Chapter 74: Tiredness/fatigue

Tiredness, which basically means ‘a desire to rest’, or chronic fatigue is not a diagnosis but rather a symptom of illness: it may occur as either a presenting or a supporting symptom. Tiredness is interchangeable with terms such as weariness, lethargy, loss of energy, listlessness and exhaustion. It is a common and difficult presenting symptom often known by the acronym TATT—‘tired all the time’. The symptom of tiredness is likely to be ‘hidden’ behind the request for a tonic or a physical check-up.¹

Tiredness can be a symptom of a great variety of serious and uncommon diseases, including malignant disease. The challenge for the family doctor is to diagnose such disorders quickly without extravagant investigation.

Analysing the symptom and reaching a diagnosis demands considerable skill, since tiredness may indicate the first subtle manifestation of a serious physical disease or, more commonly, may represent a patient’s inability to deal with the problems of everyday life. Chronic tiredness or fatigue is a feature of the ‘high pressure’ nature of many people’s lifestyles.

Careful consideration must be given to the differentiation of physiological tiredness, as a result of excessive physical activity, from psychological tiredness. Furthermore, before diagnosing tiredness as psychological, pathological as well as physical causes must be excluded.

A summary of causes of chronic tiredness is presented in TABLE 74.1.

A summary of the diagnostic strategy model is presented in TABLE 74.2.

Probability diagnosis

The most probable diagnoses to consider are:

• tension, stress and anxiety

• depression

• inappropriate lifestyle and psychosocial factors

• viral or postviral infection

• sleep-related disorders

Research studies have reported that over 50% (and in some cases as many as 80%) of reported cases of fatigue have been of psychological causation.³ Overwork is a common cause of fatigue and is often obvious to everyone but the patient. The modern approach to sleep-related disorders has revealed several important factors causing excessive tiredness.

Serious disorders not to be missed

Many serious disorders such as anaemia, malignant disease and subacute or chronic infections (e.g. hepatitis, bacterial endocarditis and tuberculosis) can be ‘hidden’ or masked in the initial stages or not readily apparent. Neuromuscular diseases such as myasthenia gravis and multiple sclerosis, connective tissue disorders and HIV infection also have to be excluded.

Pitfalls

The symptom of tiredness is fraught with pitfalls. Common ones include depression and other psychoneurotic disorders, and incipient congestive cardiac failure. Drug intake is a very common pitfall, whether it be by self-administration (including alcohol) or iatrogenic.

Tiredness is a feature of pregnancy in many women, so this association is worth keeping in mind, especially in the early stages when a change in menstrual history is not given or a young single woman will attempt to conceal the fact. It is also a presenting symptom of the menopause syndrome, which should not be misdiagnosed. Two classic causes of tiredness are haemochromatosis and coeliac disease.

Seven masquerades checklist

All these important problems are capable of being responsible for tiredness, especially depression, diabetes, drugs, anaemia and urinary infection. Thyroid disorder could certainly be responsible. Spinal pain can indirectly cause tiredness. Drugs that commonly cause tiredness are listed in TABLE 74.3.

Antihypertensives require special consideration. Drug withdrawal, especially for illicit drugs such as amphetamines, marijuana, cocaine and heroin, has to be considered.

Psychogenic considerations

Tiredness is a symptom that may represent a ‘ticket of entry’: a plea for help in a stressed, anxious or depressed patient. Any of the primary psychiatric disorders can present as tiredness.

In routine history taking, it is mandatory that questions be asked about the following if the information is not volunteered by the patient:

• sleep pattern (it is not uncommon for patients to say they sleep well and yet on questioning it is found they have initial insomnia, or middle insomnia, or both, with or without early morning waking). It is most relevant to talk to any sleeping partners to obtain a history of sleep disturbance

• weight fluctuations

• energy—performance—ability to cope

• sexual activity/sexual problems

• suicidal ideas

• self-medication—OTC preparations (e.g. bromides, stimulants, analgesics, alcohol, cigarettes, other drugs); this is particularly important in the drug addiction-prone group: doctors, chemists, nurses, workers in the liquor industry, truck drivers

• fears (including phobic symptoms, hypochondriasis)

• precipitating factors (present in over 50% of patients with depressive illness):

  • – postpartum

  • – postoperative

  • – associated with chronic physical illness

  • – bereavement

  • – pain—chronic pain conditions

  • – retirement

  • – medication

  • – post trauma (e.g. motor vehicle accident)

  • – postviral infections, especially hepatitis, mononucleosis, influenza

• work history—determine whether the patient is a workaholic; ask about bullying at work

• dietary history—determine pattern, including fad diets or skipped meals

• psychological history—stress, anxieties, phobias, depression

• menstrual history and symptoms related to the menopause syndrome

• final questions: ‘Is there anything else you feel you should tell me?’ ‘Do you have any explanation for your tiredness?’

