Chronic Inflammatory Features Research Articles

Mapping cutaneous field carcinogenesis of nonmelanoma skin cancer using mesoscopic imaging of pro-inflammation cues.

Nonmelanoma skin cancers remain the most widely diagnosed types of cancers globally. Thus, for optimal patient management, it has become imperative that we focus our efforts on the detection and monitoring of cutaneous field carcinogenesis. The concept of field cancerization (or field carcinogenesis), introduced by Slaughter in 1953 in the context of oral cancer, suggests that invasive cancer may emerge from a molecularly and genetically altered field affecting a substantial area of underlying tissue including the skin. A carcinogenic field alteration, present in precancerous tissue over a relatively large area, is not easily detected by routine visualization. Conventional dermoscopy and microscopy imaging are often limited in assessing the entire carcinogenic landscape. Recent efforts have suggested the use of noninvasive mesoscopic (between microscopic and macroscopic) optical imaging methods that can detect chronic inflammatory features to identify pre-cancerous and cancerous angiogenic changes in tissue microenvironments. This concise review covers major types of mesoscopic optical imaging modalities capable of assessing pro-inflammatory cues by quantifying blood haemoglobin parameters and hemodynamics. Importantly, these imaging modalities demonstrate the ability to detect angiogenesis and inflammation associated with actinically damaged skin. Representative experimental preclinical and human clinical studies using these imaging methods provide biological and clinical relevance to cutaneous field carcinogenesis in altered tissue microenvironments in the apparently normal epidermis and dermis. Overall, mesoscopic optical imaging modalities assessing chronic inflammatory hyperemia can enhance the understanding of cutaneous field carcinogenesis, offer a window of intervention and monitoring for actinic keratoses and nonmelanoma skin cancers and maximise currently available treatment options.

2-Styrylchromones Prevent IL-1β-Induced Pro-Inflammatory Activation of Fibroblast-like Synoviocytes while Increasing COX-2 Expression

Rheumatoid arthritis (RA) is characterized by systemic immune and chronic inflammatory features, leading to the destruction of the joints. Presently, there are no effective drugs able to control synovitis and catabolism in the process of RA. 2-Styrylchromones (2-SC) are a small group of compounds characterized by the attachment of a styryl group to the chromone core that have already been associated to a wide range of biological activities, including antioxidant and anti-inflammatory activities. The present study investigated the effect of a set of six 2-SC on the interleukin-1β (IL-1β)-induced increase of nitric oxide (•NO), inducible form of nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and matrix metalloproteinase-3 (MMP-3) expression levels in human fibroblast-like synoviocytes (HFLS), pointing to the role of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation in the process. From a set of six 2-SC, presenting hydroxy and methoxy substituents, the one presenting two methoxy substituents at C-5 and C-7 of A ring and a catechol group on B ring, significantly reduced •NO production and the expression of its inducible synthase (iNOS). It also significantly reduced the catabolic MMP-3 protein expression. This 2-SC inhibited the NF-κB pathway by reversing the IL-1β - induced levels of cytoplasmatic NF-kB inhibitor alpha (IκBα), and decreasing the p65 nuclear levels, suggesting the involvement of these pathways in the observed effects. The same 2-SC significantly increased the COX-2 expression, which may indicate a negative feedback loop mechanism of action. The properties of 2-SC may be of great value in the development of new therapies with improved efficacy and selectivity towards RA, and thus deserve further exploitation and evaluation to disclose the full potential of 2-SC.

