Correlation between Peripheral Blood Eosinophilia and the Histopathological Changes in Nasal Mucosal in Chronic Rhinosinusitis

Background: Chronic rhinosinusitis(CRS) has emerged as one of the major causes of significant morbidity in otorhinolaryngology, as it is often noted to be refractory to medical management and has a tendency to recur post-surgery. Limited research has shown that peripheral eosinophilia is related to the presence of nasal polyps, the extent of the mucosal disease, the severity of tissue eosinophilia, and the risk of recurrence. Aim: This study aimed to establish the significance of peripheral blood eosinophilia, both differential (EC) and absolute eosinophil counts (AEC) - in adult CRS, to correlate the tissue eosinophilia and peripheral blood eosinophilia, and compare the observations in the two types of CRS with nasal polyp and without nasal polyp. Material and Methods: A total of 50 adult patients with CRS who underwent FESS were included in the study and were divided based on the presence (Group 1) or absence (Group 2) of peripheral blood eosinophilia. Results: There were equal number of cases of chronic rhinosinusitis with nasal polyp (CRSwNP) and without polyp (CRSsNP); 25 each. With regard to clinical features, Group 1 had a higher number of cases with nasal obstruction (p-value = 0.023), post-nasal drip (p-value = 0.035), and hyposmia (p-value = 0.021) when compared to Group 2. On histopathology, Group 1 had more areas of edema (p-value = 0.027), and mucous gland hyperplasia (p-value = 0.013) while Group 2 had prominent lymphoplasmacytic infiltrates (p-value = 0.035), neutrophilia (p-value = 0.047), and tissue infiltration of macrophages (p-value = 0.027). Tissue eosinophilia was present in 32 out of the total cases; 20 (71.43%) in Group 1 and 12 (53.33%) in Group 2. The group with tissue eosinophilia had significantly higher eosinophil count (9.24 ± 4.26% vs 5.32 ± 2.9%; p-value < 0.01) as well as AEC (823.335 ± 434.357/µl vs 485.128 ± 285/µl. 907; p-value < 0.01). Conclusion: The study demonstrated that CRS cases with tissue eosinophilia exhibit an elevated peripheral eosinophil count when compared to non-eosinophilic CRS.

miRNA-205-5p can be related to T2-polarity in Chronic Rhinosinusitis with Nasal Polyps

Background: microRNAs (miRNAs) are directly associated with inflammatory response, but their direct role in CRSwNP (chronic rhinosinusitis with nasal polyps) remains evasive. This study aimed to compare the expression of several miRNAs in tissue samples obtained from patients with CRSwNP and controls and to evaluate if miRNAs correlate to a specific inflammatory pattern (T1, T2, T17, and Treg) or intensity of symptoms in CRSwNP. Methods: nasal polyps (from patients with CRSwNP – n=36) and middle turbinate mucosa (from control patients – n=41) were collected. Microarray determined human mature miRNA expression, and the results obtained were validated by qPCR. miRNAs that were differentially expressed were then correlated to cytokine proteins (by Luminex), tissue eosinophilia, and SNOT-22. Results: After microarray and qPCR analyses, six microRNAs were up-regulated in CRSwNP samples when compared with controls: miR-205-5p, miR-221-3p, miR-222-3p, miR-378a-3p, miR-449a and miR-449b-5p. All these miRNAs are directly implicated with cell cycle regulation and apoptosis, and to a minor extent, with inflammation. Importantly, miR-205-5p showed a significantly positive correlation with IL-5 concentration and eosinophil count at the tissue and with the worst SNOT-22 score. Conclusions: miRNA 205-5p was increased in CRSwNP compared to controls, and it was especially expressed in CRSwNP patients with higher T2 inflammation (measured by both IL-5 levels and local eosinophilia) and worst clinical presentation. This miRNA may be an interesting target to be explored in patients with CRSwNP.

619 HIGH DISCOVERY RATE OF GASTRODUODENAL EOSINOPHILIA BUT NOT EOSINOPHILIC ESOPHAGITIS IN PATIENTS WITH CHRONIC GASTROINTESTINAL SYMPTOMS

