Neutrophilia is an increase in the absolute neutrophil count in the peripheral circulation. Normal blood values vary by age. Neutrophilia can be caused by a direct problem with blood cells (primary disease). It can also occur as a consequence of an underlying disease (secondary). Most cases of neutrophilia are secondary to inflammation.

Primary causes

- Conditions with normally functioning neutrophils – hereditary neutrophilia, chronic idiopathic neutrophilia

- Pelger–Huet anomaly

- Down syndrome

- Leukocyte adhesion deficiency

- Familial cold urticaria

- Leukemia (chronic myelogenous (CML)) and other myeloproliferative disorders

- Surgical removal of spleen

Secondary causes

- Infection

- Chronic inflammation – especially juvenile rheumatoid arthritis, rheumatoid arthritis, Still's disease, Crohn's disease, ulcerative colitis, granulomatous infections (for example, tuberculosis), and chronic hepatitis

- Cigarette smoking – occurs in 25–50% of chronic smokers and can last up to 5 years after quitting

- Stress – exercise, surgery, general stress

- Medication induced – corticosteroids (for example, prednisone, β-agonists, lithium)

- Cancer – either by growth factors secreted by the tumor or invasion of bone marrow by the cancer

- Increased destruction of cells in peripheral circulation can stimulate bone marrow. This can occur in hemolytic anemia and idiopathic thrombocytopenic purpura

An increase in eosinophils, i.e., the presence of more than 500 eosinophils/microlitre of blood is called an eosinophilia, and is typically seen in people with a parasitic infestation of the intestines; autoimmune and collagen vascular disease (such as rheumatoid arthritis) and Systemic lupus erythematosus; malignant diseases such as eosinophilic leukemia, clonal hypereosinophilia, and Hodgkin's disease; lymphocyte-variant hypereosinophilia; extensive skin diseases (such as exfoliative dermatitis); Addison's disease and other causes of low corticosteroid production (corticosteroids suppress blood eosinophil levels); reflux esophagitis (in which eosinophils will be found in the squamous epithelium of the esophagus) and eosinophilic esophagitis; and with the use of certain drugs such as penicillin. But, perhaps the most common cause for eosinophilia is an allergic condition such as asthma. In 1989, contaminated L-tryptophan supplements caused a deadly form of eosinophilia known as eosinophilia-myalgia syndrome, which was reminiscent of the Toxic Oil Syndrome in Spain in 1981.

Eosinophils play an important role in asthma as the number of accumulated eosinophils corresponds to the severity of asthmatic reaction. Eosinophilia in mice models are shown to be associated with high interleukin-5 levels. Furthermore, mucosal bronchial biopsies conducted on patients with diseases such as asthma have been found to have higher levels of interleukin-5 leading to higher levels of eosinophils. The infiltration of eosinophils at these high concentrations causes an inflammatory reaction. This ultimately leads to airway remodelling and difficulty of breathing.

Eosinophils can also cause tissue damage in the lungs of asthmatic patients. High concentrations of eosinophil major basic protein and eosinophil-derived neurotoxin that approach cytotoxic levels are observed at degranulation sites in the lungs as well as in the asthmatic sputum.

Granulocytopenia is an abnormally low concentration of granulocytes in the blood. This condition reduces the body's resistance to many infections. Closely related terms include agranulocytosis (etymologically, "no granulocytes at all"; clinically, granulocyte levels less than 5% of normal) and neutropenia (deficiency of neutrophil granulocytes). Granulocytes live only one to two days in circulation (four days in spleen or other tissue), so transfusion of granulocytes as a therapeutic strategy would confer a very short-lasting benefit. In addition, there are many complications associated with such a procedure.

There is usually a granulocyte chemotactic defect in individuals suffering from insulin-dependent diabetes mellitus.

