Pediatric Autoimmune and Chronic Benign Neutropenia 

Updated: Sep 09, 2019
Author: Susumu Inoue, MD; Chief Editor: Lawrence C Wolfe, MD 

Overview

Practice Essentials

Pediatric chronic autoimmune neutropenia (pediatric chronic AIN, also called chronic benign neutropenia or chronic idiopathic neutropenia) is a benign, self-limiting condition affecting infants and toddlers.[1]  The name usually refers to primary, not secondary, AIN.

Neutropenia is defined as an absolute neutrophil count (ANC) of less than 1000/μL in infants and less than 1500/μL in older children. The condition is usually discovered during the workup of a febrile illness, with the treatment of autoimmune neutropenia being focused on intercurrent infections.

Despite the fact that the condition is called autoimmune neutropenia, antibodies against neutrophils may not be demonstrated in a significant number of cases. When antibodies do occur, their presence has no prognostic or therapeutic implications, since equal proportions of antibody-positive and antibody-negative cases recover spontaneously. In addition, antibodies were demonstrated in patients who were proven to have severe congenital neutropenia due to a mutation of the ELANE gene.[2]

ANC alone does not allow differentiation of AIN from severe congenital neutropenia, since in both disorders the ANC may be extremely low. Indeed, differentiation from severe congenital neutropenia and benign ethnic neutropenia may be difficult. When severe congenital neutropenia is suspected, a molecular diagnostic test is indicated.

Secondary AIN occurs in a setting of systemic autoimmune disease, infection, neoplasia, bone marrow or organ transplantation, drug administration, or immunodeficiency. Secondary AIN develops in much older children than does primary AIN, is more common in girls, and is clinically more prone to serious infections; spontaneous recovery is rare.[3]

Chronicity means that neutropenia persists longer than 3 months. Primary AIN in infants and children lasts, on average, 20 months. Although the clinical course of AIN is usually benign, a minority of children experience frequent infections.

Signs and symptoms of autoimmune neutropenia

Physical examination may reveal signs of a local infection, including mouth ulcer, gingivitis, upper respiratory tract infections, impetigo, otitis media, pneumonia, and, very rarely, cellulitis, abscesses, or sepsis.

Workup in autoimmune neutropenia

Points to remember in patient workup include the following:

  • Determine whether neutropenia is acute and transient or chronic by obtaining frequent complete blood counts (CBCs)
  • Determine the severity of neutropenia and the severity of concurrent infection
  • Progressive neutropenia over a course of days requires rapid workup, including hematology consultation
  • History of parent consanguinity, family history of neutropenia, or past or current life-threatening infection suggests severe congenital neutropenia rather than AIN and requires genetic workup
  • When the history and serial laboratory studies are consistent with AIN, a test to detect neutrophil antibodies (human neutrophil antigens [HNA]-1, 2, and 4) is not needed
  • Be aware that there are multiple systemic diseases whose features include neutropenia, such as Hermansky-Pudlak syndrome, Barth syndrome, and Shwachman-Diamond syndrome; look for nonhematologic abnormalities and incorporate them into the differential diagnosis

Management of autoimmune neutropenia

AIN has an excellent prognosis. In patients with frequent infections, prophylactic antibiotics with trimethoprim and sulfamethoxazole may help, although the benefits are anecdotal.[4] If the patient is free from significant infection, treatment is unnecessary. Spontaneous recovery after 6-24 months is typical. In severe cases of the disease, treatment usually consists of regular administration of granulocyte colony-stimulating factor (G-CSF) (filgrastim).

Background

The definition of neutropenia in infants is different from that in adults. In infants aged 2 weeks to 1 year, the lower limit of the normal neutrophil count is 1000/µL. After the first year of life, the lower limit is 1500/µL, as in adults.

The most common form of neutropenia in infants and young children is transient neutropenia occurring with or following a viral illness. It resolves itself within 2 weeks. If it lasts longer than that, or if the child is very ill, then a full workup for neutropenia is in order.

