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This article discusses a case of eosinophilic angiocentric fibrosis (EAF) with atypical clinical presentation involving the skin and upper respiratory tract. EAF is a rare fibroinflammatory condition that primarily affects the orbit and upper respiratory tract. The patient in this case initially presented with a firm plaque on her thigh, which later became inflamed and coincided with upper respiratory tract infections. The diagnosis was confirmed through skin and nasal mucosa biopsies, which revealed characteristic histopathological findings, including eosinophils and IgG4+ plasma cells. The patient's symptoms improved with treatment using methotrexate and prednisone. This case highlights the importance of recognizing the diverse and atypical manifestations of EAF for accurate diagnosis and management. [Extracted from the article]

Background: Crohn's disease (CD) is a chronic intestinal inflammatory disorder, the etiology of which remains unknown, and is characterized by symptoms such as chronic abdominal pain, diarrhea, obstruction, and perianal lesions. Histopathology is widely regarded as the preferred method for diagnosing CD, although the histological diagnosis may lack specificity. The identification of granulomas is commonly believed to be the most reliable diagnostic indicator for CD, surpassing all other clinical features in significance. Nevertheless, research indicates that the detection rate of granulomas in CD exhibits considerable variability. Furthermore, granulomas can manifest in various specific infections including tuberculosis and Yersinia, as well as in a range of diseases characterized by macrophage reactions such as sarcoidosis and drug-induced enteritis. Granulomas associated with CD typically do not exhibit necrosis. However, the formation of caseous granulomas may occur as a result of secondary infections related to anti-CD drug treatment or perforation of the intestinal wall. Case presentation: In this study, we present a case of a 28-year-old female patient diagnosed with CD exhibiting histologic granulomas, including both caseating and non-caseating forms, which demonstrated a positive response to medical treatment. Conclusion: In clinical practice, various forms of granulomas may indicate diverse underlying diseases, yet lack specificity. It is suggested that the presence of caseous granulomas should not be considered as a definitive exclusion criterion for the diagnosis when clinical, endoscopic, imaging and other histopathological features are consistent with CD. This study is the first report of caseous granulomas in CD without concomitant tuberculosis infection. [ABSTRACT FROM AUTHOR]

Background: Anisakiasis, a zoonotic disease caused by the nematode Anisakis, poses a significant concern for public health, particularly in regions with high consumption of raw or undercooked fish. Case Presentation: We present a case report of a 41-year-old woman who developed severe abdominal symptoms, ultimately diagnosed with intestinal obstruction due to Anisakis infestation, requiring surgery. Despite the absence of prominent eosinophilia or specific radiological findings, the diagnosis was confirmed through histological examination, highlighting the importance of considering anisakiasis in patients with a history of raw seafood consumption. Conclusion: The case underscores the diagnostic challenges associated with anisakiasis, emphasizing the need for increased awareness among healthcare professionals and the public regarding the risks of consuming raw or undercooked seafood. Effective management requires a multidisciplinary approach, including clinical assessment, imaging studies, and histological evaluation, to ensure timely diagnosis and appropriate treatment. [ABSTRACT FROM AUTHOR]

The article discusses the case of a Belgian Malinois dog with colorectal pythiosis with partial obstruction and marked colonic dilatation. Topics discussed include tenesmus, hematochezia, intermittent chronic diarrhea and weight loss presented by the dog, the cytological, histopathological and laboratory findings, and euthanasia performed on the dog due to financial constraints and poor prognosis.

This article presents a case study of an 8-year-old cat with a skull mass diagnosed as osteosarcoma, a type of bone cancer. The mass was found to be located in the right frontoparietal region of the skull and caused a shift in the right cerebral hemisphere. The study discusses the clinical signs, imaging findings, and histopathological examination of the mass. It emphasizes the rarity of skull involvement in osteosarcoma and the importance of advanced imaging techniques in diagnosis. The article also provides information on the prognosis and survival rate associated with different types of osteosarcoma in cats. [Extracted from the article]

Influenza A virus (IAV) infections in swine are usually subclinical, but they can reach high morbidity rates. The mortality rate is normally low. In this study, six vaccinated, spontaneously deceased sows revealed IAV infection and enhanced neutrophilic bronchopneumonia with unexpectedly large numbers of infiltrating eosinophils. The purpose of this study was to characterize these lung lesions with special emphasis on the phenotypes of inflammatory cells, the presence of eosinophilic peroxidase (EPO), and neutrophil extracellular traps (NETs). The number of Sirius red-stained eosinophils was significantly higher in the lungs of IAV-infected sows compared to healthy pigs, indicating a migration of eosinophils from blood vessels into the lung tissue stimulated by IAV infection. The detection of intra- and extracellular EPO in the lungs suggests its contribution to pulmonary damage. The presence of CD3+ T lymphocytes, CD20+ B lymphocytes, and Iba-1+ macrophages indicates the involvement of cell-mediated immune responses in disease progression. Furthermore, high numbers of myeloperoxidase-positive cells were detected. However, DNA-histone-1 complexes were reduced in IAV-infected sows, leading to the hypothesis that NETs are not formed in the IAV-infected sows. In conclusion, our findings in the lungs of IAV-infected vaccinated sows suggest the presence of so far unreported field cases of vaccine-associated enhanced respiratory disease. [ABSTRACT FROM AUTHOR]

Background: Diascopy is a point‐of‐care diagnostic test used to differentiate skin erythema due to vascular dilation from haemorrhage. In the veterinary literature, only a handful of diseases have been described to be associated with a negative (nonblanching) diascopy result, and histological investigation of haemorrhage has been inconsistent. Objectives: Retrospective study to undertake a histopathological investigation of canine, nonblanching erythematous dermatoses for the presence or absence of haemorrhage and vascular changes. Materials and Methods: Skin biopsies from dogs presented with moderate‐to‐severe nonblanching erythema were evaluated histologically. Additionally, clinical data about each patient were analysed. Results: Twenty cases were identified with nonblanching erythema. Diagnoses included vasculopathy (n = 6), canine eosinophilic dermatitis (n = 3), cutaneous epitheliotropic T‐cell lymphoma (n = 2), and one case each of sterile granuloma and pyogranuloma syndrome, German shepherd dog pyoderma, multiple mast cell tumours, haemangiosarcoma, exfoliative cutaneous lupus erythematosus, canine leishmaniosis with sebaceous adenitis, sebaceous adenitis with concurrent dermatophytosis, calcinosis cutis and canine atopic dermatitis with insect‐bite reaction. One or more vascular changes were present in all 20 cases and included perivascular oedema, endothelial swelling and neutrophilic infiltration of vessel walls. Haemorrhage was identified in 17 of 20 cases (85%). Three cases without dermal haemorrhage were calcinosis cutis, sebaceous adenitis with dermatophytosis and canine atopic dermatitis with insect‐bite reaction. Conclusions and Clinical Relevance: Negative diascopy was associated with haemorrhage and vascular pathological findings in the majority of cases, yet not all. Haemorrhage was identified histologically in all diseases previously reported as nonblanching as well as in a few additional diseases. [ABSTRACT FROM AUTHOR]

