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Introduction: The concept of gut-to-brain communication via microbial or inflammatory pathways is gaining increased attention but genuine pathology directly linking gut perturbation to anxiety is lacking. We hypothesized that duodenal eosinophilia, as known to occur in functional dyspepsia (FD), may be an underlying cause of anxiety and may help explain the striking association between FD and anxiety., Methods: Randomly selected subjects from the national population register of Sweden completed the validated Abdominal Symptom Questionnaire; 1000 completed esophagogastroduodenoscopy and the Hospital Anxiety and Depression Scale questionnaire. Duodenal biopsies were obtained from 1 st (D1) and 2 nd portion (D2). Eligible subjects who underwent endoscopy (n = 887) were invited to participate in a 10-year follow-up study with the same questionnaires. Among endoscopy normal subjects, FD was identified by Rome criteria, and controls were symptom free. Duodenal eosinophilia was based on pre-defined cut-offs. Finding are reported as odds ratios (ORs) with 95% confidence interval and p-value., Results: The study population comprised 89 cases with FD and 124 healthy controls (mean age 62 years, SD 12, 34% male). Clinical anxiety at follow-up was elevated in those with D1 eosinophilia at baseline considering either new-onset anxiety (OR = 4.5, 95% CI 0.8, 23.8; p = 0.08) or follow-up anxiety adjusting for baseline anxiety (OR = 4.51 (95% CI 1.03, 19.81; p = 0.046)., Conclusion: Duodenal eosinophilia may potentially be a mechanism linked to anxiety independent of FD., (© 2021 John Wiley & Sons Ltd.)

Two sporadic cases of eosinophilic solid and cystic renal cell carcinoma (ESC RCC), at our institution, are presented in this study to contribute to the growing literature on this novel renal neoplasm. The first patient was a 38-year-old female with two synchronous renal masses measuring 3.5 and 1.9 cm on preoperative imaging. The second patient was a 44-year-old female with an incidental renal mass measuring 4 cm. Both patients underwent uncomplicated radical nephrectomies. The 1.9 cm mass in the first patient was consistent with clear cell RCC. The dominant mass in the first patient and the tumor in the second patient had microscopic and macroscopic findings in keeping with ESC RCC including a tan appearance, abundant eosinophilic cytoplasm, and CK20+ and CK7- staining. Both patients had an uncomplicated course following surgery with no evidence of local recurrence or distant metastatic disease for 1 and 2 years for the first and second patient accordingly. These cases contribute to a growing body of literature regarding ESC RCC including, to our knowledge, the first reported case of synchronous ESC RCC and clear cell RCC. Further research about this novel renal neoplasm is needed.

Background: Duodenal eosinophilia may play a role in functional dyspepsia (FD), but existing study results are conflicted. We investigated the association between duodenal eosinophils (count and degranulation) and FD symptoms, accounting for atopic conditions, medications, and seasonal variations., Methods: In a cross-sectional study conducted in the Michael E. DeBakey VA Medical Center in Houston, Texas, we analyzed duodenal histopathology of 436 patient samples from a prospective cohort with a validated symptom survey data and chart reviews. FD was defined using Rome II symptom criteria. Eosinophil count was number per 5 high-power fields (HPF), and eosinophil degranulation was eosinophilic granules in the stroma both determined by two independent investigators., Results: The study cohort was predominantly male (87.4%) with a mean age of 59.3 (standard deviation (SD) ± 9.8). Mean and median eosinophil counts were 75.5 (± 47.8) and 63 (IQR: 43, 101) per five HPF, respectively. Duodenal eosinophilia (defined as ≥ 63 per 5 HPF) and eosinophil degranulation were present in 50.5% and 23.1% of patient samples, respectively. FD was observed in 178 patients (41.7%), but neither the mean eosinophil count nor duodenal eosinophilia was associated with FD. Eosinophil degranulation was independently associated with FD overall (OR 1.74; 95% CI 1.08, 2.78; p = 0.02) and early satiety (OR 2.04; 95% CI 1.26, 3.30; p = 0.004)., Conclusions: In this large, ethnically diverse cohort of adult patients, we found no significant association between duodenal eosinophilia and FD. However, the presence of duodenal eosinophilic degranulation, an activated eosinophil marker, was significantly associated with FD, especially early satiety., (© 2020. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objectives/hypothesis: To explore the clinically feasible diagnosis criteria and treatment outcomes of allergy-related sialodochitis (ARS)., Study Design: Prospective Cohort Study., Methods: Ninety-six consecutive patients were enrolled by the following criteria: 1) recurrent swelling of ≥2 large salivary glands that lasted for ≥3 months; 2) with mucus plug exudations; 3) with atopic diseases; 4) ductal stenosis and/or ectasia. Sixty-four patients with elevation of peripheral blood eosinophil (PBE) and/or serum IgE level comprised group A (highly-suspected ARS group), while the remaining 32 comprised group B (patients without confirmed evidence of ARS). These patients were treated with interventional endoscopy. A chronic obstructive sialadenitis symptom (COSS) questionnaire was used to quantify the treatment outcomes., Results: In group A, Serum IgE was elevated in 84.4% of patients and PBE was elevated in 34.4% of patients. Percentage of submandibular gland involvement was higher in group A than group B (48.4% vs. 18.8%). On sialograms, the snowflake changes of branch ducts were seen in higher percentage of group A compared with group B (59% vs. 35% for parotid glands, 27% vs. 8% for submandibular glands, respectively). Mucus plug smears showed abundant eosinophils in 14 group A patients. Biopsy of five group A patients revealed significant eosinophil infiltration around the main and interlobular ducts. During follow-up, the COSS scores were significantly decreased in both groups, and group B was improved better than group A., Conclusion: PBE and serum IgE are important diagnostic indexes of ARS. Mucus plug smear or histopathology verifies the diagnosis. Interventional endoscopy is helpful for ARS cases., Level of Evidence: 3 Laryngoscope, 131:2030-2035, 2021., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc..)

