Tuberculosis extrapulmonar en paciente embarazada. Reporte de caso / Extrapulmonary Tuberculosis in Pregnant Patient. Case Report

Introducción: La tuberculosis (TB) extrapulmonar es la afectación de cualquier órgano, sin compromiso pulmonar demostrado, como consecuencia de la diseminación hematógena/linfática del bacilo de Koch. Presentación de caso: Paciente en puerperio inmediato cursando cuadro clínico de gonalgia que se estudió con resonancia magnética que mostró lesión endomedular en región distal del fémur izquierdo. Se estudió con tomografía de tórax, abdomen y pelvis que evidenciaron otras lesiones a nivel esplénico, sin compromiso hepático ni pulmonar. Se realizó punción diagnóstica femoral con evidencia de granulomas con necrosis central. Se interpretó tuberculosis extrapulmonar y se inició tratamiento antifímico con mejora sintomática. Discusión: La TB extrapulmonar puede impactar a nivel de pleura, ganglios linfáticos, vías urinarias, sistema osteoarticular, sistema nervioso central y abdomen. En el embarazo, la prevalencia de TB extrapulmonar es baja. Conclusión: La TB femoral y esplénica concomitante en pacientes embarazadas es un hallazgo infrecuente por lo que su análisis resulta de gran importancia. Arribar al diagnóstico requiere un elevado índice de sospecha. El retraso diagnóstico conlleva a un aumento de la morbimortalidad

Introduction: Extrapulmonary tuberculosis (TB) is the involvement of any organ, without demonstrated pulmonary involvement, as a consequence of the hematogenous/lymphatic dissemination of the Koch bacillus. Case presentation: Patient in the immediate postpartum period with clinical symptoms of gonalgia that was studied with magnetic resonance imaging showing intramedullary lesion in the distal region of the left femur. A CT scan of the chest, abdomen and pelvis showed other lesions at the splenic level, without liver or lung involvement. A femoral diagnostic puncture was performed with evidence of granulomas with central necrosis. Extrapulmonary tuberculosis was interpreted and antifimic treatment was started with symptomatic improvement. Discussion: Extrapulmonary TB can impact the pleura, lymph nodes, urinary tract, osteoarticular system, central nervous system and abdomen. During pregnancy, the prevalence of extrapulmonary TB is low. Conclusion: Concomitant femoral and splenic TB in pregnant patients is a rare finding, which is why its analysis is of great importance. Arriving at a diagnosis requires a high index of suspicion. Delayed diagnosis leads to an increase in morbidity and mortalit

Prevalencia de cristales de colesterol en granulomas perirradiculares de origen endodóntico / Prevalence of cholesterol crystals in periradicular granulomas of endodontic origin

Objetivos: Identificar y determinar la prevalencia de cristales de colesterol (CRCo) en granulomas perirradiculares de origen endodóntico y el tipo de reacción que provocan en los tejidos circundantes. Material y métodos: Se estudiaron con microscopía óptica 75 preparados histológicos de archivo pertenecientes a lesiones perirradiculares humanas correspondientes a piezas dentarias que habían recibido un tratamiento endodóntico pre- vio y que, según los informes que acompañaban las muestras, habían sido obtenidas mediante una apicectomía. Del total, 68 muestras fueron diagnosticadas como granulomas, mientras que los 7 restantes se diagnosticaron como quistes inflamato- rios y fueron descartadas. Resultados: 39 granulomas pertenecían a pacientes de sexo femenino con presencia de CRCo en el 58,97% de los ca- sos. Los 29 granulomas restantes pertenecían al sexo mascu- lino y presentaron CRCo en un 41,37%. La mayor proporción de CRCo fue hallada en granulomas pertenecientes a pacien- tes mayores de 62 años. Los CRCo se observaron rodeados de macrófagos y células gigantes multinucleadas, provocando una reacción a cuerpo extraño. También se observaron células espumosas en áreas circundantes. Conclusiones: La presencia de CRCo en granulomas perirradiculares de origen endodóntico provoca una reacción a cuerpo extraño que puede interferir con el proceso de re- paración posendodóntico especialmente en pacientes de edad avanzada (AU)

Aim: Identify and determine the prevalence of cholester- ol crystals (CRCo) in periradicular granulomas of endodontic origin and the type of reaction they produce in the surround- ing tissues. Material and methods: 75 archival histological preparations were studied with optical microscopy. They be- longed to human periradicular lesions corresponding to teeth that had received a previous endodontic treatment and that, according to the reports accompanying the samples, had been obtained by an apicoectomy. Of the total, 68 samples were diagnosed as granulomas, while the remaining 7 were diag- nosed as inflammatory cysts and were discarded. Results: 39 granulomas corresponded to female patients in which the presence of CRCo was observed in 58.97% of the cases. The remaining 29 granulomas were from male patients and showed CRCo in 41.37% of the cases. The highest pro- portion of CRCo was found in patients over 62 years of age. The CRCo were surrounded by macrophages and multinucle- ated giant cells causing a foreign body reaction. Foam cells were also observed in the surrounding areas. Conclusions: The presence of CRCo in periradicular granulomas of endodontic origin could be a factor interfering with periapical healing after conventional endodontic thera- py, especially in elderly patients (AU)

DNA methylation profile discriminates sporadic giant cell granulomas of the jaws and cherubism from their giant cell-rich histological mimics.

