This is a Twitter summary from the 2018 WSAAI meeting. This summary was compiled from the tweets posted by @MatthewBowdish, an allergist/immunologist, who attended the 2018 Western Society of Allergy, Asthma and Immunology (WSAAI) meeting. The tweets were labeled #WSAAI. The text was edited and modified by me.
Amy Klion on Eosinophilia, Etiology, Pathogenesis, and DDx.
Eosinophil life cycle: https://twitter.com/MatthewBowdish/status/956003850846011392
Eosinophils and pathology:
1. Direct cytotoxic effects (eos granule proteins, reactive oxygen intermediates)
2. Recruitment of other inflammatory cells
3. Fibrogenesis
4. Hypercoagulability
Serum levels of eosinophil granule proteins have been correlated to disease activity in some settings.
Eosinophil. Image source: Wikipedia.
Eosinophil. Image source: Wikipedia.
Eosinophil: Friend or Foe? https://twitter.com/MatthewBowdish/status/956005049238372353
Eosinophils are also involved in homeostatic pathways involving glucose metabolism and interactions with Tregs in the gut, plasma cells, and B cells
Are eosinophils essential? PRO: found in all vertebrates, congenital eosinophil deficiency has not been reported in humans. CON: rare cases of acquired eosinophil def reports in humans, eosinophil-less mouse models do fine, profound depletion in humans using targeted therapies does not appear to have adverse consequences.
Percent of eosinophils is not helpful in evaluating eosinophilia. Absolute numbers are important.
Peripheral blood eos count higher than 450/uL occurs in 5-10% of returned travelers. Remember, lab mistakes can occur with eosinophil counts.
Even mild eosinophilia can be associated with disease, but the differential depends on the level (eg EoE is a significant disease but blood eos count is often normal).
Clinical disorders associated with eosinophilia: https://twitter.com/MatthewBowdish/status/956007603196186625
Idiopathic Hypereosinophilic Syndrome (HES):
-blood eos count higher than 1500 for longer than 6 months
-lack of evidence of parasitic or other known causes
-presumptive signs of organ involvement (eg heart failure, GI dysfunction, CNS abns, fever, weight loss)
Secondary causes of eosinophilia can mimic idiopathic HES: https://twitter.com/MatthewBowdish/status/956008313929457664
Clinical subtypes of HES: https://twitter.com/MatthewBowdish/status/956009161682112512
Elevated serum tryptase identifies a myeloproliferative subtype of HES (Klion, Blood 2003). About 80% of myeloid variant of HES is PDGFRA-positive MN, making them susceptible to treatment with Imatinib. No response to imatinib with Lymphocytic variant HES.
HES is a heterogenous group of disorders with different etiologies, presentations and treatments. Identification and characterization of new HES subtypes is likely to depend on a combo of serendipity, intellectual curiosity and persistence.
Eval of the patient with HE: https://twitter.com/MatthewBowdish/status/956014428876505088
Initial testing in HE: https://twitter.com/MatthewBowdish/status/956014634359599104
Eosinophilic pulmonary disease can be Asthma, HES, ABPA, CEP and even EGPA.
Amy Klion on Eosinophilia, Etiology, Pathogenesis, and DDx.
Eosinophil life cycle: https://twitter.com/MatthewBowdish/status/956003850846011392
Eosinophils and pathology:
1. Direct cytotoxic effects (eos granule proteins, reactive oxygen intermediates)
2. Recruitment of other inflammatory cells
3. Fibrogenesis
4. Hypercoagulability
Serum levels of eosinophil granule proteins have been correlated to disease activity in some settings.
Eosinophil. Image source: Wikipedia.
Eosinophil. Image source: Wikipedia.
Eosinophil: Friend or Foe? https://twitter.com/MatthewBowdish/status/956005049238372353
Eosinophils are also involved in homeostatic pathways involving glucose metabolism and interactions with Tregs in the gut, plasma cells, and B cells
Are eosinophils essential? PRO: found in all vertebrates, congenital eosinophil deficiency has not been reported in humans. CON: rare cases of acquired eosinophil def reports in humans, eosinophil-less mouse models do fine, profound depletion in humans using targeted therapies does not appear to have adverse consequences.
Percent of eosinophils is not helpful in evaluating eosinophilia. Absolute numbers are important.
Peripheral blood eos count higher than 450/uL occurs in 5-10% of returned travelers. Remember, lab mistakes can occur with eosinophil counts.
Even mild eosinophilia can be associated with disease, but the differential depends on the level (eg EoE is a significant disease but blood eos count is often normal).
Clinical disorders associated with eosinophilia: https://twitter.com/MatthewBowdish/status/956007603196186625
Idiopathic Hypereosinophilic Syndrome (HES):
-blood eos count higher than 1500 for longer than 6 months
-lack of evidence of parasitic or other known causes
-presumptive signs of organ involvement (eg heart failure, GI dysfunction, CNS abns, fever, weight loss)
Secondary causes of eosinophilia can mimic idiopathic HES: https://twitter.com/MatthewBowdish/status/956008313929457664
Clinical subtypes of HES: https://twitter.com/MatthewBowdish/status/956009161682112512
Elevated serum tryptase identifies a myeloproliferative subtype of HES (Klion, Blood 2003). About 80% of myeloid variant of HES is PDGFRA-positive MN, making them susceptible to treatment with Imatinib. No response to imatinib with Lymphocytic variant HES.
