Medically Unexplained Symptoms

Definition

A medically unexplained symptom (MUS) can be described as a physical symptom for which no organic cause can be demonstrated. Consider a diagnosis of MUS in any patient who has physical symptoms, present for 3 months or more, that are affecting functioning but that cannot be readily explained [Royal College of General Practitioners (RCGP)/Royal College of Psychiatrists/National Mental Health Development Unit/Trailblazers, 2011]. Often, the patient is sent for multiple investigations with little reassurance and this may lead to being labelled as a ‘heartsink’ patient or a ‘frequent flyer’.

Such patients are also often described as having a ‘functional’ or ‘somatoform’ disorder. The International Classification of Disease (ICD-10) lists six different types of somatoform disorder alone, including somatization disorder, undifferentiated somatoform disorder, hypochondriacal disorder and pain disorder related to psychological factors. In primary care, these conditions all present with MUS and the precise label is usually not important.

MUS can be divided into three main types of complaint:

pain of a specific location, e.g. back pain or headache

As shown in Box 1, a vast array of symptom clusters have been described for which no organic cause can be found, covering all medical specialities. The three most common are IBS, CFS and fibromyalgia. There is significant diagnostic controversy over the cause and existence of a number of these syndromes. Although symptoms can be very diverse, there are striking similarities between the patients that present with them.

It is estimated that MUS costs the National Health Service (NHS) around £3.1 billion every year. When other costs are taken into consideration, such as inability to work, the bill for MUS rises to a staggering £18 billion/year in the UK (RCGP/Royal College of Psychiatrists/National Mental Health Development Unit/Trailblazers, 2011). Therefore, effective diagnosis and management are essential to keep costs down.

Epidemiology

Estimates of prevalence of MUS vary due to diagnostic difficulties and labelling, but it is thought that up to a quarter of primary care consultations and up to a half of secondary care consultations are due to MUS (RCGP/Royal College of Psychiatrists/National Mental Health Development Unit/Trailblazers, 2011). Women are more likely to have MUS than men. Symptoms can be precipitated by organic illness, accidents, stressful life events and other environmental factors such as media campaigns that highlight specific diseases. Other possible risk factors for MUS include severe illness or death of a close relative, childhood adversity or abuse and domestic violence.

Many patients have more than one MUS. There are also common overlaps of symptoms. For example, those with IBS often meet the criteria for chronic pelvic pain and vice versa. Patients may have concurrent psychological illness and the risk of this increases with the number of symptoms that a patient experiences. For example, 20% of patients with one MUS have underlying psychological issues, but this rises to 80% if they have 10 or more symptoms.

The psychology of MUS

There are a number of psychological processes thought to contribute to MUS. Patients with MUS may have a preoccupation with fears of having a serious illness, based on the misinterpretation of bodily symptoms, despite investigation and reassurance. Many patients also have an enhanced sense of bodily awareness. This is the tendency to notice and amplify benign physical sensations, such as the heartbeat. Over awareness increases anxiety and, in a vicious circle, actually makes the sensation more likely. Enhanced bodily awareness is often a feature in IBS, fibromyalgia and CFS.

In addition, patients may have difficulties in the way in which they attribute symptoms. Burton (2003) describes attribution as ‘the cognitive process by which somatic sensations are interpreted in the context of the body and its environments’. For example, fatigue attributions can be

Normalizing—‘I am tired because I am unfit and overworked’

It is thought that patients with MUS are less able to normalize symptoms than other patients and although they do not seem to think that the symptoms are serious, they are unable to come up with other rational explanations. Interestingly, although the symptom may change over time, the attribution style tends to stay similar.

Assessment of patients with MUS

Patients present with their symptoms for a variety of reasons: the severity of the symptom, the disruption to the patient's life or fear of an underlying serious illness. Whether the patient is known to present with unexplained symptoms or not, in all cases, all symptoms should be assessed without judgement. Patients with MUS have the same chance of developing serious new illnesses as any other patients.

Take a history about the presenting symptom, taking care to rule out any red flags so that patients realize that they are being taken seriously from the outset. Take time to engage with patients and explore their ideas and expectations. Box 2 gives a framework for assessing patients with MUS.

It is vital to rule out any possible anxiety or depressive disorder as these conditions regularly present with somatic symptoms. Overall, around 30% of patients with MUS have underlying psychiatric disorder, usually anxiety or depression. Also, explore the possibility of emotional distress: is there something else going on in the patient's life at this time? Consider screening all patients with MUS for depression using a standard questionnaire such as the PHQ-9. Anxiety screening tools such as the Generalized Anxiety Disorder Assessment (GAD-7) may also be helpful.

Asking patients to explain their understanding of the disorder can often uncover interesting thought processes. For example, in an obese patient: ‘my knee pain is caused by exercise, so I am unable to undertake any exercise while my knee is sore (or while I am overweight)’.