Sporadic giant cell granulomas (GCGs) of the jaws and cherubism-associated giant cell lesions share histopathological features and microscopic diagnosis alone can be challenging. Additionally, GCG can morphologically closely resemble other giant cell-rich lesions, including non-ossifying fibroma (NOF), aneurysmal bone cyst (ABC), giant cell tumour of bone (GCTB), and chondroblastoma. The epigenetic basis of these giant cell-rich tumours is unclear and DNA methylation profiling has been shown to be clinically useful for the diagnosis of other tumour types. Therefore, we aimed to assess the DNA methylation profile of central and peripheral sporadic GCG and cherubism to test whether DNA methylation patterns can help to distinguish them. Additionally, we compared the DNA methylation profile of these lesions with those of other giant cell-rich mimics to investigate if the microscopic similarities extend to the epigenetic level. DNA methylation analysis was performed for central (n = 10) and peripheral (n = 10) GCG, cherubism (n = 6), NOF (n = 10), ABC (n = 16), GCTB (n = 9), and chondroblastoma (n = 10) using the Infinium Human Methylation EPIC Chip. Central and peripheral sporadic GCG and cherubism share a related DNA methylation pattern, with those of peripheral GCG and cherubism appearing slightly distinct, while central GCG shows overlap with both of the former. NOF, ABC, GCTB, and chondroblastoma, on the other hand, have distinct methylation patterns. The global and enhancer-associated CpG DNA methylation values showed a similar distribution pattern among central and peripheral GCG and cherubism, with cherubism showing the lowest and peripheral GCG having the highest median values. By contrast, promoter regions showed a different methylation distribution pattern, with cherubism showing the highest median values. In conclusion, DNA methylation profiling is currently not capable of clearly distinguishing sporadic and cherubism-associated giant cell lesions. Conversely, it could discriminate sporadic GCG of the jaws from their giant cell-rich mimics (NOF, ABC, GCTB, and chondroblastoma).

Mycobacterium bovis naturally infected calves present a higher bacterial load and proinflammatory response than adult cattle.

Granulomas are characteristic bovine tuberculosis lesions; studying this structure has improved our understanding of tuberculosis pathogenesis. However, the immune response that develops in granulomas of young cattle naturally infected with Mycobacterium bovis (M. bovis) has not been fully studied. Our previous work described an atypical pattern in granulomatous lesions of cattle younger than 4 months (calves) naturally infected previously M. bovis that did not correspond to the histological classification previously proposed. Histologically, granulomas from calves lack a connective tissue capsule and have fewer multinucleated giant cells (MGCs) and more acid-fast bacilli (AFB) than the classic tuberculosis lesions found in cattle older than 1 year (adults); this suggests a deficient immune response against M. bovis infection in young animals. Therefore, we used IHC and digital pathology analysis to characterize the in situ immune response of granulomas from young and adult cattle. The immunolabeling quantification showed that granulomas from calves had more mycobacteria, CD3+ cells, IFN-γ, TNF-α, and inducible nitric oxide synthase (iNOS) than those of adult cattle. Furthermore, calf granulomas showed lower immunolabeling of MAC387+, CD79+, and WC1+ cells without connective tissue surrounding the lesion and were associated with less vimentin, Alpha Smooth Muscle Actin (α-SMA), and TGF-ß compared with granulomas from adult cattle. Our results suggest that the immune responses in granulomas of cattle naturally infected with M. bovis may be age dependent. This implies that an exacerbated proinflammatory response may be associated with active tuberculosis, producing more necrosis and a lower microbicidal capacity in the granulomas of calves naturally infected with M. bovis.

Canine Leproid Granuloma (CLG) Caused by Mycobacterial Species Closely Related to Members of Mycobacterium Simiae Complex in a Dog in Brazil.

This report describes the clinical features and molecular diagnosis of a case of canine leproid granuloma (CLG) caused by mycobacterial strains of the Mycobacterium simiae complex in Brazil. A 12-year-old non-neutered male Labrador Retriever dog was presented with a 2-week history of progressive painless cutaneous lesions. Ulcerated nodules with hematic crusts were observed on the dorsal surface of the right and left pinna and on the metacarpal, metatarsal, and digits. Complete blood count, serum biochemistry, aspiration cytology of cutaneous lesions, biopsy for histopathological evaluation, culture for aerobic and anaerobic bacteria, polymerase chain reaction and DNA sequencing to identify mycobacterial species were performed. According to the clinical and histopathological findings, a diagnosis of CLG was established. Despite the negative result of the bacterial culture, mycobacterial identification was made by sequencing the hsp65 gene. Our findings highlight that mycobacterial species closely related to members of the M simiae clade can be causative agents of CLG.

[Infectious and inflammatory gastrointestinal manifestations of chronic granulomatous disease]. / Manifestaciones gastrointestinales inflamatorias e infecciosas de la enfermedad granulomatosa crónica.

Chronic granulomatous disease (CGD) is an inborn error of immunity caused by a defect in one of the components of the NADPH oxidase complex, which is responsible for generating reactive oxygen species (ROS) during the respiratory burst in phagocytes. The absence of ROS produced by NADPH oxidase in neutrophils and in macrophages leads to greater susceptibility to certain bacterial and fungal infections, and also to inflammatory manifestations due to a deregulated inflammatory response, which suggests that the ability to adequately regulate inflammatory signaling depends on ROS produced by NADPH oxidase. The disease course in patients with X-linked CGD is more severe, with recurrent invasive infections; in contrast, patients with non-classic CGD do not present invasive bacterial or fungal infections, but have more prominent inflammatory manifestations. The most frequent gastrointestinal manifestations are stomatitis, gingivitis, chronic diarrhea, liver abscesses that are similar to inflammatory bowel disease (IBD), and granulomas that can cause obstruction or stenosis in the esophagus, stomach or intestine. It has been observed that the deficiency of p40phox and ROS (non-classic CGD) are associated with greater susceptibility to colitis and the development of severe inflammation; therefore, it is presented that these proteins participate in the resolution of inflammation. In general, the inflammatory findings in CGD, including gastrointestinal manifestations, are seldom described. In international cohorts, manifestations that are similar to IBD are reported in up to 58% of patients with CGD; however, in the only Mexican cohort, its finding is described in only 4 out of 93 patients (4.3%). In this review, we summarize the gastrointestinal clinical findings of CGD, including infectious and inflammatory manifestations, emphasizing on the latter.

