Causes of Neutropenia in Children

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1. Viral. Most common cause of transient neutropenia in childhood; typically lasts 3 days to 1 week. Causes include hepatitis A and B, parvovirus, respiratory syncytial, Epstein-Barr, cytomegalovirus, HIV, influenza A and B, and varicella viruses.

2. Benign ethnic neutropenia. Racial variation is seen in normal WBC counts. For children aged 2 weeks to 1 year, the lower limit of normal is 1000/mm3 for white infants and 500/mm3 for black infants. Similarly, for white and black children older than 1 year of age, the lower limits of normal are 1500/mm3 and 1000/mm3, respectively.

3. Drug-induced. Abrupt drop in ANC to < 500/mm3 usually occurs 1-2 weeks after exposure to drug. Spontaneous recovery is the rule, but in some patients neutropenia can last for months. Drugs commonly associated with drug-induced neutropenia include:

a. Indomethacin, ibuprofen.

b. Penicillins, sulfonamides.

c. Phenytoin, carbamazepine.

d. Hydralazine.

e. Phenothiazines.

f. Cimetidine, ranitidine.

g. Chemotherapeutic agents.

4. Cancer. Results in infiltration and replacement of normal marrow with malignant cells.

a. Leukemias. Acute lymphoblastic leukemia and acute myelogenous leukemia (neutropenia alone is rarely a presenting sign).

b. Solid tumors metastatic to bone marrow. Rhabdomyosarcoma, retinoblastoma, or neuroblastoma; it would be very unusual to see neutropenia alone as sole presenting sign of these tumors.

5. Severe congenital neutropenia. Patients are younger than 1 year of age with neutropenia and severe infections. May be autosomal dominant or autosomal recessive (Kostmann syndrome). ANC is usually < 200/mm3; often 0. Platelets and hemoglobin are usually normal.

6. Cyclic neutropenia. Rare, relatively benign disorder with oscillations of ANC. Often patients have remarkably regular 21-day cycles. ANC nadir is usually < 100/mm3; often 0. Reticulocytes and platelets may cycle, too. Patients may have fever, malaise, and mucositis. Diagnosis is made by checking CBC 2-3 times per week for 2-3 months.

7. Shwachman-Diamond syndrome. Very rare exocrine pancreatic insufficiency with neutropenia. Patients present in early childhood with short stature and failure to thrive. Neutropenia may be chronic or cyclic. Patients may also have anemia or thrombocytopenia.

8. Reticular dysgenesis. Very rare congenital absence of neutrophils. Patients present in infancy with severe immunodeficiency, absence of lymph nodes and tonsils, and thymic shadow. Most patients die by 6 months of age.

9. Chronic idiopathic neutropenia. Diagnosis of exclusion; may be difficult to differentiate from autoimmune neutropenia. Most patients have mild disease.

10. Fanconi anemia. Autosomal-recessive inheritance; 80% of patients have phenotypic anomalies (including skeletal anomalies of thumb). Initial blood problem is usually thrombocytopenia, not neutropenia.

11. Myelokathexis. Very rare, moderately severe neutropenia with increased myeloid elements in marrow but decreased circulating neutrophils. Primarily affects females. Patients have frequent airway infections and pneumonia.

12. Familial benign neutropenia. Rare, often autosomal-dominant, mild neutropenia. Patients have no significant increased risk of infections.

13. Chediak-Higashi syndrome. Rare, moderate neutropenia associated with partial albinism and neuropathy.

14. Acquired aplastic anemia. Neutropenia alone, as the only manifestation of aplastic anemia, would be unusual.

15. Autoimmune neutropenias. The most common causes of chronic neutropenia in childhood. Approximately one in five patients has a positive ANA finding. Serious infections are rare. Patients usually have an ANC < 500/mm3. Almost all patients recover fully within months to 2 years. May be triggered by infections, drugs, other autoimmune disorders, or cancer.

16. Splenic sequestration. Patients rarely have neutropenia as the sole manifestation.

17. Metabolic diseases. Very rare causes of neutropenia are Barth syndrome and glycogen storage disease type IB.

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