Paracoccidioidomycosis

Paracoccidioidomycosis (PCM) is a systemic fungal infection endemic in South America that, although asymptomatic in most infected patients, may progress to debilitating symptomatic forms. The chronic disease commonly affects adult males and manifest with lung and mucocutaneous lesions.

Epidemiology

PCM represents the most prevalent systemic mycosis in South America and, in particular, in Brazil, where it is estimated to affect about 10% of the population in the endemic regions, particularly in the rural areas ¹. There is a strong male preference of the chronic symptomatic form, with a ratio of 13:1 ^1,2.

Clinical presentation

The primary pulmonary infection is usually self-limited and subclinical, confirmed only by laboratory tests such a positive paracoccidin intradermal test ².

Only about ~2% of the infected patients will manifest the clinical forms ². The clinical disease is divided into two main types:

• acute or juvenile type
  • represents the most severe form, commonly affecting children, adolescents, and young adults, with a course of weeks or months
  • involvement of the reticuloendothelial system, presenting with fever, weight loss, hepatosplenomegaly and lymphadenopathy
  • bone marrow dysfunction and osteolytic lesions are less frequently present
• chronic or adult type
  • represents the majority of cases (>90%) and it usually results from the reactivation of a quiescent lung infection in adulthood
  • the presentation is usually nonspecific and includes a cough, dyspnea, expectoration hemoptysis, weight loss, and fever.
  • mucous oropharyngeal lesions characteristically prompt patients to seek medical attention. These range from bleeding gingivitis, loose of teeth, to painful granulomas involving the lips, tongue, gums, and palate. Granulomatous lesions may also involve the larynx and vocal chords

Pathology

Paracoccidioides brasiliensis is a thermally dimorphic fungus. Microscopically, it shows a characteristic yeastlike appearance with multiple peripheral budding resembling a pilot’s wheel, or, when only two buds around the mother cell, resembling a ‘Mickey Mouse’’ head ². Staining is usually performed with methenamine–silver nitrate (Grocott-Gomori) or periodic acid–Schiff ^1,2.

PCM is acquired by the inhalation of the fungal conidia from free-living mycelial forms, which commonly leads to a self-limited lung infection inciting a predominantly granulomatous tissue reaction, which also shows a less prominent suppurative infiltrates ^1,2. The vast majority of the infected patients will then remain asymptomatic throughout life. Years later, due to a not fully understood mechanism of loss of the immune balance, there is a reactivation of latent pulmonary foci formed during the primary infection and patients progress to the chronic clinic form. Extrapulmonary manifestations occur due to hematogenous spread from the primary pulmonary foci.  

The strong male prevalence is explained by the presence of beta-estradiol membrane receptors in the P. brasiliensis, which inhibits the switch of forms from the conidia-mycelial propagules to the yeast form ².  Postmenopausal women are no longer protected by this mechanism and may also present with the chronic clinical form of the disease.

Treatment and prognosis

P. brasiliensis is a very sensitive fungus and responds to a great range of antifungal drugs. Most mild and moderate clinical forms of PCM are managed with itraconazole or sulfamethoxazole plus trimethoprim and, the severe cases, with amphotericin B ^2,3. 

History and etymology  

The disease was first described by Adolpho Lutz (1855-1940), Brazilian physician, in 1908 ².