La enfermedad granulomatosa crónica (EGC) es un error innato de la inmunidad causado por un defecto en uno de los componentes del complejo NADPH oxidasa, responsable de generar especies reactivas de oxígeno (ERO) durante el estallido respiratorio en los fagocitos. La ausencia de ERO producidos por la NADPH oxidasa en los neutrófilos y en los macrófagos produce mayor susceptibilidad a infecciones bacterianas y fúngicas, además de manifestaciones inflamatorias por una respuesta inflamatoria desregulada, lo que sugiere que la capacidad para regular adecuadamente la señalización inflamatoria depende de las ERO derivadas de la NADPH oxidasa. Los pacientes con EGC ligada al cromosoma X tienen un curso de enfermedad más grave con infecciones invasivas recurrentes, a diferencia de los pacientes con EGC no clásica, quienes no presentan infecciones bacterianas o fúngicas invasivas, pero con manifestaciones inflamatorias más prominentes. Las manifestaciones gastrointestinales más frecuentes son estomatitis, gingivitis, diarrea crónica, abscesos hepáticos, similares a las de la enfermedad inflamatoria intestinal (EII) y granulomas, que pueden provocar obstrucción o estenosis en esófago, estómago o intestino. Se ha observado que la deficiencia de p40phox y EROS (EGC no clásica) se asocia a mayor susceptibilidad a colitis y al desarrollo de inflamación severa, por lo que se plantea que estas proteínas participan en la resolución de la inflamación. En general, los hallazgos inflamatorios en la EGC, incluyendo los gastrointestinales, han sido poco descritos. En las cohortes internacionales se reportan manifestaciones similares a EII hasta en 58 % de los pacientes con EGC; en cambio, en la única cohorte mexicana se describe su hallazgo solo en cuatro de 93 pacientes (4.3 %). En esta revisión resumimos los hallazgos clínicos gastrointestinales de la EGC, incluidas las manifestaciones infecciosas e inflamatorias, con énfasis en las últimas.

Isolation and characterization of pathology in case of massive mortality by Photobacterium damselae subsp. piscicida in Rachycentron canadum / Isolamento e caracterização da patologia em caso de mortalidade maciça por Photobacterium damselae subsp. piscicida em Rachycentron canadum

This study aimed to investigate outbreak with high mortality in cultured juvenile cobiaoccurred in Southeast Brazil in 2011. Fish displayed retarded growth rates, lethargy, fin ulceration, skin depigmentation, corneal opacity, and physical deformities. Internally, livers were increased in volume and pale in different degrees. Firm whitish nodules were disseminated in the liver, kidney and spleen. A moderate number of parasites identified as Neobenedenia melleni were recovered from the body surface. Microscopically, severe hepatic steatosis and extensive granulomatous lesion were identified in all fish sampled. Microbiological analysis of moribund fish revealed the presence in pure culture of a Gram-negative bacterium identified as Photobacterium damselae subsp. piscicida using biochemical and molecular characteristics. Analysis of the partial 16S rRNA sequences confirmed the results demonstrating high identity (98%). The isolates were sensitive to chloramphenicol and enrofloxacin and resistant to ciprofloxacin, florfenicol, doxycycline hydrochloride, norfloxacin, oxytetracycline, and tetracycline. Chronic pasteurellosis was considered as the main problem in the farm, while hepatic steatosis and parasitic infestation may have contributed to the development of the process.

Este estudo objetivou investigar um surto com alta mortalidade em cobia juvenis cultivadas na região Sudeste do Brasil em 2011. Os peixes apresentavam baixa taxa de crescimento, letargia, ulceração nas nadadeiras, despigmentação da pele, opacidade da córnea e deformidades físicas. Internamente o fígado apresentava aumentado e pálido em diferentes graus, com nódulos esbranquiçados e firmes disseminados no fígado, rins e baço. Na superfície corporal dos peixes foram observados moderado número de parasitas identificados como Neobenedenia melleni. Microscopicamente verificou-se esteatose hepática grave e extensa lesão granulomatosa em todos os peixes amostrados. A análise microbiológica dos peixes moribundos revelou a presença, em cultura pura de uma bactéria Gram-negativa identificada como Photobacterium damselae subsp. piscicida usando características bioquímicas e moleculares. A análise das sequências parciais de 16S rRNA confirmou os resultados demonstrando alta identidade (98%). Os isolados foram sensíveis a cloranfenicol e enrofloxacina e resistente a ciprofloxacina, florfenicol, cloridrato de doxiciclina, norfloxacina, oxitetraciclina e tetraciclina. A pasteurelose crônica foi considerada como o principal problema na maricultura, enquanto a esteatose hepática e a infestação parasitária podem ter contribuído para o desenvolvimento do processo.

Endometritis granulomatosa por tuberculosis en mujer postmenopaúsica / Granulomatous tuberculosis endometritis in a posmenopausal woman

INTRODUCCIÓN: La tuberculosis (TBC) genital es una infección relativamente poco frecuente en la mujer. Afecta principalmente a mujeres menores de 40 años, y el motivo de consulta más usual es la esterilidad, de ahí la importancia de su diagnóstico precoz. CASO CLÍNICO clínico: Se presenta el caso de una paciente con dolor pélvico crónico que acude a nuestras consultas para valoración. Durante el estudio se toma biopsia dirigida de la cavidad endometrial diagnosticándose la presencia de granulomas no necrotizantes. Posteriormente se realiza un cultivo microbiológico que resulta positivo para micobacterias y se determina el DNA, mediante reacción en cadena de la polimerasa, de mycobacterium tuberculosis, como causante del cuadro. DISCUSIÓN: El diagnóstico definitivo de TBC requiere el aislamiento en cultivo del bacilo de Koch, aunque en los casos de TBC genital, al ser una entidad paucibacilar, puede no resultar positivo. En éste caso, sería suficiente el diagnóstico de presunción basado en la sospecha clínica y el hallazgo histológico de granulomas. CONCLUSIÓN: La tuberculosis genital es una entidad poco frecuente en nuestro medio, aunque es una causa importante de infertilidad femenina y su predominio generalmente se subestima debido a la naturaleza paucisintomática de la misma. El diagnóstico temprano y el tratamiento multidisciplinar son fundamentales.