Although the prevalence of eosinophilic gastrointestinal disorders (EGIDs) is increasing, there is evidence that eosinophilic gastritis and/or duodenitis (EG/EoD) are underdiagnosed. Patients with EG/EoD often present with chronic, non-specific gastrointestinal (GI) symptoms, similar to patients with functional GI disorders. We hypothesized that systematic evaluation, including multiple esophageal, gastric and duodenal biopsies, of patients with chronic GI symptoms might reveal a high rate of gastroduodenal eosinophila, with or without eosinophilic esophagitis (EoE). Methods We performed a prospective multi-center study of patients with non-specific GI symptoms for ≥6 months, from 20 sites. Patients completed a questionnaire assessing abdominal pain, abdominal cramping, early satiety, bloating, nausea, vomiting, diarrhea, and loss of appetite. Those with daily average symptom severity scores ≥3/10 for any single symptom underwent esophagogastroduodenoscopy (EGD) with collection of 4 esophageal (EoE), 8 gastric, and 4 duodenal biopsies, analyzed by central pathologists. Histologic criteria for EoE was ≥15eos/hpf in ≥1 esophageal site and for EG/EoD was peak eosinophil counts ≥30/hpf in ≥5 gastric hpfs and/or 3 duodenal hpfs—criteria used in randomized trials. Results Of 556 patients screened, 405 (73%) met symptom criteria and underwent EGD; 181 patients (45%, mean age 45, 73% female) who underwent EGD met the histologic criteria for EG/EoD, and of these, 7% also had EoE diagnosed. Overall 2% met histologic criteria for EoE alone. Of patients who met the histologic criteria for EG/EoD, 93% were previously diagnosed with gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), or functional dyspepsia (FD) (Figure 1). The average duration of GI symptoms in the screened population as well as those that met histologic criteria for EG/EoD was 11 years. Conclusion Forty-five percent of patients with moderate-to-severe GI symptoms who underwent EGD met histologic criteria for EG/EoD. Over 90% of these patients had previously been diagnosed with GERD, IBS, and/or FD, and had minimal overlap with EoE. EGD with systematic gastroduodenal biopsies, and intentional evaluation for tissue eosinophilia, should be performed in patients with chronic GI symptoms. Accurate diagnosis of EG/EoD is required for appropriate, targeted treatment and improved outcomes of patients with moderate-to-severe GI symptoms.

The role of tumour-associated tissue eosinophilia as a prognostic indicator in head and neck squamous cell carcinoma

Background Eosinophils are bone marrow-derived granulocytes known to have an imperative role in tissue inflammation. The mechanism of tumour-associated tissue eosinophilia (TATE) in head and neck cancers is however not well understood, and its role as a prognosticator is under evaluation. The aim of this study was to evaluate the association of TATE with factors associated with head and neck cancer and to assess its role as a prognostic marker in such patients. Results 102 males and 24 females comprised the study population, and 34.9% of which were in the age group of 41 to 50 years. Amongst these 126 patients, most (37.3%) presented in stage III followed by stage IV (28.6%). 29.4% had well-differentiated SCC, 55.6% had moderately differentiated SCC, and 15% were diagnosed with poorly differentiated SCC. 42.8% had TATE grade II, followed by grade III (29.4%) and grade I (27.8%). Correlation studies showed that factors significantly associated with TATE were age, site and tumour differentiation. While 45.7% poorly differentiated tumours showed grade I eosinophilia, 51.4% of well-differentiated tumours had grade III TATE. Conclusions TATE showed a highly significant association with tumour differentiation, suggestive of eosinophils partaking a tumouricidal role. This association may be utilised as a convenient early prognosticator for head and neck cancers and should be made a regular feature of biopsy reports. Furthermore, it may be utilised in planning and adopting appropriate treatment modalities in malignancies predicted to have an aggressive course.

Age Related Non-Type 2 Inflammation and its Association with Treatment Outcome in Patients with Chronic Rhinosinusitis with Nasal Polyp in Korea

This study aimed to investigate the effect of age in patients with chronic rhinosinusitis with nasal polyp (CRSwNP). 296 patients were divided into eosinophilic and non-eosinophilic groups based on tissue eosinophilia, defined by eosinophils accounting for more than 20% of the total inflammatory cells. Patients were then further divided into younger and older groups based on the age of 35 years. Clinical characteristics including blood eosinophil, Lund Mackay score, and modified Lund-Kennedy(mLK) scores were compared. Levels of 14 cytokines from nasal tissues of an additional 58 patients were analyzed. Tissue eosinophilia was significantly associated with age, and the proportion of non-eosinophilic CRSwNP was significantly higher in younger patients as compared to older patients (79.2% vs 56.6%). There was no difference in clinical characteristics and cytokine levels between the younger and older patients with eosinophilic CRSwNP. In contrast, younger patients had significantly lower preoperative blood eosinophils and higher mLK scores at three and six months, postoperatively, compared to older patients in patients with non-eosinophilic CRSwNP. Alpha-1 antitrypsin and IL-5 levels were significantly lower in younger patients than in older patients in non-eosinophilic CRSwNP. This study suggests a potential association between age, non-type 2 inflammation and treatment outcome in CRSwNP.

Allergic Aspects of IgG4-Related Disease: Implications for Pathogenesis and Therapy

IgG4-related disease (IgG4-RD) is a rare systemic fibroinflammatory disease frequently associated with allergy. The pathogenesis of IgG4-RD is poorly understood, and effective therapies are limited. However, IgG4-RD appears to involve some of the same pathogenic mechanisms observed in allergic disease, such as T helper 2 (Th2) and regulatory T cell (Treg) activation, IgG4 and IgE hypersecretion, and blood/tissue eosinophilia. In addition, IgG4-RD tissue fibrosis appears to involve activation of basophils and mast cells and their release of alarmins and cytokines. In this article, we review allergy-like features of IgG4-RD and highlight targeted therapies for allergy that have potential in treating patients with IgG4-RD.

