Chronic Fatigue Syndrome - PowerPoint Presentation

Slide1

Chronic Fatigue Syndrome

Dr.Demet

Demircioğlu

Slide2

Introduction

Fatigue

-

a

feeling

of

weariness, sleepiness

or

irritability after

a

period

of

mental

or

bodily

activity

Tiredness

-

A

feeling

of a lessened

capacity

for

work

and

reduced

efficiency

of accomplishment, usually accompanied

by

a sense of

weariness

and

fatigue

Weakness

-

a

weak

bodily

state

as

expressed by

reluctance

to

an d

difficulty in

rising,

a shuffling,

disinclination

to

mov e,

eating slowly

and a

drooping

posture

Slide3

CDC

Guidelines

MAJOR

CRITERION

Severe chronic fatigue for ≥ 6 months

Not due to ongoing exertion or other

medical

conditionsNot substantially relieved by restSignificant interference with daily activities

(Fukuda

et al,

1994)

Slide4

CDC

Guidelines

MINOR

CRITERION

Concurrent presence of 4 or more of 8 symptoms:

Post-exertion malaise lasting > 24 hoursUnrefreshing sleepImpairment of memory or concentrationMuscle painPain in multiple

joints without swelling or rednessHeadaches of a

new type, pattern, or severityTender lymph nodes in the neck or armpitFrequent or recurring sore

throat

that

(Fukuda

et al,

1994)

Slide5

ICD 10 CM (clinical

modification)

Chronic

Fatigue

Unspecified - R53.82Fo

r ≥ 6 months  tired most of the time, tro

uble concentrating and carrying out daily activities

Other symptoms includemild feverlymphadenopathyheadachemyalgia

arthralgia

depression,

and memory

loss

Not

caused

by

ongoing

exertion,

not

relieved by

rest

Slide6

Epidemiology

Prevalence

0.4% -2.5%

0.2-0.4%

Mean age of

onset 29-35 yrs75% of affected patients are women

Slide7

Etiology- Biological

Viral

infection

Ebstein-Barr

virus initially proposed

Later found to be not conclusiveNo clear causal relationship between infections and CFSHypothalamic pituitary adrenal Axis dysfunctionMild hypocortisolism

observed in cases of CFSHPA

axis dysfunction not specific to CFS, symptoms like inactivty in CFS can decrease Cortisol levelsHypocortisolemia may

predict

a

poorer

response

to

CBT

Slide8

Etiology- Biological

Immunologic

basis

Hig

h pro inflam

matory cytokines, high IL-1 levels in CFS(Maes M.,2012)NK cell

dysfunction- eith

er decrease in number or impaired functionincreased levels of T

regulatory

cells

(CD25+/FOXP3+)

CD4 T

cells

Lower

activation of

CD8 T

cells

(Currio

M.,

2013)

Allergies

(atopy)

and

CFS

(Y’bars

et

al

2005)

Slide9

Etiology- Biological

3. Immunological basis

(contd)

–

Serotonin an

d CFS – anti 5-HTautoimmuneactivity could play a role

in the pathophysiology of CFS an

d the onset of physio-somatic s

ymp

t

oms

(Maes et al

2013)

Slide10

Etiology- Biological

Genetics

Concordance

55%

in

monozygotic and 20% in dizygotic twins

(Buchwald et al, 2001)Sequence variation in genes coding for HTR2A serotonergic receptor potentially enhancing its activity may be involved in pathophysiology of CFS(Smith et al.,2008)

Differences observed in gene expression in exercise responsive genes in

terms of gene ontology in attempt to explain fatigue which worsens post exercise in CFS(Whistler et al.,2005)

Slide11

Etiology- Biological

5.

Neuroimaging

Functional

Reduced

basal ganglia function in terms of decreased activity

of right caudate and right globus pallidus on fMRI(Miller et al, 2014)StructuralReduced grey and white matter volume in the occipital lobe and reduced grey matter in

the right angular gyrus and right parahippocampal gyrus on VBM in CFS

patients(Puri et al, 2012)

Slide12

Etiology -

Psychological

Increased

prevalence

of maladaptive personality features and personality disordersPrevalence

of paranoid, schizoid, avoidant, obsessive- compulsive and depressive personality disorders significantly higher in CFS compared to normalsNeuroticism frequently associated with CFS; patients with CFS were found to be less extraverted(Nater et al,

