Signs and symptoms of neutropenia include fever, painful swallowing, gingival pain, skin abscesses, and otitis. These symptoms may exist because individuals with neutropenia often have infection

Children may show signs of irritability, and poor feeding. Additionally, hypotension has also been observed in individuals who suffer from this condition

Neutropenia or neutropaenia is an abnormally low concentration of neutrophils (a type of white blood cell) in the blood. Neutrophils make up the majority of circulating white blood cells and serve as the primary defense against infections by destroying bacteria, bacterial fragments and immunoglobulin-bound viruses in the blood. Patients with neutropenia are more susceptible to bacterial infections and, without prompt medical attention, the condition may become life-threatening (neutropenic sepsis).

Neutropenia can be acute (temporary) or chronic (long lasting). The term is sometimes used interchangeably with "leukopenia" ("deficit in the number of white blood cells").

Autoimmune neutropenia is a form of neutropenia which is most common in infants and young children where the body identifies the neutrophils as enemies and makes antibody to destroy them.

Primary autoimmune neutropenia (AIN) is an autoimmune disease first reported in 1975 that primarily occurs in infancy. In autoimmune neutropenia, the immune system produces autoantibodies directed against the neutrophilic protein antigens in white blood cells known as granulocytic neutrophils (granulocytes, segmented neutrophils, segs, polysegmented neutrophils, polys). These antibodies destroy granulocytic neutrophils. Consequently, patients with autoimmune neutropenia have low levels of granulocytic neutrophilic white blood cells causing a condition of neutropenia. Neutropenia causes an increased risk of infection from organisms that the body could normally fight easily.

Who is Affected?

Primary autoimmune neutropenia has been reported as early as the second month of life although most cases are diagnosed in children between 5 and 15 months of age. Girls have a slightly higher risk of developing AIN than boys. In neutropenia discovered at birth or shortly after birth, a diagnosis of allo-immune neutropenia (from maternal white blood cell antibodies passively transferred to the infant) is more likely.

Neutropenia

In infants neutropenia is defined by absolute neutrophil counts less than 1000/uL. After the first year of life neutropenia is defined by absolute counts less than 1500/uL. Neutropenia may be primary in which it is the only blood abnormality seen. In secondary neutropenia, other primary conditions occur, including other autoimmune diseases, infections, and malignancies. Neutropenia is considered chronic when it persists for more than 6 months.

Symptoms and Disease Course

Neutropenia, which may be discovered on routine blood tests, typically causes benign infections even when the condition is severe. Ear infections (otitis media) are the most common infection seen in autoimmune neutropenia and typically infection responds to antibiotic treatment alone. Infections associated with primary AIN are usually mild and limited, including skin infections such as impetigo, gastroenteritis, upper respiratory tract infections, and ear infections. Rarely, cellulitis and abscesses may occur.

Studies of children studied for up to six years showed that most cases of autoimmune neutropenia resolved spontaneously after a median of 17 months. In 80 percent of patients, neutropenia persisted for 7 to 24 months.

Diagnosis

Patients with autoimmune neutropenia are diagnosed on the basis of blood tests showing neutropenia and the presence of granulocyte-specific antibodies. In some cases, tests for granulocyte-specific antibodies need to be repeated several times before a positive result is seen. Bone marrow aspiration, if performed, is typically normal or it can show increased cell production with a variably diminished number of segmented granulocytes.

s association with prior parvovirus B19 has been made, but this hasn’t been confirmed. Similar to the platelet deficiency idiopathic thrombocytopenic purpura, vaccines are suspected of triggering this disorder.

Treatment

Treatment consists of corticosteroids to reduce autoantibody production, antibiotics to prevent infection and granulocyte colony-stimulating factor (G-CSF) to temporarily increase neutrophil counts. In cases of severe infection or the need for surgery, intravenous immunoglobulin therapy may be used.

Febrile neutropenia can develop in any form of neutropenia, but is most generally recognized as a complication of chemotherapy when it is myelosuppressive (suppresses the bone marrow from producing blood cells).

Agranulocytosis may be asymptomatic, or may clinically present with sudden fever, rigors and sore throat. Infection of any organ may be rapidly progressive (e.g., pneumonia, urinary tract infection). Septicemia may also progress rapidly.

Agranulocytosis, also known as agranulosis or granulopenia, is an acute condition involving a severe and dangerous leukopenia (lowered white blood cell count), most commonly of neutrophils causing a 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.

In agranulocytosis, the concentration of granulocytes (a major class of white blood cells that includes neutrophils, basophils, and eosinophils) drops below 500 cells/mm³ of blood.

Monocytosis is an increase in the number of monocytes circulating in the blood. Monocytes are white blood cells that give rise to macrophages and dendritic cells in the immune system.

