Mastocytosis and Mast Cell Activation Syndrome

Cutaneous mastocytosis typically occurs in children. Most patients present with urticaria pigmentosa, a local or diffusely distributed salmon or brown maculopapular rash caused by multiple small mast cell collections. Nodular lesions and plaques can also develop. Less common are diffuse cutaneous mastocytosis, which is skin infiltration without discrete lesions, and mastocytoma, which is a large (1 to 5 cm) solitary collection of mast cells.

Cutaneous forms rarely progress to systemic disease in children but may do so in adults.

Systemic mastocytosis most commonly occurs in adults and is characterized by multifocal bone marrow lesions; it often involves other organs, most commonly skin, lymph nodes, liver, spleen, and/or gastrointestinal (GI) tract.

Systemic mastocytosis is classified as

Mast cell activation syndrome is characterized by increased and inappropriate activation of mast cells with mediator release but without clonal proliferation or organ infiltration by mast cells (1 Classification reference Mastocytosis is mast cell proliferation with infiltration of skin or other tissues and organs. Mast cell activation syndrome is increased and inappropriate activation of mast cells without clonal... read more ). The syndrome was originally diagnosed only when mediator release was idiopathic, but it has since been expanded to include release triggered by allergen-specific IgE, certain drugs, or physical factors. Genetic causes are suspected but not proved. Most cases do not involve clonal proliferation of mast cells but are due to a lower threshold for mast cells to degranulate. Mast cell activation syndrome has frequently been associated with postural orthostatic tachycardia syndrome (POTS) Postural orthostatic tachycardia syndrome (POTS) Orthostatic (postural) hypotension is an excessive fall in blood pressure (BP) when an upright position is assumed. The consensus definition is a drop of > 20 mm Hg systolic, > 10 mm Hg... read more and Ehlers-Danlos syndrome Ehlers-Danlos Syndromes Ehlers-Danlos syndromes are hereditary collagen disorders characterized by joint hypermobility, dermal hyperelasticity, and widespread tissue fragility. Diagnosis is clinical. Treatment is supportive... read more , although the nature of the connection is unclear.

The manifestations of mast cell activation syndrome are frequently similar to those of patients with systemic mastocytosis; they include tachycardia, syncope, urticaria, flushing, nausea, vomiting, and brain fog.

It is unclear whether mast cell activation syndrome can progress to systemic mastocytosis or another form of mast cell disease and, if so, how many patients are affected.

H1 blockers Antihistamines Allergic (including atopic) and other hypersensitivity disorders are inappropriate or exaggerated immune reactions to foreign antigens. Inappropriate immune reactions include those that are... read more are effective for symptoms. Children with cutaneous forms require no additional treatment because most cases resolve spontaneously.

Adults with cutaneous forms may be treated with psoralen plus ultraviolet light or with topical corticosteroids once or twice a day.

Mastocytoma usually involutes spontaneously and requires no treatment.

Management of anaphylactic reactions Treatment Anaphylaxis is an acute, potentially life-threatening, IgE-mediated allergic reaction that occurs in previously sensitized people when they are reexposed to the sensitizing antigen. Symptoms... read more includes parenteral epinephrine, inhaled beta-agonists for wheezing, and IV fluid replacement for hypotension.

All patients with systemic mastocytosis should be treated with H1 and H2 blockers and should carry a prefilled, self-injecting epinephrine syringe.

Aspirin controls flushing but may enhance leukotriene production, thereby contributing to other mast cell–related symptoms; it should not be given to children because Reye syndrome is a risk.

Cromolyn 200 mg orally 4 times a day (100 mg 4 times a day for children 2 to 12 years; not to exceed 40 mg/kg/day) may help by preventing mast cell degranulation. Ketotifen 2 to 4 mg orally twice a day may also be effective. No treatment can reduce the number of tissue mast cells.

Omalizumab is an anti-IgE antibody that is sometimes used for moderate to severe asthma and chronic urticaria; it has sometimes been used in patients with mastocytosis or mast cell activation syndrome to try to prevent anaphylaxis.

In patients with an aggressive form of mastocytosis, characterized by increasing mast cell accumulation in different organs, leading to dysfunction, the multikinase inhibitors midostaurin or avapritinib (1 Treatment references Mastocytosis is mast cell proliferation with infiltration of skin or other tissues and organs. Mast cell activation syndrome is increased and inappropriate activation of mast cells without clonal... read more ) can be used to help control end-organ damage, cytopenias, and mast cell accumulation in bone marrow (2 Treatment references Mastocytosis is mast cell proliferation with infiltration of skin or other tissues and organs. Mast cell activation syndrome is increased and inappropriate activation of mast cells without clonal... read more ). Dosages are

Interferon alfa-2b 4 million units subcutaneously once a week to a maximum of 3 million units a day induces regression of bone lesions. Corticosteroids (eg, prednisone 40 to 60 mg orally once a day for 2 to 3 weeks) may be required as adjunctive treatment for severe cases. Some limited evidence suggests that splenectomy may improve survival in patients with aggressive disease.

Cytotoxic drugs (eg, daunomycin, etoposide, 6-mercaptopurine) may be indicated for treatment of mast cell leukemia, but efficacy is unproved. Imatinib (a tyrosine kinase receptor inhibitor) may be useful when treating adults with aggressive systemic mastocytosis but is ineffective in patients with the D816V c-kit mutation.

Treatment is directed at preventing mediator release (eg, with cromolyn and/or ketotifen) and blocking mediator effects with some regimen of H1 and H2 blockers to block histamine, aspirin to block prostaglandins and montelukast to block leukotrienes.

Known triggers should be avoided.