1. Presumed Mast Cell Activation Syndrome - A single centre cohort
review
A Herwadkar, S Elkhalifa, L Goodwin
Salford Royal NHS Foundation Trust, 2nd Floor Turnberg Building, Stott Lane, Salford, M6 8HD
Table [1-1] summarize the results of 11 patients’ cohort “6 males and 5 females” with presumed Mast Cell Activation Syndrome; the
presenting symptoms, baseline mast cell tryptase levels, management and response to treatment with antihistamines and mast cell stabilisers:
Aim
The aim of the study was to review patients with presumed Mast cell activation syndrome (MCAS), review salient clinical features
and highlight important management issues.
Methods
Electronic patient records were reviewed for 11 patients seen in immunology clinic at SRFT with a diagnosis of presumed MCAS.
Any available ED “Emergency Department” records following patient’s attendance to local ED centres were previously reviewed as
part of their clinical management.
Results and discussion
Our index case was Mr L who is 44 years old man. He was reviewed in immunology and allergy clinic in 2011. He has been
complaining of recurrent attacks of Paroxysmal Atrial Fibrillation (PAF) since 2004 not responding to Sotalol and or Flecainide, as
well as recurrent episodes of urticarial skin rash, facial angioedema, hot flushes and diarrhoea. He was provided with an emergency
management plan in case of future attacks, and maintained symptoms diary. He then sustained an attack of idiopathic anaphylaxis
which presented with documented hypotension, and raised Mast cell tryptase “37.2” compared to baseline of “3.3”.
Based on Akin’s proposed diagnostic criteria for Mast cell activation Syndrome [1]. Mr L was diagnosed with MCAS and started on
triple therapy of Fexofenadine, Montelukast, and Ranitidine. Other potential causes for the recurrent attacks have been explored
which included: Carcinoid syndrome, Intermittent Porphyria, and phaeochromocytoma, and were all negative. He has had
abdominal USS “normal” and underwent gastroscopy, colonoscopy with biopsies and capsule endoscopy under gastroenterologist
which showed reflux oesophagitis Grade C and suspected small bowel polyps. He was started on Omeprazole for the oesophagitis
and underwent double balloon enteroscopy and biopsies for the small bowel which showed normal histology with no evidence
mast cell aggregates. Skeletal survey were performed which ruled out lytic lesions. From above investigations no evidence to
support systemic Mastocytosis were identified.
He underwent ablation therapy for the atrial fibrillation “pulmonary vein isolation “as he needed to use the adrenaline auto
injectors for idiopathic anaphylactic attacks which accompanied by PAF in few occasions.
Mr L required multiple changes to his medication to control his mast cell activation symptoms, which included Sodium
Cromoglycate, Ketotifen and loratadine, were added to his previous therapy which resulted in good symptoms control. He
successfully managed to reduce the medication regime for MCAS to only Ketotifen and Levocetirizine with no further MCAS
attacks.
This case represents a typical medical journey of MCAS patient, who has been through many specialists for their various systemic
symptoms before getting the diagnosis of MCAS.
We reviewed all presumed MCAS patients who presented to our centre. The presenting symptoms, baseline mast cell tryptase
levels, management and response to treatment with antihistamines and mast cell stabilisers have been reviewed and summarized
in table [1-1]. The challenges faced in achieving a definitive diagnosis in this cohort were mainly the lack of evidence of raised mast
cell tryptase during the attacks. This has been the case for few patients either because they forget to tell the medical staff in ED
department even with our prior advice, or the ED team were not aware of such diagnosis and requirement for confirming the
diagnosis.
In 2010 Akin and colleagues[1] proposed the term MCAS to designate a multisystem syndrome presenting with variable mast cell
activation symptoms documented by increased mast cell mediator levels during attacks, which was distinct from clonal and IgE-
mediated disorders. In our patient cohort, there were no suggestions of clonal or IgE mediated disorders. Although all patients
have had episodic symptoms consistent with mast cell activation, and have shown response to mast cell mediator therapy. It’s not
been possible to document rise in mast cell tryptase level in all patients. Thus the term” Presumed MCAS” has been used. Although
many patients have presented with urticarial skin rash; their overall presentation is quite different from common clinical entity of
chronic spontaneous urticaria.
Conclusion
Mast cell activation syndrome is a differential diagnosis to be considered in patients presented with various clinical symptoms
affecting multiple systems, who do not entirely fit the clinical criteria of chronic urticaria or idiopathic anaphylaxis.
