Diagnosis unforthcoming

How do you approach patients with medically unexplained symptoms? Professor Chris Burton offers some insights


MEDICALLY unexplained symptoms (MUS) is an umbrella term commonly used to refer to physical symptoms in the absence of a diagnosed organic disease. It includes both individual symptoms (e.g. headache or abdominal pain) and syndromes (e.g. tension type headache or irritable bowel syndrome).

An estimated 20 to 30 per cent of consultations in primary care involve patients experiencing MUS with no clear diagnosis. Recent developments in neuroscience and physiology mean we are becoming increasingly able to explain these symptoms, and the term MUS should probably be abandoned: both because it’s no longer accurate and patients dislike the term. However, it is still in use and these symptoms cause distress to patients, concern to doctors and occasionally lead to medico-legal consequences. For these reasons, it is important to think about what these symptoms are and how to manage them safely and effectively.


Current thinking about symptoms takes a similar approach to the definition of pain: symptoms can be thought of as bodily sensations which indicate the presence or possibility of disease. Symptoms are sensed in the brain and all symptoms, whether explained or unexplained by disease, involve both peripheral and central processes.

In some symptoms, for instance an injured limb, it is simple to separate the peripheral and the central. We can see the injury which is triggering pain-sensing peripheral nerves and we know in turn that these nerves activate brain circuits which provide automatic protective responses (e.g. withdrawal) and a feeling of pain. For a patient with irritable bowel syndrome it is more difficult to separate the central and the peripheral. Visceral nerves may be triggered by modest changes in distension (perhaps in response to fermentation products of gut bacteria to certain foods) and in turn they activate brain circuits which also provide protective responses and feelings. But those circuits may, because of biology, past events or current concerns, be sensitised to produce a response which is more intense or more prolonged than expected from the size of the stimulus.

This model of peripheral triggers with central amplification can be applied to most symptoms. The key point is that medically “unexplained” symptoms involve disproportionate central processes relative to the peripheral triggers when compared to “explained” diseases. This central processing approach is replacing older views that MUS represent the result of somatisation – the expression of mental distress as physical symptoms. While common mental disorders do have an increased prevalence in patients with MUS, the relationship between the two is complex and there is strong evidence that causes apply in both directions – symptoms can lead to distress and distress can amplify symptoms.


There are good guidelines for common MUS syndromes which include clear diagnostic criteria. These guidelines and criteria are useful for setting practice protocols and are also a valuable resource for occasional use – to look up information about specific syndromes. Guidelines typically recommend appropriate screening tests to exclude other conditions. Carrying these out (and documenting their use) is a valuable way of ensuring safe practice in this area of inherent uncertainty.

In less specific symptoms it is important to look for (and document) both the absence of features of peripheral disease and the presence of features suggesting increased central processing. Positive indicators of heightened central processing include symptom features which are biologically implausible (e.g. non-anatomic pain distribution), signs of sensitisation such as the presence of allodynia or abdominal wall tenderness (Carnett’s sign) and the occurrence of symptoms on examination despite signs of normal function (e.g. during a stepping test for dizziness). The level of distress is generally not a helpful measure in deciding whether a symptom is due to organic disease or not.

Clinicians often worry about missing organic disease due to gaps in their knowledge but there is evidence that mistakes are much more likely to be due to errors in thinking about clinical features (for instance closing down a differential diagnosis too early) than to gaps in knowledge or faulty examination technique.

Investigations have a mixed role in patients with suspected medically unexplained symptoms. Simple investigations (e.g. full blood count or C-reactive protein) represent an important safety net for patients with uncertain symptoms and, along with documentation of weight, represent an important part of safe management.

On the other hand investigations “to reassure the patient” have very little value. Negative tests may reassure doctors (sometimes falsely) but there is good evidence from a systematic review that diagnostic tests produce very little sustained reassurance in patients. Patients may show relief about negative tests in the consulting room but that relief does not translate into longer-term assurance that ongoing symptoms are not concerning.


Central to managing patients with MUS is some form of explanation. Patients expect explanations for their symptoms, regardless of whether they are due to organic disease or to central processing of sensations. Simply reassuring them that there is nothing wrong is generally not helpful, particularly when the patient has had repeated consultations and tests. Syndrome labels can be useful in this setting – where patients meet criteria for a syndrome such as fibromyalgia or IBS, there is no good reason not to discuss it. Some patients find more detailed explanations of dysfunctional bodily mechanisms very useful. These can commonly be found on patient-oriented websites such as for chronic pain or in books on the topic.

Patients given effective explanations for their symptoms may benefit from techniques to limit symptoms and reduce symptom-related distress or limitations. Treatments include self-management support, specialist psychological treatment and pharmacotherapy. Self-management support aims to teach symptom-control techniques, including progressive muscle relaxation as well as more advanced techniques such as sensory grounding.

Specialist psychological support may be appropriate for patients with multiple symptoms or high levels of disability. Cognitive behavioural therapy (CBT) is the most commonly used approach but other treatments can be effective in some situations. Pharmacotherapy is largely limited to pain management (avoiding strong opioids in fibromyalgia) and to treatment of comorbid depression or anxiety.

Patients with MUS vary greatly: from those with occasional relatively minor and self-limiting symptoms in one body system to others with severe disability due to multiple symptoms. A recent prognostic classification for use in generalist settings employs the notion of “multiple symptoms, multiple systems, multiple occasions” as a way of assessing the likelihood of sustained problems. In this scheme, the more systems (e.g. cardiopulmonary, GI, musculoskeletal) involved and the more occasions, the less likely it is that symptoms will resolve without specific action.


Doctors in any specialty can manage patients with MUS. Doing so effectively requires confidence in explaining symptoms in a way that patients find acceptable, supporting self-management and being able to handle emotional distress and mental health problems if they emerge. Doing so safely requires attention to clinical detail, judicious use of diagnostic tests and a balance between firm reassurance with symptom management and closing down other diagnostic possibilities too quickly. As the science which enables us to explain MUS becomes stronger, the art of maintaining this balance will remain.

Dr Chris Burton is professor of primary medical care at the University of Sheffield