The document discusses a case of iatrogenic transmission of vascular Aß40 amyloid, highlighting the prion-like transmission of amyloid in amyloidosis pathogenesis. A 42-year-old male developed cerebral amyloid angiopathy 29 years after receiving a cadaveric dural graft, leading to multiple intracranial hemorrhages. The case is unique due to the detailed clinical course and histological findings, suggesting a probable case of vascular Aß40 amyloid transmission. The study emphasizes the need for further research on iatrogenic transmission of amyloid and effective treatments for cerebral amyloid angiopathy. [Extracted from the article]

This article discusses a case report of a 15-year-old female with scalp and skin lesions caused by syphilis. The patient presented with a firm lump on her forehead and violaceous, brown papules on her scalp, trunk, and extremities. Laboratory tests and imaging confirmed the diagnosis of syphilis, and further examination revealed additional lesions consistent with secondary syphilis. The article emphasizes the variable clinical presentations of syphilis and the importance of early detection and treatment. Treatment options for syphilitic osteitis are also discussed. [Extracted from the article]

This article discusses a case report of a patient with eosinophilic granulomatosis with polyangiitis (EGPA), a rare systemic antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. The patient presented with a choroidal granuloma near the optic disk, which was highlighted through multimodal imaging. The article describes the patient's medical history, examination findings, and treatment. The authors emphasize the importance of optical coherence tomography (OCT) in diagnosing and imaging retinal pseudo-tumors. This case report provides valuable insights into the ophthalmologic manifestations of EGPA and the utility of multimodal imaging in diagnosing and monitoring the condition. [Extracted from the article]

Objective: SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a highly malignant neoplasm with an undifferentiated or rhabdoid phenotype, posing a diagnostic challenge. This case report aims to create awareness about this rare neoplasm while dealing with cases presenting with undifferentiated morphology. Case Report: A 55-year-old gentleman with constitutional symptoms and lymphadenopathy. Imaging revealed a mass lesion in the right upper lobe of the lung. A biopsy of the cervical lymph node showed diffusely effaced architecture replaced by sheets of undifferentiated pleomorphic cells with vesicular nuclei, prominent nucleoli, eosinophilic cytoplasm, and multiple necrotic foci. An extensive immunohistochemistry (IHC) panel was applied, which showed positivity for synaptophysin, vimentin, and focal CD34 and EMA expression. Other markers like pan-cytokeratin, p40, TTF1, CD56, INSM1, calretinin, CD45, SOX10, S100, CD30, CD117, SMA, and Desmin were negative, with INI1 retained. The IHC panel excluded the morphological differentials of carcinoma, lymphoma, rhabdomyosarcoma, melanoma, and germ cell tumor. Further literature review led to the possibility of the SMARCA4-UT entity, which had a morphology and IHC profile similar to the present case. Testing for SMARCA4 (BRG-1) by IHC showed a complete loss in the tumor cells, favoring the diagnosis of Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT). Conclusion: SMARCA4-UTs are rare, highly aggressive, and poorly differentiated thoracic tumors. Recognizing them is vital as there is potential for therapeutic interventions such as immunotherapy and SMARCA4-targeted therapies, offering promising prospects for the future. [ABSTRACT FROM AUTHOR]

NK/T-cell lymphoma (NKTCL) is a highly aggressive malignant tumour with a very poor prognosis, which often poses diagnostic difficulties due to the non-specificity of its clinical presentation. NK/T-cell lymphoma with eosinophilic hyperplasia syndrome is extremely rare. This article describes a patient with NKTCL misdiagnosed as vasculitis who presented with sinusitis, abdominal pain, anorexia, and lung shadows. Additionally, the patient exhibited extremely high eosinophilia levels, which led to a further misdiagnosis of eosinophilic granuloma. We describe the clinical features, diagnostic methods and differential diagnosis of lymphoma and highlights the importance of a multidisciplinary approach in accurate diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Asthma is a prevalent chronic non-communicable disease, affecting approximately 300 million people worldwide. It is characterized by significant airway inflammation, hyperresponsiveness, obstruction, and remodeling. Eosinophilic asthma, a subtype of asthma, involves the accumulation of eosinophils in the airways. These eosinophils release mediators and cytokines, contributing to severe airway inflammation and tissue damage. Emerging evidence suggests that targeting eosinophils could reduce airway remodeling and slow the progression of asthma. To achieve this, it is essential to understand the immunopathology of asthma, identify specific eosinophil-associated biomarkers, and categorize patients more accurately based on the clinical characteristics (phenotypes) and underlying pathobiological mechanisms (endotypes). This review delves into the role of eosinophils in exacerbating severe asthma, exploring various phenotypes and endotypes, as well as biomarkers. It also examines the current and emerging biological agents that target eosinophils in eosinophilic asthma. By focusing on these aspects, both researchers and clinicians can advance the development of targeted therapies to combat eosinophilic pathology in severe asthma. [ABSTRACT FROM AUTHOR]

This article discusses the lack of detection of aluminum-reactive T-lymphocytes in patients with subcutaneous immunotherapy (SCIT)-induced granulomas. Aluminum contact allergy is commonly seen in children with itching vaccination granulomas, but it can also occur in adults following SCIT. The traditional method of detecting sensitization to aluminum is patch testing, but it has limitations. The study investigates the use of the blood in vitro lymphocyte proliferation test (LPT) as an alternative to patch testing. The results suggest that there may be few or no circulating aluminum-reactive cells in adults with SCIT-induced granulomas, and both patch testing and LPT may have low sensitivity for detecting aluminum contact allergy in adults. [Extracted from the article]

This article discusses a case study of a 72-year-old woman with persistent cutaneous granulomatous lesions on her right arm. Despite numerous treatments, including antibiotics and corticosteroids, the lesions did not improve. The patient was eventually diagnosed with rubella virus (RuV)-associated cutaneous granulomatous disease, which is a rare condition that has been reported in immunocompetent patients. The article highlights the importance of considering RuV infection as a differential diagnosis in cases of cutaneous granulomas of unknown origin, especially when resistant to treatment. Treatment for this condition remains challenging, and further research is needed to develop effective therapies. [Extracted from the article]

