Pyrexia of Unknown Origin History Taking


Pyrexia of unknown origin (PUO) is defined as fever of 38.3°C or greater for at least 3 weeks with no identified cause after three days of hospital evaluation or three outpatient visits.¹
Additional categories of PUO have since been added, including nosocomial, neutropenic and HIV-associated PUO. ²,³


The most common causes of PUO include the following: 4

  • Bacterial infections (e.g. abscesses, endocarditis, tuberculosis, osteomyelitis)
  • Viral infections (e.g. CMV, EBV, HIV)
  • Autoimmune conditions (e.g. rheumatoid arthritis, mixed connective tissue disease, polymyalgia rheumatica)
  • Malignancy (e.g. Hodgkin’s/non-Hodgkin’s/leukaemias)

Check out the pyrexia of unknown origin history taking mark scheme here.

Opening the consultation

Introduce yourself

Confirm patient details name and age (age-appropriate malignancies can be screened for)

Explain the need to take a history

Gain consent

Presenting complaint

It’s important to use open questioning to elicit the patient’s presenting complaint

“So what’s brought you in today?”  or  “Tell me about your symptoms”

Allow the patient time to answer, trying not to interrupt or direct the conversation

Facilitate the patient to expand on their presenting complaint if required

“Ok, so tell me more about your fevers”

History of presenting complaint

Fever history

Onset – clarify when the patient first noticed their fevers

Duration – infectious causes become less likely with increasing duration of the fever

Severity check if the patient has been recording their temperatures, and if so, ask about the readings



  • Is there a pattern to the fever?
  • Is the frequency of fever changing?


Precipitating factors:

  • Was there any obvious trigger that preceded the onset of fevers?


Relieving factors:

  • Does anything help alleviate or minimise the fever? (e.g. paracetamol)


Associated features:

  • Malaise
  • Nausea/vomiting
  • Night sweats
  • Fatigue
  • Rigors
  • Weight loss
  • Pain (clarify location)
  • Swelling (abscess, lymphadenopathy)
  • Skin changes (e.g. rash, itch)


Previous episodes:

  • Have you ever experiences prolonged episodes of fever in the past?


Infectious disease

Recent infections:

  • Type of infection
  • Symptoms
  • Check if all of the symptoms have fully resolved
  • Ask what treatment the patient received and if they took it as prescribed (e.g. did they finish their course of antibiotics?)


Local exposures:

  • Sick contacts
  • Food and water consumption
  • Recent injuries (e.g. breaks in the skin)
  • Contact with animals/pets/birds
  • Sexual activity without contraception
  • Tattoos/piercing


Travel history:

  • Location (rural vs urban)
  • Departure and return dates
  • Chemoprophylaxis and compliance (e.g. Malarone for malaria)
  • Vaccinations for trip
  • Activity (e.g. water-based activity/animal contact)
  • Accommodation (e.g. malaria bed nets provided)
  • Insect bites
  • Injuries (e.g. breaks in the skin)
  • Food and water consumption
  • Sick contacts
  • Sexual activity
  • Tattoos/piercing


Autoimmune disease

Symptoms associated with autoimmune disease include:

  • Morning joint stiffness
  • Joint swelling and pain
  • Rashes
  • Fatigue
  • Dry eyes/mouth
  • Red/painful eyes
  • Dry cough
  • Progressive shortness of breath




Symptoms associated with malignancy include:

  • Night sweats
  • Weight loss
  • Fatigue
  • Change in bowel habit (including blood in stool)
  • Haemoptysis/haematuria
  • Enlarging masses
  • Bone pain

Past medical history

Immunisations – take a detailed history of immunisation status to ensure the patient is up to date will all relevant vaccinations


Previous infectious diseases:

  • Type of infections
  • Symptoms
  • Frequency of infections (if very frequent may suggest partial treatment or immune deficit)
  • Ask specifically about common causes of PUO such as HIV/Tuberculosis/Endocarditis/Abscesses/Osteomyelitis


Past medical history:

  • Conditions that increase the risk of infectious disease (e.g. diabetes, Crohn’s disease, immune system impairment)
  • Organ transplant recipient – patient may be on immunosuppressive medication


Autoimmune conditions:

  • Type of autoimmune condition (e.g. inflammatory bowel disease, rheumatoid arthritis, mixed connective tissue disease, sarcoidosis)
  • The current level of disease control (is the patient currently experiencing a flare?)
  • Current treatments (often immunosuppressive in nature)



  • Type of malignancy
  • Extent of malignancy (e.g. metastases)
  • Treatments received (e.g. chemotherapy/radiotherapy)
  • Date of the last cycle of chemotherapy (if recent the patient may be immunocompromised)


Past surgical history:

  • Recent surgery
  • Splenectomy
  • Prosthetic joint replacements
  • Prosthetic heart valves
  • Metallic implants (e.g. spinal rods)
  • Intravenous lines and drains

Family history

Malignancies (e.g. leukaemias, lymphoma) – clarify age of onset and environmental risk factors

Autoimmune conditions (e.g. inflammatory bowel disease, rheumatoid arthritis, mixed connective tissue disease)

Infectious diseases (e.g. TB) – relevant if the patient has regular contact with the individual 


Regular medications:

  • Clarify the patient’s current regular medicines
  • Ask about any recent changes, such as new medications or changes in dose



  • Type of antibiotics
  • Duration of treatment


Patients with autoimmune disease or organ transplant recipients are often taking immunosuppressive medication, so you need to clarify what they are currently (or have recently) taken:

  • Long-term steroids
  • Azothiaprine
  • Methotrexate
  • Tacrolimus
  • Mycophenolate mofetil
  • Monoclonal antibodies (e.g. rituximab)


Chemotherapy – if a patient is receiving chemotherapy there are several details you should clarify:

  • Type of chemotherapy
  • Number of cycles of chemotherapy
  • When last chemotherapy was administered


Over-the-counter medications (e.g. paracetamol/herbal remedies)

ALLERGIES – always ask about drug allergies and clarify the details surrounding each

Social history

Occupational exposure (e.g. healthcare workers, exposure to animals)

Hobbies (exposure to water/animals/etc)

Home environment (consider exposure risks at home)

Smoking history (risk factor for malignancy and infection)

Alcohol history (risk factor for malignancy and infection)

Recreational drug use – clarify if drugs are administered intravenously as this is a significant risk factor for infection (e.g. endocarditis)

Systems review

Localising symptoms associated with infection:

  • Respiratory cough, dyspnoea, haemoptysis (e.g. tuberculosis)
  • Cardiovascular – chest pain (e.g. pericarditis)
  • Gastrointestinal abdominal pain/diarrhoea (e.g. inflammatory bowel disease)
  • Hepatic jaundice, nausea, right upper quadrant tenderness (e.g. hepatitis)
  • Genitourinary dysuria, frequency, haematuria (e.g. urinary tract infection)
  • Central nervous system headache, photophobia, seizures, confusion (e.g. cerebral abscess/encephalitis)


Localising symptoms associated with malignancy:

  • Weight loss – a common symptom amongst most malignancies
  • Haematological malignancies bone pain, night sweats, weight loss
  • Solid organ tumours –  lungs (e.g. hoarse voice, finger clubbing, persistent cough, haemoptysis),  colorectal cancer (e.g. change in bowel habits, melaena, tenesmus), abdominal (masses, organomegaly, ascites)


Localising symptoms associated with autoimmune conditions:

  • Rashes – lupus (butterfly rash), sarcoidosis (erythema nodosum), adult-onset Still’s disease (salmon-pink coloured)
  • Morning stiffness and joint swelling – rheumatoid arthritis, psoriatic arthritis
  • Raynaud’s phenomenon can occur in many connective tissue diseases (e.g. rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis)
  • Headache, jaw claudication, scalp tenderness, vision loss suggestive of giant cell arteritis which is associated with polymyalgia rheumatica

Closing the consultation

Thank the patient

Summarise findings

Wash hands


1. Petersdorf RG, Beeson PB; Fever of unexplained origin: report on 100 cases. Medicine (Baltimore). 1961 Feb40:1-30.

2.Hayakawa K, Ramasamy B, Chandrasekar PH; Fever of unknown origin: an evidence-based review. Am J Med Sci. 2012 Oct344(4):307-16.

3. Roth AR, Basello GM; Approach to the adult patient with fever of unknown origin. Am Fam Physician. 2003 Dec 168(11):2223-8.

4. Dr Laurence Knott. Pyrexia of Unknown Origin. Published 19th Oct 2016.



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