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Seminars in Hematology Apr 2012
Topics: Animals; Eosinophilia; Humans
PubMed: 22449620
DOI: 10.1053/j.seminhematol.2012.01.004 -
The Journal of Allergy and Clinical... Jun 2022Previous studies of targeted eosinophil biologics in eosinophilic esophagitis have yielded mixed results. Possible explanations include incomplete eosinophil depletion...
BACKGROUND
Previous studies of targeted eosinophil biologics in eosinophilic esophagitis have yielded mixed results. Possible explanations include incomplete eosinophil depletion with anticytokine (anti-IL-5) treatments and/or irreversible fibrotic tissue changes contributing to symptomatology.
OBJECTIVE
To characterize the therapeutic effect of eosinophil depletion in patients with hypereosinophilic syndrome with varied eosinophilic gastrointestinal (GI) disorders.
METHODS
Hematologic, histologic, endoscopic, and clinical symptoms for a subset (n = 7) of hypereosinophilic syndrome patients with GI tissue eosinophilia enrolled in a phase 2 clinical trial of benralizumab (anti-IL-5RA) were assessed before and after treatment (NCT02130882).
RESULTS
Blood and GI tissue eosinophils were completely depleted in all segments of the GI tract, and all patients reported improved GI symptoms, in some cases as early as after the first monthly dose. Some patients had recurrent symptomatic flares without recurrent peripheral or tissue eosinophilia, in most cases after prolonged symptomatic remission and in the setting of liberalization of dietary restrictions and/or tapering of background therapy. Although eosinophil-associated histologic changes improved in all segments, epithelial changes persisted in the esophagus and stomach in patients with recurrent disease flares even after 1 year of treatment. Serum tryptase and GI mast cells were generally unchanged with treatment, and increases were not associated with disease flares. Serum levels of IL-4 and IL-5 increased with benralizumab treatment (both P < .05).
CONCLUSIONS
Benralizumab treatment completely depleted blood and GI tissue eosinophilia in patients with eosinophilic GI disorders, but clinical response, while encouraging, was heterogeneous. Residual symptoms in some patients may reflect persistent epithelial changes in the upper GI tract.
Topics: Antibodies, Monoclonal, Humanized; Enteritis; Eosinophilia; Eosinophilic Esophagitis; Eosinophils; Gastritis; Humans; Hypereosinophilic Syndrome
PubMed: 35283330
DOI: 10.1016/j.jaip.2022.02.037 -
Comprehensive Therapy 2009Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory disease of the esophagus characterized by abnormal infiltration of eosinophils. The incidence of the... (Review)
Review
Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory disease of the esophagus characterized by abnormal infiltration of eosinophils. The incidence of the disease that occurs in children and adults has been rapidly increasing in the last decade. Diagnosis and management of EoE warrants consultation with an allergist and a gastroenterologist.
Topics: Diet; Eosinophilia; Esophagitis; Glucocorticoids; Humans
PubMed: 20043612
DOI: No ID Found -
Allergology International : Official... Apr 2022Non-HIV immune reconstitution inflammatory syndrome (non-HIV IRIS) is associated with the recovery from an immunocompromised condition. It is defined as inflammatory... (Review)
Review
Non-HIV immune reconstitution inflammatory syndrome (non-HIV IRIS) is associated with the recovery from an immunocompromised condition. It is defined as inflammatory disorders caused by antigens, including drugs or pathogenic microorganisms present prior to immune recovery, or by the exacerbation of an inflammatory disorder that was already present. Drug-induced hypersensitivity syndrome is a prototype of IRIS, and the pathophysiology of non-HIV IRIS can be recognized in several disorders treated with corticosteroids, immunosuppressants, molecular-targeted drugs, TNF-α antibody drugs, immune checkpoint inhibitors, and dipeptidyl peptidase-4 inhibitors. This review focuses on the relationship between the immune mechanism of non-HIV IRIS and drug allergies, especially severe drug eruption. The antigen recognition mechanism in drug allergy varies depending on the clinical type and the causative drug. The p-i concept is the main mechanism in severe drug eruption such as Stevens-Johnson syndrome/toxic epidermal necrolysis, and drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms. Lymphocytes activated by an antigen other than a drug, such as a virus, can also develop drug allergy by the loose binding of drugs with immune receptors of T cells or human leukocyte antigen. Therefore, fluctuations in the immune environment affect the onset of severe drug eruption. Novel agents that cause major changes in immunity have been marketed mainly for autoimmune diseases and malignant tumors; therefore, it is necessary to consider their effects when treating severe drug eruptions. Moreover, although a list of diagnostic criteria for this syndrome has been drafted, predictive and diagnostic biomarkers for this syndrome needs to be urgently developed.