INTRODUCTION: Genital tuberculosis (TB) is a relatively rare afection in women. It mainly affects women younger than 40 years, and the most frequent reason for consultation is sterility, therefore early diagnosis is important. CLINICAL CASE: We presented the case of a patient with chronic pelvic pain who comes to our consultations. During the study, we take an endometrial biopsy diagnosing the presence of non-necrotizing granulomas. Finally, we determined the mycobacterium tuberculosis DNA through the polymerase chain reaction and positive microbiological culture, as the cause of pathology. DISCUSSION: The definitive diagnosis of TB requires the isolation in culture of the Koch bacillus, although in genital TB cases, as it is a paucibacillary entity, it may not be positive. In this case, the presumptive diagnosis based on clinical suspicion and the histological granulomas would be enough. CONCLUSIONS: Genital tuberculosis is a rare entity in our environment, although it is an important cause of female infertility and its prevalence is generally underestimated due to its paucisymptomatic nature. Early diagnosis and multidisciplinary treatment are essential.

Diagnóstico diferencial en pacientes con granulomas en biopsias de pulmón, pleura y/o ganglios mediastínicos del Instituto Nacional del Tórax / Differential diagnosis in patients with granulomas in the biopsy of the lung, pleura and/or mediastinal nodes

Las enfermedades granulomatosas incluyen una amplia gama de enfermedades. Sin embargo, en la práctica clínica, muchos casos de enfermedad granulomatosa permanecen sin etiología después del examen histológico. Nuestro objetivo fue determinar, a partir de las biopsias de pulmón, pleura y ganglios linfáticos mediastínicos, en los que se informaron granulomas, las características clínicas y los diagnósticos de estos pacientes. Así también la mortalidad a un año de seguimiento. Metodología: Analizamos retrospectivamente biopsias de pulmón, pleura y/o ganglios linfáticos mediastínicos con granulomas de 75 pacientes del Instituto Nacional del Tórax (2012-2016), sus características clínicas y de laboratorio. La información se obtuvo de los registros médicos. Los datos de mortalidad se obtuvieron del registro civil. Resultados: Se determinó una etiología en todos los casos, excepto en 3 (4%). Los diagnósticos más frecuentes fueron tuberculosis (n = 37; 49%) y sarcoidosis (n = 18; 24%). Otras causas fueron silicosis (5,3%), vasculitis (4%) y neumonitis por hipersensibilidad (2,7%). Los pacientes con tuberculosis (TB) tenían parámetros inflamatorios más altos, como velocidad de eritrosedimentación y proteína C reactiva. Además, sólo se encontraron granulomas con necrosis caseosa en pacientes con tuberculosis. En cambio, los pacientes con sarcoidosis tenían lesiones cutáneas y una mayor frecuencia de linfadenopatías. Cuatro (5.3%) pacientes fallecieron a un año de seguimiento: dos debido a neumonía, uno por hipersensibilidad crónica y uno por TB. Conclusión: La tuberculosis y la sarcoidosis fueron las causas más frecuentes de granulomas respiratorios en este estudio retrospectivo. Se logró determinar una etiología en el 96% de los casos, considerando variables clínicas, de laboratorio e histopatológicas para un diagnóstico diferencial correcto.

Granulomatous diseases comprise a wide range of pathologies. However, in clinical practice, many pulmonary granulomas remain without etiology after the histologic examination. Our aim was to determine from the biopsies of the lung, pleura and mediastinal lymph nodes in which granulomas were reported, the clinical characteristics and diagnoses of the patients. Methodology: We analyzed retrospectively biopsies of the lung, pleura and mediastinal lymph nodes with granulomas from 75 patients handled at our institution (2012-2016), as well as their clinical and laboratory data. The information was obtained from medical records. A one-year mortality date was obtained from the civil registry. Main results: A cause was determined in all the cases, except in three of them (4%). The most frequent diagnoses were tuberculosis (n =37; 49%) and sarcoidosis (n =18; 24%). Other causes were silicosis (5.3%), vasculitis (4%) and hypersensitivity pneumonitis (2.7%). Patients with tuberculosis (TB) had higher inflammatory parameters such as erythrocyte sedimentation rate and C-reactive protein. Besides granulomas with caseous necrosis were only found in TB patients. Instead, patients with sarcoidosis had skin lesions and a higher frequency of lymphadenopathy. Four patients (5.3%) died in a one-year of follow-up: two of them because of pneumonia and the other two patients because of chronic hypersensitivity and TB respectively. Conclusion: Tuberculosis and sarcoidosis were the most common causes of respiratory granulomas in this retrospective study. A specific cause was determined in 96% of cases, considering clinical, laboratory and histopathological variables to do a right differential diagnosis.

[Clinical and molecular inflammatory alterations in chronic granulomatous disease]. / Alteraciones inflamatorias clínicas y moleculares en enfermedad granulomatosa crónica.

Chronic granulomatous disease (CGD) is an inborn error of immunity. CGD is characterized by a deficiency in the function of the NADPH oxidase complex. CGD has been an opportunity to study the function of reactive oxygen species (ROS) in the innate immune system. The absence of ROS produced by NADPH oxidase in neutrophils and macrophages leads to an increased susceptibility to bacterial and fungal infections since ROS participate in the elimination of microorganisms. Inflammatory and autoimmune manifestations are also present in CGD; however, the causal connection between the lack of ROS and inflammatory symptoms is not entirely clear. Different in vitro assays have been conducted in humans and clinical trials have been conducted in mice in order to try to understand this relationship. Studies show that ROS react with different molecules of the immune system, either by inhibiting or by stimulating their function, which explains why various inflammation pathways that are not related to each other are affected in CGD; therefore, the described mechanisms of affectation have been diverse, such as a greater production of proinflammatory cytokines, an increase in TH17 lymphocytes, and an alteration in processes like spherocytosis, apoptosis, autophagy, and inflammosome. Understanding the mechanisms that lead to inflammation in the deficiency of the NADPH oxidase complex has led to the proposal of new treatments that act on processes like autophagy, inflammosome, or blocking proinflammatory cytokines. In this review, we describe the different inflammatory manifestations in CGD and the molecular mechanisms through which the lack of ROS leads to hyperinflammation.

