Understanding ME-CFS and MCAS: A Q&A with Dr. Reddy
Written by Julie Woon, MSJ
Dr. Reddy, an osteopathic physician with personal experience living with Ehlers-Danlos syndrome and long COVID, shares her expertise on chronic fatigue syndrome, mast cell activation syndrome, and their connections to other complex conditions.
What is ME-CFS and why is it much more than just being tired?
Dr. Reddy: ME-CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) is a chronic debilitating multi-system biological illness that affects multiple body systems. The symptoms can fluctuate from mild to severe, and it affects all age groups, including children.
Describing ME-CFS as just being tired is a significant understatement. The fatigue is so debilitating and the exhaustion becomes so severe that people are homebound and bedridden for long periods of time. We don't get relief from rest - ordinary tiredness improves with rest, but in ME-CFS, any small amount of exertion leads to a dramatic and prolonged worsening of symptoms.
Basic activities like brushing your teeth, taking a shower, cooking, or going to get groceries become so difficult or impossible. There's a significant lifestyle change that comes with this condition.
What is post-exertional malaise and why is it so important?
Post-exertional malaise (PEM) is the key difference between having fatigue versus having ME-CFS - it's the cardinal feature. It's a biological explainable phenomenon where there's a marked rapid physical and cognitive fatigability in response to exertion, which could be minimal like simple daily living activities or cognitive mental tasks.
When you do something and exert yourself, within 12 to 48 hours (sometimes up to 96 hours), ME-CFS patients hit what we call a crash or collapse. You feel like you have the flu, you've ran a 10K, you've been up for 24/7, and you have a hangover - all at the same time.
A normal person might recover from exercise within 48 hours, but someone with ME-CFS could take 10 days or weeks to recover from just a brief 10-minute exercise. Each patient has their own threshold, and once they cross that red line, they could be stuck in a crash for days, weeks, or months.
How common is ME-CFS and why is it so underdiagnosed?
ME-CFS affects about 1.3% of the United States - that's almost 3 to 4 million people, and that was pre-pandemic. After COVID-19, the prevalence has skyrocketed. Globally, it was estimated at 67 million people before the pandemic, but now it's probably over 100 million.
The shocking part is that 84% to 90% of people with ME-CFS have yet to be diagnosed. The condition is misdiagnosed because of physicians not being aware and a lack of education. It's considered the most neglected condition in history and the biggest medical scandal of the 21st century because it's been psychologized for decades.
Many medical professionals still don't accept that ME-CFS is a legitimate medical condition, which complicates research and treatment. The symptoms are broad, vary between patients, and overlap with other conditions like autoimmune disorders, sleep disorders, and thyroid issues.
What is Mast Cell Activation Syndrome (MCAS)?
MCAS is a syndrome where mast cells - immune cells that patrol our body and are found everywhere, including connective tissue and our neurological system - become overactive. When activated, they release excessive amounts of inflammatory chemicals. According to Dr. Afrin, a leading expert, there are over 1,200 different mediators that can be released.
Since mast cells are present throughout multiple body systems, MCAS affects every system and leads to a very wide, unpredictable range of symptoms that can wax and wane depending on triggers. It's completely independent of traditional allergic reactions and much more complex to manage.
What are common triggers for MCAS that people might not recognize?
The triggers are incredibly broad and can include:
Environmental: Sudden temperature changes, heat, cold, humidity, sunlight, smoke, fragrances, perfumes, cleaning products, dust mites, pollen, pet dander
Physical: Exercise, certain clothing, infections (COVID is a big one), vaccines, spider bites, mosquito bites
Dietary: High-histamine foods, alcohol with sulfites, food additives like MSG
Medical: New medications (often delayed reactions 24-48 hours later), contrast dyes for imaging, anesthetics
Hormonal: Menstrual cycle changes, ovulation
Other: Lack of sleep, excipients (inactive substances in foods and medications)
Many patients develop new food allergies to things they were perfectly fine with before. The challenge is that sometimes you have multiple triggers at once, and sometimes we can't identify the trigger at all.
