Unexplained Chronic Fatigue: When to Consider Mould and CIRS

Most constant tiredness has a common cause, and your doctor checks those first. The usual suspects are sleep disorders such as sleep apnoea, depression and stress, anaemia, an underactive thyroid, diabetes, medicines and recent infections [1][2].

If the fatigue lasts for months, limits your daily life and gets worse after effort, it may be chronic fatigue syndrome (ME/CFS). There is no single test for ME/CFS. Doctors diagnose it from a set pattern of symptoms [3][4].

Mould and CIRS (Chronic Inflammatory Response Syndrome) are worth considering when two things come together. Your fatigue comes with symptoms in many parts of the body, and it seems tied to a particular home, school or workplace.

This article follows the order a doctor would usually take:

Why am I always tired when my tests are normal?

Tiredness is one of the most common reasons people see a doctor. It is the main or a side reason for 10–20% of all visits to a general practitioner [1]. That is between one in ten and one in five visits.

In most cases, doctors find no serious physical disease. A systematic review of primary care studies looked at people who saw a doctor because of tiredness. It found [2]:

• anaemia in about 3 in 100
• cancer in about 6 in 1,000 (0.6%)
• any serious physical disease in about 4 in 100
• depression in nearly 1 in 5 (about 18.5%)

In studies with a comparison group, the rates of physical disease were the same as in patients who were not tired. Depression, by contrast, was clearly more common among the tired patients [2].

So “your tests are normal” does not mean “nothing is wrong”. It usually means the most common dangerous causes have been ruled out. The next question is what else fits your symptoms.

What are the most common causes of constant fatigue?

A review based on the German general practice guideline on fatigue names three causes as the most common [1]:

• sleep disorders, including sleep-related breathing disorders such as sleep apnoea
• depression
• too much psychosocial stress (pressure from work, relationships or life situations)

Well studied The table lists the causes doctors usually think of first.

Possible cause	What is known	How it is usually checked
Sleep apnoea and other sleep disorders	Among the most common causes. Clues include loud snoring, breathing pauses that others notice and falling asleep at the wheel [1]	Screening questionnaire and, if needed, a sleep study
Depression and long-term stress	Depression is found in about 18.5% of people who see a doctor for tiredness [2]	Talking with the doctor, questionnaires
Anaemia or iron deficiency	Anaemia is found in about 3% [2]	Full blood count; ferritin (iron stores) in women before menopause [1]
Underactive thyroid	Can cause fatigue. But thyroid hormone does not relieve fatigue in mild (subclinical) hypothyroidism [1]	TSH blood test [1]
Diabetes	One of the physical diseases that can cause fatigue [1]	Blood glucose or HbA1c (long-term blood sugar) [1][3]
Coeliac disease	Can cause fatigue [1]	Coeliac antibody test [3]
Medicines and substances	E.g. antihistamines, benzodiazepines, antidepressants, antipsychotics, blood pressure medicines and opioids; also alcohol or drug use [1]	Going through all your medicines with your doctor
Infections	E.g. glandular fever (mononucleosis) [1]	History, examination, blood tests
Cancer	Rare: 0.6% of people who see a doctor for tiredness [2]	Further tests only if there are other warning signs

Which blood tests are usually done?

According to the same review, the basic lab tests for fatigue are [1]:

• blood glucose
• a full blood count
• ESR or CRP (markers of inflammation)
• liver enzymes
• TSH (thyroid)
• ferritin, for women before menopause

Further tests are needed only if your history or examination points to something specific. If the cause stays unclear, the authors recommend a check-up every four to six weeks rather than ever more tests [1].

When ME/CFS is suspected, the UK NICE guideline lists a broader set. It includes a urine test, kidney and liver function, calcium and phosphate, HbA1c, coeliac screening and creatine kinase (a muscle enzyme) [3].

Is there a test for chronic fatigue syndrome (ME/CFS)?

No. There is currently no blood test, scan or other test that can diagnose ME/CFS. Doctors recognise it from the symptoms and examination alone [3]. Tests are still important. Their job is to find or rule out other conditions that look similar.

The US Institute of Medicine (now the National Academy of Medicine) published diagnostic criteria in 2015. They require all three of these [4]:

1. Much less ability to function. You can do far less work, study, social life or self-care than before you fell ill. This has lasted more than six months. The fatigue is new, is not caused by ongoing overexertion and is not clearly relieved by rest.
2. Post-exertional malaise (PEM). Your symptoms get worse after physical or mental effort.
3. Unrefreshing sleep. You do not wake up rested.

You must also have either problems with thinking and memory or orthostatic intolerance (symptoms when you stand or sit upright). The symptoms should be there at least half of the time and be at least moderate [4].

