Targeted drugs that block abnormal KIT signaling can reduce life-threatening allergic reactions and improve quality of life for people with systemic mastocytosis (SM), according to a review published recently in Current Allergy and Asthma Reports.
Experts now recommend these agents for patients with severe, drug-resistant symptoms or advanced disease, while continuing first-line treatments such as antihistaminesAntihistamines Medications that block the effects of histamine, the chemical found in mast cells that is responsible for many of the symptoms of SM, as well as many allergic reactions. and trigger avoidance.
In SM, too many abnormal mast cells build up in organs such as the bone marrow, skin, spleen and gastrointestinal tract. Mast cells normally help defend against infections, but in this disease they release excessive chemicals including histamineHistamine A chemical released by mast cells when they are activated. Histamine causes many of the allergy-type symptoms in mastocytosis, including flushing, itching and hives., tryptaseTryptase A protein enzyme that is primarily produced by mast cells and stored in small pockets within the cells, known as granules. High levels of tryptase are a key indicator of SM., prostaglandins and leukotrienes. These substances can cause flushing, abdominal pain, diarrhea, low blood pressure and in some cases life-threatening anaphylaxisAnaphylaxis A severe allergic reaction that can turn fatal without treatment. Patients with SM are at a higher risk of developing anaphylaxis..
Even patients with a low mast cellMast cell A type of white blood cell produced in the bone marrow. They help defend against infections and play a key role in allergic reactions. In SM, mast cells become overactive and build up throughout the body. burden, such as those with bone marrow mastocytosisBone marrow mastocytosis A subtype of indolent SM that occurs when the excess mast cells accumulate in the bone marrow, but not the skin or other organs., may experience severe allergic reactions, particularly to Hymenoptera venom from bees or wasps. Higher baseline tryptase levels and greater mast cell infiltration often correlate with more severe reactions, although this is not universal.
Read more about treatment and care for SM
Genetic traits can also play a role in the severity of reactions. Hereditary alpha tryptasemia, found in about 5% of the general population and roughly 15% to 17% of patients with SM, is linked to more intense mediator-related symptoms in some individuals. However, not all carriers develop severe reactions, and the exact contribution of this trait remains under study.
“In patients with SM, mediator-related symptoms remain a major clinical challenge, especially when a concomitant IgE-dependent allergy is present,” stated the authors of this review.
Initial management of SM generally focuses on strict avoidance of known triggers and daily medications that block histamine receptors. Mast cell stabilizers, leukotriene blockers and, for severe episodes, epinephrineEpinephrine Also called adrenaline, this hormone is used in emergency situations to reverse symptoms during a severe allergic reaction (anaphylaxis). are commonly used. Patients with confirmed insect venom allergy are advised to undergo lifelong venom immunotherapy. In difficult cases driven by IgE antibodies, treatment with omalizumab may reduce recurrent anaphylaxis.
For patients with persistent, severe symptoms or advanced disease, newer tyrosine kinase inhibitors that target KIT D816V offer another option. Midostaurin and avapritinib not only shrink abnormal mast cell populations but also dampen activation signals that lead to mediator release. Avapritinib has produced complete or near-complete hematologic remission in about 20% to 30% of selected patients with smoldering or advanced disease. While for most patients these drugs are generally used only when first-line treatments are found to be ineffective, research indicates they may provide sustained symptom control and fewer anaphylactic events, allowing many patients to live more safely and with greater confidence.
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