Eosinopenia | |
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An eosinophil in peripheral blood | |
Specialty | Hematology |
Eosinopenia is a condition where the number of eosinophils, a type of white blood cell, in circulating blood is lower than normal. [1] Eosinophils are a type of granulocyte and consequently from the same cellular lineage as neutrophils, basophils, and mast cells. [1] [2] Along with the other granulocytes, eosinophils are part of the innate immune system and contribute to the defense of the body from pathogens. The most widely understood function of eosinophils is in association with allergy and parasitic disease processes, though their functions in other pathologies are the subject of ongoing research. [3] The opposite phenomenon, in which the number of eosinophils present in the blood is higher than normal, is known as eosinophilia.
The definition of eosinopenia varies in clinical practice, and normal eosinophil levels vary among the population. [4] One common definition is an absolute eosinophil count of less than 50 cells/μLiter of blood. [5] [6] [7] Other definitions include less than 10 cells/μLiter, while some clinical laboratories classify 0 cells/μLiter as within the acceptable range. [3] The diagnosis of eosinopenia is challenging due to the low number of eosinophils normally present in blood and the fluctuations in eosinophil levels throughout the day. [1] [4]
Eosinopenia is associated with several disease states and conditions, including inflammation and sepsis, endogenous catecholamines, and use of glucocorticoids. [1] There are also medications that deliberately target eosinophils in order to treat eosinophil-mediated diseases, causing drug-induced eosinopenia. [8]
Unlike other granulocytes, eosinophil count decreases in response to release of catecholamines. [1] A hypothesized mechanism contributing to this change is decreased eosinophil production by the bone marrow in response to catecholamines. Epinephrine is also believed to stimulate receptors through the β-adrenergic pathway to decrease eosinophils in peripheral blood. [1]
Use of glucocorticoids has been known to affect several blood components, including decreasing eosinophils. [1] This cause of this effect is multifactorial. Glucocorticoids decrease the number of eosinophils in the circulation by causing them to exit the bloodstream and move into the tissue. The number of eosinophils released by the bone marrow is suppressed by glucocorticoids. It has also been theorized that glucocorticoids eliminate eosinophils in the blood by causing them to undergo apoptosis. [1]
Due to the harmful role of eosinophils in diseases such as eosinophilic asthma and eosinophilic granulomatosis with polyangiitis, drugs have been developed to purposefully diminish eosinophils in order to alleviate symptoms. [8] Some examples of these drugs include mepolizumab, reslizumab, and benralizumab. [9]
Although eosinopenia has long been recognized as a laboratory marker for infection, the mechanism for this phenomenon is currently unknown. [2] [10] One potential explanation is that eosinopenia may be an indication of immune dysregulation. [5] In the body's response to a pathogen, the immune system activates "type 1 inflammation" which mobilizes certain immune cells to clear pathogens. This response can produce collateral damage of host tissue. To balance this, eosinophils are one component of "type 2 inflammation" that can begin to mend the tissue. As a result, eosinopenia may be a sign that the body has not mounted an appropriate type 2 inflammation response, so it may be doing more damage than normal to surrounding tissue. [5] Another theory postulates that eosinophils in sepsis travel out of the blood and may contribute to tissue damage, causing relative eosinopenia in the blood with elevated eosinophils in affected tissue. [5] Eosinophils have been shown to have a cytotoxic effect on bacteria, which contributes to surrounding tissue damage. [2] [3]
Persistent eosinopenia in sepsis is independently associated with worse clinical outcomes, including increased mortality and increased rates of hospital readmission. [5] It is unknown if eosinophils contribute directly to clearing pathogens in sepsis or if their absence is only an indicator that the immune system is dysregulated. [5] The causative role of eosinopenia to poor survival in sepsis, if it exists, has yet to be established. [5]
The use of eosinopenia as a diagnostic tool in sepsis is debatable. [10] Although there is a high incidence of eosinopenia in sepsis, it is not more effective as a biomarker than more commonly utilized indicators of sepsis, such as procalcitonin (PCT) and C-reactive protein (CRP). [10] One advantage it does have compared these biomarkers is that it is generally a faster and cheaper test. [10]