Treatments used to combat autoimmune diseases and conditions caused by eosinophils include:

- corticosteroids – promote apoptosis. Numbers of eosinophils in blood are rapidly reduced

- monoclonal antibody therapy – e.g., mepolizumab or reslizumab against IL-5, prevents eosinophilopoiesis

- antagonists of leukotriene synthesis or receptors

- imatinib (STI571) – inhibits PDGF-BB in hypereosinophilic leukemia

Monoclonal antibodies such as dupilumab and lebrikizumab target IL-13 and its receptor, which reduces eosinophilic inflammation in pateints with asthma due to lowering the number of adhesion molecules present for eosinophils to bind to, thereby decreasing inflammation. Mepolizumab and benralizumab are other treatment options that target the alpha subunit of the IL-5 receptor, thereby inhibiting its function and reducing the number of developing eosinophils as well as the number of eosinophils leading to inflammation through antibody-dependent cell-mediated cytotoxicity and eosinophilic apoptosis.

Neutropenia can be acquired or intrinsic. A decrease in levels of neutrophils on lab tests is due to either decreased production of neutrophils or increased removal from the blood. The following list of causes is not complete.

- Medications - chemotherapy, sulfas or other antibiotics, phenothiazenes, benzodiazepines, antithyroids, anticonvulsants, quinine, quinidine, indomethacin, procainamide, thiazides

- Radiation

- Toxins - alcohol, benzenes

- Intrinsic disorders - Fanconi's, Kostmann's, cyclic neutropenia, Chédiak–Higashi

- Immune dysfunction - disorders of collagen, AIDS, rheumatoid arthritis

- Blood cell dysfunction - megaloblastic anemia, myelodysplasia, marrow failure, marrow replacement, acute leukemia

- Any major infection

- Miscellaneous - starvation, hypersplenism

Symptoms of neutropenia are associated with the underlying cause of the decrease in neutrophils. For example, the most common cause of acquired neutropenia is drug-induced, so an individual may have symptoms of medication overdose or toxicity.

Treatment is also aimed at the underlying cause of the neutropenia. One severe consequence of neutropenia is that it can increase the risk of infection.

Granulocytes are a category of white blood cells characterized by the presence of granules in their cytoplasm. They are also called polymorphonuclear leukocytes (PMN, PML, or PMNL) because of the varying shapes of the nucleus, which is usually lobed into three segments. This distinguishes them from the mononuclear agranulocytes. In common parlance, the term "polymorphonuclear leukocyte" often refers specifically to "neutrophil granulocytes", the most abundant of the granulocytes; the other types (eosinophils, basophils, and mast cells) have lower numbers. Granulocytes are produced via granulopoiesis in the bone marrow.

Primary immunodeficiency diseases are inborn errors in the immune system due to defective genes. Certain of these disorders are sometimes or often associated with hypereosinophilia. The list of such diorders includes ZAP70 deficiency (defective "ZAP70" gene), CD3gamma chain deficiency (defective "CD3G" gene), MCHII deficiency (defective "RFXANK" gene), Wiskott–Aldrich syndrome (defective "WAS" gene), IPEX syndrome (defective "IPEX" gene), "CD40" gene defect, and autoimmune lymphoproliferative syndrome (defective "Fas receptor" gene). More than 30 other primary immunodeficiency diseases are sometimes associated with modest increases in eosinophil counts, i.e. eosinophilia. The hyperimmunoglobulin E syndrome is associated with hypereosionphilia or eosinophilia due to mutations in any one of the following genes: "STAT3, DOCK8, PGM3, SPINK5", and "TYK2" (see mutations in the hymperimmoglobulin E syndrome). Omenn syndrome is a severe combined immuodeficiency disease characterized by skin rash, slenomegaly, and lymphadenopathy due to a causative mutation in "RAG1, RAG2]]", or, more rarely, one of several other genes.

Lymphocyte-variant hypereosinophila, also termed lymphocyte variant eosinophilia, is a rare disorder in which eosinophilia or hypereosinophilia (i.e. a large or extremely large increase in the number of eosinophils in the blood circulation) is caused by 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.

The overly stimulated CFU-Eos cells mature to apparently normal eosinophils, enter the circulation, and may accumulate in, and severely damage, various tissues. The disorder is usually indolent or slowly progressive but may proceed to a leukemic phase and at this phases is sometimes classified as acute eosinophilic leukemia. Hence, lymphocyte-variant hypereosinophilia can be regarded as a precancerous disease.

