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Chronic fatigue syndrome: Aetiology, diagnosis and treatment

Article  in  BMC Psychiatry · October 2009

DOI: 10.1186/1471-244X-9-S1-S1 · Source: PubMed

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BMC Psychiatry BioMed Central

Review Open Access

Chronic fatigue syndrome: aetiology, diagnosis and treatment
Alfredo Avellaneda Fernández*1, Álvaro Pérez Martín2, Maravillas Izquierdo
Martínez3, Mar Arruti Bustillo4, Francisco Javier Barbado Hernández5,
Javier de la Cruz Labrado6, Rafael Díaz-Delgado Peñas7, Eduardo Gutiérrez
Rivas8, Cecilia Palacín Delgado9, Javier Rivera Redondo10 and José Ramón
Ramón Giménez11

Address: 1Carlos III Health Institute. Sinesio Delgado, n° 6, 28029, Madrid. Spanish Society of Primary Care Physicians. Narváez, 15 1° Izda,
28009, Madrid, Spain, 2Spanish Society of Family and Community Medicine. Portaferrissa 8 pral., 08002, Barcelona, Spain, 3Public Health and
Health Management Chair, European University of Madrid. Tajo s/n., Urb. El Bosque, 28670, Villaviciosa de Odón, Madrid, Spain, 4Coordinating
Institution for the National Associations of Fibromyalgia and Chronic Fatigue. Rafael Bonilla 19, local, 28028, Madrid, Spain, 5Spanish Society of
Internal Medicine. Pintor Ribera 3, 28016, Madrid, Spain, 6Spanish Society of Psychosomatic Medicine and Medical Psychology. Avda. de los
Angeles, 14 Portal 2 - 2° C, 28223, Pozuelo de Alarcón, Madrid, Spain, 7Spanish Association of Paediatrics. Aguirre 1, bajo derecha, 28009, Madrid,
Spain, 8Spanish Society of Neurology. Via Laietana, 23, entlo A-D, 08003, Barcelona, Spain, 9Spanish Society of Physiotherapy. Calle Rodriguez
Marín 69, bajo D, 28016, Madrid, Spain, 10Spanish Society of Rheumatology. Marqués de Duero,5, 1°, Madrid, 28001, Spain and 11Carlos III
Health Institute. Sinesio Delgado, n° 6, 28029, Madrid, Spain
Email: Alfredo Avellaneda Fernández* - [email protected]; Álvaro Pérez Martín - [email protected]; Maravillas Izquierdo
Martínez - [email protected]; Mar Arruti Bustillo - [email protected]; Francisco Javier Barbado
Hernández - [email protected]; Javier de la Cruz Labrado - [email protected]; Rafael Díaz-Delgado
Peñas - [email protected]; Eduardo Gutiérrez Rivas - [email protected]; Cecilia Palacín Delgado - [email protected];
Javier Rivera Redondo - [email protected]; José Ramón Ramón Giménez - [email protected]
* Corresponding author

Published: 23 October 2009

<supplement>
Institute de Salud
<title>
Carlos
<p>Chronic
III and the fatigue
Public Health
syndrome:
and aetiology,
Health Administration
diagnosis andoftreatment</p>
the Universidad
</title>
Europea
<editor>Maravillas
de Madrid.</note>
Izquierdo
</sponsor>
Martínez,
<note>Review</note>
Alfredo Avellaneda <url>http://www.biomedcentral.com/content/pdf/1471-244X-9-S1-info.pdf</url>
Fernández and Álvaro Pérez Martín</editor> <sponsor> <note>The publication </supplement>
of this supplement was made possible with help from the

