Paracoccidioidomycosis pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Danitza Lukac

Overview

Spores of Paracoccidioides spp. are commonly transmitted via the respiratory route to the human host. Following transmission, Paracoccidioides spp. particles invade the terminal bronchioles and alveoli where granulomas are formed, but can be inactive for up to 40 years.^[1] On microscopic histopathological analysis, a "pilot's wheel" or a "Mickey mouse ears-like" appearance is a characteristic finding of paracoccidioidomycosis (PCM).^[2]^[3]^[4]

Pathopysiology

Transmission

Spores of Paracoccidioides spp. are transmitted via the respiratory route to the human host.
Rarely in can be transmitted via skin trauma, where the fungus attaches the skin and mucous membranes. Or via the digestive system, after consuming contaminated food.^[1]^[4]
Following transmission, Paracoccidioides spp. conidia and mycelial particles invade the terminal bronchioles and alveoli where they convert into yeast cells.^[1]

Pathogenesis

The organisms response to the primo-infection is: bronchoalveolitis, which is normally asymptomatic.^[4]
Following the primary infection, granulomas may form. Granulomas can be inactive for several years.^[4]
If the infection is active or gets activated, it can spread through lymphatic and hematologic routes to other tissues such as: spleen, kidneys, adrenal glands, liver, bone, central nervous system, and airways.^[1]^[5]
Paracoccidioides spp. have developed different mechanisms to avoid mucus and eradication by cilliary cells.^[6]
The powerful adherence characteristic of the species provides a rapid takeover of host cells and consequently the avoidance of the immune system.^[6]

Genetics

The majority of patients in countries such as Colombia and Brazil, with high prevalence of PCM, had HLA-A9, HLA-B13, and HLA-B4 antigens.^[7]
Chronic PCM is associated with patients that have C4B*-00 antigen of the class III major histocompatibility complex.^[7]

Associated Conditions

Paracoccidiodomycosis has been associated with:

Concomitant infections
- The most important infectious disease that can be found concomitant with PCM is pulmonary tuberculosis (TB). TB can hold up the diagnosis of PCM, because they have similar clinical manifestations. Other infectious diseases associated with PCM because they have the same risk factors are: leishmaniasis, leprosy, Chagas disease and strongyloidiasis.^[7]

Cancer
- The majority of patients with carcinoma and PCM, have the same organ or adjacent tissues involved. A risk factor for carcinoma is chronic inflammation with squamous metaplasia, which has been described in 33% cases of PCM in a study.^[8]

Paracoccidioidomycosis is also considered an opportunistic infection in Latin America. Associated conditions are:

HIV/AIDS:
- Endemic areas of Paracoccidioides spp. in Brazil have the majority of HIV/AIDS patients.^[9] Nevertheless, the incidence of HIV/AIDS and paracoccidioidomycosis is minimum, this may be because the prophylaxis (trimethoprim-sulfamethoxazole) used for Pneumocystis jiroveci is the one of the possible treatments for PCM.^[10]

Cancer:
- The majority of patients have been diagnosed at the same time (40%) or after the neoplasm diagnostic (60%). PCM is highly associated with solid organ and hematologic neoplasias.^[7]
Organ Transplantation:
- PCM has been described in cases of renal transplantation.^[7] The small amount of cases may be because of the use of trimethoprim-sulfamethoxazole as prophylaxis for Pneumocystis jiroveci, which is one of the possible treatments for PCM.^[11]

Carpal Tunnel Syndrome:
- Only seen in Immunosupressed patients.^[12]

Gross Pathology

Granulomas merge and form different shape nodules which can be seen macroscopically in the lungs. With time, the nodules tend to necrose and then cavitate.^[13]

Microscopic Pathology

The most important microscopically characteristic is the “ship’s wheel” or “Mickey mouse ears” appereance^[4]