Background: Eosinophilic cystitis is a rare inflammatory disease of the bladder characterized by eosinophilic infiltration of the bladder wall. Most Eosinophilic cystitis cases present with mucosal lesions of the urinary bladder. We present a very rare case of large mass-forming eosinophilic cystitis, involving the inside and outside of the bladder associated with an infected urachal cyst., Case Presentation: A 59-year-old man presented with gross hematuria, fever, dysuria, and suprapubic pain. Computed tomography showed a heterogeneously enhancing mass that measured 7.6 cm × 4 cm located on the anterosuperior portion of the bladder with an internal fluid collection. Cystoscopy revealed a raspberry-like mass lesion on the bladder dome. Transurethral resection of the bladder was initially performed. The mass lesion protruding from inside the bladder was removed, and pus-like fluid was drained. The pathologic diagnosis was eosinophilic cystitis. Follow-up computed tomography showed a remnant mass outside the bladder and urachal cyst. To eliminate the remnant lesion, robot-assisted partial cystectomy was performed. The patient showed no evidence of recurrent disease on follow-up cystoscopy and computed tomography for up to 2 years., Conclusions: Clinicians should consider the possibility of eosinophilic cystitis in patients who present with hematuria, fever, and suprapubic pain and have both intravesical and extravesical masses., (© 2021. The Author(s).)

Eosinophilic fasciitis (EF) and generalized morphea (GM) are rare and difficult-to-treat sclerosing skin diseases which may occur in association with hematologic disorders. We present a 66-year-old man with EF and associated Waldenström macroglobulinemia who received combination therapy with rituximab (375mg/m2 every other week, gradually extended to every eight weeks), prednisolone (1.25-30mg/d), and methotrexate (7.5-15mg/w). Three months after rituximab initiation, his skin condition improved steadily accompanied by a significant improvement in joint mobility with only mild and transitory flares (observation period: 59 months under treatment with rituximab). To date, there are five case reports on rituximab treatment of EF/GM with an association to hypergammaglobulinemia in three of those cases. Therapy effected significant improvement in four patients. Our case adds to the hitherto limited evidence that rituximab may be a promising therapeutic strategy for EF/GM in association with hypergammaglobulinemia.

Introduction: Diagnosis of a polysymptomatic, rare parasitosis requires collaboration of internal specialists, tropical disease specialists, parasitologists and dermatologists., History: The course of disease is shown in a 66-year-old woman who regularly travels to Cameroon and presented with remarkable hypereosinophilia and pruritus with urticarial swellings., Findings and Diagnosis: Using interdisciplinary diagnostics based on travel history, symptoms and laboratory results an occult amicrofilaraemic Loa loa infection with immunological hyperreaction to the parasite antigen, reactive hypereosinophilia and high antibody titers was diagnosed., Therapy and Course: Anthelmintic therapy was inducted with ivermectin and diethylcarbamazine. Treatment with ivermectin alone resulted in a prompt regression of symptoms and decrease of eosinophil levels and antibody titers., Conclusions: Parasitic diseases like L. loa infections are extremely rare in Europe but should be considered as differential diagnosis at an early stage when patients present with appropriate travel history and clinical findings. There is a lack of standardized therapy and follow-up recommendations. A precise recording of all new diagnoses with therapy progress/response should be established in an international registry., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Children undergoing colonoscopy and mucosal biopsies may show increased colonic mucosal eosinophils, which may or may not be associated with inflammatory bowel disease. There is not much clinical data on American children who have isolated increased colonic mucosal eosinophils. We sought to study the clinical correlates of children without inflammatory bowel disease who show increased mucosal eosinophils to understand their clinical presentation, etiological associations, and outcome. A retrospective analysis of children seen at a tertiary-level Children's hospital was performed by reviewing their medical charts and extracting pertinent data. There were 110 children in the study who had increased colonic mucosal eosinophils. Most children presented with abdominal pain, but several of them also had constipation, blood in stools, and diarrhea. Food allergies, irritable bowel syndrome, asthma, and lactase deficiency were the top four conditions present in these patients. Pathology of the colonic distribution revealed involvement of more than two colonic regions in 86% of the subjects, and only two subjects showing epithelial or crypt involvement by eosinophils. All subjects had a good outcome. Children with colonic mucosal eosinophilia (CME) who do not have an inflammatory bowel disease most frequently present with abdominal pain and primarily an increase of lamina propria eosinophils in two or more colonic regions. Based on the etiological associations we noted in the study, a work-up of children with CME may encompass detailed history for functional gastrointestinal disorders and lactose intolerance, testing for food and environmental allergies, stool examination for parasites, and peripheral blood counts. Almost all children had resolution of symptoms in the studied period suggesting that CME in children has a good clinical outcome., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) is a rare malignancy in the thyroid: only 56 cases with histologic descriptions are reported in the literature and fewer reports describe the cytomorphology. Given the rarity of SMECE, data on the cytomorphologic and molecular features are limited. We report a case of a 53-year-old woman with a 5 cm left thyroid mass. Fine-needle aspiration (FNA) revealed atypia of undetermined significance and pathology of left thyroid lobectomy specimen showed SMECE. Additionally, a left pre-auricular lump was noted and FNA followed by left superficial parotidectomy showed basal cell adenoma. Next-generation sequencing showed point mutations in NTRK3 and NF1. Unlike salivary gland mucoepidermoid carcinoma, MAML2 translocations are not present in SMECE. Even though it is a rare entity, awareness of SMECE of the thyroid is important. In this case report we review the cytomorphologic, histologic, and molecular features., (© 2021 Wiley Periodicals LLC.)

Thanatochemistry also known as chemistry of death and is used to determine post mortem interval (PMI). It is arguably one of the critical steps in forensic investigation. Recent addition of analyzing biochemical changes along with the traditional methods have gained importance, as they help us to record very early changes in the tissue specimens. In this view, our study aimed to correlate both histological changes and enzymatic changes in gingival tissue samples at intervals of immediate, 1 h, 5 h, 24 h and 48 h after death. Histologic changes noted were loss of epithelial architecture, chromatin clumping, nuclear vacuolation, karryopyknosis, eosinophilia and wide intercellular junctions. Two enzymes which differentiate between the autolytic phase (acid phosphatase) and putrefactive phase (ammonia) of decomposition were evaluated using UV spectrometer. Results in our study demonstrated there were variations as in gradual increase in ammonia levels (1.13±0.24-26.6±2.09) and gradual decrease in acid phosphatase levels (5.61±0.67-1.25±0.53) at different time intervals till 48 h. The cellular changes in gingival tissue could also be related to time. The result of our study helps us to identify potential of enzymatic changes which when correlated with histological reports helps us to predict the time of death accurately. Replicating this experiment in various known taphonomic conditions and other enzymes could highlight the usefulness of gingival tissue samples in determining time of death., Competing Interests: Funding and conflict statement The authors did not receive any external funding towards this study. The authors also state that there is no conflict of interest among them for this study., (Copyright © 2021. Published by Elsevier B.V.)

