Doctor, I Think I Am Suffering from MCAS: Differential Diagnosis and Separating Facts from Fiction

Mast cell activation syndrome (MCAS) is a rare condition defined by a severe systemic reaction to mast cell (MC)-derived mediators. Most cases present with clinical signs of anaphylaxis, and some have an underlying IgE-dependent allergy. A primary MC disease (mastocytosis) may also be detected. Severe recurrent MCAS episodes requiring intensive care or even resuscitation are typically found in patients who suffer from both mastocytosis and allergy against certain triggers, such as hymenoptera venom components. A less severe form and a local form of MC activation (MCA) also exist. For these patients, diagnostic criteria are lacking. Moreover, a number of different, unrelated, conditions with overlapping symptoms may be confused with MCAS. As a result, many patients believe that they are suffering from MCAS but have in fact a less severe form of MCA or another underlying disease. In the current article, we review the potential differential diagnoses of MCA and MCAS and discuss available diagnostic criteria and diagnostic tools. These criteria and assays may be useful in daily practice and help avoid unnecessary referrals and unjustified fears in patients.