We have considered MCAS as the most likely diagnosis in 11 of our patients who presented with multisystem mast cell activation
symptoms that characterized by remarkable response to mast cell mediator therapy (H1, and H2 antihistamines, leukotrienes,
cromolyn, and ketotifen). The diagnosis could not be confirmed on at least 6 patients due to lack of Mast cell tryptase level during
the attack. Differential diagnoses have been excluded in these patients by working closely with colleagues in gastroenterology,
endocrinology and haematology.
No. Symptoms PMH Investigations: Treatment for MCAS Clinical course
MCT as
baseline
MCT during
an attack
1st time MCAS was
suspected.
1 Pruritis, skin Rash, Lightheaded Diarrhoea,
and Abdominal pain,
Asthma, NIDDM*, High
cholesterol
5.9 Not available** Daily: Fexofenadine.
Emergency plan: C, A, P ***
July 2014, Symptoms for few years
prior to IMM clinic****
Last time seen in clinic February 2015.
2 Pruritis , skin rash, angioedema, flushing,
breathlessness, diarrhoea and Idiopathic
Anaphylaxis
HTN, DM, IHD 12.9 16.4 Daily: Fexofenadine, Loratadine
(stopped recently)
Emergency plan: C, A, P ***
July 2011, Symptoms for few years
prior to IMM clinic
Last time seen in clinic May 2015.
3 Diarrhoea, Flushing, and Abdominal pain. IDDM 3.8 12.8 Daily: Fexofenadine.
Emergency plan: C, A, P ***
March 2010, symptoms for 10 years
prior to IMM clinic.
Last time seen in clinic April 2014.
4 Idiopathic anaphylaxis, angioedema,
urticarial,tachyarrhythmia and diarrhoea
Systemic
Hypertension, Gout,
paroxysmal Atrial
fibrillation.
2.9 37.2 Daily: Ketotifen and
Levocetirizine.
Multiple medications were
changed during the clinical course
of his illness.
Emergency plan: C, A, P ***
May 2011, symptoms for 6 years prior
to IMM clinic.
Last time seen in clinic December
2014.
5 Wheezes, Urticarial rash, angioedema and hyperthyroidism 17.2 – 23.3 Persistently
elevated
Daily: Fexofenadine.
Emergency plan: C, A, P ***
April 2011, symptoms for 18 months
prior to IMM clinic.
Last time seen in clinic May 2015
6 idiopathic anaphylaxis , Diarrhoea,
abdominal pain, and urticarial rash
none 4.6 Not available Daily: Loratadine “stopped
recently”
Emergency plan: C, A, P ***
April 2012- October 2013
Last time seen in clinic October 2013
7 Diarrhoea, Vomiting, flushing and urticarial
rash.
Asthma, DM, allergic
rhinits
7.1 8.2 Daily: Fexofenadine.
Emergency plan: C, A, P ***
January 2011
Last time seen in clinic July 2014
8 hot flushes, Sweats , urticarial rash and
angioedema
Epilepsy, Asthma 2.3 Not available Daily: Fexofenadine, Loratadine,
Ranitidine “stopped”,
Hydroxyzine “stopped”
Emergency plan: C, A, P ***
July 2013
Last time seen in clinic July 2015.
9 Diarrhoea, abdominal pain, urticarial rash Epilepsy 3.8 (not available) Daily: Loratadine (stopped)
Emergency plan: C, A, P ***
November 2014 symptoms for 10
years prior to IMM clinic.
Last time seen in clinic May 2015.
10 Diarrhoea, Pruritis, urticarial rash HTN, DM, GORD 3.7 (not available) Daily: Fexofenadine.
Emergency plan: C, A, P ***
February 2015
Last time seen in clinic May 2015.
11 Urticarial rash, light-headedness,
palpitations,
Abdominal colic
Migraine 2.3 (not available) Daily: Cetirizine, Fexofenadine,
Prednisolone (reducing course)
Emergency plan: C, P *** no
adrenaline been prescribed
August 2015
Last time seen in clinic August 2015.
*NIDDM: Non-insulin dependent Diabetes Mellitus. ** Not available: No sample taken during acute attack. *** Emergency management
plan: C, A, P “Chlorpheniramine, AAI (e.g EpiPen) and Prednisolone. **** IMM clinic: immunology clinic, *****5HIAA: 5-Hydroxyindole-
acetic acid.