BMC Psychiatry 2009, 9(Suppl 1):S1 doi:10.1186/1471-244X-9-S1-S1

This article is available from: http://www.biomedcentral.com/1471-244X/9/S1/S1
© 2009 Avellaneda Fernández et al; licensee BioMed Central Ltd.
This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract
Chronic fatigue syndrome is characterised by intense fatigue, with duration of over six months and
associated to other related symptoms. The latter include asthenia and easily induced tiredness that
is not recovered after a night's sleep. The fatigue becomes so severe that it forces a 50% reduction
in daily activities. Given its unknown aetiology, different hypotheses have been considered to
explain the origin of the condition (from immunological disorders to the presence of post-
traumatic oxidative stress), although there are no conclusive diagnostic tests. Diagnosis is
established through the exclusion of other diseases causing fatigue. This syndrome is rare in
childhood and adolescence, although the fatigue symptom per se is quite common in paediatric
patients. Currently, no curative treatment exists for patients with chronic fatigue syndrome. The
therapeutic approach to this syndrome requires a combination of different therapeutic modalities.
The specific characteristics of the symptomatology of patients with chronic fatigue require a rapid
adaptation of the educational, healthcare and social systems to prevent the problems derived from
current systems. Such patients require multidisciplinary management due to the multiple and
different issues affecting them. This document was realized by one of the Interdisciplinary Work
Groups from the Institute for Rare Diseases, and its aim is to point out the main social and care
needs for people affected with Chronic Fatigue Syndrome. For this, it includes not only the view of
representatives for different scientific societies, but also the patient associations view, because they

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know the true history of their social and sanitary needs. In an interdisciplinary approach, this work
also reviews the principal scientific, medical, socio-sanitary and psychological aspects of Chronic
Fatigue Syndrome.

Background course and without any apparent cause, which interferes

The chronic fatigue syndrome (CFS) is fundamentally with daily activities, does not decrease with rest, worsens
characterized by intense fatigue of unknown cause, which with exercise, and is usually associated to systemic, physi-
is permanent and limits the patient's functional capacity, cal and neuropsychological manifestations [6,7].
producing various degrees of disability.
The aetiology, diagnosis and therapeutic options for
In medical terminology, fatigue is the early onset of tired- chronic fatigue syndrome in adults and pediatric patients
ness after an activity has been started; it is a sensation of are discussed below.
exhaustion or difficulty to carry out physical or intellec-
tual activities, without recovery after a period of rest. The aetiology and the pathogenic mechanisms of CFS
Fatigue has been categorized as recent fatigue, prolonged As the criteria for CFS diagnosis are not based on the
fatigue and chronic fatigue, according to the time of evo- understanding of aetiopathogenic mechanisms, some
lution (less than one month, more than one month and patients present similar clinical manifestations but are
more than six months, respectively) [1]. diagnosed with other conditions because fatigue is not the
primary symptom. Some of those conditions are fibromy-
It is advisable to differentiate fatigue from other medical algia, irritable bowel syndrome, and temporomandibular
concepts with which the symptom is often confused: first, joint syndrome. Furthermore, in addition to sharing sev-
from asthenia, defined as the lack of strength or feeling of eral symptoms with CFS, currently available evidence sug-
inability to carry out daily tasks, which is more intense at gests that those diseases also share similar
the end of the day, and usually improves after a period of pathophysiologic mechanisms [8,9].
sleep; second, from weakness, which is the reduction or
loss of muscular strength, and the key symptom in mus- Although the aetiology and the pathogenic mechanisms
cular diseases. of CFS are not fully understood, several hypotheses have
been postulated and described below, being the disorders
In addition to fatigue, CFS is associated to a wide spec- of the central nervous system neuromodulator the one
trum of symptoms, including arthralgias, muscle pain, supported by more evidence to explain the possible path-
headaches, anxiety, depressive symptoms, cognitive disor- ogenic mechanisms involved in CFS [5].
ders, sleep disorders, or intolerance to physical exertion,
among the most frequent [2,3]. Infectious theory
Epstein Barr virus, Candida albicans, Borrelia burgdorferi,
The little understanding of CFS aetiopathogeny, together Enterovirus, Citomegalovirus, Human Herpesvirus, Espu-
with the difficulties to achieve an objective and quantita- mavirus, Retrovirus, Borna virus, Coxsackie B virus, and
tive assessment of the symptoms that affected patients hepatitis C virus (HCV) have been associated to CFS, but
have, has prevented for a long time the establishment of a their pathogenic relationship with the syndrome has not
diagnosis [4]. A consequence of such a problem is the been demonstrated [10].
variety of names CFS is known for, including allergic
encephalomyelitis, immune dysfunction syndrome, neu- Immunological theory
roendocrine immune dysfunction syndrome, post viral Although different disorders have been found in the
syndrome, Iceland disease, neurasthenia, and Royal Free immune system or its function, currently there is no scien-
disease, among others [5]. tific evidence to attribute the cause of this syndrome to a
primary disorder of the immune system. There are a large
The various criteria established in recent years have number of studies on immune disorders in the CFS assess-
allowed a more accurate delineation of CFS, and this has ing identical parameters, but they frequently yield contra-
contributed to a better understanding of its clinical pic- dictory results [11-14].
ture, and potential therapeutic interventions [1].
Neuroendocrinological theory
CFS is, therefore, a complex, chronic disorder of unknown Several disorders in the hypothalamic-pituitary-adrenal
aetiology, characterized by the presence of intense and axis (HPA) and in the production of related hormones
disabling fatigue (physical and mental), with a clinical have been found in CFS, as well as a disorder of the regu-