In humans, 950/μL is regarded as at the upper limit of normal; monocyte counts above this level are regarded as monocytosis.

Monocytosis has sometimes been called mononucleosis, but that name is usually reserved specifically for infectious mononucleosis.

Low white cell count may be due to acute viral infections, such as a cold or influenza. It has been associated with chemotherapy, radiation therapy, myelofibrosis, aplastic anemia (failure of white cell, red cell and platelet production), stem cell transplant, bone marrow transplant, HIV, AIDS, and steroid use.

Other causes of low white blood cell count include systemic lupus erythematosus, Hodgkin's lymphoma, some types of cancer, typhoid, malaria, tuberculosis, dengue, rickettsial infections, enlargement of the spleen, folate deficiencies, psittacosis, sepsis, Sjögren's syndrome and Lyme disease. It has also been shown to be caused by deficiency in certain minerals, such as copper and zinc.

Pseudoleukopenia can develop upon the onset of infection. The leukocytes (predominately neutrophils, responding to injury first) start migrating toward the site of infection, where they can be scanned. Their migration causes bone marrow to produce more WBCs to combat infection as well as to restore the leukocytes in circulation, but as the blood sample is taken upon the onset of infection, it contains low amount of WBCs, which is why it is termed "pseudoleukopenia".

Monocytopenia is a form of leukopenia associated with a deficiency of monocytes. The causes of monocytopenia include: acute infections, stress, treatment with glucocorticoids, aplastic anemia, hairy cell leukemia, acute myeloid leukemia, treatment with myelotoxic drugs and genetic syndromes, as for example MonoMAC syndrome.

It has been proposed as a measure to predict neutropenia, though some research indicates that it is less effective than lymphopenia.

Febrile neutropenia is the development of fever, often with other signs of infection, in a patient with neutropenia, an abnormally low number of neutrophil granulocytes (a type of white blood cell) in the blood. The term neutropenic sepsis is also applied, although it tends to be reserved for patients who are less well. In 50% of cases, an infection is detectable; bacteremia (bacteria in the bloodstream) is present in approximately 20% of all patients with this condition.

Leukopenia can be identified with a complete blood count.

Below are blood reference ranges for various types leucocytes/WBCs. The 2.5 percentile (right limits in intervals in image, showing 95% prediction intervals) is a common limit for defining leukocytosis.

Immunodeficiency (or immune deficiency) is a state in which the immune system's ability to fight infectious disease and cancer is compromised or entirely absent. Most cases of immunodeficiency are acquired ("secondary") due to extrinsic factors that affect the patient's immune system. Examples of these extrinsic factors include HIV infection, extremes of age, and environmental factors, such as nutrition. In the clinical setting, the immunosuppression by some drugs, such as steroids, can be either an adverse effect or the intended purpose of the treatment. Examples of such use is in organ transplant surgery as an anti-rejection measure and in patients suffering from an overactive immune system, as in autoimmune diseases. Some people are born with intrinsic defects in their immune system, or primary immunodeficiency. A person who has an immunodeficiency of any kind is said to be immunocompromised. An immunocompromised person may be particularly vulnerable to opportunistic infections, in addition to normal infections that could affect everyone. Immunodeficiency also decreases cancer immunosurveillance, in which the immune system scans the body's cells and kills neoplastic ones.

Monocytosis often occurs during chronic inflammation. Diseases that produce such a chronic inflammatory state:

- Infections: tuberculosis, brucellosis, listeriosis, subacute bacterial endocarditis, syphilis, and other viral infections and many protozoal and rickettsial infections (e.g. kala azar, malaria, Rocky Mountain spotted fever).

- Blood and immune causes: chronic neutropenia and myeloproliferative disorders.

- Autoimmune diseases and vasculitis: systemic lupus erythematosus, rheumatoid arthritis and inflammatory bowel disease.

- Malignancies: Hodgkin's disease and certain leukaemias, such as chronic myelomonocytic leukaemia (CMML) and monocytic leukemia.

- Recovery phase of neutropenia or an acute infection.

- Obesity (cf. Nagareddy et al. (2014), Cell Metabolism, Vol. 19, pp 821-835)

- Miscellaneous causes: sarcoidosis and lipid storage disease.

Bone marrow suppression also known as myelotoxicity or myelosuppression, is the decrease in production of cells responsible for providing immunity (leukocytes), carrying oxygen (erythrocytes), and/or those responsible for normal blood clotting (thrombocytes). Bone marrow suppression is a serious side effect of chemotherapy and certain drugs affecting the immune system such as azathioprine. The risk is especially high in cytotoxic chemotherapy for leukemia.

