The history provides the bulk of the information necessary in diagnosing the cause of fatigue. Physical examination and laboratory investigations only provide a support to the facts already established by the history.
A step-wise approach involves the following:
- Characterise the fatigue
- Ask questions on sleep quantity and/or quality
- Look for features suggestive of organic illness
- Review medications and/or substances abused
- Do a psychiatric assessment
- Perform a thorough physical examination
- Request investigations.
Characterise the fatigue based on:
- Sudden or progressive onset (e.g., chronic fatigue syndrome is usually of sudden onset)
- Intermittency (e.g., chronic fatigue syndrome is associated with intermittent periods of recovery lasting hours or days)
- Relief by rest (physiological versus non-physiological fatigue)
- Aggravation by physical or mental activity (e.g., chronic fatigue syndrome is typically aggravated by relatively minor physical or mental activity)
- Level of physical activity (sedentary lifestyle is a cause of fatigue, and patients may benefit from exercise therapy) and concomitant presence of weakness (e.g., reduced muscle power at rest may point to a neuromuscular disorder)
- Seasonality and any current influenza outbreak (which occur most commonly in the dry seasons).
- Assess the quantity and/or quality of sleep to find out if the symptom is due to or causing sleep disturbance:
Look for features suggestive of organic illness:
- Age: an underlying cause for chronic fatigue is usually found in people 60 years or older. In younger age groups such as 30 to 39 years, the cause is more likely to be prolonged fatigue with no obvious organic illness
- The presence of a chronic cough and other features suggestive of TB infection; Residence in, or travel to, TB-endemic areas
- Exposure to infections like brucellosis (contact with cows or consumption of unpasteurised milk and other dairy products), or toxoplasmosis (ingestion of uncooked meat and contact with a kitten)
- Features suggestive of immunosuppression eg cancer, HIV status, chronic steroid use (cytomegalovirus infection)
- Intravenous drug use and unprotected sexual intercourse (HIV/hepatitis B or C virus infection)
- Cardiovascular risk factors (acute coronary syndrome)
- Steatorrhoea, weight loss (coeliac disease)
- Sore throat (EBV infection)
- Fever with cough, sore throat, runny nose (influenza infection)
- Dysfunctional Uterine Bleeding or Heavy Menstrual Bleeding (anaemia)
- Polyuria, polydipsia (diabetes mellitus, hypopituitarism)
- Dyspnoea (cardiac failure, chronic lung disease)
- Visual field defect (multiple sclerosis)
- Cold intolerance, overweight (hypothyroidism)
- Heat intolerance, weight loss despite increased appetite (hyperthyroidism)
- Arthralgia or rash (autoimmune disease)
- Weight loss, blood in stool (malignancy, anaemia)
- Recent viral infection (post-viral illness)
- Neurological symptoms such as paraesthesias, blurred vision, psychiatric changes, cognitive decline, tremor, ataxia (heavy metal toxicity)
- History of stroke.
- An occupational history should be taken if heavy metal toxicity is suspected.
- Lead toxicity: Battery production, Glassware production, Painters using very old household paints
- Mercury toxicity: Consumption of fish and use of amalgam dental fillings.
Review medications and/or substances abused. Drugs frequently associated with fatigue include the following:
- Neuroleptic agents.
Do a psychiatric assessment to check for: (depression, anxiety disorders, somatisation disorders, and substance abuse):
- Anxiety disorders
- Somatisation disorders
- Substance abuse. The CAGE Questionnaire may be used to assess alcohol dependence: Have you ever felt the need to cut down on drinking? Have you ever felt annoyed by criticism of your drinking? Have you ever had guilty feelings about your drinking? Do you ever take a ‘morning eye opener’ (a drink first thing in the morning to steady your nerves or get rid of a hangover)?
- The Alcohol Use Disorders Identification Test (AUDIT) adapted from the WHO Guidelines for use in primary care (2004) may also be used especially for identifying less severe drinking problems.
