Paracoccidioidomycosis

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

Paracoccidioidomycosis (PCM) is a mycosis caused by the fungus Paracoccidioides brasiliensis or Paracoccidioides lutzii. Paracoccidioidomycosis may be classified based on the onset and duration of symptoms. Paracoccidioidomycosis may be classified into acute, subacute or chronic. The chronic form can be further subclassified into unifocal and multifocal.^[1][2] 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.^[2] On microscopic histopathological analysis, a “pilot’s wheel” or a “Mickey mouse ears-like” appearance is a characteristic finding of PCM.^[3][4][5] Among all infected patients 5% are acute with a more rapid and severe progression compared to the chronic subtype. Acute PMC primarily affects the reticuloendothelial system organs.^[6][7] Meanwhile, chronic paracoccidioidomycosis represents 90% of infected patients and has a slower progression. Patients with chronic PCM frequently develops pulmonary symptoms.^[8][9] Complications that can develop as a result of PCM are chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, bullae, pulmonary hypertension, dyspnea, adrenal gland insufficiency, dysphonia, laryngeal lesions (such as glottis estenosis), microstomia, seizures, and motor deficiency.^[7][9][10] The prognosis of paracoccidioidomycosis is good with adequate treatment. Without treatment, death is due to PCM related complications.^[11] Symptoms of acute PCM include high fever, generalized lymphadenopathy and pulmonary involvement with milliary lesions. Symptoms of acute PCM include dry cough, dyspnea and asthenia.^[12] Patients with acute paracoccidioidomycosis usually appear ill. Chronic PCM patients can appear healthy at early stages. Physical examination of patients with juvenile PCM is usually remarkable for lymphadenopathy and hepatosplenomegaly. Adult PCM is characterized by the presence of pulmonary abnormalities and skin lesions.^[8] Pharmacologic medical therapy is indicated in paracoccidioidomycosis. The preferred regimens for both mild and moderate-to-severe include antifungals either azoles (such as itraconazole, ketoconazole, voriconazole) or amphotericin B and antimicrobials such as trimethoprim-sulfamethoxazole.^[13] Surgical procedures are usually reserved for patients with PCM sequelae. There are no vaccines and no other primary preventive measures available for paracoccidioidomycosis.

Paracoccidioidomycosis, also known as Lutz-Splendore-de Almeida disease, is named after Adolfo Lutz, Alfonso Splendore, and Floriano Paulo de Almeida, three physicians who first characterized the disease in Brazil in the early 20th century.^[14]

Paracoccidioidomycosis may be classified based on the onset and duration of symptoms, paracoccidioidomycosis disease may be classified into acute, subacute or chronic. The chronic form can be further subclassified into unifocal and multifocal.^[1][2]

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.^[2] On microscopic histopathological analysis, a “pilot’s wheel” or a “Mickey mouse ears-like” appearance is a characteristic finding of PCM.^[15][4][5]

Paracoccidioidomycosis may be caused by either Paracoccidioides brasiliensis or Paracoccidioides lutzii.

Acute paracoccidioidomycosis must be differentiated from leukemia, lymphoma, toxoplasmosis and sarcoidosis.^[4] Chronic paracoccidioidomycosis must be differentiated from tuberculosis, histoplasmosis and metastasis.^[16]

Paracoccidioidomycosis has been reported as an autochthonous disease, that tends to affect agriculture workers from southern Mexico to northern Argentina. Paracoccidioidomycosis is prevalent in Brazil, Colombia, Venezuela, and Argentina, and is classically associated with individuals from rural areas. The typical patient is a man aged 30 to 50 years.^[17] PCM affects men, more commonly than women. However, latent paracoccidioides infection can affect anyone.^[2]

Common risk factors in the development of paracoccidioidomycosis disease include age, gender, poor hygiene, occupation, malnutrition, tobacco and alcohol consumption.^[1][18]

Among all infected patients 5% are acute with a more rapid and severe progression compared to the chronic subtype. Acute PMC primarily affects the reticuloendothelial system organs.^[6][7] Meanwhile, chronic paracoccidioidomycosis represents 90% of infected patients and has a slower progression. Patients with chronic PCM frequently develops pulmonary symptoms.^[8][9] Complications that can develop as a result of PCM are chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, bullae, pulmonary hypertension, dyspnea, adrenal gland insufficiency, dysphonia, laryngeal lesions (such as glottis estenosis), microstomia, seizures, and motor deficiency.^[7][9][10] The prognosis of paracoccidioidomycosis is good with adequate treatment. Without treatment, death is due to PCM related complications.^[11]