The order merits therapeutic intervention to avoid or reduce eosinophil-induced tissue injury and to treat its leukemic phase. The latter phase of the disease is aggressive and typically responds relatively poorly to anti-leukemia chemotherapeutic drug regimens.

Certain malignancies cause a secondary eosinophilia or, less commonly, hypereosinophilia. These increases in blood eosinophils appear due to the release of stimulatory cytokines or invasion of the bone marrow and thereby irritation of resident eosinophils or their precursors. Malignancies associated with these effects include gastric, colorectal, lung, bladder, and thyroid cancers, as well as squamous cell cancers of the cervix, vagina, penis, skin, and nasopharyrnx. Some hematological malignancies are likewise associated with secondary rises in blood eosinophil counts; these include Hodgkin disease, certain T-cell lymphomas, acute myeloid leukemia , the myelodysplastic syndromes, many cases of systemic mastocytosis, chronic myeloid leukemia, polycythemia vera, essential thrombocythemia, myelofibrosis, chronic myelomonocytic leukemia, and certain cases of T-lymphoblastic leukemia/lymphoma-associated or myelodysplastic–myeloproliferative syndrome-associated eosinophilias.

Lymphocyte-variant hypereosinophilia usually takes a benign and indolent course. Long term treatment with corticosteroids lowers blood eosinophil levels as well as suppresses and prevents complications of the disease in >80% of cases. However, signs and symptoms of the disease recur in virtually all cases if corticosteroid dosages are tapered in order to reduce the many adverse side effects of corticosteroids. Alternate treatments used to treat corticosteroid resistant disease or for use as corticosteroid-sparing substitutes include interferon-α or its analog, Peginterferon alfa-2a, Mepolizumab (an antibody directed against IL-5), Ciclosporin (an Immunosuppressive drug), imatinib (an inhibitor of tyrosine kinases; numerous tyrosine kinase cell signaling proteins are responsible for the growth and proliferation of eosinophils {see clonal eosinophilia}), methotrexate and Hydroxycarbamide (both are chemotherapy and immunosuppressant drugs), and Alemtuzumab (a antibody that binds to the CD52 antigen on mature lymphocytes thereby marking them for destruction by the body). The few patients who have been treated with these alternate drugs have exhibited good responses in the majority of instances. Reslizumab, a newly developed antibody directed against interleukin 5 that has been successfully used to treat 4 patients with the hypereosinophilic syndrome, may also be of use for lymphocyte-variant eosinophilia. Patients suffering minimal or no disease complications have gone untreated.

In 10% to 25% of patients, mostly 3 to 10 years after initical diagnosis, the indolent course of lymphocyte-variant hypereosinophilia changes. Patients exhibit rapid increases in lymphadenopathy, spleen size, and blood cell numbers, some cells of which take on the appearance of immature and/or malignant cells. Their disease soon thereafter escalates to an angioimmunoblastic T-cell lymphoma, peripheral T cell lymphoma, Anaplastic large-cell lymphoma (which unlike most lymphomas of this type is Anaplastic lymphoma kinase-negative), or Cutaneous T cell lymphoma. The malignantly transformed disease is aggressive and has a poor prognosis. Recommended treatment includes chemotherapy with Fludarabine, Cladribine, or the CHOP combination of drugs followed by bone marrow transplantation.

Hodgkin lymphoma (Hodgkin's disease) often elicits severe eosinophilia; however, non-Hodgkin lymphoma and leukemia produce less marked eosinophilia. Of solid tumor neoplasms, ovarian cancer is most likely to provoke eosinophilia, though any other cancer can cause the condition. Solid epithelial cell tumors have been shown to cause both tissue and blood eosinophilia, with some reports indicating that this may be mediated by interleukin production by tumor cells, especially IL-5 or IL-3. This has also been shown to occur in Hodgkin lymphoma, in the form of IL-5 secreted by Reed-Sternberg cells. In primary cutaneous T cell lymphoma, blood and dermal eosinophilia are often seen. Lymphoma cells have also been shown to produce IL-5 in these disorders. Other types of lymphoid malignancies have been associated with eosinophilia, as in lymphoblastic leukemia with a translocation between chromosomes 5 and 14 or alterations in the genes which encode platelet-derived growth factor receptors alpha or beta. Patients displaying eosinophilia overexpress a gene encoding an eosinophil hematopoietin. A translocation between chromosomes 5 and 14 in patients with acute B lymphocytic leukemia resulted in the juxtaposition of the IL-3 gene and the immunoglobulin heavy-chain gene, causing overproduction production of IL-3, leading to blood and tissue eosinophilia.