Background: Kimura's disease (KD) is a rare chronic inflammatory disease and the etiology remains uncharacterized. The typical manifestations are painless lymph node or subcutaneous masses. There is currently no report of prominent renal interstitial injury and cardiac insufficiency in KD., Case Presentation: A 45-year-old man was referred to our hospital with dark urine, subcutaneous masses in forehead and right retroauricular, multiple lymphadenopathy and unexplained cardiac insufficiency. Renal biopsy demonstrated eosinophilic interstitial nephritis. Laboratory tests revealed eosinophilia and a high level of serum IgE. A biopsy of cervical lymph node was performed and KD was diagnosed. Treatment with oral prednisone resulted in a decrease of eosinophil, serum IgE, improvement of cardiac function, and regression of the subcutaneous mass., Conclusions: We describe an extremely rare KD case presenting with eosinophilic interstitial nephritis, cardiac insufficiency and significant response to prednisone. The clinicians should improve the disease awareness and find optimal treatment.

Cardiac disease is of importance in captive chimpanzee ( Pan troglodytes ) health. Here we report an eosinophilic and necrotizing myocarditis in a 17-y-old chimpanzee with no previous history of cardiac disease that progressed to death within 48 h. Toxic and infectious causes were ruled out. The chimpanzee had eosinophilia at different occasions in previous years. The animal had a severe, diffuse, and acute monophasic necrotizing myocarditis, with a moderate lymphoplasmacytic infiltrate that was rich in eosinophils. Ante- and postmortem investigations are compatible with an unusual eosinophilic myocarditis with clinical evolution and morphology comparable with human eosinophilic myocarditis secondary to hypereosinophilic syndrome.

The parasitic nematode Trichinella spiralis causes trichinellosis, a serious food-borne parasitic zoonosis worldwide. Infection with T. spiralis may also cause myocarditis. In the present study, we used mouse models to assess the impact of blockage of galectin-receptor interactions by α-lactose on cardiac immunopathology during acute T. spiralis experimental infection. Our data demonstrated that, after T. spiralis infection, blockage of galectin-receptor interactions resulted in cardiac dysfunction detected by transthoracic conventional echocardiography, and increased serum Gal-3 level, a biomarker of myocardial damage. In addition, there were increased eosinophil number in peripheral blood, and increased eosinophil infiltration in the heart and spleen tissues accompanied with increased mRNA levels of eosinophil granule proteins (including eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO)) and IL-5 in these organs; increased cardiac fibrosis accompanied with increased Gal-3 and collagen 1 expressions in the hearts of mice with blockage of galectin-receptor interactions after T. spiralis infection. Correlation analysis showed that significant positive correlations existed between the mRNA levels of Gal-3 and ECP/EPO/eosinophil major basic protein/IL-5/CCL11/CCR3/α-SMA/collagen 1 in the hearts of both T. spiralis -infected mice and T. spiralis -infected mice with blockage of galectin-receptor interactions. Our data suggest that galectin-receptor interactions play a pivotal role during acute T. spiralis infection, and lack of galectin-receptor interactions upregulates Gal-3 which, in turn, leads to elevated heart eosinophil recruitment, exacerbated heart pathology and fibrosis, and heart functional damage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yan, Huang and Lu.)

Eosinophilic annular erythema is an idiopathic acute eosinophilic dermatosis. It is a rare condition, with approximately 30 cases reported in the English literature. It features annular, figurate urticarial edematous plaques primarily affecting the trunk and proximal limbs. During evaluation of a patient, secondary causes of eosinophilic inflammation such as allergy-related conditions (eczema, drug, urticaria, contact dermatitis), parasitic infestations, and autoimmune dermatoses will need to be excluded. We present an unusual case of a 47-year-old patient who developed this condition.

Background: Eosinophilic chronic rhinosinusitis (ECRS) is a chronic inflammatory disease, characterized by eosinophilic infiltration, T-helper type 2 (Th2-type) response, and olfactory dysfunction. A master regulator of Th2-type inflammation, thymic stromal lymphopoietin (TSLP), is important for basophil activation. TSLP-elicited basophils are a key factor in the pathogenesis of ECRS., Methods: In order to elucidate the mechanisms of ECRS in humans, we aimed to establish a murine model of ECRS based on TSLP production in response to the topical application of MC903 (a vitamin D3 analog) and the subsequent TSLP-induced basophil activation. Histological analyses were performed to assess immune cell infiltration into the nasal mucosa and to explore the impact of eosinophilic inflammation on the olfactory epithelium. The status of Th2-type inflammation was evaluated by quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA)., Results: Eosinophils, basophils, and M2 macrophages increased significantly in the nasal mucosa of the mice treated with MC903 and ovalbumin (OVA), compared to those treated with OVA alone or the controls. Quantitative real-time PCR and ELISA revealed elevated expression of interleukin (IL)-4, IL-5, IL-13, TSLP, the chemokine CCL11, and CCL24 in the nasal mucosa of the ECRS mice. In parallel, thinned olfactory epithelium and decreased mature olfactory sensory neurons were observed in the ECRS mice., Conclusions: Our model of ECRS displayed Th2-type inflammation in the sinonasal region, including both eosinophil infiltration and basophil infiltration. Additionally, olfactory epithelium turned out to be affected by eosinophilic inflammation. These features are consistent with the characteristics of the human ECRS., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Gastrointestinal inflammatory neuropathy, namely, eosinophilic myenteric ganglioneuronitis (EMG) and lymphocytic ganglioneuronitis (LG), is a form of chronic intestinal pseudo-obstruction and results from the infiltration of the myenteric plexus by eosinophils and lymphocytes, respectively. The literature related to the clinicopathological features of adult inflammatory neuropathy is scarce. We aim to elucidate the clinical and histological details of 7 cases of inflammatory neuropathy (EMG, n = 4, and LG, n = 3) and compare the features of EMG and LG retrospectively. There was no difference between these two entities in terms of clinical, hematological, or biochemical parameters. Histologically, almost all cases (n = 6/7) showed accompanying elements of ganglion cell vacuolization, mesenchymopathy, and partial/complete desmosis in addition to the disease-defining pathology. Besides, all cases of EMG showed infiltration of the inner circular muscle of muscularis propria by eosinophils. Two cases of LG showed additional muscular pathology pertaining to the muscularis propria. Inflammatory infiltration of the myenteric plexus is pathognomonic for the diagnosis of gastrointestinal inflammatory neuropathy although additional features in the form of ganglion cell vacuolization, reduction in the number of ganglia, desmosis, mesenchymopathy, and inflammation of the muscularis propria (eosinophils in EMG) can be seen. The pathologists need proper awareness along with judicious use of special and immunostains for clinching the diagnosis.

