cutaneous coccidioidomycosis: Incidental finding. J Clin Exp Dermatol Res. 2012;3:147. doi:10.4172/2155-9554.1000147.

    Google Scholar 

  17. Narang V, Garg B, Sood N, Goraya SK. Primary cutaneous coccidioidomycosis: first imported case in north India. Indian J Dermatol. 2014;59:422.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Kantarcioglu AS, Sandoval-Denis M, Aygun G, et al. First imported coccidiodomycosis in Turkey: a potential health risk for laboratory workers outside endemic areas. Med Mycol Case Rep. 2014;3:20–5. doi:10.1016/j.mmcr.2014.01.002.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Al-Daraji WI, Al-Mahmoud RM, Ali MA. Disseminated Coccidioidomycosis: a case report from the United Kingdom. Int J Clin Exp Pathol. 2009;2:494–7. www.ijcep.com/IJCEP803007.

    PubMed  Google Scholar 

  20. Tortorano AM, Carminati G, Tosoni A, et al. Primary cutaneous coccidioidomycosis in an Italian nun working in South America and review of published literature. Mycopathologia. 2015;180(3-4):229–35. doi:10.1007/s11046-015-9895-0.

    Article  CAS  PubMed  Google Scholar 

  21. Whiston E, Taylor JW. Comparative phylogenomics of pathogenic and nonpathogenic species. G3: Genes Genomes Genetics. 2016;6(2):235–44. doi:10.1534/g3.115.022806. Phylogenetic study on Coccidioides spp. gene family expansion/contraction and their metabolism.

    Article  Google Scholar 

  22. Nguyen C, Barker BM, Hoover S, et al. Recent advances in our understanding of the environmental, epidemiological, immunological, and clinical dimensions of coccidioidomycosis. Clin Microbiol Rev. 2013;26(3):505–25. doi:10.1128/CMR.00005-13. This is a complete review of the disease.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Gaidici A, Saubolle MA. Transmission of coccidioidomycosis to a human via a cat bite. J Clin Microbiol. 2009;47(2):505–6. doi:10.1128/JCM.0186008.

    Article  PubMed  Google Scholar 

  24. Johnson L, Gaab EM, Sanchez J, et al. Valley fever: danger lurking in a dust cloud. Microbes Infect. 2014;16(8):591–600. doi:10.1016/j.micinf.2014.06.011. This is a review comprehending pathogenic aspects and host immune response.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Lewis ERG, Bowers JR, Barker BM. Dust devil: the life and times of the fungus that causes valley fever. PLoS Pathog. 2015;11(5):e1004762. doi:10.1371/journal.ppat.1004762.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Vinh DC, Schwartz B, Hsu AP, et al. Interleukin-12 receptor b1 deficiency predisposing to disseminated coccidioidomycosis. Clin Infect Dis. 2011;52(4):e99–102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Hung C-Y, Seshan K, Yu J, et al. A metalloproteinase of Coccidioides posadasii contributes to evasion of host detection. Infect Immune. 2005;73(10):6689–703.

    Article  CAS  Google Scholar 

  28. Fanning S, Mitchell AP. Fungal biofilms. PLoS Pathog. 2012;8(4):e1002585. doi:10.1371/journal.ppat.1002585.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Sharpton TJ, Stajich JE, Rounsley SD, et al. Comparative genomic analyses of the human fungal pathogens Coccidioides and their relatives. Genome Res. 2009;19:1722–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Li J, Yu L, Tian Y, Zhang KQ. Molecular evolution of the deuterolysin (M35) family genes in Coccidioides. PLoS One. 2012;7(2):e31536. doi:10.1371/journal.pone.0031536.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Mirbod-Donovan F, Schaller R, Hung C-Y, et al. Urease produced by Coccidioides posadasii contributes to the virulence of this respiratory pathogen. Infect Immun. 2006;74(1):504–15. doi:10.1128/IAI.74.1.504-515.2006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Wise HZ, Hung C-Y, Whiston E, Taylor JW, Cole GT. Extracellular ammonia at sites of pulmonary infection with Coccidioides posadasii contributes to severity of the respiratory disease. Microb Pathog. 2013;0:19–28. doi:10.1016/j.micpath.2013.04.003.