Neutrophils (also known as neutrocytes) are the most abundant type of granulocytes and the most abundant (40% to 70%) type of white blood cells in most mammals. They form an essential part of the innate immune system. Their functions vary in different animals.

They are formed from stem cells in the bone marrow. They are short-lived and highly motile, or mobile, as they can enter parts of tissue where other cells/molecules cannot. Neutrophils may be subdivided into segmented neutrophils and banded neutrophils (or bands). They form part of the polymorphonuclear cells family (PMNs) together with basophils and eosinophils.

The name "neutrophil" derives from staining characteristics on hematoxylin and eosin (H&E) histological or cytological preparations. Whereas basophilic white blood cells stain dark blue and eosinophilic white blood cells stain bright red, neutrophils stain a neutral pink. Normally, neutrophils contain a nucleus divided into 2–5 lobes.

Neutrophils are a type of phagocyte and are normally found in the bloodstream. During the beginning (acute) phase of inflammation, particularly as a result of bacterial infection, environmental exposure, and some cancers, neutrophils are one of the first-responders of inflammatory cells to migrate towards the site of inflammation. They migrate through the blood vessels, then through tissue, following chemical signals such as Interleukin-8 (IL-8), C5a, fMLP, Leukotriene B4 and HO in a process called chemotaxis. They are the predominant cells in pus, accounting for its whitish/yellowish appearance.

Neutrophils are recruited to the site of injury within minutes following trauma, and are the hallmark of acute inflammation; however, due to some pathogens being indigestible, they can be unable to resolve certain infections without the assistance of other types of immune cells.

Neutrophils display highly directional amoeboid motility in infected footpad and phalanges. Intravital imaging was performed in the footpad path of LysM-eGFP mice 20 minutes after infection with "Listeria monocytogenes".

Allergic reactions to drugs are a common cause of eosinophilia, with manifestations ranging from diffuse maculopapular rash, to severe life-threatening drug reactions with eosinophilia and systemic symptoms (DRESS). Drugs that have been shown to cause DRESS are aromatic anticonvulsants and other antiepileptics, sulfonamides, allopurinol, nonsteroidal anti-inflammatory drugs (NSAIDs), some antipsychotics such as risperidone, and certain antibiotics. Phenibut, an analogue of the neurotransmitter GABA, has also been implicated in high doses. The reaction which has been shown to be T-cell mediated may also cause eosinophilia-myalgia syndrome.

In cardiovascular disease, increased white blood cell counts have been shown to indicate a worse prognosis.

An increase in eosinophil granulocyte is known as eosinophilia.

Granulocytosis can be a feature of a number of diseases:

- Infection, especially bacterial

- Malignancy, most notably leukemia (it is the main feature of chronic myelogenous leukemia, CML)

- Autoimmune disease

There are many causes of eosinophilia that may underlie eosinophilic myocarditis. These causes are classified as primary (i.e. a defect intrinsic to the eosinophil cell line), secondary (induced by an underlying disorder that stimulates the proliferation and activation of eosinophils), or idiopathic (i.e. unknown cause). Non-idiopathic causes of the disorder are sub-classified into various forms of allergic, autoimmune, infectious, or malignant diseases and hypersensitivity reactions to drugs, vaccines, or transplanted hearts. While virtually any cause for the elevation and activation of blood eosinophils must be considered as a potential cause for eosinophilic myocarditis, the follow list gives the principal types of eosinophilia known or thought to underlie the disorder.

Primary conditions that may lead to eosinophilic myocarditis are:

- Clonal hypereosinophilia.

