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Journal of Clinical Immunology Jul 2021The hyper-IgE syndromes (HIES) are a heterogeneous group of inborn errors of immunity sharing manifestations including increased infection susceptibility, eczema, and... (Review)
Review
The hyper-IgE syndromes (HIES) are a heterogeneous group of inborn errors of immunity sharing manifestations including increased infection susceptibility, eczema, and raised serum IgE. Since the prototypical HIES description 55 years ago, areas of significant progress have included description of key disease-causing genes and differentiation into clinically distinct entities. The first two patients reported had what is now understood to be HIES from dominant-negative mutations in signal transduction and activator of transcription 3 (STAT3-HIES), conferring a broad immune defect across both innate and acquired arms, as well as defects in skeletal, connective tissue, and vascular function, causing a clinical phenotype including eczema, staphylococcal and fungal skin and pulmonary infection, scoliosis and minimal trauma fractures, and vascular tortuosity and aneurysm. Due to the constitutionally expressed nature of STAT3, initial reports at treatment with allogeneic stem cell transplantation were not positive and treatment has hinged on aggressive antimicrobial prophylaxis and treatment to prevent the development of end-organ disease such as pneumatocele. Research into the pathophysiology of STAT3-HIES has driven understanding of the interface of several signaling pathways, including the JAK-STAT pathways, interleukins 6 and 17, and the role of Th17 lymphocytes, and has been expanded by identification of phenocopies such as mutations in IL6ST and ZNF341. In this review we summarize the published literature on STAT3-HIES, present the diverse clinical manifestations of this syndrome with current management strategies, and update on the uncertain role of stem cell transplantation for this disease. We outline key unanswered questions for further study.
Topics: Hematopoietic Stem Cell Transplantation; Humans; Job Syndrome; Quality of Life; STAT3 Transcription Factor
PubMed: 33932191
DOI: 10.1007/s10875-021-01051-1 -
Minerva Gastroenterologica E Dietologica Jun 2020Eosinophilic colitis (EC) is a rare inflammatory disease included in the chapter of eosinophilic gastrointestinal disorders (EGIDs), diagnosed by the presence of primary... (Review)
Review
Eosinophilic colitis (EC) is a rare inflammatory disease included in the chapter of eosinophilic gastrointestinal disorders (EGIDs), diagnosed by the presence of primary eosinophilic infiltrate in the colon wall in symptomatic patients. While the etiology of primary colonic eosinophilia is unknown, several conditions are involved in the pathogenesis of secondary eosinophilic colonic infiltrate (food allergens, parasitic infections, drugs), which have to be excluded in order to correctly diagnose the primary form of the disease. Up to now, EC is lacking of codified guidelines regarding diagnostic criteria (especially eosinophil threshold values) and treatment, thus a correct approach to EC remains very challenging. Imaging, laboratory tests and endoscopy might be helpful in ruling out other mimic conditions, but EC is still a diagnosis of exclusion. Several treatment options are feasible, but most of the evidences are drawn from case reports and small case series, thus limiting their value. We carried out a review of the current literature to evaluate the more appropriate and modern clinical strategy for diagnosis and management of EC.