Objectives: The Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway play a key role in immune modulation, especially in the polarization of T helper cells. JAK inhibitors reduce inflammation by inhibiting the phosphorylation of STAT. We investigated whether a JAK inhibitor, tofacitinib, can reduce inflammation in a mouse model of chronic rhinosinusitis with nasal polyps (CRSwNP)., Methods: An eosinophilic CRSwNP model was induced using 4-week-old BALB/c mice. The therapeutic effects of topical tofacitinib were compared with the effects of triamcinolone acetonide (TAC). Polyp formation and eosinophilic infiltration were assessed by histology. Levels of phosphorylated STAT (pSTAT), eosinophil cationic protein, and eotaxin were measured by immunohistochemistry. Gene expression levels of GATA-3 was measured using quantitative PCR. The production of cytokines in sinonasal tissues, including interleukin IL-4, IL-5, IL-12, and interferon-γ, were measured using enzyme-linked immunosorbent assays (ELISA)., Results: Topical tofacitinib administration significantly reduced the number of polyp-like lesions and the degree of eosinophilic infiltration, with an efficacy comparable with that of systemic TAC administration. Similarly, the levels of pSTAT6, eosinophil cationic protein, and eotaxin decreased with tofacitinib treatment. Tofacitinib decreased the gene expression level of GATA-3. Lastly, tofacitinib significantly decreased IL-4 and IL-5 production to a similar extent as that by systemic or topical TAC administration. Tofacitinib, but not TAC, significantly increased the production of interferon-γ., Conclusion: Topical tofacitinib administration may be an effective treatment for eosinophilic CRSwNP by inhibiting phosphorylation of STATs., Level of Evidence: N/A. Laryngoscope, 131:E1400-E1407, 2021., (© 2020 American Laryngological, Rhinological and Otological Society Inc, "The Triological Society" and American Laryngological Association (ALA).)

Background: Ozone (O 3 ) exposure elicits allergic rhinitis (AR) exacerbations by mechanisms that remain poorly understood. We used a rat model to investigate the effects of O 3 on eosinophilic airway inflammation and Th2-related response., Methods: Sprague-Dawley (SD) rats were sensitized and challenged with ovalbumin (OVA) to make AR models. Three groups of AR rats were exposed respectively to 0.5, 1.0, 2.0 ppm of O 3 for 2 h daily over 6 weeks consecutively and studied 24 h later. Normal rats exposed to O 3 alone were used as controls. Nasal symptoms and OVA-specific immunoglobulin E (OVA-sIg E) in the serum were evaluated. Inflammatory cells in nasal lavage fluid (NLF) were classified and counted. Cytokines protein levels in NLF were assessed by ELISA. The pathological changes in the nasal mucosa were examined by histology., Results: The combination of allergen and repeated O 3 exposure in rats induced a significant increase of the number of sneezes, nasal rubs, amount of nasal secretion and OVA-sIgE in the serum, accompanied by enhancement of eosinophils in NLF and nasal mucosa. The increase of interleukin-5 (IL-5), IL-13, Eotaxin and decrease of INF-γ protein levels in NLF were detected in AR rats after O 3 inhalation. Hematoxylin and eosin staining showed disordered arrangement of the nasal mucosa epithelium and eosinophilic infiltration in a concentration-dependent manner., Conclusions: O 3 inhalation deteriorated symptoms in AR rats, and the possible mechanism is that ozone co-exposure could enhance the expression of Th2 cytokines, eosinophilic airway inflammation dose-dependently. The observation is helpful for us to understand the synergistic effect of O 3 in the air pollution and allergen on aggravating allergic rhinitis., (Copyright © 2021 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: Patients with eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) have poorer outcomes after endoscopic sinus surgery and a higher recurrence rate. Objective: This study aimed to investigate the profile of clinical symptoms of eCRSwNP and the related risk factors. Methods: We prospectively enrolled 298 inpatients with CRSwNP from February 2019 to December 2019. The patients were divided into eCRSwNP and non-eCRSwNP groups based on the percentage of blood eosinophils; the cutoff value was set at 3.05%. Clinical data on questionnaires, visual analog scale (VAS) scores, and laboratory tests were collected. The differences in clinical symptoms, including nasal congestion, rhinorrhea, olfactory disorders, and head and/or facial pain, between the two groups were analyzed to identify the influential factors. Logistic analysis and receiver operating characteristic curves were used to determine the diagnostic benefit for the specific symptom in the patients in the eCRSwNP group. Results: Nasal congestion and olfactory disorders were significantly different between the eCRSwNP and non-eCRSwNP groups. The patients in the eCRSwNP group more frequently had concerns about olfactory disorders (p = 0.002), whereas patients in the non-eCRSwNP group mostly had nasal congestion (p = 0.001). The logistic analysis showed that the primary risk factors for olfactory disorders of eCRSwNP were disease duration (p = 0.014) and alcohol intake (p = 0.012). Olfactory disorders were not associated with the disease course of the eCRSwNP group but were correlated with the disease duration of non-eCRSwNP (p = 0.008). A VAS score for the olfactory disorders of >5.75 could be used to predict the diagnosis of eCRSwNP (area under the curve, 0.674 [95% confidence intervals, 0.559-0.689]; P < 0.001). Conclusion: Olfactory disorder might be the major nasal symptom that could be used to distinguish a peripheral eosinophilia-based definition of eCRSwNP and non-eCRSwNP. The disease duration was a limiting factor for using olfactory to distinguish two subgroups of nasal polyp. The investigation with regard to the accurate time boundary should be further addressed.