    Article  CAS  PubMed Central  Google Scholar 

  33. Ondo AL, Zlotoff J, Mings SM, et al. Primary cutaneous coccidioidomycosis: an incidental finding. Clin Exp Dermatol. 2010;35(3):e42–3.

    Article  CAS  PubMed  Google Scholar 

  34. DiCaudo DJ. Coccidioidomycosis: a review and update. J Am Acad Dermatol. 2006;55(6):929–42.

    Article  PubMed  Google Scholar 

  35. DiCaudo DJ. Coccidioidomycosis. Semin Cutan Med Surg. 2014;33:140–5.

    Article  PubMed  Google Scholar 

  36. Garcia-Garcia SC, Salas-Alanis JC, Gomez-Flores M, et al. Coccidioidomycosis and the skin: a comprehensive review. An Bras Dermatol. 2015;90(5):610–21. doi:10.1590/abd1806-4841.20153805.

    Article  PubMed  Google Scholar 

  37. Mangold AR, DiCaudo DJ, Blair JE, Sekulic A. Chronic interstitial granulomatous dermatitis in coccidioidomycosis. Br J Dermatol. 2015; 17. doi: 10.1111/bjd.14295

  38. Garza-Chapa JI, Martínez-Cabriales SA, Ocampo-Garza J, et al. Cold subcutaneous abscesses as the first manifestation of disseminated coccidioidomycosis in an immunocompromised host. Australas J Dermatol. 2015. doi:10.1111/ajd.12424.

    PubMed  Google Scholar 

  39. Langelier C, Baxi SM, Iribarne D, Chin-Hong P. Beyond the superficial: Coccidioides immitis fungaemia in a man with fever, fatigue and skin nodules: a case of an emerging and evolving pathogen. BMJ Case Reports. 2014. doi:10.1136/bcr-2014-205333.

    PubMed Central  Google Scholar 

  40. Carpenter JB, Feldman JS, Leyva WH, et al. Clinical and pathologic characteristics of disseminated cutaneous coccidioidomycosis. J Am Acad Dermatol. 2010;62(5):831–7.

    Article  PubMed  Google Scholar 

  41. Ocampo-Garza J, Castrejón-Pérez AD, Gonzalez-Saldivar G, et al. Cutaneous coccidioidomycosis: a great mimicker. BMJ Case Rep. 2015. doi:10.1136/bcr-2015-211680.

    PubMed  Google Scholar 

  42. Rodriguez R, Konia T. Coccidioidomycosis of the tongue. Arch Pathol Lab Med. 2005;129(1):e4–6.

    PubMed  Google Scholar 

  43. Ellerbrook L, Laks S, Cocciodioidomycosis osteomyelitis of the knee in a 23-year-old diabetic patient. Radiol Case Reports. (Online) 2014; 10(1); 1034.

  44. Jaramillo-Moreno G, Velázquez-Arenas L, Mendez-Olvera N, Ocampo-Candiani J. Primary cutaneous coccidioidomycosis: case report and review of the literature. Int J Dermatol. 2006;45:121–3. doi:10.1111/j.1365-4632.2004.02446.x.

    Article  Google Scholar 

  45. Rojas-García OC, Moreno-Treviño MG, González-Salazar F, et al. Primary cutaneous coccidioidomycosis in an infant. Gac Med Mex. 2014;150(2):175–6.

    PubMed  Google Scholar 

  46. Saúl A, Bonifaz A. Clasificación de la esporotricosis. Una propuesta con base en el comportamiento inmunológico. Dermatol Rev Mex. 2011;55(4):200–8.

    Google Scholar 

  47. Tchernev G, Cardoso JC, Chokoeva AA, et al. The “mystery” of cutaneous sarcoidosis: facts and controversies. Int J Immunopathol Pharmacol. 2014;27(3):321–30.

    CAS  PubMed  Google Scholar 

  48. Newlon HR, Lambiase MC. Disseminated cutaneous coccidioidomycosis masquerading as lupus pernio. Cutis. 2010;86(1):25–8.

    PubMed  Google Scholar 

  49. Crum NF. Disseminated coccidioidomycosis with cutaneous lesions clinically mimicking mycosis fungoides. Int J Dermatol. 2005;44(11):958–60.

