Medically unexplained symptoms: assessment and management

Introduction

Medically unexplained symptoms (MUS) or persistent physical symptoms (PPS) are very common. They account for up to one in five presentations in primary care.^1,2 This can be even higher in some secondary care clinics.³ Hence assessing and supporting people with unexplained symptoms is a significant part of the everyday work of most clinicians.

PPS are often associated with significant distress, impaired functioning, loss of role and high use of healthcare and welfare.⁴ Patients often report feeling that their concerns are not taken seriously by their healthcare professionals.⁵ Doctors also report feeling unprepared for helping people with PPS.⁶ PPS are also estimated to account for approximately 10% of total NHS expenditure for the working-age population in England.⁷

Much of this delivers limited value to the patient and can be counterproductive or even harmful (for example, multiple or repeat investigations).⁸

The longer the duration of untreated symptoms the poorer the prognosis.^9,10 Evidence-based treatment is available.^9,11 Yet, it is common for diagnosing, explaining the diagnosis to the patient and offering treatment to be delayed.⁵

Definitions and classification: one syndrome or many?

The language we use to describe PPS can be complex and confusing. Adjectives such as functional, somatic, unexplained and dissociative are commonly used. And there are specialty-specific diagnoses like irritable bowel syndrome, fibromyalgia and functional neurological disorder. Almost every medical specialty has an equivalent diagnostic category.

It has been proposed that PPS can be considered as one syndrome rather than many.¹² There is significant overlap in the risk factors and symptoms seen in specific diagnoses.¹³ PPS frequently present with multiple symptoms that cut across specialty boundaries (which can result in multiple referrals). A number of symptoms (such as fatigue, pain and disrupted sleep) are common across diagnoses. Indeed, many of the challenges of helping people with PPS stem from a fragmented approach to management where the symptoms cut across medical silos and divides (primary and secondary care; physical and mental health; and different medical specialties).

The Diagnostic and Statistical Manual of Mental Disorders, 5th edn (DSM-5) now defines somatic symptom disorder.¹⁴ Under DSM-IV, symptoms had to be unexplained but the new definition removes this requirement and focuses on distress and disruption of daily life. International Classification of Diseases, 11th revision (ICD-11) proposes the similar bodily distress disorder.

The term PPS has also been shown to rank highly in surveys of patient preference.^15,16 MUS and PPS describe similar symptoms but are not quite the same thing. Describing symptoms as medically unexplained can be seen by patients as dismissive.¹⁷ It has been suggested PPS should occupy a neutral space with neither a somatic disease aetiology, nor a mental disorder to reflect their complex nature (analogous to pain disorders in ICD-11).^18,19

Physical and mental health

Having a physical health diagnosis increases the risk of experiencing unexplained symptoms. For example, around a fifth of those diagnosed with non-epileptic seizures also have epilepsy, non- cardiac chest pain is common after myocardial infarction and dysfunctional breathing is frequently seen in those with asthma.^20–22 Hence, the divide between explained and unexplained symptoms is not quite as clear cut as the terms imply.

Mental health comorbidity is also common. Around 50% of individuals with PPS suffer from associated anxiety or depression, which is more than that seen in other long-term conditions.^3,23 This may be due to the impact of living with persistent symptoms and the distress and impairment they cause, it may reflect a common aetiology, or it may be a combination of the two.

Associated physical and mental health problems stress the need for a thorough assessment to ensure the treatment approach offered addresses comorbidity.

Aetiology

The most convincing models for how PPS develop take a multifactorial approach. Deary, Chalder and Sharpe have described a cognitive behavioural model of persistent physical symptoms and how they develop⁹.

Some factors which increase the risk of developing PPS are non- modifiable. These include parental ill health during childhood; illness during childhood; childhood adversity and abuse; personality traits; and having a long-term condition and a family history of someone with a long-term condition.

There can often be a ‘trigger’ (but this is not always the case). This could be an infection, a physical illness or trauma. It may be a psychosocial stressor or repeated stressors. Often both physical and psychosocial stressors precede the onset of PPS.

Then there are maintaining factors which keep the symptoms going. These can be divided into four groups.

• Physiological: autonomic dysregulation, central sensitisation, hypothalamic–pituitary–adrenal (HPA) axis dysfunction and sleep disruption.

• Social: loss of role and medical uncertainty.

• Cognitive: catastrophic misappraisal of symptoms, symptom focusing and intolerance of uncertainty.

• Behavioural: avoidance behaviour, ‘all or nothing’ behaviours and poor sleep hygiene.

Treatment focuses on addressing modifiable maintaining factors, particularly cognitive and behavioural factors.

Another model describes the brain as actively making predictions or inferences rather than passively waiting for sensory input from the body. It proposes PPS are due to ‘failures of inference’ in which expectations, cognition and emotion play a part in symptom perception.²⁴

It is now recognised that a variety of physiological processes are involved in PPS. There is increasing evidence that autonomic nervous system dysregulation plays a role. For example, a recent meta-analysis found differences in heart rate variability comparing patients with PPS to healthy controls.²⁵ Central sensitisation has also been proposed as a common physiological basis for PPS.²⁶ Other hypotheses include immune dysfunction and metabolic abnormalities.¹⁸

Assessment

As ever in medicine, assessment of PPS starts with a thorough history. Active listening with empathy is important to help the patient feel heard and understood. Table 1 outlines a suggested approach and key questions as you do this.

Physical examination (cardiovascular, respiratory, abdominal and neurological examinations) is essential to look for signs of other physical health problems. In some functional neurological disorders, there are also positive signs that can be elicited.²⁷

Baseline physical observations (heart rate, blood pressure and temperature) are required.

The following investigations should be undertaken as a minimum:

• urinalysis for protein, blood and glucose

• full blood count

• urea and electrolytes

• liver function

• thyroid function

• erythrocyte sedimentation rate and C-reactive protein

• random blood glucose

• serum creatinine

• tissue transglutaminase antibodies (tTG–IgA) for coeliac disease

• serum calcium

• creatine kinase.

Further investigations may be indicated. For example, for persistent unexplained gastrointestinal symptoms in women, particularly for those aged over 50 years, CA125 should be measured.²⁸

Common diagnoses which are sometimes missed include diabetes, coeliac disease, thyroid problems and inflammatory conditions.

While diagnoses of persistent physical symptoms should be made carefully only after a full assessment, evidence now suggests that when a diagnosis is made, they are stable diagnoses with low misdiagnosis rates.²⁹ Doctors are more likely to under-diagnose than over-diagnose unexplained symptoms.³⁰

Management

Treatment takes a stepwise approach.

Funding

Trudie Chalder is part-funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust, and King's College London at King's College Hospital NHS Foundation Trust.