Rosen & Barkin's 5-Minute Emergency Medicine Consult (307 page)

• Newborn infants have a physiologically elevated ANC in the 1st few days of life and may be granulocytopenic with levels >1,500/μL.
  
• Children >3 mo without underlying immunodeficiency or a central venous catheter unexpectedly found to have isolated moderate neutropenia are not at high risk of serious bacterial infection.
  

• Most common in patients undergoing myelosuppressive drug therapy or radiation treatment for neoplasms. Most common 5–10 days after chemo.
  
• Adverse reaction to drugs is the 2nd most common cause:
  
  • Excludes cytotoxic drugs and requires at least 4 wk of administration prior to the onset of granulocytopenia
    
  • Discontinuation usually results with correction within 30 days.
    
  • Drugs with the highest risk:
    
    • Antipsychotic: Clozapine
      
    • Antibiotic: Sulfasalazine
      
    • Antithyroid: Thioamides
      
  • Antiplatelet agents
    
  • Antiepileptic drugs
    
  • NSAIDs
    
• Drugs that suppress the bone marrow:
  
  • Methotrexate
    
  • Cyclophosphamide
    
  • Colchicine
    
  • Azathioprine
    
  • Ganciclovir
    
• Chemicals
  
• Bacterial infections:
  
  • Typhoid
    
  • Shigella enteritis
    
  • Brucellosis
    
  • Tularemia
    
  • Tuberculosis
    
• Parasitic infections:
  
  • Kala azar
    
  • Malaria
    
• Rickettsial infections:
  
  • Rickettsialpox
    
  • Ehrlichiosis
    
  • Rocky Mountain spotted fever
    
• Viral infections
  
• Postinfectious neutropenia:
  
  • Most severe and protracted following HIV, hepatitis B, and Epstein–Barr viral infections
    
• Immune-related:
  
  • Primary immune neutropenia:
    
    • Due to antineutrophil antibodies
      
  • Crohn's disease
    
  • Systemic lupus erythematosus
    
  • Rheumatoid arthritis
    
  • Goodpasture disease
    
  • Wegener granulomatosis
    
  • Thymoma
    
  • Compliment activation
    
• Bone marrow infiltration
  
• Transfusion reaction
  
• Alcoholism
  
• Vitamin deficiency (B
  ₁₂
  /folate/copper)
  
• Chronic idiopathic neutropenia
  
• Pure white cell aplasia
  

• Congenital neutropenia:
  
  • Neutropenia with abnormal immunoglobulins
    
  • Reticular dysgenesis
    
  • Severe congenital neutropenia or Kostmann syndrome
    
  • Cyclic neutropenia
    
• Chronic benign neutropenia
  
• Neonatal isoimmune neutropenia
  
• Shwachman–Diamond syndrome
  
• Cartilage–hair hypoplasia
  
• Dyskeratosis congenita
  
• Barth syndrome
  
• Chédiak–Higashi syndrome
  
• Myelokathexis
  
• Lazy leukocyte syndrome
  
• Cohen syndrome
  
• Hermansky–Pudlak syndrome type 2
  

DIAGNOSIS

• Signs of bacterial or fungal infection:
  
  • Fever
    
  • Localized erythema or fluctuance
    
• Signs of pancytopenia:
  
  • Fatigue
    
  • Pallor
    
  • Petechiae
    
  • Epistaxis and other spontaneous bleeding
    

• Medical list should be reviewed for causative drugs.
  
• Family history of granulocytopenia in neonates and children
  
• Records of past ANC levels to assess for chronicity
  
• Question the patient carefully about fever, chills, dizziness, and vomiting as indicators of an underlying serious infection.
  
• Ask about localizing signs of infection such as cough; shortness of breath; chest pain; dysuria; urinary retention, urgency, or frequency; abdominal pain; and rectal pain.
  

Focus on finding signs of infection:

• Oral exam: Thrush, ulcers, periodontal disease, mucositis
  
• Lungs: Rales, rhonchi
  
• Abdominal: Splenomegaly
  
• Skin: Rashes, ulcers, abscesses
  
• Perirectal: Although the rectal exam is relatively contraindicated until antibiotics are started, check for abscesses and mucosal lesions.
  
