Neutropenia is usually detected shortly after birth, affecting 6% to 8% of all newborns in neonatal intensive care units (NICUs). Out of the approximately 600,000 neonates annually treated in NICUs in the United States, 48,000 may be diagnosed as neutropenic. The incidence of neutropenia is greater in premature infants. Six to fifty-eight percent of preterm neonates are diagnosed with this auto-immune disease. The incidence of neutropenia correlates with decreasing birth weight. The disorder is seen up to 38% in infants that weigh less than 1000g, 13% in infants weighing less than 2500g, and 3% of term infants weighing more than 2500 g. Neutropenia is often temporary, affecting most newborns in only first few days after birth. In others, it becomes more severe and chronic indicating a deficiency in innate immunity.

The pathophysiology of neutropenia can be divided into "congenital" and "acquired". In congenital neutropenia (cyclic neutropenia) is autosomal dominant, mutations in the ELA2 gene (neutrophil elastase), is the genetic reason for this condition.

Acquired neutropenia (immune-associated neutropenia) is due to anti-neutrophil antibodies that work against neutrophil-specific antigens, ultimately altering neutrophil function.

Neutropenia fever can complicate the treatment of cancers. Observations of pediatric patients have noted that fungal infections are more likely to develop in patients with neutropenia. Mortality increases during cancer treatments if neutropenia is also present.

Congenital neutropenia is determined by blood neutrophil counts (absolute neutrophil counts or ANC) < 0.5 × 10/L and recurrent bacterial infections beginning very early in childhood.

Congenital neutropenia is related to alloimmunization, sepsis, maternal hypertension, twin-to-twin transfusion syndrome, and Rh hemolytic disease.

A large number of drugs

have been associated with agranulocytosis, including antiepileptics (such as carbamazepine and valproate), antithyroid drugs (carbimazole, methimazole, and propylthiouracil), antibiotics (penicillin, chloramphenicol and co-trimoxazole), ACE inhibitors (benazepril), cytotoxic drugs, gold, NSAIDs (indomethacin, naproxen, phenylbutazone, metamizole), mebendazole, allopurinol the antidepressants mianserin and mirtazapine, and some antipsychotics (the atypical antipsychotic clozapine in particular). Clozapine users in the United States, Australia, Canada, and the UK must be nationally registered for monitoring of low WBC and absolute neutrophil counts (ANC).

Although the reaction is generally idiosyncratic rather than proportional, experts recommend that patients using these drugs be told about the symptoms of agranulocytosis-related infection, such as a sore throat and a fever.

The Centers for Disease Control traced outbreaks of agranulocytosis among cocaine users, in the US and Canada between March 2008 and November 2009, to the presence of levamisole in the drug supply. The Drug Enforcement Administration reported that, as of February 2010, 71% of seized cocaine lots coming into the US contained levamisole as a cutting agent. Levamisole is an antihelminthic (i.e. deworming) drug used in animals. The reason for adding levamisole to cocaine is unknown, although it can be due to their similar melting points and solubilities.

Certain medications can alter the number and function of white blood cells.

Medications that can cause leukopenia include clozapine, an antipsychotic medication with a rare adverse effect leading to the total absence of all granulocytes (neutrophils, basophils, eosinophils). The antidepressant and smoking addiction treatment drug bupropion HCl (Wellbutrin) can also cause leukopenia with long-term use. Minocycline, a commonly prescribed antibiotic, is another drug known to cause leukopenia. There are also reports of leukopenia caused by divalproex sodium or valproic acid (Depakote), a drug used for epilepsy (seizures), mania (with bipolar disorder) and migraine.

The anticonvulsant drug, lamotrigine, has been associated with a decrease in white blood cell count.

The FDA monograph for metronidazole states that this medication can also cause leukopenia, and the prescriber information suggests a complete blood count, including differential cell count, before and after, in particular, high-dose therapy.

Immunosuppressive drugs, such as sirolimus, mycophenolate mofetil, tacrolimus, ciclosporin, leflunomide and TNF inhibitors, have leukopenia as a known complication. Interferons used to treat multiple sclerosis, such as interferon beta-1a and interferon beta-1b, can also cause leukopenia.

