Inc. Chronic Fatigue Syndromes – CFS, ME, FM
‘… post-viral fatigue is not, I think we can all now agree, a psychological problem. It is rather an under researched complication of viral illness with massive overlaps with dysautonomia and MCAS. Dr JM Blair Consultant Physician https://www.bmj.com/content/371/bmj.m3981/rr-0
This document is not an extensive review of the science of Long Covid which is now quite extensive. This is a discussion into what I consider is currently behind post-Covid-19 syndrome (the correct term for Long Covid), chronic fatigue syndromes (CFS) and a condition called Mast Cell Activation Syndrome (MCAS).
Currently defined stages of Covid-19 are:
- Acute COVID-19: signs and symptoms of COVID-19 for up to 4 weeks.
- Prolonged symptomatic COVID-19: signs and symptoms of COVID-19 from 4 to 12 weeks.
- ‘Long covid’ – Post-COVID-19 syndrome: signs and symptoms that develop during or after an infection consistent with COVID-19, that continue for more than 12 weeks and are not explained by an alternative diagnosis.
https://www.nice.org.uk/guidance/ng188 (Updated Nov 2021)
SARS CoV-2 being a virus means, by definition, that post-Covid-19 syndrome is a post-viral fatigue syndrome. It is fair, therefore, to conclude that whatever treatments that are available or might emerge for Long Covid may overlap with therapeutic options for those with CFS.
In straightforward terms, Post-Covid-19 syndrome is theorised to occur for 4 reasons:
- The virus persists within an individual
- The virus causes damage to cellular function possibly affecting mitochondria.
- The virus triggers MCAS
- Those with MCAS have their condition exacerbated
Mast Cell Activation Syndrome (MCAS) occurs when mast cells in your body’s defence cells release an excess of immune compounds called mediators that are geared to activating the immune system. These include histamine, cytokines, interleukins, and number up to 1000 different kinds. These also activate certain detoxification processes.
These mediators cause inflammation which, put simply, is the dilation of blood vessels leading to increased availability of oxygen, activating clotting factors, upregulating the myriad of defensive white blood cells, and enhancing production of defence compounds such as immunoglobulins (aka antibodies).
The increase in blood flow is the cause of the symptoms associated with inflammation such as redness, heat and swelling, sweating and the mediators also irritate the nerves causing pain.
Overall, this is the process of healing. When inflammation is minor it is asymptomatic, and we generally do not know anything about it. When inflammation passes a certain threshold we start to feel unwell and if the reaction is overly aggressive we can become dangerously ill as the immune system damages healthy tissue. This is case with the ‘cytokine storm’ that commonly is the main cause of hospitalisation of those with Covid-19.
Mast cells are perhaps the most important ‘sentinel cells’ guarding the membranes and tissues and recognising invading organisms and toxins. Through the release of chemical messengers mast cells communicate with other white blood cells to initiate immune responses and are critical contributors to effective immunity.
Mast cells are mostly associated with histamine release, just one of the 1000+ mediators associated not only with allergy but immune defence as a whole.
The most complained of symptoms of allergy are:
- skin: itching, flushing, hives, sweating
- eyes: itching, watering
- nose: itching, running, sneezing
- mouth and throat: itching, swelling of your lips, tongueand your throat. If severe enough this can cause air passage obstruction and anaphylaxis.
Less recognised symptoms include:
- lungs: trouble breathing, wheezing
- heart and blood vessels: low blood pressure, rapid heart rate, clotting
- stomach and intestines: cramping, diarrhoea/constipation, nausea, abdominal pain (aka ‘IBS’)
- nervous system: headache, dizziness, confusion, extreme tiredness
The action of mast cells when confronted with viruses can have both detrimental and positive impacts depending on the level of activation they create and can create any of the issues above. We of course recognise all and any of these symptoms as part of CFS.
Facts surrounding Mast Cell Activation Syndrome (MCAS)
The education given to doctors to date only correlates MCAS with severe reactions. Recently, however, MCAS is being considered as being a spectrum of disorders ranging from mild, such as hay-fever, through to the more severe anaphylactic -like responses.
https://pubmed.ncbi.nlm.nih.gov/24784142/ Furthermore, this published paper states that there is ‘…increasing appreciation that MCAS is prevalent in up to 17% of the general population’…https://www.degruyter.com/document/doi/10.1515/dx-2020-0005/html
Recently observation by UK physician, Dr Tina Peers has recognised that “Approximately 20% of people with HIT [Histamine Intolerance] also have MCAS.
https://www.drtinapeers.com/introduction-to-histamine-intolerance
Although considered a possibility for over a decade, only recently, due to research into Long Covid, has MCAS been researched as an association with post-viral issues. A researcher, Dr Lawrence Afrin considers:
- The cytokine storm is consistent with MCAS
- Recent statistics suggest that the prevalence of severe Covid-19 is similar to MCAS
- Dysfunctional Mast Cells may be responsible for Long Covid.
https://www.sciencedirect.com/science/article/pii/S1201971220307323
You can, if you wish, read more about MCAS here:
https://www.healthline.com/health/mast-cell-activation-syndrome#symptoms
Therapeutic considerations towards Long Covid and CFS
Correlating the similarity in symptoms between post-viral symptoms and MCAS leads to the possibility that whether an individual is struggling with post-Covid-19 syndrome or symptoms of chronic fatigue syndromes (CFS, ME and FM), treatment for MCAS may help.
