Regulatory T cells in cutaneous lesions of patients with Paracoccidioidomycosis

Paracoccidioidomycosis (PCM) is a systemic mycosis caused by the dimorphic fungus Paracoccidioides brasiliensis, with high incidence in Brazil and very significant in Latin America. The disease is clinically classified as acute, subacute or chronic where the primary lesion initiates in the lungs and can spread to other organs such as the skin and mucous membranes. The lesions are characterized by granulomatous formation, organized according to the type of pattern of host immune response. We demonstrated and quantified by immunohistochemistry the expression of Foxp3, CD25, TGF-beta and IL-10 in thirty cutaneous lesions with different presentation of granulomatous response. Cells expressing Foxp3 and CD25 were increased in lesions with compact granulomas. The expression of TGF-beta and IL-10 was similar in all PCM lesions. As previous studies, our data suggest the correlation of Treg cells with the chronicity of the disease and the participation in suppressing mechanism as a possible source of IL-10. TGF-β and IL-10, two important suppressor cytokines, are expressed in great amounts in the lesions but our results do not allow correlating with the differences in the granulomatous response.     

Paracoccidioidomycosis: Diagnosis by fine-needle aspiration cytology

A 4-yr-old girl presented with constitutional symptoms, abdominal swelling, ascites, and cervical lymphadenopathy. Fine-needle aspirate smears of a cervical lymph node revealed numerous round yeasts, many of them with several peripheral buds fitting the pattern of Paracoccidiodes brasilensis. This appears to be the first case in which the diagnosis of this deep mycosis was achieved by FNAC. The procedure may prove useful for rapid diagnosis in cases like the present one which represents the so-called acute disseminated form which affects mainly children and immunosupressed patients and can be rapidly fatal. © 1995 Wiley-Liss, Inc.     

Head and neck manifestations of paracoccidioidomycosis: A retrospective study of histopathologically diagnosed cases in two medical centers in southern Brazil

BackgroundParacoccidoidomycosis (PCM) is a granulomatous systemic mycosis endemic in southern Brazil.ObjectivesAnalyze the clinical and epidemiological characteristics of cases of PCM with head and neck manifestations in southern Brazil.Material and methodsRetrospective study of histopathologically diagnosed cases of PCM with head and neck manifestations referred to two medical centers in the municipality of Santa Cruz do Sul, state of Rio Grande do Sul, Brazil, during a 10-year period (2011–2020).ResultsTwenty-eight patients were selected. The number of cases usually ranged from one to four per year, although 11 cases were diagnosed in 2019. Most patients were between 40 and 59 years old. In total, 21 patients were men and seven were women (male:female ratio 3:1). Most (92%) were Caucasian and 46% were smokers. Patients were from 12 municipalities in the central-eastern region of the state. The most frequent site of the lesions was the larynx. Associated HIV and squamous cell carcinoma were both present in three cases.ConclusionsThis is the first study to analyze PCM cases from central-eastern Rio Grande do Sul. PCM is endemic in southern Brazil, and more epidemiological data are needed, considering that its incidence may be higher than currently estimated, as demonstrated by our results.     

Therapeutic effect of DNA vaccine encoding the 60-kDa-heat shock protein from Paracoccidoides brasiliensis on experimental paracoccidioidomycosis in mice

Paracoccidioidomycosis (PCM) is a systemic mycosis autochthonous to Latin America and endemic to Brazil, which has the majority of the PCM cases. PCM is acquired through the inhalation of propagules of fungi from genus Paracoccidioides spp. and mainly affects the lungs. We have previously shown that P. brasiliensis-infected mice treated with single-dose of recombinant 60-kDa-heat shock protein from P. brasiliensis (rPbHsp60) had a worsening infection in comparison to animals only infected. In this study, we investigate whether the treatment of infected mice with PB_HSP60 gene cloned into a plasmid (pVAX1-PB_HSP60) would result in efficient immune response and better control of the disease. The harmful impact of single-dose therapy with protein was not seen with plasmid preparations. Most importantly, three doses of pVAX1-PB_HSP60 and protein induced a beneficial effect in experimental PCM with a reduction in fungal load and lung injury when compared with infected mice treated with pVAX1 or PBS. The increase of the cytokines IFN-γ, TNF, and IL-17 and the decrease of IL-10 observed after treatment with three doses of pVAX1-PB_HSP60 appears to be responsible for the control of infection. These results open perspectives of the therapeutic use of Hsp60 in PCM.     

