Medically unexplained symptoms (MUS) may be defined as ‘persistent bodily complaints for which adequate examination does not reveal sufficiently explanatory structural or other specified pathology’.¹ Accounting for up to 20% of GP consultations,² they are among the most common and frustrating presentations in primary care. GPs experience many difficulties in caring for these patients,³ including fears of missed diagnoses or litigation, despite low misdiagnosis rates comparable to those linked with disorders such as idiopathic epilepsy or schizophrenia.

What do we call this problem? 

Terms such as somatisation, psychogenic, conversion, heart-sink and psychosomatic have been widely used in the past, along with the implied or explicit understanding that “it’s all in your head”. MUS had become the accepted term in primary and secondary care, with more recent research supporting the use of ‘functional symptoms’ as the term best understood and acceptable to patients.⁴ The concept of health anxiety is now gaining traction and may prove to be more helpful in the long term, given its usefulness in patients with comorbid organic disorders. 

MUS are associated with considerable healthcare costs,⁵ significant patient disability, and iatrogenic harm (eg. inappropriate abdominal surgery in patients with irritable bowel syndrome, opiate dependency in somatoform pain disorders) in the setting of over-investigation and treatment.⁶ Although often transient and self-limiting, MUS may become chronic in 20-25% of patients in primary care.⁷ Early recognition is of paramount importance, especially given the overall good prognosis for the majority of these patients if identified before becoming chronic.⁸

As physicians, we tend to assess physical illness by focusing on physical complaints and likewise psychological illness by psychological symptoms, despite the inextricable intertwining of both. In essence, there is no significant illness that does not affect both mind and body. When patients are physically ill with symptoms such as pain, breathlessness or weakness, they often experience associated psychological symptoms such as depression, anxiety or fatigue, and vice-versa.

The subjective symptoms of illness experienced by patients with MUS are often met with a fruitless search for objective signs on physical examination and negative tests for disease. The doctor-patient relationship can become challenging and fraught with communication difficulties and frustration for both patient and doctor. Patients with MUS complain that ‘doctors don’t listen’ and this is mirrored by the frustrated doctors’ similar assertion about patients.

Pathophysiological basis for symptoms

Most of our routine medical investigations are focused on the (internal) structure of body part. However, a central component of our adaptive response to (external) change in our environment, since prehistoric times, has been our functional stress response triggering an acute activation of our autonomic nervous system (ANS). This leads to the adaptive ‘fight, flight or freeze’ response in the body, which becomes maladaptive if it persists beyond this acute period. 

Chronic ANS hyperarousal may be triggered by ongoing stress including early adversity in life, interpersonal conflict and social isolation. This will lead to a range of symptoms that may include palpitations and muscle pain (due to tightened muscles cramping) and biochemical shifts (hyperventilation triggering hypocapnia and alkalosis with associated light-headedness, shortness of breath and paraesthesia). 

Psychoneuroimmunological responses include a pro-inflammatory cascade involving a complex interplay between the sympathetic, immunological and endocrine systems, contributing to increased vulnerability to inflammation and infection. Abnormal production of the hormone CRH in the hypothalamus leads to higher cortisol secretion with release of NF-κB causing increased pro-inflammatory cytokines, chemokines and excitotoxicity associated wit a reduction in monoamines and trophic factors.⁹

Improved radiological imaging with SPECT studies and fMRI supports hypotheses that emotional stressors act via the limbic system to modulate basal ganglia thalamocortical circuits in these conditions,¹⁰ with a shift from acute pain to different chronic pain neural pathways and central sensitisation of pain regions.

Differential diagnoses

The differential diagnoses comprise a network of conditions, covering five main areas. MUS could be due to:

• • Somatisation (most commonly) 
• • Hypochondriasis 
• • Factitious disorder 
• • Malingering 
• • Missed organic disease.

Somatisation 

This is defined as the experiencing of psychological distress as physical symptoms. The psychological distress triggers ongoing activation of the ANS, causing these physical symptoms. It may be a core component of the illness (the ‘functional somatic syndromes’) or as part of a long-standing pattern of behaviour (somatisation disorder is now termed ‘somatic symptom disorder’ in DSM-5).