Tuberculosis (TB) is caused by a bacterium called Mycobacterium tuberculosis (Mtb). When Mtb enters inside the pulmonary alveolus, it is phagocytosed by the alveolar macrophages, followed by a cascade of immune responses. This leads to the recruitment and accumulation of additional macrophages and T cells in the pulmonary tissues. A key outcome of this is the formation of granuloma, the hallmark of TB infection. In this paper, we develop a mathematical model of the evolution of granuloma by a system of partial differential equations that is based on the classical Keller–Segel chemotaxis equation. We investigate the effect of different parameters on the formation of granuloma. We present numerical simulation results that illustrate the impact of different parameters. The implication of our result on the disease progression is also discussed. [ABSTRACT FROM AUTHOR]

Introduction. Recently, an increased risk of celiac disease or eosinophilic esophagitis has been postulated among patients with either of these disorders, prompting some to suggest a common underlying mechanism, whereas others maintain that their co-existence is coincidental. Methods. We compared clinical and pathological features of 29 patients meeting criteria for both celiac disease and eosinophilic esophagitis to 26 celiac disease and 26 eosinophilic esophagitis controls to determine whether any distinguished study patients from controls. Results. Eight (28%) study patients presented with symptoms of both celiac disease and eosinophilic esophagitis, whereas 14 (48%) had celiac disease symptoms only and 5 had (17%) esophageal symptoms only. Study patients had similar autoimmune and atopic conditions seen in both control groups. Histological severity of disease, including Marsh II-III duodenal histology (study specimens: 87%; controls: 89%), mean peak esophageal eosinophil counts (study specimens: 55/400x field; controls: 80/400X field, P =.1), and presence of eosinophil microabscesses, scale crust, and subepithelial fibrosis were also similar to controls. Gluten-free diet resolved celiac disease-related symptoms (19 of 20, 95%) and histology (10 of 12, 83%), but not esophageal symptoms or eosinophilia in most study patients. Conclusion. Patients with concomitant celiac disease and eosinophilic esophagitis lack distinguishing features compared to controls with celiac disease or eosinophilic esophagitis alone. The occurrence of both disorders is likely coincidental in most cases. [ABSTRACT FROM AUTHOR]

Skull lesions in pediatric population are common findings on imaging and sometimes with heterogeneous manifestations, constituting a diagnostic challenge. Some lesions can be misinterpreted for their aggressiveness, as with larger lesions eroding cortical bone, containing soft tissue components, leading to excessive and, in some cases, invasive inappropriate etiological investigation. In this review, we present multiple several conditions that may present as skull lesions or pseudolesions, organized by groups (anatomic variants, congenital and development disorders, traumatic injuries, vascular issues, infectious conditions, and tumoral processes). Anatomic variants are common imaging findings that must be recognized by the neuroradiologist. Congenital malformations are rare conditions, such as aplasia cutis congenita and sinus pericranii, usually seen at earlier ages, the majority of which are benign findings. In case of trauma, cephalohematoma, growing skull fractures, and posttraumatic lytic lesions should be considered. Osteomyelitis tends to be locally aggressive and may mimic malignancy, in which cases, the clinical history can be the key to diagnosis. Vascular (sickle cell disease) and tumoral (aneurismal bone cyst, eosinophilic granuloma, metastases) lesions are relatively rare lesions but should be considered in the differential diagnosis, in the presence of certain imaging findings. The main difficulty is the differentiation between the benign and malignant nature; therefore, the main objective of this pictorial essay is to review the main skull lytic lesions found in pediatric age, describing the main findings in different imaging modalities (CT and MRI), allowing the neuroradiologist greater confidence in establishing the differential diagnosis, through a systematic and simple characterization of the lesions. [ABSTRACT FROM AUTHOR]

Background: Giant intracranial 'IgG4-related' lesions are uncommon. They may present as pachymeningitis or localized mass. Here we report, probably, the largest IgG4 skull base mass ever to be reported. Case: A 40-year male presented with headache, diplopia, right-sided sensori-neuronal hearing loss, and left spastic hemiparesis. Magnetic resonance imaging showed a lesion of 8.5 cm extending from the paranasal sinuses to the right petroclival region with uniform contrast enhancement and T2 hypointensity. Endonasal biopsy revealed respiratory epithelium with fibrosis, and lymphoplasmacytic infiltrate having IgG4 positive cells >30/HPF suggestive of 'IgG4-related' disease. Serum IgG4 was within normal levels. With oral prednisolone 60 mg given daily for 6 weeks and then tapered off over 8 weeks, he improved symptomatically. Conclusion: Though rare, 'IgG4-related' disease can also present as a giant skull base mass and should be kept as a differential to fungal granulomas and meningiomas. As they improve dramatically with medical management, extensive skull base resection should not be planned before obtaining a tissue biopsy, especially when there is extension into paranasal sinuses and T2 hypointensity. [ABSTRACT FROM AUTHOR]

Summary: Background: Predictive models for eosinophilic oesophagitis (EoE) may not fully rule in the diagnosis. Aim: To develop a reverse model that predicts against EoE to eliminate the need for oesophageal biopsies. Methods: In this two‐centre study, a predictive model was developed (Mayo Clinic) and validated (University of North Carolina [UNC]). Cross‐sectional data from consecutive adult patients without prior EoE who underwent upper enoscopy with oesophageal biopsies were used. EoE cases had ≥15 eosinophils/high‐power field while controls had no eosinophils. Data were collected on patient clinical and endoscopic features. Multiple variable logistic regression was used to identify predictors of non‐EoE status while maintaining specificity ≥95%. A secondary model was developed to predict against the need for endoscopy in patients suspected of having EoE without alarm symptoms. Results: The Mayo and UNC cohorts consisted of 345 (EoE = 94, non‐EoE = 251) and 297 patients (EoE = 84, non‐EoE = 213), respectively. A primary model based on clinical and endoscopic features predicted against EoE with c‐statistic 0.92 (95% CI: 0.88–0.96), specificity 95%, and sensitivity 65%. This model was validated (UNC) with c‐statistic 0.87 (95% CI: 0.82–0.92). A simplified scoring system was created and a threshold of ≥12 points excluded EoE with 95% specificity and 50% sensitivity. A secondary model based on clinical characteristics alone predicted against EoE with c‐statistic 0.86 (95% CI: 0.82–0.90), specificity 95% and sensitivity 39% and validated (UNC) with c‐statistic 0.78 (95% CI: 0.71–0.85). Conclusion: A simplified scoring system accurately identified a group of patients with a low likelihood of EoE where unnecessary oesophageal biopsies can be avoided, potentially resulting in resource and cost savings. [ABSTRACT FROM AUTHOR]