The most common type of chronic neutropenia (neutropenia lasting for 3 months or longer) in pediatric patients is chronic benign neutropenia of childhood. Chronic benign neutropenia can be regarded as a synonym for primary AIN in children.[5]  Some investigators have also used the term chronic idiopathic neutropenia as a synonym for chronic benign neutropenia when the presence of antibodies cannot be demonstrated.[1]

The mean age at diagnosis of AIN is 6-12 months, with a range of 3-30 months. Spontaneous recovery occurs by age 5 years, and the mean duration of neutropenia is approximately 20 months.

Go to Neutropenia for complete information on this topic.

Primary and secondary autoimmune neutropenia

AIN is either primary or secondary. In primary AIN, neutropenia is the only abnormality. Infections associated with the primary form are usually limited and mild.[6] Primary neutropenia occurs in infants and toddlers, and spontaneous recovery is the rule.

Older children, adolescents, and young adults predominantly develop secondary AIN. In this condition, other primary pathologies occur, including systemic autoimmune disease, infections, malignancy, or immunodeficiency. It can also be associated with drug administration and bone marrow or organ transplantation. AIN that occurs in the older pediatric age group and adolescents must be regarded as a totally distinct entity from chronic benign neutropenia. The clinical course of secondary AIN is not benign. It is more common in females and is associated with severe infections, with spontaneous recovery being very rare. Lymphopenia, direct antiglobulin test (DAT)–positive hemolytic anemia, and/or thrombocytopenia are common in secondary AIN, developing later or at the same time.[3]  Antiphospholipid antibody syndrome is common, and ultimately, systemic lupus, Felty syndrome, Sjögren syndrome, autoimmune thyroiditis, celiac disease, and/or a lupuslike illness predominate. Therefore, in this age group, a rigorous search for evidence of other autoimmune phenomena should be made.

A case of secondary autoimmune neutropenia. This p A case of secondary autoimmune neutropenia. This patient presented with recurrent otitis and areas of cellulitis in the diaper area. Pseudomonas aeruginosa and Staphylococcus aureus were isolated from the skin lesions. Autoimmune hemolytic anemia and autoimmune neutropenia were confirmed based on the presence of autoantibodies. The patient has a mutation on exon 15, A504T, which changed an asparagine residue to a valine residue.

 

Etiology

Lalezari and colleagues demonstrated neutrophil antibodies in 119 of 121 infants and children with chronic neutropenia, thereby establishing the autoimmune nature of the disease.[7] In the study, all patients had at one time an absolute neutrophil count of less than 500/µL (see the Absolute Neutrophil Count calculator).

AIN is similar to immune thrombocytopenic purpura (ITP) of young children, a more common cytopenia in children. ITP is believed to be triggered by a viral infection and, in some individuals, by immunization. Whether autoimmune neutropenia is commonly triggered by similar etiologies is not known. A similar age group is affected, and recovery is expected in both. Some studies have shown an association with parvovirus B19 infection. Recently, Nakamura et al showed deficiencies in regulatory T cell (CD4+, CD25+) in children with autoimmune neutropenia.[8] Thus, it may be a phenomenon of physiologically delayed maturation of immune regulation.

A study by Farmer et al found autoimmune cytopenias, including autoimmune neutropenia (AIN), to make up 84.1% of autoimmune and/or hyperinflammatory complications of recombination activating gene (RAG) protein deficiency. The median age of onset for AIN in RAG-deficient patients was 2.6 years. The investigators also found that in 71.4% of cases, RAG deficiency–associated AIN was refractory to intravenous immunoglobulin, steroids, and rituximab.[9]

When identified in AIN, antibodies most commonly include immunoglobulin G (IgG) antibodies against neutrophil glycosylated isoforms of FC gamma RIIIb (or CD 16b) and human neutrophil antigen 1 (HNA1) and, less commonly, against HNA4, which are linked to the plasma membrane via a glycosylphosphatidylinositol anchor.

