Patients with mast cell activation disorders present with recurrent symptoms of mast cell activation, in combination with objective evidence of mast cell mediator release. Two mast cell activation disorders have been recently proposed and defined:
- Monoclonal mast cell activation syndrome (MMAS)
- Mast cell activation syndrome (MCAS)
This topic will review the classification of mast cell disorders and then focus on MMAS and MCAS, describing the clinical manifestations, evaluation, diagnosis, and treatment of these disorders. By the time a mast cell disorder is considered, patients have typically undergone evaluation for a wide array of disorders, both allergic and nonallergic. Disorders that can mimic allergic reactions and anaphylaxis are discussed separately. (See "Differential diagnosis of anaphylaxis in children and adults".)
CLASSIFICATION OF MAST CELL DISORDERS
Mast cell disorders can be broadly divided into three types: primary, secondary, and idiopathic (table 1). All of these disorders present with signs and symptoms of mast cell activation and differ in severity and involvement of various organ systems. Within this framework, MMAS is best classified as a primary mast cell disorder, while MCAS is considered an idiopathic disorder.
Primary mast cell disorders — Primary disorders of mast cells are associated with intrinsic defects in mast cells affecting proliferation or activation pathways. In these disorders, clonal populations of mast cells arise from an affected progenitor and display abnormal genetic and surface markers. Stem cell factor (SCF) is critical for mast cell growth and differentiation from hematopoietic progenitors, as well as their survival and chemotaxis. The transmembrane receptor for SCF is KIT (encoded by the protooncogene c-kit). (See "Mast cells: Surface receptors and signal transduction", section on 'Stem cell factor receptor'.)