Pulmonary Paracoccidioidomycosis Research Articles

Depletion of Neutrophils Exacerbates the Early Inflammatory Immune Response in Lungs of Mice Infected with Paracoccidioides brasiliensis.

Neutrophils predominate during the acute phase of the Paracoccidioides brasiliensis infection. Herein, we determined the role of the neutrophil during the early stages of experimental pulmonary paracoccidioidomycosis using a monoclonal antibody (mAb) specific for neutrophils. Male BALB/c mice were inoculated intranasally with 1.5 × 106 or 2 × 106 P. brasiliensis yeast cells. The mAb was administered 24 h before infection, followed by doses every 48 h until mice were sacrificed. Survival time was evaluated and mice were sacrificed at 48 h and 96 h after inoculation to assess cellularity, fungal load, cytokine/chemokine levels, and histopathological analysis. Neutrophils from mAb-treated mice were efficiently depleted (99.04%). Eighty percent of the mice treated with the mAb and infected with 1.5 × 106 yeast cells died during the first two weeks after infection. When mice were treated and infected with 2 × 106 yeast cells, 100% of them succumbed by the first week after infection. During the acute inflammatory response significant increases in numbers of eosinophils, fungal load and levels of proinflammatory cytokines/chemokines were observed in the mAb-treated mice. We also confirmed that neutrophils are an important source of IFN-γ and IL-17. These results indicate that neutrophils are essential for protection as well as being important for regulating the early inflammatory immune response in experimental pulmonary paracoccidioidomycosis.

Loss- and Gain-of-Function Approaches Indicate a Dual Role Exerted by Regulatory T Cells in Pulmonary Paracoccidioidomycosis.

Paracoccidioidomycosis (PCM), is a pulmonary fungal disease whose severity depends on the adequate development of T cell immunity. Although regulatory T (Treg) cells were shown to control immunity against PCM, deleterious or protective effects were described in different experimental settings. To clarify the function of Treg cells in pulmonary PCM, loss-and gain-of-function approaches were performed with Foxp3GFP knock-in mice and immunodeficient Rag1-/- mice, respectively, which were intratracheally infected with 106 yeast cells. The activity of Foxp3-expressing Treg cells in pulmonary PCM was determined in Foxp3GFP transgenic mice. First, it was verified that natural Treg cells migrate to the lungs of infected mice, where they become activated. Depletion of Treg cells led to reduced fungal load, diminished pathogen dissemination and increased Th1/Th2/Th17 immunity. Further, adoptive transfer of diverse T cell subsets to Rag1-/- mice subsequently infected by the pulmonary route demonstrated that isolated CD4+Foxp3+ Treg cells were able to confer some degree of immunoprotection and that CD4+Foxp3- T cells alone reduced fungal growth and enhanced T cell immunity, but induced vigorous inflammatory reactions in the lungs. Nevertheless, transfer of Treg cells combined with CD4+Foxp3- T cells generated more efficient and balanced immune Th1/Th2/Th17 responses able to limit pathogen growth and excessive tissue inflammation, leading to regressive disease and increased survival rates. Altogether, these loss- and gain-of-function approaches allow us to clearly demonstrate the dual role of Treg cells in pulmonary PCM, their deleterious effects by impairing T cell immunity and pathogen eradication, and their protective role by suppressing exacerbated tissue inflammation.

CT morphological features of the reversed halo sign in pulmonary paracoccidioidomycosis.

