The Southern Endemic Zone of Paracoccidioidomycosis: Epidemiological Approach in Northeast Argentina

Purpose of Review

Paracoccidioidomycosis (PCM) is one of the most prevalent systemic endemic mycosis in Latin America caused by species of an environmental fungus of the genus Paracoccidioides. In Argentina, the endemic area with the highest incidence is located in the Northeast. This review presents the current aspects of PCM epidemiology influenced by global and particular climatic anomalies.

Recent Findings

An increase of cases with particularly features, in the diagnosis and clinical manifestations, delaying the diagnosis was observed. Two genotypes of Paracoccidioides are circulating and, probably, are related to a considerable percentage of non-reactive serological tests obtained in proven cases of PCM.

Summary

The traditional view of the PCM epidemiology in the southern endemic zone area must be reconsidered. A higher level of premonition is now required in Northeast Argentina and, may be, in bordering countries. The particular characteristics both in the clinic and in the diagnosis currently observed suggest a new trend in PCM.

     

Traffic of Leukocytes and Cytokine Up-regulation in the Central Nervous System in a Murine Model of Neuroparacoccidioidomycosis

Background

Paracoccidioidomycosis is the most important systemic mycosis in South America. In the last decades, it was observed that central nervous system involvement is frequent, occurring in 12.5 % of the cases. The aim of this study was to report the early inflammatory changes associated with an experimental model of neuroparacoccidioidomycosis (NPCM).

Methods

C57BL/6 mice were infected by intracranial route with 10⁶ yeast cells of PB18 strain of Paracoccidioides brasiliensis. Leukocyte–endothelium interactions were assessed by intravital microscopy 1, 2, 4, and 8 weeks post-infection (p.i.). Chemokine/cytokine levels in the brain and histopathological changes were assessed 4 and 8 weeks p.i..

Results

Intravital microscopy analysis revealed a progressive increase in leukocyte recruitment in the vessels of pia mater with a peak 4 weeks p.i. The chemokine CXCL9 was increased at 4 and 8 weeks p.i., while CCL2, CCL3, and CCL5 were increased at 8 weeks p.i. Histopathological analysis revealed the infiltration of inflammatory cells and the development of progressive granulomatous meningoencephalitis. CCL3 levels correlated with clinical manifestations of disease, as measured by the SHIRPA battery.

Conclusions

The experimental model of NPCM showed increased leukocyte recruitment associated with increased expression of chemokines and nervous tissue inflammation which correlated with clinical manifestations of disease.     

Paracoccidioidomycosis Mimicking Squamous Cell Carcinoma on the Dorsum of the Tongue and Review of Published Literature

Introduction

Paracoccidioidomycosis is a disease that is endemic to southern and southeastern Brazil, caused by the fungus Paracoccidioides brasiliensis. The most common clinical oral manifestation is the presence of multiple granulomatous ulcers with hemorrhagic dots, located mainly on the lips, palate, and buccal mucosa. However, the disease can manifest atypically as a single ulcer, mimicking oral squamous cell carcinoma (SCC) or tuberculosis.

Case report

A 65-year-old male patient presented with a complaint of a single ulcerated lesion on the dorsum of the tongue; the lesion had evolved over 6 months. The diagnostic hypotheses were SCC and oral manifestation of tuberculosis. An incisional biopsy was performed, and histopathological analysis of the specimen revealed pseudoepitheliomatous hyperplasia, a granulomatous structure of epithelioid histiocytes, multinucleated giant cells, and lymphocytes in the connective tissue. Grocott staining confirmed the presence of the fungus in the lesion, and a diagnosis was made of paracoccidioidomycosis. The patient was treated with 200 mg/day of itraconazole for 12 months and now shows no signs or symptoms of recurrence of the disease.

Conclusion

Correct diagnosis is essential for a successful therapeutic approach and resolution of the lesion.     

Estrogen Receptor-α Correlates with Higher Fungal Cell Number in Oral Paracoccidioidomycosis in Women

Background

Paracoccidioidomycosis is a neglected tropical fungal infection with great predilection for adult men, indicating the participation of female hormone estrogen in preventing paracoccidioidomycosis development in women. Estrogen has an immunologic effect leading to polarization toward the Th2 immune response, which favors the disease evolution.

Objectives

To evaluate estrogen and progesterone receptors in oral paracoccidioidomycosis lesions and to verify any association with tissue fungi counting in women and men.