• Evaluate indwelling catheter sites
  

Complete physical exam:

• Detailed exam of oral mucosa and perianal area
  
• Palpation of skin
  
• Location of fluctuance or tenderness
  
• Careful lung exam and abdominal
  
• Rectal exam after antibiosis if symptoms suggest perirectal abscess
  

• CBC with differential:
  
  • ANC
    
• LFTs
  
• Blood culture before antibiosis from 2 different sites, with 1 from IV catheter site if present
  
• Urinalysis and urine culture:
  
  • May not show WBCs or leukocytes esterase OR may be normal
    
• Sputum Cx if applicable
  
• Stool Cx if applicable
  
• Culture indwelling catheters
  
• Cerebrospinal fluid analysis for altered mental status/signs of meningitis
  

CXR even in absence of lung findings

• Lab error
  
• Neoplasm and chemotherapy
  
• Medication reaction
  
• Chemical exposure
  
• Infections (viral/bacterial/rickettsial)
  
• Autoimmune syndrome
  
• Genetic etiology
  
• Transfusion reaction
  
• Nutritional deficiency
  
• Tumor lysis syndrome
  
• Hypersplenism
  
• African Americans may have a lower but normal ANC value of 1,000 cells/mm
  ³
  

TREATMENT

For patients presenting in shock:

• Administer 1 L 0.9% NS IV fluid bolus (peds: 20 cc/kg).
  
• Initiate pressors as needed to stabilize BP if no response to IV fluids.
  
• Consider starting goal-directed therapy.
  

• Strict isolation in a negative airflow room if possible
  
• Administer broad-spectrum combination antibiotics after cultures for suspected or documented infection:
  
  • Imipenem/cilastatin or fluoroquinolone
    
  • Ceftazidime alone or with aminoglycoside (amikacin, tobramycin, gentamicin)
    
• Cefepime alone
  
• Aminoglycoside + antipseudomonal β-lactam (mezlocillin, piperacillin, or ticarcillin)
  
• Vancomycin if patient is at risk to be carrier of
  MRSA
  

• Amikacin: 15 mg/kg/24 h (peds: 15–30 mg/kg/24 h) div. q8–12h IV
  
• Cefepime: 0.5–2 g q12h
  
• Ceftazidime: 1–2 g (peds: 30–50 mg/kg q8h) q8–12h IV
  
• Gentamicin: 1 mg/kg (peds: 2–2.5 mg/kg) q8h or 5 mg/kg q24h
  
• Imipenem/cilastatin: 250–1,000 mg q6–8h
  
• Levofloxacin: 500 mg IV QID
  
• Mezlocillin: 3 g q4h over 30 min
  
• Tobramycin: 1 mg/kg q8h IV (peds: 2–2.5 mg/kg q8h IV)
  
• Vancomycin: 15 mg/kg q8–12h IV
  

FOLLOW-UP

MASCC Score: Identifies febrile neutropenic patients who are at a lower risk of complications.

• Signs of infection
  
• Unreliable patient
  
• Close follow-up unavailable
  

• Previously diagnosed granulocytopenia
  
• Completely asymptomatic
  
• Close follow-up ensured
  
• Reliable patient
  

All patients with granulocytopenia should be referred to their physician or a hematologist.

• Patient should return immediately to the ED with fever.
  
• Follow-up within 48 hr with the patient’s physician
  

• Usual signs of infection may be masked because of the impaired immune response in patients with granulocytopenia.
  
• Rectal exams and rectal temperatures are relatively contraindicated in neutropenic patients but should be performed once antibiotics are started to avoid missing a perirectal abscess.
  
• Patients with fever and an ANC <500 requires immediate and aggressive therapy with broad-spectrum antibiotics and IV fluids.
  
• Hepatosplenic candidiasis: Complication of resolving neutropenia. Abscess formation as ANC rises. Treat with amphotericin B.
  

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  Clin Infect Dis.
  2011;52:e56–e93.
  
• Kaufman DW, Kelly JP, Levy M, et al.
  The Drug Etiology of Agranulocytosis and Aplastic Anemia
  . New York, NY: Oxford University Press; 1991.
  
• Melendez E, Harper MB. Risk of serious bacterial infection in isolated and unsuspected neutropenia.
  Acad Emerg Med
  . 2010;17:163–167.
  
• Mushlin SB, Greene HL.
  Decision Making in Medicine: An Algorithmic Approach.
  3rd ed. Boston, MA: Elsevier Inc.; 2010.
  
• Perrone J, Hollander JE, Datner EM. Emergency Department evaluation of patients with fever and chemotherapy-induced neutropenia.
  J Emerg Med.
  2004;27(2):115–119.
  
• Segel GB, Halterman JS. Neutropenia in pediatric practice.
  Pediatr Rev.
  2008;29:12–23.