Functional somatic symptoms that follow a particular pattern or clinical course are termed ‘functional somatic syndromes’. These syndromes share underlying malfunction of a particular organ system, eg. irritable bowel syndrome, chronic pelvic pain, fibromyalgia and conversion disorder; affecting the gastrointestinal, reproductive, neuromuscular and neurological systems respectively. It has been suggested that these are all different manifestations of one general functional somatic syndrome, in the context of ANS hyperarousal.

Somatisation disorder represents the severe end of the spectrum. It is a specific disorder where the patient has multiple ‘medically unexplained symptoms’, more than one system is involved, symptoms are more than of two years duration, typically will be life-long, there is preoccupation with symptoms, repeated seeking of consultations/investigations and an inability to accept reassurance. Two-thirds of these patients will meet criteria for another psychiatric disorders such as depression, anxiety or personality disorders.

Aetiological factors for this condition are female gender, previous history of MUS, high rates of adverse life events predating the onset of MUS, and childhood experience of trauma and/or neglect. Somatisation is strongly associated with depression and anxiety (a high percentage of depressed patients present with somatic symptoms in primary care). These conditions all share similar predisposing, precipitating and perpetuating risk factors and respond to similar treatments, including anxiety management techniques and antidepressant therapy.¹¹

Given the contribution of genetic and childhood learning to our sense of bodily integrity and emotional language, the transgenerational transmission of somatisation and health anxiety is understandable.

Hypochondriasis

Hypochondriasis is the fear that one has a particular illness despite evidence to the contrary. It will generally be secondary to a mood or psychotic disorder. Body dysmorphic disorder is a particular form of hypochondriasis where there is a preoccupation with a perceived defect in appearance. The term ‘hypochondriasis’ has been replaced in the American DSM-5 with the new ‘illness anxiety disorder’ and ‘somatic symptom disorder’, of which health anxiety is a core feature.

Health anxiety is a relatively new and useful term, and is described in a recent BMJ editorial as ‘reaching epidemic proportions’ with prevalence rates of up to 10% in primary care and rapidly rising incidence rates due to an increase in excessive use of health internet sites (cyberchondria).¹²  It is a disabling condition characterised by rumination, excessive fears of having or developing serious illnesses, with misinterpretation of bodily symptoms and maladaptive behaviours such as excessive use of health websites and reassurance seeking.¹³

The pathology is under-recognised and treated inappropriately with reassurance and investigations, which are likely to perpetuate ongoing health anxiety. CBT, group-based mindfulness and internet-CBT with guided self-help are of proven effectiveness in the treatment of health anxiety.^14,15

Factitious disorder 

This is characterised by the deliberate feigning of symptoms driven by the unconscious motivation to be cared for), for example, self-administration of thyroxine before presenting with symptoms of thyrotoxicosis. Munchausen syndrome is a severe type of factitious disorder.

Malingering 

This is the deliberate production of symptoms with conscious motivation for external gain, for example, exaggerating whiplash injury for monetary compensation. 

Missed organic disease 

This is rare. Health anxiety is common in patients who are chronically polysymptomatic despite routine structural investigations that show no abnormalities.

Management strategies 

A minority of patients with MUS will respond to normalising of symptoms and treating empirically. But most patients do best when engaged with emotional support, explanation and psycho-education around their symptoms.¹⁶ It is not uncommon for GPs, especially if there is uncertainty, to respond to the patient’s distress by assuming that the patient is seeking more investigations and referrals. 

Management of MUS includes careful assessment, making an accurate and confident diagnosis, explaining this to the patient using appropriate language and initiating suitable treatment.