Asthma exacerbations are associated with significant childhood morbidity and mortality. Recurrent asthma attacks contribute to progressive loss of lung function and can sometimes be fatal or near-fatal, even in mild asthma. Exacerbation prevention becomes a primary target in the management of all asthmatic patients. Our work reviews current advances on exacerbation predictive factors, focusing on the role of non-invasive biomarkers and genetics in order to identify subjects at higher risk of asthma attacks. Easy-to-perform tests are necessary in children; therefore, interest has increased on samples like exhaled breath condensate, urine and saliva. The variability of biomarker levels suggests the use of seriate measurements and composite markers. Genetic predisposition to childhood asthma onset has been largely investigated. Recent studies highlighted the influence of single nucleotide polymorphisms even on exacerbation susceptibility, through involvement of both intrinsic mechanisms and gene-environment interaction. The role of molecular and genetic aspects in exacerbation prediction supports an individual-shaped approach, in which follow-up planning and therapy optimization take into account not only the severity degree, but also the risk of recurrent exacerbations. Further efforts should be made to improve and validate the application of biomarkers and genomics in clinical settings.

Rationale: Eosinophilic fasciitis (EF) is an uncommon connective tissue disorder characterized by limb and trunk erythema, with symmetrical thickening of the skin. Its pathogenesis is poorly understood. Treatment consists mainly of glucocorticoids. Yet, no randomized trials have evaluated therapies for this rare disease and the optimal treatment modality remains unclear. Although most patients show partial or complete response to glucocorticoids, many relapse upon drug tapering, while others either do not respond at all or fail to sustain prolonged remission. Second-line therapy for this rare disorder includes mainly methotrexate (MTX), azathioprine, cyclosporine and hydroxychloroquine. Recently, several attempts using rituximab and intravenous immunoglobulins (IVIG) have shown good clinical results., Patient Concerns: The three patients had good clinical response to glucocorticoid treatment, followed by disease flare when the drug dose was tapered. Adding methotrexate in all patients and azathioprine to patient 3 did not lead to remission., Diagnoses: EF was diagnosed in all patients based on clinical presentation accompanied by fascia biopsy that demonstrated eosinophilic fasciitis., Interventions: The patients were successfully treated with rituximab or IVIG, achieving sustained remission., Outcomes: The three cases had good clinical response to glucocorticoid treatment, followed by disease flare when the drug dose was tapered. The patients were then successfully treated with rituximab or IVIG, achieving sustained remission., Lessons: This review of three cases of EF supports the results of previous reports, suggesting addition of rituximab and IVIG is an effective treatment for patients with refractory disease., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Eosinophils have widespread procoagulant effects. Eosinophilic cardiovascular toxicity mostly consists of endomyocardial damage or eosinophilic vasculitis, while reported cases of venous thrombosis (VT) are scarce. We aimed to report on the clinical features and treatment outcomes of patients with unexplained VT and eosinophilia, and to identify predictors of relapse. This retrospective, multicenter, observational study included patients aged over 15 years with VT, concomitant blood eosinophilia ≥ 1G/L and without any other moderate-to-strong contributing factors for VT. Fifty-four patients were included. VT was the initial manifestation of eosinophil-related disease in 29 (54%) patients and included pulmonary embolism (52%), deep venous thrombosis (37%), hepatic (11%) and portal vein (9%) thromboses. The median [IQR] absolute eosinophil count at VT onset was 3.3G/L [1.6-7.4]. Underlying eosinophil-related diseases included FIP1L1-PDGFRA-associated chronic myeloid neoplasm (n = 4), Eosinophilic Granulomatosis with Polyangiitis (n = 9), lymphocytic (n = 1) and idiopathic (n = 29) variants of hypereosinophilic syndrome. After a median [IQR] follow-up of 24 [10-62] months, 7 (13%) patients had a recurrence of VT. In multivariate analysis, persistent eosinophilia was the sole variable associated with a shorter time to VT relapse (HR 7.48; CI95% [1.94-29.47]; p = 0.015). Long-term normalization of eosinophil count could prevent the recurrence of VT in a subset of patients with unexplained VT and eosinophilia ≥ 1G/L.

Exposure to various antigens derived from house dust mites (HDM) is considered to be a risk factor for development of certain allergic diseases such as atopic asthma, atopic dermatitis, rhinitis and conjunctivitis. Chitin is an insoluble polysaccharide (β-(1-4)-poly-N-acetyl-D-glucosamine) and a major component in the outer shell of HDMs. Mice exposed to chitin develop asthma-like airway eosinophilia. On the other hand, several lines of evidence show that the effects of chitin on immune responses are highly dependent on the size of chitin particles. In the present study, we show that chitin induced production of IL-33 and TSLP by alveolar and bronchial epithelial cells, respectively, in mice. IL-25, IL-33 and TSLP were reported to be important for group 2 innate lymphoid cell (ILC2)-, but not Th2 cell-, dependent airway eosinophilia in a certain model using chitin beads. Here, we show that-in our murine models-epithelial cell-derived IL-33 and TSLP, but not IL-25, were crucial for activation of resident lung Th2 cells as well as group 2 innate lymphoid cells (ILC2s) to produce IL-5, resulting in development of chitin-induced airway eosinophilia. Our findings provide further insight into the underlying mechanisms of development of HDM-mediated allergic disorders.

Tyrosine kinase inhibitors (TKIs) have emerged as a new frontier of cancer therapy. These agents include inhibitors of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), BRAF, mitogen‑activated protein kinase kinase (also referred to as MEK), bcr‑abl, c‑KIT, platelet‑derived growth factor (PDGFR), fibroblast growth factor receptor (FGFR), anaplastic lymphoma kinase (ALK) and vascular endothelial growth factor (VEGF). Along with the evolving applications of TKIs, there has been an increased recognition of the breadth of potential cutaneous toxicities to these agents. In this review, we provide an overview of potentially life‑threatening severe cutaneous adverse reactions (SCARs) that may occur during therapy with TKIs. These toxicities include Stevens‑Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP).