Methods

Thirty-two cases of chronic oral paracoccidioidomycosis were included. Immunohistochemical analyses for anti-estrogen receptor-α, anti-progesterone receptor and anti-Paracoccidioides brasiliensis antibodies were performed. The differences between women and men and the relations among the immunomarkers for each gender were also evaluated.

Results

A significant positive correlation was observed between estrogen receptor-α and the amount of fungi in women. In addition, estrogen receptor-α was mildly expressed in the inflammatory cells of female patients, while progesterone receptor was expressed in both genders, with similar expression between women and men. Moreover, fungi counting revealed no differences between genders.

Conclusions

Estrogen receptor-α was expressed only in women and showed a positive correlation with the amount of fungi in oral paracoccidioidomycosis, while progesterone receptor was observed in both genders and exhibited no correlation with estrogen receptor-α or fungi counting.

     

Paracoccidioidomicosis en pediatría: descripción de 4 casos

BackgroundParacoccidioidomycosis is the most frequent systemic mycosis in Latin America, caused by the dimorphic fungus Paracoccidioides. Paracoccidioidomycosis in children is uncommon. Our aim is to describe clinical features of patients who had a confirmed diagnosis of paracoccidioidomycosis in our hospital in the last 10 years.Case reportsWe describe 4 cases of paracoccidioidomycosis in previously healthy children from the north of our country. Diagnoses were made by biopsy or culture.ConclusionsThe diagnosis of paracoccidioidomycosis should be considered in a patient coming from regions where Paracoccidioides is endemic, and presenting with a lymphoproliferative syndrome, anemia, eosinophilia and hypergammaglobulinemia.     

Animal Models and Antifungal Agents in Paracoccidioidomycosis: An Overview

Paracoccidioides brasiliensis is the etiologic agent of paracoccidioidomycosis, the most prevalent systemic mycosis in Latin America. The morbidity and mortality associated with paracoccidioidomycosis necessitate our understanding of fungal pathogenesis and discovering of new agents to treat this infection. Animal models have contributed much to the knowledge of fungal infections and their corresponding therapeutic treatments. This is true for animal models of the primary fungal pathogens such as P. brasiliensis. This review describes the development, details and utility of animal models of paracoccidioidomycosis for studying and developing the current antifungal agents used for therapy of this fungal disease and novel agents with antifungal properties against P. brasiliensis.     

Invasive Mycosis in Medical Intensive Care Unit Patients with Severe Alcoholic Hepatitis

Background

Severe alcoholic hepatitis (AH) has a poor short-term prognosis often caused by infections. However, the incidence of invasive mycosis in patients with AH treated with corticosteroids and its impact still remains unknown.

Methods

Retrospective analyses of twelve medical ICU patients (out of 120 patients with liver cirrhosis) with histological proven AH.

Results

Twelve patients were diagnosed with histological proven AH during there stay at the ICU. All patients were treated with corticosteroids; three patients were treated with corticosteroids and pentoxifylline. Five patients had invasive aspergillosis (IA); three patients had candidemia; and two had fungal colonization with candida species. Only two patients had no evidence for fungals. IA was associated with death in all cases. Death occured in most cases shortly after diagnosis despite antifungal medication. Two patients with candidemia died; one patient died in the group with fungal colonization. Overall, the mortality rate was 100 % in patients with IA and 70 % in the group with candidemia.

Conclusions

Patients with severe AH have an increased susceptibility to invasive mycosis associated with high mortality. A high level of suspicion of invasive mycosis in AH patients and prophylactic strategies are needed in those patients.     

The effect of radiotherapy on NKT cells in patients with advanced head and neck cancer

Background

Cancer immunotherapy with NKT cells is a potential new treatment strategy for advanced head and neck cancer. NKT cell therapy is promising due to its unique anti-tumor activity and higher degree of safety compared to current therapies. Radiotherapy is indispensable as a standard treatment for advanced head and neck cancer. To elucidate the possibility of using NKT cells as an adjuvant immunotherapy with radiotherapy, we examined the effect of radiotherapy on NKT cells in patients with head and neck cancer.

Methods

The number, IFN-γ production and proliferation capacity of NKT cells were analyzed before and after 50 Gy radiation therapy in 12 patients with stage IV head and neck squamous cell carcinoma. The cytotoxic activity of NKT cells was examined in vitro.

Results

The number of NKT cells in the blood varied widely between patients. After radiation therapy, the population of CD3 T cells decreased significantly, while the NKT cell population remained stable. The number of NKT cells was the same after radiation therapy as before. IFN-γ production from NKT cells collected just after radiotherapy was impaired after stimulation with exogenous ligand, but the proliferative responses of these NKT cells was enhanced in comparison to those collected before radiation therapy. Furthermore, the proliferated NKT cells displayed a significant level of anti-tumor activity.