Topics: Colitis; Enteritis; Eosinophilia; Gastritis; Humans
PubMed: 31994372
DOI: 10.23736/S1121-421X.20.02656-2 -
Hematology. American Society of... Dec 2022Hypereosinophilic syndromes (HES) are a heterogenous group of rare disorders with clinical manifestations ranging from fatigue to life-threatening endomyocardial... (Review)
Review
Hypereosinophilic syndromes (HES) are a heterogenous group of rare disorders with clinical manifestations ranging from fatigue to life-threatening endomyocardial fibrosis and thromboembolic events. Given the broad differential diagnosis of HES, a comprehensive approach is needed to identify potential secondary (treatable) causes and define end-organ manifestations. Classification by clinical HES subtype is also useful in terms of assessing prognosis and guiding therapy. Corticosteroids remain the mainstay of initial therapy in the setting of acute, life-threatening PDGFR mutation-negative HES. Whereas the recent availability of eosinophil-targeted therapies with extraordinary efficacy and little apparent toxicity is changing the treatment paradigm, especially for idiopathic HES and overlap syndromes, questions remain unanswered regarding the choice of agent, impact of combination therapies, and long-term effects of eosinophil depletion. This review provides a case-based discussion of the differential diagnosis of HES, including the classification by clinical HES subtype. Treatment options are reviewed, including novel eosinophil-targeted agents recently approved for the treatment of HES and/or other eosinophil-associated disorders. Primary (myeloid) disorders associated with hypereosinophilia are not be addressed in depth in this review.
Topics: Humans; Hypereosinophilic Syndrome; Antineoplastic Agents; Adrenal Cortex Hormones; Prognosis
PubMed: 36485140
DOI: 10.1182/hematology.2022000367 -
Allergology International : Official... Oct 2019Eosinophilic fasciitis is a disease originally proposed as "diffuse fasciitis with eosinophilia" by Shulman in 1974. The patients with this disease often have history of... (Review)
Review
Eosinophilic fasciitis is a disease originally proposed as "diffuse fasciitis with eosinophilia" by Shulman in 1974. The patients with this disease often have history of strenuous exercise or labor a few days to 1-2 weeks before the onset. The chief symptoms are symmetrical, full-circumference swelling and plate-like hardness of the distal limbs. This is accompanied by redness and pain in the early stages, with many cases exhibiting systemic symptoms such as fever or generalized fatigue. The lesions have been observed extending to the proximal limbs, though never on the face or fingers. En bloc biopsies from the skin to the fascia show marked fascial thickening and inflammatory cell infiltration by the lymphocytes and plasma cells. Eosinophilic infiltration is useful for the diagnosis but is only seen in the early stages of the disease. Recently, "Diagnostic criteria, severity classification, and clinical guidelines for eosinophilic fasciitis" were published. This review article discusses about eosinophilic faciitis in detail, from its pathophysiology to the treatment.
Topics: Biopsy; Cytokines; Disease Management; Disease Susceptibility; Eosinophilia; Fasciitis; Humans; Phenotype; Skin
PubMed: 30910631
DOI: 10.1016/j.alit.2019.03.001 -
Allergy Jan 2023Eosinophilia and eosinophil activation are recurrent features in various reactive states and certain hematologic malignancies. In patients with hypereosinophilia (HE),... (Review)
Review
Eosinophilia and eosinophil activation are recurrent features in various reactive states and certain hematologic malignancies. In patients with hypereosinophilia (HE), HE-induced organ damage is often encountered and may lead to the diagnosis of a hypereosinophilic syndrome (HES). A number of known mechanisms and etiologies contribute to the development of HE and HES. Based on these etiologies and the origin of eosinophils, HE and HES are divided into primary forms where eosinophils are clonal cells, reactive forms where an underlying reactive or neoplastic condition is detected and eosinophils are considered to be "non-clonal" cells, and idiopathic HE and HES in which neither a clonal nor a reactive underlying pathology is detected. Since 2012, this classification and the related criteria have been widely accepted and regarded as standard. However, during the past few years, new developments in the field and an increasing number of markers and targets have created a need to update these criteria and the classification of HE and HES. To address this challenge, a Working Conference on eosinophil disorders was organized in 2021. In this conference, a panel of experts representing the relevant fields, including allergy, dermatology, hematology, immunology, laboratory medicine, and pathology, met and discussed new markers and concepts as well as refinements in definitions, criteria and classifications of HE and HES. The outcomes of this conference are presented in this article and should assist in the diagnosis and management of patients with HE and HES in daily practice and in the preparation and conduct of clinical trials.