Symptoms of acute PCM include high fever, generalized lymphadenopathy and pulmonary involvement with milliary lesions. Symptoms of acute PCM include dry cough, dyspnea and asthenia.^[12]

Patients with acute paracoccidioidomycosis usually appear ill. Chronic PCM patients can appear healthy at early stages. Physical examination of patients with juvenile PCM is usually remarkable for lymphadenopathy and hepatosplenomegaly. Adult PCM is characterized by the presence of pulmonary abnormalities and skin lesions.^[8]

Laboratory findings consistent with the diagnosis of acute PCM include anemia, Hypergammaglobulinemia, Eosinophilia, Hypoalbuminemia, mild increase in AST and ALT and conjugated hyperbilirubinemia.^[7]

Common chest x-ray findings in chronic PCM include bilateral and symmetric opacities, butterfly wing pattern, architectural distorsion, paracicatricial emphysema and traction bronchiectasis. Chest x-ray finding in acute PCM are characterized by mediastinal and hiliar lymphadenopathy and pleural effusions.^[6] On thoraxic CT scan, chronic paracoccidioidomycosis is characterized by ground-glass attenuation, airspace consolidations, interlobular septal thickening, nodular pattern, fibrotic pattern, cavitary lesions, halo sign and reversed halo sign.^{[6][19][20][21]}

Pharmacologic medical therapy is indicated in paracoccidioidomycosis. The preferred regimens for both mild and moderate-to-severe include antifungals either azoles (such as itraconazole, ketoconazole, voriconazole) or amphotericin B and antimicrobials such as trimethoprim-sulfamethoxazole.^[13]

Surgery is not the first-line treatment option for patients with paracoccidioidomycosis. Different surgical procedures are usually reserved for patients with PCM sequelae.

There are no vaccines and no other primary preventive measures available for paracoccidioidomycosis.

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

Paracoccidioidomycosis, also known as Lutz-Splendore-de Almeida disease, is named after Adolfo Lutz, Alfonso Splendore, and Floriano Paulo de Almeida, three physicians who first characterized the disease in Brazil in the early 20th century.^[1]

• Adolfo Lutz, a Brazilian physician, first discovered Paracoccidioides brasiliensis in 1908.
• In 1912, another Brazilian physician, Luigi Splendore, described the fungus and changed its name to Zimonema brasiliense.
• In 1930, Floriano de Almeida created the genus Paracoccidioides, noting significant differences from the Coccidioides genus.^[2]

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

Paracoccidioidomycosis may be classified based on the onset and duration of symptoms. Paracoccidioidomycosis may be classified into: acute, subacute or chronic. The chronic form can be further subclassified into: unifocal and multifocal.^[1][2]

• Patients have no clinical manifestations
• Positive reaction to the paracoccidioidin skin test

• Acute form (Juvenile)
  • Usually affects patients under 35 years
• Chronic form (Adult)
  • Unifocal: Affects one organ or system
  • Multifocal: Affects two or more organs or systems

• Most frequently, chronic pulmonary obstructive disease

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

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]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Paracoccidioidomycosis (PCM) is a mycosis caused by the fungus Paracoccidioides brasiliensis or Paracoccidioides lutzii

Paracoccidioides brasiliensis was first discovered by Adolfo Lutz in 1908 in Brazil.^[1] Although Lutz did not suggest a name for the disease caused by this fungus, he made note of structures he called “pseudococcidica” together with mycelium in cultures grown at 25°C.^[1] In 1912, Alfonse Splendore^[2] proposed the name Zymonema brasiliense and described the features of the fungus in culture.^[1] Finally in 1930, Floriano de Almeida created the genus Paracoccidioides to accommodate the species, noting its distinction from Coccidioides immitis.^[1]