It is possible to design a protocol that uses entirely natural extracts and supplements, but the evidence-base behind this is weak and mostly theoretical and obtaining the products difficult. Also, using purely natural extracts is expensive. The majority of doctors educating themselves in MCAS for Long Covid tend to use, therefore, an integrated approach of combining inexpensive over-the-counter (OTC) antihistamines with OTC nutrients and, if required, prescription-only (POM) antihistamines, mast cell stabilisers and anti-inflammatory or anti-viral medication.
My protocol as it stands at this time is as follows (dosages must be supervised by a doctor):
Trial antihistamines from the H1 agonist group and see which is most beneficial for each individual patient.
A. Each one needs to be trialled for 2-3 weeks, with increasing doses as stated below, and if some benefit is noted within that time. continued for four weeks. If no benefit is forthcoming then move on to the next one.
For those who do not have neurological symptoms (such as marked brain fog, concentration issues or, say, paraesthesia, neuralgia et cetera) use the non-sedative H1 agonists:
- Loratadine (OTC)
- Cetirizine (OTC)
- Fexofenadine (POM)
For those who do have neurological symptoms (including depression, anxiety, brain fog etc) then the sedating H1 agonists would be those to try first:
- Chlorphenamine (Piriton- OTC)
- Promethazine (Phenergan, Night Nurse – OTC)
- Hydroxyzine (POM)
At any point where a patient seems to be improved but that improvement is not marked, or effects are negligible, we introduce the H2 agonist antihistamines.
B. Again, these H2 agonists need to be trialled for 2-3 weeks, with doses increased as required, and considering the next one based on benefit.
- Famotidine
- Nizatidine
Both are POM
It can be swift, or take several weeks, to identify which combination of H1 and H2 agonist is of most benefit. If improvement plateaus or remains insufficient then one considers the addition of mast cell stabilisers.
C. Mast cell Stabilizers as with the antihistamines, are prescribed sequentially to identify best option
- Ketotifen
- Cromolyn sodium
- Rupatadine
D. One can then use Leukotriene inhibitors in refractory (non-responders):
- MontelukasT
E. Antidepressanst. For those that are depressed or anxious these can be initiated at any point.
- Fluvoxamine (This seems to be the first choice as it ‘sedates’ H1 receptors in the brain (and can be considered in those with neurological symptoms).
- Amitriptyline & Nortriptyline can be considered.
F. These naturopathic supplements alone or alongside conventional treatments can be uses as they have antihistamine, mast cell stabilising effects or influence the immune and inflammatory systems in alternative ways
- Alpha lipoic acid 500 mg 2 x daily
- Quercetin initially 900 mg 2 x daily bd dropping with improvement to 300 mg bd.
- N-acetyl cysteine 500 mgs 2 x daily
- Probiotics (low histamine form) – BioKult is such a brand
- Diamine Oxidase – enzymes that break down histamine in food. (An inexpensive brand is available form Dispensary). One with each meal but as quite expensive can be given as one with any meal containing high histamine food.
- Multi-nutrient or individual supplements providing: Vitamins C 2000mgs 2 x daily; Vitamin D 4000iu-5000iu each day (some authorities suggest 10,000iu daily in severe cases); Zinc 30-40 mgs taken at night but take some copper if used for longer than 1 month
Boswellia, Butterbur & Bromelain are natural compounds that act as H3 blockers and can be used simultaneously to H1 & H2.
Diet
Following an antihistamine diet is not easy. This is an important life-change for those who know they have histamine issues (sufferers of hayfever, allergic asthma, eczema (perhaps) and allergic responses to house dust mites, pets et cetera).
Therefore I suggest Intermittent Fasting where by one eats within a 11 hour gap, fasting for 13 hours, and incrementally increases the gap until meals are eaten within 8 hour and fasting over 16 hours
https://covid19criticalcare.com/?s=fasting&post_type%5B%5D=any&search_limit_to_post_titles=0&fs=1
The use of Diamine oxidase supplements (DAO) when eating foods with high histamine can certainly help.
You can meet with a nutritionist for full guidance and the design of a suitable diet.
Investigations
Tests and investigations should only be undertaken if they are likely to alter diagnosis or therapeutic approach.
Tests that are available are not particularly specific and the markers degrade quickly so accuracy is not assured and may be found raised regardless of MCAS. The only test I currently use looks at levels of histamine and also identifies levels of Diamine oxidase (DAO) which we make to break down histamine. If low, I recommend supplementation of this.
Low levels of DAO may be due to a genetic variation or inflammatory bowel issues so this is also tested. The sample also tests for compounds called Zonulin & LPS associated with bowel inflammation and increased intestinal permeability (the leaky gut syndrome). The investigation costs £475 inclusive of my written report. Here is an example report:
Those who choose to afford the test may have their program altered by the results but a trial on the therapeutic approach is a perfectly acceptable process to start with.