The purpose of this study was to identify morphological characteristics of the reversed halo sign (RHS) on chest CT in patients with pulmonary paracoccidioidomycosis (PCM) that may aid the diagnosis of this fungal disease. We retrospectively reviewed chest CT images from 23 patients with proven pulmonary PCM who demonstrated the RHS. Two chest radiologists analysed the morphological characteristics of the lesions and reached decisions by consensus. We identified 64 RHSs on CT images from the 23 patients. Multiple lesions were observed in all cases, with middle and lower lung zone predominance occurring in 17 patients (73.9% of cases). 34 (53.1%) RHSs were round and 30 (46.9%) were oval. Outer borders of the RHSs were smooth in 32 (50%) lesions, nodular in 16 (25%) lesions and irregular/spiculated in 16 (25%) lesions. Ground-glass opacity was observed inside 63 (98.4%) lesions. Our data suggest that morphological characteristics of the RHS on chest CT, such as the presence of multiple lesions, middle and lower lung zone predominance and a spiculated RHS ring, as well as the association with other parenchymal patterns, should lead radiologists to include PCM in the differential diagnosis of PCM in endemic areas. This is the largest series of patients with RHS due to PCM and is also the first study to report RHS lesions with spiculated or irregular walls. The study adds information regarding morphological characteristics of the RHS that may raise suspicion of PCM on chest CT, particularly in endemic areas of the disease.

Pentoxifylline immunomodulation in the treatment of experimental chronic pulmonary paracoccidioidomycosis.

BackgroundPentoxifylline (PTX) is a methylxanthine compound with immunomodulatory and antifibrotic properties. The simultaneous use of PTX and antifungal therapy (itraconazole) has previously been evaluated in an experimental model of pulmonary paracoccidioidomycosis (PCM), a systemic fungal disease caused by the fungus Paracoccidioides brasiliensis (Pb) and characterized by chronic inflammation and lung fibrosis that appears even after a successful course of antifungal therapy. The results revealed prompt and statistically significant reductions in inflammation and fibrosis when compared to itraconazole alone. However, the effect of monotherapy with PTX on the host response to PCM has not been well-documented. Our aim was to determine the effect of PTX on the course of pulmonary lesions and on the local immune response.ResultsAt the middle and end of treatment, the Pb-infected-PTX-treated mice exhibited significant reductions in lung density compared to the Pb-infected-non-treated mice as assessed by the quantification of Hounsfield units on high-resolution computed tomography (HRCT) (p <0.05 by Kruskal-Wallis test); additionally, at the end of therapy, the lung areas involved in the inflammatory reactions were only 3 vs. 22 %, respectively, by histomorphometry (p <0.05 by Mann–Whitney test), and this reduction was associated with a lower fungal burden and limited collagen increment in the pulmonary lesions. PTX treatment restored the levels of IFN-γ, MIP-1β, and IL-3 that had been down-regulated by Pb infection. Additionally, IL-12p70, IL-10, IL-13, and eotaxin were significantly increased, whereas Regulated upon Activation, Normal T cell Expressed and Secreted (RANTES) levels were decreased in the lungs of the Pb-infected-PTX-treated mice compared to the non-treated group.Conclusions/significanceThis study showed that PTX therapy administered at an “early” stage of granulomatous inflammation controlled the progress of the PCM by diminishing the pulmonary inflammation and the fungal burden and avoiding the appearance of collagen deposits in the pulmonary lesions.

Computed tomography findings of paracoccidiodomycosis in musculoskeletal system.

ObjectiveTo evaluate musculoskeletal involvement in paracoccidioidomycosis at computed tomography.Materials and MethodsDevelopment of a retrospective study based on a review of radiologic and pathologic reports in the institution database. Patients with histopathologically confirmed musculoskeletal paracoccidioidomycosis and submitted to computed tomography were included in the present study. The imaging findings were consensually described by two radiologists. In order to avoid bias in the analysis, one patient with uncountable bone lesions was excluded from the study.ResultsA total of seven patients were included in the present study. A total of 18 bone lesions were counted. The study group consisted of 7 patients. A total number of 18 bone lesions were counted. Osteoarticular lesions were the first manifestation of the disease in four patients (57.14%). Bone lesions were multiple in 42.85% of patients. Appendicular and axial skeleton were affected in 85.71% and 42.85% of cases, respectively. Bone involvement was characterized by well-demarcated osteolytic lesions. Marginal osteosclerosis was identified in 72.22% of the lesions, while lamellar periosteal reaction and soft tissue component were present in 5.55% of them. One patient showed multiple small lesions with bone sequestra.ConclusionParacoccidioidomycosis can be included in the differential diagnosis of either single or multiple osteolytic lesions in young patients even in the absence of a previous diagnosis of pulmonary or visceral paracoccidioidomycosis

Lipoxin Inhibits Fungal Uptake by Macrophages and Reduces the Severity of Acute Pulmonary Infection Caused by Paracoccidioides brasiliensis.

