The most common kind of chronic neutropenia in pediatric patients is chronic benign neutropenia of youth, ie, neutropenia lasting over 6 months. Chronic benign neutropenia can be considered as a synonym for autoimmune neutropenia (main autoimmune neutropenia [AIN] in children.
The most typical kind of neutropenia in babies and young children is short-term neutropenia with or following a viral health problem. It resolves itself within 2 weeks. If it lasts longer than that, or the child is very ill, then a complete workup for neutropenia is in order.
The definition of neutropenia in babies is various from that in grownups. In babies aged 2 weeks to 1 year, the lower limit of the regular neutrophil count is 1000/ µL. After the first year of life, the lower limitation is 1500/ µL, as in grownups.
The mean age at medical diagnosis of autoimmune neutropenia is 6-12 months, with a series of 3-30 months. Spontaneous recovery happens by age 5 years, and the mean duration of neutropenia is approximately 20 months.
Clinicians have the tendency to differentiate in between neutropenia secondary to chemotherapy for the treatment of malignancies and those unassociated to chemotherapy-related bone marrow toxicity. The etiology varies in the pediatric population, and ranges from benign causes, such as associated with a viral health problem, to acquired conditions, chronic inflammatory illness, auto-antibody production, and malignancy.
Primary and secondary autoimmune neutropenia
Autoimmune neutropenia is either main or secondary. In primary autoimmune neutropenia, neutropenia is the only abnormality. Infections connected with the primary form are usually limited and moderate.
In secondary autoimmune neutropenia, other primary pathologies take place, consisting of systemic autoimmune disease, infections, and malignancy. Autoimmune neutropenia that happens in the older pediatric age group and teenagers should be considered a completely distinct entity separate from chronic benign neutropenia (AIN). The clinical course of the secondary autoimmune neutropenia is not benign. In babies, secondary autoimmune neutropenia is extremely uncommon.
Older children, adolescents, and young people mainly establish secondary autoimmune neutropenia, and autoimmune hemolytic anemia or immune thrombocytopenia often occur later or at the very same time. Antiphospholipid antibody syndrome prevails, and ultimately, systemic lupus, Felty syndrome, Sjögren syndrome, and/or a lupuslike disease predominate. For that reason, in this age group, a strenuous search for evidence of other autoimmune phenomena should be made.
Lalezari and colleagues demonstrated neutrophil antibodies in 119 of 121 babies and children with chronic neutropenia, thus developing the autoimmune nature of the disease. In the study, all patients had at one time an outright 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 typical cytopenia in children. ITP is believed to be triggered by a viral infection and, in some individuals, by immunization. Whether autoimmune neutropenia is typically activated by similar etiologies is not known. A similar age group is impacted, and recovery is expected in both. Some research studies have actually revealed an association with parvovirus B19 infection. Just recently, Nakamura et al showed deficiencies in regulative T cell (CD4+, CD25+) in children with autoimmune neutropenia. Hence, it may be a phenomenon of physiologically delayed maturation of immune regulation.
When recognized in AIN, antibodies most typically consist of immunoglobulin G (IgG) antibodies versus neutrophil glycosylated isoforms of FC gamma RIIIb (or CD 16b) and human neutrophil antigen 1 (HNA1) and, less typically, against HNA4, which are linked to the plasma membrane through a glycosylphosphatidylinositol anchor.
The human neutrophil antigen (HNA) system includes HNA-1 through HNA-5. Of these, most common antibodies are directed versus HNA-1, which consists of NA-1, NA-2, and SH. They are not anti– human leukocyte antigen (HLA) antibodies. Anti-HLA antibodies might exist, however it is very hardly ever the reason for AIN.
Bruin et al showed that in patients with AIN, antibodies were specifically directed versus the NA alloantigens, whereas in patients with secondary autoimmune neutropenia, antibodies had pan-FC gamma RIIIb uniqueness. though other researchers have shown that at the start of AIN, antibodies against FCγRIIIb might be present (see listed below).