Conclusion

NKT cells are relatively resistant to radiation and might therefore be suitable for adjuvant immunotherapy to eradicate remnant cancer cells in patients who have undergone radiation therapy.     

Les manifestations hématologiques du lupus érythémateux systémique. A propos de 70 cas dans une série de 80 LES

Abstract

Systemic lupus erythematosus is a non-organ specific auto-immune disease which commonly has haematological manifestations. The aim of this study was to assess the epidemiological aspects of haematological manifestations among 80 patients with systemic lupus erythematosus (SLE).

Methods

A retrospective study of 80 SLE patients covering the period between 1990 and May 2005.

Results

From among the 80 patients with SLE, 70 had haematological manifestations, of which 65 women and 5 men. Average age was 32.41 years. The most commonly-observed haematological manifestation was anaemia (83.75%), followed by bicytopaenia (63.75%) then leukocytopaenia and/or lymphocytopaenia (62.5).     

In-hospital cerebrovascular complications following orthotopic liver transplantation: A retrospective study

Background

Cerebrovascular complications are severe events following orthotopic liver transplantation (OLT). This study aimed to observe the clinical and neuroimaging features and possible risk factors of in-hospital cerebrovascular complications in the patients who underwent OLT.

Patients and methods

We retrospectively reviewed 337 consecutive patients who underwent 358 OLTs. Cerebrovascular complications were determined by clinical and neuroimaging manifestations, and the possible risk factors were analyzed in the patients with intracranial hemorrhage.

Results

Ten of 337 (3.0%) patients developed in-hospital cerebrovascular complications (8 cases experienced intracranial hemorrhage and 2 cases had cerebral infarction), and 6 of them died. The clinical presentations were similar to common stroke, but with rapid deterioration at early stage. The hematomas on brain CT scan were massive, irregular, multifocal and diffuse, and most of them were located at brain lobes and might enlarge or rebleed. Infarcts presented lacunar and multifocal lesions in basal gangliar but with possible hemorrhagic transformation. The patients with intracranial hemorrhage had older age and a more frequency of systemic infection than non-intracranial hemorrhage patients. (P = 0.011 and 0.029, respectively).

Conclusion

Posttransplant cerebrovascular complications have severe impact on outcome of the patients who received OLT. Older age and systemic infection may be the possible risk factors of in-hospital intracranial hemorrhage following OLT.     

Immunohistochemical Cross-Reactivity Between <Emphasis Type="Italic">Paracoccidioides</Emphasis> sp. from Dolphins and <Emphasis Type="Italic">Histoplasma capsulatum</Emphasis>

Paracoccidioidomycosis ceti is a cutaneous disease of cetaceans caused by uncultivated Paracoccidioides brasiliensis or Paracoccidioides spp. Serological cross-reactions between paracoccidioidomycosis ceti and paracoccidioidomycosis, paracoccidioidomycosis and histoplasmosis, and paracoccidioidomycosis and coccidioidomycosis have been reported before. The present study aimed to detect immunohistochemical cross-reaction between antibodies to Paracoccidioides sp. and Histoplasma capsulatum, and vice versa. Thirty murine sera, obtained from experimental infections of 6 isolates of H. capsulatum, were reacted with paraffin-embedded yeast-form cells of Paracoccidioides sp. derived from a case of paracoccidioidomycosis ceti in Japan. The murine sera were also reacted with human isolates of H. capsulatum yeast cells, with P. brasiliensis yeast cells, and with fungal cells of Coccidioides posadasii. Three dolphins’ sera from cases of paracoccidioidomycosis ceti, two human sera from patients with paracoccidioidomycosis, and a serum from a healthy person with a history of coccidioidomycosis were used in order to determine that the tested fungal cells reacted properly. Sera derived from mice infected with an isolate of H. capsulatum reacted positively against yeast cells of Paracoccidioides sp., yeast cells of P. brasiliensis, and fungal cells of C. posadasii, while those derived from other strains were negative. The present study recorded for the first time the cross-reaction between the yeast cells of H. capsulatum and antibodies against Paracoccidioides spp., the yeast cells of Paracoccidioides sp. and antibodies against H. capsulatum, the yeast cells of Paracoccidioides sp. and antibodies against Coccidioides sp., and fungal cells of C. posadasii and antibodies against Paracoccidioides spp.     

