Recognizing Red Flags in General Practice

Abstract

Being able to sort the majority of patients who have self-limiting and benign medical conditions from those who need more urgent investigation or referral because they may have a potentially serious underlying disorder remains a key challenge for GPs. This can be a difficult task, given the wide range of medical problems in general practice and the time constraints under which GPs often have to work. Searching for alarm symptoms, signs or diagnostic tests—or ‘red flags’—can help with ‘ruling in’ and ‘ruling out’ serious diagnoses, such as cancer, myocardial infarction or stroke. This article discusses the usefulness—and limitations—of red flags in clinical practice.

The GP curriculum and alarm symptoms

GP curriculum statement 2 refers to The General Practice Consultation. GPs should:

Be able to formulate appropriate diagnoses, rule out serious illness and manage clinical uncertainty

Be able to make timely and appropriate referrals, using relevant information

Definition

‘Red flags’ are alarm or warning symptoms, signs and near-patient diagnostic tests that suggest a potentially serious underlying disease. All red flags can be regarded as ‘diagnostic tests’, in that their presence or absence adjusts the probability of a serious diagnosis. They can be used to ‘rule in’ and ‘rule out’ serious conditions like cancer. In the context of primary care, further investigation or referral is usually required if red flag features are present. However, absence of such features can also provide a useful diagnostic clue when ruling out a serious underlying condition. For instance, in a patient presenting with symptoms of low back pain, absence of radiation effectively rules out a prolapsed vertebral disc as an underlying cause.

Red flags in context

Duration

Usually, harmless symptoms can, in certain situations, become red flags. For example, clinical complaints like ‘cough’, ‘tiredness’ or ‘diarrhoea’ are common in acute self-limiting viral illnesses but can transform into red flag symptoms should they persist. The precise period varies, but the upper limit is usually around 4–6 weeks.

Associated features

The wider context in which a red flag symptom is present is also important. For example, ‘chest pain’ is widely regarded as a red flag symptom as GPs need to consider underlying life threatening differential diagnoses. However, the significance of chest pain depends on whether the main symptom, for example, is a well-defined localized pain on one side of the chest that is tender to pressure and is related to an injury in a young rugby player (which is likely due to musculoskeletal pain) or whether the presenting complaint is a constant central chest tightness radiating to the left arm that is associated with vomiting and sweating in an older smoker (suggesting possible myocardial infarction).

Demographics

The demographic characteristics of the patient are also important contextual issues when considering the diagnostic importance of a symptom or sign that might be thought of as a red flag. For instance, age is an important determinant of cancer risk in patients who present with rectal bleeding. Similarly, the symptom of epigastric pain is not viewed as a red flag in a person aged under 40 years as the probability of gastric cancer is so low in this age group, and other less serious diagnoses, such as reflux or gastritis, are much more likely.

Clinical signs

Lastly, the presence or absence of additional clinical features also provides important contextual information when considering serious underlying conditions and associated red flags. For instance, the absence of abnormal vital signs makes serious underlying infection unlikely in children presenting with acute respiratory symptoms in primary care. For an example of tachycardia being a red flag sign, see Case study 1. Other examples for important clinical red flag signs include a new breast lump, a nodular enlarged prostate gland in a man, a rectal mucosal abnormality or an abdominal mass.

Case study 1: Checking the vital signs

A 50-year-old previously well woman phoned for a home visit because she felt extremely tired and ‘could not get up from the sofa’. She did not have any other symptoms and because a diagnosis could not be made over the telephone received a home visit. The history revealed that she had felt increasingly tired for the preceding 2 days. She did not admit to any chest pain, shortness of breath or any other significant symptoms —and neither did she have any obvious risk factors for feeling tired. On examination, she had a pulse of 160 beats/minute together with quiet heart sounds, but there were no other significant findings. She was admitted to hospital and found to have a large pericardial effusion, although a cause could not be established. She made an uneventful recovery.