In recent years, increased molecular testing and improved immunohistochemical panels have facilitated more specific classification of salivary gland carcinomas, leading to recognition of several novel tumor types and unique histologic variants. Sclerosing microcystic adenocarcinoma, microsecretory adenocarcinoma, and secretory myoepithelial carcinoma are three such recently described entities that demonstrate low-grade cytology, production of prominent secretory material, and variable amounts of sclerotic stroma. This review provides a practical overview of these important and overlapping emerging entities in salivary gland pathology with a focus on distinctive histologic features and helpful ancillary studies that differentiate them from a wide range of familiar morphologic mimics., Competing Interests: Disclosure The author has nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Within the literature, there is overlap in the histopathological features described in eosinophilic folliculitis associated with chronic lymphocytic leukemia (CLL), eosinophilic dermatosis of hematologic malignancy, and acneiform follicular mucinosis. These disorders are described with varying degrees of superficial and deep lymphocytic and eosinophilic inflammation demonstrating perivascular, perifollicular, and folliculocentric involvement with or without follicular mucin deposition. Given significant histopathological overlap, these diagnoses may represent a continuum on a spectrum of dermatoses. Here, we present two cases with histopathological elements that reflect components of this clinicopathological spectrum and compare our findings with previously reported cases to compare and contrast reported features. Our first case is a 71-year-old African American man with long-standing CLL who developed a pruritic erythematous papular eruption on the face and chest with biopsy revealing a dense folliculotropic lymphocytic infiltrate with conspicuous eosinophils and follicular mucinosis. Our second case is a 70-year-old Caucasian man recently diagnosed with CLL/small lymphocytic lymphoma who developed an erythematous papular rash on the neck and face with biopsy revealing superficial and deep perivascular and periadnexal lymphocytic inflammation with scattered eosinophils. Characterization of our two cases and comparison with available literature suggest that these disorders may represent a continuum of dermatoses., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: To investigate the clinical, laboratory, radiological, histopathological, and immunohistochemical features, and the expression of allergy-related cytokines in eosinophilic sialodochitis (ES)., Methods: Thirty-eight patients diagnosed with chronic obstructive sialadenitis (COS) who had undergone glandular excision or incisional biopsy were enrolled. Seventeen patients with comorbid atopic disease and increased ductal tissue eosinophils comprised the ES group, while 21 patients comprised the COS group. The clinicopathological features and allergy-related cytokine expression were compared between groups., Results: The ES group frequently involved multiple, bilateral major salivary glands, and the number of glands was significantly greater than the COS group (2.8 ± 1.1 vs. 1.2 ± 0.4, P < .001). Serum immunoglobulin (Ig) E was elevated in 91% of patients in ES group (419 ± 357 kU/L) and peripheral blood eosinophil was significantly greater compared with the COS group (7.6% ± 4.6% vs. 2.5% ± 1.4%, P < .001). Histologically, eosinophil infiltration in ES group was observed around the main and interlobular ducts (50 ± 39/high power field [HPF]). Follicular hyperplasia (76%), epithelial mucous metaplasia (82%), and mucus plugs with eosinophils (41%) were observed. IgE-positive cell count was 20.7 ± 18.3/HPF and tryptase-positive mast cell count was 23.5 ± 15.1/HPF, which was significantly greater than the respective cell counts in COS group, which mainly infiltrated around the ducts. The levels of interleukin-4, interleukin-13, and eotaxin in tissue were significantly greater in ES than the COS group., Conclusions: The clinicopathological characteristics of ES are significantly different from COS and ES might have an allergy-related pathogenesis., Level of Evidence: 4 Laryngoscope, 131:E800-E806, 2021., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

2'3'-cGAMP is known as a nonclassical second messenger and small immune modulator that possesses potent antitumor and antiviral activities via inducing the stimulator of IFN genes-mediated (STING-mediated) signaling pathway. However, its function in regulating type 2 immune responses remains unknown. Therefore, we sought to determine a role of STING activation by 2'3'-cGAMP in type 2 inflammatory reactions in multiple mouse models of eosinophilic asthma. We discovered that 2'3'-cGAMP administration strongly attenuated type 2 lung immunopathology and airway hyperreactivity induced by IL-33 and a fungal allergen, Aspergillus flavus. Mechanistically, upon the respiratory delivery, 2'3'-cGAMP was mainly internalized by alveolar macrophages, in which it activated the STING/IFN regulatory factor 3/type I IFN signaling axis to induce the production of inhibitory factors containing IFN-α, which blocked the IL-33-mediated activation of group 2 innate lymphoid (ILC2) cells in vivo. We further demonstrated that 2'3'-cGAMP directly suppressed the proliferation and function of both human and mouse ILC2 cells in vitro. Taken together, our findings suggest that STING activation by 2'3'-cGAMP in alveolar macrophages and ILC2 cells can negatively regulate type 2 immune responses, implying that the respiratory delivery of 2'3'-cGAMP might be further developed as an alternative strategy for treating type 2 immunopathologic diseases such as eosinophilic asthma.