Chemotherapy targets cells that grow rapidly, such as tumors, but can also affect white blood cells, because they are characterized by bone marrow as rapid growing. A common side effect of cancer treatment is neutropenia, the lowering of neutrophils (a specific type of white blood cell).

Decreased white blood cell count may be present in cases of arsenic toxicity.

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".

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.

Mutations in the ELANE gene cause cyclic neutropenia. The ELANE gene provides instructions for making a protein called neutrophil elastase, which is found in neutrophils. When the body starts an immune response to fight an infection, neutrophils release neutrophil elastase. This protein then modifies the function of certain cells and proteins to help fight the infection.

ELANE gene mutations that cause cyclic neutropenia lead to an abnormal neutrophil elastase protein that seems to retain some of its function. However, neutrophils that produce abnormal neutrophil elastase protein appear to have a shorter lifespan than normal neutrophils. The shorter neutrophil lifespan is thought to be responsible for the cyclic nature of this condition. When the affected neutrophils die early, there is a period in which there is a shortage of neutrophils because it takes time for the body to replenish its supply.

Read more about the ELANE gene.

Cyclic neutropenia is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

In most cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

Cyclic neutropenia (or cyclical neutropenia) is a form of neutropenia, a white blood cell deficiency, that tends to occur every three weeks and lasts three to six days at a time due to changing rates of cell production by the bone marrow.

Cyclic neutropenia is the result of autosomal dominantly inherited mutations in ELA2, the gene encoding neutrophil elastase,

and is estimated to occur in 1 in 1 million individuals worldwide. Treatment includes G-CSF and usually improves after puberty.

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.

The various mutations may be responsible for the untimely initiation of apoptosis in myelocytes, producing their premature destruction. There may be, in addition, other underlying molecular/genetic changes producing DNA mutations and genome instability, which contribute to initiation and progression of this disease.

Regular administration of exogenous granulocyte colony-stimulating factor (filgrastim) clinically improves neutrophil counts and immune function and is the mainstay of therapy, although this may increase risk for myelofibrosis and acute myeloid leukemia in the long term.

Over 90% of SCN responds to treatment with granulocyte colony-stimulating factor (filgrastim), which has significantly improved survival.

The thalassemia trait may confer a degree of protection against malaria, which is or was prevalent in the regions where the trait is common, thus conferring a selective survival advantage on carriers (known as heterozygous advantage), thus perpetuating the mutation. In that respect, the various thalassemias resemble another genetic disorder affecting hemoglobin, sickle-cell disease.

Basopenia (or basocytopenia) is a form of agranulocytosis associated with a deficiency of basophils.

It has been proposed as an indicator of ovulation.It is difficult to detect without flow cytometry, because normal levels are so low.

It can be defined as less than 0.01 x 10 / L.

Eosinopenia is a form of agranulocytosis where the number of eosinophil granulocytes is lower than expected. Leukocytosis with eosinopenia can be a predictor of bacterial infection. It can be induced by stress reactions, Cushing's syndrome, or the use of steroids. Pathological causes include burns and acute infections.

The disorder affects all genders but is more prevalent in certain ethnicities and age groups. 20 people die per year causing thalassemia to be listed as a “rare disease”. In the United States, thalassemia’s prevalence is approximately 1 in 272,000 or 1,000 people. There have been 4,000 hospitalized cases in England in 2002 and 9,233 consultant episodes for thalassemia. Men accounted for 53% of hospital consultant episodes and women accounted for 47%. The mean patient age is 23 with only 1% of consultants the patient is older than 75 and 69% were 15-59 year olds. The Children’s Hospital Oakland formed an international network to combat thalassemia. “It is the world’s most common genetic blood disorder and is rapidly increasing”. 7% of the world’s population are carriers and 400,000 babies are born with the trait annually. It is usually fatal in infancy if blood transfusion are not initiated immediately.

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.

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.