Paracoccidioides brasiliensis is a nonphotosynthetic eukaryote with a rigid cell wall and organelles very similar to those of higher eukaryotes.^[3][4] Being a dimorphic fungus, it has the ability to grow an oval yeast-like form at 37°C and an elongated mycelial form produced at room temperature.^[5] The mycelial and yeast phases differ in their morphology, biochemistry, and ultrastructure.^[4] The yeast form contains large amounts of α-(1,3)-linked glucan.^[6][7] The chitin content of the mycelial form is greater than that of the yeast form, but the lipid content of both phases is comparable.^[6] The yeast reproduces by asexual budding, where daughter cells are borne asynchronously at multiple, random positions across the cell surface. Buds begin by layers of cell wall increasing in optical density at a point that eventually gives rise to the daughter cell.^[3] Once the bud has expanded, a cleavage plane develops between the nascent cell and the mother cell. Following dehiscence, the bud scar disappears.^[4] In tissue, budding occurs inside the granulomatous center of the disease lesion, as visualized by hematoxylin and eosin (H&E) staining of histologic sections.^[6] Nonbudding cells measure 5–15 µm in diameter, whereas those with multiple spherical buds measure from 10–20 µm in diameter.^[6] In electron microscopy, cells with multiple buds have been found to have peripherally located nuclei and cytoplasm surrounding a large central vacuole.^[8] In the tissue form of P. brasiliensis, yeast cells are larger with thinner walls and a narrower bud base than those of the related dimorphic fungus, Blastomycosis dermatitidis.^[6] The yeast-like form of P. brasiliensis contains multiple nuclei, a porous two-layered nuclear membrane, and a thick cell wall rich in fibers, whereas the mycelial phase has thinner cell walls with a thin, electron-dense outer layer.^[4]

The yeast form of P. brasiliensis can be converted to the mycelial form in vitro by growth on brain heart infusion agar or blood-glucose-cysteine agar when incubated for 10–20 days at 37°C.^[6] Under these conditions, hyphal cells either die or convert to transitional forms measuring 6–30 µm in diameter, which ultimately detach or remain on the hyphal cells, yielding buds.^[6] New buds develop mesosomes and become multinucleated.^[6] In contrast, yeast-like cultures can be converted to the mycelial form by reducing the incubation temperature from 37 to 25°C.^[9] Initially it, nutritional requirements of both the yeast and mycelial phases of P. brasiliensis were thought to be identical;^[10] however, later studies demonstrated the yeast form to be auxotrophic, requiring exogenous sulfur-containing amino acids including cysteine and methionine for growth.^[11]

Although the habitat of P. brasiliensis remains unknown, it is commonly associated with soils in which coffee is cultivated.^[12]>^[13][14] It has also been associated with the nine-banded armadillo, Dasypus novemcinctus.^[15] The disease caused by P. brasiliensis is mostly geographically restricted to Latin American countries such as Brazil, Colombia, and Venezuela, with the greatest number of cases seen in Brazil.^[6] The endemic areas are characterized by hot, humid summers, dry temperate winters, average annual temperatures between 17 and 23°C, and annual rainfall between 500 and 800 mm.^[16] However, the precise ecology regularities of the fungus remain elusive, and P. brasiliensis has rarely been encountered in nature outside the human host.^[3] One such rare example of environmental isolation was reported in 1971 by Maria B.de Albornoz and colleagues who isolated P. brasiliensis from samples of rural soil collected in Paracotos in the state of Miranda, Venezuela.^[17] In in vitro studies, the fungus has been shown to grow when inoculated into soil and sterile horse or cow excrement.^[18] The mycelial phase has also been shown to survive longer than the yeast phase in acidic soil.^[19] Despite a sexual state not having been documented, molecular investigations suggest the existence of recombining populations of P. brasiliensis, potentially by means of an undiscovered sexual state.^[20]

P. brasiliensis causes a disease known as paracoccidioidomycosis characterized by slow, progressive granulomatous changes in the head mucosa, notably the nose and sinuses or the skin. Uncommonly, the disease affects the lymphatic system, the central nervous system, the gastrointestinal tract, or the skeletal system.^[6] Due to the high proportion of cases affecting the oral mucosa, these tissues were originally thought to be the primary route of entry of fungus.^[3] However, strong evidence now indicates the respiratory tract is the chief point of entry^[6] and P. brasiliensis lung lesions occur in nearly a third of progressive cases.^[21] The disease is not contagious.^[6] Paracoccidioidomycosis is more frequently seen in adult males than females.^[6][22] The hormone estrogen is thought to inhibit the transformation of the mycelial to the yeast form, as supported by in vitro experimental data, and this factor may account for the relative resistance of women to infection.^[23]

A number of serologic tests have been employed for the diagnosis of paracoccidioidomycosis.^[6] Double diffusion in agar gel and complement fixation test, are amongst the most commonly used tests in serodiagnosis.^[6] Culture extracts of the yeast or mycelia are exploited to produce effective, quick, and reproducible antigens.^[6][24] A study reported detection of 43 kD antigen in pooled sera of affected individuals, which might provide a basis for the development of a diagnostic test.^[25] Tests targeting the presence of serum antibodies to P. brasiliensis simultaneously detect both active and historical infections and cannot descriminate active infection. The evaluation of populations in endemic zones has shown roughly equal rates of seroconversion between men and women, suggesting equal rates of exposure, despite the strong male predominance shown by the clinical disease.^[6]

