Clinical Approach to MCAS Diagnosis and Cutaneous Mastocytosis

The diagnosis of MCAS hinges on 3 indicators of MC mediator release:  

1) symptoms consistent with effects of MC mediators in at least 2 organ systems (respiratory,  mucocutaneous, gastrointestinal, cardiovascular) 

2) biochemical evidence of MC mediators in the blood or urine 

3) improvement with medications targeting MC mediators [8-11] 

When a patient has characteristic symptoms that respond to treatment with MC-directed therapy, MCAS may be suspected, but without biochemical evidence the diagnosis of MCAS cannot be  made. The term MC activation disorder (MCAD) has been proposed for these patients, but will not be discussed further [3, 9].

The first step in the diagnosis of MCAS is to obtain a detailed clinical history, thorough review of systems (ROS), and comprehensive physical exam (PE). Critical assessment of the reported  symptoms and physical exam findings must be made to determine whether the symptoms can be  attributed to MC activation (Figure 1). MCAS may be over-diagnosed [12], since many of the symptoms are non-specific and can overlap with a wide variety of other conditions (Figure 3).  A broad differential diagnosis (including neoplastic, vascular, infectious, inflammatory, endocrine, and toxic conditions) is essential to rule out other potential causes, such as inflammatory bowel disease for bloody diarrhea (Table 2).

Figure 3: MCAS clinical criterion vs nonspecific symptoms and conditions that do not qualify as features of MCAS

Table 2: Differential diagnosis of MCAS