La enfermedad granulomatosa crónica (EGC) es un error innato de la inmunidad. Se caracteriza por deficiencia en la función del complejo de la NADPH oxidasa. La EGC ha sido una oportunidad para estudiar la función de las especies reactivas de oxígeno (ROS) en el sistema inmune innato. La ausencia de ROS producidas por la NADPH oxidasa en los neutrófilos y en los macrófagos lleva a mayor susceptibilidad a infecciones bacterianas y fúngicas, debido a que las ROS participan en la eliminación de los microorganismos. Las manifestaciones inflamatorias y autoinmunes también están presentes en la EGC, sin embargo, no es del todo clara la relación de causalidad entre la falta de ROS y los síntomas inflamatorios. Se han realizado diversos ensayos in vitro en humanos y experimentales en ratones para tratar de entender esta relación. Los estudios muestran que las ROS reaccionan con diferentes moléculas del sistema inmune, inhibiendo o estimulando su función, lo que explica que en la EGC se afecten varias vías de la inflamación que no están relacionadas entre sí; por lo tanto, han sido diversos los mecanismos de afectación descritos, como por ejemplo una mayor producción de citocinas proinflamatorias, un incremento en los linfocitos TH17 y una alteración en procesos como eferocitosis, apoptosis, autofagia e inflamasoma. El entendimiento de los mecanismos que llevan a la inflamación en la deficiencia del complejo de la NADPH oxidasa ha llevado a plantear nuevos tratamientos que actúan en procesos como la autofagia, el inflamosoma o el bloqueo de citocinas proinflamatorias. En esta revisión describimos las diferentes manifestaciones inflamatorias en EGC y los mecanismos moleculares a través de los cuales la falta de ROS conduce a la hiperinflamación.

Treatment of post-intubation laryngeal granulomas: systematic review and proportional meta-analysis / Treatment of post-intubation laryngeal granulomas: systematic review and proportional meta-analysis

Abstract Introduction: Laryngeal granulomas post intubation are benign but recurrent lesions. There is no consensus for its treatment. Objective: To describe the effectiveness of different treatment modalities for primary or recurrent laryngeal granulomas resulting from endotracheal intubation. Methods: Systematic review and proportional meta-analysis. Eligibility criteria - experimental or observational studies with at least five subjects. Outcomes studied - granuloma resolution, recurrence, and time for resolution. Databases used - Pubmed, Embase, Lilacs, and Cochrane. The Stats Direct 3.0.121 program was used. Results: Six studies were selected, with 85 patients. The treatments registered were: antireflux therapy, speech therapy, anti-inflammatory drugs, steroids, antibiotics, zinc sulfate and surgery. 85 patients from six studies had primary treatment: surgery ± associations (41 patients), resolution chance 75% (95% CI: 0.3-100%, I 2 = 90%), absolute relapse risk 25% (95% CI: 0.2-71%); medical treatment (44 patients), resolution chance 86% (95% CI: 67-97%); and absolute relapse risk 14% (95% CI: 3-33%). There was no significant difference between groups. Three studies, encompassing 19 patients, analyzed secondary treatment (failure or recurrence after primary treatment); three subjects presented new recurrence. The time needed to resolve the lesions varied from immediate, after surgery, to 23 months, for inhaled steroid. Conclusion: There is no evidence of high quality that proves the efficacy of any treatment for laryngeal granulomas resulting from endotracheal intubation.

Resumo: Introdução: Granulomas laríngeos pós-intubação são lesões laríngeas benignas, porém recorrentes. Não há um consenso na literatura em relação ao seu tratamento. Objetivo: Descrever a eficácia de diferentes modalidades de tratamento para granulomas laríngeos primários ou recorrentes resultantes da intubação endotraqueal. Método: Estudo-revisão sistemática e metanálise proporcional. Critérios de elegibilidade: estudos experimentais ou observacionais com pelo menos cinco indivíduos. Desfechos estudados: resolução do granuloma, recorrência e tempo de resolução. Bases de dados usadas: Pubmed, Embase, Lilacs e Cochrane. Foi usado o software Stats Direct 3.0.121. Resultados: Foram selecionados seis estudos, com 85 pacientes. Os tratamentos registrados foram: terapia antirrefluxo, terapia da voz, medicamentos anti-inflamatórios, esteroides, antibióticos, sulfato de zinco e cirurgia. Receberam tratamento primário 85 pacientes de seis estudos: cirurgia ± associações (41 pacientes), chance de resolução de 75% (IC 95% 0,3% a 100%, I2 = 90%) e risco absoluto de recorrência de 25% (IC 95%: 0,2% a 71%); tratamento clínico (44 pacientes), chance de resolução de 86% (IC 95%: 67% a 97%) e risco absoluto de recorrência de 14% (IC 95%: 3% a 33%). Não houve diferença significante entre os grupos. Três estudos, que abrangeram 19 pacientes, analisaram o tratamento secundário (falha ou recorrência após o tratamento primário); três indivíduos apresentaram nova recorrência. O tempo necessário para resolver as lesões variou de imediato, logo após a cirurgia, até 23 meses, com tratamento com esteroides inalados. Conclusão: Não há evidências de alta qualidade que provem a eficácia de qualquer tratamento para granulomas laríngeos resultantes da intubação endotraqueal.

Pólipo y/o granuloma aural en niños. Estudio prospectivo en 75 casos / Aural polyp and/or granuloma in children. A prospective study of 75 cases