Topics: Humans; Eosinophils; Eosinophilia; Syndrome; Hypersensitivity; Hypereosinophilic Syndrome
PubMed: 36207764
DOI: 10.1111/all.15544 -
Saudi Medical Journal Jul 2023Eosinophilic esophagitis (EoE) is an atopic disease in which eosinophils infiltrate the esophageal mucosa and may result in a variety of upper gastrointestinal symptoms.... (Review)
Review
Eosinophilic esophagitis (EoE) is an atopic disease in which eosinophils infiltrate the esophageal mucosa and may result in a variety of upper gastrointestinal symptoms. Chief among these are dysphagia, heartburn, and food bolus obstruction in adults whereas children often present with abdominal pain or vomiting. Eosinophilic esophagitis is a chronic condition that if not detected and left untreated could lead to the development of subepithelial fibrosis and esophageal stenosis. The diagnosis of EoE is confirmed in a patient presenting with characteristic EoE symptoms, classic signs on endoscopy, and biopsy results showing >15 eosinophils/hpf. A number of useful treatments against EoE are currently available with new therapeutics on the horizon. The former include PPIs, topical steroids, and elimination diet; the latter comprise novel biologics including the monoclonal antibody dupilumab. All these treatments can improve symptoms and reduce esophageal eosinophil count. This brief introductory review describes the detection, diagnosis, and management of EoE.
Topics: Adult; Child; Humans; Eosinophilic Esophagitis; Deglutition Disorders; Endoscopy
PubMed: 37463709
DOI: 10.15537/smj.2023.44.7.20220812 -
Frontiers in Immunology 2021Gene therapy is an innovative treatment for Primary Immune Deficiencies (PIDs) that uses autologous hematopoietic stem cell transplantation to deliver stem cells with... (Review)
Review
Gene therapy is an innovative treatment for Primary Immune Deficiencies (PIDs) that uses autologous hematopoietic stem cell transplantation to deliver stem cells with added or edited versions of the missing or malfunctioning gene that causes the PID. Initial studies of gene therapy for PIDs in the 1990-2000's used integrating murine gamma-retroviral vectors. While these studies showed clinical efficacy in many cases, especially with the administration of marrow cytoreductive conditioning before cell re-infusion, these vectors caused genotoxicity and development of leukoproliferative disorders in several patients. More recent studies used lentiviral vectors in which the enhancer elements of the long terminal repeats self-inactivate during reverse transcription ("SIN" vectors). These SIN vectors have excellent safety profiles and have not been reported to cause any clinically significant genotoxicity. Gene therapy has successfully treated several PIDs including Adenosine Deaminase Severe Combined Immunodeficiency (SCID), X-linked SCID, Artemis SCID, Wiskott-Aldrich Syndrome, X-linked Chronic Granulomatous Disease and Leukocyte Adhesion Deficiency-I. In all, gene therapy for PIDs has progressed over the recent decades to be equal or better than allogeneic HSCT in terms of efficacy and safety. Further improvements in methods should lead to more consistent and reliable efficacy from gene therapy for a growing list of PIDs.
Topics: Genetic Therapy; Granulomatous Disease, Chronic; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Primary Immunodeficiency Diseases; Severe Combined Immunodeficiency; Treatment Outcome; Wiskott-Aldrich Syndrome; X-Linked Combined Immunodeficiency Diseases
PubMed: 33717203
DOI: 10.3389/fimmu.2021.648951 -
Revista Espanola de Quimioterapia :... Sep 2019Febrile neutropenia is a common complication in patients with hematologic malignancies receiving chemotherapy, and is associated with high morbidity and mortality.... (Review)
Review
Febrile neutropenia is a common complication in patients with hematologic malignancies receiving chemotherapy, and is associated with high morbidity and mortality. Infections caused by multidrug-resistant bacteria represent a therapeutic challenge in this high-risk patient population, since inadequate initial empirical antibiotic treatment can seriously compromise prognosis. Besides, reducing antimicrobial exposure is a cornerstone in the fight against resistance.