In addition, find out if patients have been seeking information elsewhere; do they have friends and relatives who have some clinical knowledge or have they looked up the symptoms on the Internet. This is vital for both understanding patients' psychosocial context and also for ensuring that they have a consistent management plan.

If a thorough history ruling out red flags and other symptoms that might point you to an organic cause for the patient's symptoms, and an examination directed by the history, fail to find any abnormalities, it is unlikely that there will be an organic cause for the complaint. However, depending on the presenting symptom, some investigations may be indicated. It is important to find the right balance between appropriate investigation and the risk of possible iatrogenic harm through over-investigation.

Investigations are used in MUS to reassure both the doctor and the patient; however, this is not always effective. Up to half of all patients are not reassured following negative investigations and continue to be concerned about serious illness. To improve the usefulness of investigations, explain what the investigation is, why the investigation is being done, what it will involve and what a negative result means. Table 1 highlights some investigations that are recommended in the most common syndromes. However, the VAMPIRE trial in the Netherlands (van Bokhoven et al., 2009) suggested that if no serious illness was suspected, it was worth considering waiting 4 weeks before initiating tests as the majority of patients never re-consulted.

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Table 1.

Investigations for the most common MUSs

Symptom	Possible investigations
Chronic fatigue	Urinalysis Full blood count (FBC) Biochemistry: renal, liver and thyroid function tests; serum glucose; serum calcium Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) Creatine kinase Antibody testing for coeliac disease (together with IgA levels)
IBS	Patients under 40 years of age : FBC, ESR and antibody testing to exclude coeliac disease (together with IgA levels) Patients over 40 years of age : Colonic cancer must be excluded for any patient with a persistent unexplained change in bowel habit—particularly towards looser stools. Other investigations to consider Thyroid function tests if other symptoms/signs of thyroid disease Stool samples to exclude gastrointestinal infection if diarrhoea Endocervical swabs for Chlamydia
Fibromyalgia	Urinalysis FBC ESR and CRP Biochemistry: renal, liver and thyroid function tests; serum glucose; serum calcium Creatine kinase, rheumatoid factor and anti-nuclear antibody (but beware the risk of false positives)

Before requesting a test, consider carefully if that test is required. Apart from the iatrogenic risk of investigations, over-investigating patients with MUS may be seen as collusion which increases the risk of ‘illness behaviour’. In addition, the possibility of a false positive result provides more uncertainty and may possibly lead to further investigation.

Management

The RCGP, in conjunction with the Royal College of Psychiatrists, Trailblazers and the National Mental Health Development Unit, has recently issued helpful guidance for health professionals on the topic of MUS (2011). They suggest four key areas of management:

Connecting —go back to the beginning, listen to the patient, acknowledge suffering, use existing knowledge of the individual (or recognize that you have no knowledge of the individual)

Due to the diverse nature of symptoms, management of MUS must be tailored to the individual patient. Offer patients regular appointments. It might be appropriate to schedule longer appointments initially as time spent at the outset might reduce subsequent health care use and help patients to accept their diagnosis.

There is also a role for performing a brief physical examination at each visit and looking for signs of disease rather than relying on symptoms. Investigations and referral should be avoided unless indicated.

Explanation and reassurance are often the most useful tools that doctors have in the management of MUS. However, for this to be effective, it needs to be done well. Simply telling the patient that there is nothing wrong is not usually helpful. This is because often, for the patient, that is not actually true. There is something wrong, but no cause has been found for it and it is highly unlikely to be medically serious. Even when done well, although initial reassurance may be high, those with heightened health anxiety appear to increase their concern back to original levels after just 1 week.

Good doctor—patient relationship and acknowledgment of concerns are important. Make sure that you engage with patients' concerns and beliefs. Take their suffering seriously and acknowledge their distress. Try to give reasonable, tangible and non-judgemental explanations for the symptoms that link both physical and psychological mechanisms. Avoid ambiguous statements and be cautious in the use of words that patients may misinterpret.

It can also be useful to offer suggestions for self-management of the symptoms. For example, encourage patients to increase their activity levels. This is especially important in back pain, chronic fatigue and fibromyalgia. It also helps to prevent loss of fitness and enhances self-esteem. In addition, exercise may help to take patients away from their usual, possibly difficult, environment. Ensure that the activity levels are gradually increased and set realistic obtainable goals. Explain that initially feeling worse after an appropriate increase in activity is usual and does not mean that patients have damaged themselves. A minimum of three 20 minute sessions/week is recommended increasing up to five 30 minute sessions if possible.

Encourage patients to go to work if at all possible. Use the ‘fit note’ system, recommending altered hours, amended duties or workplace adaptations to return patients back to work as soon as possible because it is difficult for patients to get back to work once they have been ‘off sick’ for a period of time in excess of 6 months. Discuss the importance for patients of relaxing and taking time for themselves. Activities such as yoga or walking may be helpful.

