Diagnosis of Mast Cell Activation Disease

This diagnostic tool was developed to aid clinicians in considering a clinical diagnosis of mast cell activation disease, whether that is mastocytosis or mast cell activation syndrome and is based on the extensive patient data and experiences of Dr Afrin and Professor Molderings.

It is now understood that the various forms of systemic mastocytosis – diseases of inappropriate activation and proliferation of MCs seemingly driven by a small set of rare, usually constitutively activating mutations in assorted MC regulatory elements – comprise merely the tip of the mast cell activation disease (MCAD) iceberg, whereas the far larger and far more clinically heterogeneous (and thus more difficult to recognize) bulk of the iceberg consists of assorted forms of MC activation syndrome (MCAS) which manifest little to no abnormal MC proliferation and may originate from a far more heterogeneous set of MC mutations.

It is reasonable to suspect MCAD when symptoms and signs of MC activation are present and no other diagnosis better accounting for the full range of findings is present.

Whether assessing for mastocytosis or MCAS, testing is fraught with potential pitfalls which can easily yield false negatives leading to erroneous rejection of diagnostic consideration of MCAD in spite of a clinical history highly consistent with MCAD. Efforts at accurate diagnosis of MCAD are worthwhile, as many patients then respond well to appropriately directed therapeutic efforts.

Diagnosticians willing to pursue the possibility of MCAD in their patients whose chronic multisystem polymorbidity (often, but not always, of a generally inflammatory theme) has defied extensive prior diagnostic efforts (typically focused on subspecialty-oriented symptom subsets rather than broad multisystem considerations) currently face many challenges including controversies in precise diagnostic criteria (particularly for MCAS), uncertainty regarding the utility of various diagnostic tests, and difficulties properly managing specimens for such testing. Whether assessing for mastocytosis or MCAS, testing is fraught with potential pitfalls which can easily yield erroneous conclusions that MCAD is not present and thereby potentially add yet much more time and cost to the very long and expensive path most patients with MCAD (particularly MCAS) require to establish diagnosis, let alone effective therapy.

• Author
• Release Date 10/05/2015

Start application and complete patient data forms (indicated by tabs) according to available information.

The “assessment tab” gives a summary of indicants that are suggestive of mast cell activation disease, with their scores. The “triage” tab indicates whether systemic mast cell mediator release syndrome is clinically verified.

This diagnostic tool was developed to aid clinicians in considering a clinical diagnosis of mast cell activation disease, whether that is mastocytosis or mast cell activation syndrome and is based on the extensive patient data and experiences of Dr Afrin and Professor Molderings.

It is now understood that the various forms of systemic mastocytosis – diseases of inappropriate activation and proliferation of MCs seemingly driven by a small set of rare, usually constitutively activating mutations in assorted MC regulatory elements – comprise merely the tip of the mast cell activation disease (MCAD) iceberg, whereas the far larger and far more clinically heterogeneous (and thus more difficult to recognize) bulk of the iceberg consists of assorted forms of MC activation syndrome (MCAS) which manifest little to no abnormal MC proliferation and may originate from a far more heterogeneous set of MC mutations.

It is reasonable to suspect MCAD when symptoms and signs of MC activation are present and no other diagnosis better accounting for the full range of findings is present.

Whether assessing for mastocytosis or MCAS, testing is fraught with potential pitfalls which can easily yield false negatives leading to erroneous rejection of diagnostic consideration of MCAD in spite of a clinical history highly consistent with MCAD. Efforts at accurate diagnosis of MCAD are worthwhile, as many patients then respond well to appropriately directed therapeutic efforts.

Diagnosticians willing to pursue the possibility of MCAD in their patients whose chronic multisystem polymorbidity (often, but not always, of a generally inflammatory theme) has defied extensive prior diagnostic efforts (typically focused on subspecialty-oriented symptom subsets rather than broad multisystem considerations) currently face many challenges including controversies in precise diagnostic criteria (particularly for MCAS), uncertainty regarding the utility of various diagnostic tests, and difficulties properly managing specimens for such testing. Whether assessing for mastocytosis or MCAS, testing is fraught with potential pitfalls which can easily yield erroneous conclusions that MCAD is not present and thereby potentially add yet much more time and cost to the very long and expensive path most patients with MCAD (particularly MCAS) require to establish diagnosis, let alone effective therapy.

Developed from “A concise practical guide to diagnostic assessment for mast cell activation disease” Lawrence B Afrin, Gerhard J Molderings,  World Journal of Haematology February 2014

B Afrin, Gerhard J Molderings,  World Journal of Haematology February 2014 ISSN 2218-6204