Paracoccidioidomycosis pathophysiology

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]

• 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]

• 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]

• 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]

• 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]

• 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]

• 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]

• 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]