The UK NICE guideline from 2021 uses similar core symptoms. It tells doctors to suspect ME/CFS when the symptoms have lasted at least six weeks in adults, and to confirm the diagnosis after three months [3].

PEM is what most clearly separates ME/CFS from ordinary tiredness [3]:

• it often starts hours or days after the effort
• it is out of proportion to what you did
• it can take days or weeks to settle

How common is ME/CFS?

ME/CFS is not common among tired patients. Fewer than 2 in 100 people who see a doctor about fatigue have it [1].

Expert view At the same time, it is underdiagnosed. A group of 21 ME/CFS clinicians estimated that up to 91% of patients in the United States, about 9 in 10, have never been diagnosed [5].

If you recognise PEM in yourself, ask your doctor specifically about ME/CFS. How it differs from CIRS is explained in ME/CFS vs CIRS.

Can mould and water damage cause fatigue?

Several population studies link damp and mouldy buildings with fatigue and poor sleep. However, fatigue is not the best-established health effect of damp buildings.

• Sweden: In a nationwide survey of 5,775 adults in apartment buildings, dampness, mould and mould odour were risk factors for weekly symptoms such as fatigue and headache [6].
• Five Nordic and Baltic countries: 11,318 adults from Iceland, Norway, Sweden, Denmark and Estonia were followed for ten years. Dampness and mould at home or at work raised the risk of developing insomnia symptoms and too much daytime sleepiness [7]. Poor sleep is itself one of the most common causes of fatigue.
• Finland: One small study Among nurses and midwives in a moisture-damaged hospital building, 77% reported fatigue, about 3 in 4. In an unexposed comparison group the figure was 24%, about 1 in 4 [8]. This small questionnaire study shows a link, not proof of cause.

The World Health Organization’s guidelines on dampness and mould say the best-documented effects are breathing symptoms, allergies, asthma and immune system disturbances [9].

The German fatigue review notes that sick building syndrome and other environmental causes have been discussed as causes of fatigue. It adds that this has nearly always been without enough evidence [1].

In other words, mould is a possible explanation for your tiredness, not a proven one. Consider it alongside the common causes, not instead of them.

What is CIRS, and how does it relate to fatigue?

CIRS is an illness described by Dr Ritchie Shoemaker. In CIRS, the body’s innate immune system (its fast, first line of defence) keeps reacting after exposure to biotoxins [10]. Biotoxins are natural poisons made by living things such as moulds and bacteria. The exposure is most often the indoor air of a water-damaged building.

Fatigue is one of the most common CIRS symptoms, but rarely the only one. The CIRS consensus statement uses 37 symptoms grouped into 13 clusters [10]. They include:

• fatigue
• memory and concentration problems
• muscle and joint pain
• headache
• breathing and digestive symptoms
• sensitivity to light
• problems regulating body temperature
• numbness or tingling

In Shoemaker’s 2006 study of people who fell ill in water-damaged buildings, the participants had on average 23 of these 37 symptoms, well over half [11].

The defining feature is the link to a building. In the same study, symptoms fell sharply with treatment. All participants relapsed after only three days back in the water-damaged building [11].

Preliminary research These findings come from Shoemaker’s own research group and a small number of patients. Independent studies that repeat them are few.

In CIRS, fatigue often comes together with unrefreshing sleep and brain fog. Read more in CIRS and sleep and CIRS and neuroinflammation.

When should you consider mould and CIRS?

The CIRS approach starts from two things: symptoms in many body systems and a history of exposure [10]. It may be worth asking your doctor about mould and CIRS if:

• your fatigue began or clearly worsened after moving house, changing jobs or a water leak
• you feel better away from a particular building and worse when you return
• you have symptoms in many body systems at once, not just tiredness
• other people in the same building have similar symptoms
• the building has signs of water damage, such as a musty smell, stains or flaking paint (how to recognise water damage)

	Common causes (sleep, mood, anaemia, thyroid…)	ME/CFS	CIRS (Shoemaker’s definition)
How it is identified	History, examination and basic blood tests [1]	Symptom criteria; no diagnostic test [4][3]	Exposure history, multi-system symptoms, VCS test and specific blood tests [10]
Typical pattern	Depends on the cause	Worse after effort (PEM) [4]	Symptoms in many organ systems, linked to a building [10]
First step in treatment	Treating the cause	Energy management (pacing) and symptom relief [3]	Ending the exposure [12]

What should you do next?