Histopathology of paracoccidioidomycosis. Budding cells of Paracoccidioides brasiliensis: ships wheel appearance. Methenamine silver stain.^[14]
Histopathology of paracoccidioidomycosis. Budding cells of Paracoccidioides brasiliensis: ships wheel appearance. Methenamine silver stain.^[15]
This is a Lowenstein-Jensen slant culture of the fungus Paracoccidioides brasiliensis grown at 37°C.^[16]

References

↑ ^1.0 ^1.1 ^1.2 ^1.3 Fortes MR, Miot HA, Kurokawa CS, Marques ME, Marques SA (2011). "Immunology of paracoccidioidomycosis". An Bras Dermatol. 86 (3): 516–24. PMID 21738969.
↑ Paracoccidioidomycosis. Wikipedia.https://en.wikipedia.org/wiki/Paracoccidioidomycosis. Accessed on January 12, 2016
↑ Manns B.J, Baylis B.W, Urbanski S.J, Gibb A.P, Rabin H.R. Paracoccidioidomycosis: Case Report and Review. CID. 1996; 23: 1026-1032
↑ ^4.0 ^4.1 ^4.2 ^4.3 ^4.4 Vargas J, Vargas R. Paracoccidiodomicosis. Rev. enferm. infecc. trop.2009(1):49-56
↑ Barreto MM, Marchiori E, Amorim VB, Zanetti G, Takayassu TC, Escuissato DL; et al. (2012). "Thoracic paracoccidioidomycosis: radiographic and CT findings". Radiographics. 32 (1): 71–84. doi:10.1148/rg.321115052. PMID 22236894.
↑ ^6.0 ^6.1 de Oliveira HC, Assato PA, Marcos CM, Scorzoni L, de Paula E Silva AC, Da Silva Jde F; et al. (2015). "Paracoccidioides-host Interaction: An Overview on Recent Advances in the Paracoccidioidomycosis". Front Microbiol. 6: 1319. doi:10.3389/fmicb.2015.01319. PMC 4658449. PMID 26635779.
↑ ^7.0 ^7.1 ^7.2 ^7.3 ^7.4 Martinez, R.Epidemiology of Paracoccidioidomycosis. Rev. Inst. Med. trop. S. Paulo. 2015;57(19), 11-20
↑ Da Silva G, Bittencourt C, De Mattos F, Da Silva J, Prolla J Severo L. Association between paracoccidioidomycosis and cancer. J. bras. pneumol. 2010;36(3), 356-362
↑ Brummer E, Castaneda E, Restrepo A. Paracoccidioidomycosis: An Update. 'Clin. Microbiol. Rev.1993;Vol 6(2):89-117
↑ Amoroso A. A Man With Newly Diagnosed HIV/AIDS With Unusual Severe Opportunistic Infection and No AIDS-Defining Disease. CID. 2014;58:1484-1485
↑ Zavascki A, Bienardt J, Severo L. Paracoccidioidomycosis in organ transplant recipient: case report. Rev. Inst. Med. trop. S. Paulo 2004;46(5), 279-281
↑ Lytkin MI, Petlenko VP (1988). "[A methodological analysis of the theory of traumatic disease]". Voen Med Zh (4): 11–4. PMID 3414040.
↑ Marchiori E, Valiante PM, Mano CM, Zanetti G, Escuissato DL, Souza AS; et al. (2011). "Paracoccidioidomycosis: high-resolution computed tomography-pathologic correlation". Eur J Radiol. 77 (1): 80–4. doi:10.1016/j.ejrad.2009.06.017. PMID 19608361.
↑ Paracoccidioidomycosis. CDC Public Health Image Library (PHIL).http://phil.cdc.gov/phil/details.asp. Accessed on January 20, 2016
↑ Paracoccidioidomycosis. CDC Public Health Image Library (PHIL).http://phil.cdc.gov/phil/details.asp. Accessed on January 20, 2016
↑ Paracoccidioidomycosis. CDC Public Health Image Library (PHIL).http://phil.cdc.gov/phil/details.asp. Accessed on January 20, 2016

[pmid21738969-1] 1.0 ^1.1 ^1.2 ^1.3 Fortes MR, Miot HA, Kurokawa CS, Marques ME, Marques SA (2011). "Immunology of paracoccidioidomycosis". An Bras Dermatol. 86 (3): 516–24. PMID 21738969.

