Pathology of the human pulmonary paracoccidioidomycosis

Abstract

Lungs of twelve patients with chronic paracoccidioidomycosis (Pb) were studied in an attempt to understand the pathogenesis of the pulmonary disease. Ribbons of the lung parenchyma including the hilar region and directed towards apical, basal and lateral regions were subdivided into sections from the hilar, intermediate and peripheral segments. The following histopathological reactions directly or indirectly related to P. brasiliensis were described and analysed in relation to the number of slides studied and the pulmonary region involved: pneumonic reaction; early granulomatous formation; mature and healed granulomata; mixed pattern (early and mature granuloma in the same pulmonary area visualized in the slide); pulmonary fibrosis. It was concluded that chronic pulmonary Pb is a recurrent disease affecting equally both lungs. Fibrosis was connected mainly with the progressive evolution of the granulomata towards cicatrization and to a lesser degree probably to a direct induction by the fungi. Based chiefly on the tendency of the fibrosis to run around bronchi and to make up septa interconnecting bronchi and vessels it was hipothesized that these findings were the result of a previous chronic specific lymphangitis by the fungi. Hilar fibrosis would be the result of this lymphangitis and/or of the progression of the specific granulomatous reaction seen in the hilar lymph nodes. Non specific forms of arteritis and areas of destructive emphysema related to granulomatous inflammation and fibrosis were described. Three cases developed pulmonary hypertension.

Differential gene expression analysis of Paracoccidioides brasiliensis during keratinocyte infection

“…The mechanism of internalization in oral keratinocytes, described here for the first time to our knowledge, suggests that this ability may be important in disease development. P. brasiliensis is not essentially an intracellular parasite (Tuder et al, 1985), but epithelial and endothelial cells can be used as a place to escape defence cells, as demonstrated in other diseases (Kumamoto & Vinces, 2005;Qazi et al, 2001;Vázquez-Boland et al, 2001). …”

Pulmonary Paracoccidioidomycosis: Clinical, Immunological and Histopathological Aspects

“…Physical examination reveals few abnormalities even if extensive radiographic alterations are noted. The scarcity of respiratory symptoms explains why patients seek medical consultation based mainly on extrapulmonary manifestations, such as the presence of mucosal and skin lesions (Gomes et al, 2008;Marchiori et al, 2011;Mendes, 1994;Tuder et al, 1985). Besides the lungs, the most frequently compromised organs are the oral mucosa (involving oropharynx and larynx), skin and adrenal glands.…”

“…This is exemplified by the chronic form of the mycosis where the lungs support the most prominent fibrotic changes, a complication recorded in approximately 60% of the patients (Funari et al, 1999;Naranjo et al, 1990;Tobón et al, 1995Tobón et al, , 2003Tuder et al, 1985). The chronic progressive adult form often precedes the establishment of the residual form.…”

“…It is noteworthy that residual lesions do not respond to antifungal treatment. Pulmonary fibrosis is an incapacitating disorder that may lead to core pulmonale and, finally, to death (Tobón et al, 2003;Tuder et al, 1985). In the differential diagnosis of PCM, various diseases including tuberculosis, histoplasmosis, leishmaniasis, malignancies, lymphomatous disorders and certain abdominal syndromes should be considered Nogueira et al, 2006;Ramos & Saraiva, 2008).…”

“…In contrast with idiopathic pulmonary fibrosis (IPF) for which current research indicates that inflammation is of lesser importance with fibrosis appearing primarily as a disorder of fibroblast proliferation and activation in response to an as yet unknown trigger (Meltzer & Noble, 2008), the development of fibrosis in PCM is a progressive event, resulting from a persistent antigenic stimulus leading to chronic inflammation and establishment of fibrosis mainly located in the perihilar region, the main bronchi and their branches, and the large pulmonary vessels . The functional limitation caused by the development of fibrosis may advance toward cor pulmonale, progressive lung incapacity and finally death Tobón et al, 2003;Tuder et al, 1985). The fibrosis process begins with acute injury caused by the interaction of P. brasiliensis conidia with ECM proteins and lung epithelial cells; this interaction is followed by chronic granulomatous inflammation with fibroblast proliferation and activation, an increase in ECM proteins predominantly composed of fibronectin, fibrinogen, collagen type I and III, as observed in the surroundings of the granulomas.…”