Fatigue. Causes, epidemiology, treatment

Fatigue is one of the most common symptoms characterizing both the psychological and physical state of a person. Fatigue accounts for about 20% of the overall primary visits to a family doctor. The authors of the article “Fatigue as the Chief Complaint. Epidemiology, Causes, Diagnosis, and Treatment” (Maisel, P et al.) analyzed sources of literature on the epidemiology, etiology, and diagnosis of the fatigue symptom complex, including the German clinical guidelines for general and family practitioners (Deutsche Gesellschaft für Allgemeinmedizin und Familienmedizin, DEGAM), allowing for the synthesis of results and organization of existing information. The search was conducted in the Medline and Scopus databases. Search depth: 2015 - 2019.

Definition of fatigue

There is no single universal definition of the term “fatigue.” Many sources define fatigue as a state that impairs a person’s ability to perform their usual daily activities, requiring more time for sleep and rest, and a longer recovery of energy balance (Mota DDCF: Self-report instruments for fatigue assessment: a systematic review, 2006). 

Patients describe their condition as lethargy, lack of energy, tiredness, sleepiness, and physical weakness. Fatigue is associated with mental, physical, and professional activities. Fatigue is a subjective symptom for approximately 60% of oncological patients.

Types of fatigue

Patients may describe various types of fatigue:

• Emotional (loss of interest and motivation)
• Cognitive (reduced mental activity and work capacity)
• Behavioral (reduced productivity)
• Physical (muscle weakness)

Fatigue lasting more than six months is called chronic fatigue.

It is worth mentioning a symptom complex known as chronic fatigue syndrome (CFS), recently renamed as systemic exertion intolerance disease (SEID). According to most definitions, this is a syndrome lasting at least 6 months, manifesting with a minimum of 4–6 symptoms:

• Increased fatigue after physical exertion
• Sleep disturbances
• Muscle and joint pain
• Head and neck pains
• Cognitive impairments
• Orthostatic disorders
• Significant limitation of daily activities unrelated to any specific illness.

Moreover, these symptoms tend to worsen under stress. The prevalence of this syndrome in the population is at least 2%. In 2% of patients presenting complaints of fatigue to a family doctor, chronic fatigue syndrome is diagnosed.

Epidemiology

Due to different diagnostic methods, various countries have a fairly wide range of prevalence of the fatigue symptom complex. For example, the overall European diagnostic rate for fatigue varies from 22% to 38%, while in Germany, this rate ranges from 20% to 60%.

The prevalence of fatigue increases with age, and women typically experience more pronounced symptoms. Individuals with fatigue seek medical attention when, from their perspective, the disruption cannot be adequately explained, is unacceptable, and individual coping methods are no longer effective.

Despite the high variability in studies, fatigue is the cause of approximately 20% of outpatient visits.

Diagnosis

Due to the wide range of biological, psychological, and social factors, it is not always possible to establish a direct cause-and-effect relationship with the manifestation of fatigue. The patient’s history and clinical manifestations of the disease should be taken into account. When making a differential diagnosis, the following aspects should be considered:

• Mental disorders: Fatigue often occurs in the context of mental disorders such as depression and anxiety disorders. Approximately 75% of individuals with depression suffer from fatigue.
• Somatoform disorders, such as irritable bowel syndrome and fibromyalgia, are present in 75% of cases with fatigue.
• Cancer: Fatigue is the main symptom in 65% of cancer patients.
• Anemia: There is only a weak link between low hemoglobin levels and fatigue. An exception may be acute blood loss when fatigue is a mandatory symptom.
• Endocrine disorders: Thyroid dysfunction, diabetes, and premenstrual syndrome can cause fatigue.
• Infectious diseases and liver diseases: Viral respiratory diseases such as mononucleosis, giardia infections (causing giardiasis), and viral hepatitis are significant causes of fatigue. Patients with viral hepatitis often suffer from fatigue. Long-term data on fatigue as the main complaint after COVID-19 infection are not available.
• Chronic somatic diseases: Fatigue is a very common and unpleasant symptom of many chronic diseases, including heart failure, multiple sclerosis, Parkinson's disease, stroke, chronic kidney disease, rheumatoid arthritis, sarcoidosis, chronic kidney disease, and ischemic heart disease.
• Sleep disorders and sleep-related respiratory disorders: Primary insomnia, parasomnias (sleep disorders often associated with the use of psychoactive substances), and chronic allergic rhinitis disrupt sleep and cause daytime fatigue due to impaired nasal breathing. Obstructive sleep apnea during sleep is associated with impaired wakefulness and fatigue.
• Drugs and psychotropic substances: The main complaint of fatigue is the use of groups of drugs such as antidepressants, opioids, interferons, benzodiazepines, antipsychotics, antihypertensives, antihistamines, antivirals, cytostatics, and antiparkinsonian drugs. Alcohol and psychoactive substance use are also causes of fatigue.
• Environmental factors: Studies of electromagnetic hypersensitivity syndrome, multiple chemical sensitivity, job dissatisfaction confirm complaints of fatigue, although the study of these conditions poses certain difficulties.
• Socioeconomic factors: Low income, low education level, and occupational stress are causes of fatigue.

The basic series of tests, regardless of the patient’s age, include collecting a history and physical examination with a focus on possible causes of fatigue, including sleep disturbances, changes in body weight, cardiovascular, respiratory, gastrointestinal, urinary and central nervous system function, drug and psychotropic substance use, problems in the patient's social, family, or professional environment, exposure to chemicals or excessive noise, similar symptoms in family members or colleagues, snoring, and sleep onset disturbance. Attention should also be paid to the infectious history.

Targeted laboratory tests should include the determination of blood sugar levels, complete blood count, γ-GT (gamma-glutamyltransferase – an enzyme of the liver and pancreas whose activity increases in liver diseases and alcohol abuse), and TSH (thyroid-stimulating hormone – the main regulator of the thyroid gland; TSH).

Treatment

If treatment is possible and indicated, its effect on fatigue should be documented in the patient's medical history. If fatigue remains unexplained, the clinical approach should involve a watchful waiting strategy with regular monitoring of the somatic or mental condition at intervals of 4 to 6 weeks. Problem-oriented and cognitive-behavioral therapy are also recommended. Keeping a symptom diary is advised for discussion with the patient. Psychoeducational measures aim to inform the patient about the disease process and ways to cope with it by taking personal responsibility for the outcome. An adapted physical activity program is also recommended.

General recommendations for managing patients with the fatigue symptom complex include symptomatic treatment considering the identified cause and regular scheduled monitoring.