• self-question: ‘Is this patient depressed?’

Physical examination—key features

• General inspection noting facial features, skin appearance and colour, hyperpigmentation, conjunctivae

• Vital signs

• Anthropometric measurements

• Basic respiratory and cardiovascular

• Abdominal examination with focus on masses and inguinal lymphadenopathy

• Urinalysis

Key investigations (screening) guidelines⁵

• FBE

• ESR/CRP

• Blood sugar

• Serum electrolytes, calcium, magnesium

• Kidney function tests

• Liver function tests

• Iron studies

• Gluten sensitivity screening blood tests

• Faecal occult blood

• Thyroid function tests

• CXR

• Urine—dipstick/MCU

Consider others according to clinical features e.g. chronic infection and HIV screening, autoimmune disorders, cancer markers and sleep disorder studies.

The diagnosis of CFS can be made only when the minimum investigations have been shown to be normal or to demonstrate minor abnormalities in liver function or blood film (atypical lymphocytes).

Tiredness in children is caused by a range of predictable conditions, such as physiological factors (excessive exercise, lack of sleep, poor diet), infections, allergies including asthma, drugs, depression and various illnesses in general.

Overweight children are likely to fatigue more rapidly than children of normal weight.⁶ Any bacterial, viral or other infection may be associated with tiredness, with EBV being very significant in adolescents. Chronic EBV infection causing recurrent episodes of fever, pharyngitis, malaise and adenopathy can occur, especially in teenagers, who present with chronic exhaustion that is frequently mistaken for malignancy.⁶

Tiredness is a presenting feature of depression in adolescents, a serious problem that often goes unrecognised. Tonsillar–adenoidal hypertrophy may be large enough to compromise air exchange, particularly during sleep. Snoring may be a feature plus tiredness and lethargy in the waking state.

Elderly people tend to tire more quickly and recover more slowly and incompletely than younger ones. Sleep in older people is generally shorter in duration and of lesser depth, and they feel less refreshed and sometimes irritable on awakening.

Fatigue may be present as a result of emotional frustration. Whenever the prospect of gratification is small, a person tends to tire quickly and to remain so until something stimulating appears. Since the prospects for gratifying experience wane with the years, easy ‘fatigueability’ or tiredness is common in this age group.

Bereavement

Although a bereavement reaction is common and a normal human response that occurs at all ages, it is more frequently encountered in the elderly, with the loss of a spouse or a child (young or middle-aged). Fatigue that occurs during the initial mourning period is striking and might represent a protective mechanism against intense emotional stress. With time, usually around 6 to 12 months, a compensated stage is reached, fatigue gradually abates, and the patient resumes normal activities as the conflicts of grief are gradually resolved. Freud pointed out the complexities of mourning as the bereaved person slowly adjusts to the loss of the loved one. In others, various symptoms persist as an ‘abnormal grief reaction’, including persistence of fatigue. Some factors that may lead to this include:

• unexpected death

• high dependence upon the dead person

• guilt feelings, especially in a love/hate relationship

Studies in general practice have shown that widows see their family doctors for psychiatric symptoms at three times the usual rate in the first 6 months after bereavement. The consultation rate for non-psychiatric symptoms also increases, by almost 50%.

Role of the family doctor

Following bereavement it is important to watch for evidence of depression, drug dependency, especially on alcohol, and suicidal tendencies. In cases of expected death, management should, if possible, start before the bereavement. Supportive care and ongoing counselling are very important.

Burnout is a clinical syndrome with three components:

• long-term emotional exhaustion

• depersonalisation of others and

• lack of personal accomplishment⁷

It is similar to stress-related depression but mood lowering is temporary and work-specific.

Burnout is not a recognised disorder in the DSM-5 criteria, although the ICD-10 classifies it under ‘problems related to life management’ as a ‘state of vital exhaustion’.⁸

Patients sometimes claim that they feel ‘burnout’. Burnout can mean many things and include a whole constellation of psychogenic symptoms, such as exhaustion, boredom and cynicism, paranoia, detachment, heightened irritability and impatience, depression and psychosomatic complaints, such as headache and tiredness. Ellard⁹ defines burnout as the syndrome that arises when a person who has a strong neurotic need to succeed in a particular task becomes confronted with the impossibility of success in that task. This seems a realistic explanation, but the important factor is to clarify the nature of the problem with care and determine whether the patient has a psychoneurotic disorder, such as hypomania, anxiety state or depression, or a personality disorder or simply unrealistic goals.

Another viewpoint is that it is caused by chronic emotional stress resulting from prolonged intensive involvement with people.¹⁰ Burnout can be work related. Those who tend to be prone to it are musicians, authors, health professionals, teachers, athletes, engineers, emergency service workers, soldiers, reporters and high-technology professionals. Management involves appropriate counselling, which aims to help the patient to identify life stressors, set realistic personal goals and develop good support mechanisms.

