Investigating Unexplained Persistent Fatigue with a Particular Emphasis on CFS/ME

By Dr Amolak S Bansal – Consultant in Immunology/Allergy and CFS/ME, Department of Immunology and Allergy, St Helier Hospital, Carshalton, Surrey.

Persistent fatigue is a frequent problem with a diverse range of causes. Unfortunately there is little or no attention to this subject in the curriculum of many medical degrees. The non-depressed patient with exhausting fatigue, normal clinical examination and routine investigations is particularly challenging for general practitioners. Uncertainty in investigating and managing such patients can contribute to stress which in some individuals can perpetuate and aggravate symptoms. However, while fatigue is a feature of many common illnesses, it is one of the main problems in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). Specialised services for the diagnosis and management of CFS/ME are markedly deficient in the UK and all around the world. This is despite a prevalence of between 0.2% and 2.6% and cost to the UK economy totalling several billions of pounds.

In a report published recently in the journal BMC Family Practice and accessed free online I provide details on how unexplained fatigue and CFS/ME may be investigated and confidently diagnosed in the community. This uses a simple clinical scoring system and the results of routine blood tests that assess inflammation, autoimmunity, endocrine dysfunction and gluten sensitivity. In my estimation the costs of these blood tests undertaken in the NHS is approximately £80. The results of this assessment can help to discriminate CFS/ME from other causes of continued fatigue. In my opinion early diagnosis and intervention in general practice can do much to allay patient anxiety, encourage improvement and prevent expensive unnecessary investigations. Thus far too often patients have been encouraged to undergo a vast array of expensive laboratory, radiological and other investigations that are aimed at excluding unusual and rare causes of persistent fatigue. It is not unusual for me to see patients who have undergone whole body Magnetic Resonance Imaging (MRI), echocardiography, tests of mitochondrial function, nutrient analysis, complex tests of immune dysfunction and rare infections totalling well over £10,000. These tests with frequent minor abnormalities cause significant worry and prolong the uncertainty of a precise diagnosis. This in turn impacts negatively on employment, finances, social life, physical and mental health and overall quality of life. This is especially so when suggested supplements provide little long term improvement.

The report goes into some detail about how the scoring system should be used. In particular it highlights the importance of the delayed worsening of fatigue and other symptoms with any physical or mental over activity that is characteristic of CFS/ME. As such this is heavily weighted in the scoring system as indeed is non-restorative sleep. For a confident diagnosis of CFS/ME patients should have eight or more points out of a maximum of thirteen and there should be no abnormality in the routine blood tests.

Although there are few consistent physical signs in CFS/ME the report does provide information on unusual signs in CFS/ME which have not been noted previously. These include a paradoxical dilation of the pupils when these undergo prolonged illumination with a torch, frequent coldness of the hands and feet with purplish discolouration in some (called acrocyanosis) and an imperceptible increase in the resting rate of breathing. Additionally there is discussion of alcohol and drug sensitivity in CFS/ME which leads many to give up ‘drinking’ and also means that many medications need to be introduced slowly and starting with a very low dose. This is particularly so with those drugs that affect mood and sleep. An especially important section of the report deals with several conditions which while presenting with persistent fatigue require distinction so that appropriate specific treatment may be provided. It also highlights the frequent misconception that fatigue with normal blood tests equals depression. Several clinical points that help distinguish depression and CFS/ME are tabulated which hopefully will prevent routine commencement of antidepressant therapy and/or psychiatric referral for patients with underlying CFS/ME.

The report also discusses the recent work on joint hypermobility syndrome (JHS) which is now increasingly recognised as a significant cause of persistent fatigue and often with many of the other symptoms seen in CFS/ME. However, there are several unanswered questions regarding JHS not least of which is why a condition affecting collagen should be associated with such a high frequency of low mood and anxiety. Additionally, we have no idea how JHS links with CFS/ME; is it a totally separate condition or is it a cofactor that predisposes people subjected to specific infections or prolonged stress to CFS/ME type symptoms. There is certainly a marked overlap between these conditions and we need more research in this interesting area.

The report finishes with suggestions for the treatment of CFS/ME based on current evidence. The value of pacing and deep relaxation is emphasised as stress has a very significant ability to exacerbate the symptoms of CFS/ME by impairing the function of the immune system and possibly by promoting endocrine dysfunction. Graded exercise therapy (GET) is mentioned as beneficial but only when used sympathetically and flexibly and when commenced at the right baseline. The value of GET in significantly improving CFS/ME symptoms and allowing a return to employment has not been established. Regarding the use of supplements, few have a significant supportive evidence base. Some can certainly be beneficial, but the doses need not be as high as those often suggested. Patients with CFS/ME should withdraw supplements that cease to provide benefit to prevent a creeping increase in the number used.