Topics: Adrenal Cortex Hormones; Drug Hypersensitivity Syndrome; Eosinophilia; Humans; Immune Reconstitution Inflammatory Syndrome; Stevens-Johnson Syndrome
PubMed: 35236619
DOI: 10.1016/j.alit.2021.12.002 -
Journal of Translational Medicine Aug 2019Eosinophilic esophagitis (EoE) is a chronic immune-mediated inflammatory disorder and represents the leading cause of food impaction. The pathogenesis of EoE is the... (Review)
Review
BACKGROUND
Eosinophilic esophagitis (EoE) is a chronic immune-mediated inflammatory disorder and represents the leading cause of food impaction. The pathogenesis of EoE is the result of an interplay between genetic, environmental and host immune system factors. New therapeutic approaches for EoE have been proposed. In this manuscript we review the current evidence regarding EoE management in pediatric age, with a particular focus on new findings related to the efficacy and safety of monoclonal antibodies.
MAIN BODY
Conventional therapies have failed in treating some patients with EoE, which then requires aggressive procedures such as esophageal dilatation. The most effective available medical therapy for EoE is swallowed topic corticosteroids (fluticasone propionate and budesonide), which have two main drawbacks: they are related to well-known adverse effects (especially in the paediatric population), and there are not enough long-term data to confirm that they are able to reverse the remodelling process of the esophageal mucosa, which is the major cause of EoE symptoms (including dysphagia, abdominal pain, nausea, obstruction, perforation and vomiting). The monoclonal antibodies appear to be an interesting therapeutic approach. However, the studies conducted until now have shown substantial histological improvement not coupled with significant clinical improvements and no significant relationship between a decreasing number of eosinophils and clinical symptoms, highlighting the importance in the pathogenesis of EoE of cells such as T-helper cells, mast cells, B cells, epithelial cells and natural killer cells.
CONCLUSIONS
Monoclonal antibodies targeting a signal involved in the pathogenesis of EoE may not break the complex self-propagating inflammatory activation responsible for perpetuation of the inflammatory response and the development of symptoms and complications. We speculate that combined biological therapies targeting more than one molecule or cell may provide better results, with conventional therapies potentially enhancing the effects of antibodies. However, further studies should aim to find the best therapeutic approach to target the cells involved in the remodelling process and to reverse the histological changes in this complex clinical condition.
Topics: Antibodies, Monoclonal; Child; Eosinophilic Esophagitis; Humans
PubMed: 31399124
DOI: 10.1186/s12967-019-2014-0 -
The Indian Journal of Medical Research Sep 2013Tropical pulmonary eosinophilia (TPE) is a syndrome of wheezing, fever and eosiniphilia seen predominantly in the Indian subcontinent and other tropical areas. Its... (Review)
Review
Tropical pulmonary eosinophilia (TPE) is a syndrome of wheezing, fever and eosiniphilia seen predominantly in the Indian subcontinent and other tropical areas. Its etiological link with Wuchereria bancrofti and Brugia malayi has been well established. The pathogenesis is due to an exaggerated immune response to the filarial antigens which includes type I, type III and type IV reactions with eosinophils playing a pivotal role. Peripheral blood eosinophilia is usually striking with levels over 3000/μl being common. High serum levels of IgE and filarial-specific IgE and IgG are also found. The pathology may vary from an acute eosinophilic alveolitis to histiocytic infiltration depending on the stage of the disease. While earlier studies had suggested that the disease runs a benign course, more recent work has shown that untreated TPE could result in a fair degree of respiratory morbidity. Pulmonary function tests may show a mixed restrictive and obstructive abnormality with a reduction in diffusion capacity. The bronchoalveolar lavage (BAL) eosinophil count has a negative correlation with the diffusion capacity. Treatment consists of diethylcarbamazine (DEC) for at least three weeks. Despite treatment with DEC, about 20 per cent of patients may relapse. Steroids have shown to have a beneficial effect but the exact dose and duration is yet to be confirmed by randomized controlled trials. A specific and easily available marker is required for TPE in order to distinguish it from other parasitic and non-parasitic causes of pulmonary eosinophilia.