Objectives: To summarize cases submitted to the 2019 Society for Hematopathology/European Association for Haematopathology Workshop under the category of myeloid/lymphoid neoplasms with eosinophilia and PDGFRA, PDGFRB, or FGFR1 or with PCM1-JAK2 rearrangements, focusing on recent updates and relevant practice findings., Methods: The cases were summarized according to their respective gene rearrangement to illustrate the spectrum of clinical, laboratory, and histopathology manifestations and to explore the appropriate molecular genetic tests., Results: Disease presentations were heterogeneous, including myeloproliferative neoplasms (MPNs), myelodysplastic syndromes (MDSs), MDS/MPN, acute myeloid leukemia, acute B- or T-lymphoblastic lymphoma/acute lymphoblastic lymphoma (ALL/LBL), or mixed-lineage neoplasms. Frequent extramedullary involvement occurred. Eosinophilia was common but not invariably present. With the advancement of RNA sequencing, cryptic rearrangements were recognized in genes other than PDGFRA. Additional somatic mutations were more frequent in the FGFR1-rearranged cases. Cases with B-ALL presentations differed from Philadelphia-like B-ALL by the presence of an underlying MPN. Cases with FLT3 and ABL1 rearrangements could be potential candidates for future inclusion in this category., Conclusions: Accurate diagnosis and classification of this category of myeloid/lymphoid neoplasms has important therapeutic implications. With the large number of submitted cases, we expand our understanding of these rare neoplasms and improve our ability to diagnose these genetically defined disorders., (© American Society for Clinical Pathology, 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To report the findings of the 2019 Society for Hematopathology/European Association for Haematopathology Workshop within the categories of reactive eosinophilia, hypereosinophilic syndrome (HES), germline disorders with eosinophilia (GDE), and myeloid and lymphoid neoplasms associated with eosinophilia (excluding entities covered by other studies in this series)., Methods: The workshop panel reviewed 109 cases, assigned consensus diagnosis, and created diagnosis-specific sessions., Results: The most frequent diagnosis was reactive eosinophilia (35), followed by acute leukemia (24). Myeloproliferative neoplasms (MPNs) received 17 submissions, including chronic eosinophilic leukemia, not otherwise specified (CEL, NOS). Myelodysplastic syndrome (MDS), MDS/MPN, and therapy-related myeloid neoplasms received 11, while GDE and HES received 12 and 11 submissions, respectively., Conclusions: Hypereosinophilia and HES are defined by specific clinical and laboratory criteria. Eosinophilia is commonly reactive. An acute leukemic onset with eosinophilia may suggest core-binding factor acute myeloid leukemia, blast phase of chronic myeloid leukemia, BCR-ABL1-positive leukemia, or t(5;14) B-lymphoblastic leukemia. Eosinophilia is rare in MDS but common in MDS/MPN. CEL, NOS is a clinically aggressive MPN with eosinophilia as the dominant feature. Bone marrow morphology and cytogenetic and/or molecular clonality may distinguish CEL from HES. Molecular testing helps to better subclassify myeloid neoplasms with eosinophilia and to identify patients for targeted treatments., (© American Society for Clinical Pathology, 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Eosinophilic gastroenteritis is a rare inflammatory disorder of the gastrointestinal tract. Although commonly associated with allergic diseases, it is also rarely associated with autoimmune disorders. This case report describes a 17-year-old Filipino male with eosinophilic gastroenteritis, manifesting as abdominal pain, vomiting and diarrhoea. He had no allergic diseases, but he was previously diagnosed with chronic bullous disease. His symptoms improved with the initiation of corticosteroids. To date, this is the first case report of a patient with eosinophilic gastroenteritis and chronic bullous disease., Competing Interests: Competing interests: MSTR serves in the advisory board of A Menarini, Abbott Nutrition and Sanofi Aventis; a speaker for A Menarini, Abbott Nutrition, Abbott Pharma, Nutricia, RB Mead Johnson, Kalbe, Glenmark, Leo pharma, Mylan, Bayer, Natrapharm, AstraZeneca and Galderma; and received research grants from Galderma and Novartis. MARC served as a speaker and facilitator for a series of research workshop sponsored by Wyeth., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

We evaluated simple laboratory variables to discriminate COVID-19 from bacterial pneumonia or influenza and for the prospective grading of COVID-19. Multivariate logistic regression and receiver operating characteristic curve were used to estimate the diagnostic performance of the significant discriminating variables. A comparative analysis was performed with different severity. The leukocytosis (P = 0.017) and eosinopenia (P = 0.001) were discriminating variables between COVID-19 and bacterial pneumonia with area under the curve (AUC) of 0.778 and 0.825. Monocytosis (P = 0.003), the decreased lymphocyte-to-monocyte ratio (P < 0.001), and the increased neutrophil-to-lymphocyte ratio (NLR) (P = 0.028) were predictive of influenza with AUC of 0.723, 0.895, and 0.783, respectively. Serum amyloid protein, lactate dehydrogenase, CD3 + cells, and the fibrinogen degradation products had a good correlation with the severity of COVID-19 graded by age (≥50) and NLR (≥3.13). Simple laboratory variables are helpful for rapid diagnosis on admission and hierarchical management of COVID-19 patients., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Recurrent cutaneous necrotising eosinophilic vasculitis (RCNEV) is a rare disease that was first described in 1994. We report a case of RCNEV treated with corticosteroid, and 18 cases that we identified in the literature. Our review of the literature shows that RCNEV was frequently identified in middle-aged females from Asia and usually presents as erythematous to purpuric papuloplaques, angio-oedema on the extremities, as well as peripheral eosinophilia. Histopathologically, RCNEV is characterised by exclusively eosinophilic infiltration around the vascular plexus, the absence of leukocytoclasis and fibrinoid degeneration of vascular walls. Although, RCNEV responds to corticosteroid treatment, relapses have occurred during dose tapering. We also discuss the mechanisms of vascular destruction, the differential diagnosis and steroid-sparing therapies for RCNEV., (© 2020 The Australasian College of Dermatologists.)

Introduction: Nasal inverted papilloma (NIP) is a benign tumour with multiple inflammatory cell infiltration. Tertiary lymphoid organs (TLOs) support local antibody production and play important roles in airway inflammation. However, the evidence of TLOs and local immunoglobulins in NIP has not been reported yet. We investigated the presence of TLOs and immunoglobulins in NIP tissues and their association with the clinical-pathological characteristics of NIPs., Methods: We analyzed the occurrence and composition of TLOs and local immunoglobulins by immunohistochemistry and evaluated the lymph organogenesis associated genes and cytokines by quantitative qPCR and Luminex assays, respectively, in papilloma tissues from 84 NIP cases., Results: TLOs were present in 54% (45/84) of the NIP patients but not in control subjects. TLOs were composed of T cells, B cells, follicular dendritic cells, macrophages, and natural killer cells. Compared to NIP tissues without TLOs, tissues with TLOs showed significantly higher eosinophil infiltration levels (3.5-fold), elevation of lymphorganogenic genes (CXCL12, CXCL13, CCL20, CCL21, CD21L, and lymphotoxin alpha and beta), and increased Th17 (IL-21, IL-22, and GM-CSF) and Th2 (IL-5 and IL-13) cytokine production. Moreover, NIP with TLOs demonstrated a higher number of follicular T helper cells and immunoglobulin-producing plasma cells (CD138+ IgA+, CD138+ IgM+, CD138+ IgE+, and CD138+ IgG+) than those without TLOs, and these antibody-producing cells were positively correlated with the eosinophil number., Conclusion: The high frequency of TLOs and excess local immunoglobulin production are associated with an eosinophilic and Th2 skew microenvironment in the NIP mucosa, which would contribute to an important immunopathogenic response during NIP pathogenesis., (© 2020 S. Karger AG, Basel.)