Cysteinyl leukotrienes (CysLTs) and lipoxins (LXs) are lipid mediators that control inflammation, with the former inducing and the latter inhibiting this process. Because the role played by these mediators in paracoccidioidomycosis was not investigated, we aimed to characterize the role of CysLT in the pulmonary infection developed by resistant (A/J) and susceptible (B10.A) mice. 48 h after infection, elevated levels of pulmonary LTC4 and LXA4 were produced by both mouse strains, but higher levels were found in the lungs of susceptible mice. Blocking the CysLTs receptor by MTL reduced fungal loads in B10.A, but not in A/J mice. In susceptible mice, MLT treatment led to reduced influx of PMN leukocytes, increased recruitment of monocytes, predominant synthesis of anti-inflammatory cytokines, and augmented expression of 5- and 15-lipoxygenase mRNA, suggesting a prevalent LXA4 activity. In agreement, MTL-treated macrophages showed reduced fungal burdens associated with decreased ingestion of fungal cells. Furthermore, the addition of exogenous LX reduced, and the specific blockade of the LX receptor increased the fungal loads of B10.A macrophages. This study showed for the first time that inhibition of CysLTs signaling results in less severe pulmonary paracoccidioidomycosis that occurs in parallel with elevated LX activity and reduced infection of macrophages.

Indoleamine 2,3-dioxygenase controls fungal loads and immunity in Paracoccidioidomicosis but is more important to susceptible than resistant hosts.

BackgroundParacoccidioidomycosis, a primary fungal infection restricted to Latin America, is acquired by inhalation of fungal particles. The immunoregulatory mechanisms that control the severe and mild forms of paracoccidioidomycosis are still unclear. Indoleamine 2,3-dioxygenase (IDO), an IFN-γ induced enzyme that catalyzes tryptophan metabolism, can control host-pathogen interaction by inhibiting pathogen growth, T cell immunity and tissue inflammation.Methodology/Principal FindingsIn this study, we investigated the role of IDO in pulmonary paracoccidioidomycosis of susceptible and resistant mice. IDO was blocked by 1-methyl-dl-tryptophan (1MT), and fungal infection studied in vitro and in vivo. Paracoccidioides brasiliensis infection was more severe in 1MT treated than untreated macrophages of resistant and susceptible mice, concurrently with decreased production of kynurenines and IDO mRNA. Similar results were observed in the pulmonary infection. Independent of the host genetic pattern, IDO inhibition reduced fungal clearance but enhanced T cell immunity. The early IDO inhibition resulted in increased differentiation of dendritic and Th17 cells, accompanied by reduced responses of Th1 and Treg cells. Despite these equivalent biological effects, only in susceptible mice the temporary IDO blockade caused sustained fungal growth, increased tissue pathology and mortality rates. In contrast, resistant mice were able to recover the transitory IDO blockade by the late control of fungal burdens without enhanced tissue pathology.Conclusions/SignificanceOur studies demonstrate for the first time that in pulmonary paracoccidioidomycosis, IDO is an important immunoregulatory enzyme that promotes fungal clearance and inhibits T cell immunity and inflammation, with prominent importance to susceptible hosts. In fact, only in the susceptible background IDO inhibition resulted in uncontrolled tissue pathology and mortality rates. Our findings open new perspectives to understand the immunopathology of paracoccidioidomycosis, and suggest that an insufficient IDO activity could be associated with the severe cases of human PCM characterized by inefficient fungal clearance and excessive inflammation.

