Cytopathology and Polymerase Chain Reaction of Vitreous Fluid in Tubercular Intermediate Uveitis.

Purpose: Cytopathology of vitreous is most commonly done to diagnose vitreoretinal lymphoma in eyes with nonspecific inflammation. Vitreous cytopathology features of tuberculous intermediate uveitis have not been described in literature.Case report: We report a case of a healthy 35-year-old female who showed granulomatous inflammatory changes on vitreous cytopathology with polymerase chain reaction confirming a diagnosis of intraocular tuberculosis.Conclusion: This case highlights the role of cytopathology in determining the etiology and pathogenesis behind the elusive diagnosis of intermediate uveitis. Polymerase chain reaction can further help in confirming the diagnosis and allowing commencement of appropriate therapy.

Overlap Syndromes in Sarcoidosis: Clinical Features and Outcomes.

Sarcoidosis is a multisystem inflammatory disease characterized by noncaseating granulomatous inflammation. While pulmonary sarcoidosis is most common, extrapulmonary involvement occurs in 50 to 74% of patients and can be the presenting abnormality in some patients. The diagnosis of sarcoidosis is based on a compatible clinical presentation in combination with granulomas on histology and exclusion of other causes. However, the absence of a diagnostic biomarker for sarcoidosis, in addition to the overlap of granulomatous inflammation and nonspecific clinical findings with other diseases, often results in a delayed diagnosis. Sarcoidosis overlap syndromes are typically described when sarcoidosis is diagnosed in the presence of another disease (concurrently or sequentially) with shared clinical and histologic features, or when sarcoidosis presents with clinical features typically observed in, but not diagnostic of, other diseases. Awareness of overlap syndromes is important for clinicians to avoid diagnostic errors and evaluate for concomitant diagnoses that may impact the management and outcome of sarcoidosis. This article is intended to provide an overview of these presentations and the most commonly associated diseases, with attention to their prevalence, clinical features, and reciprocal impacts on disease outcomes.

Granulomatous lung disease: clinical aspects.

INTRODUCTION: Granulomatous lung diseases (GLD) are heterogeneous group of diseases that can be broadly categorized as infectious or noninfectious. This distinction is extremely important, as the misdiagnosis of a GLD can have serious consequences. In this manuscript, we describe the clinical manifestations, histopathology, and diagnostic approach to GLD. We propose an algorithm to distinguish infectious from noninfectious GLD. AREAS COVERED: We have searched PubMed and Medline database from 1950 to December 2019, using multiple keywords as described below. Major GLDs covered include those caused by mycobacteria and fungi, sarcoidosis, hypersensitivity pneumonitis, and vasculidities. EXPERT OPINION: The cause of infectious GLD is usually identified through microbiological culture and molecular techniques. Most noninfectious GLD are diagnosed by clinical and laboratory criteria, often with exclusion of infectious pathogens. Further understanding of the immunopathogenesis of the granulomatous response may allow improved diagnosis and treatment of GLD.

A Patient with Necrotizing Vasculitis Related to Sarcoidosis, which Was Diagnosed via Immunohistochemical Methods Using Propionibacterium acnes-specific Monoclonal Antibodies.

Propionibacterium acnes (P. acnes) is a commensal bacterium indigenous to the skin. Previous reports have suggested that infection with P. acnes causes sarcoidosis, a systemic granulomatous disease. We present the case of a 63-year-old woman who developed subcutaneous nodules. A skin biopsy revealed necrotizing vasculitis and noncaseating granulomas, which are characteristic of sarcoidosis. Immunohistostaining revealed a P. acnes skin infection, which led to the diagnosis of sarcoidosis. Minocycline treatment resolved the infection and improved the patient's symptoms. We herein report a case in which immunohistochemistry was useful in the diagnosis of sarcoidosis.

Decidual Granulomata of Unclear Significance.

Granulomatous inflammation is a histologic finding with a relatively wide variety of causes. In general, considerations include infectious etiologies, autoimmune conditions, or foreign body reactions. Granulomatous inflammation is uncommonly seen in the placenta. We present a unique case of a young woman with preterm labor and rupture of membranes whose placenta demonstrated perivascular decidual granulomata in the membranes and the basal plate.

Histopathology of nonspecific granulomatous prostatitis with special reference to eosinophilic epithelial metaplasia: Pathophysiologic, diagnostic and differential diagnostic correlations.