Comment:

This case highlights the importance of assessing a patient (and visiting if necessary) if the diagnosis is unclear or in doubt. The only ‘giveaway’ in this case was the tachycardia, which illustrates that checking the vital signs can give important clues when trying to differentiate between minor and more serious underlying diagnoses and in this context is an important red flag in a situation of non-specific symptoms.

The role of red flags

Identifying and interpreting red flags are an important part of clinical practice. However, wrongly over-interpreting the significance of a red flag can lead to over-investigation and over-referral and increase patient anxiety. Not spotting or ignoring red flags may result in malpractice (see Case study 2), missed diagnoses and—in the worst case—death. Red flags can help to decide whether a referral needs to be immediate, urgent within 2 weeks or routine.

Case study 2: Importance of not missing red flags

A 32-year-old mother of three presented with gradual onset of shortness of breath and chest pain but no other relevant symptoms. Her heart rate was 104 beats/minute, she was mildly tachypnoeic with a respiratory rate of 24 and she had a slightly raised body temperature of 37.6°C. After a course of antibiotics, she failed to improve and was referred to a cardiologist. She underwent various cardiac investigations, but no cause for her chest pain was found.

One week after her review cardiology appointment, she suddenly died and a post-mortem examination confirmed the presence of multiple pulmonary emboli, which were identified as the likely cause for her persistent breathlessness and the cause of death. Both the GP and the cardiologist were sued for damages, and the case was settled for an undisclosed sum.

Comment:

In this case, the combination of shortness of breath and chest pain should have alerted the GP and cardiologist as possible red flags for pulmonary embolism, even in the absence of further clinical symptoms and signs, which should have led to appropriate further diagnostic testing.

Red flag symptoms have limitations. Like any diagnostic test, the presence or absence of a red flag can lead to false positive or false negative conclusions about the underlying diagnosis. It is therefore easy to misinterpret the value of red flags in a clinical situation and over-investigation as well as under-investigation are important consequences. Remember that red flags can become ‘red herrings’ if their significance is rated more highly than is appropriate.

Diagnosing serious disease

Most patients presenting in general practice have minor and often self-limiting disorders, for whom using ‘time’ as a diagnostic and therapeutic tool is often appropriate. However, serious medical conditions (such as cancer) sometimes present with relatively minor or non-specific symptoms initially, and so a serious underlying diagnosis is often not suspected until symptoms persist or worsen.

Earlier diagnosis of cancer

Cancer continues to be the leading cause of mortality in people under the age of 75 years (Department of Health, 2007). The key challenge is to pick up cancer symptoms early —making the diagnosis in advanced disease is often fairly straightforward. Not surprisingly, many patients with cancer visit their GP several times before being referred to a specialist. This can lead to a delay in the diagnosis, which contributes to poor cancer survival rates. But identifying cancer symptoms earlier is easier said than done. Although cancer is common, it is still a relatively rare diagnosis to make for an individual GP.

To ensure that specialist referral in suspected cancer takes place at the earliest opportunity, you need to be vigilant to symptoms, signs and results from laboratory tests—the red flags—that may predict serious underlying conditions. Also be aware of non-specific symptoms, which are common but may sometimes suggest the presence of cancer (see Box 1).

Techniques for identifying red flags

Spotting red flags is not always easy. Box 2 lists possible reasons why red flags may easily be missed (Scott, 2009). A number of consultation and communication techniques can help you with identifying red flags early (see Box 3).

Box 1.

Non-specific red flag symptoms

Anorexia and/or weight loss for no apparent reason

Malaise and/or lethargy with no apparent cause

Fever or sweats

Generalized itching

Breathlessness

Bone pain

Lymphadenopathy

Source: NICE Referral guidelines for suspected cancer (2005).

Box 2.