Clinicopathological characteristics of anti-PD-1 associated gastroenteritis

Objective: To investigate the clinicopathological features of anti-PD-1 related gastroenteritis, understand and recognize the disease, and avoid misdiagnoses. Methods: Three cases of anti-PD-1 related gastroenteritis diagnosed and treated at the Zhongshan Hospital Affiliated to Fudan University, Shanghai, China from 2020 to 2021 were collected. The clinical and pathological features were analyzed and the patients were followed up by telephone. Results: The three patients were all male and aged 63, 39 and 73 years, respectively. They had previously developed gastrointestinal symptoms as a result of immunotherapy for a malignant tumor. Endoscopically, 2 patients presented with pancolitis, and 1 patient presented with a large antral ulcer involving the pyloric canal in the stomach. Histologically, there were marked atrophy and thinning of the epithelium, diffuse infiltration of numerous neutrophils in the lamina propria, formation of micro-abscesses in the crypt/glandular lumen, structural changes (branching and distortion) of the glands, and significant glandular dilatation. In addition, chronic inflammatory features (e.g., lymphoplasmacytosis) were focally seen in 2 cases. Cytomegalovirus immunohistochemical stains were negative in all 3 cases. Based on the history and morphology, all 3 cases were diagnosed as anti-PD-1 related gastroenteritis. According to the above diagnosis, the treatment for all 3 patients was to stop anti-PD-1 therapy and use corticosteroids. Clinical follow-up was conducted. The gastrointestinal symptoms of all 3 patients improved significantly and diarrhea symptoms were relieved after stopping immunotherapy. Conclusions: Anti-PD-1 related gastroenteritis is not rare, but pathologists may lack sufficient understanding of it. Combined with clinical history and pathologic characteristics of the lesion, pathologists should consider this disease to avoid the misdiagnoses and missed diagnoses.

Pathological features of Brucella spondylitis: A single-center study

ObjectiveTo explore the pathological features of Brucella spondylitis (BS) under the optical microscope, thus providing pathological references for the diagnosis. MethodsWe retrospectively analyzed 70 BS patients (42 males and 28 females, mean age 52.01 ± 10.77 [20–74] years) admitted in the Department of Spine Surgery, the General Hospital of Ningxia Medical University, from January 2013 to December 2020. Their medical history, clinical manifestations, laboratory test results, imaging findings and bacteriological culture results were collected. Among them, 5, 5, 43, 4 and 13 cases demonstrated involvement into the cervical vertebra, thoracic vertebra, lumbar vertebra, thoracolumbar vertebra and lumbosacral vertebra, respectively. Notably, L4 showed pathology in 32 cases. Pathological features of BS were analyzed by H&E staining of granulation tissues, sclerotic bones, sequestrums, and intervertebral discs. Results42 cases underwent bacterial culture, of which 4 were positive, and the positive rate of bacterial culture was only 9.5%. The highest Vas score was 7, the lowest was 4, and the average was 5.76 ± 0.89. The highest CRP was 153 mg/L, the lowest was 0.98 mg/L, and the average was 30.98 ± 33.79 mg/L. The highest ESR is 112 mm/h, the lowest is 5 mm/h, and the average is 49.34 ± 27.73 mm/h. Under the optical microscope, BS manifested acute or chronic inflammation. Acute inflammatory features included neutrophil and eosinophil infiltration, necrosis, and abscesses, while chronic inflammatory features included lymphocyte, plasma cell, fibrous tissue and monocyte infiltration, hyaline degeneration, angiogenesis and hyperplasia of other tissues. Other features included vasodilation, hemorrhage, granulomas and multinucleated giant cell infiltration. In the present study, chronic inflammation was observed in 25 cases, in-acute-phase chronic inflammation in 45 cases, and acute inflammation in no cases. Pathological features of BS under the microscope included foam cell reaction in 46 cases, histiocytic reaction in 24 cases and eosinophilic abscesses in 6 cases. Eosinophil infiltration was observed in 45 cases (mainly during the acute phase of chronic inflammation) and massive eosinophilic abscesses in 6 cases. Granulation tissue hyperplasia followed inflammatory repair in 25 BS cases, and was generally boosted in the acute phase of chronic inflammation. Multinucleated giant cell infiltration and granulomas were less observed in BS cases, which differed from pathological features of spinal tuberculosis. ConclusionsChronic inflammation or in-acute-phase chronic inflammation is the main pathological feature of BS, while the single acute inflammation is less observed in BS cases. Foam cell reaction and histiocytic reaction scale up during the acute phase of chronic inflammation, and some BS patients may develop massive eosinophilic abscesses. Granulation tissue hyperplasia, rather than multinucleated giant cell infiltration and granulomas, serve as pathological reference for the differential diagnosis of BS and spinal tuberculosis.