BACKGROUND: Recently, we publish two case reports about association of nonspecific granulomatous prostatitis (NSGP) and eosinophilic metaplasia (EM) in benign prostatic epithelium. There is no investigation of large series of this association in medical literature. Aim of the current study is to investigate the frequency of association of NSGP and prostatic EM in a large series of cases and their relationship with the basic prostate pathology: benign prostatic hyperplasia (BPH), National Institutes of Health-category IV prostatitis (so-called histologic prostatitis (HP)), and prostatic adenocarcinoma (PCa). MATERIALS AND METHODS: A retrospective record review for NSGP was performed on a total of 2366 prostatic specimens of all types of material. All cases of NSGP were reviewed for the presence of EM, BPH, and HP. NSGP with EM-cases and control cases with high grade PCa with endocrine differentiation (so-called Paneth cell-like changes) were evaluated immunohistochemically. RESULTS: NSGP was found in nine cases (0.38%). EM was detected in benign perigranulomatous secretory epithelial cells in 100% of cases with NSGP and were closely associated with BPH and HP. Immunohistochemically, in 55.5% of cases with EM, there was weak focal apical false-positive staining for p504s. CONCLUSION: EM is a very common lesion in NSGP and reflects histologically a nonspecific cellular response, connected with repeated inflammation, in close relation with BPH and HP. We speculate that EM might serve as a morphological precursor of the immunologic phase of NSGP. This constant morphological finding could facilitate the histopathological differential diagnosis of NSGP with other types of granulomatous prostatitis and high grade PCa with or without endocrine differentiation.

Anterior chamber granuloma: conservative treatment versus surgical intervention.

PURPOSE: A distinct pattern of granulomatous anterior uveitis, with white anterior chamber (AC) granuloma, has been reported in certain endemic areas. The aim of this work was to compare the outcome of conservative treatment to surgical intervention for the treatment of large AC granulomas presenting with moderate-severe anterior uveitis. The secondary outcome is ultrasound biomicroscopy (UBM) characterization of AC granulomas. METHODS: This is a prospective randomized interventional study including 41 eyes of 39 patients with active AC granuloma ≥3 mm (flare & cells ≥ +2). Patients were randomly assigned to either conservative treatment in the form of topical prednisolone and cycloplegic drops with orbital floor (transseptal) injection of Triamcinolone acetonide (20 eyes) or surgery in the form of granuloma excision and AC wash (21 eyes). As a perioperative care, topical steroids and cycloplegic drops were given few days before surgery and tapered gradually over 6 weeks. Patients were followed up at first day, 2 weeks, 1 and 3 months. RESULTS: Thirty-seven patients were males, and 2 were females (13.0 ± 3.5 years). After 2 weeks, disappearance/healing of granuloma was achieved in 20 eyes in the surgical group versus 2 eyes in the conservative group (p < 0.0001). This effect was maintained throughout the follow-up period, for the surgical group and reached up to 70%, for the medical group. At every follow-up, BCVA was better in the surgical group, but this was only statistically significant at 1 and 3 months. The granuloma appeared as a homogenous hyperreflective lesion in examined eyes (16 eyes of 15 patients). CONCLUSION: Surgical treatment of large granulomas leads to a more complete and rapid resolution of inflammation.

Granulomatous infective spondylitis in a patient presenting with progressive difficulty in walking: the differential between tuberculosis and brucellosis.

We report a case of infectious spondylitis in a 52-year-old woman who presented with progressive difficulty in walking. The patient had a 2-month long history of neurological symptoms, which progressed rapidly to paraplegia, following her admission. Imaging studies demonstrated the presence of vertebral lesions as well as additional tissue with inflammatory elements in the spinal canal, which caused a mass effect. In combination with the presence of increased cells and protein in the cerebrospinal fluid (CSF), the differential was steered towards causes of infectious spondylitis, primarily tuberculosis. However, brucellosis was also considered, as it is endemic in our area. Prompt surgical decompression produced biopsy samples, which confirmed the presence of granulomatous inflammation. The patient was started on an empiric regimen covering both for tuberculosis and brucellosis, and gradually regained full mobility in her lower limbs. The differential of infectious spondylitis is discussed, with an emphasis on the differentiation between tuberculosis and brucellosis.

New concepts in the pathogenesis of sarcoidosis.

Introduction: The pathogenesis of sarcoidosis is not yet completely understood, although in recent years our knowledge has made considerable progress. Areas covered: This review aims to highlight the latest findings, identified from PubMed, EMBASE, and Web of Science, on the pathogenetic mechanisms of sarcoidosis, considering the studies on potential environmental antigens, genetic background and host immune responses. Particular emphasis has been on recent studies on antigens, as it now seems clear that it is not a single, but various antigens of microbial and non-microbial origin that share the ability to induce the series of immune-inflammatory events that lead to granuloma formation, activating host genetically influenced immune responses that involve innate and even more adaptive immunity. The dysregulation of Th17, Th17.1 cells and Tregs, and their role in the resolution and maintenance of granulomatous inflammation has been reported. Expert opinion: The considerable amount of data that has been accumulated on sarcoidosis pathogenesis will have to be carefully interpreted, particularly to discover which pathways lead to severe forms with organ damage. There is an urgent need for a panel of biomarkers indicating the involvement of the various pathways, to be used for better characterizing patient phenotypes and developing targeted therapies.

