IACFS/ME Conference:  Dr Larry Afrin on an overview of Mast Cell Activation Disease

October 4, 2021

The 2nd Virtual Scientific Conference for the International Association for Chronic Fatigue Syndrome/ Myalgia Encephalomyelitis was held on the 19th – 21st August 2021 (streamed on zoom). The conference promoted unpublished data and included both clinicians and biomedical researchers. 

The talks were grouped into different sections, including the longer 45 minute talks in the Professional Workshops and shorter talks covering topics of infectious diseases, immunology and clinical cases. 

We have chosen a selection of the talks which will hopefully be of interest to you, which are listed below. Here we report on our fourth talk in this series with a talk from Dr Larry Afrin who’s presentation focused on an overview of Mast Cell Activation Disease, with his presentation titled “Mast Cell Activation Disease: Current Concepts”. The further talks we will cover are shown below and these will be available in one report by the end of October 2021. 

Due to the format of the conference and the focus on unpublished data, no direct recordings or pictures are available freely as this may jeopardise publication. The full conference programme can be found on the IACFS/ME website here, where recorded presentations may be purchased. 

4. Mast Cell Activation Disease: Current Concepts  

Larry Afrin, MD  
AIM Center for Personalized Medicine; Purchase, NY, USA 

Dr Larry Afrin is a senior consultant in haematology (specialist area in diagnosis and management of problems with blood cells) and oncology (dealing with the prevention, diagnosis, and treatment of cancer). His talk provided an outline on what is currently known about mast cell activation disease (MCAS). His talk started with a disclaimer that there is currently no FDA approved treatments, and all treatment options that were discussed in the presentation are experts opinion. 

Dr Afrin started by introducing some case examples of patients incorrectly diagnosed, as diagnosis is extremely difficult and the disease has many different presentations for the same disease. A brief history of the disease was given, starting in 1869 with many different genetic and environmental factors which interplay in the disease. The biology of MCAS is extremely complex with many different systems involved, many different protein coding genes are involved, but KIT (KIT Proto-Oncogene, Receptor Tyrosine Kinase, a cytokine receptor) is often seen as the most important (Okayama and Kawakami, 2006). There are a range of triggers that can be involved, such as: IgE receptors, physical stimuli, histamine and cannabionoids etc. Mast cells produce more than 100 mediators (compounds that are either locally released or carried in blood or tissue fluids and that may participate in initiating, perpetuating, or aggravating a pathological process). The prevalence of MCAS is increasing (1-17% of the population). Importantly there is increasing evidence for the role of critical mast cell involvement in many chronic multiple system inflammatory diseases, such as: IBS, fibromyalgia, and asthma. Currently we do not know if one form of mast cell disease is involved in these conditions, but Dr Afrin feels it is likely that there is. The biology we know behind MCAS is evolving, with the mutations involved being acquired. 

Dr Afrin then went through the presentation of MCAS- it is important to note that this disease presents in many different ways as mast cells produce and reduce many mediators, with these mediators having many different effects on the body. MCAS is a chronic multiple system disease and all patients show some signs of inflammation which can be across many different body systems (eyes, nodes, skin, joints, GI, CNS). There may or may not be an allergic reaction phenomena present (anaphylaxis) and growth or development of tissue. MCAS has an early onset most likely in childhood and it is likely to be present for decades without being noticed as symptoms are up and down for years at a time, until a physical or mental stressor activates the disease (but not always). Tryptase is often a good marker for MCAS being present (but doesn’t show activation) 

There are a few studies which suggest an association between MCAS and CFS/ME (Afrin et al., 2017), however, association does not mean causation and more research studies are needed. Dr Afrin suggested possible mediators that may be involved in MCAS, such as interleukins, prostaglandins and leukotrienes. Current research methods looking at the whole genome are unlikely to answer these questions as mast cells only make up 0.02%. Therefore, research will need to look into sequencing the mast cells only. The opportunities for future research into MCAS are huge, such as improving diagnosis, looking at etiology and therapy options. 

Diagnosing MCAS is difficult, a complete history needs to be taken, inflammation examined (it is likely that many different systems being inflamed are linked) but also consider other autoinflammatory syndromes. Once suspicion is likely initial testing would look at tryptase before looking into specific mast cell testing. Potential treatment options look at avoiding triggers as well as medication that can inhibit mediators or their release, or block mediators. Non-pharmacological treatment can also be helpful. With management and treatment, prognosis is good and a normal life can be had. 

Katrina Pears, Research Correspondent, ME Association  


Professional Workshops

Alison Bested, MD, FRCPC, ABOIM
Chair, Integrative Medicine, Associate Professor
Nova Southeastern University; Weston, FL, USA  

Blair Grubb, MD
University of Toledo; Toledo, OH, USA

Carmen Scheibenbogen, MD  
Institute for Medical Immunology, Charité University Medicine (Germany)  

Larry Afrin, MD
AIM Center for Personalized Medicine; Purchase, NY, USA    


Avindra Nath, MD
US National Institutes of Health, NINDS; Bethesda, MD, USA    

Infectious Disease

Leonard Jason, PhD
DePaul University; Chicago, Illinois, USA  

Provocation Studies 1


Neurology/ Epidemiology

Clinical cases

Hector Bonilla, MD
Stanford University; Stanford, CA, USA  

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