Mast Cell Disorders - 2018 WSAAI update

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.

Cem Akin on Mast Cell Disorders-Update on Diagnosis and Management. Clinically relevant mediators released from mast cells and putative effects:

One way to think about mast cell disorders:

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:

Images of Mastocytomas: Google search.

Urticaria Pigmentosa is now called Maculopapular cutaneous mastocytosis.

Mutations in the tyrosine kinase portion of ckit associated with mastocytosis:

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:

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:

Two proposed classification schemes for Mast Cell Activation Syndrome:

How Cem Akin sees these conditions overlapping- JACI 2017:

Mast cell disorder diagnostic algorithm: it is heavily reliant on bone marrow biopsy:

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

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:

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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