- Chronic eosinophilic leukemia.

- The idiopathic hypereosinophilic syndrome.

Secondary conditions that may lead to eosinophilic myocarditis are:

- Infections agents:

- Parasitic worms: various "Ascaris, Strongyloides, Schistosoma, filaria, Trematoda", and "Nematode" species. Parasitic infestations often cause significant heart valve disease along with myocarditis and the disorder in this setting is sometimes termed Tropical endomyocardial fibrosis. While commonly considered to be due to the cited parasites, this particular form of eosinophilic myocarditis may more often develop in individuals with other disorders, e.g. malnutrition, dietary toxins, and genetic predisposition, in addition to or place of round worm infestation.

- Infections by protozoa: various "Toxoplasma gondii, Trypanosoma cruzi, trichinella spiralis, Entamoeba", and "Echinococcus" species.

- Viruses: While some viral infections (e.g. HIV) have been considered causes of eosinophilic endocarditis, a study of 20 patients concluded that viral myocarditis lacks the characteristic of eosinophil-induced damage in hearts taken during cardiac transplantation.

- Allergic and autoimmune diseases such as severe asthma, rhinitis, or urticarial, chronic sinusitis, aspirin-induced asthma, allergic bronchopulmonary aspergillosis, chronic eosinophilic pneumonia, Kimura's disease, polyarteritis nodosa, eosinophilic granulomatosis with polyangiitis (i.e. Churg-Strauss syndrome), and rejection of transplanted hearts.

- Malignancies and/or premalignant hematologic conditions not due to a primary disorder in eosinophils such as Gleich's syndrome, Lymphocyte-variant hypereosinophilia Hodgkin disease, certain T-cell lymphomas, acute myeloid leukemia, the myelodysplastic syndromes, systemic mastocytosis, chronic myeloid leukemia, polycythemia vera, essential thrombocythemia, myelofibrosis, chronic myelomonocytic leukemia, and T-lymphoblastic leukemia/lymphoma-associated or myelodysplastic–myeloproliferative syndrome-associated eosinophilias; IgG4-related disease and Angiolymphoid hyperplasia with eosinophilia as well as non-hematologic cancers such as solid tumors of the lung, gastrointestinal tract, and genitourinary tract.

- Hypersensitivity reactions to agents include:

- Antibiotics/anti-viral agents: various penicillins (e.g. penicillin, ampicillin), cephalosporins (e.g. cephalosporin), tetracyclins (e.g. tetracycline), sulfonamides (e.g. sulfadiazine, sulfafurazole), sulfonylureas, antituburcular drugs (e.g. isoniazid, 4-aminosalicylic acid), linezolid, amphotericin B, chloramphenicol, streptomycin, dapsone, nitrofurantoin, metronidazole, nevirapine, efavirenz, abacavir, nevirapine.

- Anticonvulsants/Antipsychotics/antidepressants: phenindione, phenytoin, phenobarbital, lamotrigine, lamotrigine, clozapine, valproic acid, carbamazepine, desipramine, fluoxetine, amitriptyline, olanzapine.

- Anti-inflammatory agents: ibuprofen, indomethacin, phenylbutazone, oxyphenbutazone, acetazolamide, piroxicam, diclofenac.

- Diuretics: hydrochlorothiazide, spironolactone, chlortalidone.

- ACE inhibitors: captopril, enalapril.

- Other drugs: digoxin, ranitidine, lenalidomide, methyldopa, interleukin 2, dobutamine, acetazolamide.

- Contaminants: Unidentified contaminants inrapeseed oil cause the toxic oil syndrome and in commercial batches of the amino acid, L-tryptophan, cause the eosinophilia–myalgia syndrome.

- Vaccinations: Tetanus toxoid, smallpox, and diphtheria/pertussis/tetanus vaccinations.

