Review Diagnosis, Classification and Management of Mast Cell Activation Syndromes (MCAS) in the Era of Personalized Medicine, 2020, Valent et al

[Yann04]

Abstract:
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.

LINK (MDPI)

 

[Yann04]

Whether MCAS may also present as a chronic disease in the absence of recognized systemic anaphylactic events is controversial. Non-specific symptoms such as headache, fatigue, nausea and sleep disturbance do not fulfill well-established criteria of MCA and therefore of MCAS. Nevertheless, these symptoms are clinically relevant and thus should be treated appropriately to provide symptomatic relief. Also, it is important to recognize that the differential diagnoses to be considered in such patients are broad, including neurologic, infectious and cardiac disorders [20,21,22,23].

In most patients with severe systemic reactions, increased levels of MC-derived mediators are measurable in biological fluids (serum, plasma, urine) [20,21,22,23,24,25,26]. Some of these mediators, such as tryptase or prostaglandin D2, are more specific for MCs [1,2,3,4]. Other mediators are less specific and also produced by other cell types. Whereas histamine is released from MCs and basophils in similar quantities, tryptase is considered rather specific for MCs, although basophils can also express and release small quantities of the enzyme [27,28,29,30]. Therefore, most experts agree that for daily clinical practice, a rapid increase in the serum tryptase level from the individual’s baseline is MCA-specific and thus a reliable diagnostic parameter [20,21,22,23,24,25,26,31,32]. If no pre-therapeutic baseline is available, the baseline serum tryptase level has to be assessed after complete recovery (at least 24–48 h after complete resolution of symptoms) or in a symptom-free interval [20,21,22,23].
Apart from tryptase, other mediators, when increasing transiently over baseline during a clinically defined attack (MCA-related event), may also serve as supportive evidence of systemic MCA. These include, among others, histamine (plasma, urine), histamine metabolites (urine) and prostaglandin D2 metabolites (Table 3) [31,32,33,34,35,36,37].

 

[Jonathan Edwards]

I wonder why Lawrence Afrin is not an author.