2010)

Slide13

Cognitive deficits in

CFS

(reaction

Impai

red inf

ormation processing speed time)(Cockshell et al, 2013)Imp

aired working

memory and poor learning of information(Mitchiels 2001)

Imp

a

i

r

ed

w

ork

i

n

g

memory

a

n

d

al

t

e

r

a

tio

n

s

i

n

m

o

t

or speed

(Majer et

al.,`2008)

Slide14

Differential Diagnoses -

Medical

VERY

COMMON

(~1 PER 100)AnemiaThyroid disorders Medications

(statins) Sleep apneaCOMMON (~1 PER 1,000)Chronic infection: HIV, Hepatitis C endocarditis, osteomyelitis, Lyme disease, occult abscessCancerPulmonary conditions: asthma, obstructive lung disease,

interstitial lung diseaseSymptomatic hyperparathyroidism

UNCOMMON (~1 PER 10,000)Polymyositis, Dermatomyositis, Myopathy Myasthenia gravis, Multiple sclerosis NarcolepsyInflammatory bowel diseases

Slide15

Overlapping “Functional

Syndromes”

Functional

Somatic Syndromes by

Speciality

GastroenterologyIrritable Bowel Syndrome, Non-Ulcer DyspepsiaGynaecology

Chronic Pelvic PainPre-menstrual syndrome

RheumatologyFibromyalgia

Cardiology

Atypical/Non-cardiac chest

pain

DaCosta’s

Syndrome

Respiratory

Medicine

Hyperventilation

Syndrome

Dentistry

Temporomandibular

Joint

Dysfunction/Atypical

facial

pain

ENT

Globus

Hystericus

Allergy

Multiple Chemical

Sensitivity

Slide16

Fibr

o

m

y

algia

American College of Rheumatology (ACOR) Criteria for Fibromyalgia; Adaptedfrom

Wolfe et al, 1990

Slide17

Fibromyalgia vs

CFS

Most

patients

who have received the diagnosis of one are also likely

to meet the diagnostic criteria for the otherSimply put,CFS is fatigue with painFibromyalgia is pain with

fatigue(Sullivan et al, 2002)

Slide18

D/D vs Comorbidity -

Psychiatric

whether

/

Causep

sychiatric conditions are/ Co-incident

al overlap of

Major DepressionAnxiety disordersSomatoform disorder

Hypochondriasis

Neurasthenia

Debated

-

Conse

q

uen

ce

symptoms

Ma

i

n

o

v

er

l

apping

s

ym

p

t

om

s

-

f

a

t

i

gue,

sleep disturbance,

and

poor

concentration

Slide19

CFS vs

Mood &

Anxiety

disorders

A psychiatric disorder (in patients with an existing

diagnosis of CFS) was diagnosed in 45.2%; mostly mood and anxiety disorder.(Mariman et al.,2013)Studies of clinic attenders with CFS reported that more than 25% have

a current DSM major depression diagnosis, and 50%–75% have a lifetime

diagnosis(Skapinakis et al, 2000)

General

Population

CFS

Patients

GAD

3.5%

30%

Panic

Disorder

5.1%

25%

Slide20

Barriers to

making

diagnosis

Illness model- a

biomedical approach by both doctors (GP) and patients

Poor communication between the patient and the health professionalKnowledge and attitudes- limited understanding, limited training

Low priority in the health care setup

(Kerin Bayliss et al, 2014)

Slide21

Treatment -

Principles

En

g

agement: Build

ing rapport, empathic understanding of distressDeveloping a therapeutic rationale - individualizeEvolution

of a treatment pl

an: defined by objective performance targets and time frames.Use psychopharmacology sparingly

: Only

when a

demonstrable

symptom

target

can

be

seen

Avoid

invasive

and/or expensive

medical

testing

.