Topics: Adolescent; Adult; Diagnosis, Differential; Diethylcarbamazine; Eosinophilia; Female; Filaricides; Humans; Male; Pulmonary Eosinophilia; Respiratory Function Tests; Young Adult
PubMed: 24135173
DOI: No ID Found -
Immunology and Allergy Clinics of North... Aug 2007Gastrointestinal eosinophilia, a broad term for abnormal eosinophil accumulation in the gastrointestinal tract, involves many different disease identities. These... (Review)
Review
Gastrointestinal eosinophilia, a broad term for abnormal eosinophil accumulation in the gastrointestinal tract, involves many different disease identities. These diseases include primary eosinophil associated gastrointestinal diseases, gastrointestinal eosinophilia in hypereosinophilic syndrome, and all gastrointestinal eosinophilic states associated with known causes. Each of these diseases has its unique features but there is no absolute boundary between them. All three groups of gastrointestinal eosinophila are described in this article, although the focus is on primary gastrointestinal eosinophilia.
Topics: Cytokines; Eosinophilia; Eosinophils; Gastrointestinal Diseases; Humans; Hypereosinophilic Syndrome
PubMed: 17868858
DOI: 10.1016/j.iac.2007.06.002 -
Revista de Gastroenterologia de Mexico Aug 2012
Topics: Eosinophilic Esophagitis; Humans
PubMed: 22939463
DOI: 10.1016/j.rgmx.2012.07.002 -
Chest Jun 1998Tropical pulmonary eosinophilia (TPE) usually affects people living in the tropics, especially those in Southeast Asia, India, and certain parts of China and Africa.... (Review)
Review
Tropical pulmonary eosinophilia (TPE) usually affects people living in the tropics, especially those in Southeast Asia, India, and certain parts of China and Africa. However, owing to the rising frequency of world-wide travel and the migration between continents, this disease is increasingly seen in the West, where the diagnosis can be easily missed since it is rarely encountered and can mimic many other conditions. Cases of TPE have typically been reported to masquerade as acute or refractory bronchial asthma. TPE results from a hypersensitivity reaction to lymphatic filarial parasites found in endemic regions. There is evidence that it is more likely to occur in nonimmune individuals, ie, visitors to endemic regions, than in individuals of endemic populations who have developed immunity to filarial infections. Clinical features include paroxysmal cough, wheezing and dyspnea, and systemic manifestations such as fever and weight loss. A history of residence in a filarial endemic region and a finding of peripheral eosinophilia >3,000/mm3 should initiate a consideration of this disease. Other criteria for the diagnosis of TPE include absence of microfilariae in the blood, high titers of antifilarial antibodies, raised serum total IgE >1,000 U/mL, and a favorable response to the antifilarial, diethylcarbamazine, which is the recommended treatment. This disease, if left untreated or treated late, may lead to long-term sequelae of pulmonary fibrosis or chronic bronchitis with chronic respiratory failure. Herein lies the importance of early diagnosis and treatment of TPE.
Topics: Animals; Diagnosis, Differential; Filariasis; Humans; Microfilariae; Pulmonary Eosinophilia; Tropical Climate
PubMed: 9631810
DOI: 10.1378/chest.113.6.1673 -
Current Opinion in Hematology Jan 2022Myeloid diseases are often characterized by a disturbed regulation of myeloid cell proliferation, survival, and maturation. This may either result in a severe paucity of... (Review)
Review
PURPOSE OF REVIEW
Myeloid diseases are often characterized by a disturbed regulation of myeloid cell proliferation, survival, and maturation. This may either result in a severe paucity of functional neutrophils (neutropenia), an excess production of mature cells (myeloproliferative disorders) or in clonal expansions of dysplastic or immature myeloid cells (myelodysplasia and acute myeloid leukemia). Although these conditions can be regarded as separate entities, caused by the accumulation of distinct sets of somatic gene mutations, it becomes increasingly clear that they may also evolve as the prime consequence of a congenital defect resulting in severe neutropenia. Prominent examples of such conditions include the genetically heterogeneous forms of severe congenital neutropenia (SCN) and Shwachman-Diamond Syndrome. CSF3 treatment is a successful therapy to alleviate neutropenia in the majority of these patients but does not cure the disease nor does it prevent malignant transformation. Allogeneic stem cell transplantation is currently the only therapeutic option to cure SCN, but is relatively cumbersome, e.g., hampered by treatment-related mortality and donor availability. Hence, there is a need for new therapeutic approaches.
RECENT FINDINGS
Developments in disease modeling, amongst others based on induced pluripotent stem cell and CRISPR/Cas9 based gene-editing technologies, have created new insights in disease biology and possibilities for treatment. In addition, they are fueling expectations for advanced disease monitoring to prevent malignant transformation.
SUMMARY
This review highlights the recent progress made in SCN disease modeling and discusses the challenges that are still ahead of us to gain a better understanding of the biological heterogeneity of the disease and its consequences for patient care.
Topics: Congenital Bone Marrow Failure Syndromes; Humans; Mutation; Myelodysplastic Syndromes; Neutropenia
PubMed: 34854832
DOI: 10.1097/MOH.0000000000000696