Topics: Antineoplastic Agents; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Febrile Neutropenia; Hematologic Neoplasms; Humans; Immunocompromised Host
PubMed: 31475812
DOI: No ID Found -
American Journal of Hematology Jan 2022The eosinophilias encompass a broad range of nonhematologic (secondary or reactive) and hematologic (primary or clonal) disorders with potential for end-organ damage.
DISEASE OVERVIEW
The eosinophilias encompass a broad range of nonhematologic (secondary or reactive) and hematologic (primary or clonal) disorders with potential for end-organ damage.
DIAGNOSIS
Hypereosinophilia (HE) has generally been defined as a peripheral blood eosinophil count greater than 1.5 × 10 /L. After exclusion of secondary causes of eosinophilia, diagnostic evaluation of primary eosinophilias relies on morphologic review of the blood and marrow, standard cytogenetics, fluorescence in situ hybridization, next generation sequencing gene assays, and flow immunophenotyping to detect histopathologic or clonal evidence for an acute or chronic hematolymphoid neoplasm.
RISK STRATIFICATION
Disease prognosis relies on identifying the subtype of eosinophilia. After evaluation of secondary causes of eosinophilia, the 2016 World Health Organization endorses a semi-molecular classification scheme of disease subtypes. This includes the major category "myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1 or with PCM1-JAK2", and the myeloproliferative neoplasm subtype, "chronic eosinophilic leukemia, not otherwise specified" (CEL, NOS). Lymphocyte-variant HE is an aberrant T-cell clone-driven reactive eosinophila, and idiopathic hypereosinophilic syndrome (HES) is a diagnosis of exclusion.
RISK-ADAPTED THERAPY
The goal of therapy is to mitigate eosinophil-mediated organ damage. For patients with milder forms of eosinophilia (eg, < 1.5 × 10 /L) without symptoms or signs of organ involvement, a watch and wait approach with close follow-up may be undertaken. Identification of rearranged PDGFRA or PDGFRB is critical because of the exquisite responsiveness of these diseases to imatinib. Corticosteroids are first-line therapy for patients with lymphocyte-variant HE and HES. Hydroxyurea and interferon-α have demonstrated efficacy as initial treatment and in steroid-refractory cases of HES. Mepolizumab, an interleukin-5 (IL-5) antagonist monoclonal antibody, was recently approved by the US Food and Drug Administration for patients with idiopathic HES. The use of the IL-5 receptor antibody benralizumab, as well as other targeted therapies such as JAK2 and FGFR1 inhibitors, is under active investigation.
Topics: Adrenal Cortex Hormones; Antibodies, Monoclonal, Humanized; Disease Management; Eosinophilia; Eosinophils; Humans; Hydroxyurea; Interferon-alpha; Interleukin-5; Prognosis; Risk Assessment; World Health Organization
PubMed: 34533850
DOI: 10.1002/ajh.26352 -
The Medical Clinics of North America Jan 2020Physicians may encounter blood or tissue eosinophilia through a routine complete blood count with differential or a tissue pathology report. In this article, the basic... (Review)
Review
Physicians may encounter blood or tissue eosinophilia through a routine complete blood count with differential or a tissue pathology report. In this article, the basic biology of eosinophils is reviewed and definitions of blood eosinophilia, as well as the challenges of defining tissue eosinophilia, are discussed. Conditions associated with eosinophilia are briefly discussed as well as a general approach to evaluating eosinophilia. Future challenges include determining which eosinophil-associated diseases benefit from eosinophil-targeted therapy and identifying biomarkers for disease activity and diagnosis.
Topics: Biomarkers; Eosinophilia; Eosinophils; Humans; Leukocyte Count; Severity of Illness Index
PubMed: 31757229
DOI: 10.1016/j.mcna.2019.08.005