Bone marrow assessment findings vary and not diagnostic. Bone marrow may be regular, reveal late-stage maturation arrest, be hyperplastic, or be hypoplastic. In unusual cases, granulocyte phagocytosis has been reported.
In a study by Perdikogianni et al, circulating granulocyte colony-stimulating factor (G-CSF) levels (serum or plasma) were discovered to be regular, even during the neutropenic duration, except when patients had infections.  On the other hand, Kobayashi et al found that the patient’s sera contained slightly however significantly elevated concentration of G-CSF compared to the control sera.
The incidence of autoimmune neutropenia does not vary among different ethnic populations.
A Scottish research study approximated that in the Scottish population, the occurrence of autoimmune neutropenia is 1 in 100,000 children each year. This may have been an underestimate, nevertheless, due to the fact that lab tests are not normally carried out in most cases of autoimmune neutropenia.
Autoimmune neutropenia has a minor prevalence in girls in one research study, however not in others.  The mean age at medical diagnosis of autoimmune neutropenia is 6-12 months, with a range of 3-30 months.
A high frequency of benign neutropenia is extensively recognized in African Americans, Yemenite and Falasha Jews, Black Beduin, blacks of South African extraction, Ethiopians, West Indians, Arab Jordanians, and different tribal groups populating the United Arab Emirates. The gene responsible for this ethnic neutropenia is now determined to be DARC (Duffy antigen/receptor chemokine gene), although the exact system that causes neutropenia is still to be elucidated. In the age group (6 months to 3 years) when autoimmune neutropenia is common, it might be impossible to identify these 2 entities in a given child.
Infections associated with AIN, which, as formerly pointed out, are normally restricted and mild, include just fever, otitis media, upper breathing tract infection, acute rhinitis, viral gastroenteritis, skin infection, stomatitis, and gingivitis. Sepsis and pneumonia are unusual. In a research study done at St Jude Children’s Research Health center on children with all types of chronic neutropenia, otolaryngological infections predominated, including frequent otitis media (81%), viral upper respiratory tract infection (67%), oral ulcers or gingivitis (53%), tonsillitis (39%), and sinusitis (37%).
This remains in contrast to severe, lethal infections (frequently systemic) experienced by babies with severe congenital neutropenia (Kostmann disease and other types), children with aplastic anemia, or children with neutropenia who are receiving chemotherapy.
The factors for this distinction between main autoimmune and severe congenital neutropenia might be connected to that individuals with autoimmune neutropenia have an appropriate bone marrow neutrophil reserve and can for that reason install some level of neutrophil reaction to an infection, although these neutrophils are rapidly damaged; this remains in contrast to patients with poor or no bone marrow reserve.
In a research study of infections in 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 genetic neutropenia). This figure for AIN might be an overestimate, however, given that might have been a selection predisposition, in that the neutropenia windows registry used in the research study contained more severly affected AIN patients.
Although febrile health problems appear to be more typical in children with AIN than in healthy children, AIN generally does not affect the child’s development and advancement, although some exceptions happen. (See History.)
The diagnosis is outstanding. The condition usually lasts only 2-3 years prior to spontaneous resolution, and essentially all patients recover by age 5 years.
Spontaneous recovery after 6-24 months is typical. If it continues beyond age 4-5 years, consider other diagnoses. It is important to follow these patients into recovery for this factor.
Completely going over the nature with the patient’s parents and/or caretakers is necessary, because this can prevent undue stress and anxiety produced by low neutrophil counts.
In addition, since medical recommendations is usually searched for infections have occurred in a child with autoimmune neutropenia, talking about the condition’s nature verifies the experience of the parents and/or caretakers and, in turn, increases their confidence in the doctor’s medical diagnosis and treatment.
It is important for patients to keep excellent dental health in order to prevent gingivitis, stomatitis, and other mucous membrane infections of the mouth.
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