Examples of reasons for missing red flags and making diagnostic errors

Paying too much attention to other findings and ‘closing out’ the diagnosis prematurely

Not considering the correct diagnosis

Not listening enough to the patient's story

Rushing too much

Not knowing enough about the correct diagnosis

Failing to reassess the patient if the working diagnosis does not fit—a rule of thumb is that is the patient's symptoms persist after two alternative diagnoses have been considered, referral or further diagnostic testing may be indicated—a ‘two strikes and you are out’ diagnostic approach • Failure to focus if a patient presents with more than one problem at a time

Being influenced by previous rare but similar cases

Recurrent infections or failure to recover from infections as expected

Source: Scott I. Errors in clinical reasoning: causes and remedial strategies. British Medical Journal (2009) 338: b1860

Box 3.

Techniques for identifying red flags

Use open questions and start generally (e.g. ‘What can I do for you?’, followed by further ‘open’ probing, e.g. ‘Can you tell me a bit more about your symptoms and how they all started’, ‘Is there anything else that you think may be important?’ or ‘And what happened then?’

Find out exactly what the reason for the consultation is and explore the presenting symptom(s) in detail

Be alert all the time and actively search for important ‘hidden’ red flags—defying their name, they are not always obvious!

Be aware of combinations of symptoms that may suggest serious disease (e.g. older age AND tiredness AND weight loss AND rectal bleeding can indicate bowel cancer)

The value of warning symptoms also depends on the patient's account of an illness and symptom description, which may be influenced by your questioning style, which is why—generally speaking—information obtained through open questioning and descriptions that are ‘volunteered’ by a patient are usually of higher value. Because cancer is rare in children, detecting a new malignancy can be difficult, and so it is important to listen carefully and respond empathically to parents' concerns. Red flag features also do not always present in a ‘typical’ textbook fashion and may be difficult to spot, as Case study 3 shows.

Recent developments

The evidence base for the significance of many red flag symptoms in primary care has until recently been surprisingly weak. A growing body of research evidence is now emerging in this rapidly developing field, which increasingly informs decision making in clinical practice.

Case study 3: Revising your diagnosis

A 64-year-old keen runner requested a repeat prescription for ibuprofen, which he needed for treating a pain behind his shoulder blades. On further questioning by the GP, he explained that the ‘muscular’ pain in his back always started after about 10 minutes of running and improved with rest. He also felt a bit more breathless than usual at the times when he developed the pain.

Physical examination and an ECG performed in the practice were normal. Because of the atypical nature of his pain, he was referred for an exercise test, which suggested marked cardiac ischaemia at moderate exercise levels. He saw a cardiologist soon afterwards and underwent angiography and angioplasty for what was found to be severe coronary heart disease. He subsequently made an uneventful recovery and resumed running without any further pain.

Comment:

This case illustrates the value of revisiting a diagnosis when symptoms do not improve or do not fit. The red flag here was not the symptom itself, but the fact that the pain was ‘atypical’, exacerbated by a certain level of exercise and immediately relieved by rest. In situations of ongoing unresolved symptoms, revisiting all important differential diagnoses is an important way of making sure serious diagnostic error is avoided.

Cancer

Improving the earlier diagnosis of cancer is currently high on the National Health Service agenda (Richards, 2009). Jones et al. (2007) evaluated the association between alarm symptoms (including haematuria, haemoptysis, dysphagia and rectal bleeding) and the later diagnosis of cancer in a large cohort study using the General Practice Research Database and found that a new onset of alarm symptoms—i.e. red flags—was associated with an increased likelihood of cancer, particularly in older people. From this study, however, it was not entirely clear for how long alarm symptoms had been present prior to diagnosis. Detailed descriptions of the symptoms were also not available.

New evidence has emerged on how well specific symptoms can predict individual cancers. Hamilton (2009) found that seven symptoms independently appear to predict ovarian cancer:

abdominal distension

postmenopausal bleeding

loss of appetite

urinary frequency

abdominal pain

rectal bleeding

abdominal bloating

Although many symptoms of cancer point to a particular area of the body and should focus your attention to that part of the anatomy, cancer often also presents with non-specific symptoms—symptoms that are also commonly found in benign disease, such as weight loss, tiredness and lymphadenopathy (Hamilton and Peters, 2007).