Nonsteroidal anti-inflammatory drugs (NSAIDs), in some rare instances, may also cause bone marrow suppression. The decrease in blood cell counts does not occur right at the start of chemotherapy because the drugs do not destroy the cells already in the bloodstream (these are not dividing rapidly). Instead, the drugs affect new blood cells that are being made by the bone marrow. When myelosuppression is severe, it is called myeloablation.

Because the bone marrow is the manufacturing center of blood cells, the suppression of bone marrow activity causes a deficiency of blood cells. This condition can rapidly lead to life-threatening infection, as the body cannot produce leukocytes in response to invading bacteria and viruses, as well as leading to anaemia due to a lack of red blood cells and spontaneous severe bleeding due to deficiency of platelets.

Parvovirus B19 inhibits erythropoiesis by lytically infecting RBC precursors in the bone marrow and is associated with a number of different diseases ranging from benign to severe. In immunocompromised patients, B19 infection may persist for months, leading to chronic anemia with B19 viremia due to chronic marrow suppression.

Among the presentation consistent with hyper IgM syndrome are the following:

- Infection/"Pneumocystis" pneumonia (PCP), which is common in infants with hyper IgM syndrome, is a serious illness. PCP is one of the most frequent and severe opportunistic infections in people with weakened immune systems. Many CD40 Ligand Deficiency are first diagnosed after having PCP in their first year of life. The fungus is common and is present in over 70% of healthy people’s lungs, however, Hyper IgM patients are not able to fight it off without the administration of Bactrim)

- Hepatitis (Hepatitis C)

- Chronic diarrhea

- Hypothyroidism

- Neutropenia

- Arthritis

- Encephalopathy (degenerative)

Cyclic neutropenia is a disorder that causes frequent infections and other health problems in affected individuals. People with this condition have recurrent episodes of neutropenia during which there is a shortage (deficiency) of neutrophils. Neutrophils are a type of white blood cell that plays a role in inflammation and in fighting infection. The episodes of neutropenia are apparent at birth or soon afterward. For most affected individuals, neutropenia recurs every 21 days and lasts about 3 to 5 days.

Neutropenia makes it more difficult for the body to fight off pathogens such as bacteria and viruses, so people with cyclic neutropenia typically develop recurrent infections of the sinuses, respiratory tract, and skin. Additionally, people with this condition often develop open sores (ulcers) in the mouth and colon, inflammation of the throat (pharyngitis) and gums (gingivitis), recurrent fever, or abdominal pain. People with cyclic neutropenia have these health problems only during episodes of neutropenia. At times when their neutrophil levels are normal, they are not at an increased risk of infection and inflammation.

Evans syndrome is an autoimmune disease in which an individual's antibodies attack their own red blood cells and platelets. Both of these events may occur simultaneously or one may follow on from the other.

Its overall pathology resembles a combination of autoimmune hemolytic anemia and immune thrombocytopenic purpura. Autoimmune hemolytic anemia is a condition in which the red blood cells that normally carry oxygen and carbon dioxide are destroyed by an autoimmune process. Immune thrombocytopenic purpura is a condition in which platelets are destroyed by an autoimmune process. Platelets are a component of blood that contribute to the formation of blood clots in the body to prevent bleeding.

The syndrome was first described in 1951 by R. S. Evans and colleagues.

All people with ALPS have signs of lymphoproliferation, which makes it the most common clinical manifestation of the disease. The increased proliferation of lymphoid cells can cause the size of lymphoid organs such as the lymph nodes and spleen to increase (lymphadenopathy and splenomegaly, present in respectively over 90% and over 80% of patients). The liver is enlarged (hepatomegaly in 30 - 40% of patients).

Autoimmune disease is the second most common clinical manifestation and one that most often requires treatment. Autoimmune cytopenias: Most common. Can be mild to very severe. Can be intermittent or chronic. These include: Autoimmune hemolytic anemia, Autoimmune neutropenia, Autoimmune thrombocytopenia.

Other signs can affect organ systems similar to systemic lupus erythematosus (least common, affecting <5% of patients) Symptoms of the nervous system include: Autoimmune cerebellar ataxia; Guillain–Barré syndrome; transverse myelitis. Gastrointestinal signs like Autoimmune esophagitis, gastritis, colitis, hepatitis, pancreatitis can be found or (Dermatologic) Urticaria, (Pulmonary) bronchiolitis obliterans, (Renal) Autoimmune glomerulonephritis, nephrotic syndrome.

Another sign are cancers such as Hodgkin and non-Hodgkin lymphomas which appear to be increased, possibly due to Epstein–Barr virus-encoded RNA-positivity. Some carcinomas may occur. Unaffected family members with genetic mutations are also at an increased risk of developing cancer.