In mostly European experience with 69 patients during 1996-2016, the 5- and 10-year survival rates for SCLS patients were 78% and 69%, respectively, but the survivors received significantly more frequent preventive treatment with IVIG than did non-survivors. Five- and 10-year survival rates in patients treated with IVIG were 91% and 77%, respectively, compared to 47% and 37% in patients not treated with IVIG. Moreover, better identification and management of this condition appears to be resulting in lower mortality and improving survival and quality-of-life results as of late.

While inherited deficiencies in uroporphyrinogen decarboxylase often lead to the development of PCT, there are a number of risk factors that can both cause and exacerbate the symptoms of this disease. One of the most common risk factors observed is infection with the Hepatitis C virus. One review of a collection of PCT studies noted Hepatitis C infection in 50% of documented cases of PCT. Additional risk factors include alcohol abuse, excess iron (from iron supplements as well as cooking on cast iron skillets), and exposure to chlorinated cyclic hydrocarbons and Agent Orange.

It can be a paraneoplastic phenomenon.

Porphyria cutanea tarda has a prevalence estimated at approximately 1 in 10,000. An estimated 80% of porphyria cutanea tarda cases are sporadic. The exact frequency is not clear because many people with the condition never experience symptoms and those that do are often misdiagnosed with anything ranging from idiopathic photodermatitis and seasonal allergies to hives.

Persistent generalized lymphadenopathy (PGL) is enlarged painful lymph nodes occurring in a couple of different areas for more than three to six months for which no other reason can be found. This condition occurs frequently in people in the latency period of HIV/AIDS.

The lymphatic system is part of the immune surveillance system. Blood contains fluid and blood cells. The fluid, which may contain suspended foreign material such as bacteria and viruses, seeps through blood vessel walls into the tissues, where it bathes the body cells and exchanges substances with them. Some of this lymph fluid is then taken up by lymphatic vessels and passed back to the heart, where it is again mixed with the blood. On its way, the fluid passes through the lymph nodes, small nodular organs located throughout the body but concentrated in certain areas such as the armpits or groin. These lymph nodes are also known as "glands" or "lymphoid tissue". If they detect something foreign passing through them, they enlarge. This is called "lymphadenopathy" or "swollen glands". Usually this is localized (for example, an infected spot on the scalp will cause lymph nodes in the neck on that same side to swell). However, when two or more lymph node groups are involved, it is called "generalized lymphadenopathy". Usually this is in response to a significant systemic disease and will subside once the person has recovered. Sometimes it can persist long-term, even when no explanation for the lymphadenopathy can be found.

PGL is often found in cases of autoimmune disease (where the body is attacking itself). These include diseases such as rheumatoid arthritis, lupus and sarcoidosis. Some forms of cancer will also cause PGL. Sometimes, despite exhaustive investigation, no cause for PGL is found. For the patient and the physician, this can continue to be a source of concern, but many adults have had PGL all their lives and suffered no ill effects. In others, the PGL may persist for a decade or more and then mysteriously subside. Children often have generalized lymphadenopathy of the head and neck, or even PGL, without the finding of a sinister cause. At puberty this usually disappears.

The immune system of some people may be sensitized by exposure to a living exogenous irritant such as a bacterial or viral infection, which then results in PGL after the organism has been cleared from the body. In some cases the sensitization is caused by non-living exogenous irritants such as cyclic hydrocarbons (for example, resinous vapours) or pesticides and herbicides.

OM is usually a polymicrobial, opportunistic infection, caused primarily by a mixture of alpha hemolytic streptococci and anaerobic bacteria from the oral cavity such as "Peptostreptococcus", "Fusobacterium" and "Prevotella", (in contrast to OM of the long bones, usually caused by isolated "Staphylococcus aureus" infection). These are the same as the common causative organisms in odotonogenic infections. However, when OM in the jaws follows trauma, is the likely cause is still staphylococcal (usually "Staphylococcus epidermis".

Other risk factors can be any familial hypercoagulation tendency, including for example, Factor V (Five) Leiden heterozygosity.