1. See a doctor first. Ask for basic blood tests and a check of your sleep, mood and medicines. Don’t skip this step, even if you strongly suspect mould. The common causes are common, and many are easy to treat.
2. Keep a symptom diary for a few weeks. See the box below.
3. Check the buildings. Look for signs of water damage at home and at work. If you suspect your workplace, raise it with your employer and your occupational health service.
4. Consider the VCS test. The visual contrast sensitivity (VCS) test measures how well you see faint grey patterns. It is a cheap online screening test used in the CIRS approach. An abnormal result supports further investigation. It cannot diagnose CIRS on its own, and a normal result does not rule it out.
5. Ask about CIRS testing. How CIRS is diagnosed explains the blood tests (such as MSH, MMP-9, TGF-β1, C4a and HLA-DR) and how doctors put the results together. Few doctors know CIRS, so bring the information with you.
6. Reduce the exposure. If a building turns out to be water-damaged, getting out of the exposure is the first step of CIRS treatment [12]. Do not start or stop prescription medicines without your doctor.

Joel Hakala, who founded this site, describes years of fatigue, brain fog and gut problems with normal blood tests in his own CIRS story. He was diagnosed with CIRS in 2023.

How strong is the evidence?

Topic	How certain	Why
Common causes of fatigue and how to check them	Strong	Well documented in primary care research and guidelines [2][1]. ME/CFS has established diagnostic criteria [4][3]
Damp and mouldy buildings and fatigue	Moderate	Linked to fatigue and sleep problems in population studies [6][7][8]. These are mostly questionnaire studies that show links, and the WHO regards breathing effects as the best documented [9]
CIRS: the concept, its markers and treatment	Limited	Comes mainly from Dr Shoemaker’s group and practitioners trained in his protocol [10][11]. Even CIRS practitioners call it under-recognised, while ME/CFS is more widely known in medicine [13]. Large independent studies are lacking

Remember these

Check yourself: Can you explain why normal blood tests don’t mean nothing is wrong? And what makes PEM different from ordinary tiredness?

What next?

• Read ME/CFS vs CIRS to compare the two illnesses.
• Go through the CIRS symptom checklist.
• Read how CIRS is diagnosed.

References

1. Maisel P, Baum E, Donner-Banzhoff N. Fatigue as the chief complaint – epidemiology, causes, diagnosis, and treatment. Dtsch Arztebl Int. 2021;118(33–34):566–576. PubMed
2. Stadje R, Dornieden K, Baum E, et al. The differential diagnosis of tiredness: a systematic review. BMC Fam Pract. 2016;17(1):147. PubMed
3. National Institute for Health and Care Excellence (NICE). Myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome: diagnosis and management. NICE guideline NG206. London: NICE; 2021. NICE
4. Institute of Medicine. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. Washington, DC: The National Academies Press; 2015. DOI
5. Bateman L, Bested AC, Bonilla HF, et al. Myalgic encephalomyelitis/chronic fatigue syndrome: essentials of diagnosis and management. Mayo Clin Proc. 2021;96(11):2861–2878. PubMed
6. Yang Q, Wang J, Norbäck D. The home environment in a nationwide sample of multi-family buildings in Sweden: associations with ocular, nasal, throat and dermal symptoms, headache, and fatigue among adults. Indoor Air. 2021;31(5):1402–1416. PubMed
7. Wang J, Janson C, Lindberg E, et al. Dampness and mold at home and at work and onset of insomnia symptoms, snoring and excessive daytime sleepiness. Environ Int. 2020;139:105691. PubMed
8. Hyvönen S, Lohi J, Tuuminen T. Moist and mold exposure is associated with high prevalence of neurological symptoms and MCS in a Finnish hospital workers cohort. Saf Health Work. 2020;11(2):173–177. PubMed
9. World Health Organization. WHO Guidelines for Indoor Air Quality: Dampness and Mould. Geneva: World Health Organization; 2009. PubMed
10. Shoemaker R, Johnson K, Jim L, et al. Diagnostic process for chronic inflammatory response syndrome (CIRS): a consensus statement report of the Consensus Committee of Surviving Mold. Internal Medicine Review. 2018;4(5):1–47. PDF
11. Shoemaker RC, House DE. Sick building syndrome (SBS) and exposure to water-damaged buildings: time series study, clinical trial and mechanisms. Neurotoxicol Teratol. 2006;28(5):573–588. PubMed
12. Noble AM. Treatment of Chronic Inflammatory Response Syndrome. Surviving Mold certification paper, 2021. PDF
13. Dooley M, Vukelic A, Jim L. Chronic inflammatory response syndrome: a review of the evidence of clinical efficacy of treatment. Ann Med Surg (Lond). 2024;86(12):7248–7254. PubMed

Please note: this article is for information only and does not replace a diagnosis or treatment from a doctor. If you are persistently tired, see a healthcare professional.