Angiomyomatous hamartoma of subglottic tracheal wall in a 12-year-old adolescent: a case report

BackgroundAllergic rhinitis is the most common allergic disease encountered in a primary care setting. Diagnosis is often made clinically based on response to empiric therapy. However, with long-term treatment failure and/or atypical disease presentation, a differential diagnosis should be considered. The following is a report of an unusual and rare presentation of a subglottic tracheal angiomyomatous hamartoma in an adolescent, treated for many years as allergic rhinoconjunctivitis and asthma.Case presentationA 12-year-old Caucasian was referred to the allergy clinic with a lifetime history of bronchospasms and rhinoconjunctivitis symptoms, treated for many years for asthma and environmental allergies. Cough, posterior nasal drainage, self-described “choking on phlegm,” and a sensation of “a flap in the throat,”, worsened 5 months prior to the initial evaluation. Puncture skin testing for common environmental allergens was negative. Spirometry, performed due to history of chronic cough, showed blunting of the forced expiratory phase. A chest X-ray, immediately ordered to rule out possible extrapulmonary obstruction, showed bilateral bibasilar infiltrates. A noncontrast computerized tomographic scan of the chest, ordered to further elucidate X-ray findings, revealed a subglottic tracheal mass. Following a subsequent transfer and admission to a tertiary hospital center, microlaryngoscopy, bronchoscopy, and microsuspension laryngoscopy were performed to remove the tracheal mass. Pathology confirmed squamous mucosa with polypoid angiomyomatous changes and chronic inflammatory features consistent with angiomyomatous hamartoma. Surgical intervention was successful, and follow-up 1 year postoperatively revealed a healthy, asymptomatic adolescent child with normal lung function.ConclusionsAlthough posterior nasal drainage and cough are typical presenting symptoms in the general patient population, they may be clinically impactful as they could disguise more serious medical conditions. A detailed history and careful physical examination may provide a high index of suspicion of disease, and can help work the differential diagnosis. This case presentation is the first documentation of subglottic hamartoma reported in the pediatric literature with clinical manifestation of environmental allergy and asthma symptoms.

An unusual presentation of pemphigus foliaceus following COVID‐19 vaccination

An unusual presentation of pemphigus foliaceus following COVID‐19 vaccination

P584 Mucosal Eosinophilia is an Independent Predictor of Vedolizumab Effectiveness in Ulcerative Colitis

Abstract Background Ulcerative Colitis (UC) is characterized by intestinal inflammation with chronic inflammatory features. Along with the typical neutrophil-predominant inflammation, there has been growing understanding of the role of eosinophils in UC and the potential therapeutic benefit of Vedolizumab (VDZ) in those cases. VDZ blocks gastrointestinal homing of T lymphocytes and eosinophil recruitment to the intestinal mucosa via blocking α4β7 which plays a major role in eosinophils localization to the intestinal mucosa. We aimed to assess whether mucosal eosinophilia can predict response to VDZ. Methods A retrospective study in a single IBD center. Active UC patients who were initiated on VDZ were identified. All patients had at least one documented encounter of VDZ infusion, colonoscopy prior to initiation of VDZ and afterwards with mucosal biopsies at both time points. The endoscopic activity was scored using Mayo endoscopic subscore (MES) with remission as MES 0 or 1. Clinical response was assessed using Physician’s Global Assessment (PGA) as no response, partial or complete clinical response and clinical remission. Histology was reported by an expert GI pathologist and the response was assessed as none, partial or complete. Mucosal eosinophilia was graded at initial and follow-up biopsies as not conspicuous vs. conspicuous with predominance of eosinophils (>100 eosinophils in at least 2 hpf). Eosinophil activity defined as presence of at least 1 of the 3 histologic features: eosinophilic microabscesses, eosinophilic cryptitis, or degranulated eosinophils Results 107 UC patients were included in the study with a mean age of 44.9 years, majority were males (N = 61, 55.5%), Caucasians (N = 96, 87.3%) and with pancolonic location (N = 100, 90.9%). Mean disease duration was 11.3 yrs (SD, 8.6). 55.5% of patients had prior aTNF exposure. Clinical remission was observed in (N = 63, 57.3%) and endoscopic remission (N = 73, 66.4%) after initiating VDZ. Complete histological response was observed in (N=50, 46.7%). Baseline characteristics based on endoscopic remission is shown where male sex, disease location and the proportion of patients with conspicuous eosinophils with abnormal activity in mucosal biopsies as well as no improvement in eosinophil activity compared to pre-treatment biopsies is greater among those not in endoscopic remission. In a stepwise backward logistic regression model including sex and disease location, improvement in abnormal eosinophilic activity was independently associated with increased odds of endoscopic remission after initiating vedolizumab (OR 4.3; CI, 1.1 - 16.4, p = 0.03). Conclusion In ulcerative colitis, change in mucosal eosinophilia after initiating VDZ was an independent predictor of endoscopic remission with VDZ.

