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.¹Additional 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 lymphoma)
Opening the consultation
Wash your hands and don PPE if appropriate.
Introduce yourself to the patient including your name and role.
Confirm the patient’s name and date of birth.
Explain that you’d like to take a history from the patient.
Gain consent to proceed with history taking.
General communication skills
It is important you do not forget the general communication skills which are relevant to all patient encounters. Demonstrating these skills will ensure your consultation remains patient-centred and not checklist-like (just because you’re running through a checklist in your head doesn’t mean this has to be obvious to the patient).
Some general communication skills which apply to all patient consultations include:
- Demonstrating empathy in response to patient cues: both verbal and non-verbal.
- Active listening: through body language and your verbal responses to what the patient has said.
- An appropriate level of eye contact throughout the consultation.
- Open, relaxed, yet professional body language (e.g. uncrossed legs and arms, leaning slightly forward in the chair).
- Making sure not to interrupt the patient throughout the consultation.
- Establishing rapport (e.g. asking the patient how they are and offering them a seat).
- Signposting: this involves explaining to the patient what you have discussed so far and what you plan to discuss next.
- Summarising at regular intervals.
Use open questioning to explore the patient’s presenting complaint:
- “What’s brought you in to see me today?”
- “Tell me about the issues you’ve been experiencing.”
Provide the patient with enough time to answer and avoid interrupting them.
Facilitate the patient to expand on their presenting complaint if required:
- “Ok, can you tell me more about that?”
Open vs closed questions
History taking typically involves a combination of open and closed questions. Open questions are effective at the start of consultations, allowing the patient to tell you what has happened in their own words. Closed questions can allow you to explore the symptoms mentioned by the patient in more detail to gain a better understanding of their presentation. Closed questions can also be used to identify relevant risk factors and narrow the differential diagnosis.
History of presenting complaint
When taking a history from a patient with PUO you need to ask a broad range of questions to help narrow the differential diagnosis. We’ve broken down the history of presenting complaint into several areas of focus including:
- Infectious disease
- Autoimmune disease
Take a comprehensive history of the patient’s fever.
Onset and duration
Clarify when the fever developed:
- “When did you first notice the fever?”
- “How long have you been experiencing fevers?”
Ask how the fever has changed over time:
- “How frequently have you been experiencing the fever?”
- “Has the frequency of the fever changed since it first started?”
- “Is there any clear pattern to the fever?”
Ask if there are any triggers or exacerbating factors for the fever:
- “Was there any obvious trigger that preceded the onset of fevers?”
Ask if anything seems to improve the fevers:
- “Does anything reduce the frequency or severity of the fevers?”
Ask if there are other symptoms which are associated with the fever:
- Night sweats
- Weight loss
- Pain (clarify location)
- Swelling (abscess, lymphadenopathy)
- Skin changes (e.g. rash, itch)
Ask the patient if they have been recording their fevers and if so what those readings were:
- “Did you measure your temperature at home?”
- “Do you remember what your highest temperature was?”
Explore the patient’s history for evidence of underlying infectious disease.
Current infectious symptoms
Screen for current symptoms suggestive of underlying infection including:
- Respiratory: cough, dyspnoea, haemoptysis (e.g. tuberculosis)
- Cardiovascular: chest pain (e.g. pericarditis)
- Gastrointestinal: abdominal pain, diarrhoea (e.g. Campylobacter jejuni)
- Hepatic: jaundice, nausea, right upper quadrant tenderness (e.g. hepatitis)
- Genitourinary: dysuria, frequency, haematuria, urethral discharge (e.g. urinary tract infection, sexually transmitted infection)
- Central nervous system: headache, photophobia, seizures, confusion (e.g. cerebral abscess, encephalitis)
- Musculoskeletal: joint pain and swelling (e.g. septic arthritis)
- Dermatological: rash, erythema, skin breaks (e.g. cellulitis, Kawasaki’s disease)
Ask the patient if they have had any recent infections and if so gather more details including:
- the type of infection and if this was confirmed (e.g. culture or PCR)
- the symptoms the patient experienced and if these have fully resolved
- the treatments the patient received and if these were taken as prescribed (e.g. completing a course of antibiotics)
Ask the patient if they have potentially been exposed to sources of infection locally including:
- close contact with others who were unwell at the time
- contaminated water or food
- recent injuries (e.g. breaks in the skin)
- contact with animals
- sexual activity without contraception
- recreational drug use (intravenous and intranasal)
Take a thorough travel history to identify areas in which the patient may have been infected:
- Location (e.g. rural, urban)
- Departure and return dates
- Chemoprophylaxis and compliance (e.g. malarone for malaria)
- Activities (e.g. water-based activity, animal contact)
- Accommodation (e.g. malaria bed nets)
- Insect bites
- Injuries (e.g. breaks in the skin)
- Food and water consumption
- Sick contacts
- Sexual activity
- Tattoos and piercings
Screen for clinical features of autoimmune disease including:
- Morning joint stiffness and swelling: associated with rheumatoid arthritis and psoriatic arthritis.
