Home

helps physicians and healthcare professionals

Erectile Dysfunction

helps physicians and healthcare professionals

Doctor123.org

helps physicians and healthcare professionals

Neutropenia, Pediatric


Basics


Description


A decrease in the number of circulating neutrophils (both segmented and band forms), strictly defined as an absolute total neutrophil count (ANC) of <1,500/ Ž ¼L in children older than 1 year of age, <1,000/ Ž ¼L in children younger than 1 year of age, and <5,000/ Ž ¼L in the 1st week of life ‚  
  • To calculate ANC, multiply the total WBC count by the percentage of segmented neutrophils and band forms.
  • For example: WBC count 5,200/ Ž ¼L with 15% segs/polys, 4% bands, 76% lymphocytes, 5% monocytes: ANC = 5,200 ƒ — (0.15 + 0.04) = 988
  • Severe neutropenia is defined as an ANC <500/ Ž ¼L.

Epidemiology


  • Normal values for total WBC counts and ANC vary with age and race.
  • Children of some ethnic groups, including African and Middle-Eastern groups, have lower total WBC counts and lower ANCs than do white children.
    • Lower end of normal range for ANC may be 800/ Ž ¼L in 30% of African Americans and does not represent an increased risk for infection.
  • Infants have a higher total WBC count and a higher percentage of lymphocytes in their differential counts.
  • Prevalence of congenital and idiopathic neutropenia: 2.1 cases per million in the United States
  • Incidence of neonatal alloimmune neutropenia: 2 per 1,000 live births

Risk Factors


Genetics
  • A number of mutations causing severe congenital neutropenia have been identified.
    • Autosomal recessive: Kostmann syndrome (HAX1)
    • Autosomal dominant: ELA2, GFL1, GATA2, others
    • X-linked: WASP
  • Cyclic neutropenia: autosomal dominant or sporadic (ELA2)

Etiology


  • Decreased production of neutrophils
    • Viral suppression
    • Marrow suppression by drugs, chemotherapy, or radiation
    • Nutritional deficiencies
    • Primary disorders of myelopoiesis
  • Increased destruction of neutrophils
    • Immune-mediated destruction
    • Increased use (usually with overwhelming infection)
    • Sequestration in the spleen

Diagnosis


History


  • Recent or current viral infection
  • Current or recurrent fever, skin abscesses, infections, or oral ulceration
  • Temporal pattern of symptoms
  • Symptoms of malabsorption, such as diarrhea or failure to thrive
  • Delayed cord separation
  • Medication use or toxin exposure
  • Diet: evidence of nutritional deficiency
  • Developmental history
  • Ethnicity
  • Family history of neutropenia, recurrent infection, or early death; consanguinity
  • Results of prior CBC with differential: Prior normal WBC count and ANC essentially rule out severe congenital neutropenia.

Physical Exam


  • Growth curve
  • Oral ulceration or gingival irritation
  • Phenotypic abnormalities (thumb anomalies, dwarfism, partial albinism)
  • Hepatosplenomegaly or lymphadenopathy
  • Bruises, petechiae, pallor
  • Birthmarks (cafe au lait spots)
  • Neurologic exam
  • Signs of infection
    • Fever (temperature should not be taken rectally)
    • Tachycardia or hypotension
    • Pharyngitis or thrush
    • Cellulitis, perirectal or labial abscesses
    • Signs of local infection (such as inflammation, pus) may be diminished due to lack of neutrophils.

Diagnostic Tests & Interpretation


Lab
  • Repeat CBC with differential
    • Neutropenia due to viral suppression is extremely common and counts may normalize on repeat exam.
    • Hemoglobin and platelets are important as well; can help determine if this is an isolated neutropenia or pancytopenia
  • Serial CBCs, twice weekly for 6 weeks, to rule out cyclic neutropenia
  • Evaluation of exocrine pancreatic function if Shwachman-Diamond syndrome is a consideration
  • Immunologic evaluation (immunoglobulins, lymphocyte subsets) to rule out immunodeficiency
  • Antineutrophil antibodies: can often be detected in autoimmune neutropenia if multiple methods of testing are used; use unclear, however, given imperfect sensitivity and specificity
  • Cross-typing maternal serum and paternal neutrophils in evaluation of neonatal alloimmune neutropenia
  • Genetic testing for certain disorders

Diagnostic Procedures/Other
  • Bone marrow aspirate and biopsy indicated in severe chronic neutropenia, pancytopenia, or when there is other concern for a marrow disorder
  • Biopsy may be normal, or may reveal a decrease in the number of myeloid precursors or a maturational arrest of the myeloid line (usually in the later stages), depending on the cause of neutropenia.

