Fatigue and Tiredness: History Taking and Differential Diagnoses

History of Presenting Complaint

Overview

With each symptom, always (if relevant) ask about:

• When did it start?
• Did it come on suddenly or gradually?
• Is it continuous or intermittent?
• Has this ever happened before?

Fatigue

Initial questions to ask are:

• Onset – when did it start?
• Character – what do they mean by fatigue?
• Timeline – how long has it been going on?
• Exacerbating/alleviating factors – what makes it better/worse?
• Severity – how much of an impact does this have on their life?

Other questions to ask:

• Is there a pattern to their fatigue throughout the day?
• Have they had any menstrual disturbances? (if relevant)
• How is their sleep and what is their sleeping pattern?
• Have they been ill recently?
• Has this ever happened before?

Screen for depression:

• How has their mood been?
• Have they ever had a history of mental health problems?

Review of systems

• Screen for hypothyroidism:
  • Any sweating?
  • Any feeling excessively cold?
  • Any dry hair?
  • Any weight gain?
  • Any menstrual irregularities (if relevant)
• Screen for anaemia:
  • Any shortness of breath?
  • Any chest pain?
  • Any palpitations?
• Screen for diabetes mellitus:
  • Any polyuria?
  • Any polydipsia?
• Screen for malignancy:
  • Any unexplained weight loss?
  • Any night sweats?
  • Any anorexia?
  • Any swollen glands (lymphadenopathy)?
• Screen for infection:
  • Any fever?
  • Any cough?
  • Any diarrhoea?
• Screen for chronic fatigue syndrome:
  • Is there any muscle pain?
  • Is it worse on exertion?
• Screen for obstructive sleep apnoea:
  • Do they wake up unrefreshed?
  • Do they feel sleepy during the day?
  • Do they snore?
  • Do they wake up suddenly at night?
• Screen for depression:
  • How has their mood been?
  • Any anhedonia?
  • How is their sleep?
  • How is their appetite?
  • How is their concentration

Past Medical History

Questions include:

• Do they have any other medical conditions?
• Have they ever had any previous surgery?
• Do they take any regular medications?
• Do they take any over-the-counter medications, herbal remedies, or supplements?

Family History

• Is there any family history of anything similar?

Allergy History

• Are they allergic to anything?
  • What happens during the allergic reaction?

Social History

• Do they smoke?
  • If so, how much and how long?
• Do they drink alcohol?
  • If so, how much and how long?
• Do they use any illicit drugs?
  • If so, how much and how long?
• What is their occupation?
• Who’s at home?
  • What support do they have?
• How has this impacted their activities of daily living?
• Has there been any recent foreign travel?

Investigations

Overview

When suggesting investigations in an OSCE, the BOXES (Blood tests, orifice tests, x-rays, ECGs, special tests) mnemonic is useful for deciding the order of investigations:

• Blood tests:
  • Full blood count:
    • May show anaemia
    • May show leukocytosis
  • Serum ferritin:
    • May identify iron deficiency anaemia
  • Serum B12 and folate
    • May identify deficiency
  • C-reactive protein (CRP)/erythrocyte sedimentation rate (ESR):
    • Non-specific markers of inflammation
    • May be elevated in systemic inflammatory disease or cancer
  • Urea and electrolytes (U&Es):
    • May show renal impairment
  • Liver function tests (LFTs):
    • May show liver impairment
  • Serum calcium:
    • Hypercalcaemia can cause lethargy
  • Fasting blood glucose:
    • If diabetes mellitus is suspected
• Orifice tests:
  • Urinalysis:
    • May show features suggesting renal impairment
• X-rays:
  • Chest x-ray:
    • May show masses suspicious of lung cancer
    • May show features suggesting heart failure (e.g. cardiomegaly)
• Special tests:
  • Sleep studies:
    • If obstructive sleep apnoea is suspected

Differential Diagnoses

Depression

A history may reveal:

• Low mood
• Anhedonia
• Feeling hopeless
• Low self-esteem
• Problems with sleep (e.g. not enough or sleeping too much)
• Loss of energy
• Loss of appetite
• Poor concentration

Diabetes mellitus

A history may reveal:

• Polyuria
• Polydipsia
• If diabetic ketoacidosis is developing, dehydration, abdominal pain, and altered consciousness may be seen 

Investigations may show:

• Elevated blood glucose

Hypothyroidism

A history may reveal:

• Cold intolerance
• Dry skin
• Weight gain
• Constipation
• Low mood
• Shortness of breath on exertion

Investigations may reveal:

• Elevated TSH
• Low T4

Iron-deficiency anaemia

A history may reveal:

• Shortness of breath on exertion
• Chest pain
• Palpitations
• Hair loss
• Brittle nails

A physical examination may reveal:

• Pallor
• Tachycardia

Investigations may show:

• Full blood count:
  • Decreased haemoglobin
  • Decreased mean cell volume
• Ferritin:
  • Decreased
• Transferrin saturation:
  • Decreased
• Total iron binding capacity:
  • Increased

