Cem Akin on Mast Cell Disorders-Update on Diagnosis and Management. Clinically relevant mediators released from mast cells and putative effects: https://twitter.com/MatthewBowdish/status/955512765417844737
One way to think about mast cell disorders: https://twitter.com/MatthewBowdish/status/955513053675532289
Recent developments in mast cell diseases:
- updates to the WHO classification of mastocytosis
- change in terminology of cutaneous disease
- familial hypertryptasemia
- approval of midostaurin for advanced systemic mastocytosis
Basophil granulocyte. Image source: Wikipedia.
If you put all of the mast cells in the body into a single organ, it would be the size of the spleen.
Mastocytosis in children is usually cutaneous and tends to improve as the children age (up to 10 yo) vs. adult patients who have mast cell collections in their bone marrow. This adult-onset disease doesn't usually resolve.
Common presentation of mastocytosis:
- urticaria pigmentosa or mastocytomas (70%)
- hematologic abnormalities (10-15%)
- pathological fractures (5%)
- anaphylaxis w/o urticaria pigmentosa (10-15%)
Images of Urticaria Pigmentosa from Google Search: https://www.google.com/search?q=urticaria+pigmentosa&source=lnms&tbm=isch&sa=X&ved=0ahUKEwits-iioezYAhUK52MKHXKuDsUQ_AUICigB&biw=779&bih=531
Images of Mastocytomas: Google search.
Urticaria Pigmentosa is now called Maculopapular cutaneous mastocytosis.
Mutations in the tyrosine kinase portion of ckit associated with mastocytosis: https://twitter.com/MatthewBowdish/status/955518917887148032
WHO Diagnostic Criteria for Systemic Mastocytosis: Major +1 minor or 3 minor.
Major: characteristic multifocal dense infiltrates of mast cells (MC) in bone marrow bx.
Minor: spindle-shaped MCs, codon 816 c-kit mutation, CD25 in bone marrow MCs, serum tryptase more than 20 ng/ml.
GI biopsies can be difficult because the lesions can be focal and therefore missed if not enough biopsies are done.
Wide range of normal mast cell numbers in the GI tract: https://twitter.com/MatthewBowdish/status/955520445792468992
You can see elevated mast cells in the biopsies of IBS patients. Doesn't mean IBS is a mast cell mediated disease as many IBS pts don't have elevated MCs in their GI biopsies.
A new form of systemic mastocytosis is part of the WHO classification system: Smoldering systemic mastocytosis - B findings, tryptase higher than 20 and MCs more than 35% of bone marrow, splenomegaly w/o cytopenias, dysmyelopoiesis without MDS/MPN.
TMS survey of 426 patients: https://twitter.com/MatthewBowdish/status/955521796530294784
Two proposed classification schemes for Mast Cell Activation Syndrome: https://twitter.com/MatthewBowdish/status/955522877486333952
How Cem Akin sees these conditions overlapping- JACI 2017: https://twitter.com/MatthewBowdish/status/955523468744802304
Mast cell disorder diagnostic algorithm: it is heavily reliant on bone marrow biopsy:
https://twitter.com/MatthewBowdish/status/955524710128742401
Treatment of non-clonal mast cell disorders, step by step:
- H1+H2 antihistamines, anti-leukotrienes, cromolyn
- ketotifen
- omalizumab, glucocorticoids
1 out of 3 patients who will not respond to H1+H2 antihistamines will respond to ketotifen 1 mg bid up to 2 mg bid (not FDA approved, but some compounding pharmacies will make it).
Treatment of clonal mast cell disorders, step by step:
- H1+H2 antihistamines, anti-leukotrienes, cromolyn
- omalizumab, glucocorticoids
- cytoreduction with IFN-alpha, cladribine
Midostaurin may ultimately replace IFN-alpha and cladribine for cytoreduction in severe clonal mastocytosis, recently approved and better tolerated than the others.
Survival benefit with Midostaurin is significant in clonal mastocytosis, works by inhibiting MC tyrosine kinase: https://twitter.com/MatthewBowdish/status/955527642844819457
New therapies in the pipeline for mastocytosis: Blueprint-BLU 285 (D816V KIT specific inhibitor), Deciphera-DCC-2618 (switch tyrosine kinase inhibitor), Allakos-Siglec 8 monoclonal antibody, combo therapies.
- hematologic abnormalities (10-15%)
- pathological fractures (5%)
- anaphylaxis w/o urticaria pigmentosa (10-15%)
Images of Urticaria Pigmentosa from Google Search: https://www.google.com/search?q=urticaria+pigmentosa&source=lnms&tbm=isch&sa=X&ved=0ahUKEwits-iioezYAhUK52MKHXKuDsUQ_AUICigB&biw=779&bih=531
Images of Mastocytomas: Google search.
Urticaria Pigmentosa is now called Maculopapular cutaneous mastocytosis.
Mutations in the tyrosine kinase portion of ckit associated with mastocytosis: https://twitter.com/MatthewBowdish/status/955518917887148032
WHO Diagnostic Criteria for Systemic Mastocytosis: Major +1 minor or 3 minor.
Major: characteristic multifocal dense infiltrates of mast cells (MC) in bone marrow bx.
Minor: spindle-shaped MCs, codon 816 c-kit mutation, CD25 in bone marrow MCs, serum tryptase more than 20 ng/ml.
GI biopsies can be difficult because the lesions can be focal and therefore missed if not enough biopsies are done.
Wide range of normal mast cell numbers in the GI tract: https://twitter.com/MatthewBowdish/status/955520445792468992
You can see elevated mast cells in the biopsies of IBS patients. Doesn't mean IBS is a mast cell mediated disease as many IBS pts don't have elevated MCs in their GI biopsies.
A new form of systemic mastocytosis is part of the WHO classification system: Smoldering systemic mastocytosis - B findings, tryptase higher than 20 and MCs more than 35% of bone marrow, splenomegaly w/o cytopenias, dysmyelopoiesis without MDS/MPN.
TMS survey of 426 patients: https://twitter.com/MatthewBowdish/status/955521796530294784
Two proposed classification schemes for Mast Cell Activation Syndrome: https://twitter.com/MatthewBowdish/status/955522877486333952
How Cem Akin sees these conditions overlapping- JACI 2017: https://twitter.com/MatthewBowdish/status/955523468744802304
Mast cell disorder diagnostic algorithm: it is heavily reliant on bone marrow biopsy:
https://twitter.com/MatthewBowdish/status/955524710128742401
Treatment of non-clonal mast cell disorders, step by step:
- H1+H2 antihistamines, anti-leukotrienes, cromolyn
- ketotifen
- omalizumab, glucocorticoids
1 out of 3 patients who will not respond to H1+H2 antihistamines will respond to ketotifen 1 mg bid up to 2 mg bid (not FDA approved, but some compounding pharmacies will make it).
Treatment of clonal mast cell disorders, step by step:
- H1+H2 antihistamines, anti-leukotrienes, cromolyn
- omalizumab, glucocorticoids
- cytoreduction with IFN-alpha, cladribine
Midostaurin may ultimately replace IFN-alpha and cladribine for cytoreduction in severe clonal mastocytosis, recently approved and better tolerated than the others.
Survival benefit with Midostaurin is significant in clonal mastocytosis, works by inhibiting MC tyrosine kinase: https://twitter.com/MatthewBowdish/status/955527642844819457
New therapies in the pipeline for mastocytosis: Blueprint-BLU 285 (D816V KIT specific inhibitor), Deciphera-DCC-2618 (switch tyrosine kinase inhibitor), Allakos-Siglec 8 monoclonal antibody, combo therapies.
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