Merkel cell carcinoma

Background

Merkel cell carcinoma (MCC) is an unusual primary neuroendocrine carcinoma of the skin. MCC is a fatal disease, and patients have a poor chance of survival. Moreover, MCC lacks distinguishing clinical features, and thus by the time the diagnosis is made, the tumour usually have metastasized. MCC mainly affects sun-exposed areas of elderly persons. Half of the tumours are located in the head and neck region.

Methods

MCC was first described in 1972. Since then, most of the cases reported, have been in small series of patients. Most of the reports concern single cases or epidemiological studies. The present study reviews the world literature on MCC. The purpose of this article is to shed light on this unknown neuroendocrine carcinoma and provide the latest information on prognostic markers and treatment options.

Results

The epidemiological studies have revealed that large tumour size, male sex, truncal site, nodal/distant disease at presentation, and duration of disease before presentation, are poor prognostic factors. The recommended initial treatment is extensive local excision. Adjuvant radiation therapy has recently been shown to improve survival. Thus far, no chemotherapy protocol have achieved the same objective.

Conclusion

Although rare, the fatality of this malignancy makes is important to understand the etiology and pathophysiology. During the last few years, the research on MCC has produced prognostic markers, which can be translated into clinical patient care.     

New species of Ruellia (Acanthaceae) from southern South America

Two new species ofRuellia,R. epallocaulos from northeastern Argentina, southern Brazil, and eastern Paraguay, andR. kleinii from southern Brazil, are described, illustrated and compared to related species.     

Evaluation of Current Knowledge, Awareness and Practice of Spirometry among Hospital -based Nigerian Doctors

Background

The association between systemic sclerosis and pulmonary arterial hypertension (PAH) is well recognized. Vascular endothelial growth factor (VEGF) has been reported to play an important role in pulmonary hypertension. The aim of the present study was to examine the relationship between systolic pulmonary artery pressure, clinical and functional manifestations of the disease and serum VEGF levels in systemic sclerosis.

Methods

Serum VEGF levels were measured in 40 patients with systemic sclerosis and 13 control subjects. All patients underwent clinical examination, pulmonary function tests and echocardiography.

Results

Serum VEGF levels were higher in systemic sclerosis patients with sPAP ≥ 35 mmHg than in those with sPAP < 35 mmHg (352 (266, 462 pg/ml)) vs (240 (201, 275 pg/ml)) (p < 0.01), while they did not differ between systemic sclerosis patients with sPAP < 35 mmHg and controls. Serum VEGF levels correlated to systolic pulmonary artery pressure, to diffusing capacity for carbon monoxide and to MRC dyspnea score. In multiple linear regression analysis, serum VEGF levels, MRC dyspnea score, and D_LCO were independent predictors of systolic pulmonary artery pressure.

Conclusion

Serum VEGF levels are increased in systemic sclerosis patients with sPAP ≥ 35 mmHg. The correlation between VEGF levels and systolic pulmonary artery pressure may suggest a possible role of VEGF in the pathogenesis of PAH in systemic sclerosis.     

Neuroparacoccidioidomycosis (NPCM): Magnetic Resonance Imaging (MRI) Findings

Objective

To describe the magnetic resonance imaging (MRI) patterns of the central nervous system (CNS) involvement by neuroparacoccidioidomycosis (NPCM).

Methods

Between January 1999 and March 2011, a review of MRI data analysis from 8 cases of NPCM was performed. The following MRI characteristics were examined by an experienced neuroradiologist: topography of lesions, aspects on T1- and T2-weighted images (WI), contrast enhancement, diffusion and spectroscopy.

Results

All patients had evidence of paracoccidioidomycosis infection outside the nervous system. Regarding CNS involvement, five patients had only supratentorial lesions; three had infra- and supratentorial ones. Meningeal extension occurred in three patients. The lesions were predominantly hyperintense on T1WI. At T2WI, a hypointense component was present in five cases as well as a perilesional abnormal white matter. A ring-enhancement pattern was seen in five cases. Spectroscopy was performed in three patients and showed an increased lipid peak in all of them. In one case, there was also an increased choline peak.

Conclusion

NPCM is rare, and MRI may help its differentiation from other inflammatory lesions. However, the presence of active infection outside CNS and some imaging characteristics should point to this diagnosis.     

Helicobacter species are associated with possible increase in risk of biliary lithiasis and benign biliary diseases

Background

Late relapses of testicular germ cell tumor are uncommon. We report a case of cervical mature teratoma appeared 17 years after treatment of testicular teratocarcinoma.