The onset of HLH occurs under the age of 1 year in ~70% of cases. Familial HLH should be suspected if siblings are diagnosed with HLH or if symptoms recur when therapy has been stopped. Each full sibling of a child with familial HLH has a 25% chance of developing the disease, a 50% chance of carrying the defective gene (which is very rarely associated with any risk of disease) and a 25% chance of not being affected and not carrying the gene defect.

Patients with HLH, especially when untreated, may need intensive therapy. Therefore, HLH should be included in the differential diagnosis of ICU (Intensive Care Unit) patients with cytopenia and hyperferritinemia.

HLH clinically manifests with fever, enlargement of the liver and spleen, enlarged lymph nodes, yellow discoloration of the skin and eyes, and a rash.

Distinction between primary versus secondary immunodeficiencies are based on, respectively, whether the cause originates in the immune system itself or is, in turn, due to insufficiency of a supporting component of it or an external decreasing factor of it.

The symptoms of Felty's syndrome are similar to those of rheumatoid arthritis. Patients suffer from painful, stiff, and swollen joints, most commonly in the joints of the hands, feet, and arms. In some affected individuals, Felty's syndrome may develop during a period when the symptoms and physical findings associated with rheumatoid arthritis have subsided or are not present; in this case, Felty's syndrome may remain undiagnosed. In more rare instances, the development of Felty's syndrome may precede the development of the symptoms and physical findings associated with rheumatoid arthritis.

Felty's syndrome is also characterized by an abnormally enlarged spleen (splenomegaly) and abnormally low levels of certain white blood cells (neutropenia). As a result of neutropenia, affected individuals are increasingly susceptible to certain infections. Keratoconjunctivitis sicca may occur due to secondary Sjorgen's syndrome. Individuals with Felty's syndrome may also experience fever, weight loss, and/or fatigue. In some cases, affected individuals may have discoloration (abnormal brown pigmentation) of the skin, particularly of the leg, sores (ulcers) on the lower leg, and/or an abnormally large liver (hepatomegaly). In addition, affected individuals may have abnormally low levels of circulating red blood cells (anemia), a decrease in circulating blood platelets that assist in blood clotting functions (thrombocytopenia), abnormal liver function tests and/or inflammation of the blood vessels (vasculitis).

Cytopenia is a reduction in the number of mature blood cells. It takes a number of forms:

- Low red blood cell count: resulting in anemia.

- Low white blood cell count: leukopenia or neutropenia. Because neutrophils make up at least half of all white cells, they are almost always low in leukopenia .

- Low platelet count: thrombocytopenia.

- Low granulocyte count: granulocytopenia

- Low red blood cell, white blood cell, and platelet counts: pancytopenia.

A range of disorders can cause decreases in white blood cells. This type of white blood cell decreased is usually the neutrophil. In this case the decrease may be called neutropenia or granulocytopenia. Less commonly, a decrease in lymphocytes (called lymphocytopenia or lymphopenia) may be seen.

XMEN patients have splenomegaly, chronic Epstein Barr Virus (EBV) infection, and are developmentally normal. They have an increased susceptibility for developing EBV+ lymphoma. Additionally, XMEN patients have excessive infections consistent with the underlying immunodeficiency. These infections included recurrent otitis media, sinusitis, viral pneumonia, diarrhea, upper respiratory infections, epiglottitis, and pertussis. Although autoimmune symptoms do not feature prominently in XMEN autoimmune cytopenias were observed in two unrelated patients.

In the figure to the left, major features are present in all XMEN patients, while minor features are found only in some.

Morning pseudoneutropenia is a transient reduction in the measured neutrophil count from peripheral samples. This is noticed in some patients who are taking antipsychotic medication. Morning pseudoneutropenia is thought to be due to diurnal variation in the amount of circulating white blood cells and changes in the levels of hematopoietic cytokines and granulocyte colony stimulating factor (GCSF). Antipsychotics may amplify the natural variation in these hematopoietic factors.

Neutropenia is a hematological disorder characterized by an abnormally low number of neutrophils in the blood. Neutrophils usually make up 50-70% of circulating white blood cells and serve as the primary defense against infections. There is some variability in the neutrophil counts depending upon when the sample is taken, where the blood sample is taken from, and the system used by the medical lab for measuring the blood cells, but any significant reduction in function or number below the appropriate range may predispose individuals to infections.

Case reports of such incidences are reported with Clozapine and Risperidone and Aripiprazole.

These case reports suggest that the observed cases of the morning pseudoneutropenia did not proceed to become agranulocytosis which is a significant and dangerous side effect of some of antipsychotics. Hence it was suggested that although the morning neutrophil count may appear low, if the antipsychotic medication were considered efficaceous then white cell counts may be repeated in the afternoon prior to making a decision based only on the morning counts.