Treatments of SM are of two types: medications to control MC mediator-related symptoms and cytoreductive treatments to limit MC burden and increase survival mainly in ASM and MCL. In ISM and SSM, the management is mainly symptomatic plus a correct monitoring to identify signs of progression. Additionally, all SM patients should be aware of potential triggers of MC activation. The triggers of MC degranulation may be different, including emotional stress, physical stimuli, infections, allergies, and drugs such as alcohol, aspirin, non-steroid anti-inflammatory drugs, and opioids.
Treatments of MC mediator GI symptoms rely on anti-mediator therapy such as antihistamines 
receptor antagonists are often used in combination. H1
antagonists can treat skin symptoms 
. To control GI symptoms, H2 antagonists are generally used as 1st-line therapy and proton pump inhibitors as 2nd-line 
. Cromolyn sodium as a MC stabilizer has been reported to be effective in reducing GI symptoms (especially diarrhea, abdominal pain, and nausea) and it is used as 3rd-line therapy 
. Leukotriene antagonists and IgE-binding treatment with the monoclonal antibody omalizumab are included among therapies to treat MC activation symptoms 
. The use of systemic steroids is limited to specific situations, for instance in the setting of organ damage; low-dose corticosteroids are reported to reduce malabsorption and ascites 
In ASM, treatments interfering with MC proliferation and survival are used. Tyrosine kinase inhibitors (TKIs), chemotherapy, and allogenic stem cell transplantation (allo-SCT) are considered the best therapeutic options for ASM, including MCL 
. Imatinib and Nilotinib demonstrate effect against wild-type KIT and a limited activity against KIT D816V; however, there are reports of response to these drugs in patients with atypical KIT mutations 
. Midostaurin, a TKI with activity against KIT D816V, represents the only approved therapy for advanced SM, including MCL 
. In advanced SM, most responses with Midostaurin are only partial and not sustained. Other medications potentially effective for SM patients are under investigation. Recent and promising results have been obtained with Avapritinib, a KIT and PDGFRA inhibitor 
. Interferon alpha and cladribrine have also been used 
. Allo-SCT needs to be considered in young and otherwise healthy patients with ASM, as this is the only option for a sustained response 
. Prior to SCT, therapies such as either midostaurin or cladribrine should be used to bring the patients to the best response.