[2] Paracoccidioidomycosis. Wikipedia.https://en.wikipedia.org/wiki/Paracoccidioidomycosis. Accessed on January 12, 2016

[?-3] Manns B.J, Baylis B.W, Urbanski S.J, Gibb A.P, Rabin H.R. Paracoccidioidomycosis: Case Report and Review. CID. 1996; 23: 1026-1032

[paper-4] 4.0 ^4.1 ^4.2 ^4.3 ^4.4 Vargas J, Vargas R. Paracoccidiodomicosis. Rev. enferm. infecc. trop.2009(1):49-56

[pmid22236894-5] Barreto MM, Marchiori E, Amorim VB, Zanetti G, Takayassu TC, Escuissato DL; et al. (2012). "Thoracic paracoccidioidomycosis: radiographic and CT findings". Radiographics. 32 (1): 71–84. doi:10.1148/rg.321115052. PMID 22236894.

[pmid26635779-6] 6.0 ^6.1 de Oliveira HC, Assato PA, Marcos CM, Scorzoni L, de Paula E Silva AC, Da Silva Jde F; et al. (2015). "Paracoccidioides-host Interaction: An Overview on Recent Advances in the Paracoccidioidomycosis". Front Microbiol. 6: 1319. doi:10.3389/fmicb.2015.01319. PMC 4658449. PMID 26635779.

[kkk-7] 7.0 ^7.1 ^7.2 ^7.3 ^7.4 Martinez, R.Epidemiology of Paracoccidioidomycosis. Rev. Inst. Med. trop. S. Paulo. 2015;57(19), 11-20

[ccc-8] Da Silva G, Bittencourt C, De Mattos F, Da Silva J, Prolla J Severo L. Association between paracoccidioidomycosis and cancer. J. bras. pneumol. 2010;36(3), 356-362

[aaa-9] Brummer E, Castaneda E, Restrepo A. Paracoccidioidomycosis: An Update. 'Clin. Microbiol. Rev.1993;Vol 6(2):89-117

[bbb-10] Amoroso A. A Man With Newly Diagnosed HIV/AIDS With Unusual Severe Opportunistic Infection and No AIDS-Defining Disease. CID. 2014;58:1484-1485

[ddd-11] Zavascki A, Bienardt J, Severo L. Paracoccidioidomycosis in organ transplant recipient: case report. Rev. Inst. Med. trop. S. Paulo 2004;46(5), 279-281

[pmid3414040-12] Lytkin MI, Petlenko VP (1988). "[A methodological analysis of the theory of traumatic disease]". Voen Med Zh (4): 11–4. PMID 3414040.

[pmid19608361-13] Marchiori E, Valiante PM, Mano CM, Zanetti G, Escuissato DL, Souza AS; et al. (2011). "Paracoccidioidomycosis: high-resolution computed tomography-pathologic correlation". Eur J Radiol. 77 (1): 80–4. doi:10.1016/j.ejrad.2009.06.017. PMID 19608361.

[14] Paracoccidioidomycosis. CDC Public Health Image Library (PHIL).http://phil.cdc.gov/phil/details.asp. Accessed on January 20, 2016

[15] Paracoccidioidomycosis. CDC Public Health Image Library (PHIL).http://phil.cdc.gov/phil/details.asp. Accessed on January 20, 2016

[16] Paracoccidioidomycosis. CDC Public Health Image Library (PHIL).http://phil.cdc.gov/phil/details.asp. Accessed on January 20, 2016

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