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Mast cell

Mast Cell Disorders

Mast cell activation disorders requiring comprehensive evaluation and specialized testing.

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Overview

Mast cell disorders are a group of conditions characterized by abnormal activation or proliferation of mast cells. These disorders can cause a wide range of symptoms affecting multiple organ systems. Mast cell disorders include mastocytosis (abnormal accumulation of mast cells) and mast cell activation syndrome (MCAS) (normal number of mast cells but abnormal activation). These conditions require specialized evaluation and management.

types

mastocytosis

name

Mastocytosis

definition

Rare condition characterized by abnormal accumulation of mast cells in tissues

subtypes

  • Cutaneous mastocytosis (CM) - limited to skin
  • Systemic mastocytosis (SM) - involves internal organs
  • Indolent systemic mastocytosis (ISM) - most common form, generally good prognosis
  • Aggressive systemic mastocytosis (ASM) - organ dysfunction
  • Mast cell leukemia (MCL) - rare, aggressive

hallmark

Increased number of mast cells in tissues

mcas

name

Mast Cell Activation Syndrome (MCAS)

definition

Condition with normal mast cell numbers but recurrent episodes of mast cell activation

criteria

  • Recurrent symptoms affecting ≥2 organ systems
  • Response to mast cell mediator-targeting medications
  • Elevated mast cell mediators during episodes

note

Diagnosis requires careful evaluation to exclude other causes

symptoms

skin

  • Flushing
  • Urticaria (hives)
  • Pruritus (itching)
  • Dermatographism
  • Pigmented lesions (in mastocytosis)

gastrointestinal

  • Abdominal pain
  • Nausea and vomiting
  • Diarrhea
  • Gastroesophageal reflux
  • Malabsorption

cardiovascular

  • Tachycardia
  • Hypotension or hypertension
  • Dizziness
  • Syncope
  • Chest pain

respiratory

  • Wheezing
  • Shortness of breath
  • Cough
  • Nasal congestion

neurological

  • Headaches
  • Brain fog
  • Fatigue
  • Anxiety
  • Depression
  • Cognitive difficulties

other

  • Bone pain
  • Musculoskeletal symptoms
  • Anaphylaxis-like episodes
  • Temperature dysregulation

triggers

  • Foods
  • Medications
  • Temperature changes
  • Stress
  • Exercise
  • Insect stings
  • Alcohol
  • Odors/fragrances

red Flags

systemic

  • Recurrent anaphylaxis without clear trigger
  • Multisystem symptoms
  • Symptoms triggered by multiple unrelated triggers
  • Poor response to standard allergy treatments
  • Elevated baseline tryptase (> 11.4 ng/mL)
  • Organomegaly (enlarged liver, spleen, lymph nodes)
  • Bone lesions
  • Unexplained cytopenias

cutaneous

  • Pigmented skin lesions (urticaria pigmentosa)
  • Dermatographism
  • Flushing episodes
  • Blistering (in children with mastocytosis)

when To Suspect

  • Recurrent anaphylaxis without IgE-mediated trigger
  • Multisystem symptoms not explained by other conditions
  • Symptoms triggered by non-allergic triggers (heat, stress, exercise)
  • Elevated tryptase
  • Poor response to standard treatments

evaluation

history

  • Detailed symptom history across all organ systems
  • Timing and triggers of symptoms
  • Response to medications
  • Family history
  • Previous diagnoses and treatments
  • Impact on quality of life

physical

  • Skin examination for urticaria pigmentosa, dermatographism
  • Abdominal examination for organomegaly
  • Lymph node examination
  • Cardiovascular assessment
  • Complete physical examination

laboratory

tryptase

test

Serum tryptase - key screening test

baseline

Baseline tryptase > 11.4 ng/mL suggests mastocytosis

acute

Acute tryptase (within 4 hours of episode) - should be > baseline + 2 ng/mL or > 20% increase for MCAS

