Experiencing a ‘Mystery’ Flare? Here Are 5 Possible Causes

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Key Points:

  • Sickness, stress, allergies and hormonal changes can trigger inflammation
  • These factors can be asymptomatic (do not display any other obvious symptoms) as in the case of COVID-19 for 40.5% of victims
  • One (or more) could combine to trigger ‘mystery’ autoimmune disease flares

A few days before writing this article someone I know started an extended fast (water only, no food) to kick an autoimmune disease flare…

But it just wasn’t working.

She was way into the fast and yet nothing. No relief.

It seemed so unfair. I had done two extended fasts previously and the results, for me, were so profound it almost felt like a miracle.

My flare was gone, completely, both times. So I was devastated to hear this. I really wanted her to succeed.

Then something happened. I went into flare the very next day.

I had just got back from a holiday. On my return I felt ok for the first couple of days but was achy. I put this down to everything but my autoimmune disease. I blamed an uncomfortable flight, lack of sleep, stress back home, starting up yoga for the first time in a week…

And then on the third day, BANG! Big flare.

Flare for AS

I woke up unable to walk, with huge of pain in my right sacroiliac joint. It was brutal and unrelenting. No more sleep from now on, just 10 – 15 minutes snatches.

But I couldn’t understand it…

My super strict (and crazily effective) diet was intact. I hadn’t cheated. I had done yoga, everyday since my return. I had even fasted, after I had started feeling achy, and still nothing.

Fasting had worked quickly and emphatically the first two times I tried it. It was so effective, in fact, that I felt like I’d had a whole body transfusion. Total pain relief, more energy.

This time I fasted for 72 hours, my longest yet, and nothing. Just crazy dreams, hunger and disappointment.

So this article is an attempt to make sense of what could be happening. An exploration of ‘mystery flares’: how we can look at them and what proactive steps we can take.

First we’ll look at:

1) Possible causes of ‘mystery’ flares

2) What to do when the things you try to get out of flare (which normally work) stop working

5 Possible Causes of ‘Mystery’ Flares

Let’s start with the usual mantra.

We are all different.

We have different biologies, different genetics and different microbiomes. We all have different environmental factors at play. So it’s very difficult to say, with any certainty, what is effecting a given person at a given time.

With that said, there are a number of factors which could cause ‘mystery’ flares (flares where we cannot obviously identify the cause or trigger).

They often sit outside of our direct awareness, making them harder to spot, but their impact can be just as devastating.

Let’s run through them:

1. Stress

We can never dismiss stress as a flare trigger.

It is right up there, in terms of importance, with any food or drug you put into your body.

When you’re stressed, your body releases hormones that can weaken the immune system and make it more likely to attack itself. This can worsen symptoms of autoimmune disease or trigger flares.

Both types of stress (physical and emotional) can impact your immune system, even if you might not be consciously be aware of it.

This is so important.

You can’t see stress or touch it. It’s not an ingredient in the food you eat, or a stretch you can do in yoga.

Stress takes many forms and has outsized effect on your immune system behaviour and intestinal barrier function which can lead to a cascade of problems, including autoimmune disease flares.

Stress induced inflammation

What the science says:

Inflammation is at the heart of autoimmune disease and stress causes inflammation.

As this study shows, “through disturbing the balance of immune system, stress induces inflammation.” Specifically it “engenders central microglia and astrocytes, blood vessel, immune system and liver by mainly activating SNS and the HPA axis.”

A further study “highlight(s) the importance of both intestinal barrier defect and stress” and how “Stress is well known to have long-lasting deleterious consequences on the intestinal barrier” for people with autoimmune disease.

What does all this mean?

It suggests that two major factors involved in the development and progression of autoimmune disease are: 1) intestinal barrier defects and 2) stress.

The intestinal barrier, which is essentially the wall of the intestines, plays an important role in preventing harmful substances from the gut entering our bloodstream. When this barrier is compromised, it can lead to or exacerbate autoimmune disease activity.

And we can go further.

Stress could even be one of the primary factors in triggering the onset of autoimmune disease in the first place.

