Fever in adults - red flag symptoms

Pyrexia in adults has a wide range of differential diagnoses. Dr Pipin Singh provides tips on how to identify potentially serious causes, including COVID-19, sepsis or malignancy, and when to refer.

(Photo: Kmatta/Getty Images)
(Photo: Kmatta/Getty Images)

Red flag symptoms associated with pyrexia

  • Red flags related to COVID-19
  • Persistent fever defined as > 3 weeks with no clear cause after initial assessment
  • History of foreign travel
  • Persistent cough, shortness of breath, expectorate, haemoptysis
  • New onset headache with or without focal neurological symptoms
  • New onset headache with associated photophobia, neck stiffness
  • New onset rashes, and in particular non-blanching petechial rash
  • New onset facial swelling or facial pain
  • Persistent neck swelling/lymph glands for >6 weeks.
  • Night sweats for more than 6 weeks
  • Unintentional weight loss
  • New onset abdominal pain
  • Bloody diarrhoea
  • New onset urinary symptoms - dysuria, haematuria, loin pain
  • New onset vaginal discharge in association with lower abdominal pain (and any history of recent pregnancy)
  • New onset testicular swelling with or without erythema
  • New onset significant low back pain
  • New onset joint swelling
  • Any recent exposure to HIV
  • New onset leg swelling
  • Any obvious redness to the skin
  • Any skin breakdown, such as pressure sores in nursing home patients or leg ulcers (arterial or venous)
  • Any indwelling devices, for example chest drains, catheters, PEG tubes
  • Recent intravenous drug use
  • Recent chemotherapy treatment. Any immunosuppressants such as steroids or disease modifying drugs (DMARDS)
  • History of pregnancy within last 6 weeks and any associated birth complications such as preterm ruptured membranes, or forceps delivery
  • Trismus

Common scenarios and use of NEWS2

Due to the broad range of differential diagnoses causing pyrexia, this article aims to cover the most common scenarios faced by GPs in the context of a pyrexial illness and the red flag symptoms that should prompt an urgent secondary care assessment.

Sepsis is a leading cause of mortality. There are numerous tools available for recognising sepsis such as the UK Sepsis Trust clinical tools and the RCGP Sepsis Toolkit.1,2

NICE’s 2016 guideline on recognition, diagnosis and management of sepsis allows the physician to risk stratify sepsis into moderate to high or high risk.3 The main parameters include assessment of breathing, circulation, urine output, change in mental state, history of fever and skin changes.

The NEWS2 score can be used for assessment of illness severity in adults.4 However, the accuracy of NEWS2 in primary care is not fully established and should be used as an aid in conjunction with your history and other examination findings.5

The NEWS2 Score
Respiratory rate (breaths per minute)8 or less
25 or more
Hypercapnic respiratory failureNo
If yes, Sp02 measurement to produce further score
Room air/supplemental oxygenRoom air
Supplemental oxygen
Temperature (degrees Centigrade)35.0 or below
39.1 or more
Systolic BP (mmHg)90 or below
220 or more
Pulse (bpm)40 or below
131 or more
New-onset confusion

Possible causes including COVID-19

True pyrexia is unlikely to be a presenting problem but more likely to be uncovered as part of your data gathering for another presentation. Pyrexia in adults has a broad range of differentials, thus a focused history and examination is critical to the outcome of your assessment.

Pyrexia is defined as a temperature of >37.2 degrees Centigrade and can be graded into low, intermediate or severe with severe pyrexia being defined as a temperature of >40 degrees. Note temperatures of <36.0 degrees should also alert the clinician to infective pathology.

Possible causes

  • COVID-19
  • Acute respiratory tract infections such as tonsillitis, glandular fever, bronchitis, whooping cough, pneumonia. These can be bacterial or viral infections.
  • Chronic respiratory infections such as TB
  • ENT infections - sinusitis, parotitis, otitis externa/media, quinsy
  • Dental infections
  • Cerebral causes - cerebral abscess, meningitis, encephalitis
  • Tropical infections - malaria, Lyme disease
  • Gastrointestinal infection, for example bacterial/viral gastroenteritis, diverticulitis, cholecystitis, pancreatitis, peritonitis (for example, secondary to a perforation)
  • Uncomplicated or complicated urinary tract infection
  • Obstructive uropathy secondary to renal calculus
  • Pelvic inflammatory disease
  • Epididymo-orchitis
  • Septic joint
  • Infective endocarditis
  • Discitis
  • Cellulitis of any origin
  • Seroconversion illness associated with HIV infection
  • Cancer. Any malignancy can cause fever as a direct result of tumour or as a complication associated with that tumour
  • Malignant hyperthermia - for example with ecstasy use
  • Abdominal collections, pelvic collections or empyema
  • Infected pressure sores, particularly in chair- or bed-bound patients
  • Postoperative complications