En otorrinolaringología (ORL) infantil es habitual el hallazgo de pólipos y granulomas de oído en niños que consultan especialmente por otorrea de evolución prolongada. El pólipo y/o granuloma aural es una masa de carácter inflamatorio, que ocupa parte de la luz del conducto auditivo externo, generalmente pediculado, de aspecto congestivo, a veces friable y fácilmente sangrante, cuyo origen generalmente es a nivel de la mucosa del oído medio. Con el objetivo de describir las características clínicas, otológicas, bacteriológicas e histopatológicas de los pólipos y granulomas de oído diagnosticados en un servicio de ORL pediátrico se realizó un estudio prospectivo, descriptivo, observacional y longitudinal. Se estudió a la población pediátrica con diagnóstico de pólipo y/o granuloma aural en su primera consulta en el servicio de ORL del Hospital de Pediatría "Prof. Dr. Juan P. Garrahan". Se incluyeron 75 pacientes en el estudio, evaluados consecutivamente desde el 02 de diciembre 2013 y hasta 30 enero del 2015, con una edad media: 93 meses (rango 2­180). Se realizó otomicroscopía y, en los casos de granulomas y pólipos accesibles, se realizó toma de muestra para estudio bacteriológico e histopatológico y evaluaciones audiológicas y radiológicas con tomografía computarizada (TC) en los casos necesarios. Se indicó el tratamiento médico o quirúrgico adecuado a cada patología. El motivo de consulta principal fue la otorrea como único síntoma en el 81,33% de los casos y, en menor porcentaje, asociada a otros síntomas. Tiempo medio de evolución de los síntomas: 13,5 meses (rango 1-96). No se pudo extraer material en el 20% de los pacientes. Se tomaron muestras para estudio de 60/75 granulomas óticos accesibles. El informe anatomo-patológico fue: granuloma o pólipo inflamatorio en el 50%, tejido epidermoide compatible con colesteatoma en el 41,7%, tuberculosis (TBC) en 3,3%, granuloma por cuerpo extraño en 1,7%, histiocitosis de células de Langerhans (HCL) en 3,3% muestras de pólipos. Se realizó estudio bacteriológico en 57/75 casos. Se desarrollaron gérmenes en 52/57 cultivos. El 32,7% (17/52) fueron cultivos polimicrobianos. Dos casos desarrollaron Mycobacterium tuberculosis. Se observó velamiento de caja, ático o mastoides con erosión ósea en el 46,2% (24/52) de los casos evaluados con TC. Diagnóstico final: colesteatoma 39 pacientes, OMA con pólipo de Scheibe o complicada con mastoiditis 16, OMC simple granulomatosa 13, TBC 2, HCL 2, otitis externa y celulitis en conducto auditivo externo 2 y granuloma a cuerpo extraño 1. Conclusiones: es importante obtener el diagnóstico histológico y microbiológico de los pólipos aurales en niños precozmente para excluir neoplasia u otras enfermedades granulomatosas específicas y evitar cirugías que pueden provocar secuelas al no estar indicadas en el tratamiento adecuado de ciertos tumores e infecciones (AU)

In pediatric otolaryngology (ENT) ear polyps and granulomas are a common finding in children who consult especially for prolonged otorrhea. The aural polyp and/or granuloma is an inflammatory mass occupying part of the lumen of the external auditory canal. It is usually pedunculated, congestive, sometimes friable, and may bleed easily. Its origin is usually at the level of the mucosa of the middle ear. With the aim to describe the clinical, otological, bacteriological, and histopathological features of ear polyps and granulomas diagnosed in a Department of pediatric ENT, a longitudinal, prospective, descriptive, observational study was conducted. Pediatric patients diagnosed with an aural polyp and/or granuloma at the first visit at the Department of ENT of Hospital de Pediatría "Prof. Dr. Juan P. Garrahan" were studied. Seventy-five patients were included in the study, evaluated consecutively from December 2, 2013 to January 30, 2015; Mean age was 93 months (range 2 ­ 180). Otomicroscopy was performed and, in cases of accessible granulomas and polyps, a sample was taken for bacteriological and histopathological study. Audiological and radiological evaluations with computed tomography (CT scan) were performed when necessary. Appropriate medical or surgical treatment was indicated accordingly. The main reason for the consultation was otorrhea as the only symptom in 81.33% of cases and, in a lesser percentage, associated with other symptoms. Mean time from symptom onset to diagnosis: 13.5 months (range 1-96). No sample could be harvested in 20% of patients. Samples were taken for study of 60/75 accessible ear granulomas. Pathology report was: Inflammatory granuloma or polyp in 50%, epidermoid tissue compatible with cholesteatoma in 41.7%, tuberculosis (TBC) in 3.3%, granuloma due to a foreign body in 1.7%, and Langerhans cell histiocytosis (LHC) in 3.3% of the samples of polyps. Bacterial cultures, performed in 57/75 cases, were positive in 52/57. Polymicrobial microorganisms were found in 32.7% (17/52). Mycobacterium tuberculosis was found in two cases. Opacification of the antrum, attic, and mastoid cavities with bone erosion was observed in 46.2% (24/52) of the cases evaluated with CT. Final diagnosis: Cholesteatoma in 39 patients, OMA with a Scheibe polyp or complicated with mastoiditis in 16, simple granulomatous OMC in 13, TBC in 2, LHC in 2, external otitis and cellulitis in the external ear canal in 2, and granuloma due to a foreign body in 1. Conclusions: Histological and microbiological diagnosis of aural polyps in children should be obtained early to rule out neoplasia other granulomatous diseases to avoid surgery that may cause sequelae and is not the adequate management of certain tumors and infections (AU)

Treatment of post-intubation laryngeal granulomas: systematic review and proportional meta-analysis.

INTRODUCTION: Laryngeal granulomas post intubation are benign but recurrent lesions. There is no consensus for its treatment. OBJECTIVE: To describe the effectiveness of different treatment modalities for primary or recurrent laryngeal granulomas resulting from endotracheal intubation. METHODS: Systematic review and proportional meta-analysis. Eligibility criteria - experimental or observational studies with at least five subjects. Outcomes studied - granuloma resolution, recurrence, and time for resolution. Databases used - Pubmed, Embase, Lilacs, and Cochrane. The Stats Direct 3.0.121 program was used. RESULTS: Six studies were selected, with 85 patients. The treatments registered were: antireflux therapy, speech therapy, anti-inflammatory drugs, steroids, antibiotics, zinc sulfate and surgery. 85 patients from six studies had primary treatment: surgery±associations (41 patients), resolution chance 75% (95% CI: 0.3-100%, I2=90%), absolute relapse risk 25% (95% CI: 0.2-71%); medical treatment (44 patients), resolution chance 86% (95% CI: 67-97%); and absolute relapse risk 14% (95% CI: 3-33%). There was no significant difference between groups. Three studies, encompassing 19 patients, analyzed secondary treatment (failure or recurrence after primary treatment); three subjects presented new recurrence. The time needed to resolve the lesions varied from immediate, after surgery, to 23 months, for inhaled steroid. CONCLUSION: There is no evidence of high quality that proves the efficacy of any treatment for laryngeal granulomas resulting from endotracheal intubation.