Differential Diagnosis


  • Neutropenia associated with infection
    • Viral suppression is a very common cause of transient neutropenia.
    • Viral: hepatitis A and B, parvovirus B19, respiratory syncytial virus (RSV), influenza A and B, rubeola, rubella, varicella, cytomegalovirus (CMV), Epstein-Barr virus (EBV), HIV
    • Bacterial: group B streptococcal disease, tuberculosis, brucellosis, tularemia, typhoid, paratyphoid
    • Other: malaria, visceral leishmaniasis, scrub typhus, sandfly fever
  • Drug induced
    • Antibiotics: sulfonamides (trimethoprim/sulfamethoxazole is a common offender), penicillin, chloramphenicol (may be irreversible)
    • Chemotherapy agents: alkylating agents, antimetabolites, anthracyclines
    • Antipyretics: aspirin, acetaminophen (uncommon)
    • Sedatives: barbiturates, benzodiazepines
    • Phenothiazines: chlorpromazine, promethazine
    • Antirheumatic agents: gold, penicillamine, phenylbutazone
  • Immunologic
    • Benign neutropenia of childhood: very common cause of chronic neutropenia; immune-mediated; onset usually <2 years of age; typically a benign course with resolution within several years
    • Isoimmune neonatal neutropenia: due to transplacental transfer of maternal antibodies against paternal antigens
    • Manifestation of an autoimmune disease: systemic lupus erythematosus, autoimmune lymphoproliferative syndrome (ALPS), Felty syndrome (neutropenia, splenomegaly, and rheumatoid arthritis), others
  • Congenital
    • Severe congenital neutropenia
    • Cyclic neutropenia: regular oscillations in the number of circulating neutrophils (periodicity every 7 " “36 days; duration of neutropenia, 3 " “10 days)
  • Marrow failure syndromes
    • Shwachman-Diamond Syndrome: neutropenia and exocrine pancreatic insufficiency
    • Part of evolving aplastic anemia: acquired (idiopathic), Fanconi anemia, dyskeratosis congenital, Diamond-Blackfan anemia
  • Primary immunodeficiencies
    • Cartilage/hair hypoplasia: neutropenia, dwarfism, abnormal cellular immunity
    • Reticular dysgenesis
    • Chediak-Higashi syndrome: oculocutaneous albinism, platelet dysfunction, leukocyte inclusions
    • Other abnormalities in T and B lymphocytes
  • Bone marrow infiltration
    • Malignancy: leukemia or solid tumors metastatic to bone marrow
    • Osteopetrosis
    • Gaucher disease (lysosomal storage disorder)
  • Metabolic
    • Nutritional: malnutrition, copper deficiency, zinc deficiency, megaloblastic anemia secondary to folate or vitamin B12 deficiency
    • Inborn errors of metabolism: Barth syndrome (skeletal myopathy, dilated cardiomyopathy, neutropenia), glycogen storage disease I, others
  • Miscellaneous
    • Hypersplenism
    • Radiation injury

Treatment


Medication


  • Granulocyte colony-stimulating factor (G-CSF)
    • Indicated for severe congenital neutropenia and cyclic neutropenia (decreases infections and mortality)
    • May be used in some patients with neutropenia due to other causes

Additional Therapies


General Measures
  • Isolation of hospitalized patient: prudent until the cause of the neutropenia is identified
  • "Neutropenic precautions "  Standard hand hygiene is sufficient (no need for masks/gowns/gloves).
  • Correction of underlying cause of neutropenia (discontinue drug, treat infection, correct nutritional deficiency)
  • Treatment of fever and suspected infection when neutropenic: Initially, broad-spectrum antibiotics are indicated; after the diagnosis has been established, this may not always be necessary (i.e., individuals with chronic benign neutropenia).
  • Prophylactic antibiotics are not usually beneficial and may predispose to systemic fungal infection.
  • Stool softeners may be helpful in the profoundly neutropenic patient at risk for constipation to prevent development of a perirectal abscess.
  • No therapy may be required if neutropenia is not severe and there are no serious or recurrent infections (often the case in chronic benign neutropenia).

