This form usually lessens in severity within two years of diagnosis.

The use of prophylactic antibiotics has been proposed.

See article at BioMed Central site:

Recombinant granulocyte-colony stimulating factor preparations, such as filgrastim can be effective in patients with congenital forms of neutropenia including severe congenital neutropenia and cyclic neutropenia, the amount needed (dosage) varies considerably (depending on the individual's condition) to stabilize the neutrophil count. Guidelines for neutropenia regarding diet are currently being studied.

Most cases of neonatal neutropenia are temporary. Antibiotic prophylaxis is not recommended because of the possibility of encouraging the development of multidrug-resistant bacterial strains.

Neutropenia can be treated with hematopoietic Growth Factors, granulocyte-colony stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF). These are cytokines (inflammation-inducing chemicals) that are present naturally in the body. These factors are used regularly in cancer treatment with adults and children. The factors promote neutrophil recovery following anticancer therapy.

The administration of intravenous immunoglobulins (IVIGs) has had some success in treating neutropenias of alloimmune and autoimmune origins with a response rate of about 50%. Blood transfusions have not been effective.

If left untreated, patients with fever and absolute neutrophil count <500 have a mortality of up to 70% within 24 hours. The prognosis of neutropenia depends on the cause. Antibiotic agents have improved the prognosis for individuals with severe neutropenia. Neutropenic fever in individuals treated for cancer has a mortality of 4-30%.

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.

Generally, patients with febrile neutropenia are treated with empirical antibiotics until the neutrophil count has recovered (absolute neutrophil counts greater than 500/mm) and the fever has abated; if the neutrophil count does not improve, treatment may need to continue for two weeks or occasionally more. In cases of recurrent or persistent fever, an antifungal agent should be added.

Guidelines issued in 2002 by the Infectious Diseases Society of America recommend the use of particular combinations of antibiotics in specific settings; mild low-risk cases may be treated with a combination of oral amoxicillin-clavulanic acid and ciprofloxacin, while more severe cases require cephalosporins with activity against "Pseudomonas aeruginosa" (e.g. cefepime), or carbapenems (imipenem or meropenem). A subsequent meta-analysis published in 2006 found cefepime to be associated with more negative outcomes, and carbapenems (while causing a higher rate of pseudomembranous colitis) were the most straightforward in use.

In 2010, updated guidelines were issued by the Infectious Diseases Society of America, recommending use of cefepime, carbapenems (meropenem and imipenem/cilastatin), or piperacillin/tazobactam for high-risk patients and amoxicillin-clavulanic acid and ciprofloxacin for low-risk patients. Patients who do not strictly fulfill the criteria of low-risk patients should be admitted to the hospital and treated as high-risk patients.

The Multinational Association for Supportive Care in Cancer (MASCC) risk index can be used to identify low-risk patients (score ≥21 points) for serious complications of febrile neutropenia (including death, intensive care unit admission, confusion, cardiac complications, respiratory failure, renal failure, hypotension, bleeding, and other serious medical complications). The score was developed to select patients for therapeutic strategies that could potentially be more convenient or cost-effective. A prospective trial demonstrated that a modified MASCC score can identify patients with febrile neutropenia at low risk of complications, as well.

In contrast, the Clinical Index of Stable Febrile Neutropenia (CISNE) score is specific of patients with solid tumors and seemingly stable episodes. CISNE is able to discriminate groups of patients who are at low, intermediate, and high risk of complications in this population. With the CISNE, the complication rate was determined to be 1.1% for low-risk patients, 6.2% for intermediate-risk patients, and 36.0% for high-risk patients. The prime purpose of this model was to avoid complications from an early hospital release. On the contrary, CISNE should not be used so much to select low-risk patients for outpatient treatment.

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.

In patients that have no symptoms of infection, management consists of close monitoring with serial blood counts, withdrawal of the offending agent (e.g., medication), and general advice on the significance of fever.

Transfusion of granulocytes would have been a solution to the problem. However, granulocytes live only ~10 hours in the circulation (for days in spleen or other tissue), which gives a very short-lasting effect. In addition, there are many complications of such a procedure.

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.