Other serious disease

Jones et al. (2009) demonstrated that red flags are not only relevant for the diagnosis of cancer but also play an important role in the diagnosis and management of other serious disease. In a recent systematic review, van den Bruel et al. (2010) investigated the importance of clinical features to predict serious infection in previously well children in ambulatory settings and found that cyanosis, rapid breathing, poor peripheral perfusion and a petechial rash were identified as important red flags in several studies. Interestingly, parental concern and the clinician's ‘instinct’ also appeared to be associated with serious underlying infection and can be construed as red flags, particularly in situations where the underlying diagnosis is unclear and the differential diagnoses are being reconsidered.

NICE (2007) have produced useful guidance for identifying red flags in feverish children and use the ‘green’, ‘amber’ and ‘red’ features for guiding clinical management. Other guidelines provide helpful tips on how to recognize red flags for specific conditions, such as the British Guideline for the Management of Asthma (British Thoracic Society and Scottish Intercollegiate Guidelines Network, 2009), which highlights red flags suggesting severe asthma.

Decision support and clinical prediction rules

Clinical prediction rules (CPRs) are clinical tools based on the combined diagnostic (or prognostic) value of symptoms, signs or diagnostic tests that relate to a particular target condition. For instance, the Centor Score (history of fever, absence of cough, presence of exudates on tonsils and cervical lymphadenopathy) enables GPs to rule in or rule out group A beta-haemolytic streptococcus in patients with a sore throat. CPRs are thus extensions of red flags and are becoming more commonplace in clinical practice. Other examples of CPRs include the CRB-65 rule for pneumonia or the ABCD2 rule for risk of stroke in patients who have suffered a transient ischaemic attack (see Table 1).

Table 1.

Useful CPRs

CPR	Clinical condition	Clinical factors	Scoring and interpretation
Centor (1981)	Risk of Group A beta-haemolytic streptococcal (GABHS) throat infection in sore throat	Tonsillar exudate Tender anterior cervical lymph nodes Absence of cough History of fever	If three or four of these clinical signs are present, this suggests that the patient has a 40–60% chance of having GABHS so that antibiotics may be beneficial. If three or four of these signs are absent, the chance of the patient not having GABHS infection is 80% so that antibiotics probably will not be necessary.
ABCD2 (Johnston, 2007)	Risk of stroke after transient ischaemic attack (TIA)	A—age: 60 years of age or older, 1 point.	Add the points to calculate the ABCD2 score. People with a score of 4 or higher have an increased risk of early stroke after a TIA.
		B—blood pressure at presentation: 140/90 mmHg or greater, 1 point.
		C—clinical features: unilateral weakness, 2 points; speech disturbance without weakness, 1 point.
		D—duration of symptoms: 60 minutes or longer, 2 points; 10–59 minutes, 1 point.
		D—presence of diabetes: 1 point.
CRB-65 (Capelastegui, 2006)	Severity of community acquired pneumonia	Confusion—1 point Respiratory rate greater than 30 breaths per minute—1 point Systolic blood pressure less than 90 mm Hg or diastolic blood pressure less than 60 mm Hg—1 point Age greater than 65 years—1 point	A score of 0—indicates low risk of death and admission to hospital is usually not needed.
			A score of 1–2—indicates an increased risk of mortality and hospital admission will usually be required.
			A score of 3 or more—suggests a high risk of death, and urgent admission to hospital should be considered.

Research limitations

Because many studies on clinical symptoms were, in the past, conducted retrospectively, results have to be interpreted with caution. This is because patient records used for the studies often failed to give information on the time that symptoms had been present and lacked details about the diagnosis and the presence or absence of additional symptoms. These retrospective studies are also prone to recall bias—which means that affected patients are more likely to remember the presence or absence of symptoms when compared with unaffected comparison patients. For this reason, further prospective studies are needed to identify and confirm the value of red flag features in the clinical encounter in general practice.