Recent advances on the role of cytotoxic T lymphocytes in the pathogenesis of spondyloarthritis.

Spondyloarthritis (SpA) is a chronic inflammatory disorder with complex etiology and pathogenesis. Its pathogenesis likely involves a combination of different factors. These factors include host genetics, environmental triggers, and immune and microbiota dysregulation. One of the strongest genetic associations with SpA is HLA-B27, implicating the involvement of cytotoxic T lymphocytes (CTLs) in SpA pathogenesis. Despite this discovery dating back decades ago, the CTL compartment that underlies SpA inflammation has yet to be fully defined until recently. Indeed, recent published studies support a significant role that CTLs play in contributing to chronic joint inflammation, which is a hallmark of SpA pathology. In this review chapter, we discuss emerging evidence that supports a newfound role of CTLs in SpA pathogenesis. This emerging evidence includes enrichment of CTL-related genes from genome-wide association studies, overrepresentation of pathogenic synovial CTL phenotype, clonal expansion, and immune dysregulation of CTLs. The discoveries of this mounting evidence suggest that CTL homeostasis is altered, and a disrupted adaptive immunity underlies the chronic inflammatory features seen in SpA pathology.

Outcomes of inflammatory bowel disease in patients with eosinophil-predominant colonic inflammation

BackgroundInflammatory bowel disease (IBD) is characterised by acute intestinal mucosal inflammation with chronic inflammatory features. Various degrees of mucosal eosinophilia are present along with the typical acute (neutrophil-predominant) inflammation. The...

Quercetin Exposure Suppresses the Inflammatory Pathway in Intestinal Organoids from Winnie Mice.

Inflammatory bowel diseases (IBDs) are chronic and relapsing immune disorders that result, or possibly originate, from epithelial barrier defects. Intestinal organoids are a new reliable tool to investigate epithelial response in models of chronic inflammation. We produced organoids from the ulcerative colitis murine model Winnie to explore if the chronic inflammatory features observed in the parental intestine were preserved by the organoids. Furthermore, we investigated if quercetin administration to in vitro cultured organoids could suppress LPS-induced inflammation in wild-type organoids (WT-organoids) and spontaneous inflammation in ulcerative colitis organoids (UC-organoids). Our data demonstrate that small intestinal organoids obtained from Winnie mice retain the chronic intestinal inflammatory features characteristic of the parental tissue. Quercetin administration was able to suppress inflammation both in UC-organoids and in LPS-treated WT-organoids. Altogether, our data demonstrate that UC-organoids are a reliable experimental system for investigating chronic intestinal inflammation and pharmacological responses.

Calcific aortic valve stenosis: Immunohistochemical analysis of inflammatory infiltrate

Calcific aortic valve disease is considered a form of atherosclerosis and, like the latter, possibly of inflammatory origin. The aim of our work was to study the pattern of cellular infiltrate in calcific aortic valve stenosis (CAS). Fifteen operatively excised calcified aortic valves were examined by histology and immunohistochemistry (CD20, CD79α, CD3, CD4, CD8, CD68, CD138, CD117, BJK, BJL, IgA, IgD, IgG, IgG4 and IgM). The findings revealed that in CAS, there were chronic inflammatory features with infiltrates comprising lymphocytes, polyclonal plasma cells, histiocytes and mast cells. In T-lymphocytes, CD4 prevailed over CD8. In B-lymphocytes, there was a slight preponderance of CD20 over CD79α. The BJL (lambda)-positive plasma cells prevailed over the BJK (kappa) ones. The CD138-positive plasma cells comprised 24% IgA-, 20% IgD-, 41% IgG- (including 11% of IgG4-) and 15% IgM-positive cells. CAS did not fulfill the criteria of the recently described clinicopathological entity IgG4-related sclerosing systemic disease. The inflammatory process was the same in both subsets of CAS - those with trileaflet (normally formed) valves and those with congenitally bicuspid valves.