    Article  PubMed  Google Scholar 

  50. Arora NP, Taneja V, Reyes Sacin C, et al. Coccidioidomycosis masquerading as malignancy. BMJ Case Rep. 2012. doi:10.1136/bcr.12.2011.5357.

    Google Scholar 

  51. Wilson JW, Smith CE, Plunkett OA. Primary cutaneous coccidioidomycosis. The criteria for diagnosis and a report of a Case. Calif Med. 1953;79(3):233–9. PMCID: PMC1521839.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Pappagianis D. The phenomenon of locus minoris resistentiae in coccidioidomycosis. In: Coccidioidomycosis, Proceedings of the 4th International Conference on Coccidioidomycosis, San Diego, Calif. March, 14-17, 1984. Washington, DC: The National Foundation for Infectious Diseases; 1985:319–329.

  53. Ruocco V, Brunetti G, Puca RV, Ruocco E. The immunocompromised district: a unifying concept for lymphoedematous, herpes-infected and otherwise damaged sites. J Eur Acad Dermatol Venereol. 2009;23(12):1364–73. doi:10.1111/j.1468-3083.2009.03345.x.

    Article  CAS  PubMed  Google Scholar 

  54. Ruocco V, Ruocco E, Piccolo V, et al. The immunocompromised district in dermatology: a unifying pathogenic view of the regional immune dysregulation. Clin Dermatol. 2014;32(5):569–76. doi:10.1016/j.clindermatol.2014.04.004.

    Article  PubMed  Google Scholar 

  55. Muñoz-Hernández B, Palma-Cortés G, Carlos Cabello-Gutiérrez C, et al. Parasitic polymorphism of Coccidioides spp. BMC Infect Dis. 2014;14:213. http://www.biomedcentral.com/1471-2334/14/213 . In this study, the authors observed parasitic morphological diversity of Coccidioides in clinical samples.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Kappel ST, Wu JJ, Hillman JD, et al. Histopathologic findings of disseminated coccidioidomycosis with hyphae. Arch Dermatol. 2007;143(4):548–9. doi:10.1001/archderm.143.4.548.

    Article  PubMed  Google Scholar 

  57. Ampel NM. The diagnosis of coccidioidomycosis. F1000 Med Rep. 2010;2:2. doi:10.3410/M2-2.

    PubMed  PubMed Central  Google Scholar 

  58. Berg N, Ryscavage P, Kulesza P. The utility of fine needle aspiration for diagnosis of extrapulmonary coccidioidomycosis: a case report and discussion. Clin Med Res. 2011;9(3-4):130–3.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Aly FZ, Millis R, Sobonya R, et al. Cytologic diagnosis of coccidiodomycosis: spectrum of findings in Southern Arizona patients over a 10 year period. Diagn Cytopathol. 2016;44(3):195–200. doi:10.1002/dc.23419.

    Article  PubMed  Google Scholar 

  60. Khalbuss WE, Michelow P, Benedict C, et al. Cytomorphology of unusual infectious entities in the Pap test. Cyto J. 2012;9:15. doi:10.4103/1742-6413.97763.

    Google Scholar 

  61. Guarner J, Brandt ME. Histopathologic diagnosis of fungal infections in the 21st century. Clin Microbiol Rev. 2011;24(2):247–80. doi:10.1128/CMR.00053-10.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Fernandez-Flores A, Saeb-Lima M, Arenas-Guzman R. Morphological findings of deep cutaneous fungal infections. Am J Dermatopathol. 2014;36(7):531–56.

    Article  PubMed  Google Scholar 

  63. Jehangir W, Tadepalli GS, Sen S, et al. Coccidioidomycosis and blastomycosis: endemic mycotic co-infections in the HIV patient. J Clin Med Res. 2015;7(3):196–8. doi:10.14740/jocmr2036w.

    Article  PubMed  Google Scholar 

  64. Miller JM, Astles R, Baszler T, et al. Guidelines for safe work practices in human and animal medical diagnostic laboratories. Recommendations of a CDC-convened, Biosafety Blue Ribbon Panel. MMWR. 2012;61(1):1–102.

    Google Scholar 

  65. Johnson R, Kernerman SM, Sawtelle BG, et al. Reformulated spherule-derived coccidioidin (Spherusol) to detect delayed-type hypersensitivity in coccidioidomycosis. Mycopathologia. 2012;174(5-6):353–8. doi:10.1007/s11046-012-9555-6.