As this study suggests: “the onset of at least 50% of autoimmune disorders has been attributed to “unknown trigger factors” and “Moreover, many retrospective studies found that a high proportion (up to 80%) of patients reported uncommon emotional stress before disease onset.”

In other words, stress is could be not only be a driving force in the onset of ‘mystery flares’ (where diet, stretching, exercise and every other variable has stayed a constant). It could actually, in some cases, lead to the onset of the disease itself.

When looking at “106 464 patients with stress-related disorders… [and] 1 064 640 matched unexposed individuals”, this study found that the “increased risk of autoimmune disease… was 9.1 per 1000 person-years in exposed patients compared with 6.0 and 6.5 per 1000 person-years”.

2. Sickness

When you’re unwell and fighting off an infection it can put a major strain on your immune system.

When this happens it can sometimes cause your immune system to attack healthy tissue, which can worsen symptoms of your autoimmune disease and triggers flares.

The autoimmune disease, on the hand other, may have different ideas and so the symptom free sickness potentially triggers an autoimmune disease flare.

Sickness and autoimmune-disease

What the science says:

Wouldn’t you notice if you were unwell?

Not necessarily. You might present as asymptomatic. That means your body is still fighting, even if you don’t have any of the ‘traditional’ symptoms (whether it’s a runny nose or a headache).

COVID-19 is a great example of this, with “asymptomatic infections among the confirmed population [at] 40.50%”.

In other words nearly half of patients displayed no symptoms! As this study showed in 2021 “COVID-19 [patients] exhibited significantly higher risks of rheumatoid arthritis… ankylosing spondylitis… systemic lupus erythematosus… dermatopolymyositis… systemic sclerosis.” That study had 3,814,479 participants (888,463 cases and 2,926,016 controls).

This study looks into why “Infections and exposure to pathogens or opportunistic organisms are among the environmental factors and may induce the initiation or exacerbation of [autoimmune diseases]”.

It explains that “infections can participate in the activation and later clonal proliferation of autoreactive T and B lymphocytes that are crucial for the development of an [autoimmune disease].” and that “Almost all [autoimmune diseases] have been associated with at least one infection”.

A sickness lasting a week, two weeks or more could explain a mystery flare that just doesn’t seem to clear up, no matter how strict you are with diet or how much you fast or try other inflammation busting strategies.

3. Hormones

Hormones are the chemicals in your body that play a vital role in many different functions, including your immune system.

When your hormone levels change, it can have a dramatic impact on the way your immune system works.

Here are a few examples of the hormones many of us are familiar with:

Estrogen, Progesterone and Testosterone:

These hormones play a major role in immune response. For instance, estrogen has been shown to stimulate immune response, and its levels vary throughout the menstrual cycle.

Some autoimmune diseases, such as lupus and rheumatoid arthritis, tend to be more common in women and can exhibit symptom fluctuations with hormonal changes. This can of course be exacerbated even further during pregnancy.

Pregnancy Ankylosing Spondylitis Hormones


Often known as the “stress hormone,” cortisol is produced by the adrenal glands and is part of the body’s fight-or-flight response. It suppresses the immune system’s inflammatory response, and alterations in cortisol levels can impact autoimmune diseases.

Testosterone, on the other hand, tends to suppress immune response, which might be why men have lower rates of many autoimmune diseases.

Vitamin D:

Technically, vitamin D is a hormone, not a vitamin but it plays a key role in modulating the immune system.

Vitamin D deficiency has been associated with several autoimmune diseases, including multiple sclerosis and rheumatoid arthritis.


Irregularities in insulin production and sensitivity can cause of inflammation in the body, which can worsen autoimmune disease symptoms.

Thyroid Hormones (T3, T4):

These hormones are crucial in regulating metabolism, growth, and development. Autoimmune thyroid diseases, such as Hashimoto’s thyroiditis and Graves’ disease, can cause the immune system to attack the thyroid gland, which the affects the production of these hormones.

What the science says:

As Ronald Wilder notes, “Hormonal factors linked to age, gender, and reproductive status are undoubtedly involved in regulating the onset of numerous autoimmune diseases”.