Langerhans cell histiocytosis (LCH) is a disease characterized by localized and generalized proliferation of the histiocytes. It is a locally aggressive condition. The clinical presentation is highly variable and can range from isolated, self-healing skin or bone lesions to life-threatening multisystem disease. It can present as a unifocal or multifocal disease. The majority are present in the head and neck region, but the involvement of Paranasal sinuses is rare. Here we describe a 64-years-old female who presented with a slow-growing left nasal mass for 1 year. Evaluation of the patient was suggestive of malignancy, but the biopsy report turned out to be Langerhans cell histiocytosis; subsequently left, total maxillectomy was done. We hereby present a unique case of LCH with isolated nose and paranasal sinus involvement. [ABSTRACT FROM AUTHOR]

A 46-year-old man who had been diagnosed with eosinophilic otitis media (EOM) and eosinophilic chronic rhinosinusitis was referred to our department. He suffered from bilateral earache, clogged ear sensation, and otorrhea associated with EOM. He had been treated with a myringotomy and a ventilation tube (VT) insertion. However, his symptoms did not improve, and the VT repeatedly fell out. We performed canal wall down mastoidectomy via a retro-auricular incision to remove the presumed cholesterol granuloma (CG) and a long-term VT insertion. The VT fell out repeatedly. Therefore, a large VT that Komune devised was inserted. Four months after reinsertion, there was no evidence of recurrent otorrhea or fallout of a large VT. A large VT insertion could be useful in the severe case of EOM with CG. [ABSTRACT FROM AUTHOR]

This article discusses the delayed occurrence of foreign body reactions caused by poly-L-lactic acid (PLLA) fillers, which are commonly used for tissue augmentation and cosmetic purposes. The article presents a case study of a 52-year-old woman who developed granuloma formation over 100 months after receiving PLLA injections in the nasolabial fold. The article emphasizes the importance of healthcare providers recognizing the potential adverse effects of PLLA fillers and informing patients about these risks. It also highlights the effectiveness of intralesional steroid therapy in managing complications associated with PLLA injections. [Extracted from the article]

Bone defects have recently surfaced as an important topic to discuss in orthopedic clinics, and as a result, they have captured the attention of the biomedical community as well as the general public. Because of their unique characteristics, such as high water content, softness, flexibility, and biocompatibility, hydrogels are gaining more and more traction in the field of tissue regeneration research within the medical industry. Intelligent biomaterials, like hydrogels, are much better than their predecessors because they can respond to new stimuli on multiple levels, such as the physical, chemical, and biological. Because they are sensitive to different outside cues, like shape in three dimensions and conditions between solid and liquid phases, they show certain traits. This indicates that they have the capability of developing into a more efficient material in the future, which would make them better suited to facilitate the localized repair of bone lesions. This article takes a look at hydrogels that alter their shape in response to the environment they are in. Some of the topics covered in this article include the classification of these materials, the concepts that underlie their synthesis, and the current state of research in this potentially fruitful field. This research was conducted with the intention of finding novel ways to treat severe bone defects. [ABSTRACT FROM AUTHOR]

Patients with inborn errors of immunity (IEI) may develop granulomas in multiple organ systems including the skin. Vaccine strain rubella virus (RuV), part of the live attenuated measles, mumps, and rubella (MMR) vaccine, has been identified within these granulomas. RuV is typically found in macrophages; however, recently neutrophils have been identified as a novel cell type infected. Here, we present a case of RuV‐associated cutaneous granuloma with RuV localized to neutrophils. A 46‐year‐old female with common variable immunodeficiency presented with verrucous papules and crusted plaques from the right knee to the distal shin of 20 years duration, associated with prior physical trauma. Biopsy specimen showed palisaded granulomas surrounding central necrosis with scattered aggregates of neutrophils. Vaccine‐derived RuV was detected by molecular sequencing in lesional skin. Fluorescent immunohistochemistry with CD206, myeloperoxidase (MPO), and RV capsid (RVC) antibodies demonstrated that RuV localized to neutrophils but not macrophages. The clinical presentation, cutaneous findings, and likely presence of RVC‐positive granulocytes in bone marrow provide potential support to the evolving hypothesis of persistent RuV within neutrophils contributing to chronic granulomatous inflammation in a milieu of immune dysregulation. [ABSTRACT FROM AUTHOR]

Bovine tuberculosis still represents a universal threat that creates a wider range of public and animal health impacts. One of the most important steps in the pathogenesis of this disease and granuloma formation is the phagocytosis of tuberculous bacilli by macrophages. Mycobacteria replicate in macrophages, which are crucial to the pathophysiology of mycobacterial infections; however, scarce information is available about the dynamics of the granuloma-stage immunological response. Therefore, immunohistochemistry was used in this work to evaluate the expression of CD68, iNOS, and HLA-DR in different stages of TB granulomas from naturally infected cattle with tuberculosis. Two thousand, one hundred and fifty slaughtered beef cattle were examined during the period from September 2020 to March 2022. Sixty of them showed gross tuberculous pulmonary lesions and samples were collected from all of them for histopathological examination, Ziehl-Neelsen (ZN) staining, and bacteriological culturing. Selected samples that yielded a positive result for ZN and mycobacterial culturing were subjected to an immunohistochemical study of CD68, iNOS, and HLA-DR expression by macrophages according to granuloma stages. Immunohistochemical analysis revealed that the immunolabeling of CD68+, iNOS+, and HLA-DR+ macrophages significantly reduced as the stage of granuloma increased from stage I to stage IV (P < 0.003, P < 0.002, and P < 0.002, respectively). The distribution of immunolabeled macrophages was similar for the three markers, with immunolabeled macrophages distributed throughout early-stage granulomas (I, II), and surrounding the necrotic core in late-stage granulomas (III, IV). Our results suggest a polarization to the pro-inflammatory environment and increased expression of CD68+, iNOS+, and HLA-DR+ macrophages in the early stages of granulomas (I, II), which may play a protective role in the immune response of naturally infected beef cattle with tuberculosis. [ABSTRACT FROM AUTHOR]

A male patient in his early sixties with recurrent diarrhea was transferred to our hospital. The patient did not have any pulmonary or upper respiratory symptoms. He was noted to have peripheral eosinophilia. Further workup revealed a negative antineutrophilic cytoplasmic antibody titer but a positive myeloperoxidase antibody and positive proteinase 3 antibodies. A colon biopsy also revealed eosinophilic-rich granulomas in the mucosa, confirming a diagnosis of eosinophilic granulomatosis with polyangiitis. On cardiac imaging, eosinophilic myocarditis was also discovered. To treat active severe EGPA, the patient received high-dose corticosteroids and intravenous cyclophosphamide. The occurrence of gastrointestinal involvement as an initial manifestation of eosinophilic granulomatosis with polyangiitis is infrequent, emphasizing the significance of its recognition. This case underscores the importance of identifying and diagnosing such atypical presentations to facilitate timely and appropriate management. [ABSTRACT FROM AUTHOR]