Intra cranial granulomatous disease in common variable immunodeficiency: Case series and review of the literature.

BACKGROUND/PURPOSE: Common variable immunodeficiency (CVID) is typically characterized by hypogammaglobulinemia and often but not always recurrent infections. Paradoxically, 8-22% of patients with CVID develop granulomatous disease. Granulomata have been described in many organs including the lungs, skin, liver, spleen, kidneys, eyes, lymph nodes, and intestines. Data about central nervous system (CNS) involvement in CVID are extremely rare. We aim to describe a case series and include an extensive literature review of CNS involvement in CVID to understand the different features and patterns of the disease. METHODS: We searched the English Pubmed database for relevant articles between 1950 and 2014 using the Key Words "common variable immunodeficiency", "granulomatous disease", "brain", "sarcoidosis", and "sarcoid-like syndrome". Data from all case series, surveys, systematic reviews, and individual case reports, as well as retrospective studies were extracted. A total of 15 patients were reported in the literature. We combined our experience with four additional patients from The Cleveland Clinic between 2009 and 2014. Demographics, clinical features, laboratory and imaging findings, treatment and follow-up were extracted for the 19 patients and summarized descriptively. RESULTS: Female sex and Caucasian race represented 63.2% (12/19), and 80% of the patients, respectively. The mean age of CVID diagnosis was 24 years; mean age when the CNS disease was diagnosed was 21.5 years. 68.4% of the patients (13/19) had granulomas involving ≥2 organs including the central nervous system, 31.6% (6/19) had CNS granulomas only. Associated granulomatous diseases occurred in lungs (72.7%), lymph nodes (27.2%), spleen (27.2%), eyes (18.1%), liver (18.1%), parotid glands (9%), and skin (9%). Fifty-three percent (10/19) of the patients had documented recurrent infections, all of them being upper respiratory tract infections. CNS manifestations included seizures (31.6%), headaches (21%), vision loss (15.7%), decreased cognition (10.5%), focal weakness (5.2%), nystagmus (5.2%), ataxia (5.2%), coma (5.2%), polyuria, and polydipsia (5.2%). Brain mass was the most common radiologic finding (70%) followed by leptomeningeal enhancement (10%), non-specific white matter lesions (10%) and absence of normal signal of the neurohypophysis (10%). Brain pathology was available in 12 patients: findings included granulomatous disease in 83.3%, angiocentric granulomas in 50%, vasculitis without granulomas in 8.3%, and lymphocytic infiltrate of the meninges with diffuse non-caseating granulomas in 8.3%. Cerebrospinal fluid analysis revealed elevated total proteins with/or without lymphocytic pleocytosis in 80%. CONCLUSION: CNS disease is a rare challenging complication of CVID. Patients with brain involvement are generally female, Caucasian, and likely have lung involvement. Although immunoglobulin and steroids remain the first line of treatment, other immunosuppressive agents have shown some promise with regards to recurrent relapsing presentations.

Diferential diagnosis between esophageal granuloma and pulmonary metastasis

Background: Spirocercosis is a parasitic infection caused by Spirocerca lupi. This pathology affects canid carnivores, especially domestic dogs. Early diagnosis has been proven challenging and most infected animals are diagnosed when disease is in advanced stage. Exams such as computed tomography scans or radiographs can aid in disease confirmation. Radiographic exam frequently reveals the presence of a mass located in mediastinal region, which can be erroneously diagnosed as pulmonary mass. The aim of this study was to report the differential diagnosis between paraesophageal granuloma, possibly due to spirocercosis, and pulmonary metastasis in a dog with a history of neurofibrosarcoma.Case: A 8 year-old male Cocker Spaniel dog, weighing 17.4 kg, was presented with anterior limb suspension and a recurrent nodule of 2.0 cm diameter, located on the main pad, with previous diagnosis of neurofibrosarcoma (malignant Schwannoma). Routine evaluation work-up included thoracic radiographs and abdominal ultrasound for clinical staging, electrocardiogram, complete blood count (CBC), coagulogram, renal and hepatic function tests, with results within the normal range for the species. The dog submitted to left anterior limb amputation due to recurrent neurofibrosarcoma in the carpal region. Histopathological exam confirmed recurrent neurofibrosarcoma without vascular invasion. Considering neoplasm biological behavior and clean surgical margins, only routine follow-up was established, with clinical exams. The dogwas presented to the Veterinary Hospital five months after surgical treatment and it was presented with fever, prostration, and history of vomiting. Radiographic exam showed a circumscribed mass in caudal mediastinal area. Computed tomography scan was performed to best evaluate the mass and the result was compatible with paraesophageal abscess.[...](AU)

Diferential diagnosis between esophageal granuloma and pulmonary metastasis

Background: Spirocercosis is a parasitic infection caused by Spirocerca lupi. This pathology affects canid carnivores, especially domestic dogs. Early diagnosis has been proven challenging and most infected animals are diagnosed when disease is in advanced stage. Exams such as computed tomography scans or radiographs can aid in disease confirmation. Radiographic exam frequently reveals the presence of a mass located in mediastinal region, which can be erroneously diagnosed as pulmonary mass. The aim of this study was to report the differential diagnosis between paraesophageal granuloma, possibly due to spirocercosis, and pulmonary metastasis in a dog with a history of neurofibrosarcoma.Case: A 8 year-old male Cocker Spaniel dog, weighing 17.4 kg, was presented with anterior limb suspension and a recurrent nodule of 2.0 cm diameter, located on the main pad, with previous diagnosis of neurofibrosarcoma (malignant Schwannoma). Routine evaluation work-up included thoracic radiographs and abdominal ultrasound for clinical staging, electrocardiogram, complete blood count (CBC), coagulogram, renal and hepatic function tests, with results within the normal range for the species. The dog submitted to left anterior limb amputation due to recurrent neurofibrosarcoma in the carpal region. Histopathological exam confirmed recurrent neurofibrosarcoma without vascular invasion. Considering neoplasm biological behavior and clean surgical margins, only routine follow-up was established, with clinical exams. The dogwas presented to the Veterinary Hospital five months after surgical treatment and it was presented with fever, prostration, and history of vomiting. Radiographic exam showed a circumscribed mass in caudal mediastinal area. Computed tomography scan was performed to best evaluate the mass and the result was compatible with paraesophageal abscess.[...]

