Clinical and Laboratory Parameters of Mast Cell Activation as Basis for the Formulation of Diagnostic Criteria

Abstract

Mast cell (MC) activation occurs in a number of different pathologic conditions. Acute activation is commonly seen in patients with allergic reactions, with consecutive massive release of vasoactive and proinflammatory mediator substances from MCs, leading to the clinical signs and symptoms of anaphylaxis. In these patients, serum tryptase concentrations usually increase subtantially above baseline levels. Chronic MC activation is more difficult to diagnose, especially when symptoms are mild or atypical, and no underlying disease is found. In these patients, serum tryptase levels usually are normal. In a smaller group of patients, tryptase levels are constantly elevated and may point to an occult form of mastocytosis. These patients have to be examined for MC monoclonality, other criteria of a primary MC disease, non-MC hematopoietic neoplasms, and reactive disorders producing chronic MC activation or MC accumulation. In most patients in whom MC activation is found, histamine-induced symptoms can be documented and usually respond to treatment with histamine receptor antagonists or MC stabilizers. If this is not the case, alternative explanations for symptoms and differential diagnoses have to be considered.

Mast cell activation syndromes: definition and classification

“…The term MCAS should be applied when i) clinical signs of severe recurrent (or chronic) systemic MCA are present, ii) involvement of mast cells can be documented by biochemical measurements (preferably increase in tryptase following the 20% + 2 formula), and iii) the symptoms respond to therapy with mast cell-stabilizing agents or drugs directed against mast cell mediator production, mediator release, or mediator effects (24)(25)(26)(27) (Fig. 1).…”

“…Mast cell activation syndrome usually develops on the basis of a known underlying systemic disease, which can be an IgE-dependent disorder, another inflammatory disease, or a mast cell neoplasm (20)(21)(22)(23)(24)(25)(26)(27). In most patients, the mast cell neoplasm, if detected, is classified as systemic mastocytosis (SM).…”

“…In addition, KIT D816V has been discussed as contributing to the enhanced releasability of mast cells in SM, although this point is still a matter of discussion. An important aspect is that KIT D816V is sometimes also expressed in mast cells in patients with cutaneous mastocytosis (CM) (61)(62)(63) or even in otherwise healthy individuals in whom neither criteria for CM nor criteria for SM are fulfilled (21)(22)(23)(24)(25)(26). In these patients, the KIT-mutated mast cells may contribute to the symptoms of MCAS in the same way as in SM.…”

“…More recently, however, MCA has also been studied in the context of other diseases, including systemic mastocytosis (21)(22)(23)(24)(25). During the past 3 years, criteria for MCA and MCAS have been developed by a consensus panel consisting of experts in the fields of allergy, dermatology, hematology, pathology, and molecular medicine (25)(26)(27).…”

Cissampelos sympodialis (Menispermaceae): A Novel Phytotherapic Weapon Against Allergic Diseases?

“…All of these conditions are consequence of sensitized mast cell degranulation which releases several mediators (histamine, CisLT or prostaglandins) that cause smooth muscle contraction. Histamine is also of fundamental importance in triggering the allergic symptoms such as swelling (Baroody & Naclerio, 2000), itching (Davidson & Giesler, 2010), bronchospasm (Larsen, 2001) and anaphylactic shock (Valent et al, 2011). Warifteine effect in mast cell degranulation was then investigated.…”