Pediatric Autoimmune and Chronic Benign Neutropenia Differential Diagnoses
- Author: Susumu Inoue, MD; Chief Editor: Max J Coppes, MD, PhD, MBA more...
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.[7]
Differentiating autoimmune neutropenia 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.[6] Ethnic neutropenia does not cause frequent infections.
Autoimmune neutropenia of infancy usually lasts only 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.[8] 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–NA-1 or anti–NA-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 chronic benign neutropenia. In their analysis of 240 children with autoimmune neutropenia, Bux et al detected granulocyte-specific antibodies during the first investigations in only 74% of patients.[9] In 26% of patients, "Repeated antibody testing with additional samples up to 3 times was necessary for detection of antibodies."
In a patient with an enlarged spleen, consider hypersplenism in the differential diagnosis. A significantly enlarged spleen suggests this diagnosis.
The following should alert physicians to a diagnosis other than autoimmune neutropenia:
- Severe illness
- Life-threatening infections
- Significant hepatosplenomegaly
- Neutrophil count fewer than 200 from day 1 of life
- Purpura
- Hemorrhagic findings
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
- *Chediak-Higashi syndrome
- *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
- Cyclic neutropenia
- Ethnic neutropenia/leukopenia
- Human Immunodeficiency Virus Infection
- Hypersplenism
- Iso (allo)-immune neutropenia in neonates
- May-Hegglin Anomaly
- Neutropenia associated with congenital immunodeficiency
- Neutropenia associated with systemic autoimmune disease
- Neutropenia due to drugs
- Transient leukopenia/neutropenia associated with viral infection
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Bruin MC, von dem Borne AE, Tamminga RY, Kleijer M, Buddelmeijer L, de Haas M. Neutrophil antibody specificity in different types of childhood autoimmune neutropenia. Blood. Sep 1 1999;94(5):1797-802. [Medline].
Perdikogianni Ch, Dimitriou H, Stiakaki E, Markaki EA, Kalmanti M. Adhesion molecules, endogenous granulocyte colony-stimulating factor levels and replating capacity of progenitors in autoimmune neutropenia of childhood. Acta Paediatr. Nov 2003;92(11):1277-83. [Medline].
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Hsieh MM, Everhart JE, Byrd-Holt DD, Tisdale JF, Rodgers GP. Prevalence of neutropenia in the U.S. population: age, sex, smoking status, and ethnic differences. Ann Intern Med. Apr 3 2007;146(7):486-92. [Medline].
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Jonsson OG, Buchanan GR. Chronic neutropenia during childhood. A 13-year experience in a single institution. Am J Dis Child. Feb 1991;145(2):232-5. [Medline].
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