PARRY ROMBERG SYNDROME AND LINEAR SCLERODERMA IN COUP DE SABRE MIMICKING RASMUSSEN ENCEPHALITIS

We present one patient with Parry Romberg syndrome and another with linear scleroderma in coup de sabre, with focal neurologic deficits and intractable seizures arising from the hemisphere ipsilateral to the cutaneous lesion. Brain MRI showed progressive hemispheric atrophy. Pathology after functional hemispherectomy showed chronic inflammatory features suggestive of Rasmussen encephalitis.

Parry Romberg syndrome and linear scleroderma in coup de sabre mimicking Rasmussen encephalitis

We present one patient with Parry Romberg syndrome and another with linear scleroderma in coup de sabre, with focal neurologic deficits and intractable seizures arising from the hemisphere ipsilateral to the cutaneous lesion. Brain MRI showed progressive hemispheric atrophy. Pathology after functional hemispherectomy showed chronic inflammatory features suggestive of Rasmussen encephalitis.

Naturally occurring subclinical ovine mastitis associated with Listeria monocytogenes

Mammary infection with and faecal excretion of Listeria monocytogenes and somatic cell counts in milk were monitored in 98 ewes in a population of 335 in two flocks. From these 98 ewes, three samples were obtained throughout lactation: first at 15–30 days after lambing, second 6–7 weeks later and third 6–7 weeks after the second sampling. No clinical mastitis was recorded in any ewe, but the prevalence of subclinical mammary infection with L. monocytogenes was 3.1% on the first and the second sampling and 6.2% on the third; in 83% of these ewes, bilateral infection was recorded. Somatic cell counts in the milk of ewes with mammary infection ranged from 1.75×10 6 to 2.96×10 6 cells ml −1. Furthermore, L. monocytogenes was isolated from faecal samples of 19.4% of the 98 ewes. Four ewes with L. monocytogenes subclinical mammary infection were euthanatized. L. monocytogenes was isolated from mammary tissue samples of the four ewes and from the liver of two. Chronic inflammatory features predominated in histological sections of mammary tissue samples. It is concluded that L. monocytogenes causes subclinical mastitis in ewes; infection of the mammary gland appeared to be haematogenous.

The effects of inoculation of Listeria monocytogenes into the ovine mammary gland

In each of two experiments, the effects of inoculation of Listeria monocytogenes into the ovine mammary gland were studied. In the first experiment, ewes were challenged with one or other of five different Listeria spp. isolates to study differences in their pathogenicity. In the second, ewes were challenged with L. monocytogenes serotype 1 2 a to study the sequential features of the infection. The reaction of the mammary glands was assessed by bacteriological, cytological and histological methods. No distinct variation in the pathogenicity of L. monocytogenes isolates was evident: all produced subclinical mastitis, independently of their origin or serotype; a L. innocua isolate caused only a transient increase of milk somatic cell counts. After challenge, L. monocytogenes was isolated for 88 days from the milk of inoculated glands, whose milk somatic cell counts were greater than 1.0 × 10 6 cells ml −1. The organism was also isolated from the mammary lymph nodes, but not from any internal organ of any inoculated ewe. In early stages of the infection neutrophilic infiltration was the predominant histological feature, but hyperaemia, and degeneration of alveolar epithelial cells were also recorded. Later, chronic inflammatory features predominated, with lymphocytes as the principal cell types, destruction of alveoli and fibrous tissue proliferation. In the final stage of the experiment, fibrosis was the salient finding. It is concluded that L. monocytogenes can cause subclinical mastitis after intramammary inoculation into ewes.