References
[1] Akin C, Valent P, Metcalfe DD. Mast cell activation syndrome: proposed diagnostic criteria. J Allergy Clinical Immunology 2010
[2] Akin C, Mast Cell Activation Syndromes Presenting as Anaphylaxis, Immunology & Allergy Clinics of North America, April 2015
![Presumed Mast Cell Activation Syndrome - A single centre cohort
review
A Herwadkar, S Elkhalifa, L Goodwin
Salford Royal NHS Foundation Trust, 2nd Floor Turnberg Building, Stott Lane, Salford, M6 8HD
Table [1-1] summarize the results of 11 patients’ cohort “6 males and 5 females” with presumed Mast Cell Activation Syndrome; the
presenting symptoms, baseline mast cell tryptase levels, management and response to treatment with antihistamines and mast cell stabilisers:
Aim
The aim of the study was to review patients with presumed Mast cell activation syndrome (MCAS), review salient clinical features
and highlight important management issues.
Methods
Electronic patient records were reviewed for 11 patients seen in immunology clinic at SRFT with a diagnosis of presumed MCAS.
Any available ED “Emergency Department” records following patient’s attendance to local ED centres were previously reviewed as
part of their clinical management.
Results and discussion
Our index case was Mr L who is 44 years old man. He was reviewed in immunology and allergy clinic in 2011. He has been
complaining of recurrent attacks of Paroxysmal Atrial Fibrillation (PAF) since 2004 not responding to Sotalol and or Flecainide, as
well as recurrent episodes of urticarial skin rash, facial angioedema, hot flushes and diarrhoea. He was provided with an emergency
management plan in case of future attacks, and maintained symptoms diary. He then sustained an attack of idiopathic anaphylaxis
which presented with documented hypotension, and raised Mast cell tryptase “37.2” compared to baseline of “3.3”.
Based on Akin’s proposed diagnostic criteria for Mast cell activation Syndrome [1]. Mr L was diagnosed with MCAS and started on
triple therapy of Fexofenadine, Montelukast, and Ranitidine. Other potential causes for the recurrent attacks have been explored
which included: Carcinoid syndrome, Intermittent Porphyria, and phaeochromocytoma, and were all negative. He has had
abdominal USS “normal” and underwent gastroscopy, colonoscopy with biopsies and capsule endoscopy under gastroenterologist
which showed reflux oesophagitis Grade C and suspected small bowel polyps. He was started on Omeprazole for the oesophagitis
and underwent double balloon enteroscopy and biopsies for the small bowel which showed normal histology with no evidence
mast cell aggregates. Skeletal survey were performed which ruled out lytic lesions. From above investigations no evidence to
support systemic Mastocytosis were identified.
He underwent ablation therapy for the atrial fibrillation “pulmonary vein isolation “as he needed to use the adrenaline auto
injectors for idiopathic anaphylactic attacks which accompanied by PAF in few occasions.
Mr L required multiple changes to his medication to control his mast cell activation symptoms, which included Sodium
Cromoglycate, Ketotifen and loratadine, were added to his previous therapy which resulted in good symptoms control. He
successfully managed to reduce the medication regime for MCAS to only Ketotifen and Levocetirizine with no further MCAS
attacks.
This case represents a typical medical journey of MCAS patient, who has been through many specialists for their various systemic
symptoms before getting the diagnosis of MCAS.
We reviewed all presumed MCAS patients who presented to our centre. The presenting symptoms, baseline mast cell tryptase
levels, management and response to treatment with antihistamines and mast cell stabilisers have been reviewed and summarized
in table [1-1]. The challenges faced in achieving a definitive diagnosis in this cohort were mainly the lack of evidence of raised mast
cell tryptase during the attacks. This has been the case for few patients either because they forget to tell the medical staff in ED
department even with our prior advice, or the ED team were not aware of such diagnosis and requirement for confirming the
diagnosis.
In 2010 Akin and colleagues[1] proposed the term MCAS to designate a multisystem syndrome presenting with variable mast cell
activation symptoms documented by increased mast cell mediator levels during attacks, which was distinct from clonal and IgE-
mediated disorders. In our patient cohort, there were no suggestions of clonal or IgE mediated disorders. Although all patients
have had episodic symptoms consistent with mast cell activation, and have shown response to mast cell mediator therapy. It’s not
been possible to document rise in mast cell tryptase level in all patients. Thus the term” Presumed MCAS” has been used. Although
many patients have presented with urticarial skin rash; their overall presentation is quite different from common clinical entity of
chronic spontaneous urticaria.
Conclusion
Mast cell activation syndrome is a differential diagnosis to be considered in patients presented with various clinical symptoms
affecting multiple systems, who do not entirely fit the clinical criteria of chronic urticaria or idiopathic anaphylaxis.