A potential role of toll-like receptors, IFN-γ and the phosphatidylinositol 3-kinase pathway in the pathogenesis of acquired mediastinal lymphatic malformation.

Sarcoidosis is a multisystem disorder with non-caseating granulomas in various organs. The etiology of sarcoid granuloma formation is not clear and likely an antigen-induced process. We came across a previously treated sarcoidosis patient who presented with worsening dyspnea on exertion for several months and several days of difficulty swallowing. On Chest CT imaging, large posterior mediastinal mass was found that subsequently diagnosed as macrocystic lymphatic malformation after surgical resection. Pathophysiology of development of acquired lymphatic malformations in a sarcoidosis patient is currently not clear. We hypothesize there might be a complex interplay of Toll-like receptors, IFN-γ and the phosphatidylinositol 3-kinase pathway in the pathogenesis.

Sarcoidosis.

Sarcoidosis is an inflammatory disorder of unknown cause that is characterized by granuloma formation in affected organs, most often in the lungs. Patients frequently suffer from cough, shortness of breath, chest pain and pronounced fatigue and are at risk of developing lung fibrosis or irreversible damage to other organs. The disease develops in genetically predisposed individuals with exposure to an as-yet unknown antigen. Genetic factors affect not only the risk of developing sarcoidosis but also the disease course, which is highly variable and difficult to predict. The typical T cell accumulation, local T cell immune response and granuloma formation in the lungs indicate that the inflammatory response in sarcoidosis is induced by specific antigens, possibly including self-antigens, which is consistent with an autoimmune involvement. Diagnosis can be challenging for clinicians because of the potential for almost any organ to be affected. As the aetiology of sarcoidosis is unknown, no specific treatment and no pathognomic markers exist. Thus, improved biomarkers to determine disease activity and to identify patients at risk of developing fibrosis are needed. Corticosteroids still constitute the first-line treatment, but new treatment strategies, including those targeting quality-of-life issues, are being evaluated and should yield appropriate, personalized and more effective treatments.

Enfermedad granulomatosa hepática.

Granulomas are circumscribed lesions mainly composed of mononuclear cells that arise in response to poorly degradable antigenic stimuli. They are found in 2-15 % of liver biopsies and the meaning of their finding can range from an incidental phenomenon to the manifestation of a systemic disease of infectious, autoimmune or neoplastic origin. Clinical presentation usually points at the underlying pathology; however, the list of associated conditions is extensive, and differs based on patient epidemiological history and baseline characteristics. The most useful element for their study is a thorough medical history, with an emphasis on recent trips, exposures and consumption of drugs or raw or exotic foods. Detailed histopathological analysis may help identify the etiology. For example, the presence of epithelioid granulomas with caseous necrosis indicates tuberculosis and, its absence, sarcoidosis; eosinophil abundance can be associated with drug reactions or parasitic infections; and the presence of foreign bodies can be the cause of granulomatous liver disease (GLD). In this article, we describe the basic clinical-pathological aspects of GLD, and provide a brief summary of the most common etiologies, with an emphasis on the Latin-American region.

Los granulomas son lesiones circunscritas compuestas principalmente por células mononucleares que surgen en respuesta a estímulos antigénicos pobremente degradables. Se encuentran en 2 a 15 % de las biopsias hepáticas; su hallazgo puede significar desde un fenómeno incidental, hasta la manifestación de una enfermedad sistémica de origen infeccioso, autoinmune o neoplásico. El cuadro clínico suele apuntar a la patología subyacente, sin embargo, la lista de condiciones asociadas es amplia y difiere con base en los antecedentes epidemiológicos y a las características basales del paciente. El elemento de mayor utilidad para su estudio es la historia clínica exhaustiva, con énfasis en viajes recientes, exposición de riesgo y consumo de fármacos o alimentos crudos o exóticos. El análisis histopatológico detallado puede auxiliar en la identificación de la etiología, por ejemplo, la presencia de granulomas epitelioides con necrosis caseosa indica tuberculosis y su ausencia, sarcoidosis; la abundancia de eosinófilos es señal de reacciones farmacológicas o infecciones parasitarias; la presencia de cuerpos extraños puede ser la causa de la enfermedad granulomatosa hepática. En este artículo describimos los aspectos clínico-patológicos básicos de esta enfermedad y proveemos un breve resumen de las etiologías más comunes, principalmente en la región de Latinoamérica.

Revisiting hypoxia therapies for tuberculosis.