The human neutrophil antigen (HNA) system consists of HNA-1 through HNA-5. Of these, most common antibodies are directed against HNA-1, which consists of NA-1, NA-2, and SH. They are not anti–human leukocyte antigen (HLA) antibodies. Anti-HLA antibodies may be present, but it is very rarely the cause of AIN.

Bruin et al demonstrated that in patients with AIN, antibodies were exclusively directed against the NA alloantigens, whereas in patients with secondary autoimmune neutropenia, antibodies had pan-FC gamma RIIIb specificity.[10] though other researchers have shown that at the outset of AIN, antibodies against FCγRIIIb may be present (see below).

Bone marrow examination findings are variable and not diagnostic. Bone marrow may be normal, show late-stage maturation arrest, be hyperplastic, or be hypoplastic. In rare cases, granulocyte phagocytosis has been reported.[11]

In a study by Perdikogianni et al, circulating granulocyte colony-stimulating factor (G-CSF) levels (serum or plasma) were found to be normal, even during the neutropenic period, except when patients had infections.[12] On the other hand, Kobayashi et al found that the patient’s sera contained mildly but significantly elevated concentration of G-CSF compared with the control sera.[13]

Epidemiology

The incidence of autoimmune neutropenia does not vary among different ethnic populations.

A Scottish study estimated that in the Scottish population, the incidence of autoimmune neutropenia is 1 in 100,000 children per year.[14] This may have been an underestimate, however, because laboratory tests are not usually performed in most cases of autoimmune neutropenia.

Autoimmune neutropenia has a slight preponderance in girls in one study,[7] but not in others.[15] The mean age at diagnosis of autoimmune neutropenia is 6-12 months, with a range of 3-30 months.

A high frequency of benign neutropenia is widely recognized in African Americans, Yemenite and Falasha Jews, Black Beduin, blacks of South African extraction, Ethiopians, West Indians, Arab Jordanians, and various tribal groups inhabiting the United Arab Emirates.[16]   A study showed the median ANC of children with benign ethnic neutropenia to be 893 x 106/L.[17] The gene responsible for this form of neutropenia is identified as the DARC (Duffy antigen/receptor chemokine) gene, although the exact mechanism that causes neutropenia is still to be elucidated.[18, 19] In the age group (6 months to 3 years) when AIN is common, it may be impossible to distinguish these two entities in a given child.

Morbidity

Infections associated with primary AIN, which are usually limited and mild, include just fever, otitis media, upper respiratory tract infection, common colds, viral gastroenteritis, skin infection, stomatitis, and gingivitis. Sepsis and pneumonia are rare. Hajishengallis et al reported on the development of AIN-related periodontal disease in a child aged 2 years.[20] In a study done at St Jude Children’s Research Hospital on children with all types of chronic neutropenia, otolaryngological infections predominated, consisting of recurrent otitis media (81%), viral upper respiratory tract infection (67%), oral ulcers or gingivitis (53%), tonsillitis (39%), and sinusitis (37%).[21]

A case of secondary autoimmune neutropenia. This p A case of secondary autoimmune neutropenia. This patient presented with recurrent otitis and areas of cellulitis in the diaper area. Pseudomonas aeruginosa and Staphylococcus aureus were isolated from the skin lesions. Autoimmune hemolytic anemia and autoimmune neutropenia were confirmed based on the presence of autoantibodies. The patient has a mutation on exon 15, A504T, which changed an asparagine residue to a valine residue.