Dectin-1 Induces M1 Macrophages and Prominent Expansion of CD8+IL-17+ Cells in Pulmonary Paracoccidioidomycosis

Dectin-1, the innate immune receptor that recognizes β-glucan, plays an important role in immunity against fungal pathogens. Paracoccidioides brasiliensis, the etiological agent of paracoccidioidomycosis, has a sugar-rich cell wall mainly composed of mannans and glucans. This fact motivated us to use dectin-1-sufficient and -deficient mice to investigate the role of β-glucan recognition in the immunity against pulmonary paracoccidioidomycosis. Initially, we verified that P. brasiliensis infection reinforced the tendency of dectin-1-deficient macrophages to express an M2 phenotype. This prevalent antiinflammatory activity of dectin-1(-/-) macrophages resulted in impaired fungicidal ability, low nitric oxide production, and elevated synthesis of interleukin 10 (IL-10). Compared with dectin-1-sufficient mice, the fungal infection of dectin-1(-/-) mice was more severe and resulted in enhanced tissue pathology and mortality rates. The absence of dectin-1 has also impaired the production of T-helper type 1 (Th1), Th2, and Th17 cytokines and the activation and migration of T cells to the site of infection. Remarkably, dectin-1 deficiency increased the expansion of regulatory T cells and reduced the differentiation of T cells to the IL-17(+) phenotype, impairing the migration of IL-17(+)CD8(+) T cells and polymorphonuclear cells to infected tissues. In conclusion, dectin-1 exerts an important protective role in pulmonary paracoccidioidomycosis by controlling the innate and adaptive phases of antifungal immunity.

Central Nervous System Paracoccidioidomycosis in an AIDS Patient: Case Report

Up to now, over 200 patients with paracoccidioidomycosis (PCM) associated to HIV infection have already been reported; however, the central nervous system involvement in this coinfection was rarely reported. This paper presents a 35-year-old Brazilian male AIDS patient who developed pulmonary PCM successfully treated with itraconazole. At the antiretroviral therapy starting, he had 32 CD4(+) T cells baseline count and high viral load levels. After 9 months, he presented severe fungal meningoencephalitis diagnosed by sublenticular enhanced nodular lesion at computerized tomography and magnetic resonance brain imaging and a positive Paracoccidiodes brasiliensis smear and culture from cerebrospinal fluid. At the time, a sixfold increase in CD4(+) T cell count and undetectable viral load level were evidenced. The patient received amphotericin B during 1 year presenting slow but progressive clinical improvement, and he is currently asymptomatic and without neurological disabilities. To our knowledge, this is the second case report of a patient with neuroparacoccidioidomycosis associated to HIV infection.

In Pulmonary Paracoccidioidomycosis IL-10 Deficiency Leads to Increased Immunity and Regressive Infection without Enhancing Tissue Pathology

BackgroundCellular immunity is the main defense mechanism in paracoccidioidomycosis (PCM), the most important systemic mycosis in Latin America. Th1 immunity and IFN-γ activated macrophages are fundamental to immunoprotection that is antagonized by IL-10, an anti-inflammatory cytokine. Both in human and experimental PCM, several evidences indicate that the suppressive effect of IL-10 causes detrimental effects to infected hosts. Because direct studies have not been performed, this study was aimed to characterize the function of IL-10 in pulmonary PCM.Methodology/Principal FindingsWild type (WT) and IL-10−/− C57BL/6 mice were used to characterize the role of IL-10 in the innate and adaptive immunity against Paracoccidioides brasiliensis (Pb) infection. We verified that Pb-infected peritoneal macrophages from IL-10−/− mice presented higher phagocytic and fungicidal activities than WT macrophages, and these activities were associated with elevated production of IFN-γ, TNF-α, nitric oxide (NO) and MCP-1. For in vivo studies, IL-10−/− and WT mice were i.t. infected with 1×106 Pb yeasts and studied at several post-infection periods. Compared to WT mice, IL-10−/− mice showed increased resistance to P. brasiliensis infection as determined by the progressive control of pulmonary fungal loads and total clearance of fungal cells from dissemination organs. This behavior was accompanied by enhanced delayed-type hypersensitivity reactions, precocious humoral immunity and controlled tissue pathology resulting in increased survival times. In addition, IL-10−/− mice developed precocious T cell immunity mediated by increased numbers of lung infiltrating effector/memory CD4+ and CD8+ T cells. The inflammatory reactions and the production of Th1/Th2/Th17 cytokines were reduced at late phases of infection, paralleling the regressive infection of IL-10−/− mice.Conclusions/SignificanceOur work demonstrates for the first time that IL-10 plays a detrimental effect to pulmonary PCM due to its suppressive effect on the innate and adaptive immunity resulting in progressive infection and precocious mortality of infected hosts.