See

k

opportun

i

ties

t

o cl

a

r

i

f

y

i

m

por

t

a

n

c

e

of

psychological

factors

as the

therapy proceeds

(Comprehensive

Textbook

of

Psychiatry

9

th

ed)

Slide22

Treatment -

Guidelines

NICE

Guidelines

(2007)General strategiesSymptom

managementFunction and quality of life management (sleep,

rest period, relaxation, pacing, diet)Equipment to maintain

independenceEducation and employmentComplementary and supplementary careReferral to

specialist

Slide23

Treating

Co-Morbidities

Depression/Anxiety

-

SSRIs/SNRIs

Pain symptoms -

TCAs/DuloxetineSleep Disturbance - BZDs/Non-BZD Hypnotic

Slide24

Pharmacological

treatment

Pharmacological

interventions

for

symptom controlIf chronic pain is a predominant feature - referral

to a pain management clinicPrescribing of low-dose tricyclic antidepressants, specifically amitriptyline, for poor sleep or painMelatonin may be considered for children and

young people with CFS/ME who have sleep difficulties(NICE, 2007)

Slide25

Pharmacological

treatment

Drugs with some evidence

for

CFSvitamin B1

vitamin Cco-enzyme Q10magnesiumNADH (nicotinamide adenin

e dinucleotide) or multivitamins and

minerals(NICE, 2007)

Slide26

Pharmacological

treatment

Drugs with

no

evidence in

CFSmonoamine oxidase inhibitors

glucocorticoids (such as hydrocortisone)mineralocorticoids (such as fludrocortisone)dexamphetaminemethylphenidatethyroxineantiviral agents(NICE Guidelines,

2007)

Slide27

RINTATOLIMOD

(Ampligen)

Immunological

and

Anti-Viral

AgentSupported by 2 RCTs, awaiting

FDA approvalActs by stimulating the innate immune systemBinds to Toll-like

Receptor-3 (

TLR-3) and increases production of interferonsAc

ti

v

a

t

es

i

n

t

r

a

-

cellular

R

NAse

en

z

yme

–

Ca

u

ses destruction

of

viral

RNA

(Chambers et al,

2006)

Slide28

Psychological

treatment

Best

evidence base

for CBT

and GETactivity-

relatedCBT includeseducating patient about the etiologic modelsetting goalsrestoring fixed

bedtime and wake-up timechallenging and changing fatigue-

andcognitionsreducing symptom focusingspreading activities evenly throughout the day

gradually increasing

physical

activity

planning

a

return

to

work,

and

resuming other

activities

The

intervention, which

typically

consists

of

12–14

sessions

spread

over

6

months, helps

CFS

patients

gain control

over

their

symptoms

Slide29

Psychological

treatment

Graded

Exercise Therapy

is based

on the model of deconditioning and exercise intolerance and usually involves

a home exercise program that continues for 3–5 months.Walking or cycling is systematically increased, with set target heart ratesThe primary component of CBT and GET is

a reduction in fatigue is the change in the patient's perception of

fatigue and focus on symptoms

Slide30

PACE

Trial

Large-scale five-year

trial funded

by

the UK government- compared the efficacy and safety of four

treatments:Specialist medical care (SMC)SMC with CBTSMC with GETSMC with adaptive pacing therapy (APT)

Randomized control trial Sample size- 641

Slide31

PACE

Trial

The

percentages

(number/total) meeting

trial criteria for recovery were 22% (32/143) after CBT, 22%

(32/143) after GET, 8% (12/149) after APT and 7% (11/150) after SMCCBT or GET, when added to SMC, is an effective treatment for chronic fatigue syndrome, and that the size of this

effect is moderateCBT and GET are

the therapies most likely to lead to recovery(White et al, 2012)

Slide32

Course and

Outcome

Small

minority of

patients recover completelyMost patients either achieve some

improvement or remain status quoLong term follow up studies - Over time many individuals will not maintain a CFS diagnosis but will not return to their premorbid level of functioning.

Psychological factors such as illness attitudes and coping style seem

more important predictors of long term outcome than immunological or demographic variables(Wilson et al, 1994; Brown et al 2012)

Slide33

Con

clusions

C

F

S

predominantly descri

bed in the western literatureSignificant burden associatedDilemma over stat

us as a psychiatric or medic

al conditionNo clarity over etiologyEvidence lacking for pharmacological treatments

Poor

outcome

Lack

of

studies

in

the

Indian

population

Slide34

Future

Directions

M

ultidis

c

iplinary approach t

o research and treatmentInterplay of biological and psy

cho-social fa

ctors in etiopathogenesis to be studiedNeed for cross-cultural research

Enh

a

nce

m

e

n

t

of

aw

a

r

eness

i

n

p

r

a

c

tic

i

n

g

p

h

y

s

icia

n

s and

psychiatrists

Slide35

Thank

you