Anaphylaxis and Mastocytosis Flashcards
Classification of mast cells disorders
- Primary - MC more activatible either spont. or unknown trigger
- Secondary - MCs are activated by an ext. trigger like an allergen and antigens
MCAS definition (AAAAI)
A primary clinical condition with spont. episodic signs and symptoms of systemic anaphylaxis concurrently affecting two or more organ systems, resulting from secreted MC mediators
List the Anaphylaxis Criteria (WAO)
Criteria 1: Acute onset of illness involving skin/mucosal tissue with either a. resp sx or b. reduced BP
Criteria 2 - two or more of the following after exposure to a likely allergen
- skin/mucosal tissue
- resp sx
- reduced BP
- persistent GI sx
Criteria 3 - reduced BP after a known allergen
- in adults: <90 or 30%
What is Carmine allergy?
- red food dye
- from dried bodies of cost insects
- used in food like candy, ice cream etc
- confirm with skin testin
What is Anato allergy?
Yellow food colouring
- produced from fruit of a tropical annatto tree, Bixa orellana
Man develops anaphylaxis after eating a muffin and jumping into a pool, whats your ddx?
- FDEIA
- CIU
- EIA
- Local heat, cold or cholinergic urticaria
6 ways to differentiate exercise anaphylaxis vs cholinergic urticaria
- wheal size (cholinergic are small and pinpoint, EIA are larger)
- triggers - cholinergic triggers include warm baths, sweating, strong emotions
- Occlusive body suit test - CU have a drop in FEV1, EIA does not
- CU is responsive to hydroxyzine, EIA is not
- Hyperthermic blanket test or submersion into warm water
- Systemic symptoms are present in EIA not in CU
DDx for idiopathic anaphylaxis
- Food allergy - overlooked foods include spices, food containing aeroallergens, mislabeled foods, and food ingested with cofactors
- Medication allergy - NSAIDs
- Mast cell disorders
- Carcinoid syndrome
- Pheo
- CU
- Flushing reactions
- Restaurant syndromes: MSG, sulfites, scromboid
Work up for idiopathic anaphylaxis
- history and exam
- SPT, and rast
- tryptase, 24 hr urine histamine, 5-HIAA, VMA, and urinary catecholamines
- AI work up- lytes, TSH, T4
risk factors for severe anaphylaxis
- asthma
- CV disease
- mast cell disorder
- older age
- acute infections
- meds - BB, Alpha blocks, Acei
Criteria for mastocytosis
need 1 major and 1 minor OR 3 minor
Major
- presence of multifocal, dense mast cell infiltrates (>15 in aggregates in BM or other exogenous organs)
Minor
- > 25% mast cells spindle shaped or with abnormal morphology in bone or other exo organs
- detection of c-kit point mut at codon 816 in BM
- mast cells that co express CD117 with CD2 or CD25
- persistent serum tryptase> 20
Criteria for mast cell disorders
- Episodic multi system symptoms consistent with anaphylaxis
- Increase in validated markers of mast cell activation (serum or urine)
- response to medications that target mast cell activation syndrome
Classify mastocytosis
- systemic mastocytosis
- cutaneous mastocytosis
- solid organ tumours
pathogenesis of mastocytosis
- SCF (stem cell factor) is a growth factor which controls the production of mast cells
- this mutation is in KIT (CD117) receptor on codon 816 which is a receptor for SCF
- usually GOF CD 117
clinical features of mastocytosis
- dariers sign
- UP or MPCM
- diffuse cut. mastocytosis (DCM)
- mastocytomas
- telengectasia macularis eruptive perstand (TMEP)
- Anaphylaxis
- GI disturbance
- Neurophysiatric - mixed organic brain syndrome
- Heme
- MSK
lab evaluation in mastocytosis
- CBC with differential to look for cytopenias, eosinophils, circulating mast cells and any abnormal myeloid or lymphoid leuks
- LFTs
- Bone density
- KIT mutation evaluation on peripheral blood or bone marrow
- Serum total tryptase at baseline on two occasions
- subtypes if possible
- would expect total tryptase to mature tryptase ratio to be very high
differential for mastocytosis
- MCAS - monoclonal
- MCAS - idiopathic
- Anaphylaxis
- HAE
- Pheo
- VIP secreting GI tumors
- Carcinoid tumours
- medullary thyroid cancer
- Zollinger Ellison syndrome
differential for a high tryptase
- HES
- AML
- MDS
- Refractory anemia
- ESRD
- famililal hypertrypsinemia
- transient or reactive
Management of mastocytosis
- Non pharma
- avoid triggers - heat, cold, stress, alcohol, exercise, infections, surgery
- medic alert bracelet - Pharm
- EpiPens
- VIT if indicated
- H1 and H2 blockers can be used
- Ketotifen (can be sedating)
- Singulair
- Flushing - try ASA which reduced PGD2 released by mast cells
- for GI sx - try cromolyn which gradually increases to 200 mg QID
- for osteo and #s - Ca, Vit D, pamidotronate - SM- AHNMD tx the underlying heme disorder
- Agressive SM - INFa, Cladribine, Steroids, Hydroxyurea, TK inhibitors
factors associated with poor px in mastocytosis
- older age
- low albumin
- high LDH
- HSM
- Ascites
- BM blasts
- cytopenias
What is hereditary a-trypsinemia
- an AD disorder with a phenotype which can include dysautonomia with POTs, flushing, GI hypomotility, joint hyperextensibility, vibratory urticaria
- due to 1 or more extra copies of a tryptase gene encoded by TBSAB1 resulting in over expression of a tryptase and increased mast cells in BM
surgical considerations in mastocytosis
Pre-medication prior to procedures - can consider administering 1 hr prior, but efficacy not studied:
○ Diphenhydramine 25-50mg
○ Famotidine 20 mg
○ Montelukast 10mg
○ Prednisone (preferred if pt has frequent hypoTN episodes or problems with anesthesia in the past) 25-50mg PO 12 hrs and 1-2 hrs prior
classify MCAS
- monoclonal mast cell activation disorder (MMAS)
2. idiopathic mast cell activation disorder (MCAS)
algorithm for diagnosis MCAS
- recurrent sx consistent with mast cell activation with involvement of two organs
- evaluation of one or more validated mast cell mediators in associated with symptoms
- response to targeted therapeutic interventions
- peripheral blood or bone marrow GOF KIT mutation or buccal swab increased TPSAB1 a tryptase CNV
- if positive: then primary MCAS with somatic or germline mutation
- if negative: then MCAS without a known mutation