note

Normal tryptase does not rule out MCAS

mediators

  • 24-hour urine for N-methylhistamine
  • 24-hour urine for prostaglandin D2 metabolite
  • Plasma heparin (if available)
  • Serum chromogranin A

other

  • Complete blood count (CBC) - look for cytopenias
  • Comprehensive metabolic panel
  • Bone marrow biopsy (if systemic mastocytosis suspected)
  • KIT D816V mutation testing (if mastocytosis)

imaging

  • Bone scan or skeletal survey (for bone lesions in mastocytosis)
  • Abdominal imaging (for organomegaly)
  • Bone density scan (osteoporosis common in mastocytosis)

biopsy

indication

If systemic mastocytosis suspected

sites

  • Bone marrow (most common)
  • Skin (if lesions present)
  • GI tract (if GI symptoms)

findings

Increased mast cells, abnormal morphology, KIT mutation

diagnosis

mastocytosis

major

Multifocal dense infiltrates of mast cells in bone marrow or other extracutaneous organs

minor

  • >25% of mast cells are spindle-shaped or have atypical morphology
  • KIT D816V mutation
  • CD25 expression on mast cells
  • Serum tryptase persistently > 20 ng/mL

criteria

1 major + 1 minor OR 3 minor criteria

mcas

  • Recurrent symptoms affecting ≥2 organ systems
  • Response to mast cell mediator-targeting medications
  • Elevated mast cell mediators (tryptase, N-methylhistamine, prostaglandin D2 metabolite)

challenges

Diagnosis can be challenging, requires specialized expertise

treatment

avoidance

  • Identify and avoid triggers
  • Temperature regulation
  • Stress management
  • Medication review (avoid mast cell activators)

medications

h1 Antihistamines

  • Second-generation H1 blockers (cetirizine, loratadine, fexofenadine)
  • May need higher doses or multiple daily doses
  • First-generation (diphenhydramine) for breakthrough symptoms

h2 Antihistamines

  • Famotidine, ranitidine
  • Help with GI symptoms and flushing

mast Cell Stabilizers

  • Cromolyn sodium (oral) - for GI symptoms
  • Ketotifen (if available)

leukotriene

Montelukast, zileuton - for respiratory and other symptoms

aspirin

For prostaglandin-mediated symptoms (use with caution, can trigger reactions)

corticosteroids

For severe symptoms, short courses

biologics

Omalizumab (Xolair) - may help some patients with MCAS

epinephrine

Carry epinephrine auto-injectors for anaphylaxis risk

mastocytosis

additional

  • Tyrosine kinase inhibitors (imatinib, midostaurin) for advanced disease
  • Interferon alpha (for some forms)
  • Cladribine (for aggressive disease)
  • Bone marrow transplant (for mast cell leukemia)

monitoring

symptoms

Regular assessment of symptom frequency and severity

tryptase

Periodic tryptase levels

organ Function

Monitor for organ dysfunction in systemic mastocytosis

bone

Bone density monitoring (osteoporosis risk)

quality Of Life

Assess impact on daily activities

complications

anaphylaxis

Risk of severe anaphylaxis, especially with mastocytosis

osteoporosis

Common in systemic mastocytosis

organ Dysfunction

In aggressive forms of mastocytosis

quality Of Life

Significant impact on daily activities and mental health

referral

  • All patients with suspected mast cell disorders should be referred to allergist/immunologist
  • Refer to hematologist/oncologist if systemic mastocytosis suspected
  • Refer to dermatologist if cutaneous mastocytosis
  • Refer to gastroenterologist if significant GI involvement
  • Consider referral to specialized mast cell disorder center

prognosis

mcas

MCAS is typically manageable with medications and trigger avoidance. Quality of life can be significantly improved with proper treatment.

mastocytosis

indolent

Indolent systemic mastocytosis generally has good prognosis with normal life expectancy

aggressive

Aggressive forms require specialized treatment and have variable prognosis

cutaneous

Cutaneous mastocytosis in children often resolves by adulthood

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