- Assessing for diminished level of alertness, psychomotor agitation or retardation, and poor grooming (pointers to a psychiatric disorder)
- Check for lymphadenopathy, a possible sign of chronic infection or malignancy
- Examine for pallor (anaemia), a bluish tinge to the sclera (iron deficiency)
More specific examinations are usually guided by the history to elucidate specific signs particular to the suspected pathology.
Perform cardiovascular and respiratory systems examinations to exclude congestive heart failure and chronic lung disease.
The patient is also entitled to a preliminary neurological examination. This should include assessment of muscle bulk, tone, and strength. Abnormal findings would suggest an underlying neurological disorder causing the fatigue.
Specific clinical signs of organic diseases associated with fatigue include the following:
- Pallor, tachycardia, systolic ejection murmurs: anaemia
- Blue sclera: iron deficiency
- Jaundice, palmar erythema, Dupuytren’s contracture: chronic liver disease
- Goitre or thyroid nodule, dry skin, delayed deep tendon reflexes, peri-orbital puffiness, ophthalmological changes: hypothyroidism
- Weight loss, hyper-reflexia, tachycardia, atrial fibrillation, fine tremor, goitre: hyperthyroidism
- Hypotension, pigmentation in skin creases, scars, and buccal mucosa: Addison’s disease
- Increased central adiposity, dry skin, reduced muscle mass and strength, visual field defects, circulatory collapse (if acute presentation): hypopituitarism
- Lip pursing, prolonged expiration, wheezing, cyanosis: COPD
- Pulmonary stasis, elevated jugular venous pressure, ankle oedema: heart failure
- Lymphadenopathy and/or hepatosplenomegaly: malignancy, chronic liver disease, HIV infection, EBV, cytomegalovirus, brucellosis
- Decreased breath sounds and presence of rales (secondary bacterial pneumonia): influenza infection
- Pruritus, excoriations, xanthelasma: primary biliary cirrhosis
- Red butterfly rash on the face, joint deformity: SLE
- Tender points assessment: fibromyalgia
- Tremor, rigidity, bradykinesia: Parkinson’s disease
- Loss of sensation to light touch and vibration: diabetes mellitus
- Babinski’s reflex, ataxic nystagmus: multiple sclerosis
Laboratory investigations are rarely contributory in the absence of a suggestive history or positive physical examination. However, they could be used to exclude underlying organic illness.
- FBC with differential
- ESR (in patients ≥65 years, to screen for systemic disease and neoplasia)
- Kidney function tests (SEUCr)
- Liver function tests
- Fasting blood glucose
- Serum creatine kinase, calcium, phosphate, and TSH levels
- Serum levels for heavy metals (e.g., lead, mercury, cobalt, chrome) where available, if heavy metal toxicity is suspected.
- An ECG, cardiac enzymes, and CXR are indicated if an underlying cardiac or pulmonary disorder is suspected
Further testing for specific underlying causes
This depends on the clinical findings.
- Ferritin level to screen for iron deficiency
- Urinalysis for the presence of protein, blood, and glucose.
- Urine and serum toxicology are indicated if a history of drug dependence is suspected
- B-type natriuretic peptide (BNP) and echocardiogram for suspected cardiac failure
- Serum cortisol level +/- a short ACTH stimulation test for Addison’s disease
- Cortisol, TSH, free T4, free T3, FSH, LH, oestrogen, testosterone, prolactin, and GH levels (for suspected hypopituitarism)
- HIV testing and hepatitis serology
- The monospot test +/- EBV antibody test if EBV is suspected (e.g., history of fever, sore throat, rash, drowsiness, myalgia, loss of appetite)
- The tuberculin skin test, sputum microscopy and culture, and CXR for TB
- Toxoplasmosis and cytomegalovirus serology when such diagnoses are suspected
- CT or MRI of the head for patients with neurological examination findings suggestive of stroke or multiple sclerosis
- Radioiodine scan for patients with suspected hyperthyroidism
- ANAs, dsDNA, and Smith antigen testing for SLE
- Serum vitamin D level for suspected vitamin D deficiency
- Investigations for possible underlying malignancy.