Chronic heart failure

A history may reveal:

• Shortness of breath on exertion
• Orthopnoea
• Paroxysmal nocturnal dyspnoea
• A previous history of cardiac disease

A physical examination may reveal:

• Oedema
• Cardiomegaly
• S3 heart sounds
• Jugular venous pulse distention
• Hepatomegaly

Investigations may show:

• N-terminal prohormone brain natriuretic peptide (NT-proBNP):
  • Elevated
• ECG:
  • May show ventricular hypertrophy
• Chest x-ray:
  • May show cardiomegaly or pleural oedema

Chronic kidney disease

A history may reveal:

• Weakness
• Pruritus
• Muscle cramps
• A physical examination may reveal:
• Generalised oedema
• Hypertension

Initial tests may show:

• U&Es:
  • Elevated creatinine with or without elevated urea

COPD

A history may reveal:

• Shortness of breath
• A chronic cough
• A history of smoking
• A physical examination may show:
• Wheezing
• Hyperresonance
• A barrel chest

Initial investigations may show:

• Full blood count:
  • May show erythrocytosis (if polycythaemia secondary to COPD develops)
• Chest x-ray:
  • May show hyperinflation
• Spirometry:
  • Shows an FEV1/FVC ratio <0.7

Obstructive sleep apnoea

A history may reveal:

• Excessive daytime sleepiness
• Snoring
• Waking up at night
• Headaches in the morning
• Waking up unrefreshed
• A physical examination may show:
• Obesity

Initial investigations may show:

• Epworth sleepiness scale:
  • Score ≥11

Coeliac disease

A history may reveal:

• Diarrhoea
• Steatorrhoea
• Weight loss
• Abdominal pain

A physical examination may reveal:

• Easy bruising
• Pallor
• Mouth ulcers
• Dermatitis herpetiformis

Initial tests may show:

• Full blood count:
  • May show low haemoglobin
  • May show a low mean cell volume
• Anti-tissue transglutaminase (anti-TTG) antibodies:
  • Elevated

Addison’s disease

A history may reveal:

• Weakness
• Loss of appetite
• Nausea
• Abdominal pain
• Muscle pain
• Fever

A physical examination may reveal:

• Dehydration, tachycardia, and altered consciousness if an Addisonian crisis develops
• Skin hyperpigmentation may be seen, particularly in the palmar creases

Initial investigations may show:

• U&Es:
  • Hyponatraemia with or without hyperkalaemia
• Morning serum cortisol:
  • Decreased

Underlying malignancy (in general)

A history may reveal:

• Unexplained weight loss
• Fevers
• Anorexia
• Night sweats
• A family history of cancer

Lymphoma

A history may reveal:

• Painless cervical and/or supraclavicular lymphadenopathy
• There may be B-symptoms (fevers, night sweats, and/or weight loss)
• There may be pruritus
• Alcohol may induce pain in lymphadenopathy (suggesting Hodgkin’s lymphoma)

A physical examination may reveal:

• Lymphadenopathy, which may be generalised

Investigations may show:

• Lymph node biopsy:
  • May show Reed-Sternberg cells (suggesting Hodgkin’s lymphoma)

Leukaemia

A history may reveal:

• Fever
• Night sweats
• Weight loss
• Easy bruising

A physical examination may show:

• Pallor
• Hepato- and/or splenomegaly
• Petechiae and purpura

Initial investigations may show:

• Full blood count and blood smear:
• May show elevated white cell counts and abnormal cell morphology

Fibromyalgia

A history may reveal:

• Widespread musculoskeletal pain
• Generalised pain overall

Diagnosis is clinical

Chronic fatigue syndrome (myalgic encephalomyelitis)

A history may reveal:

• Severe, debilitating fatigue >6 months
• Fatigue that is not relieved with rest or reduced activity
• Memory problems and problems with concentration
• Muscle pains
• Unrefreshing sleep

Diagnosis is clinical

Osteomalacia

A history may reveal:

• Diffuse bone pain
• Muscle pain
• Muscle weakness

Initial investigations:

• Serum 25-hydroxyvitamin D:
  • Low

Systemic lupus erythematosus

A history may reveal:

• A malar ‘butterfly-shaped’ rash over the face
• Photosensitivity
• Chest pain
• Mouth ulcers
• A physical examination may reveal:
• Mouth ulcers
• A malar rash over the face
• Lymphadenopathy
• Raynaud’s phenomenon

Initial tests may show:

• Anti-nuclear antibody (ANA):
  • Positive
• Anti-double-stranded DNA (anti-dsDNA):
  • Positive

Multiple sclerosis

A history may reveal:

• A history of vision blurring and features of optic neuritis
• Numbness
• Tingling
• Urinary and/or bowel dysfunction

A physical examination may reveal:

• Abnormalities with muscle tone and tendon reflexes
• Abnormalities in vision

Initial tests may show:

• MRI brain and spinal cord with contrast:
  • May show white matter lesions