TNF-α and CD8+ T cells mediate the beneficial effects of nitric oxide synthase-2 deficiency in pulmonary paracoccidioidomycosis.

BackgroundNitric oxide (NO), a key antimicrobial molecule, was previously shown to exert a dual role in paracoccidioidomycosis, an endemic fungal infection in Latin America. In the intravenous and peritoneal models of infection, NO production was associated with efficient fungal clearance but also with non-organized granulomatous lesions. Because paracoccidioidomycosis is a pulmonary infection, we aimed to characterize the role of NO in a pulmonary model of infection.Methodology/Principal FindingsC57Bl/6 wild type (WT) and iNOS−/− mice were i.t. infected with 1×106 Paracoccidioides brasiliensis yeasts and studied at several post-infection periods. Unexpectedly, at week 2 of infection, iNOS−/− mice showed decreased pulmonary fungal burdens associated with an M2-like macrophage profile, which expressed high levels of TGF-β impaired ability of ingesting fungal cells. This early decreased fungal loads were concomitant with increased DTH reactions, enhanced TNF-α synthesis and intense migration of activated macrophages, CD4+ and CD8+ T cells into the lungs. By week 10, iNOS−/− mice showed increased fungal burdens circumscribed, however, by compact granulomas containing elevated numbers of activated CD4+ T cells. Importantly, the enhanced immunological reactivity of iNOS−/− mice resulted in decreased mortality rates. In both mouse strains, depletion of TNF-α led to non-organized lesions and excessive influx of inflammatory cells into the lungs, but only the iNOS−/− mice showed increased mortality rates. In addition, depletion of CD8+ cells abolished the increased migration of inflammatory cells and decreased the number of TNF-α and IFN-γ CD4+ and CD8+ T cells into the lungs of iNOS−/− mice.Conclusions/SignificanceOur study demonstrated that NO plays a deleterious role in pulmonary paracoccidioidomycosis due to its suppressive action on TNF-α production, T cell immunity and organization of lesions resulting in precocious mortality of mice. It was also revealed that uncontrolled fungal growth can be overcome by an efficient immune response.

Nanobiotechnological Approaches to Delivery of DNA Vaccine Against Fungal Infection

Vaccines play an essential role in keeping humans healthy. Innovative approaches to their use include the utilization of plasmid DNA encoding sequences to express foreign antigens. DNAhsp65 from Mycobacterium leprae is suitable for this purpose due to its ability to elicit a powerful immune response. Controlled release systems represent a promising approach to delivering vaccines. In this work, we used liposomes or PLGA systems to deliver DNAhsp65 to treat the pulmonary fungal infection Paracoccidioidomycosis. Both formulations modulated a protective immune response and reduced the pulmonary fungal burden even in the groups receiving less than four times the amount of the DNAhps65 entrapped within the nanoparticles. Although both systems had the same effective therapeutic results, the advantage of the liposome formulation was that it was administered intranasally, which may be more easily accepted by patients. These systems are a great alternative to be considered as adjuvant vaccine therapy for systemic mycosis.

Myeloid Dendritic Cells (DCs) of Mice Susceptible to Paracoccidioidomycosis Suppress T Cell Responses whereas Myeloid and Plasmacytoid DCs from Resistant Mice Induce Effector and Regulatory T Cells