Research into AM functionality has been on the rise since AMs are one of the first lines of a defense against invasive pathogens. One of the most prominent fields is investigating liposomes as deliverers of antibiotics for treatment of respiratory intracellular infections. Intracellular parasites, such as M. tuberculosis, C. pneumoniae, L. monocytogenes, L. pneumophila, and F. tularensis, (to name a few) are taken up by AMs via phagocytosis, but are resistant to the biocidal mechanisms of AMs and can survive intracellularly, thus inducing severe respiratory infections. Pulmonary tuberculosis is caused by M. tuberculosis, and is now a major infectious disease worldwide and its incidence is increasing, especially in association with the AIDS pandemic. For sterilization of intracellular parasites in AMs, antibiotics are normally given orally or intravenously, but much of the antibiotics disperse to many different tissues, diminishing its effectiveness. Pulmonary administration of mannosylated liposomes is a much more direct, efficient route in targeting AMs; it enhances antimicrobial effect, reduces the dosage needed, and avoids unnecessary distribution to the blood. Since mannose receptors are exclusively expressed on the surface of AM, mannosylation of liposomes is an appealing approach to cell-selective targeting to AM. The efficacy of pulmonary administration of ciprofloxacin (CPFX) incorporated into mannosylated liposomes (mannosylated CPFX-lipososomes) was examined in rats, and determined to be an efficient means to target AMs.

Of all cancers involving the same class of blood cell, 2% of cases are cutaneous T cell lymphomas. CTCL is more common in men and in African-American people. The incidence of CTCL in men is 1.6 times higher than in women.

There is some evidence of a relationship with human T-lymphotropic virus (HTLV) with the adult T-cell leukemia/lymphoma subtype. No definitive link between any viral infection or environmental factor has been definitely shown with other CTCL subtypes.

The second stage features the reabsorption of the initially extravasated fluid and albumin from the tissues, and it usually lasts 1 to 2 days. Intravascular fluid overload leads to polyuria and can cause flash pulmonary edema and cardiac arrest, with possibly fatal consequences. Death from SCLS typically occurs during this recruitment phase because of pulmonary edema arising from excessive intravenous fluid administration during the earlier leak phase. The severity of the problem depends on to the quantity of fluid supplied in the initial phase, the damage that may have been sustained by the kidneys, and the promptness with which diuretics are administered to help the patient discharge the accumulated fluids quickly. A recent study of 59 acute episodes occurring in 37 hospitalized SCLS patients concluded that high-volume fluid therapy was independently associated with poorer clinical outcomes, and that the main complications of SCLS episodes were recovery-phase pulmonary edema (24%), cardiac arrhythmia (24%), compartment syndrome (20%), and acquired infections (19%).

The prevention of episodes of SCLS has involved two approaches. The first has long been identified with the Mayo Clinic, and it recommended treatment with beta agonists such as terbutaline, phosphodiesterase-inhibitor theophylline, and leukotriene-receptor antagonists montelukast sodium.

The rationale for use of these drugs was their ability to increase intracellular cyclic AMP (adenosine monophosphate) levels, which might counteract inflammatory signaling pathways that induce endothelial permeability. It was the standard of care until the early 2000s, but was sidelined afterwards because patients frequently experienced renewed episodes of SCLS, and because these drugs were poorly tolerated due to their unpleasant side effects.

The second, more recent approach pioneered in France during the last decade (early 2000s) involves monthly intravenous infusions of immunoglobulins (IVIG), with an initial dose of 2 gr/kg/month of body weight, which has proven very successful as per abundant case-report evidence from around the world.

IVIG has long been used for the treatment of autoimmune and MGUS-associated syndromes, because of its potential immunomodulatory and anticytokine properties. The precise mechanism of action of IVIG in patients with SCLS is unknown, but it is likely that it neutralizes their proinflammatory cytokines that provoke endothelial dysfunction. A recent review of clinical experience with 69 mostly European SCLS patients found that preventive treatment with IVIG was the strongest factor associated with their survival, such that an IVIG therapy should be the first-line preventive agent for SCLS patients. According to a recent NIH survey of patient experience, IVIG prophylaxis is associated with a dramatic reduction in the occurrence of SCLS episodes in most patients, with minimal side effects, such that it may be considered as frontline therapy for those with a clear-cut diagnosis of SCLS and a history of recurrent episodes.