P. brasiliensis causes mucous membrane ulceration of the mouth and nose with spreading through the lymphatic system. A hypothesis for entry of the fungus to the body is through periodontal membrane.^[26][27] The route of infection is assumed to be inhalation following which the infective propagule gives rise to the distinctive multipolar budding yeast forms in the lung resembling a “ship’s wheel” seen in histological sections.^[5][28] Both immunologically normal and compromised people are at risk for infection.^[5] The lungs, lymph nodes, and mucous membrane of the mouth are the most frequently infected tissues.^[6] The pathological features of paracoccidioidomycosis are similar to those seen in coccidioidomycosis and blastomycosis.^[29] However in the former, the lesions first appear in the lymphoid tissue and then extend to mucous membranes,^[29] producing localized to diffusive tissue necrosis of the lymph nodes.^[29] The typically extensive involvement of lymphoid tissue and the limited occurrence of the gastrointestinal tract, bone and prostate set the clinical picture of paracoccidioidomycosis apart from that of blastomycosis.^[6][29]

• 
  Fungal infection of the face affecting his right eye, upper lip, nares, and tongue. Brazilian blastomycosis, is caused by the fungal organism, Paracoccidioides brasiliensis. From Public Health Image Library (PHIL). ^[30]
• 
  Slant culture growing the fungus Paracoccidioides brasiliensis during its yeast phase. From Public Health Image Library (PHIL). ^[30]
• 
  Photomicrograph depicts budding cells of the fungus Paracoccidioides brasiliensis during its yeast phase.. From Public Health Image Library (PHIL). ^[30]
• 
  Photomicrograph depicts budding cells of the fungus Paracoccidioides brasiliensis during its yeast phase.. From Public Health Image Library (PHIL). ^[30]

• Paracoccidioides at the US National Library of Medicine Medical Subject Headings (MeSH)
• http://botit.botany.wisc.edu/toms_fungi/jan2005.html

Template:Mycoses

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

Acute paracoccidioidomycosis must be differentiated from leukemia, lymphoma, toxoplasmosis and sarcoidosis.^[1] Chronic paracoccidioidomycosis must be differentiated from tuberculosis, histoplasmosis and metastasis.^[2]

• Lymphoma
• Leukemia
• Toxoplasmosis
• Sarcoidosis

• Tuberculosis
• Leishmaniasis
• Histoplasmosis
• Coccidioidomycosis
• Cryptococcosis
• Actinomycosis
• Sporotrichosis
• Chromoblastomycosis
• Squamous cell carcinoma
• Metastasis
• Wegener’s granulomatosis

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

Paracoccidioidomycosis has been reported as an autochthonous disease, that tends to affect agriculture workers from southern Mexico to northern Argentina. Paracoccidioidomycosis is prevalent in Brazil, Colombia, Venezuela, and Argentina, and is classically associated with individuals from rural areas. The typical patient is a man aged 30 to 50 years.^[1] PCM affects men, more commonly than women. However, latent Paracoccidioides infection can affect anyone.^[2]

• It is difficult to establish the true prevalence and incidence of paracoccidioidomycosis because disease reporting is not always required.

• In endemic areas, the prevalence of paracoccidioidomycosis may be as high as 1 in 9 people.^[3]

• In endemic areas, the incidence of paracoccidioidomycosis is estimated to be 1-3 per 100,000 persons.^[4]

• In endemic areas, the mortality rate of paracoccidioidomycosis is estimated to be 0.14 deaths per 100,000 population.^[4]

• Paracoccidioidomycosis most commonly affects individuals 30 to 60 years old.^[5]
• Paracoccidioidomycosis is rarely diagnosed in children (3%) and young adults (10%).^[3]

• Men are more commonly affected with paracoccidioidomycosis than women.
• This could be a result of the protection that estrogen imparts in women.^[2]
• The male to female ratio is approximately 13 to 1.^[3][6]

• There is no racial predilection for paracoccidioidomycosis.^[4]

• Cases have been reported in non-endemic areas among patients who have traveled or lived in Central or South America.^[7]