This complex syndrome, which causes profound and persistent tiredness, is also referred to as myalgic encephalomyelitis, chronic neuromuscular viral syndrome,¹¹ postviral syndrome, chronic EBV syndrome, viral fatigue state, epidemic neuromyasthenia, neurasthenia, Icelandic disease, Royal Free disease and Tapanui disease. CFS is not to be confused with the tiredness and depression that follow a viral infection such as infectious mononucleosis, hepatitis or influenza. These postviral tiredness states are certainly common but resolve within 6 months or so.

Typical features of CFS (see FIG. 74.1):¹¹

• extreme exhaustion (with minimal physical effort)

• headache or a vague ‘fuzzy’ feeling in the head

• aching in the muscles and legs

• poor concentration and memory

• hypersomnia or other sleep disturbance

• waking feeling tired

• emotional lability/anxiety

• depressive-type illness, mood swings

• arthralgia (without joint swelling)

• sore throat

• subjective feeling of fever (with a normal temperature)

• shortness of breath

• tender, swollen lymph nodes

• usually occurs between 20 and 40 years of age

Epidemiologically it has been related to Coxsackie B virus infections. The responsible organism is referred to as a slow virus infection by some authorities.⁸

In approximately two-thirds of patients the illness follows a clearly defined viral illness. However, no single virus has been consistently associated with the development of the syndrome, which is known to develop following a wide range of viral and non-viral infective illness. Immune system dysfunction with chronic overproduction of cytokines (e.g. interferon) is a possible pathogenetic mechanism.

Every family doctor probably has patients with this disorder and the syndrome has been observed in isolated endemics from time to time. Hickie et al³ found that only 0.3% of those with prolonged fatigue had been diagnosed with CFS by their family doctor. Veterans of the Gulf War show a tenfold incidence of CFS compared with non-deployed military personnel.¹⁰

There is no doubt that the syndrome is real in these patients. One of the major problems confronting clinicians is that there is no diagnostic test for this illness, so it remains a clinical diagnosis backed up by normal baseline investigations.

Diagnostic criteria for CFS have been published¹³ (see TABLE 74.4), which emphasise the positive clinical features of the syndrome and the chronicity of symptoms (greater than 6 months), in addition to the need for careful exclusion of alternative diagnoses by history, physical examination and laboratory investigation.

Apart from mild pharyngeal infection, cervical lymphadenopathy or localised muscle tenderness, the physical examination is normal.

Investigations should be directed towards excluding possible diagnoses for that patient, such as chronic infection, autoimmune disorders, endocrine and metabolic disorders, primary neuromuscular disorders, malignancy and primary psychiatric disorders. The last mentioned is the most difficult of the differential diagnoses and psychiatric referral will often need to be considered.

Patients who have CFS are really suffering and unhappy people, similar to those with fibromyalgia (see CHAPTER 37). They require considerable understanding and support. Multidisciplinary intervention is recommended. Symptoms last approximately 2½ years.

Management strategies include:¹¹

• CFS recognition—explain that the illness is real but the cause unknown and tests are likely to be normal

• explanation and reassurance that the illness is usually self-limiting with no permanent complications; and that a slow, steady improvement can be anticipated, with most CFS patients returning to normal health

• provide continued psychological support

• review for diagnostic reappraisal (examine at least every 4 months)

• avoid telling patients they are depressed

• treat symptomatically—pain relief, consider NSAIDs and antidepressants if significant depression

• refer to counselling and support groups

• provide a realistic, regular, graduated exercise program

• reduce relevant stress factors (map a realistic living program)

• psychiatric referral if appropriate

• ask the patient to keep a diary of exercise/stress and symptom severity, in particular

• avoid long-distance travel, which is poorly tolerated

Cognitive behaviour therapy appears to help some patients, as do relaxation therapy, meditation, stress management and psychotherapy, where indicated.

The emphasis should be placed on caring, rather than curing, until a scientific solution is found.

A systematic review has found that cognitive behaviour therapy administered by skilled therapists and exercise are beneficial. Although few patients are cured with CBT, the therapeutic effect is substantial.¹² There is insufficient data or evidence to support the use of antidepressants, corticosteroids, complementary therapies and dietary supplements, including vitamins B12 and C and co-enzyme Q₁₀.⁵ Prolonged rest and immunotherapy was unlikely to be beneficial.¹⁴

The fibromyalgia syndrome (see CHAPTER 37) bears a clinical resemblance to CFS. Musculoskeletal pain is more prominent although tiredness (fatigue) and sleep disturbance are features. According to Schwenk,¹⁵ fibromyalgia affects 5% of the American population with a peak age of 35 years (range 20–60) and a female:male ratio of 10:1. The management is similar to CFS but the prognosis less optimistic.

Hand-out sheets from Murtagh’s Patient Education 7th edition:

• Chronic fatigue syndrome