Taking a history

Questions to consider include:

  • What does the patient mean by fever? When did it start?
  • Have they checked their temperature and if so how? What readings did they obtain?
  • Is there any pattern to the fever? Spiking temperatures are more likely to represent an abscess.
  • A detailed systems review will be necessary if no clues have already been provided. This becomes particularly more relevant in patients where history is limited - for example, in residential or nursing homes.
  • If there are limited clues from the systems review, then you may wish to explore symptoms such as weight loss, appetite loss, night sweats and foreign travel.
  • Smoking and alcohol history may be relevant, particularly if malignancy is suspected.
  • Recreational drug use may also be relevant. A sexual history may be necessary if HIV infection is suspected.
  • Has there been any recent surgery? Have any new medications been started? Is the patient taking any immunosuppressants? Has there been any recent radio- or chemotherapy?
  • Are there any chronic conditions to be aware of such as COPD, bronchiectasis, motor neurone disease?

Explore the patient’s thoughts and feelings around their problem. Is there a specific relevant concern that needs to be addressed? How is the problem impacting on their life?

Note, elderly patients with sepsis often do not have temperature spikes - instead they may present with new confusion or 'off legs'.

Assessment and examination

Remote assessment
By telephone, assessment may include asking about the following:

  • Blood pressure using a patient's own machine
  • Pulse oximetry via patient's own device
  • Temperature using the patient's thermometer
  • How fast is the patient breathing?
  • Can they check their pulse?
  • Are their peripheries cool?
  • How does their breathing sound?
  • Can they complete sentences?

By video link, you may also be able to assess how the patient looks.

If relevant, assess for signs of meningitis including severe headache, neck stiffness, photophobia and confusion.

Face-to-face examination
Examination includes general observation, BP and pulse, using appropriate personal protective equipment if conducting a face-to-face examination. You may wish to perform an abbreviated mental test score (AMTS) if there is a history of confusion.

Examination will be guided by the history but may include:

  • ENT examination
  • Chest examination
  • Auscultation of heart sounds
  • Abdominal examination
  • Gynaecological examination
  • Genitourinary examination

You may need to assess certain joints or review ulcers, which may be dressed, or pressure sores that may be difficult to visualise particularly in housebound patients. A joint assessment with a district nurse may be needed to see a wound without a dressing.


Investigations to consider in primary care include:

  • Basic bloods such as FBC, CRP, ESR, UEs
  • An HIV test if the history suggests this is a possibility
  • Further investigations will be determined by history but could include:
  • Sputum culture and sensitivity
  • Stool C/S
  • Urine dip stick +/- MSU
  • Genital swabs
  • Wound swabs
  • Throat swab
  • Eye swab
  • Plain AP chest x-ray
  • COVID-19 test

When to refer


  • Immediately if septic shock is suspected (999 response is likely to be needed)
  • If a pyrexia of unknown origin is suspected
  • If tropical illness is suspected
  • If HIV is suspected
  • If the diagnosis is in doubt
  • If a suspected condition fails to respond to multiple antibiotics in the community.

There are many other reasons to refer and your decision will be dependent on your history and examination.

Key learning points

  • Numerous tools exist for identifying sepsis and the NEWS2 score can be used to determine illness severity, although it has limitations in general practice
  • Pyrexia in adults has a broad range of differentials, with severe pyrexia defined as a temperature above 40 degrees Centigrade
  • A thorough history should be taken; a detailed systems review may be needed if history is limited
  • Explore symptoms such as weight loss, smoking and alcohol history, particularly if malignancy is suspected
  • Examination and assessment should include general observation, BP and pulse, and breathing rate
  • Refer immediately if septic shock is suspected (a 999 response may be needed)

Dr Pipin Singh is a GP in Northumberland. This article was first published in January 2017, and was updated on 23 January 2018 and 3 July 2020.

Visit MIMS Learning for an interactive version of this article and a CPD certificate.


  1. Nutbeam T, Daniels R on behalf of the UK Sepsis Trust. Clinical tools. [Accessed 20 May 2020]
  2. RCGP. Sepsis toolkit. [Accessed 3 June 2020]
  3. NICE. Sepsis: recognition, diagnosis and early management. NG51. July 2016, updated September 2017.
  4. MD Calc. National early warning score (NEWS) 2. [Accessed 3 June 2020]
  5. Finnikin S, Wilke V. What's behind the NEWS? National Early Warning Scores in primary care. BJGP 2020; 70; 272-273

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