Acting on red flags

If red flag symptoms suggestive of cancer have been present for 3 or more weeks—particularly if they do not improve—consider urgent referral. Any physical red flag signs (such as a ‘craggy’ prostate or a definite breast lump in association with skin changes) should also lead to immediate urgent referral. NICE (2005) have produced a useful summary of important red flags for important individual cancers, which is helpful for making clinical decisions (see Box 4).

Other sources exist that specify particular symptoms, which should trigger a more detailed clinical assessment, urgent investigation or specialist referral in many non-cancer presentations (Schroeder, 2010; Jones et al., 2009; van den Bruel et al., 2010). If you are not sure how to interpret the relevance of potential red flag clinical symptoms and signs (particularly if they are not typical) or if a patient fails to recover as expected, consider discussing these with your colleagues in the practice or a specialist. If a patient presents with typical features of cancer, urgent referral is indicated rather than further investigation in primary care.

Box 4.

Examples of important red flags in selected cancers

Lung cancer

Unexplained and persistent (longer than 3 weeks) chest and/or shoulder pain

Dyspnoea

Weight loss

Chest signs

Hoarseness

Finger clubbing

Cervical or supraclavicular lymphadenopathy

Cough

Signs of vena cava obstruction

Stridor

Haemoptysis in smokers or ex-smokers aged 40 years and older

A history of asbestos exposure

Upper gastro-intestinal cancer

Chronic gastro-intestinal bleeding

Progressive unintentional weight loss

Persistent vomiting

Iron deficiency anaemia

Epigastric mass

Dysphagia

Unexplained upper abdominal pain

Obstructive jaundice

Refer urgently for endoscopy patients aged 55 years and older who present with unexplained and persistent recent onset dyspepsia alone.

Lower gastro-intestinal cancer

Rectal bleeding with a change of bowel habit towards looser stools and/or increased stool frequency persisting 6 weeks or more in people aged 40 years and older

Rectal bleeding persisting for 6 weeks or more without a change in bowel habit and without anal symptoms in people aged 60 years and older

A change in bowel habit to looser and/or more frequent stools persisting for 6 weeks or more without rectal bleeding in people aged 60 years or older

A right lower abdominal mass consistent with involvement of the large bowel in people of any age

A palpable rectal mass

Unexplained iron deficiency anaemia (Hb 11 g/dl or below in men and 10 g/dl or below in non-menstruating women)

Source: NICE. Referral guidelines for suspected cancer (2005)

If patients show clinical features less typical of cancer, consider further investigations but ensure that these are marked urgent and that you actively look out for and act on their results. Even in patients with a low probability of cancer (younger age with non-serious symptoms—for example, a young person with a history of isolated rectal bleeding), it is advisable to adopt a ‘watchful waiting’ strategy, with clear instructions to the patient about when to return for further assessment if symptoms continue to persist.

Cues for action

In addition to red flag symptoms, take other considerations into account when searching for or excluding serious underlying disease, such as demographic characteristics and an additional risk factors (e.g. age, smoking or alcohol misuse) and features like symptom severity, persistence of problems or lack of response to a trial of treatment. While positive red flags should prompt you to take action in terms of focussing your clinical assessment on a particular area, arranging further investigation or referring for a specialist opinion, the absence of red flag symptoms can help with ruling out diagnoses. Unfortunately, appropriate recognition of red flags is not always easy because many symptoms that can be regarded as red flags—such as rectal bleeding—may also occur in common and benign conditions (for example, in haemorrhoids).

Keeping up-to-date with red flags

Regard the knowledge and skills that you need to identify red flags as a tool that you need to keep sharpening throughout your career. To help maintain a high level of alertness, spend some time of your ongoing professional development on learning around diagnosis and management of serious medical conditions. Taking part in educational activities (such as training days or using online educational resources), in-house peer review and significant event audits and looking out for relevant articles in medical journals help you with keeping up-to-date and improve your diagnostic and consultation skills.