The protective adaptive immune response in paracoccidioidomycosis, a mycosis endemic among humans, is mediated by T cell immunity, whereas impaired T cell responses are associated with severe, progressive disease. The early host response to Paracoccidioides brasiliensis infection is not known since the disease is diagnosed at later phases of infection. Our laboratory established a murine model of infection where susceptible mice reproduce the severe disease, while resistant mice develop a mild infection. This work aimed to characterize the influence of dendritic cells in the innate and adaptive immunity of susceptible and resistant mice. We verified that P. brasiliensis infection induced in bone marrow-derived dendritic cells (DCs) of susceptible mice a prevalent proinflammatory myeloid phenotype that secreted high levels of interleukin-12 (IL-12), tumor necrosis factor alpha, and IL-β, whereas in resistant mice, a mixed population of myeloid and plasmacytoid DCs secreting proinflammatory cytokines and expressing elevated levels of secreted and membrane-bound transforming growth factor β was observed. In proliferation assays, the proinflammatory DCs from B10.A mice induced anergy of naïve T cells, whereas the mixed DC subsets from resistant mice induced the concomitant proliferation of effector and regulatory T cells (Tregs). Equivalent results were observed during pulmonary infection. The susceptible mice displayed preferential expansion of proinflammatory myeloid DCs, resulting in impaired proliferation of effector T cells. Conversely, the resistant mice developed myeloid and plasmacytoid DCs that efficiently expanded gamma interferon-, IL-4-, and IL-17-positive effector T cells associated with increased development of Tregs. Our work highlights the deleterious effect of excessive innate proinflammatory reactions and provides new evidence for the importance of immunomodulation during pulmonary paracoccidioidomycosis.

Brazilian blood donation eligibility criteria for dermatologic patients

A focused and commented review on the impact of dermatologic diseases and interventions in the solidary act of donating blood is presented to dermatologists to better advise their patients. This is a review of current Brazilian technical regulations on hemotherapeutic procedures as determined by Ministerial Directive #1353/2011 by the Ministry of Health and current internal regulations of the Hemotherapy Center of Ribeirão Preto, a regional reference center in hemotherapeutic procedures. Criteria for permanent inaptitude: autoimmune diseases (>1 organ involved), personal history of cancer other than basal cell carcinoma, severe atopic dermatitis or psoriasis, pemphigus foliaceus, porphyrias, filariasis, leprosy, extra pulmonary tuberculosis or paracoccidioidomycosis, and previous use of etretinate. Drugs that impose temporary ineligibility: other systemic retinoids, systemic corticosteroids, 5-alpha-reductase inhibitors, vaccines, methotrexate, beta-blockers, minoxidil, anti-epileptic, and anti-psychotic drugs. Other conditions that impose temporary ineligibility: occupational accident with biologic material, piercing, tattoo, sexually transmitted diseases, herpes, and bacterial infections, among others. Thalidomide is currently missing in the teratogenic drugs list. Although finasteride was previously considered a drug that imposed permanent inaptitude, according to its short halflife current restriction of 1 month is still too long. Dermatologists should be able to advise their patients about proper timing to donate blood, and discuss the impact of drug withdrawal on treatment outcomes and to respect the designated washout periods.

Pulmonary paracoccidioidomycosis: A case report with high-resolution computed tomography findings

Paracoccidioidomycosis is a systemic mycosis which is endemic in rural areas of Latin America, an important European source of immigrants and a growing European touristic destination as well, with most cases occurring in Brazil, Argentina, Venezuela and Colombia. The authors report a case of a 43-year-old man who previously worked in Venezuela and is living in Portugal for 8 years, presenting with a single cutaneous lesion. Despite the absence of valuable respiratory complaints, severe lung damage was found with high-resolution computed tomography (HRCT). Biopsy of the cutaneous lesion and mycologic sputum examination were performed revealing Paracoccidioides brasiliensis infection.

The reversed halo sign: update and differential diagnosis

The reversed halo sign is characterised by a central ground-glass opacity surrounded by denser air-space consolidation in the shape of a crescent or a ring. It was first described on high-resolution CT as being specific for cryptogenic organising pneumonia. Since then, the reversed halo sign has been reported in association with a wide range of pulmonary diseases, including invasive pulmonary fungal infections, paracoccidioidomycosis, pneumocystis pneumonia, tuberculosis, community-acquired pneumonia, lymphomatoid granulomatosis, Wegener granulomatosis, lipoid pneumonia and sarcoidosis. It is also seen in pulmonary neoplasms and infarction, and following radiation therapy and radiofrequency ablation of pulmonary malignancies. In this article, we present the spectrum of neoplastic and non-neoplastic diseases that may show the reversed halo sign and offer helpful clues for assisting in the differential diagnosis. By integrating the patient's clinical history with the presence of the reversed halo sign and other accompanying radiological findings, the radiologist should be able to narrow the differential diagnosis substantially, and may be able to provide a presumptive final diagnosis, which may obviate the need for biopsy in selected cases, especially in the immunosuppressed population.

