Difference between revisions of "Retinoic acid syndrome"

 
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==Background==
 
==Background==
 
*Differentiation syndrome (DS) is most current term
 
*Differentiation syndrome (DS) is most current term
*APML pts undergoing ATRA treatment (Tretinoin, Vesanoid)
+
*Occurs in [[AML|Acute promyelocytic leukemia]] patients undergoing ATRA treatment (Tretinoin, Vesanoid)
 
**And/or with arsenic trioxide therapy (Trisenox, ATO)
 
**And/or with arsenic trioxide therapy (Trisenox, ATO)
**ATRA differentiates APML blasts into mature granulocytes
+
**Chemo treatment differentiates APML blasts into mature granulocytes
**Differentiation of blasts may cause "cytokine storm" and lead to tissue damage
+
**Differentiation of blasts may cause [[sepsis]]-like "cytokine storm" leading 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>
 
*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 25% of patients undergoing ATRA
**Up to 31% of pts undergoing ATO Tx
+
**Up to 31% of patients undergoing ATO
 
*Up to 40% mortality in patients requiring mechanical ventilation
 
*Up to 40% mortality in patients requiring mechanical ventilation
*Diagnosis made clinically with symptomology and includes immediate treatment with steroids
+
*Diagnosis made clinically with symptomology
**Steroid treatment highly recommended even if other ddx possible
+
**Requires immediate treatment with steroids
 +
**Steroids highly recommended even if other diagnoses 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 patient has achieved complete response
 +
 
 +
==Differential Diagnosis==
 
*[[Sepsis]]
 
*[[Sepsis]]
*Fungal infection
+
*[[Fungal infection]]
*Pulmonary hemorrhage
+
*[[diffuse alveolar hemorrhage|Pulmonary hemorrhage]]
 
*[[Pneumonia]]
 
*[[Pneumonia]]
*Renal failure
+
*[[Renal failure]]
 
*[[CHF]]
 
*[[CHF]]
 
*[[Pulmonary embolism]]
 
*[[Pulmonary embolism]]
 
*[[DIC]]
 
*[[DIC]]
  
==Clinical Features==
+
{{Template:Oncologic emergencies DDX}}
*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==
+
==Evaluation==
*Troponins for pericarditis
+
*Ultimately, a clinical diagnosis
*Severe leukocytosis on CBC
+
*[[Troponins]] for [[pericarditis]]
 +
*Severe [[leukocytosis]] on CBC
 
*[[Sepsis]] workup
 
*[[Sepsis]] workup
 
*[[CHF]] workup, echo
 
*[[CHF]] workup, echo
 
*[[Pulmonary embolism]] workup
 
*[[Pulmonary embolism]] workup
 
*[[DIC]] workup
 
*[[DIC]] workup
*Diagnostic bronchoscopy, BAL, bx usually not required
+
*Coagulation factor levels
 +
*Diagnostic bronchoscopy, BAL, biopsy usually not required
 
*Imaging
 
*Imaging
**CXR - pleural effusions, ground-glass opacities, increased cardiac silhouette
+
**[[CXR]] - pleural effusions, ground-glass opacities, increased cardiac silhouette
 
**CT chest - pleural effusions, peripheral nodules
 
**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>==
 
==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
+
*[[Dexamethasone]] 10mg IV q12hrs
 +
**Most important therapy, with possible dramatic and rapid resolution of symptoms
 
**Continue treatment until complete disappearance of signs and symptoms
 
**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)
+
*Temporary discharge ATRA or ATO only in severe cases of DS (renal failure or ICU admit)
 
*Supportive
 
*Supportive
**Mechanical ventilation for respiratory failure
+
**[[Mechanical ventilation]] for respiratory failure
**Careful IVF admin, prioritizing blood products for coagulopathies (DIC)
+
**Careful [[IVF]] admin, prioritizing [[blood products]] for coagulopathies (DIC)
**Furosemide for fluid overload
+
**[[Furosemide]] for fluid overload
**CRRT/HD for refractory renal failure
+
**CRRT/[[hemodialysis|HD]] for refractory renal failure
**Vasopressors
+
**[[Vasopressors]]
**Empiric antibiotics
+
**Empiric [[antibiotics]]
**Avoid invasive pleural/pericardial effusion diagnostics
+
**''Avoid'' invasive pleural/pericardial effusion diagnostics
 +
 
 +
==Disposition==
 +
*Admit
 +
 
 +
==See Also==
  
==Sources==
+
==External Links==
*Weerakkody Y et al. All trans retinoic acid syndrome. Radiopaedia. http://radiopaedia.org/articles/all-trans-retinoic-acid-syndrome.
 
  
 +
==References==
 
<references/>
 
<references/>
  
 
[[Category:Heme/Onc]]
 
[[Category:Heme/Onc]]

Latest revision as of 17:56, 1 October 2019

Background

  • Differentiation syndrome (DS) is most current term
  • Occurs in Acute promyelocytic leukemia patients undergoing ATRA treatment (Tretinoin, Vesanoid)
    • And/or with arsenic trioxide therapy (Trisenox, ATO)
    • Chemo treatment differentiates APML blasts into mature granulocytes
    • Differentiation of blasts may cause sepsis-like "cytokine storm" leading to tissue damage
  • Incidence of DS[1]
    • Up to 25% of patients undergoing ATRA
    • Up to 31% of patients undergoing ATO
  • Up to 40% mortality in patients requiring mechanical ventilation
  • Diagnosis made clinically with symptomology
    • Requires immediate treatment with steroids
    • Steroids highly recommended even if other diagnoses possible

Clinical Features

Differential Diagnosis

Oncologic Emergencies

Related to Local Tumor Effects

Related to Biochemical Derangement

Related to Hematologic Derangement

Related to Therapy

Evaluation

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

Management[2]

  • Dexamethasone 10mg IV q12hrs
    • Most important therapy, with possible dramatic and rapid resolution of symptoms
    • Continue treatment until complete disappearance of signs and symptoms
  • Temporary discharge ATRA or ATO only in severe cases of DS (renal failure or ICU admit)
  • Supportive

Disposition

  • Admit

See Also

External Links

References

  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).