Case presentation

A 20- year- old patient underwent left sided orchiectomy followed by systemic therapy and retroperitoneal residual mass resection in 1989. He remained in complete remission for 200 months. In 2005 a huge left supraclavicular neck mass with extension to anterior mediastinum appeared. Radical surgical resection of the mass was performed and pathologic examination revealed mature teratoma.

Conclusion

This is one of the longest long-term reported intervals of a mature teratoma after treatment of a testicular nonseminoma germ cell tumor. This case emphasizes the necessity for follow up of testicular cancer throughout the patient's life.     

<Emphasis Type="Italic">Emergomyces</Emphasis>: a New Genus of Dimorphic Fungal Pathogens Causing Disseminated Disease among Immunocompromised Persons Globally

Purpose of Review

The emergence of a group of previously unknown or unrecognized dimorphic fungal species causing systemic human disease resulted in taxonomic shifts and the creation of a new genus, Emergomyces, within Onygenales. We review the morphology, taxonomy, physiology, and ecology of Emergomyces spp., and the epidemiology, clinicopathology, diagnosis, and management of disease.

Recent Findings

Emergomyces species have been reported as causes of human disease in Europe, Asia, Africa, and North America. Es. pasteurianus is most cosmopolitan, and Es. africanus, in southern Africa, causes the largest reported disease burden; in fact, emergomycosis is the most common endemic mycosis diagnosed in South Africa. The classic clinical picture is of disseminated disease, often with cutaneous involvement, in immunocompromised individuals.

Summary

Members of the genus Emergomyces are uncommon but important agents of systemic disease in immunocompromised hosts worldwide. Knowledge gaps include the biology of the fungus, and the pathophysiology and management of disease.

     

Hepatic Disease with Portal Hypertension and Acute Juvenile Paracoccidioidomycosis: A Report of Two Cases and Literature Review

Paracoccidioidomycosis (PCM) is a neglected systemic mycosis endemic to Latin America caused by dimorphic fungi of the genus Paracoccidioides. The acute juvenile PCM is a severe type of presentation that usually affects young vulnerable patients and rarely progresses to portal hypertension. Here, two cases of liver disease and portal hypertension as complications of acute juvenile PCM are reported. Diagnosis of PCM was performed by isolation of the fungus and molecular identification of the strains provided through partial sequencing of two protein encoding genes, arf and gp43. Genotypic analysis revealed that Paracoccidioides brasiliensis S1 was the phylogenic species involved in both cases. Patients presented a good clinical response to amphotericin B and sulfamethoxazole–trimethoprim. These results highlight the importance of the interdisciplinary approach in patients with severe forms of PCM to avoid and treat complications, and the necessity of further investigations focusing on host-pathogen interaction in order to explain the broad clinical spectrum in PCM as well as the severity and poor outcome in some clinical cases.     

Increased prevalence of tumour infiltrating immune cells in oropharyngeal tumours in comparison to other subsites: relationship to peripheral immunity

Background

The nature of the tumour microenvironment immune response in head and neck cancer patients has an important role in tumour development and metastasis, but it is unknown if this differs between cancer subsites or whether it is related to the peripheral immune response.

Methods

Immune cells (CD4, CD8, Foxp3) in head and neck squamous cell carcinoma tissue (HNSCC; n = 66), detected by immunohistochemistry, have been correlated with tumour subsite and immune cells in the peripheral circulation (CD4⁺CD25^HighFoxp3⁺ Treg and CD4⁺ T cells), identified using flow cytometry.

Results

Oropharyngeal tumours had a greater number of infiltrating immune cells in both tumour and stroma compared with other subsites, but no difference was observed in the circulating levels. Immune cells in the stroma were positively related to those in the tumour with consistently higher levels in stroma. A strong relationship was found between the number of CD4⁺ and Foxp3⁺ cells but not between the number of CD8⁺ and Foxp3⁺ cells in the tumour. The number of Foxp3⁺ cells within the tumour was positively correlated with the percentage of circulating CD4⁺CD25^High cells positive for Foxp3. Late stage laryngeal tumours showed a higher number of Foxp3⁺ lymphocytes compared with early stage malignancies, and oropharyngeal tumours had more CD4⁺ cells in node negative tumours compared with node positive ones.

Conclusion

The level of immune cell infiltration in head and neck squamous cell carcinoma appears to be subsite dependent residing primarily in the stroma and is likely to be dependent on the peripheral immune response.