This is in contrast to the severe, life-threatening infections (quite often systemic) experienced by infants with severe congenital neutropenia (Kostmann disease and other types), children with aplastic anemia, older children with secondary AIN, and children with neutropenia who are receiving chemotherapy. An Italian study showed that 40% of children with secondary AIN had severe infections, as compared with 12% of children with primary AIN.[3]

In another study, of 73 children with neutropenia, Fioredda et al reported a rate of 0.66 infections per patient with AIN, compared with 5.75 infections per patient with severe congenital neutropenia.[22]  (The AIN figure may be an overestimate, however, since there may have been a selection bias; the neutropenia registry used in the study contained more severely affected AIN patients.) The reasons for this difference between primary autoimmune and severe congenital neutropenia may be related to the fact that individuals with AIN have an adequate bone marrow neutrophil reserve and can therefore mount some level of neutrophil response to an infection, even though these neutrophils are rapidly destroyed; this is in contrast to patients with poor or no bone marrow reserve.

Although febrile illnesses appear to be more common in children with AIN than in healthy children, AIN usually does not affect the child's growth and development, although some exceptions occur. (See History.)

Prognosis

The prognosis in primary chronic neutropenia is excellent. The condition usually lasts only 2-3 years before spontaneous resolution, and virtually all patients recover by age 5 years.

Spontaneous recovery after 6-24 months is typical. If it persists beyond age 4-5 years, consider other diagnoses (secondary neutropenia). It is important to follow these patients into recovery for this reason.

Patient Education

Thoroughly discussing the natural history with the patient’s parents and/or caregivers is important, since this can prevent undue anxiety created by low neutrophil counts.

In addition, because medical advice is usually sought after infections have occurred in a child with autoimmune neutropenia, discussing the condition’s natural history validates the experience of the parents and/or caregivers and, in turn, increases their confidence in the physician's diagnosis and treatment.

It is important for patients to maintain good dental hygiene in order to prevent gingivitis, stomatitis, and other mucous membrane infections of the mouth.

 

Presentation

History

Most children with autoimmune neutropenia receive initial medical attention because of the occurrence of a febrile illness during the last 6 months of infancy. Such illnesses include the following:

  • A simple febrile illness

  • Acute otitis media

  • Upper respiratory tract infection

  • Pneumonia

  • Gastroenteritis

  • Tonsillitis/pharyngitis

  • Skin infection

For primary AIN, a family history of neutropenia, leukopenia, and consanguinity is absent. This is in contrast to congenital neutropenia. If a complete blood count (CBC) is performed earlier in the child's life, it is usually within the reference range.

Children with autoimmune neutropenia may have a history of frequent upper respiratory infections or of other infections listed above. However, serious, life-threatening infections, such as sepsis, osteomyelitis, deep tissue cellulitis/abscess, or bacterial meningitis, are very rare. Some patients are asymptomatic. A CBC performed for an unrelated reason may reveal neutropenia.

A family history of neutropenia or consanguinity, a history of serious past infections, or documentation of past neutropenia in the child significantly favors the diagnosis of congenital neutropenia rather than acquired AIN and indicates a worse prognosis.[23]

Physical Examination

Physical examination may reveal signs of a local infection, including mouth ulcer, gingivitis, upper respiratory tract infections, impetigo, otitis media, pneumonia, and, very rarely, cellulitis, abscesses, or sepsis.

Many children may simply present with fever without any focal infection or they may physically be entirely normal. Patients generally do not exhibit growth failure or chronic illness.

 

DDx

Diagnostic Considerations

Acute transient leukopenia and neutropenia in small infants and young children are extremely common. Regardless of diagnosis, one needs to establish if the neutropenia is transient or chronic. Before suspecting chronic neutropenia, serial blood cell counts are needed. Most transient neutropenia associated with an infection in this age group resolves within 1-2 weeks. In a study of 143 neutropenic hospitalized patients in Greece, median duration of neutropenia was only 3.3 days (range 1-22 d).Two of these children were eventually diagnosed with autoimmune neutropenia.[24]  In a series reported by Lindqvist et al, the mean duration of an absolute neutrophil count of less than 500/μL was longer, 0.5 months with an infectious episode[25] . 