    Article  PubMed  Google Scholar 

  66. Wack EE, Ampel NM, Sunenshine RH, Galgiani JN. The return of delayed-type hypersensitivity skin testing for coccidioidomycosis. Clin Infect Dis. 2015;61(5):787–91. doi:10.1093/cid/civ388.

    Article  PubMed  Google Scholar 

  67. Mendoza N, Blair JE. The utility of diagnostic testing for active coccidioidomycosis in solid organ transplant recipients. Am J Transplant. 2013;13(4):1034–9. doi:10.1111/ajt.12144.

    Article  CAS  PubMed  Google Scholar 

  68. Arvanitis M, Anagnostou T, Fuchs BB, et al. Molecular and nonmolecular diagnostic methods for invasive fungal infections. Clin Microbiol Rev. 2014;27(3):490–526. doi:10.1128/CMR.00091-13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Navalkar KA, Johnston SA, Woodbury N, et al. Application of immunosignatures for diagnosis of valley fever. Clin Vaccine Immunol. 2014;21(8):1169–77. doi:10.1128/CVI.00228-14. This is a new technology improve Coccidioidomycosis diagnosis with a higher sensitivity and it can distinguish related infections.

    Article  PubMed Central  PubMed  Google Scholar 

  70. Duarte-Escalante E, Frias-De leon MG, et al. Molecular markers in the epidemiology and diagnosis of coccidioidomycosis. Rev Iberoam Micol. 2014;31(1):49–53.

    Article  PubMed  Google Scholar 

  71. Binnicker MJ, Buckwalter SP, Eisberner JJ, et al. Detection of Coccidioides species in clinical specimens by real-time PCR. J Clin Microbiol. 2007;45(1):173–8. doi:10.1128/JCM.01776-06.

    Article  CAS  PubMed  Google Scholar 

  72. Mitchell M, Dizon D, Libke R, et al. Development of a real-time PCR assay for identification of Coccidioides immitis by use of the BD Max system. J Clin Microbiol. 2015;53(3):926–9. doi:10.1128/JCM.02731-14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Ampel NM. The treatment of coccidioidomycosis. Rev Inst Med Trop Sao Paulo. 2015;57(S19):51–6. doi:10.1590/S0036-46652015000700010.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Welsh O, Vera-Cabrera L, et al. Coccidioidomycosis. Clin Dermatol. 2012;30(6):573–91.

    Article  PubMed  Google Scholar 

  75. Bercovitch RS, Catanzaro A, Schwartz BS, et al. Coccidioidomycosis during pregnancy: a review and recommendations for management. Clin Infect Dis. 2011;53(4):363–8. doi:10.1093/cid/cir410.

    Article  PubMed  Google Scholar 

  76. 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(5):562–8.

    Article  CAS  PubMed  Google Scholar 

  77. Chang M, Chagan L. Posaconazole (Noxafil), an extended-spectrum oral triazole antifungal agent. Pharm Ther. 2008;33(7):391–426. PMC2740948.

    Google Scholar 

  78. Lat A, Thompson III GR. Update on the optimal use of voriconazole for invasive fungal infections. Infect Drug Resist. 2011;4:43–53. doi:10.2147/IDR.S12714.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Kim MM, Vikram HR, Kusne S, et al. Treatment of refractory coccidioidomycosis with voriconazole or posaconazole. Clin Infect Dis. 2011;53(11):1060–6. doi:10.1093/cid/cir642.

    Article  CAS  PubMed  Google Scholar 

  80. Duplessis CA, Tilley D, Bavaro M, et al. Two cases illustrating successful adjunctive interferon-g immunotherapy in refractory disseminated coccidioidomycosis. J Infect. 2011;63(3):223–8. doi:10.1016/j.jinf.2011.07.006.

    Article  PubMed  PubMed Central  Google Scholar 

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    Martin Arce & Daniela Gutierrez-Mendoza

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Arce, M., Gutierrez-Mendoza, D. Primary and Disseminated Cutaneous Coccidioidomycosis: Clinical Aspects and Diagnosis. Curr Fungal Infect Rep 10, 132–139 (2016). https://doi.org/10.1007/s12281-016-0263-4

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