TY - JOUR
T1 - Diagnosis, classification and management of mast cell activation syndromes (Mcas) in the era of personalized medicine
AU - Valent, Peter
AU - Akin, Cem
AU - Nedoszytko, Boguslaw
AU - Bonadonna, Patrizia
AU - Hartmann, Karin
AU - Niedoszytko, Marek
AU - Brockow, Knut
AU - Siebenhaar, Frank
AU - Triggiani, Massimo
AU - Arock, Michel
AU - Romantowski, Jan
AU - Górska, Aleksandra
AU - Schwartz, Lawrence B.
AU - Metcalfe, Dean D.
N1 - Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Mast cell activation (MCA) is seen in a variety of clinical contexts and pathologies, including IgE‐dependent allergic inflammation, other immunologic and inflammatory reactions, primary mast cell (MC) disorders, and hereditary alpha tryptasemia (HAT). MCA‐related symptoms range from mild to severe to life‐threatening. The severity of MCA‐related symptoms depends on a number of factors, including genetic predisposition, the number and releasability of MCs, organs affected, and the type and consequences of comorbid conditions. In severe systemic reactions, MCA is demonstrable by a substantial increase of basal serum tryptase levels above the individual´s baseline. When, in addition, the symptoms are recurrent, involve more than one organ system, and are responsive to therapy with MC‐stabilizing or mediator‐targeting drugs, the consensus criteria for the diagnosis of MCA syndrome (MCAS) are met. Based on the etiology of MCA, patients can further be classified as having i) primary MCAS where KIT‐mutated, clonal, MCs are detected; ii) secondary MCAS where an underlying IgE‐dependent allergy or other reactive MCA‐triggering pathology is found; or iii) idiopathic MCAS, where neither a triggering reactive state nor KIT‐mutated MCs are identified. Most severe MCA events occur in combined forms of MCAS, where KIT‐mutated MCs, IgE‐dependent allergies and sometimes HAT are detected. These patients may suffer from life‐threatening anaphylaxis and are candidates for combined treatment with various types of drugs, including IgE‐blocking antibodies, anti‐mediator‐type drugs and MC-targeting therapy. In conclusion, detailed knowledge about the etiology, underlying pathologies and co‐morbidities is important to establish the diagnosis and develop an optimal management plan for MCAS, following the principles of personalized medicine.
AB - Mast cell activation (MCA) is seen in a variety of clinical contexts and pathologies, including IgE‐dependent allergic inflammation, other immunologic and inflammatory reactions, primary mast cell (MC) disorders, and hereditary alpha tryptasemia (HAT). MCA‐related symptoms range from mild to severe to life‐threatening. The severity of MCA‐related symptoms depends on a number of factors, including genetic predisposition, the number and releasability of MCs, organs affected, and the type and consequences of comorbid conditions. In severe systemic reactions, MCA is demonstrable by a substantial increase of basal serum tryptase levels above the individual´s baseline. When, in addition, the symptoms are recurrent, involve more than one organ system, and are responsive to therapy with MC‐stabilizing or mediator‐targeting drugs, the consensus criteria for the diagnosis of MCA syndrome (MCAS) are met. Based on the etiology of MCA, patients can further be classified as having i) primary MCAS where KIT‐mutated, clonal, MCs are detected; ii) secondary MCAS where an underlying IgE‐dependent allergy or other reactive MCA‐triggering pathology is found; or iii) idiopathic MCAS, where neither a triggering reactive state nor KIT‐mutated MCs are identified. Most severe MCA events occur in combined forms of MCAS, where KIT‐mutated MCs, IgE‐dependent allergies and sometimes HAT are detected. These patients may suffer from life‐threatening anaphylaxis and are candidates for combined treatment with various types of drugs, including IgE‐blocking antibodies, anti‐mediator‐type drugs and MC-targeting therapy. In conclusion, detailed knowledge about the etiology, underlying pathologies and co‐morbidities is important to establish the diagnosis and develop an optimal management plan for MCAS, following the principles of personalized medicine.
KW - Hereditary alpha tryptasemia
KW - IgE
KW - Mast cell activation syndrome
KW - Mastocytosis
UR - http://www.scopus.com/inward/record.url?scp=85096636135&partnerID=8YFLogxK
U2 - 10.3390/ijms21239030
DO - 10.3390/ijms21239030
M3 - Review article
C2 - 33261124
AN - SCOPUS:85096636135
SN - 1661-6596
VL - 21
SP - 1
EP - 14
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 23
M1 - 9030
ER -