Assessment first includes focused history-taking, reading available case notes/correspondence, asking carefully about symptoms, onset, illness beliefs – perceived causes, worries, disabilities and enquiring about the patient’s perception of the outcomes of previous assessments. It is important to remember that patients may present with comorbid functional and structural disorders, eg. non-epileptic attack disorder (NEAD) comorbid with epilepsy. Clarifying the contribution of both will allow appropriate dual intervention, eg. avoiding excessively high doses of steroids in the anxious hyperventilating asthma patient who is finding it difficult to catch their breath. Negative investigative tests initially can help to confirm the diagnosis, but patients do not require repeated testing. Any new symptoms must be appropriately investigated while avoiding unnecessary invasive investigations and iatrogenic harm. 

Explaining the diagnosis to the patient involves a positive and confident diagnosis. If initial investigations are performed, the likely outcomes of these investigations should be clarified with the patient at that time. The GP should acknowledge the patient’s distress and explain the ‘fight or flight’ pathophysiological mechanisms. The time spent at this stage in engaging and educating the patient will be paid off in reducing future workload. 

Few patients will disagree with the assertion that there is no significant illness that does not affect both body and mind. Expand the focus from investigations inside the body, to the impact of external events (such as bereavement) in triggering internal physiological change (through the ‘fight or flight’ cascade). Explanation of ‘structural versus functional’ investigations and the use of metaphors can be helpful: ‘computer hardware (structural) versus software (functional) problem’. This approach, coupled with a shifting of focus from curing to coping, with associated symptom management helps reduce the level of disability and improves the doctor-patient relationship.

The style of language employed by the doctor ideally should reflect the vocabulary used by the patient. Some patients (and doctors) speak a purely somatic language around autonomic hyper-arousal (eg. palpitations, abdominal pain) while others speak a psychological language (eg. anxiety, stress). Speaking a psychological language to a patient who only speaks somatically is unhelpful to both participants. 

It is important to try to involve the significant carer; co-opting them as a co-therapist at home can be very helpful. 

Treatment options

Following this important psychoeducation, the doctor and patient can then collaboratively progress with a suite of treatment options including:

• Targeted information, eg. www.neurosymptoms.org is a useful website written by a neurologist for patients to explore functional disorders further. It also has very useful links to information leaflets on health anxiety etc
• Pacing, avoiding ‘boom and bust’ cycles of rest and activity. Linkage with a physiotherapist who has experience in patients with functional disorders is invaluable. Yoga/pilates based therapies are beneficial
• Relaxation exercises, breathing exercises, and mindfulness tools can be accessed through a range of resources including the www.beaumont.ie/marc (mindfulness and relaxation centre) website
• Antidepressants can help to settle autonomic hyperarousal in patients who are not making progress. Bearing in mind that this patient group is exquisitely sensitive to side effects, it is best to start at very low doses 
• A collaborative approach between the GP and liaison psychiatry is essential in difficult cases, including consideration of specialist cognitive behavioural therapy.¹⁷

Consultation techniques

Additional good practice advises consultation techniques such as agreement on a regular fixed appointment time, focusing on the impact of the symptoms, validating the patient’s sense of suffering, indicating how common these symptoms are, reassurance regarding long-term improvement and reversibility of symptoms, which will be taken seriously. Broadening the agenda during these visits to incorporate an understanding of the triggers to the hyperarousal will encourage progress in addressing these factors using a problem-solving approach.

Lack of access to psychological services remains a considerable barrier to patient care. Furthermore, patients usually require careful explanation too around the mind-body interface in order to understand why a referral to psychiatry or psychological services might be of benefit. 

These challenges would be helped by improved guidelines being readily available. The Dutch NHG guidelines may be a starting point.¹⁸ These recommend a ‘stepped care’ approach in which the GP starts with the mildest possible effective treatment is appropriate in mild MUS, broadening out to incorporate a combination of strategies for moderate-severe presentations.

Conclusion

The role of the GP is central to the management of patients with MUS. It is clear that GPs would benefit from a strong working knowledge of the principles of diagnosis and treatment of MUS. 

Improved training on ‘mind-body’ medicine for medical students, the development of targeted education and guidelines for primary care doctors, and links with specialist services such as liaison psychiatry as part of a stepped care approach would aid both patient and doctor in the effective management of this challenging health condition. 

References

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