Eosinopenia is a possible laboratory finding in patients who present with COVID-19 and is associated with disease severity, though it is not pathognomonic. [3] One study found that 53% of patients admitted for COVID-19 had eosinopenia at time of admission; in another study of fatal COVID-19 cases, 81% of patients had eosinopenia. [8] In patients with eosinopenia who present with COVID-19, eosinophil counts usually return to normal levels as they recover. [3] [8] In fatal cases of COVID-19, eosinophil counts remain low for the duration of the disease. [3] It is unclear if this eosinopenia contributes to the disease course. [8] The presence of eosinopenia has been included in several risk stratification scores, such as the COVID-19-REAL score and PARIS score, which both use different definitions of eosinopenia as part of several factors to screen for COVID-19. [3] Eosinopenia has also been proposed as a marker for distinguishing COVID-19 from influenza virus infection, since patients diagnosed with COVID-19 have slightly lower eosinophil counts than patients diagnosed with influenza. [3]
Though the most widely known role of eosinophils is in regards to allergy and parasitic infections, recent research has found evidence for an antiviral function of eosinophils. [3] [8] Research has shown that mice that were genetically modified to have more eosinophils than normal were able to combat RSV infection more effectively than normal mice, while genetically eosinophil-depleted mice were less effective. [8] The precise mechanism for this function is undetermined, though some elements of the eosinophil response to viruses include nitric oxide production and inactivation of viruses. [3] [8] Though there is early research on the role of eosinophils in response to respiratory viruses, this function is still uncertain and requires additional research in order to define the extent to which eosinophils participate in antiviral immune response as well as clinical relevancy. [8]
The cause of eosinopenia in COVID-19 infection is also unknown at this time. Some proposed contributory mechanisms include increased movement of eosinophils out of the blood into tissue, decreased generation or output of eosinophils from the bone barrow, and shorter lifespan within the blood. [3] One aspect of severe COVID-19 that may contribute to eosinopenia is the cytokine storm. In this disorder, cytokines may interact with eosinophils and modulate their activity, movement, or survival. [3]
Inflammation is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function.
Agranulocytosis, also known as agranulosis or granulopenia, is an acute condition involving a severe and dangerous lowered white blood cell count and thus causing neutropenia in the circulating blood. It is a severe lack of one major class of infection-fighting white blood cells. People with this condition are at very high risk of serious infections due to their suppressed immune system.
Eosinophils, sometimes called eosinophiles or, less commonly, acidophils, are a variety of white blood cells and one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. Along with mast cells and basophils, they also control mechanisms associated with allergy and asthma. They are granulocytes that develop during hematopoiesis in the bone marrow before migrating into blood, after which they are terminally differentiated and do not multiply.
Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds 5×108/L (500/μL). Hypereosinophilia is an elevation in an individual's circulating blood eosinophil count above 1.5 × 109/L (i.e. 1,500/μL). The hypereosinophilic syndrome is a sustained elevation in this count above 1.5 × 109/L (i.e. 1,500/μL) that is also associated with evidence of eosinophil-based tissue injury.
Basophils are a type of white blood cell. Basophils are the least common type of granulocyte, representing about 0.5% to 1% of circulating white blood cells. They are the largest type of granulocyte. They are responsible for inflammatory reactions during immune response, as well as in the formation of acute and chronic allergic diseases, including anaphylaxis, asthma, atopic dermatitis and hay fever. They also produce compounds that coordinate immune responses, including histamine and serotonin that induce inflammation, and heparin that prevents blood clotting, although there are less than that found in mast cell granules. Mast cells were once thought to be basophils that migrated from the blood into their resident tissues, but they are now known to be different types of cells.
Myocarditis is defined as inflammation of the myocardium. Myocarditis can progress to inflammatory cardiomyopathy when there are associated ventricular remodeling and cardiac dysfunction due to chronic inflammation. Symptoms can include shortness of breath, chest pain, decreased ability to exercise, and an irregular heartbeat. The duration of problems can vary from hours to months. Complications may include heart failure due to dilated cardiomyopathy or cardiac arrest.
Granulocytes are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear, that is, they have varying shapes (morphology) of the nucleus ; and are referred to as polymorphonuclear leukocytes. In common terms, polymorphonuclear granulocyte refers specifically to "neutrophil granulocytes", the most abundant of the granulocytes; the other types have varying morphology. Granulocytes are produced via granulopoiesis in the bone marrow.
Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that affect the patient's immune system. Examples of these extrinsic factors include HIV infection and environmental factors, such as nutrition. Immunocompromisation may also be due to genetic diseases/flaws such as SCID.