Algoritmos útiles para el diagnóstico histopatológico de la enfermedad hepática con base en los patrones de daño hepático / Useful Algorithms for Histopathological Diagnosis of Liver Disease Based on Patterns of Liver Damage

En los anteriores artículos, se revisaron las patologías hepáticas más frecuentes desde el punto de vista morfológico y la importancia de una adecuada correlación, para lograr un mejor entendimiento entre clínicos y patólogos. El ejercicio que se hará a continuación, se basa en establecer una aproximación al diagnóstico histopatológico de algunas de las patologías hepáticas a las que se les realiza biopsias con mayor frecuencia, teniendo en cuenta algoritmos basados en patrones de daño hepático

Previous articles have reviewed the most frequent liver pathologies from the morphological point of view and looked at the importance of adequate correlation for obtaining better understanding between clinicians and pathologists. The next exercise is directed toward histopathological diagnosis of some of the liver diseases for which biopsies are performed most frequently. It takes into account algorithms based on patterns of liver damage

Cutaneous Granulomas in Dolphins Caused by Novel Uncultivated Paracoccidioides brasiliensis.

Cutaneous granulomas in dolphins were believed to be caused by Lacazia loboi, which also causes a similar disease in humans. This hypothesis was recently challenged by reports that fungal DNA sequences from dolphins grouped this pathogen with Paracoccidioides brasiliensis. We conducted phylogenetic analysis of fungi from 6 bottlenose dolphins (Tursiops truncatus) with cutaneous granulomas and chains of yeast cells in infected tissues. Kex gene sequences of P. brasiliensis from dolphins showed 100% homology with sequences from cultivated P. brasiliensis, 73% with those of L. loboi, and 93% with those of P. lutzii. Parsimony analysis placed DNA sequences from dolphins within a cluster with human P. brasiliensis strains. This cluster was the sister taxon to P. lutzii and L. loboi. Our molecular data support previous findings and suggest that a novel uncultivated strain of P. brasiliensis restricted to cutaneous lesions in dolphins is probably the cause of lacaziosis/lobomycosis, herein referred to as paracoccidioidomycosis ceti.

Histopathological findings in lungs of hawksbill turtles collected on the coasts of the states of Espírito Santo and Rio de Janeiro, Brazil / Achados histopatológicos em pulmões de tartarugas-de-pente procedentes dos litorais dos estados do Espírito Santo e do Rio de Janeiro, Brasil

The present work aimed to report the histopathological findings verified in lungs of hawksbill turtles (Eretmochelys imbricata) retrieved from the coasts of the states of Espírito Santo and Rio de Janeiro, Brazil. Between the years 2010 and 2014, 29 E. imbricata individuals were found stranded on the coasts, already dead or dying during treatment. Lung samples of all specimens were collected during necropsies, fixed in 10% neutral buffered formalin, subjected to routine histological processing and classified histomorphologically. The findings revealed that 37.93% of the specimens presented lung lesions. Of these, 90.91% were rescued alive and 9.09% were found dead; 63.63% were females and 36.37% were males. The mean weight was 5.44 Kg and the mean length 39 cm, characterizing young individuals. The animals originated from São Francisco de Itabapoana - RJ, Aracruz - ES, São Mateus - ES, Guarapari - ES, Linhares - ES, Itapemirim - ES, and Anchieta - ES. Macroscopic analysis revealed presence of foam, hyperemia, nodules in the parenchyma, cyst and caseous material. Microscopic examination evidenced heterophilic bronchopneumonia, parasitic granulomatous pneumonia caused by spirorchiids, bacterial granulomatous pneumonia, fungal granulomatous pneumonia, and congestion. It was concluded that juvenile specimens of Eretmochelys imbricata, females and males, originated from the states of Espírito Santo and Rio de Janeiro and found stranded both alive or dead, have significant lung lesions, mainly inflammatory ones, associated or not with infectious agents.(AU)

Objetivou-se com este trabalho relatar os achados histopatológicos em pulmões de Eretmochelys imbricata provenientes dos litorais dos estados do Espírito Santo e do Rio de Janeiro, Brasil. Amostras de pulmões de 29 E. imbricata foram coletadas, durante os anos de 2010 a 2014, em necropsias de espécimes encalhadas mortas ou que vieram a óbito durante o tratamento, nos litorais dos estados do Espírito Santo e do Rio de Janeiro, fixadas em formalina tamponada neutra a 10%, submetidas ao processamento histológico de rotina e classificadas histomorfologicamente. Os dados dos animais mostraram que 37,93% dos animais apresentaram lesões pulmonares. Destes, 90,91% foram encontrados vivos e 9,09% morto, 63,63% eram fêmeas e 36,37% machos. O peso médio foi de 5,44kg, e o comprimento médio de 39cm, o que caracterizou animais juvenis. Os animais eram provenientes de São Francisco de Itabapoana - RJ, Aracruz - ES, São Mateus - ES, Guarapari - ES, Linhares - ES, Itapemirim - ES e Anchieta - ES. Á macroscopia, observou-se: presença de espuma, hiperemia, nódulos no parênquima, cisto e cáseo. Ao exame microscópico, foram encontrados broncopneumonia heterofílica, pneumonia granulomatosa parasitária, causadas por espirorquídeos, pneumonia granulomatosa bacteriana, pneumonia granulomatosa fúngica e congestão. Conclui-se que exemplares juvenis de Eretmochelys imbricata, fêmeas e machos, provenientes dos estados do Espírito Santo e do Rio de Janeiro e encalhados tanto vivos quanto mortos, apresentam lesões pulmonares importantes, principalmente as de origem inflamatória, associadas ou não a agentes infecciosos.(AU)