HES is a heterogenous group of disorders with different etiologies, presentations and treatments. Identification and characterization of new HES subtypes is likely to depend on a combo of serendipity, intellectual curiosity and persistence.
Eval of the patient with HE: https://twitter.com/MatthewBowdish/status/956014428876505088
Initial testing in HE: https://twitter.com/MatthewBowdish/status/956014634359599104
Eosinophilic pulmonary disease can be Asthma, HES, ABPA, CEP and even EGPA.
ANCA is positive in 50% of patients with biopsy-proven EGPA.
Amy Klion discussing "New developments and novel therapies for the treatment of hypereosinophilic syndromes."
Suspected HES w/potentially life-threatening manifestations:
1. Limited diagnostic evaluation.
2. Empiric treatment with high-dose steroids (+ivermectin for Strongyloides if potential exposure)
3. Response?
Yes: proceed with evaluation
No: add second agent
85% of those with HES respond to prednisone, which is why it is the treatment of choice: https://twitter.com/MatthewBowdish/status/956651617381597184
Treatment of steroid-resistant HES: https://twitter.com/MatthewBowdish/status/956652978965893120
Imatinib has a rapid (weeks) and dramatic effect on eosinophilia - consider drug failure if minimal response (ie eos don't normalize) at 4 weeks on 400 mg daily.
Amy Klion discussing "New developments and novel therapies for the treatment of hypereosinophilic syndromes."
Suspected HES w/potentially life-threatening manifestations:
1. Limited diagnostic evaluation.
2. Empiric treatment with high-dose steroids (+ivermectin for Strongyloides if potential exposure)
3. Response?
Yes: proceed with evaluation
No: add second agent
85% of those with HES respond to prednisone, which is why it is the treatment of choice: https://twitter.com/MatthewBowdish/status/956651617381597184
Treatment of steroid-resistant HES: https://twitter.com/MatthewBowdish/status/956652978965893120
Imatinib has a rapid (weeks) and dramatic effect on eosinophilia - consider drug failure if minimal response (ie eos don't normalize) at 4 weeks on 400 mg daily.
Treatment of imatinib-resistant or intolerant PDGFRA-positive MPN: increase imatinib dose, alternative tyrosine kinase inhibitors, consider allogeneic bone marrow transplant.
IFN-alpha in HES: direct and indirect effects on eosinophilia, 2nd line agent for lymphocytic variant HES but should be given w/steroids, CI in pregnancy, monitor CBC, liver fxn, optho exam and thyroid function.
Hydroxyurea in HES: oral agent with efficacy similar to IFN, predominantly hematologic ADR, 2-4 weeks for effect, second line for idiopathic HES, alone or in combo with IFN, monitor CBC.
Second line therapy for HES: https://twitter.com/MatthewBowdish/status/956655223686098944
Other targeted HES therapies on the horizon: https://twitter.com/MatthewBowdish/status/956655497418911745
Room for other novel agents in HES: https://twitter.com/MatthewBowdish/status/956660079964516352
What is dexpramipexole?
-a drug studied for ALS that did not help with ALS but was found to decrease blood eos
-unknown target
-well tolerated and effective as a steroid-sparing agent in HES
-appears to cause maturational arrest of bone marrow eosinophilpoiesis
Targeting IL5/IL5R: https://twitter.com/MatthewBowdish/status/956655779553013760
Anti-IL5 has excellent safety profile in HES, it's FDA approved for EGPA, 85% efficacy in steroid sensitive IHES and LHES, may be less effective in more aggressive disease esp MHES.
In a small study of 22 patients, benralizumab was well-tolerated and effective in depleting eosinophils in HES.
Status of anti-IL5 for EoE? https://twitter.com/MatthewBowdish/status/956656396539277312
IFN-alpha in HES: direct and indirect effects on eosinophilia, 2nd line agent for lymphocytic variant HES but should be given w/steroids, CI in pregnancy, monitor CBC, liver fxn, optho exam and thyroid function.
Hydroxyurea in HES: oral agent with efficacy similar to IFN, predominantly hematologic ADR, 2-4 weeks for effect, second line for idiopathic HES, alone or in combo with IFN, monitor CBC.
Second line therapy for HES: https://twitter.com/MatthewBowdish/status/956655223686098944
Other targeted HES therapies on the horizon: https://twitter.com/MatthewBowdish/status/956655497418911745
Room for other novel agents in HES: https://twitter.com/MatthewBowdish/status/956660079964516352
What is dexpramipexole?
-a drug studied for ALS that did not help with ALS but was found to decrease blood eos
-unknown target
-well tolerated and effective as a steroid-sparing agent in HES
-appears to cause maturational arrest of bone marrow eosinophilpoiesis
Targeting IL5/IL5R: https://twitter.com/MatthewBowdish/status/956655779553013760
Anti-IL5 has excellent safety profile in HES, it's FDA approved for EGPA, 85% efficacy in steroid sensitive IHES and LHES, may be less effective in more aggressive disease esp MHES.
In a small study of 22 patients, benralizumab was well-tolerated and effective in depleting eosinophils in HES.
Status of anti-IL5 for EoE? https://twitter.com/MatthewBowdish/status/956656396539277312
Failure of anti-IL5 to meet clinical trial endpoints in EoE may be due to incomplete depletion of eosinophils, lack of depletion of mast cells or lymphocytes, or other factors (time duration, irreversible structural changes like fibrosis of the esophagus, etc).