疑似慢性下気道感染症モデルの作成とエリスロマイシンの効果

The possibility has been proposed that the vicious cycle which consists of basal diseases, bacterial metabolites and host persistent inflammation affected on intractability of chronic respiratory tract infections (CRTI) . To elucidate the contribution of host inflammation to the intractability of CRTI, we investigated the effect of repeated inhalations of sterilized Escherichia colisuspension on cellular and biochemical parameters in bronchoalveolar lavage fluid (BALF) and lung tissue using rats. An influx of neutrophils, a leakage of albumin and an increase of neutrophil elastase activity in airways were maintained during the repeated inhalations, which confirmed that there arose a chronic pulmonary inflammation. In histological studies, the lung tissue of inhaled rats showed chronic inflammatory features which resembled in diffuse panbronchiolitis. In the model, erythromycin reduced the number of neutrophils, the concentration of albumin, and the elastase activity in BALF. Furthermore, no or weak histological changes were observed in the lung tissue of rats treated with erythromycin, and the deterioration of pulmonary mechanics was suppressed.These results suggest that host persistent and excessive inflammation contributes markedly to the exacerbation of basal disease caused by CRTI, and that the suppression of such inflammation is promising to its medical care.

Inflammation and the allergic response

The atopic diseases--allergic rhinitis, asthma, and atopic dermatitis--are chronic inflammatory diseases characterized by an exacerbating and remitting course and can only rarely be associated causally with allergen exposure. The challenge to ascribe an allergic basis to these diseases is derived from the apparent inability to reconcile these chronic inflammatory features with a process thought to be initiated by the rapid release of mediators after the interaction of allergen with IgE-coated mast cells. The traditional understanding has been that mast cell activation results in the release of a series of preformed and rapidly synthesized substances that mediate the immediate onset of vasodilatation, vascular leakage, smooth muscle contraction, and irritant nerve receptor stimulation. These mediators, however, are rapidly degraded and are not thought to be associated with a significant inflammatory component. Recent studies, however, have established that the interaction of allergen with the immune system is, in fact, far more complex (Fig. 4). In addition to mast cell activation, allergen can interact with and activate T-lymphocytes and mononuclear phagocytic cells, leading to the secretion of cytokines and other inflammatory substances. Furthermore, the interaction of allergen with the mast cell may be far more complex, with the potential to stimulate the delayed release of newly synthesized cytokines. The interaction of allergen with the immune system also promotes the secondary release of inflammatory neuropeptides. Thus, the known spectrum of mediators released after allergen exposure has vastly been expanded. These include numerous still uncharacterized chemotactic and activating peptides; eicosanoids such as 5-HETE, 12-HETE, and leukotriene B4; platelet-activating factor; several proteases; neuropeptides and, most importantly, the cytokines. These mediators recruit and activate neutrophils, monocytes, basophils, and eosinophils, attract additional lymphocytes and mononuclear phagocytic cells, and induce mast cell proliferation with further mast cell degranulation. A vicious cycle subsequently develops, with further inflammation and tissue destruction. Thus, the interaction of allergen with the immune system has become a complex cascade capable of producing the chronic inflammatory changes characteristic of allergic diseases.

Abrasive bronchial brushing cytology: A preliminary study of 200 specimens for the diagnosis of neoplastic and nonneoplastic bronchopulmonary lesions

Two hundred subjects with chronic respiratory symptoms with a suspicion of malignancy were selected for bronchial brushing cytology. Prior sputum examination had shown malignant squamous cells in two cases only. The cytologic appearances of the brushing smears were divided into five categories: 41 (20.5%) smears with positively malignant cells; 20 (10%) smears predominantly showing chronic inflammatory features; 31 (15.5%) smears with mainly acute inflammatory changes; 60 (30%) smears with normal cytologic features; and 48 (24%) smears unsatisfactory for cytologic interpretation. Thirteen patients with a positive cytology had a positive tissue biopsy for malignancy. Among the group with chronic inflammatory changes, acid-fast bacilli were identified in nine cases, and one smear showed frank tuberculous granuloma. In the unsatisfactory group, two cases showed malignant cells in the postbrushing sputum. There was one false-negative report for malignancy in the entire study. This study confirms the sensitivity and accuracy of bronchial brushing cytology in the diagnosis of various bronchopulmonary lesions, especially malignancy and pulmonary tuberculosis, in India.