Throughout my career, whenever I would conceptualize Attention Deficit Hyperactivity Disorder (ADHD), I would associate it with possible depression, anxiety, autism or substance abuse. I never paid much attention to any association with a physical health condition but that is changing in recent years with new research. We now know there is a strong association between ADHD and many chronic conditions such as asthma, psoriasis, Crohn’s Disease, ulcerative colitis, and other autoimmune conditions especially in females. For example, people with asthma are 45% more likely to have ADHD. ADHD is diagnosed based upon a cluster of symptoms of inattentiveness, hyperactivity, impulsivity and mood instability. However, those ADHD symptoms tell us nothing about the cause of ADHD which is still believed to be due to genetic and environmental risk factors. What we thought were seemingly unrelated physical symptoms in the body may turn to be an important factor in what is actually driving ADHD symptoms. In this article, I will introduce some basic ideas about the interconnection between our immune system, chronic conditions and neuropsychiatry and what that means for treatment of this population going forward.
Without getting into all the details of how the immune system works, I would like to focus on mast cells which are white blood cells located in your connective tissues, including your skin, intestines, lungs, blood vessels, and lymph vessels—all places that interface with the environment. Even though we’ve known about mast cells for 150 years, we have only figured out the details of what they actually do in the past 20 years. Mast cells are the first responders to bodily threats and have several functions: 1) they release chemical mediators such as histamine, tryptase, and other inflammatory mediators; when your body encounters an infection, allergen, toxin, or another trigger, mast cells warn your immune system about the danger, 2) promote inflammation, 3) play roles in tissue repair, blood vessel formation, and immune regulation. This works well for most of us but we now believe 17% of the US population has mast cells that misbehave by overreacting in response to non-threatening stimuli. In this case, they continue to release their mediators even if there is no real danger. For example, if mast cells release an overabundance of histamine, that would lower blood pressure which could then worsen brain fog. This overreactive immune response is called Mast Cell Activation Syndrome (MCAS) and can lead to widespread chronic symptoms, and health issues that affect many organ systems: gastrointestinal, skin rashes, anaphylaxis, fatigue, headaches, pain, joint hypermobility, dysautonomia (like tachycardia and lightheadedness), and the brain. Inflammation of the brain is called neuroinflammation (“a brain on fire”) and can give rise to the neuropsychiatric symptoms of MCAS: fatigue, headache, heightened sensitivity, memory difficulties, anxiety, sleep disturbance, and concentration difficulties; hence, you can see the overlap with ADHD symptoms.
What should I look for to see if I have MCAS?
In general, MCAS is usually diagnosed by allergists and self-diagnosis is not encouraged. The diagnostic criteria include at least two organ systems effected in the body such that the problems suffered by an MCAS patient can be extremely different from the problems suffered by another MCAS patient. Below are some common physical symptoms which can be experienced by MCAS patients and you may also want to access the MCAS questionnaire for a more complete list:
Fatigue, malaise, suddenly feeling hot or cold, inappropriate sweats
Skin rashes, redness, flushing, itching, hives, redness in the track of a scratch (“dermatographism”)
Respiratory: painful discomfort, shortness of breath, cough, exercise induced asthma
Cardiac: palpitations, lightheadedness, unexplained/unexpected hypertension and/or hypotension
Gastrointestinal: pain, reflux, bloating, unprovoked changes in appetite and/or weight, nausea constipation, diarrhea
Joint pain and redness
Neurologic: headache, episodic lightheadedness/dizziness/vertigo, tingling/numbness, sleep disruptions
Endocrine: painful or irregular periods, thyroid abnormalities, rapidly alternating blood sugar levels
What is the treatment for MCAS?
The focus of treatment for MCAS is to lower histamine levels in the body and stabilize mast cells from misbehaving. The recommendation is to do one intervention at a time with careful evaluation for 1-2 weeks before moving to the next step:
The first step is to identify one’s own personal triggers in the environment such as: infections, physical trauma to the body, extreme temperatures, stress, ingredients in health and beauty products, caffeine, alcohol, secondhand smoke, sensitivity to inactive pill ingredients or change in hormonal milieu.
Adoption of a short-term low histamine diet to avoid foods that are high in histamine which usually means avoiding dairy, eggs, grains (except rice and quinoa), most seasonings and to make sure food is not sitting out too long at room temperature. The diet may also include avoiding sulfur, oxalates, salicylates or food additives if they are problematic. The low histamine diet may also be supplemented with the enzyme diamine oxidase (DAO) 20 minutes before each meal.
A trial of histamine blockers one at a time: an H1 antihistamine such as loratadine, cetirizine, fexofenadine (taken twice daily) and then a trial of an H2 antihistamine with famotidine as the best option at 40 mg twice daily.
The introduction, one-by-one of supplements and medications that stabilize mast cells: Chamomile tea, vitamin C, quercetin, cromolyn, and ketotifen. Benzodiazepines have also been found to stabilize mast cells.
Just to be clear, I am not an allergist or an expert in treating MCAS; the above guidelines have been developed by allergists.* My intention in writing this article and discussing with patients is to educate and become aware of this ADHD-inflammation connection. Primary care doctors are fairly busy nowadays with time limitations so this may not be something they can fully address with patients. Ultimately, MCAS should be diagnosed by an allergist but at the very least under the supervision of a practitioner familiar with MCAS although the first couple steps highlighted above can usually be done on one’s own. The other factor is that research in this field is fairly new and it may take some time to clearly establish the standard of care for addressing MCAS. Going forward, my hope is that if MCAS is properly addressed, there will also be mental health benefits as well with further improvement in ADHD and other neuropsychiatric symptoms.
*Castells, Mariana and Joseph Butterfield. The Journal of Allergy and Clinical Immunology: In Practice. 2019; 7(4): 1097-1106