We have considered MCAS as the most likely diagnosis in 11 of our patients who presented with multisystem mast cell activation
symptoms that characterized by remarkable response to mast cell mediator therapy (H1, and H2 antihistamines, leukotrienes,
cromolyn, and ketotifen). The diagnosis could not be confirmed on at least 6 patients due to lack of Mast cell tryptase level during
the attack. Differential diagnoses have been excluded in these patients by working closely with colleagues in gastroenterology,
endocrinology and haematology.
No. Symptoms PMH Investigations: Treatment for MCAS Clinical course
MCT as
baseline
MCT during
an attack
1st time MCAS was
suspected.
1 Pruritis, skin Rash, Lightheaded Diarrhoea,
and Abdominal pain,
Asthma, NIDDM*, High
cholesterol
5.9 Not available** Daily: Fexofenadine.
Emergency plan: C, A, P ***
July 2014, Symptoms for few years
prior to IMM clinic****
Last time seen in clinic February 2015.
2 Pruritis , skin rash, angioedema, flushing,
breathlessness, diarrhoea and Idiopathic
Anaphylaxis
HTN, DM, IHD 12.9 16.4 Daily: Fexofenadine, Loratadine
(stopped recently)
Emergency plan: C, A, P ***
July 2011, Symptoms for few years
prior to IMM clinic
Last time seen in clinic May 2015.
3 Diarrhoea, Flushing, and Abdominal pain. IDDM 3.8 12.8 Daily: Fexofenadine.
Emergency plan: C, A, P ***
March 2010, symptoms for 10 years
prior to IMM clinic.
Last time seen in clinic April 2014.
4 Idiopathic anaphylaxis, angioedema,
urticarial,tachyarrhythmia and diarrhoea
Systemic
Hypertension, Gout,
paroxysmal Atrial
fibrillation.
2.9 37.2 Daily: Ketotifen and
Levocetirizine.
Multiple medications were
changed during the clinical course
of his illness.
Emergency plan: C, A, P ***
May 2011, symptoms for 6 years prior
to IMM clinic.
Last time seen in clinic December
2014.
5 Wheezes, Urticarial rash, angioedema and hyperthyroidism 17.2 – 23.3 Persistently
elevated
Daily: Fexofenadine.
Emergency plan: C, A, P ***
April 2011, symptoms for 18 months
prior to IMM clinic.
Last time seen in clinic May 2015
6 idiopathic anaphylaxis , Diarrhoea,
abdominal pain, and urticarial rash
none 4.6 Not available Daily: Loratadine “stopped
recently”
Emergency plan: C, A, P ***
April 2012- October 2013
Last time seen in clinic October 2013
7 Diarrhoea, Vomiting, flushing and urticarial
rash.
Asthma, DM, allergic
rhinits
7.1 8.2 Daily: Fexofenadine.
Emergency plan: C, A, P ***
January 2011
Last time seen in clinic July 2014
8 hot flushes, Sweats , urticarial rash and
angioedema
Epilepsy, Asthma 2.3 Not available Daily: Fexofenadine, Loratadine,
Ranitidine “stopped”,
Hydroxyzine “stopped”
Emergency plan: C, A, P ***
July 2013
Last time seen in clinic July 2015.
9 Diarrhoea, abdominal pain, urticarial rash Epilepsy 3.8 (not available) Daily: Loratadine (stopped)
Emergency plan: C, A, P ***
November 2014 symptoms for 10
years prior to IMM clinic.
Last time seen in clinic May 2015.
10 Diarrhoea, Pruritis, urticarial rash HTN, DM, GORD 3.7 (not available) Daily: Fexofenadine.
Emergency plan: C, A, P ***
February 2015
Last time seen in clinic May 2015.
11 Urticarial rash, light-headedness,
palpitations,
Abdominal colic
Migraine 2.3 (not available) Daily: Cetirizine, Fexofenadine,
Prednisolone (reducing course)
Emergency plan: C, P *** no
adrenaline been prescribed
August 2015
Last time seen in clinic August 2015.
*NIDDM: Non-insulin dependent Diabetes Mellitus. ** Not available: No sample taken during acute attack. *** Emergency management
plan: C, A, P “Chlorpheniramine, AAI (e.g EpiPen) and Prednisolone. **** IMM clinic: immunology clinic, *****5HIAA: 5-Hydroxyindole-
acetic acid.
References
[1] Akin C, Valent P, Metcalfe DD. Mast cell activation syndrome: proposed diagnostic criteria. J Allergy Clinical Immunology 2010
[2] Akin C, Mast Cell Activation Syndromes Presenting as Anaphylaxis, Immunology & Allergy Clinics of North America, April 2015](https://image.slidesharecdn.com/050a9656-8626-4156-a70f-040a004b0aec-160114172918/85/mcas-poster-for-printing-1-320.jpg)