The spectre of the coming post-antibiotic age demands novel therapies for infectious diseases. Tuberculosis (TB), caused by Mycobacterium tuberculosis, is the single deadliest infection throughout human history. M. tuberculosis has acquired antibiotic resistance at an alarming rate with some strains reported as being totally drug resistant. Host-directed therapies (HDTs) attempt to overcome the evolution of antibiotic resistance by targeting relatively immutable host processes. Here, I hypothesise the induction of hypoxia via anti-angiogenic therapy will be an efficacious HDT against TB. I argue that anti-angiogenic therapy is a modernisation of industrial revolution era sanatoria treatment for TB, and present a view of the TB granuloma as a 'bacterial tumour' that can be treated with anti-angiogenic therapies to reduce bacterial burden and spare host immunopathology. I suggest two complementary modes of action, induction of bacterial dormancy and activation of host hypoxia-induced factor (HIF)-mediated immunity, and define the experimental tools necessary to test this hypothesis.

Enfermedad granulomatosa hepática / Hepatic granulomatous disease

Resumen Los granulomas son lesiones circunscritas compuestas principalmente por células mononucleares que surgen en respuesta a estímulos antigénicos pobremente degradables. Se encuentran en 2 a 15 % de las biopsias hepáticas; su hallazgo puede significar desde un fenómeno incidental, hasta la manifestación de una enfermedad sistémica de origen infeccioso, autoinmune o neoplásico. El cuadro clínico suele apuntar a la patología subyacente, sin embargo, la lista de condiciones asociadas es amplia y difiere con base en los antecedentes epidemiológicos y a las características basales del paciente. El elemento de mayor utilidad para su estudio es la historia clínica exhaustiva, con énfasis en viajes recientes, exposición de riesgo y consumo de fármacos o alimentos crudos o exóticos. El análisis histopatológico detallado puede auxiliar en la identificación de la etiología, por ejemplo, la presencia de granulomas epitelioides con necrosis caseosa indica tuberculosis y su ausencia, sarcoidosis; la abundancia de eosinófilos es señal de reacciones farmacológicas o infecciones parasitarias; la presencia de cuerpos extraños puede ser la causa de la enfermedad granulomatosa hepática. En este artículo describimos los aspectos clínico-patológicos básicos de esta enfermedad y proveemos un breve resumen de las etiologías más comunes, principalmente en la región de Latinoamérica.

Abstract Granulomas are circumscribed lesions mainly composed of mononuclear cells that arise in response to poorly degradable antigenic stimuli. They are found in 2-15 % of liver biopsies and the meaning of their finding can range from an incidental phenomenon to the manifestation of a systemic disease of infectious, autoimmune or neoplastic origin. Clinical presentation usually points at the underlying pathology; however, the list of associated conditions is extensive, and differs based on patient epidemiological history and baseline characteristics. The most useful element for their study is a thorough medical history, with an emphasis on recent trips, exposures and consumption of drugs or raw or exotic foods. Detailed histopathological analysis may help identify the etiology. For example, the presence of epithelioid granulomas with caseous necrosis indicates tuberculosis and, its absence, sarcoidosis; eosinophil abundance can be associated with drug reactions or parasitic infections; and the presence of foreign bodies can be the cause of granulomatous liver disease (GLD). In this article, we describe the basic clinical-pathological aspects of GLD, and provide a brief summary of the most common etiologies, with an emphasis on the Latin-American region.

Postinjection abscesses and granulomas in children adopted from Russia.

Up to 1.3 million children from the former Soviet Union (fSU) and Eastern Europe have been placed in institutional care worldwide. With the hope of ensuring the child's health in the immediate post-adoption period, these children are known to receive many injections of vaccines, vitamins, and medications, many unnecessary and often administered with unsafe technique. This practice can lead to formation of suppurative granulomas in these children. Though rare, dermatologists should be aware of these conditions in adoptees from Eastern Europe.

Matrix metalloproteinase-2 and matrix metalloproteinase-9 in mice with ocular toxocariasis.

In ocular toxocariasis, Toxocara canis-induced inflammatory reaction can lead to eye destruction and granuloma, which is formed by immune cell infiltration and concurrent extensive remodeling tissue. Herein, the histomorphology of granuloma and proteinase production in the eye of T. canis-infected BALB/c mice were investigated. Pathological effects substantially increased after the infection culminated in a severe leukocyte infiltration and granuloma formation from days 4 to 56 post-inoculation. The matrix metalloproteinase (MMP)-2 and MMP-9 activities remarkably increased, compared with those of uninfected control, by gelatin zymography and Western blot analysis in ocular toxocariasis. Granuloma formation had a remarkably positive correlation with MMP-2 and MMP-9 levels. We suggested that T. canis larvae and leukocytes infiltrated from blood vessel both migrated into corpus adiposum orbitae. Activated leukocytes secreted MMP-2 and MMP-9, leading to fibronectin degradation. The imbalance of MMP-2/TIMP-2 and MMP-9/TIMP-1 may play a role in inflammatory cell infiltration and extracellular matrix degradation, forming granuloma, in ophthalmological pathogenesis of T. canis infection.