Sarcoid-like paracoccidioidomycosis presenting with perineural granuloma

Paracoccidioidomycosis presenting as a sarcoid-like plaque may be misdiagnosed as leprosy, especially when shared endemic areas are concerned. We report the case of a Brazilian male patient presenting with an ulcerated plaque on his left ear and neighboring areas. The plaque simulated tuberculoid leprosy type 1 reaction, both clinically and histopathologically. A perineural granuloma with no organisms detected by routine and Fite-Faraco staining reinforced that diagnosis. Paracoccidioidomycosis was confirmed only after a second biopsy, taken from the ulcerated area.     

Paracoccidioidomycosis: a series of 66 patients with oral lesions from an endemic area

Paracoccidioidomycosis (PCM) is the most important systemic mycosis in Latin America. It has been regarded as a multifocal disease, with oral lesions as the prominent feature. To provide useful information concerning the diagnosis and management of the disease, this study describes demographic and clinical data from the medical records of a consecutive series of 66 Brazilian patients from an endemic area, evaluated in a referral centre for oral diagnosis. In this sample of patients, there was a predominance of middle‐aged male patients, who were primarily rural workers. Chronic multifocal disease was prevalent, with lesions also detected in the lungs, lymph nodes, skin or adrenal glands. Most of the cases presented with lesions at the gingival mucosa followed by the palate and lips; these conditions occurring in the oral cavity were frequently associated with pain. Importantly, most of the patients sought professional care for oral lesions. The diagnosis was obtained through exfoliative cytology and/or biopsy of the oral lesions. Medical treatment was effective, and there were no mortalities in the sample. The present findings not only confirm the importance of oral lesions in the diagnosis and management of PCM but also illustrate that questions still remain unclear, such as the possibility of direct inoculation of the fungus onto oral tissues.     

Paracoccidioidomycosis: cells expressing IL17 and Foxp3 in cutaneous and mucosal lesions

We demonstrated and quantified by immunohistochemistry the population of cells expressing IL17 and Foxp3 in cutaneous and mucosal paracoccidioidomycosis lesions, associating these populations of cells with different presentations of granulomatous response. For this purpose, 61 skin biopsies and 55 oral mucosal biopsies were evaluated. Cells expressing IL17 were distributed in the inflammatory infiltrate in both groups of lesions and were found in the vessels' wall too. Foxp3+ expression was limited to the nuclei of lymphocytes in the inflammatory infiltrate. The distribution of IL17 was similar among the groups; however, Foxp3+ cells were increased in mucosal lesions that displayed compact granulomas. The results suggest that IL17 seems to play a role in paracoccidioidomycosis cutaneous and mucosal lesions, probably as secondary cells in the clearance of the fungal antigens. The presence of Foxp3+ cells both in skin and mucosa corroborates some previous researches that suggest the role of this group of cells in the modulation of local immune response.     

DISSEMINATED FUNGAL INFECTION WITH ADRENAL INVOLVEMENT: REPORT OF TWO HIV NEGATIVE BRAZILIAN PATIENTS

Paracoccidioidomycosis and histoplasmosis are systemic fungal infections endemic inBrazil. Disseminated clinical forms are uncommon in immunocompetent individuals. Wedescribe two HIV-negative patients with disseminated fungal infections,paracoccidioidomycosis and histoplasmosis, who were diagnosed by biopsies ofsuprarenal lesions. Both were treated for a prolonged period with oral antifungalagents, and both showed favorable outcomes.