Differentiating AIN from ethnic neutropenia may be difficult. Inquiring about the ethnicity of the patient and parents is important. As previously mentioned, a high frequency of benign neutropenia is widely recognized in African Americans, Yemenite and Falasha Jews, Black Beduin, blacks of South African extraction, West Indians, Arab Jordanians, and various tribal groups inhabiting the United Arab Emirates.[16] Ethnic neutropenia does not cause frequent infections. The gene that is responsible for ethnic neutropenia is identified to be the DARC (Duffy antigen/chemokine receptor) gene.[18, 19] Thus, children with the above ethnic backgrounds, if their red blood cells are Duffy negative, are likely to have ethnic neutropenia.

AIN of infancy usually lasts at most 2-3 years before spontaneous resolution. If it persists beyond age 4-5 years with a benign course, and if the child is of one of the ethnicities listed above, one may suspect ethnic neutropenia. A family history of neutropenia may be helpful in this differentiation. However, neutrophil counts increase with age even in individuals with ethnic neutropenia.[26] Thus, the absence of a family member with neutropenia does not exclude the diagnosis of ethnic neutropenia.

In iso (allo)-immune neutropenia of infancy, evaluate maternal serum for neutrophil antibodies, usually anti–HNA-1 or anti–HNA-2. A positive result is consistent with iso (allo)-immune neutropenia. Suspect iso (allo)-immune neutropenia or severe congenital neutropenia if profound neutropenia is present at or shortly after birth.

Antineutrophil antibodies may not be detectable in children with AIN. In their analysis of 240 children with AIN, Bux et al detected granulocyte-specific antibodies during the first investigations in only 74% of patients.[27] In 26% of patients, "Repeated antibody testing with additional samples up to 3 times was necessary for detection of antibodies." Audrain et al found that only 60% of the patients were positive for the antibodies. Seventy-three percent of these cases were anti–HNA-1 antibodies.[28] They found that younger patients had a higher positivity rate than older children and children with HNA-1 antigen were overrepresented, suggesting this antigen may trigger antibody formation more frequently than other neutrophil antigens.

In a patient with an enlarged spleen, consider hypersplenism, glycogen storage disease, and lipid storage disease in the differential diagnosis.

The following should alert physicians to a diagnosis other than AIN:

  • Severe illness

  • Life-threatening infections

  • Significant hepatosplenomegaly

  • Neutrophil count fewer than 200 from day 1 of life

  • Purpura and/or thrombocytopenia

  • Hemorrhagic findings

  • Moderate to severe anemia

  • Lymphopenia

  • Monocytosis

  • Consanguinity

Aside from the diseases listed in the next subsection, disorders that can mimic the symptoms of autoimmune neutropenia include the following:

  • Iso (allo)-immune neutropenia in neonates

  • Cyclic neutropenia

  • Ethnic neutropenia/leukopenia

  • Hypersplenism

  • Neutropenia due to drugs

  • Neutropenia associated with systemic autoimmune disease

  • Severe congenital neutropenia, autosomal recessive and autosomal dominant

  • Transient leukopenia/neutropenia associated with viral infection

  • Neutropenia associated with congenital immunodeficiency

Go to Neutropenia for complete information on this topic.

Differential Diagnoses

  • **Severe congenital neutropenia, sporadic, autosomal recessive, and autosomal dominant:

  • *Barth syndrome

  • *Cartilage hair hypoplasia

  • *Glycogen storage disease type 1b

  • *Griscelli syndrome

  • *Hermansky-Pudlak syndrome

  • *Hyperimmunoglobulin M syndrome

  • *Kostmann syndrome

  • *Schwachman-Diamond syndrome

  • *WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome

  • Chediak-Higashi Syndrome

  • Cyclic neutropenia

  • Ethnic neutropenia/leukopenia

  • Glucose 6 phsophatase catalytic subunit 3 deficiency

  • Hypersplenism

  • Iso (allo)-immune neutropenia in neonates

  • May-Hegglin Anomaly

  • Myelokathexis

  • Neutropenia associated with congenital immunodeficiency

  • Neutropenia associated with systemic autoimmune disease

  • Neutropenia due to drugs

  • Pediatric HIV Infection

  • Transient leukopenia/neutropenia associated with viral infection

 

Workup

Approach Considerations

Neutropenia is usually discovered during the workup of a febrile illness. Leukopenia and neutropenia are also often discovered incidentally, as a result of a routine CBC or a CBC performed for an unrelated reason.