Only a small number of infected people are highly susceptible to schistosomiasis, showing high levels of infection or severe liver fibrosis. The susceptibility to schistosome infection is influenced by genetic background. To assess the genetic basis of susceptibility and identify the chromosomal regions involved, a backcross strategy was employed to generate high variation in schistosomiasis susceptibility. This strategy involved crossing the resistant C57BL/6J mouse strain with the susceptible CBA/2J strain. The resulting F1 females (C57BL/6J × CBA/2J) were then backcrossed with CBA/2J males to generate the backcross (BX) cohort. The BX mice exhibited a range of phenotypes, with disease severity varying from mild to severe disease, lacking a fully resistant group. We observed four levels of infection intensity using cluster and principal component analyses and K-means based on parasitological, pathological, and immunological trait measurements. The mice were genotyped with 961 informative SNPs, leading to the identification of 19 new quantitative trait loci (QTL) associated with parasite burden, liver lesions, white blood cell populations, and antibody responses. Two QTLs located on chromosomes 15 and 18 were linked to the number of granulomas, liver lesions, and IgM levels. The corresponding syntenic human regions are located in chromosomes 8 and 18. None of the significant QTLs had been reported previously. [ABSTRACT FROM AUTHOR]

Key Clinical Message: We report on a 2‐year‐old boy whose initially inconspicuous skin lesions later on evolved into a typical clinical presentation of benign cephalic histiocytosis (BCH). The diagnosis of BCH can often be made on clinical grounds without the need for an extensive diagnostic work‐up. Given the benign and self‐limited course of the disease treatment is not required and the clinical management can be limited to a watchful waiting approach. [ABSTRACT FROM AUTHOR]

Aneurysmal bone cyst (ABC) is a benign osteolytic, expansile, sometimes destructive but self-limited bone lesion, composed of blood-filled channels and cystic spaces that are separated by stromal fibrous septae. We present the case of a 29-yearold female patient who discovered a deformity of the left forearm after trauma. The imaging data (simple radiography and whole-body scintigraphy) suggested the following diagnosis: low-grade central osteosarcoma, eosinophilic granuloma, Ewing sarcoma or osteoblastoma. The histologic examination of the bone biopsy showed a benign vascular lesion with overlapping features of ABC and osteoblastoma with ABC-like changes. The immunohistochemical tests (CD31, CD56, SATB2, MDM2, CD45 and Ki-67) were in favor of aneurysmal bone cyst, but they could not definitively exclude an osteoblastoma with ABC-like changes. We discuss each of the aforementioned differential diagnoses from the histopathological point of view, and we found arguments favoring both ABC and osteoblastoma with ABC-like changes. We conclude on the importance of correlations between the imaging data and the histopathological diagnostic. [ABSTRACT FROM AUTHOR]

The first protein‐binding allosteric RNA‐cleaving DNAzyme (RCD) obtained by direct in vitro selection against eosinophil peroxidase (EPX), a validated marker for airway eosinophilia, is described. The RCD has nanomolar affinity for EPX, shows high selectivity against related peroxidases and other eosinophil proteins, and is resistant to degradation by mammalian nucleases. An optimized RCD was used to develop both fluorescence and lateral flow assays, which were evaluated using 38 minimally processed patient sputum samples (23 non‐eosinophilic, 15 eosinophilic), producing a clinical sensitivity of 100 % and specificity of 96 %. This RCD‐based lateral flow assay should allow for rapid evaluation of airway eosinophilia as an aid for guiding asthma therapy. [ABSTRACT FROM AUTHOR]

The first protein‐binding allosteric RNA‐cleaving DNAzyme (RCD) obtained by direct in vitro selection against eosinophil peroxidase (EPX), a validated marker for airway eosinophilia, is described. The RCD has nanomolar affinity for EPX, shows high selectivity against related peroxidases and other eosinophil proteins, and is resistant to degradation by mammalian nucleases. An optimized RCD was used to develop both fluorescence and lateral flow assays, which were evaluated using 38 minimally processed patient sputum samples (23 non‐eosinophilic, 15 eosinophilic), producing a clinical sensitivity of 100 % and specificity of 96 %. This RCD‐based lateral flow assay should allow for rapid evaluation of airway eosinophilia as an aid for guiding asthma therapy. [ABSTRACT FROM AUTHOR]

Objective: Pulmonary Langerhans cell histiocytosis is a cystic lung disease characterized by the proliferation of parenchymal dendritic cells. The disease can become chronic or even cause pulmonary fibrosis. Our aim in this study was to investigate the typical histological findings and interstitial fibrosis in pulmonary Langerhans cell histiocytosis cases. Material and Methods: In the study, cases that had undergone diagnostic resection were screened. Smoking, histological stage (subacute, subacute-chronic), and cystic and eosinophilic granulomas were confirmed in the cases. In addition to emphysema, chronic nonspecific bronchiolitis, interstitial fibrosis (subpleural-paraseptal fibrosis, peribronchial fibrosis, fibrotic nonspecific interstitial pneumonia), honeycomb-type fibrocysts, and unexpected lesions were investigated. Descriptive and comparative (Fisher exact test) statistical analyses were used in the study (p<0.05). Results: A total of 27 cases were detected; age distribution was 17-68 (36.4). Smoking was present in 15 (55.5%) cases. Six (22.2%) cases were subacute, and 21 (7.7%) cases were subacute-chronic histological stage. A cystic lesion was present in 22 (81.4%) cases. All cases had emphysema accompanying the underlying lesions. Chronic nonspecific bronchiolitis was detected in 14 (51.8%) cases. Interstitial fibrosis was detected in 8 (29.6%) patients. Compared to interstitial fibrosis and nonfibrosis, there was no significant difference between being younger than 39 years, gender, smoking, and histological stage (p=0.41; 1; 0.69; 0.63, respectively). Conclusion: There is a risk of developing interstitial fibrosis patterns and honeycomb-type fibrocysts in the progression of pulmonary Langerhans cell histiocytosis. Histopathological evaluation can play an important role in the detection of risk groups. [ABSTRACT FROM AUTHOR]

Kimura Disease, an eosinophilic hyperplastic granulomatous disease of idiopathic origin is most commonly seen in young males. It mostly presents with deep subcutaneous tissue swelling along with enlargement of salivary glands and regional lymphadenopathy. Diagnosis is mainly based on histopathological findings and raised serum IgE and hypereosinophilia. The radiological investigation of choice is Magnetic Resonance Imaging. Management strategy includes surgery and steroid therapy. Chemotherapeutic agents are also frequently used by some centres. Relapse and recurrence stands to be a common problem with management of this disease process. [ABSTRACT FROM AUTHOR]