Additional Therapies


  • Withdrawal of offending drug in drug-induced neutropenia
  • Treatment of underlying disorder in many cases of acquired neutropenia
  • Stem cell transplant may be indicated in some patients with severe congenital neutropenia or neutropenia due to other causes (such as bone marrow failure syndromes).

Issues for Referral


  • Chronic or profound neutropenia
  • History of recurrent unusual or severe infections
  • When bone marrow examination is indicated

Ongoing Care


Follow-up Recommendations


Management of febrile episodes (depends on etiology of neutropenia) ‚  
  • Prompt evaluation by a physician
  • Obtain CBC with differential and blood culture.
  • Treat with IV antibiotics.
  • Hospitalize if ill-appearing or high-risk for infection.
  • Monitor daily CBC with differential.

Patient Monitoring
  • CBCs and physical exams at regular intervals while the patient is neutropenic
  • Depending on the etiology of the neutropenia, annual bone marrow biopsy surveillance for leukemia or MDS

Prognosis


  • Duration of neutropenia depends on diagnosis.
    • Neutropenia resulting from infection or drug-related marrow suppression is usually short lived.
    • Autoimmune neutropenia (benign neutropenia of childhood) typically resolves within 2 years.
    • Congenital neutropenia syndromes may result in chronic lifelong neutropenia.
  • Likelihood of infection depends on severity of neutropenia (higher risk if <500/ Ž ¼L) and cause of neutropenia (higher risk in disorders of neutrophil production).

Complications


  • Systemic infections, including pneumonia and sepsis
  • Localized infections such as cellulitis, labial abscesses, perirectal abscesses, oral mucosal ulceration, thrush, otitis media, stomatitis, or gingivitis
  • Typical pathogens:
    • Bacterial: staphylococci, streptococci, enterococci, Pseudomonas, gram-negative bacilli
    • Fungal: Candida or Aspergillus
  • Transformation to leukemia or MDS

Additional Reading


  • Fioredda ‚  F, Calvillo ‚  M, Bonanomi ‚  S, et al. Congenital and acquired neutropenia consensus guidelines on diagnosis from the Neutropenia Committee of the Marrow Failure Syndrome Group of the AIEOP (Associazione Italiana Emato-Oncologia Pediatrica). Pediatr Blood Cancer.  2011;57(1):10 " “17. ‚  [View Abstract]
  • Lehrnbecher ‚  T, Phillips ‚  R, Alexander ‚  S, et al. Guideline for the management of fever and neutropenia in children with cancer and/or undergoing hematopoietic stem-cell transplantation. J Clin Oncol.  2012;30(35):4427 " “4438. ‚  [View Abstract]
  • Walkovich ‚  K, Boxer ‚  LA. How to approach neutropenia in childhood. Pediatr Rev.  2013;34(4):173 " “184. ‚  [View Abstract]

Codes


ICD09


  • 288.00 Neutropenia, unspecified
  • 288.01 Congenital neutropenia
  • 288.02 Cyclic neutropenia
  • 288.04 Neutropenia due to infection
  • 288.03 Drug induced neutropenia

ICD10


  • D70.9 Neutropenia, unspecified
  • D70.0 Congenital agranulocytosis
  • D70.4 Cyclic neutropenia
  • D70.3 Neutropenia due to infection
  • D70.2 Other drug-induced agranulocytosis

SNOMED


  • 165517008 neutropenia (finding)
  • 89655007 Congenital neutropenia (disorder)
  • 191347008 Cyclical neutropenia (disorder)
  • 46359005 Neutropenia associated with infectious disease (disorder)
  • 47318007 Drug-induced neutropenia (disorder)

FAQ


  • Q: Do all patients with neutropenia require G-CSF?
  • A: No. Patients with severe congenital neutropenia have fewer infections when treated with G-CSF. Patients with benign neutropenia generally do not need G-CSF.
  • Q: Can a neutropenic patient receive vaccinations?
  • A: Yes, if neutropenia is the only immunologic abnormality
  • Q: Should a child with neutropenia be kept in isolation?
  • A: No. Neutropenic patients may go to school and do not need to wear masks.
Copyright © 2016 - 2017
Doctor123.org | Disclaimer