IL-33-activated group 2 innate lymphoid cells critically contribute to protease allergen-induced airway inflammation models. However, IL-33 is dispensable for a subcutaneous (s.c.) papain-induced skin inflammation model, suggesting distinct mechanisms between intranasal and s.c. sensitization. Here, we examined the role of IL-17A in the s.c. model. Papain-exposed skin produced IL-17A and an excess amount of a soluble decoy receptor for IL-33, with the latter being a possible reason for the independence of the s.c. model from IL-33. An IL-17A deficiency attenuated papain-induced skin eosinophilia and serum papain-specific IgE and IgG1 levels, whereas the s.c. administration of IL-17A with enzymatically inactive papain enhanced serum papain-specific IgE and IgG1 levels and T helper 2 development in draining lymph nodes in an IL-33-independent manner, suggesting IL-33-independent enhancement of papain-specific type 2 responses by IL-17A. The s.c. papain increased IL-17A + γδ T cells in draining lymph nodes, approximately half of which were Vγ4 + , as the majority of IL-17A + cells, and increased Vγ5 + and Vγ4 + γδ T cells in the skin. Depletion of γδ TCR + cells reduced T helper cytokine production in antigen-restimulated draining lymph node cells. These results suggest a novel role for IL-17A as an enhancer of skin eosinophilia and serum antigen-specific IgE production and for γδ T cells as an enhancer of T helper cell activation in the s.c. papain model., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Eosinophils are an important subtype of leukocytes derived from bone marrow multipotent hematopoietic stem cells and represent about 1% of leukocytes in circulating blood. In homeostatic conditions, eosinophils reside in the intestine to maintain the balance of immune responses by communicating with gut microbes without causing inflammation. However, under the stressed or diseased condition, eosinophils degranulate, releasing their granule-derived cytotoxic proteins that are involved in inflammatory responses. Various eosinophil-associated inflammatory diseases are eosinophilic esophagitis (EoE), eosinophilic gastroenteritis (EG), and eosinophilic colitis (EC), together called EGID, asthma, hypereosinophilic syndrome, and eosinophilic pneumonia (EP). Eosinophil degranulation results in the release of their four toxic proteins [major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), and eosinophil-derived neurotoxin (EDN)] which promote disease pathogenesis. Pancreatitis is the inflammatory disease of the pancreas that arises due to blockage of the pancreatic duct, trypsinogen mutation, alcohol consumption, and repeated occurrence of pancreatitis leading to chronic pancreatitis (CP); subsequently some CP patients may also develop pancreatic cancer. The presence of eosinophils is now shown in various case reports with acute, recurrent acute, and chronic pancreatitis and pancreatic cancer indicating the role of eosinophils in the pathogenesis of various pancreatic inflammatory disorders. However, the details of eosinophil accumulation during pancreatic diseases are not well explored and need further attention. Overall, the chapter provides the current understanding of reported eosinophils associated with inflammatory diseases like EGID diseases, asthma, and pancreatic disorders, i.e., acute, chronic pancreatitis, and pancreatic cancer. This knowledge will be helpful for future studies to develop novel treatment options for the eosinophils associated diseases. Therefore, more efforts are needed to perform preclinical and clinical studies in this field for the successful development of eosinophil-targeting treatments for a variety of eosinophil-associated diseases.

A 62-year-old patient with bronchial asthma and chronic rhinosinusitis underwent inguinal hernia surgery. After the operation, sudden circulatory arrest occurred, requiring cardiopulmonary resuscitation. Coronary angiography revealed a 99 % proximal stenosis of right coronary artery (RCA) with unsuspicious and smooth coronary vessel walls. In the further course, several similar events occurred, but without pathological findings in the coronary angiography. Initially, echocardiography showed slightly reduced left ventricular ejection fraction of 45 %. Chest radiography revealed bilateral pulmonary infiltrates, and white blood cell count showed severe eosinophilia (37 %). Serological antibody testing including ANA, ENA and c-/p-ANCA was negative. Myeloproliferative pathologies were excluded by bone marrow puncture. The patient suffered from emerging dyspnea, weakness, and ongoing weight loss. A methylprednisolone pulse of 250 mg/d for 3 days remained without significant effect, so that the patient was eventually referred to our university hospital due to ongoing clinical deterioration. On admission, the patient suffered from weakness, progressive muscular atrophy, and dyspnea on exertion. Physical examination revealed a right-sided peroneal paralysis. Bronchial lavage detected severe eosinophil alveolitis (37 %), and laboratory findings showed elevated cardiac enzymes and NT-proBNP (Troponin-T > 700 ng/l, NT-proBNP > 10.000 ng/l). Echocardiography revealed a dramatic deterioration of cardiac function (LVEF 16 %). Interdisciplinary discussion between pulmonologists and cardiologists lead to the diagnosis of ANCA-negative eosinophilic granulomatosis with polyangiitis (EGPA) with pulmonary and cardiac involvement. Initiation of immunosuppressive therapy with methylprednisolone 1000 mg/d for 3 days followed by cyclophosphamide therapy (6 pulses, administered every 4 weeks) led to substantial symptomatic improvement, complete regression of pulmonary infiltrates and marked recovery of cardiac function (LVEF 47 %). CONCLUSION:  Serological detection of elevated ANCAs is not necessary for diagnosis of EGPA. Only 30 - 70 % of patients are positive for these, particularly if neurological and/or renal rather than cardiac and/or pulmonary involvement is present. This may be a pitfall in establishing the correct diagnosis. Induction therapy with cyclophosphamide is the preferred treatment for steroid-refractory EGPA with life-threatening organ involvement., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)