He goes onto explain that “Rheumatoid arthritis (RA), a disease characterized primarily by cell-mediated joint immunopathology linked to deficient Th2 cytokine production, is also more common in women, but, in contrast to SLE, the highest incidence is at menopause. Pregnancy-associated changes in these diseases, however, provide the most compelling evidence that hormonal factors play a major role in modulating the expression of these diseases.”

This study by Vaishali R. Moulton observes the gender bias (towards females) in autoimmunity. It claims that “Complex interactions of hormones and environmental factors in genetically susceptible individuals lead to deregulation of the immune response, leading to immune-mediated diseases including autoimmune disease.”

In summary, hormones can (when out of balance) make it more likely for your immune system to attack healthy tissue, which can worsen autoimmune disease symptoms.

4. Lack of sleep

When you don’t get enough sleep, your body is not able to repair itself as well, which can lead to inflammation.

Melatonin, known as the “sleep hormone,” regulates sleep patterns.

If you have poor or disrupted sleep it can impact the immune system and exacerbate autoimmune conditions.

What the science says:

When we are sleep deprived there is an increase in “markers of inflammation, such as increases in inflammatory molecules, including cytokines, interleukin-6, and C-reactive protein” as this article from Harvard Health suggests.

It “might alter the body’s stress response system, which could trigger cells in blood vessel walls that activate inflammation.”

A Mount Sinai study claims, “Chronic, insufficient sleep can negatively affect immune cells, which may lead to inflammatory disorders”.

The evidence is overwhelming in this regard. A research paper published in Neurol concludes: “Inconsistent sleep may be an associated feature of inflammatory dysfunction”.

A situation where someone is both stressed and sleep deprived could result in a vicious circle of inflammation which could cause and exacerbate flares.

5. Allergies

Certain environmental factors which we’re all familiar with but may not connect with our immune system (and possible flares) include:

Allergies (seasonal or otherwise)

Air pollution

Changes in weather (such as sudden drops in temperature)


These can all cause inflammation in the body and worsen symptoms.

Combined with other factors, such as stress, they could trigger or prolong a flare.

In Summary

We’ve looked at the some of main causes of inflammation which don’t always come with an obvious signpost or signal.

Such as:

✔️ Allergies, which can be often dismissed as a separate set of symptoms…

✔️ Sleep deprivation, which can creep up on us…

✔️ Stress is the famously invisible force that is responsible for a HUGE array of health issues, including inflammation…

✔️ Asymptomatic illnesses wreak havoc on our immune systems, especially for those of us with an autoimmune disease

There are also other factors that could be at play.

For example physical injuries, while not exactly invisible, can worsen symptoms of autoimmune diseases. So too can nutrient deficiencies, such as Vitamin D, Vitamin B12, selenium and zinc. These can also impact the immune system and potentially trigger an autoimmune flare.

The reality is if you’ve been sticking to a strict diet, have kept clear records and know exactly what you’ve put into your body then food or nutrient deficiencies shouldn’t be an issue. However, we can’t be in control all the time.

It is always possible there was a rogue ingredient in a dish you ate while you were away from home.

Certain foods, such as gluten, dairy, and processed foods, can trigger inflammation, which can play havoc with autoimmune diseases. Alcohol can weaken the immune system and make it more likely for the body to attack itself.

There is a lot to take in there but I think it’s really important to have a broader picture of all of the different things that can trigger our immune system and, for those of us with autoimmune disease, trigger or prolong a flare.

However you are treating your autoimmune disease not knowing what is causing a flare can be incredibly scary.

If you are on medication, such as biologics, you might wonder if your biologic has stopped working or if you need to up your dose.

If you are a following a gut health and dietary protocol you might assume it is something you have eaten but when sticking to the diet or doing a fast still doesn’t work you might panic.

The likelihood is that sometimes it is just out of our hands.

Extreme stress can trigger an autoimmune flare as can an asymptomatic illness, allergy or simply a change in hormones.

These can be hard to detect but once you are aware of these seemingly invisible forces you can start to take action and try to address them.

In the next article we’ll look at what you can do to try and address mystery flares.

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