- Rashes: associated with lupus (butterfly rash), sarcoidosis (erythema nodosum) and adult-onset Still’s disease (salmon-pink coloured rash).
- Discoloured fingers and toes: may be caused by Raynaud’s phenomenon which is associated with connective tissue diseases such as rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis.
- Headache, jaw claudication, scalp tenderness, visual loss: suggestive of giant cell arteritis which is associated with polymyalgia rheumatica.
- Dry eyes and/or mouth: associated with Sjogren’s syndrome.
- Red and/or painful eyes
- Dry cough: associated with several connective tissue diseases including sarcoidosis.
Screen for clinical features of malignancy including:
- Weight loss
- Change in bowel habit (including blood in stool)
- Shortness of breath
- Bone pain
- Night sweats
Ideas, concerns and expectations
A key component of history taking involves exploring a patient’s ideas, concerns and expectations (often referred to as ICE) to gain insight into how a patient currently perceives their situation, what they are worried about and what they expect from the consultation.
The exploration of ideas, concerns and expectations should be fluid throughout the consultation in response to patient cues. This will help ensure your consultation is more natural, patient-centred and not overly formulaic.
It can be challenging to use the ICE structure in a way that sounds natural in your consultation, but we have provided several examples for each of the three areas below.
Explore the patient’s ideas about the current issue:
- “What do you think the problem is?”
- “What are your thoughts about what is happening?”
- “It’s clear that you’ve given this a lot of thought and it would be helpful to hear what you think might be going on.”
Explore the patient’s current concerns:
- “Is there anything, in particular, that’s worrying you?”
- “What’s your number one concern regarding this problem at the moment?”
- “What’s the worst thing you were thinking it might be?”
Ask what the patient hopes to gain from the consultation:
- “What were you hoping I’d be able to do for you today?”
- “What would ideally need to happen for you to feel today’s consultation was a success?”
- “What do you think might be the best plan of action?”
Summarise what the patient has told you about their presenting complaint. This allows you to check your understanding of the patient’s history and provides an opportunity for the patient to correct any inaccurate information.
Once you have summarised, ask the patient if there’s anything else that you’ve overlooked. Continue to periodically summarise as you move through the rest of the history.
Signposting, in a history taking context, involves explicitly stating what you have discussed so far and what you plan to discuss next. Signposting can be a useful tool when transitioning between different parts of the patient’s history and it provides the patient with time to prepare for what is coming next.
Explain what you have covered so far: “Ok, so we’ve talked about your symptoms, your concerns and what you’re hoping we achieve today.”
What you plan to cover next: “Next I’d like to discuss your past medical history and then explore what medications you currently take.”
A systemic enquiry involves performing a brief screen for symptoms in other body systems which may or may not be relevant to the primary presenting complaint. A systemic enquiry may also identify symptoms that the patient has forgotten to mention in the presenting complaint.
Deciding on which symptoms to ask about depends on the presenting complaint and your level of experience.
Some examples of symptoms you could screen for in each system include:
- Systemic: weight loss (e.g. malignancy)
- Cardiology: palpitations (e.g. endocarditis)
- Respiratory: shortness of breath and cough (e.g. tuberculosis, sarcoidosis)
- Gastrointestinal: abdominal pain and diarrhoea (e.g. infective diarrhoea)
- Neurological: confusion (e.g. cerebral abscess)
- Musculoskeletal: back pain (e.g. discitis)
- Dermatological: rash, erythema, skin breaks (e.g. cellulitis, Kawasaki’s disease)
Past medical history
Ask if the patient has any medical conditions:
- “Do you have any medical conditions?”