• Paracoccidiodomycosis is an endemic disease that tends to affect agriculture workers in South and Central America, from southern Mexico to northern Argentina.^[8]
• No cases have been reported from Belize and Nicaragua in Central America, or from Chile, French Guiana, Guiana, and Suriname in South America.^[8]
• The countries with the greatest number of patients are: Argentina, Brazil, Colombia and Venezuela.^[7]
• The greatest number of cases have been reported in Brazil.
  • Approximately 80% of PCM cases have been reported in Brazil^[7]

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

Common risk factors in the development of paracoccidioidomycosis disease include: age, gender, poor hygiene, occupation, malnutrition, tabacco and alcohol consumption.^[1][2]

Common risk factors in the development of paracoccidioidomycosis disease are:

• Only 5% of all paracoccidioidomycosis cases are among children and young adults from 6-16 years.^[3] The majority of cases affect men from 30-60 years.^[4]

• Men have a higher incidence than women. Paracoccidioides spp. has 17-b estradiol receptor, this feminine hormone inhibits the fungus transformation from mycelial to yeast, which is necessary for the infections evolution.^[4]

• Rural labor such as agriculture or breeders. Paracoccidioides spp. is know to be found in soil and cattle.^[4]

• Paracoccidioidomycosis can act as an opportunistic infection in endemic areas.^[5] Some studies suggest that malnutrition is not only a risk factor, it also is due to the disease.^[6]

• Tobacco alters the mucociliary activity, decreases immunity and diminishes the reaction of macrophages; therefore it eases the development of the infection.^[2]

• Alcohol is thought to be a risk factor. However the associated about the alcohol consumption and PCM is unconfirmed and could be confunded by with smoking.^[2]

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

Among all infected patients 5% are acute with a more rapid and severe progression compared to the chronic subtype. Acute PMC primarily affects the reticuloendothelial system organs.^[1][2] Meanwhile, chronic paracoccidioidomycosis represents 90% of infected patients and has a slower progression. Patients with chronic PCM frequently develops pulmonary symptoms.^[3][4] Complications that can develop as a result of PCM are chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, bullae, pulmonary hypertension, dyspnea, adrenal gland insufficiency, dysphonia, laryngeal lesions (such as glottis estenosis), microstomia, seizures, and motor deficiency.^[2][4][5] The prognosis of paracoccidioidomycosis is good with adequate treatment. Without treatment, death is due to PCM related complications.^[6]

• Latent paracoccidioides infection can be adquired in the first decade of life.
• Patienes with latent PCM infection do not manifest symptoms.^[7]

• Acute PCM occurs in children and young adults. It constitutes only 3-5% of PCM disease.^[1]
• Symptoms take place weeks or months after the transmission.^[1]
• The reticuloendothelial system organs and gastrointestinal tract are usually involved at this stage of the disease.^[1]
• Acute PCM starts with nonspecific symptoms such as fever, weight loss, weakness, anorexia, pallor, etc.
• Patients may also report swollen lymph nodes in different body regions (cervical, axilar, paravertebral and retroperitoneal ganglia). Digestive, osteoarticular and cutaneous signs and symptoms may also be present.
• Pulmonary manifestations in the acute for are rare.^[3]

• Chronic paracoccidioidomycosis represents 90% of the disease.
• The symptoms of chronic PCM usually start to progress in the third decade of life, even though the organism can be acquired in the first decade of life.^[3]
• The symptoms of paracoccidioidomycosis typically develop 20-30 years after exposure to Paracoccidioides spp.
• PCM symptoms develop slowly through the years.
• Patients develop pulmonary symptoms (90%), with or without nonespecific symptoms. Nevertheless, other symptoms can occur such as cutaneous or mucosal lesions (51-82%).^[7][8]
• Paracoccidioides can enter the bloodstream and disseminate to CNS and cause neuroparacoccidioidomycosis.^[9]

• Bone marrow failure

• Chronic obstructive pulmonary disease (COPD)
• Pulmonary fibrosis
• Bullae
• Pulmonary hypertension
• Dyspnea
• Adrenal gland insufficiency
• Dysphonia
• Laryngeal lesions (such as glottis estenosis)
• Microstomia
• Seizures
• Motor deficiency^[2][4][5]

• The prognosis varies with the type of infection; chronic PCM have the most favorable prognosis with adequate treatment.
• Juvenile PCM has higher mortality rates than adult PCM.^[2]
• Deaths can occur because of late diagnosis, dissemination of the disease (multifocal) or development of complications.^[6]