Hypereosinophilic syndrome is a disease characterized by a persistently elevated eosinophil count in the blood for at least six months without any recognizable cause, with involvement of either the heart, nervous system, or bone marrow.
Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as allergic granulomatosis, is an extremely rare autoimmune condition that causes inflammation of small and medium-sized blood vessels (vasculitis) in persons with a history of airway allergic hypersensitivity (atopy).
Granulocyte-macrophage colony-stimulating factor (GM-CSF), also known as colony-stimulating factor 2 (CSF2), is a monomeric glycoprotein secreted by macrophages, T cells, mast cells, natural killer cells, endothelial cells and fibroblasts that functions as a cytokine. The pharmaceutical analogs of naturally occurring GM-CSF are called sargramostim and molgramostim.
Eosinophilic esophagitis (EoE) is an allergic inflammatory condition of the esophagus that involves eosinophils, a type of white blood cell. In healthy individuals, the esophagus is typically devoid of eosinophils. In EoE, eosinophils migrate to the esophagus in large numbers. When a trigger food is eaten, the eosinophils contribute to tissue damage and inflammation. Symptoms include swallowing difficulty, food impaction, vomiting, and heartburn.
Stress hormones are secreted by endocrine glands to modify one's internal environment during the times of stress. By performing various functions such as mobilizing energy sources, increasing heart rate, and downregulating metabolic processes which are not immediately necessary, stress hormones promote the survival of the organism. The secretions of some hormones are also downplayed during stress. Stress hormones include, but are not limited to:
A promyelocyte is a granulocyte precursor, developing from the myeloblast and developing into the myelocyte. Promyelocytes measure 12–20 microns in diameter. The nucleus of a promyelocyte is approximately the same size as a myeloblast but their cytoplasm is much more abundant. They also have less prominent nucleoli than myeloblasts and their chromatin is more coarse and clumped. The cytoplasm is basophilic and contains primary red/purple granules.
Eosinophilic gastroenteritis, also known as eosinophilic enteritis, is a rare and heterogeneous condition characterized by patchy or diffuse eosinophilic infiltration of gastrointestinal (GI) tissue, first described by Kaijser in 1937. Presentation may vary depending on location as well as depth and extent of bowel wall involvement and usually runs a chronic relapsing course. It can be classified into mucosal, muscular and serosal types based on the depth of involvement. Any part of the GI tract can be affected, and isolated biliary tract involvement has also been reported. The stomach is the organ most commonly affected, followed by the small intestine and the colon.
Eosinophil cationic protein (ECP) also known as ribonuclease 3 is a basic protein located in the eosinophil primary matrix. In humans, the eosinophil cationic protein is encoded by the RNASE3 gene.
White blood cells, also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. White blood cells include three main subtypes: granulocytes, lymphocytes and monocytes.
Eosinophilic myocarditis is inflammation in the heart muscle that is caused by the infiltration and destructive activity of a type of white blood cell, the eosinophil. Typically, the disorder is associated with hypereosinophilia, i.e. an eosinophil blood cell count greater than 1,500 per microliter. It is distinguished from non-eosinophilic myocarditis, which is heart inflammation caused by other types of white blood cells, i.e. lymphocytes and monocytes, as well as the respective descendants of these cells, NK cells and macrophages. This distinction is important because the eosinophil-based disorder is due to a particular set of underlying diseases and its preferred treatments differ from those for non-eosinophilic myocarditis.
Lymphocyte-variant hypereosinophilia is a rare disorder in which eosinophilia or hypereosinophilia is caused by an aberrant population of lymphocytes. These aberrant lymphocytes function abnormally by stimulating the proliferation and maturation of bone marrow eosinophil-precursor cells termed colony forming unit-eosinophils or CFU-Eos.
Familial eosinophilia is a rare congenital disorder characterized by the presence of sustained elevations in blood eosinophil levels that reach ranges diagnostic of eosinophilia or, far more commonly, hypereosinophilia. Although high eosinophil levels are associated with certain diseases and thought to contribute to the tissue destruction found in many other eosinophilia-related diseases, clinical manifestations and tissue destruction related to the eosinophilia in familial eosinophilia is uncommon: this genetic disease typically has a benign phenotype and course compared to other congenital and acquired eosinophilic diseases.