In developing new chemotherapeutics（化疗方法），the efficacy of the drug against the disease is often balanced against the likely level of myelotoxicity the drug will cause. In-vitro colony forming cell (CFC) assays using normal human bone marrow grown in appropriate semi-solid media such as ColonyGEL have been shown to be useful in predicting the level of clinical myelotoxicity a certain compound might cause if administered to humans. These predictive in-vitro assays reveal effects the administered compounds have on the bone marrow progenitor cells that produce the various mature cells in the blood and can be used to test the effects of single drugs or the effects of drugs administered in combination with others.

Bone marrow suppression due to azathioprine can be treated by changing to another medication such as mycophenolate mofetil (for organ transplants) or other disease-modifying drugs in rheumatoid arthritis or Crohn's disease.

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".

The prognosis is guarded with an overall mortality of 50%. Poor prognostic factors included HLH associated with malignancy, with half the patients dying by 1.4 months compared to 22.8 months for non-tumour associated HLH patients.

Secondary HLH in some individuals may be self-limited because patients are able to fully recover after having received only supportive medical treatment (i.e., IV immunoglobulin only). However, long-term remission without the use of cytotoxic and immune-suppressive therapies is unlikely in the majority of adults with HLH and in those with involvement of the central nervous system (brain and/or spinal cord).

Evans syndrome is rare, serious, and has a reported mortality rate of 7%.

It has been observed that there is a risk of developing other autoimmune problems and hypogammaglobulinemia, with recent research finding that 58% of children with Evans syndrome have CD4-/CD8- T cells which is a strong predictor for having autoimmune lymphoproliferative syndrome.

The treatment of primary immunodeficiencies depends foremost on the nature of the abnormality. Somatic treatment of primarily genetic defects is in its infancy. Most treatment is therefore passive and palliative, and falls into two modalities: managing infections and boosting the immune system.

Reduction of exposure to pathogens may be recommended, and in many situations prophylactic antibiotics or antivirals may be advised.

In the case of humoral immune deficiency, immunoglobulin replacement therapy in the form of intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (SCIG) may be available.

In cases of autoimmune disorders, immunosuppression therapies like corticosteroids may be prescribed.

Prognosis depends greatly on the nature and severity of the condition. Some deficiencies cause early mortality (before age one), others with or even without treatment are lifelong conditions that cause little mortality or morbidity. Newer stem cell transplant technologies may lead to gene based treatments of

debilitating and fatal genetic immune deficiencies. Prognosis of acquired immune deficiencies depends on avoiding or treating the causative agent or

condition (like AIDS).

Initial treatment is with glucocorticoid corticosteroids or intravenous immunoglobulin, a procedure that is also used in ITP cases. In children, good response to a short steroid course is achieved in approximately 80 percent of cases. Although the majority of cases initially respond well to treatment, relapses are not uncommon and immunosuppressive drugs (e.g. ciclosporin, mycophenolate mofetil, vincristine and danazol) are subsequently used, or combinations of these.

The off-label use of rituximab (trade name Rituxan) has produced some good results in acute and refractory cases, although further relapse may occur within a year. Splenectomy is effective in some cases, but relapses are not uncommon.

The only prospect for a permanent cure is the high-risk option of an allogeneic hematopoietic stem cell transplantation (SCT).

There is no real treatment for Felty's syndrome, rather the best method in management of the disease is to control the underlying rheumatoid arthritis. Immunosuppressive therapy for RA often improves granulocytopenia and splenomegaly; this finding reflects the fact that Felty's syndrome is an immune-mediated disease. A major challenge in treating FS is recurring infection caused by neutropenia. Therefore, in order to decide upon and begin treatment, the cause and relationship of neutropenia with the overall condition must be well understood. Most of the traditional medications used to treat RA have been used in the treatment of Felty's syndrome. No well-conducted, randomized, controlled trials support the use of any single agent. Most reports on treatment regimens involve small numbers of patients.

Splenectomy may improve neutropenia in severe disease.

Use of rituximab and leflunomide have been proposed.

Use of gold therapy has also been described.

Prognosis is dependent on the severity of symptoms and the patient's overall health.

Available treatment falls into two modalities: treating infections and boosting the immune system.

