Chronic Fatigue Syndrome not just tired all the time Assessment & diagnosis Alastair Miller MA FRCP FRCP(Edin) DTM&H Consultant Physician Hon Senior Lecturer University of Liverpool Chair British Association for CFS/ME (BACME)
How big is the problem? 1/10 GP appointments are about fatigue 0.2-2% fatigue persists for 4 months, is disabling and associated with other symptoms Comorbidity is high with associated depression and anxiety in up to 75% High health economic costs due to frequent contact with GPs, psychologists and other health professionals
BUT NB
Definition of CFS Fatigue clinically evaluated unexplained lasting more than 6 months, not lifelong not result of exertion not relieved by rest causing significant functional disability Fukuda et al. Ann Int Med 1994;121:953 (Previously Holmes criteria 1988)
Accompanying features At least four of sore throat tender swollen glands cognitive dysfunction myalgia arthralgia new headaches unrefreshing sleep post exertion malasie
Other definitions Oxford definition 1991 (Sharpe JRSM 19910 Fatigue is the principal syndrome Severe, disabling, affecting mental and physical functioning Other symptoms such as myalgia, mood and sleep disturbance may be present Anxiety and depression do not exclude Canadian 2003 (revised. Jason et al Am J Biochem 2010) Excludes patients with psychiatric diagnosis Requires payback and brain fog (plus pain and sleep disturbance) International 2011 (Carruthers J Intern Med 2011) Post exertional neuro immune exhasution Removed criteria for fatigue and Removed 6 months requirement NB requirement for clinical diagnosis and management v research
How do we diagnose in practice? Is it really a diagnosis of exclusion? Yes but only partially Clearly important to consider other diagnoses that cause fatigue BUT Fatigue of CFS is very characteristic Remember other conditions can co-exist History is crucial Defined onset Characteristically associated with infection and/or adverse life event Often fluctuant pattern No definite time period (NICE says 4 months) History often written or Given by relative Try not to put words in patients mouth
NICE guidelines (CG53 August 2007) Fatigue New/specific onset Persistent and/or recurrent Unexplained by other conditions Resulting in substantial reduction in activity level Characterized by post exertional malaise/fatigue
NICE Fatigue accompanied by one or more of Sleep disturbance Myalgia/arthralgia Headache Painful lymphadenopathy without pathological enlargement Sore throat Payback Brain fog Flu like symptoms Dizziness/nausea Palpitations without cardiac pathology
Post exertional fatigue or malaise Payback. Usually delayed and long lived.
Cognitive difficulties Brain fog Poor short term memory, concentration, reasoning. Unable to read or watch TV. Dysphasia. Confused behaviour Putting washing up in fridge Often most serious problem that affects ability to work
Sleep disturbance NB fatigue is lassitude/lethargy/exhaustion NOT sleepiness If daytime somnolence is the issue then consider other diagnoses. Epworth score may be useful Often have difficulty getting to sleep but may sleep in Cardinal feature is unrefreshing sleep
Pain Often myalgia or arthralgia Muscles may be tender but no objective evidence of inflammation May be very generalised Characteristically does not respond well to paracetamol or antiinflammatory drugs May respond better to neuropathic pain type drugs Drugs are frequently not tolerated well May be having treatment in pain clinic (which can make CFS treatment complex)
Physical examination Usually normal or Unrelated pathology Lymphadnopathy not significant Check for oral candida Is full examination essential? Does patient expect it? GP or secondary care responsibility?
Tests No single diagnostic test No consistent abnormal finding/biomarker Including cytokines etc NICE recommends Urinalysis Full blood count U&Es, LFTs, Thyroid function, Calcium, Creatinine, CPK, glucose CRP and ESR or plasma viscosity Test for gluten sensitivity (coeliac) Other tests to be carried out for specific indication only
No routine testing for Haematinics (ferritin, B12, folate) Tilt table Nerve conduction studies Evoked responses Tests for infection HCV, HBV, HIV, CMV, EBV, toxoplasma, Borrelia (Lyme!) Routine imaging CXR, CT, MRI Auto antibody testing
Review Reconsider diagnosis and consider alternative OR additional diagnoses if Atypical history and especially if no payback, brain fog, pain or sleep disturbance Red flag features such as severe weight loss, significant lymphadenopathy, oral candida daytime somnolence, cardiorespiratory symptoms Significant abnormalities on physical examination Abnormal investigation results
Co-existing conditions CFS commonly co-exists with other medically unexplained conditions such as Fibromyalgia syndrome Irritable bowel syndrome Chronic tension headache Other pain syndromes
Differential diagnosis Infection TB, endocarditis, HIV, hepatitis, brucella (NOT Lyme) Neoplasia lymphoma, cancer Neurological myaesthenia, MS, PD Endocrine DM, thyroid, adrenal, pituitary, calcium disorders Others SLE, narcolepsy, sleep apnoea, depression, alcohol, drugs, obesity Difficult to assess contribution of drugs (eg beta blockers)
Co-existing mental health issues Degree of depression is common Severe mental health issues such as psychotic depression would exclude Is depression a normal reaction to the chronic symptoms of CFS Can we view depression as a symptom of CFS and treat with pharmacological agents to break the vicious cycle 1/3 on anti-depressants at time of assessment 1/3 have been on anti depressants 1/3 have never been on anti-depressants
Diagnosis and assessment Often made in primary care Many services have assessment/review by non doctor prior to therapy Does this matter? Some just want a diagnostic label Work/pension Permanent health insurance Litigation Diagnosis needs to be made definitively
NICE guidlelines: Mild Mobile, can care for themselves and do light domestic tasks with difficulty May still be in work or education but has probably stopped all leisure and social pursuits Often takes days off or uses the weekend to cope with the rest of the week
Moderate Reduced mobility and is restricted in all activities of daily living Has probably stopped work, school or college and needs rest periods Sleep is generally poor quality and disturbed
Severe Unable to do any activity, or minimal daily tasks only Severe cognitive difficulties and depends on a wheelchair for mobility Unable/barely able to leave the house May spend most of their time in bed Often extremely sensitive to light and noise
Summary The strict definition of CFS remains controversial and Is linked with the mind/body debate over pathogenesis Most definitions more needed for research projects rather than clinical management There is no biomarker/diagnostic test Diagnosis is a positive one made on the basis of a good history Commonly no alternative diagnosis seems feasible based on duration Pattern of fatigue differs from other conditions but they still need to be considered and excluded
Phenotyping -?the way ahead Probable that several different conditions with different aetiologies will come under the umbrella diagnosis of CFS Distinguishing between these different pheotypes will be key to designing clinical trials BUT Without good biomarkers, phenotyping will need to be done on a clinical basis And this will be problematic
Summary 2 Other conditions may co-exist Any new symptoms require clear evaluation Medical review may be important Needs an open mind about pathogenesis and aetiology Diagnosis is start of management
Questions?