By Gary M. White, MD
Systemic mastocytosis is the abnormal proliferation of a clone of mast cells (MCs) that may invade the skin, bone marrow, and internal organs.
See also solitary mastocytoma, telangiectasia macularis eruptiva perstans (TMEP), urticaria pigmentosa, and bullous mastocytosis. Of note, the term "mast cell activation syndrome" is a new term that refers to mast cell diseases in which there is inappropriate mediator release with little to no accompanying proliferation of MCs.
The skin may be infiltrated with mast cells causing red/brown papules and plaques. If severe, the skin can take on a thickened and doughy appearance. Both the infiltration of mast cells and their degranulation products can produce edema and a typical leather-grain appearance [Indian J Dermatol Venereol Leprol 2014;80:432-47]. Urticaria and flushing may be associated. Itch is common. Systemic symptoms may include abdominal pain, gastroesophageal reflux disease (GERD), and anaphylaxis. Physical findings can include hepatosplenomegaly and lymphadenopathy. In one study, 18% of patients with mastocytosis also had osteoporosis [J Allergy Clin Immunol 2009;124(3):514-21].
According to the 2008 World Health Organization, diagnosis is made by finding the one major criterion and one of the four minor criteria OR three of the four minor criteria.
A skin biopsy should be performed to establish the diagnosis. All patients should have a CBC with differential and a bone marrow biopsy. Measuring serum tryptase levels, serum histamine levels, and urinary histamine and its metabolites helps determine the systemic load of mast cells. Tryptase levels can be elevated by higher weight, impaired renal function, and increased age. For determining the need for a bone marrow biopsy in older, higher-weight patients, urinary methylimidazole acetic acid has a greater value than tryptase [J. Allergy Clin. Immunol 2015;;135;792]. The presence of KIT D816V mutation should be determined. A bone density test is appropriate since patients are at risk for osteoporosis and even bone fractures.
Unlike children with mastocytosis, adults tend to have a chronic course but conversion to mast cell leukemia is rare (3-6%). One study summarized the belief that when onset of maculopapular mastocytosis occurs after 10 years of age, it will persist throughout adulthood in 90% of patients, and 15–30% of these patients will develop systemic involvement [BJD 2016;174;411]. Systemic oral antihistamines are helpful for symptoms--both cutaneous and gastrointestinal. Potent topical steroids can reduce the appearance of skin lesions. Narrowband UVB resulted in complete remission of the cutaneous lesions and pruritus in all of 5 patients treated after a median of 40 treatments [J Eur Acad Dermatol Venereol 2012;26:465-9]. Drugs or other triggers which may cause degranulation should be avoided. Patients at risk should routinely carry adrenaline auto-injectors. Patients undergoing general anesthesia should alert the anesthesiologist as the process of surgery (e.g., temperature change, friction, drugs given) can provoke anaphylaxis.
Omalizumab in case reports has prevented anaphylaxis associated with mastocytosis as well as decreased urticaria and itch.
The KIT D816V mutation causes resistance to imatinib mesylate (Gleevec). In contrast, the wild-type KIT and several rare KIT mutations are imatinib sensitive.
Midostaurin, a multi-targeted kinase inhibitor, helps prevent end-organ damage in patients with advanced systemic mastocytosis [NEJM 2016;374;2530].
Patients should be examined periodically for any progression of disease, e.g., tumors, thickened areas, lymphadenopathy. The tryptase level should be followed.
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