Paracoccidioidomycosis overview

# Overview
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. 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. On microscopic histopathological analysis, a "pilot's wheel" or a "Mickey mouse ears-like" appearance is a characteristic finding of PCM. 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. Meanwhile, chronic paracoccidioidomycosis represents 90% of infected patients and has a slower progression. Patients with chronic PCM frequently develops pulmonary symptoms. 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. The prognosis of paracoccidioidomycosis is good with adequate treatment. Without treatment, death is due to PCM related complications. 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. 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. 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. Surgical procedures are usually reserved for patients with PCM sequelae. There are no vaccines and no other primary preventive measures available for paracoccidioidomycosis.

# Historical Perspective
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.

# Classification
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.

# 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. On microscopic histopathological analysis, a "pilot's wheel" or a "Mickey mouse ears-like" appearance is a characteristic finding of PCM.

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

# Differential Diagnosis
Acute paracoccidioidomycosis must be differentiated from leukemia, lymphoma, toxoplasmosis and sarcoidosis. Chronic paracoccidioidomycosis must be differentiated from tuberculosis, histoplasmosis and metastasis.

# Epidemiology and Demographics
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. PCM affects men, more commonly than women. However, latent paracoccidioides infection can affect anyone.

# Risk Factors
Common risk factors in the development of paracoccidioidomycosis disease include age, gender, poor hygiene, occupation, malnutrition, tobacco and alcohol consumption.

# Natural History, Complications and Prognosis
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. Meanwhile, chronic paracoccidioidomycosis represents 90% of infected patients and has a slower progression. Patients with chronic PCM frequently develops pulmonary symptoms. 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. The prognosis of paracoccidioidomycosis is good with adequate treatment. Without treatment, death is due to PCM related complications.

# Diagnosis

## History and Symptoms
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.

## Physical Examination
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.

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

## Imaging Findings
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. 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.

# Treatment

## Medical Therapy
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.

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

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