The clinical severity and frequency of infections, rather than the severity of neutropenia, should dictate the extent of laboratory workup, since finding a periodic drop in the neutrophil count to zero is not uncommon in AIN.[6]  Lindqvist et al published an algorithm for the workup of children with neutropenia that may be practical and helpful.[25]

Go to Neutropenia for complete information on this topic.

CBC

A CBC demonstrates a white blood cell (WBC) count that is either decreased or within the reference range and a neutrophil count of less than 1000/µL in infants and < 1500/μL in older children.

Performing sequential CBCs with differential to document chronicity is important, because most neutropenia in infants resolves with recovery from an acute infection. In individuals with autoimmune neutropenia, the absolute neutrophil count often remains less than 500 (see the Absolute Neutrophil Count calculator).

Monocytosis and eosinophilia may occur, although significant eosinophilia or monocytosis is rare, unlike in severe congenital neutropenia. In individuals with primary autoimmune neutropenia, hemoglobin and platelet counts are normal. In patients with secondary autoimmune neutropenia, associated anemia, an increased reticulocyte count due to hemolysis, and thrombocytopenia may be present. Presence of immature white blood cells, including blasts, suggests leukemia.

Antinuclear antibodies may be positive in patients with secondary autoimmune neutropenia, although only rarely in infants. Direct antiglobulin test (DAT) or direct Coombs test results may be positive in individuals with secondary autoimmune neutropenia; perform this study when evidence of hemolysis or thrombocytopenia (Evan syndrome) is present.

Tests for Neutrophil Antibodies

Documentation of neutrophil antibodies is not always necessary for patients with a benign course of autoimmune neutropenia. In addition, an absence of demonstrable antineutrophil antibodies does not exclude the diagnosis. The age of onset (most commonly 3-15 mo), a benign clinical course, and normal bone marrow findings are sufficient to make a diagnosis of chronic benign neutropenia of childhood or primary autoimmune neutropenia. In addition, research has indicated that, in some patients, antibodies detected at the onset are not detectable on retesting before the patient has recovered.[28] Thus, antibody test findings may not always be positive, depending on the timing. Also, sensitivity for antibody detection varies depending on the test. The indirect granulocyte immunofluorescence test (GIFT) is more sensitive than monoclonal antibody-specific immobilization of granulocyte antigens (MAIGA). It appears that panantibodies to FcγRIIIb are positive during the early period of neutropenia, but they disappear earlier than HNA1 antibodies.[4]  (Patients with detectable antineutrophil antibodies may have congenital neutropenia due to ELANE mutation. In these instances, early initiation of G-CSF may be lifesaving.[2] ) Boxer et al found no difference in the rate of spontaneous recovery between antibody-positive and antibody-negative patients with chronic autoimmune (or idiopathic) neutropenia, casting significant doubt on the usefulness of antibody testing.[2]

Bone Marrow Examination

Bone marrow examination is often necessary to exclude other diagnoses, in particular leukemia, although bone marrow findings are not diagnostic of this disorder.

The bone marrow may be hypercellular or normocellular with myeloid hyperplasia. However, it can be completely normal, including physiologic lymphoid hyperplasia.

In clinically severe instances of autoimmune neutropenia, "maturation arrest" may be observed, in that there is a paucity or absence of mature neutrophils. However, a preponderance of myelocytes, metamyelocytes, and bands may be present. In rare instances, intramedullary phagocytosis of granulocytes may be observed.[11]

Serum Immunoglobulin Quantitation

Serum immunoglobulin quantitation helps to exclude neutropenia associated with hypogammaglobulinemia or hyper-IgM syndrome.