Relevance of tissue eosinophilia in subdural hematomata

Chronic subdural hematomata (CSDH) are treated by evacuation. Recurrence occurs in 3-20% of cases, but the factors determining its occurrence have not been determined. Having observed that eosinophil cell infiltrates are often present in the outer membrane of CSDH, our aim was to determine whether such infiltrates are associated with risk of recurrence. Histological sections of the resections from 72 patients with primary CSDH (Mean age 73.4) and 16 with recurrent CSDH (Mean age 72.1) stained with H&E were graded by blinded observers for eosinophilic cell infiltrates using a semiquantitative 0 to 3 scale. The risk of recurrence requiring reoperation (RrR) in primary CSDH was 11.1%, and 12.5% in recurrent CSDH (meaning third surgery was required). A dense (grades 2 or 3) eosinophilic infiltrate was present in 22.2% of primary CSDH; the RrR was 0% in these cases, as compared with 14.8% in cases with sparse (grades 0-1) eosinophilic infiltrate. Among recurrent CSDH cases, 12.5% (2/15) showed a dense eosinophilic infiltrate; the RrR was also 0%, contrasting with 14.3% in those with sparse eosinophilic infiltrate. We conclude that eosinophils either play a role or are a marker of a process leading to stabilizing CSDH, making them less prone to rebleeding. Abstract not previously publishedLearning ObjectivesDescribe the risk of recurrence following surgical evacuation of chronic subdural hematomataRecognize the variable presence of eosinophils in chronic subdural hematomataCite the presence of eosinophils is predictive of absence of recurrence

Clinicopathological Study of Subcutaneous Heminthicnodules : Unusual Sites and Diagnostic Dilemmas

Introduction: Superficial palpable swellings with helmintic infection as an underlying etiology is usually an accidental finding in the surgically excised specimens. Somatic nematodes and cestodes are the commonly implicated organisms, and the zoonotic nematodes show an emerging trend. The present study aims to reappraise the histopathological findings of helminthic etiology in superficial swellings which were clinically suspected to be of neoplastic/non neoplastic nature. Materials and methods: Thirty six cases of palpable superficial nodules with infective etiology over a period of five years were reviewed. 19/36 were of helminthic etiology were included in the present study. Pertinent demographic and clinical data were retrieved from the medical archives. Results: Amongst the 19 cases, 8 were males and 11 females. Chest wall (4/19), and eyelids (3/19) were the most common sites involved. The size ranged from 0.8-15 cm in greatest dimension. Presence of histiocytes (13/19), granulomas (11/19), eosinophils (10/19), and giant cells (9/19) were the most consistent histological findings. 14 cases had discernible parasite morphology with diagnosis of filarial worms (7/19), Dirofilaria (3/19), cysticercosis (4/19), and hydatid cyst (1/19). Four cases had dead and calcified parasites with no discernible morphology. Conclusion: Granulomatous inflammation and tissue eosinophilia are strong indicators of a parasitic etiology. Subcutaneous and intramuscular filariasis, cysticercosis and hydatid cyst are well documented etoiologies whereas Dirofilariasis is an emerging zoonotic infection with worldwide case reports. Imaging techniques and fine needle aspiration can point towards the diagnosis; however in the absence of characteristic features, histopathology can be relied upon to diagnose a helminthicetiology.

Аllergic Basal Deciduitis as a Reason of Recurrent Antenatal Fetal Death

BACKGROUND: Allergic diseases of pregnant women are associated with chronic placental insufficiency and the development of immunopathological conditions of unknown etiology in a child in postnatal life. Pregnancy with bronchial asthma is often complicated by intrauterine growth retardation, preeclampsia, and antenatal fetal death. AIM: The objective was to present a clinical case of recurrent antenatal fetal death in the third trimester in women with bronchial asthma under controlled course. CASE REPORT: Pregnancy proceeded without clinical signs of exacerbation of bronchial asthma and allergic status. However, chronic inflammation with eosinophilia in the intervillous space and the basal lamina was revealed in the placenta tissue. Eosinophilia of the intervillous area was accompanied by obliteration of the intervillous area by fibrin deposits. CONCLUSION: We suppose that immunological inflammation at the fetoplacental unit level can occur regardless of the mother’s allergic status. Moreover, it is likely that the objective state of the mother in the presence of an allergic disease does not reflect the presence/absence of an immunological process in the placenta, as the immunological inflammatory process can develop in different compartments (at the level of the mother’s body and the placental-fetal compartment) with varying degrees of severity.