Prevention of Pneumocystis pneumonia using trimethoprim/sulfamethoxazole is useful in those who are immunocompromised. In the early 1950s Immunoglobulin(Ig) was used by doctors to treat patients with primary immunodeficiency through intramuscular injection. Ig replacement therapy are infusions that can be either subcutaneous or intravenously administrated, resulting in higher Ig levels for about three to four weeks, although this varies with each patient.

In secondary cases, treatment of the cause, where possible, is indicated. Additionally, treatment for HLH itself is usually required.

While optimal treatment of HLH is still being debated, current treatment regimes usually involve high dose corticosteroids, etoposide and cyclosporin. Intravenous immunoglobulin is also used. Methotrexate and vincristine have also been used. Other medications include cytokine targeted therapy.

An experimental treatment, an anti IFN-gamma monoclonal antibody tentatively named NI-0501, is in clinical trials for treating primary HLH. The FDA awarded breakthrough drug status to NI-0501 in 2016.

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.

Treatment is most commonly directed at autoimmune disease and may be needed to treat bulky lymphoproliferation. First line therapies include corticosteroids (very active but toxic with chronic use), and IVIgG, which are not as effective as in other immune cytopenia syndromes.

Second line therapies include: mycophenolate mofetil (cellcept) which inactivates inosine monophosphate, most studied in clinical trials with responses varying (relapse, resolution, partial response). It does not affect lymphoproliferation or reduce DNTs, with no drug-drug interactions. This treatment is commonly used agent in patients who require chronic treatment based on tolerance and efficacy. It may cause hypogammaglobulinemia (transient) requiring IVIgG replacement.

Sirolimus (rapamycin, rapamune) which is a mTOR (mammalian target of rapamycin) inhibitor can be active in most patients and can in some cases lead to complete or near-complete resolution of autoimmune disease (>90%) With this treatment most patients have complete resolution of lymphoproliferation, including lymphadenopathy and splenomegaly (>90%) and have elimination of peripheral blood DNTs. Sirolimus may not be as immune suppressive in normal lymphocytes as other agents. Some patients have had improvement in immune function with transition from cellcept to rapamycin and it has not been reported to cause hypogammaglobulinemia. Hypothetically, Sirolimus may have lower risk of secondary cancers as opposed to other immune suppressants and requires therapeutic drug monitoring. It is the second most commonly used agent in patients that require chronic therapy. It is mostly well tolerated (though side effects include mucositis, diarrhea, hyperlipidemia, delayed wound healing) with drug-drug interactions. It has better activity against autoimmune disease and lymphoproliferation than mycophenolate mofetil and other drugs; however, sirolimus requires therapeutic drug monitoring and can cause mucositis. A risk with any agent in pre-cancerous syndrome as immune suppression can decreased tumor immunosurvellence. Its mTOR inhibitors active against lymphomas, especially EBV+ lymphomas. The Goal serum trough is 5-15 ng/ml and can consider PCP prophylaxis but usually not needed.

Other treatments may include drugs like Fansidar, mercaptopurine: More commonly used in Europe. Another is rituximab but this can cause lifelong hypogammaglobulinemia and a splenectomy but there is a >30% risk of pneumococcal sepsis even with vaccination and antibiotic prophylaxis

Bone marrow transplant may be possible for Severe Combined Immune Deficiency and other severe immunodeficiences.

Virus-specific T-Lymphocytes (VST) therapy is used for patients who have received hematopoietic stem cell transplantation that has proven to be unsuccessful. It is a treatment that has been effective in preventing and treating viral infections after HSCT. VST therapy uses active donor T-cells that are isolated from alloreactive T-cells which have proven immunity against one or more viruses. Such donor T-cells often cause acute graft-versus-host disease (GVHD), a subject of ongoing investigation. VSTs have been produced primarily by ex-vivo cultures and by the expansion of T-lymphocytes after stimulation with viral antigens. This is carried out by using donor-derived antigen-presenting cells. These new methods have reduced culture time to 10–12 days by using specific cytokines from adult donors or virus-naive cord blood. This treatment is far quicker and with a substantially higher success rate than the 3–6 months it takes to carry out HSCT on a patient diagnosed with a primary immunodeficiency. T-lymphocyte therapies are still in the experimental stage; few are even in clinical trials, none have been FDA approved, and availability in clinical practice may be years or even a decade or more away.

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.