Difference between revisions of "Retinoic acid syndrome"

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==Background==
 
==Background==
 +
*Differentiation syndrome (DS) is most current term
 +
*APML pts undergoing ATRA treatment (Tretinoin, Vesanoid)
 +
**And/or with arsenic trioxide therapy (Trisenox, ATO)
 +
**ATRA differentiates APML blasts into mature granulocytes
 +
**Differentiation of blasts may cause "cytokine storm" and lead to tissue damage
 +
*Incidence of DS<ref>Montesinos P and Sanz MA. The Differentiation Syndrome in Patients with Acute Promyelocytic Leukemia: Experience of the Pethema Group and Review of the Literature. Mediterr J Hematol Infect Dis. 2011; 3(1): e2011059.</ref>
 +
**Up to 25% of pts undergoing ATRA Tx
 +
**Up to 31% of pts undergoing ATO Tx
 +
*Up to 40% mortality in patients requiring mechanical ventilation
 +
*Diagnosis made clinically with symptomology and includes immediate treatment with steroids
 +
**Steroid treatment highly recommended even if other ddx possible
  
 +
==Differential==
 +
*[[Sepsis]]
 +
*Fungal infection
 +
*Pulmonary hemorrhage
 +
*[[Pneumonia]]
 +
*Renal failure
 +
*[[CHF]]
 +
*[[Pulmonary embolism]]
 +
*[[DIC]]
 +
 +
==Clinical Features==
 +
*Unexplained fever
 +
*Unexplained hypotension
 +
*Weight gain > 5 kg
 +
*Dyspnea with pulmonary infiltrates
 +
*[[Pericardial effusion]]
 +
*Pleural effusion
 +
*Renal failure
 +
*Vascular capillary leak syndrome
 +
*[[DIC]]
 +
*Never observed beyond induction therapy, when pt has achieved complete response
 +
 +
==Diagnostics==
 +
*Troponins for pericarditis
 +
*Severe leukocytosis on CBC
 +
*[[Sepsis]] workup
 +
*[[CHF]] workup, echo
 +
*[[Pulmonary embolism]] workup
 +
*[[DIC]] workup
 +
*Diagnostic bronchoscopy, BAL, bx usually not required
 +
*Imaging
 +
**CXR - pleural effusions, ground-glass opacities, increased cardiac silhouette
 +
**CT chest - pleural effusions, peripheral nodules
 +
 +
==Management<ref>Sanz MA and Montesinos P. How we prevent and treat differentiation syndrome in patients with acute promyelocytic leukemia. May 1, 2014; Blood: 123 (18).</ref>==
 +
*Dexamethasone 10 mg IV q12hrs
 +
**Continue treatment until complete disappearance of signs and symptoms
 +
*Temporary d/c ATRA or ATO only in severe cases of DS (renal failure or ICU admit)
 +
*Furosemide for fluid overload
 +
*CRRT for refractory renal failure
 +
*Supportive
 +
**Mechanical ventilation for respiratory failure
 +
**Careful IVF admin, prioritizing blood products for coagulopathies (DIC)
 +
**Vasopressors
 +
**Empiric antibiotics
 +
**Avoid invasive pleural/pericardial effusion diagnostics
  
 
==Sources==
 
==Sources==
 +
*Weerakkody Y et al. All trans retinoic acid syndrome. Radiopaedia. http://radiopaedia.org/articles/all-trans-retinoic-acid-syndrome.
  
==Sources==
 
 
<references/>
 
<references/>
  
 
[[Category:Heme/Onc]]
 
[[Category:Heme/Onc]]

Revision as of 22:58, 2 May 2016

Background

  • Differentiation syndrome (DS) is most current term
  • APML pts undergoing ATRA treatment (Tretinoin, Vesanoid)
    • And/or with arsenic trioxide therapy (Trisenox, ATO)
    • ATRA differentiates APML blasts into mature granulocytes
    • Differentiation of blasts may cause "cytokine storm" and lead to tissue damage
  • Incidence of DS[1]
    • Up to 25% of pts undergoing ATRA Tx
    • Up to 31% of pts undergoing ATO Tx
  • Up to 40% mortality in patients requiring mechanical ventilation
  • Diagnosis made clinically with symptomology and includes immediate treatment with steroids
    • Steroid treatment highly recommended even if other ddx possible

Differential

Clinical Features

  • Unexplained fever
  • Unexplained hypotension
  • Weight gain > 5 kg
  • Dyspnea with pulmonary infiltrates
  • Pericardial effusion
  • Pleural effusion
  • Renal failure
  • Vascular capillary leak syndrome
  • DIC
  • Never observed beyond induction therapy, when pt has achieved complete response

Diagnostics

  • Troponins for pericarditis
  • Severe leukocytosis on CBC
  • Sepsis workup
  • CHF workup, echo
  • Pulmonary embolism workup
  • DIC workup
  • Diagnostic bronchoscopy, BAL, bx usually not required
  • Imaging
    • CXR - pleural effusions, ground-glass opacities, increased cardiac silhouette
    • CT chest - pleural effusions, peripheral nodules

Management[2]

  • Dexamethasone 10 mg IV q12hrs
    • Continue treatment until complete disappearance of signs and symptoms
  • Temporary d/c ATRA or ATO only in severe cases of DS (renal failure or ICU admit)
  • Furosemide for fluid overload
  • CRRT for refractory renal failure
  • Supportive
    • Mechanical ventilation for respiratory failure
    • Careful IVF admin, prioritizing blood products for coagulopathies (DIC)
    • Vasopressors
    • Empiric antibiotics
    • Avoid invasive pleural/pericardial effusion diagnostics

Sources

  1. Montesinos P and Sanz MA. The Differentiation Syndrome in Patients with Acute Promyelocytic Leukemia: Experience of the Pethema Group and Review of the Literature. Mediterr J Hematol Infect Dis. 2011; 3(1): e2011059.
  2. Sanz MA and Montesinos P. How we prevent and treat differentiation syndrome in patients with acute promyelocytic leukemia. May 1, 2014; Blood: 123 (18).