Mast Cell Activation Syndrome MCAS

Intro

More mast cells or more hyperreactivity or both

Physiology

Mast cells live in the connective tissue of all organs with blood vessels and in mucosal tissues

  • Skin

  • Respiratory tract

  • Intestinal tract

Numbers highest where internal and external environments meet

Act as sentinels responding quickly to

  • Organisms

  • Antigens

  • Toxins

Evolutionarily most useful for venom, parasites, and bacterial infections

When active mast cells release

  • Histamine

  • Arachidonic acid metabolites

  • Generate and release cytokines and chemokines

  • These are responsible for flushing, itch, swelling, hives, bronchoconstriction, and anaphylaxis

Mast cell disorders

Primary mast cell disorders

  • Mastocytosis (systemic and cutaneous)

  • Monoclonal mast cell activation syndrome

  • Rare

Secondary mast cell disorders

  • Allergic disorders

  • Physical urticarias

  • Mast cell activation associated with chronic inflammatory or neoplastic disorders

Idiopathic mast cell disorders

  • Idiopathic anaphylaxis

  • Idiopathic urticaria (also called chronic spontaneous urticaria)

  • Idiopathic histaminergic angioedema

  • Idiopathic mast cell activation syndrome

Diagnosis

Need all of:

  • Episodic, objective signs and symptoms consistent with mast cell activation involving at least two of the following organ systems: skin, upper or lower respiratory systems, gastrointestinal, or cardiovascular

  • Evidence of systemic mast cell-mediator release, corresponding temporally to the presence of symptoms. In case of frequent recurrent episodes, mediator release should be ideally documented on at least two occasions. Serum total tryptase is the most specific for mast cell activation, and an increase from the patient’s baseline to a level of (1.2 x baseline) + 2 ng/mL is considered indicative of mast cell activation.

  • Response to medications that stabilize mast cells, reduce mast cell mediator production, block mediator release, or inhibit the actions of mediators.

Symptoms

Skin

  • Flushing

    • May be induced by exercise, alcohol, temperature, emotional events

    • Flushing in isolation e.g. of upper chest can be due to dysautonomia

    • Flushing in MCAS is longer duration, lasting minutes to hours

    • Usually no sweating

  • Pruritus

  • Dermatographia

  • Angioedema

Head and neck

  • Nasal congestion

  • Rhinorrhea

  • Conjunctival injection

Pulmonary

  • Wheezing

  • Bronchospastic cough

Gastrointestinal

  • Gastric hyperacidity

  • Nausea +/– vomiting

  • Diarrhea

  • Abdominal cramping

Cardiovascular

  • Hypotension

  • Tachycardia

  • Postural orthostatic tachycardia syndrome can be diagnosed with MCAS in some patients based on clinical grounds, although a pathologic basis for the role of mast cells in this disorder is lacking.

Constitutional

  • Fatigue

  • Lethargy

  • *Memory and concentration problems*

Brain

Headache, fatigue, lethargy, lack of concentration, and mild cognitive problems are frequent complaints in patients with primary and secondary mast cell activation

Diagnosis

Consider when symptoms consistent with mast cell activation, such as flushing, urticaria, diarrhea, abdominal cramping, wheezing, syncope, or near-syncope

Clinical Pearls

  • Recurrent or chronic urticaria, angioedema, and/or upper airway swelling are not characteristic of mastocytosis, and patients with these symptoms in the absence of other findings do not need to be evaluated for mastocytosis.

  • Anaphylaxis with hypotension in response to a bee or wasp sting is a classic manifestation of mastocytosis and may be the presenting scenario. A serum tryptase (when the patient is in the baseline state) should be measured for any patient with severe systemic reactions to Hymenoptera stings.

  • The presence of hypotension during anaphylaxis increases the odds that a patient has a clonal (primary) mast cell disorder. Clinicians should have a low threshold for referring such patients for bone marrow biopsy if an IgE-mediated cause does not explain all episodes, even if tryptase levels are normal.

Evaluation

  • Determine if skin findings of mastocytosis are present

  • Search for allergic disease and other secondary causes

  • Measure serum tryptase (collect within 1 to 4 hours of an attack if possible)

Management

Anaphylaxis - treat accordingly

Itch or urticaria

  • Non-sedating H1 antihistamines

  • Commonly used H1 antihistamines (adult dosing) include oral cetirizine (10 mg daily), fexofenadine (180 mg daily), loratadine (10 mg daily), desloratadine (5 mg daily) or levocetirizine (5 mg daily)

  • Antileukotriene agents may be added in patients with bronchospasm, flushing, itching, and abdominal cramping unresponsive to H1 and H2 antihistamines. Specific agents (adult dosing) include montelukast (10 mg daily), zafirlukast (20 mg daily), and less commonly zileuton (1200 mg twice daily, extended-release).

Gut symptoms

  • H2 antihistamines can be helpful for patients with hyperacidity and other gastrointestinal (GI) symptoms. Specific agents include famotidine (10 to 20 mg every 12 hours) and cimetidine (400 mg twice daily)

  • Cromolyn sodium stabilizes mast cell and eosinophil membranes in vitro and its oral formulation (Gastrocrom, Nalcrom in the United Kingdom) is helpful in some patients with GI symptoms

Reference