Key points

Become and stay familiar with typical presenting features of cancer and other serious conditions

Consider serious underlying disease, such as cancer when confronted by unusual symptom patterns or if patients fail to recover as expected

Ask yourself: ‘What are the diagnoses I don't want to miss?’

Keep an open mind and don't jump to conclusions

Be alert and maintain a high level of suspicion when assessing patients, particularly those who continue to have persistent symptoms over a period of time

References

British Thoracic Society and Scottish Intercollegiate Guidelines Network . British guideline on the management of asthma. Accessed via www.brit-thoracic.org.uk/Portals/0/Clinical%20Information/Asthma/Guidelines/sign101%20revised%20June%2009.pdf [date last accessed 30.07.2010].

Centor

R.M.

Witherspoon

J.M.

Dalton

H.P.

Brody

C.E.

Link

The diagnosis of strep throat in adults in the emergency room. Medical Decision Making (1981) 1: p. 239–46.

Department of Health . Cancer reform strategy (2007) London: HMSO Accessed via www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/documents/digitalasset/dh_081007.pdf [date last accessed 20 June 2010].

Capelastegui

Espana

P.P.

Quintana

J.M.

Validation of a predictive rule for the managment of communityacquired pneumonia. European Respiratory Journal (2006) 27: p. 151–7.

Hamilton

The CAPER studies: five case-control studies aimed at identifying and quantifying the risk of cancer in symptomatic primary care patients. British Journal of Cancer (2009) 101: p. S80–6.

Hamilton

Peters

T.J.

Cancer diagnosis in primary care (2007) Philadelphia: Churchill Livingstone Elsevier ISBN 13978044310367–4.

Hamilton

Peters

T.J.

Bankhead

Sharp

Risk of ovarian cancer in women with symptoms in primary care: population based case-control study. British Medical Journal (2009) 339: p. b2998.

Johnston

S.C.

Rothwell

P.M.

Nguyen-Huynh

M.N.

Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack. Lancet (2007) 369: p. 283–92.

Jones

Latinovic

Charlton

Gulliford

Alarm symptoms in early diagnosis of cancer in primary care: cohort study using General Practice Research Database. British Medical Journal (2007), 334: p. 1013–4.

10.

Jones

Charlton

Latinovic

Gulliford

Alarm symptoms and identification of non-cancer diagnoses in primary care: cohort study. British Medical Journal (2009) 339: p. b3094.

11.

NICE . Referral guidelines for suspected cancer (2005) London: NICE Accessed via www.nice.org.uk/nicemedia/pdf/cg027niceguideline.pdf [date last accessed 21.06.2010].

12.

NICE . Feverish illness in children: assessment and initial management in children younger than 5 years (2007) London: NICE Accessed via www.nice.org.uk/nicemedia/live/11010/30525/30525.pdf [date last accessed 30.06.2010].

13.

RCGP Curriculum statement 2: the general practice consultation. Accessed via www.rcgp-curriculum.org.uk/PDF/curr_2_The_GP_Consultation.pdf [date last accessed 20.08.2010].

14.

Richards

M.A.

The national awareness and early diagnosis initiative in England: assembling the evidence. British Journal of Cancer (2009) 101: p. S1–4.

15.

Schroeder

The 10-minute clinical assessment (2010) Chichester: Wiley-Blackwell/BMJ ISBN 9781405181952.

16.

Scott

Errors in clinical reasoning: causes and remedial strategies. British Medical Journal (2009) 338: p. b1860.

17.

Van den Bruel

Haj-Hassan

Thompson

Buntinx

, Mant, D for the European Research Network on Recognising Serious Infection investigators. Diagnostic value of clinical features at presentation to identify serious infection in children in developed countries: a systematic review. Lancet (2010) 375: p. 834–45.