Histologic Findings

In most instances, bone marrow findings are normal. Maturation arrest at promyelocyte or myelocyte stage typically seen in severe congenital neutropenia is absent. Absence of leukemic blasts excludes a diagnosis of leukemia.

Often, an increased number of mature lymphocytes consistent with the patient's age are present.

 

Treatment

Approach Considerations

Focus the treatment of autoimmune neutropenia on intercurrent infections. In patients with frequent infections, prophylactic antibiotics with trimethoprim and sulfamethoxazole may help, although the benefits are anecdotal,[4] and no randomized, controlled trials have been done. In children with recurrent infections, treatment with G-CSF (Neupogen) greatly decreased frequency of infections.

If the patient is free from significant infection, treatment is unnecessary.

An invasive procedure, such as a splenectomy, is not warranted, because virtually all patients spontaneously recover from chronic neutropenia.

Spontaneous recovery after 6-24 months is typical. If it persists beyond age 4-5 years, consider other diagnoses. It is important to follow these patients into recovery for this reason.

Go to Neutropenia for complete information on this topic.

Consultations

Hematologic consultation is recommended to exclude other causes of neutropenia, in particular severe congenital neutropenia and acute lymphoblastic leukemia, and to obtain assistance in the interpretation of neutrophil antibody studies.

Once the diagnosis of autoimmune neutropenia is firmly established, primary care physicians can monitor patients.

 

Medication

Medication Summary

Patients with frequent infections may benefit from prophylactic antibiotics with trimethoprim and sulfamethoxazole.

G-CSF (Filgrastim, Neupogen) has been demonstrated to raise neutrophil counts and may be useful for the treatment of persistent or recurrent infections. Intravenous gammaglobulin may be used for the same purpose. Reserve these medications for infections that do not respond to conventional antibiotics.

Colony-Stimulating Factors

Class Summary

Colony-stimulating factors (CSFs) are used for recurrent or refractory infections that are unresponsive to conventional therapy. They act as a hematopoietic growth factor that stimulates the development of granulocytes. CSFs are used to treat or prevent neutropenia in patients who are receiving myelosuppressive cancer chemotherapy and to reduce the period of neutropenia associated with bone marrow transplantation. These agents are also used to mobilize autologous peripheral blood progenitor cells for bone marrow transplantation and in the management of chronic neutropenia.

Filgrastim (G-CSF, Neupogen)

This is a G-CSF that activates and stimulates production, maturation, migration, and cytotoxicity of neutrophils. It is recommended only for patients with a clinically significant history of frequent infections.

Immunoglobulins

Class Summary

Immunoglobulins are used for infections that are unresponsive to conventional measures. Immunoglobulins are used for passive immunization, thus conferring immediate protection against some infectious diseases.

Immune Globulin, Intravenous (Carimune NF, Gammagard S/D)

This agent consists of purified IgG from human plasma; all commercially available products are viral inactivated.

Antibiotics

Class Summary

These agents are used for the prevention of frequent infections.

Trimethoprim and sulfamethoxazole (Bactrim, Septra)

This drug combination inhibits bacterial growth by inhibiting the synthesis of dihydrofolic acid. It may help frequent infections (eg, otitis media); however, the dose for this indication has not been established (no clinical studies have demonstrated the efficacy of this drug).

Corticosteroids

Class Summary

Various therapies are available that may increase the neutrophil count to normal levels temporarily in children with chronic benign neutropenia, which include corticosteroids. Corticosteroids may be useful in patients not responding to other therapies. Routine use of steroids in children with neutropenia is strongly discouraged. Do not use steroids just to increase the counts.

Prednisone

Corticosteroids such as prednisone can be used to suppress the antibody formation and increase the neutrophil count. Use of steroids in this disorder is only anecdotal Routine use of steroids in uncomplicated neutropenia is strongly discouraged. Large doses may be required, potentially leading to adverse effects such as increased risk of infection.