Table 2 shows the medical treatment possibilities for some of the more common MUSs. If self-help is ineffective, a useful first step for medical treatment is to consider an antidepressant, although antidepressants are not licensed for all MUS and thus, it may be necessary to prescribe off-license in some cases. Antidepressants have been shown to be effective but in most conditions, with the exception of IBS, there is no evidence to suggest that any one class of drug or individual drug is superior to another. In all cases, it is very important to explain to patients why you are using an antidepressant and to reassure them that you are not prescribing an antidepressant because you feel that the patient is depressed. As the effect of these drugs is not related to their antidepressant activity, initial low doses might be helpful.

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Table 2.

Treatments for common MUSs

	Pharmacological	Non-pharmacological
IBS (NICE, 2008)	Bulking agents (constipation predominant IBS), e.g. ispaghula husk Antidiarrhoeals (diarrhoea predominant IBS), e.g loperamide—avoid codeine Antispasmodics Antidepressants—low-dose amitriptyline is more effective than selective serotonin reuptake inhibitors unless the patient is depressed.	Dietary manipulation Probiotics Psychotherapy Hypnosis
Fibromyalgia (Carville et al., 2007)	Antidepressants Simple analgesia with paracetamol with or without mild opioids Tramadol Pramipexole, pregabalin and tropisetron reduce pain	Patient education CBT Exercise Hypnotherapy Multidisciplinary therapy
Chronic fatigue (NICE, 2008)	—	CBT Graded aerobic exercise
Non-ulcer dyspepsia (NICE, 2004)	Proton-pump inhibitor Helicobacter eradication H2-receptor antagonists Prokinetic	Psychotherapy
Tension headache (BASH, 2010)	Simple analgesia, e.g. paracetamol and ibuprofen, avoid codeine-containing preparations and beware of medication overuse headache Antidepressants	Behavioural therapy
Non-specific chest pain	—	Psychological interventions
Premenstrual syndrome (RCOG, 2007)	Hormonal manipulation Antidepressants Diuretics for bloating, e.g. spironolactone Non-steroidal anti-inflammatories (NSAIDs) for period pain	Exercise CBT Relaxation Vitamin and mineral supplements (vitamin B6, calcium, magnesium)
Chronic low back pain (NICE, 2009)	NSAIDs Simple analgesia with paracetamol Opioid analgesics Muscle relaxants Antidepressants	CBT Multidisciplinary treatment Exercise therapy

NICE, National Institute for Health and Clinical Excellence; BASH, British Association for the Study of Headache; RCOG, Royal College of Obstetricians and Gynaecologists.

If these first-line strategies are not effective, consider a referral for cognitive behavioural therapy (CBT) or psychotherapy. Although this might seem contentious to the patient, there is good evidence that it can be effective. Make sure that patients fully understand why you are referring and reassure them that it is not because you do not believe them or think ‘it is all in the head’. Hatcher and Arroll (2008) suggests phrasing the referral as ‘we cannot find a cure for your symptoms but we need to help you to find a way to live with them’. However, if depression or anxiety is suspected, and the patient acknowledges this, they are more likely to show a sustained improvement than those who deny it.

Psychological therapies

Psychotherapy is a ‘talking therapy’ which aids patients in gaining an insight into possible areas of difficulty and distress and looks into their motivation. It aims to help patients develop strategies or changes in thinking and behaviour that will help them cope more effectively with their problems. Psychologically, patients may regard their MUS as a threat to their health and well-being. Models of threat reduction suggest two separate processes, firstly that of calming, protecting and threat avoiding and secondly information seeking and threat analysing. Investigations and reassurance may help with the former but have limited effects upon the latter as the illness representation has not changed. This is damaging to patients as they can enter the cycle of continuous reassurance seeking.

Psychotherapy may help with threat analysis which, although initially difficult for a patient, could have long-term benefits. Psychotherapy can either be done on a one-to-one basis or be in groups. The therapist uses specific interventions targeted at MUSs as well as offering general advice regarding stress management, problem solving and social skills.

In the treatment of MUS, CBT techniques can also be used to decrease the intensity and frequency of symptoms, plus improve functioning. Initially, the patient and therapist discuss ways in which thinking and actions in respect of the condition are ineffective and even counter productive. Subsequently, the therapist is able to challenge the patient's beliefs and behaviours.

Prognosis

Between 4 and 10% of patients with MUS go on to have an organic explanation for their presentation. However, of those with true MUS, a quarter are still present after 12 months (RCGP/Royal College of Psychiatrists/National Mental Health Development Unit/Trailblazers, 2011).

Often, the most important management strategy is to use good communication skills which allow the health anxiety of the patient to be explored. There is a danger of patients becoming reliant on pain killers or sedatives and this pattern is very difficult to reverse. If the doctor—patient relationship breaks down, patients often seek reassurance from other sources or ‘doctor-shop’ which may well exacerbate the problem.

These patients are difficult to deal with and for some of them, it has to be accepted that there will be no cure. In these cases, managing symptoms and health anxieties are the main goal of treatment and management is likely to continue to be a challenge.