This investigation demonstrates the use of dimethyl fumarate (DMF) for the treatment of disseminated granuloma annulare (GAD), a rare and chronic inflammatory skin disease. In this case, progressive GAD was treated with DMF, resulting in significant improvement of skin lesions within 5 weeks and complete healing within 7 months. Clinical response was associated with a reduction in inflammatory cells, including both T cell subsets (CD4+ > CD8+), CD183+/CXCR3+ cells, Langerhans cells (CD1a+), myeloid DCs, M1- and M2-like macrophages and the activation marker HLA-DR in immunohistochemical analysis. These findings support the use of DMF as a promising treatment option for this rare skin condition. [ABSTRACT FROM AUTHOR]

Rationale and Objective: To evaluate the characteristic clinical and imaging findings of charcoal granuloma and suggest features that may differentiate charcoal granuloma from breast cancer. Materials and Methods: This retrospective study included 18 patients with a histologically confirmed breast charcoal granuloma between 2005 and 2021 at a single institution. All patients had a history of breast surgery after ultrasound (US)-guided charcoal marking. Two radiologists analyzed the radiologic findings of charcoal granulomas, including the presence of a mass or calcification; the shape, margin and density of the masses on mammography; and the location, size, shape, margin, orientation, echogenicity, vascularity, presence of an echogenic halo, and posterior acoustic shadowing on US. In cases with available follow-up images, we also investigated whether the size and shape had changed. Results: The median interval between breast surgery and the diagnosis of charcoal granuloma was 2.3 years (range, 0.7–18.3 years). Thirteen lesions (72.2%) were detected on screening images. In 11 (61.1%) cases, the surgical incision was not made in the tattooed skin area. Mammography showed positive findings in 10/15 patients, and most lesions were isodense masses (70%). There were no cases with calcification. On US, all lesions were masses and showed a taller-than-wide orientation (61.1%), round or oval shape (55.6%), and iso- or hyperechogenicity (83.3%). Echogenic halo (27.8%) and posterior acoustic shadowing (16.7%) were uncommon. On Doppler US, only four cases (22.2%) showed increased vascularity. Most were classified as BI-RADS 3 (38.9%) or 4A (50.0%). After biopsy, 12 patients had follow-up mammography and US. The size of the lesion decreased in nine cases and remained unchanged in three cases. A decrease in the lesion size after biopsy showed a negative correlation with the interval between detection on imaging and biopsy (p = 0.04). Conclusion: Charcoal granuloma is most commonly found 2–3 years after surgery and occurs more frequently when the incision site is different from the tattooed skin area. US findings of tall and round or oval masses with iso- or hyperechogenicity without increased vascularity could help to differentiate them from malignancies. [ABSTRACT FROM AUTHOR]

This article discusses the use of dupilumab, a monoclonal antibody, in the treatment of eosinophilic esophagitis (EoE). The study aimed to determine if dupilumab could improve the clinical and histologic features of EoE before 12 weeks of treatment. The researchers conducted a retrospective study on 79 patients and found that dupilumab induced histologic remission and clinical benefit even before 12 weeks of treatment. There were no significant differences in outcomes between patients on dupilumab for different durations. Further research is needed to determine the appropriate timing for repeat evaluations. [Extracted from the article]

Introduction: Eosinophilic granuloma (EG) is the most common form of Langerhans cell histiocytosis, presenting as a single osteolytic lesion of the calvarium. Its diagnosis is based on typical clinical and radiological features. While surgical resection has been the standard treatment for EG, growing evidence favors watchful waiting, as unifocal calvarial lesions appear to frequently undergo spontaneous remission. However, histopathological confirmations of this hypothesis are still very limited. Methods: Methods. Here, we report a case of EG with typical clinical and radiological features which, due to intervening circumstances, was resected in a delayed fashion. Moreover, we perform a systematic review of the literature on conservative management of EG. Results: In our case, histological examination showed ongoing bone regeneration with no traces of the disease. Through our literature review, we found 47 cases of calvarial EG managed with watchful waiting. No active intervention was required in 43 cases (91%). Four patients (9%) received surgery or chemotherapy due to the persistence/progression of symptoms or family request. Three reports other than ours documented spontaneous disease remission in surgically resected EG upon histopathological examination. Conclusion: Our report provides further evidence that watchful waiting can be a reasonable option in the management of single calvarial EG. [ABSTRACT FROM AUTHOR]

Essential thrombocythemia is a chronic myeloproliferative syndrome which usually runs its course as an asymptomatic elevated platelet count. Cutaneous manifestations secondary to microcirculation abnormalities are rare but can represent a helpful diagnostic clue in order to prevent major thromboembolic events. We report two cases of heterogeneous livedoid and "net‐like" skin lesions in the context of essential thrombocythemia with identical histopathologic findings (medium‐sized blood vessels with luminal obliteration by eosinophilic material, mostly positive for the platelet marker CD61, without vasculitis). In conclusion, we seek to raise awareness of the clinicopathological features of essential thrombocythemia to allow for prompt diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: Eosinophilic ascites is the most unusual presentation of eosinophilic gastroenteritis (EGE), caused by edema and eosinophilic inflammation of the small bowel wall's serosal layer. Case Report: We report the case of a 53-year-old man, who presented with abdominal pain and distension, moderate ascites since two-three weeks. Ultrasound, CT and Magnetic Resonance Imaging (MRI) showed the presence of ascites and diffuse thickening of small bowel wall, no malignancy in the abdominal cavity or signs of portal hypertension or liver damage. Laboratory test results revealed essential peripheral blood eosinophilia, elevated CRP and increase of eosinophils in the abdominal fluid. Treatment with corticosteroids and antihistamines normalized laboratory tests results, and the ascites resolved for about a week. Conclusions: EGE is a rare disease and it should be kept in mind in patients of unexplained ascites. The absence of primary malignancy on imaging, marked increase of peritoneal fluid eosinophilia and immediate response to treatment with steroids, confirm indirectly the diagnosis of EGE. [ABSTRACT FROM AUTHOR]