The DRESS syndrome is a severe immunological drug reaction. It differs from other drug reactions in that it: a) is caused by a particular set of drugs; b) typically occurs after a delay of 2 to 8 weeks following intake of an offending drug; c) presents with a specific set of signs and symptoms (i.e. modest or extreme elevations in blood eosinophil and atypical lymphocyte counts; acute onset of a skin rash; lymphadenopathy; fever; neuralgia; and involvement of at least one internal organ such as the liver, lung, or heart; d) develops in individuals with particular genetic predispositions; and e) involves reactivation of latent viruses, most commonly human herpesvirus 6 or more rarely human herpes virus 5 (i.e. human cytomegalovirus), human herpesvirus 7, and human herpesvirus 4 (i.e. Epstein–Barr virus). These virus usually become dormant after infecting humans but under special circumstances, such as drug intake, are reactivated and may contribute to serious diseases such as the DRESS syndrome.

Clonal hypereosinophilia, also termed Primary hypereosinophelia or clonal eosinophilia, is a grouping of hematological disorder characterized by the development and growth of a pre-malignant or malignant population of eosinophils, a type of white blood cell, in the bone marrow, blood, and/or other tissues. This population consists of a clone of eosinophils, i.e. a group of genetically identical eosinophils derived from a sufficiently mutated ancestor cell.

The clone of eosinophils bear a mutation in any one of several genes that code for proteins that regulate cell growth. The mutations cause these proteins to be continuously active and thereby to stimulate growth in an uncontrolled and continuous manner. The expanding population of eosinophils, initially formed in the bone marrow may spread to the blood and then enter into and injure various tissues and organs.

Clinically, clonal eosinophilia resembles various types of chronic or acute leukemias, lymphomas, or myeloproliferative hematological malignancies. However, many of the clonal hypereosinophilias are distinguished from these other hematological malignancies by the genetic mutations which underlie their development and, more importantly, by their susceptibility to specific treatment regiments. That is, many types of these disorders are remarkably susceptible to relatively non-toxic drugs.

Most patients with "ETV6-ACSL6"-related disease present with findings similar to eosinophilia, hypereosinophila, or chronic eosinophilic leukemia; at least 4 cases presented with eosinophilia plus findings of the red blood cell neoplasm, polycythemia vera; three cases resembled acute myelogenous leukemia; and one case presented with findings of a combined Myelodysplastic syndrome/myeloproliferative neoplasm. Best treatments for "ETV6-ACSL6"-related disease are unclear. Patients with the polycythemia vera form of the disease have been treated by reducing the circulating red blood cell load by phlebotomy or suppressing red blood cell formation using hydroxyurea. Individual case studies report that "ETV6-ACSL6"-associated disease is insensitive to tyrosine kinase inhibitors. Best treatment currently available, therefore, may involve chemotherapy and bone marrow transplantion.

The European Medicines Agency (EMA) estimated the prevalence of HES at the time of granting orphan drug designation for HES in 2004 at 1.5 in 100,000 people, corresponding to a current prevalence of about 8,000 in the EU, 5,000 in the U.S., and 2,000 in Japan.

Patients who lack chronic heart failure and those who respond well to Prednisone or a similar drug have a good prognosis. However, the mortality rate rises in patients with anaemia, chromosomal abnormalities or a very high white blood cell count.

Leukocytosis is very common in acutely ill patients. It occurs in response to a wide variety of conditions, including viral, bacterial, fungal, or parasitic infection, cancer, hemorrhage, and exposure to certain medications or chemicals including steroids.

For lung diseases such as pneumonia and tuberculosis, WBC count is very important for the diagnosis of the disease, as leukocytosis is usually present.

The mechanism that causes leukocytosis can be of several forms: an increased release of leukocytes from bone marrow storage pools, decreased margination of leukocytes onto vessel walls, decreased extravasation of leukocytes from the vessels into tissues, or an increase in number of precursor cells in the marrow.

Certain medications, including corticosteroids, lithium and beta agonists, may cause leukocytosis.

Leukocytosis is white cells (the leukocyte count) above the normal range in the blood. It is frequently a sign of an inflammatory response, most commonly the result of infection, but may also occur following certain parasitic infections or bone tumors as well as leukemia. It may also occur after strenuous exercise, convulsions such as epilepsy, emotional stress, pregnancy and labor, anesthesia, and epinephrine administration.