- “Are you currently seeing a doctor or specialist regularly?”
If the patient does have a medical condition, you should gather more details to assess how well controlled the disease is and what treatment(s) the patient is receiving. It is also important to ask about any complications associated with the condition including hospital admissions.
Ask if the patient has previously undergone any surgery or procedures (e.g. joint replacement):
- “Have you ever previously undergone any operations or procedures?”
- “When was the operation/procedure and why was it performed?”
Take an immunisation history to ensure the patient has received all of the relevant vaccinations:
- “Can I just check which vaccinations you’ve had?”
Ask if the patient has any allergies and if so, clarify what kind of reaction they had to the substance (e.g. mild rash vs anaphylaxis).
Examples of relevant medical and surgical history
Medical history relevant to PUO includes:
- Previous and current infections (e.g. HIV, tuberculosis, endocarditis, abscesses, osteomyelitis)
- Conditions associated with reduced immunity (e.g. diabetes, myeloma, transplant recipient)
- Autoimmune disease (e.g. systemic lupus erythematosus, sarcoidosis, rheumatoid arthritis)
Surgical history relevant to PUO includes:
- Recent surgery
- Previous splenectomy
- Prosthetic joint replacements
- Prosthetic heart valves
- Metallic implants (e.g. spinal rods)
- Intravenous lines (e.g. central line)
Ask if the patient is currently taking any prescribed medications or over-the-counter remedies:
- “Are you currently taking any prescribed medications or over-the-counter treatments?”
If the patient is taking prescribed or over the counter medications, document the medication name, dose, frequency, form and route.
Ask the patient if they’re currently experiencing any side effects from their medication:
- “Have you noticed any side effects from the medication you currently take?”
Relevant medications in the context of PUO include:
- Immunosuppressants (e.g. corticosteroids, methotrexate, azathioprine, tacrolimus, biologics)
Ask the patient if there is any family history of cancer or autoimmune conditions:
- “Is there any history of cancer in your close relatives?”
- “Is there any history of diseases related to the immune system in your close relatives?”
Ask if any of the patient’s close family members currently have any serious infections such as tuberculosis:
- “Do any of your family members currently have an infectious disease at the moment?”
Explore the patient’s social history to understand their social context.
General social context
Explore the patient’s general social context including:
- the type of accommodation they currently reside in (e.g. house, bungalow) and if there are any adaptations to assist them (e.g. stairlift)
- who else the patient lives with and their personal support network
- what tasks they are able to carry out independently and what they require assistance with (e.g. self-hygiene, housework, food shopping)
- if they have any carer input (e.g. twice daily carer visits)
- if there are animals in the home
Record the patient’s smoking history, including the type and amount of tobacco used.
Smoking is a significant risk factor for malignancy and impairs immune function.
Record the frequency, type and volume of alcohol consumed on a weekly basis.
Alcohol is a significant risk factor for malignancy and impairs immune function.
Recreational drug use
Ask the patient if they use recreational drugs and if so determine the type of drugs used and their frequency of use.
Intravenous drug use is associated with an increased risk of developing blood-borne infections including HIV, hepatitis B/C and bacterial infections (e.g. endocarditis).
Ask about the patient’s current occupation to identify any potential exposure to infectious diseases (e.g. healthcare worker, exposure to animals).
Ask about the patient’s current hobbies to identify potential exposure to infectious diseases (e.g. contaminated water, animals).
Closing the consultation
Summarise the key points back to the patient.
Ask the patient if they have any questions or concerns that have not been addressed.
Thank the patient for their time.
Dispose of PPE appropriately and wash your hands.
- Petersdorf RG, Beeson PB; Fever of unexplained origin: report on 100 cases. Medicine (Baltimore). 1961 Feb40:1-30. Available from: [LINK].
- Hayakawa K, Ramasamy B, Chandrasekar PH; Fever of unknown origin: an evidence-based review. Am J Med Sci. 2012 Oct344(4):307-16. Available from: [LINK].
- Roth AR, Basello GM; Approach to the adult patient with fever of unknown origin. Am Fam Physician. 2003 Dec 168(11):2223-8. Available from: [LINK].
- Dr Laurence Knott. Pyrexia of Unknown Origin. Patient.info. Published 19th Oct 2016. Available from: [LINK].