Thoracic Paracoccidioidomycosis: Radiographic and CT Findings

Paracoccidioidomycosis (PCM) is the most common systemic mycosis in Latin America. Although most cases occur in developing countries, recent immigration patterns and an increase in travel have led to a growing number of PCM cases in the United States and Europe. PCM is caused by the dimorphic fungus Paracoccidioides brasiliensis, and the chronic form may progress to severe pulmonary involvement. Several radiologic patterns have been described for pulmonary PCM, including linear and reticular opacities, variable-sized nodules, patchy ill-defined opacities, airspace consolidation, and cavitary lesions. Fibrosis and paracicatricial emphysema are common associated findings. Chest computed tomography (CT) is the method of choice for evaluating pulmonary PCM, with the most common CT findings being ground-glass attenuation, consolidation, small or large nodules, masses, cavitations, interlobular septal thickening, emphysema, and fibrotic lesions. PCM is also an important cause of the "reversed halo" sign at high-resolution CT and should be considered in the differential diagnosis. Awareness of the multiple radiologic manifestations of PCM as well as its epidemiologic and clinical characteristics may permit early diagnosis and initiation of specific treatment, thereby reducing associated morbidity and mortality.

Paracoccidioidomicose cutânea disseminada e pulmonar em paciente portador de neoplasia maligna visceral

Paracoccidioidomycosis is a systemic mycosis caused by the fungus Paracoccidioides brasiliensis that is characterized by polymorphous clinical manifestations principally affecting the skin, mucous membranes, lungs, lymph nodes, adrenal glands and the central nervous system. Depending on the site of inoculation and the individual's immunological status, the disease may take various different forms, affecting the skin, lymph nodes, viscera or a combination of these. The present report describes a patient with extensive cutaneous and pulmonary paracoccidioidomycosis, with disseminated papules and pustules, fever and pulmonary symptoms, probably related to immunosuppression caused by a renal carcinoma.

Tracheoesophageal fistula associated with paracoccidioidomicosis

Paracoccidioidomycosis is a systemic fungal disease caused by Paracoccidioides brasiliensis, agent geographically distributed to certain areas of Central and South America. The infection by P. brasiliensis has been reported from north Mexico to south Argentina. Paracoccidioidomycosis presents similar clinical findings of many other diseases whatever in acute or chronic scenarios. Chronic pulmonary paracoccidioidomycosis is frequently misdiagnosed as malignancy or tuberculosis. The authors present a case of a 57 year-old man admitted to the hospital due to a chronic consumptive syndrome. He underwent anti-tuberculous treatment with rifampin, isoniazid and pyrazinamide 1 year ago without resolution of the simptoms. During the clinical investigation, pulmonary paracoccidioidomycosis with tracheoesophageal fistula was diagnosed. The systemic infection was treated with deoxicolate B amphotericin followed by sulfametoxazole and trimetoprin due to acute renal function impairment. The fistula was endoscopically treated; inittialy with the protection of left main bronchus with a tracheal prosthesis followed by the esophageal fistula’s ostium clipping.

Disseminated Paracoccidioidomycosis (Simulating Metastatic Lung Cancer) and Strongyloides stercoralis Hyperinfestation in a Steroid-Treated Patient

We report a case of disseminated paracoccidioidomycosis, initially suggestive of metastatic lung cancer. The infection was associated with strongyloides hyperinfestation as a result of iatrogenic hypercorticoidism. Examination of a smear prepared from aspirated tracheobronchial secretion and stained by Grocott-methenamine-silver revealed structures consistent with Paracoccidioides brasiliensis and Strongyloides stercoralis. At autopsy, the central nervous system and pulmonary paracoccidioidomycosis, as well as pulmonary strongyloidiasis, were confirmed, without evidence of malignant cells.