Pilonidal sinus over sacrococcygeal area is an acquired condition which affects young male adults usually. We did a retrospective chart review in the department of general surgery,Kalinga Institute of Medical Sciences,Bhubaneswar, for patients who underwent limberg flap repair for pilonidal sinus from sept 2015 to sept 2021 (6 years and 8 months) .A total of 49 patients with 40 males and 9 females respectively, were operated and they had a minimal post operative pain,average post operative hospital stay of 6 days and early return to work in 3 weeks. Four out of 49 patients developed seroma,out of which 1 was lost to follow up .Remaining 3 took two weeks to heal with regular dressings and no recurrence so far .One patient developed stitch granuloma and was treated conservatively. Hence Limberg flap for sacrococcygeal pilonidal sinus was found to be very useful in terms of post operative pain,infection rate,patient compliance,early return to work and almost nil recurrence rates. [ABSTRACT FROM AUTHOR]

The imatinib-sensitive fusion gene FIP1L1::PDGFRA is the most frequent molecular abnormality identified in patients with eosinophilic myeloid neoplasms. Rapid recognition of this mutation is essential given the poor prognosis of PDGFRA-associated myeloid neoplasms prior to the availability of imatinib therapy. We report a case of a patient in whom delayed diagnosis resulted in cardiac transplantation for eosinophilic endomyocardial fibrosis. The delay in diagnosis was due, in part, to a false-negative result in fluorescence in situ hybridization (FISH) testing for FIP1L1::PDGFRA. To explore this further, we examined our cohort of patients presenting with confirmed or suspected eosinophilic myeloid neoplasms and found 8 additional patients with negative FISH results despite a positive reverse-transcriptase polymerase chain reaction test for FIP1L1::PDGFRA. More importantly, false-negative FISH results delayed the median time to imatinib treatment by 257 days. These data emphasize the importance of empiric imatinib therapy in patients with clinical features suggestive of PDGFRA-associated disease. [ABSTRACT FROM AUTHOR]

Benign tumours comprise the majority of primary vertebral tumours, and these are often found incidentally on imaging. Nonetheless, accurate diagnosis of these benign lesions is crucial, in order to avoid misdiagnosis as more ominous malignant lesions or infection. Furthermore, some of these tumours, despite their benign nature, can have localised effects on the spine including neural compromise, or can be locally aggressive, thus necessitating active management. Haemangiomas and osteomas (enostosis) are the commonest benign tumours encountered. Others include osteoid osteoma, osteoblastoma, fibrous dysplasia, osteochondroma, chondroblastoma, haemangioma, simple bone cysts, aneurysmal bone cysts, giant cell tumours, eosinophilic granuloma and notochordal rests. The majority of lesions are asymptomatic; however, locally aggressive lesions (such as aneurysmal bone cysts or giant cell tumours) can present with nonspecific symptoms, such as back pain, neurological deficits and spinal instability, which may be indistinguishable from more commonly encountered mechanical back pain or malignant lesions including metastases. Hence, imaging, including radiography, computed tomography (CT) and magnetic resonance imaging (MRI), plays a critical role in diagnosis. Generally, most incidental or asymptomatic regions are conservatively managed or may not require any follow-up, while symptomatic or locally aggressive lesions warrant active interventions, which include surgical resection or percutaneous treatment techniques. Due to advances in interventional radiology techniques in recent years, percutaneous minimally invasive techniques such as radiofrequency ablation, sclerotherapy and cryoablation have played an increasing role in the management of these tumours with favourable outcomes. The different types of primary benign vertebral tumours will be discussed in this article with an emphasis on pertinent imaging features. [ABSTRACT FROM AUTHOR]

Butterfly vertebras are an abnormal embryological formation of the spinal bodies that occur because of a lack of fusion of the chondrification centers of the vertebral bodies. Langerhans cell histiocytosis is an entity that frequently involves vertebral bodies resulting in flat vertebras, and recovery of the vertebral body height is a very unusual finding. We present a case report of a pediatric patient with a thoracic acquired butterfly vertebra which occurred secondary to a Langerhans cell histiocytosis involvement. It is extremely rare to find vertebra plana that regains its complete height but is even more infrequent to evidence of a butterfly vertebra deformity that is not congenital. [ABSTRACT FROM AUTHOR]

Sibling female and male Chihuahuas were evaluated for a 9‐month history of tachypnea that failed to respond to fenbendazole, doxycycline, amoxicillin‐clavulanate, and prednisone. Physical examination identified tachypnea, hyperpnea, and harsh bronchovesicular lung sounds. Fundic examination disclosed diffuse chorioretinitis, manifested as multifocal chorioretinal granulomas in the female dog and occasional chorioretinal scars in the male dog. Thoracic radiographs indicated moderate to severe interstitial to broncho‐interstitial infiltrates in both dogs. Serum and urine antigen and antibody testing in the female dog failed to identify infectious agents, but cytologic assessment of hepatic lymph node, liver, and splenic aspirates identified Pneumocystis trophozoites. Infection was confirmed in both dogs by 28S rRNA PCR sequencing from multiple tissue samples. The female dog responded well to trimethoprim‐sulfamethoxazole, but the male dog was euthanized because of liver failure, presumably related to antimicrobial treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Lameness shortens the longevity and decreases the production efficiency of commercial herds. However, little research has been conducted on its causes in boars. In this study, we evaluated the prevalence of lameness from two aspects, claw health and bone health, using them for the first time to predict lameness in boars. The results show that claw lesions are widespread in boar populations, and swelling ankle (SWE) is significantly associated with lameness. In addition, lameness affected 22.86% of the boars in the osteopenia group. The prevalence of lameness was significantly higher in boars with osteopenia. Further analysis revealed that boar bone mineral density (BMD) was corelated to age, housing types, and serum Ca. Age had a convex quadratic curve relationship with bone mineral density, and the highest value was observed at the age of 43 months. More importantly, studies show that the bone mineral density of boars in individual pens was significantly higher than that of boars in individual stalls. Therefore, boars with different bone mineral density in different housing types may serve as a guide to improve boar lameness. It is necessary to improve the claw and bone health of boars in production to reduce the occurrence of lameness and improve the breeding value of boars. To investigate the effects of claw lesion types and bone mineral density on lameness in boars, the data of claw lesion score, gait score, and bone mineral density, measured by a Miniomin ultrasound bone densitometer, were collected from a total of 739 Duroc boars. Firstly, we discovered that the prevalence of claw lesions was as high as 95.26% in boars. The percentage of lameness of boars with SWE was higher than those with other claw lesions. Meanwhile, the results showed that the probability of lameness was higher in boars with lower bone mineral density (p < 0.05). Logistic regression models, including variables of boar age, body weight, serum mineral level, and housing type, were used to identify the influencing factors of bone mineral density in this study. The results found that bone mineral density increases with age before reaching a maximum value at 43 months of age, and begins to decrease after 43 months of age. Elevated serum Ca levels were significantly associated with an increase in bone mineral density (p < 0.05). Aside from the above findings, we also made an interesting discovery that boars in the individual pen model significantly increased bone mineral density compared to those in the individual stall model. In conclusion, claw lesions and bone mineral density were significantly associated with lameness. Age, serum Ca, and housing type are the potential influencing factors for bone mineral density in boars. [ABSTRACT FROM AUTHOR]