How are these conditions connected to Ehlers-Danlos Syndrome?
There's a striking trifecta where patients have EDS, POTS (postural orthostatic tachycardia syndrome), and mast cell activation syndrome. Those with EDS and POTS have 32 times higher odds of developing mast cell activation syndrome.
The abnormal collagen production in EDS affects the immune system, triggering immune responses that activate mast cells. Blood vessels are weaker, leading to dysautonomia. About 10-20% of EDS patients also develop ME-CFS. There's actually a pentad where patients have EDS, dysautonomia, mast cell activation, plus autoimmune components and GI dysfunction.
What's the connection between COVID-19 and these conditions?
COVID-19 has significantly affected research and awareness because there's a substantial overlap between long COVID and ME-CFS. Some argue they're the same condition. The pandemic triggered unprecedented investment in studying these conditions because of this overlap.
Long COVID has over 200 documented symptoms, and patients often develop dysautonomia, POTS, mast cell activation, or ME-CFS. Some studies show about 15 times higher incidence of ME-CFS after getting COVID. With an estimated 400 million people worldwide with long COVID, we're probably looking at millions with ME-CFS or dysautonomia.
How do you diagnose these conditions when standard tests often come back normal?
For ME-CFS, there's no single test. I do a very thorough workup ruling everything out - CBC, metabolic panel, iron studies, thyroid, autoimmune panels, infection panels. I use the 2015 Institute of Medicine diagnostic criteria, which requires five core things: substantial reduction in functioning, persistent fatigue for six months, post-exertional malaise, unrefreshed sleep, and either cognitive impairment or orthostatic intolerance.
For MCAS, I use consensus criteria looking at symptoms and treatment response rather than relying solely on blood tests, because the standard tests are often normal. I always order a tryptase level - not because I expect it to be high, but to rule out mastocytosis, a more serious condition.
Red flags I look for include: new sensitivities and allergies, anaphylactic reactions to things that never caused problems before, orthostatic intolerance, sudden inability to tolerate heat, and patients seeing multiple specialists without anyone connecting the dots.
What treatment options are available?
There are no FDA-approved treatments for ME-CFS, but there's a lot of research happening. I start by treating dysautonomia/POTS with medications like midodrine and corlanor, plus increasing fluid and salt intake and using compression garments.
For ME-CFS, I use medications off-label like pyridostigmine (Mestinon), oxygen therapy, and I'm a huge advocate for hyperbaric oxygen therapy. I also use dextromethorphan for severe post-exertional malaise crashes. Some patients benefit from antivirals or even off-label HIV medications - I'm currently on an HIV medication for my ME-CFS.
For MCAS, I combine multiple antihistamines (up to four times daily), H2 blockers like famotidine, leukotriene inhibitors like Singulair, and mast cell stabilizers like quercetin. Severe cases may need IV Ativan, steroids, or monthly injections of Xolair. Many patients need EpiPens and must modify their entire lifestyle - soaps, shampoos, detergents, foods.
What advice do you give to newly diagnosed patients?
The biggest thing is to advocate for yourself. You are the expert of your body. Don't hesitate to speak up and ask questions during medical visits. Join support groups and patient organizations for connections, resources, and hope, but seek information from reputable sources.
Educate those around you - friends, family, coworkers - so they know what to watch for and can help in emergencies. Build a support system; you don't need an army, just one or two reliable people. Wear a medical bracelet for emergencies.
For those developing ME-CFS, please learn to manage your energy window. Don't over-exert because it can lead to permanent disability. Don't compare your pre-illness activity level to now, and don't compare yourself to others. You're on your own path.
Most importantly, remind yourself this isn't your fault. Be patient and gentle with yourself because you're adapting to living with new conditions that are unknown to you.
Want to hear more from Dr. Reddy? Check out the YMyHealth podcast!