There are five principle types of leukocytosis:

1. Neutrophilia (the most common form)

2. Lymphocytosis

3. Monocytosis

4. Eosinophilia

5. Basophilia

This increase in leukocyte (primarily neutrophils) is usually accompanied by a "left upper shift" in the ratio of immature to mature neutrophils and macrophages. The proportion of immature leukocytes decreases due to proliferation and inhibition of granulocyte and monocyte precursors in the bone marrow which is stimulated by several products of inflammation including C3a and G-CSF.

Although it may indicate illness, leukocytosis is considered a laboratory finding instead of a separate disease. This classification is similar to that of fever, which is also a test result instead of a disease.

"Right shift" in the ratio of immature to mature neutrophils is considered with reduced count or lack of "young neutrophils" (metamyelocytes, and band neutrophils) in blood smear, associated with the presence of "giant neutrophils". This fact shows suppression of bone marrow activity, as a hematological sign specific for pernicious anemia and radiation sickness.

A leukocyte count above 25 to 30 x 10/L is termed a "leukemoid reaction", which is the reaction of a healthy bone marrow to extreme stress, trauma, or infection. It is different from leukemia and from leukoerythroblastosis, in which either immature white blood cells (acute leukemia) or mature, yet non-functional, white blood cells (chronic leukemia) are present in peripheral blood.

As noted above, a leukemoid reaction is typically a response to an underlying medical issue. Causes of leukemoid reactions include:

- Severe hemorrhage (retroperitoneal hemorrhage)

- Drugs

- Use of sulfa drugs

- Use of dapsone

- Use of glucocorticoids

- Use of G-CSF or related growth factors

- All-trans retinoic acid (ATRA)

- Ethylene glycol intoxication

- Infections

- Clostridium difficile

- Tuberculosis

- Pertussis

- Infectious mononucleosis (lymphocyte predominant)

- Visceral larva migrans (eosinophil predominant)

- Asplenia

- Diabetic ketoacidosis

- Organ necrosis

- Hepatic necrosis

- Ischemic colitis

- As a feature of trisomy 21 in infancy (incidence of ~10%)

- As a paraneoplastic phenomenon (rare)

Allergic inflammation is an important pathophysiological feature of several disabilities or medical conditions including allergic asthma, atopic dermatitis, allergic rhinitis and several ocular allergic diseases. Allergic reactions may generally be divided into two components; the early phase reaction, and the late phase reaction. While the contribution to the development of symptoms from each of the phases varies greatly between diseases, both are usually present and provide us a framework for understanding allergic disease.

The early phase of the allergic reaction typically occurs within minutes, or even seconds, following allergen exposure and is also commonly referred to as the immediate allergic reaction or as a Type I allergic reaction. The reaction is caused by the release of histamine and mast cell granule proteins by a process called degranulation, as well as the production of leukotrienes, prostaglandins and cytokines, by mast cells following the cross-linking of allergen specific IgE molecules bound to mast cell FcεRI receptors. These mediators affect nerve cells causing itching, smooth muscle cells causing contraction (leading to the airway narrowing seen in allergic asthma), goblet cells causing mucus production, and endothelial cells causing vasodilatation and edema.

The late phase of a Type 1 reaction (which develops 8–12 hours and is mediated by mast cells) should not be confused with delayed hypersensitivity Type IV allergic reaction (which takes 48–72 hours to develop and is mediated by T cells). The products of the early phase reaction include chemokines and molecules that act on endothelial cells and cause them to express Intercellular adhesion molecule (such as vascular cell adhesion molecule and selectins), which together result in the recruitment and activation of leukocytes from the blood into the site of the allergic reaction. Typically, the infiltrating cells observed in allergic reactions contain a high proportion of lymphocytes, and especially, of eosinophils. The recruited eosinophils will degranulate releasing a number of cytotoxic molecules (including Major Basic Protein and eosinophil peroxidase) as well as produce a number of cytokines such as IL-5. The recruited T-cells are typically of the Th2 variety and the cytokines they produce lead to further recruitment of mast cells and eosinophils, and in plasma cell isotype switching to IgE which will bind to the mast cell FcεRI receptors and prime the individual for further allergic responses.