Eosinophilic-related clinical manifestations are protean and the underlying conditions underpinning eosinophilia are highly diverse. The etiological workup of unexplained eosinophilia/hypereosinophilia can be challenging, and can lead sometimes to extensive, inappropriate, costly and/or invasive investigations. To date, guidelines for the etiological workup and management of eosinophilia are mainly issued by hematologists, and thus mostly cover the scope of clonal hypereosinophilic syndromes (HES). Here, thanks to an extensive literature review, and thanks to the joint work of a large panel of experts involving physicians from both adult and pediatric medicine and from various subspecialties (as well as a representative of a patients' association representative), we provide recommendations for both the step-by step diagnostic workup of eosinophilia (whether unexplained or within specific contexts) as well as the management and follow-up of the full spectrum of eosinophilic disorders (including clonal, reactive, lymphocytic and idiopathic HES, as well as single-organ diseases). Didactic prescription summaries intended to facilitate the prescription of eosinophil-targeted drugs are also provided, as are practical diagnostic and therapeutic algorithms. Lastly, this set of recommendations also includes a summary intended for general practitioners, as well as an overview of the therapeutic patient education program set up by the French reference center for HES. Further updates will be mandatory as new validated information emerges. [ABSTRACT FROM AUTHOR]

Vertebra plana is a rare radiologic condition characterized by a uniform loss of height of a vertebral body that represents a diagnostic challenge for surgeons. The purpose of this study was to review all possible differential diagnoses that may present with a vertebra plana (VP) described in the current literature. For that purpose, we performed a narrative literature review in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, analyzing 602 articles. Patient demographics, clinical presentation, imaging characteristics and diagnoses were investigated. VP is not a pathognomonic feature of Langerhans cell histiocytosis, but other oncologic and non-oncologic conditions should be considered. The list of differential diagnoses, based on our literature review, can be recalled with the mnemonic HEIGHT OF HOMO: H—Histiocytosis; E—Ewing's sarcoma; I—Infection; G—Giant cell tumor; H—Hematologic neoplasms; T—Tuberculosis; O—Osteogenesis imperfecta; F—Fracture; H—Hemangioma; O—Osteoblastoma; M—Metastasis; O—Osteomyelitis, chronic. [ABSTRACT FROM AUTHOR]

Hypereosinophilic syndrome requires a peripheral absolute eosinophil count of ≥1.5 x 109/L with clinical manifestations attributable to peripheral or tissue hypereosinophilia. Clinical manifestations can vary greatly, with the majority of patients relatively asymptomatic and the eosinophilia detected incidentally. However, in a minority of hypereosinophilia cases, they may present with severe life-threatening organ dysfunction affecting skin, lung, heart, gastrointestinal tract, and nervous system. A case of hypereosinophilia with potentially life-threatening cardiovascular involvement is discussed. Initial laboratory investigations showed an elevated white blood cell count with 60% eosinophils. An endomyocardial biopsy revealed eosinophilic endomyocarditis with granuloma, rare giant cells, and no vasculitis, microorganisms, or malignancy. Her presentation met the criteria for either hypereosinophilic syndrome or eosinophilic granulomatosis with polyangitis. Molecular genetic analysis was negative for myelodysplastic syndrome panel/ Platelet Derived Growth Factor Receptor Beta (PDGFRB) (5q32)/Fibroblast Growth Factor Receptor 1 (FGFR1) Fluorescence In Situ Hybridization (FISH), Feline McDonough Sarcoma-related Tyrosine Kinase 3 (FLT3) Internal Tandem Duplication (ITD) mutation, Calregulin (CALR) exon 9 mutation, and T-cell gene rearrangement/polymerase chain reaction. Bone marrow biopsy revealed a mildly hypocellular marrow with multilineage hematopoiesis,+ megakaryocyte dysplasia, and focal eosinophilia. No excess blasts, no monotypic B-cell population, and no discrete pan T-cell aberrancies were found. Bone marrow cytogenetic studies showed a normal signal pattern for myeloproliferative neoplasms panel/Sec1 Family Domain Containing 2 (SCFD2)-Ligand of Numb Protein-X (LNX)-Platelet-derived Growth Factor Receptor Alpha (PDGFRA) fluorescence in situ hybridization with a normal karyotype of 46 XX. Next-generation sequencing, however, was positive for the JAK2-V617F mutation, a rare molecular abnormality in hypereosinophilic syndrome. The prevalence ranges from approximately 0% to 4%. The JAK2 point mutation leads to aberrant tyrosine phosphorylation and increased cytokine activation. The case demonstrates the complexity and challenging nature of advanced diagnostic opportunities in hypereosinophilia and the potential use, in select subsets, of targeted treatments such as tyrosine kinase inhibitors. [ABSTRACT FROM AUTHOR]

Background: Most studies assessing pathophysiological heterogeneity in asthma have been conducted in high-income countries (HICs), with little known about the prevalence and characteristics of different asthma inflammatory phenotypes in low-and middle-income countries (LMICs). This study assessed sputum inflammatory phenotypes in five centres, in Brazil, Ecuador, Uganda, New Zealand (NZ) and the United Kingdom (UK).Methods: We conducted a cross-sectional study of 998 asthmatics and 356 non-asthmatics in 2016-20. All centres studied children and adolescents (age range 8-20 years), except the UK centre which involved 26-27 year-olds. Information was collected using questionnaires, clinical characterization, blood and induced sputum.Results: Of 623 asthmatics with sputum results, 39% (243) were classified as eosinophilic or mixed granulocytic, i.e. eosinophilic asthma (EA). Adjusted for age and sex, with NZ as baseline, the UK showed similar odds of EA (odds ratio 1.04, 95% confidence interval 0.37-2.94) with lower odds in the LMICs: Brazil (0.73, 0.42-1.27), Ecuador (0.40, 0.24-0.66) and Uganda (0.62, 0.37-1.04). Despite the low prevalence of neutrophilic asthma in most centres, sputum neutrophilia was increased in asthmatics and non-asthmatics in Uganda.Conclusions: This is the first time that sputum induction has been used to compare asthma inflammatory phenotypes in HICs and LMICs. Most cases were non-eosinophilic, including in settings where corticosteroid use was low. A lower prevalence of EA was observed in the LMICs than in the HICs. This has major implications for asthma prevention and management, and suggests that novel prevention strategies and therapies specifically targeting non-eosinophilic asthma are required globally. [ABSTRACT FROM AUTHOR]