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lating mechanisms of the autonomic nervous system. It is ary to excessive activity, with no improvement associated
currently known that the relationships between the differ- with rest and worsening with stress, and directly resulting
ent parts of the nervous system are mediated by neuro- in persistent disability (physical and mental) [7].
transmitters and that their disorders lead to unbalanced
functioning of certain structures and to the development The chronic symptoms develop later [24], persisting for
of well known diseases. Many of the clinical features in weeks or months. Predominant symptoms vary for the
patients with CFS are similar to those found in patients individual patient, and include fatigue, fever or intermit-
with fibromyalgia, and it can therefore be postulated that tent dysthermia, migratory arthralgias, generalised mus-
the physiopathological mechanisms are probably similar clar pain, pharyngitis or sore throat, headache, tender
in both conditions. cervical or axillary lymph nodes, and other less common
symptoms.
In patients with fibromyalgia, the research on neurotrans-
mitter disorders has started to yield positive findings, and Fatigue is usually associated to neurocognitive and sleep
it is known that different clinical manifestations will disorders. Patients have difficulty in concentrating,
appear according the type and the site of action of affected insomnia or hypersomnia, and occasionally depression.
neurotransmitters [8,15]. Palpitations, thoracic pain, night sweating, or weight loss/
increase are less common [10].
Prevalence and clinical features
It is difficult to establish the prevalence of CFS, since it In general, clinical evolution is characterized by regular
depends on the diagnostic criteria used and the study pop- and even seasonal recurrences. Each outbreak can be dif-
ulation. Initial research suggested a prevalence between ferent from the previous one, and periods between each
0.002% and 0.04%. [16,17]. However, latest epidemio- recurrence are rarely completely asymptomatic [1]. CFS's
logical studies in the USA and in the United Kingdom symptomatology worsens with physical or emotional
show prevalence rates ranging from 0.007% to 2.5% of stress, interfering or limiting previous activities (including
the general population. [18] These rates increase up to family, work, and social activities); in some cases, patients
0.5-2.5% when the population assessed includes individ- may need help for their basic daily activities.
uals seen in primary care facilities instead of the global
population. [19] In the United Kingdom, according the The main co-morbidity is related with psychiatric disor-
Oxford criteria [20], the prevalence in the global popula- ders, such as depression or anxiety, with an approximate
tion has been estimated in 0.6%. In Japan the prevalence incidence of 28% in the Western population [25,26].
has been found to be 1.5% in the general popula-
tion[21,22]. Thus, the prevalence in the general popula- Diagnosis
tion appears to be much higher than previously indicated. As there is no pathognomonic sign or specific test for CFS,
Even with strict criteria for CFS, it is estimated that the diagnosis of the syndrome is clinical. Other causes of
approximately 1% of the adult population experiences fatigue should be ruled out, through a complete and
this condition. Interestingly, a large part of this group detailed medical history, focused on the characteristics of
remains unrecognized by the general practitioner. A strik- fatigue, delineating its form and time of onset, duration,
ing similarity in lifestyle pattern between SF, CF and CFS triggering factors, relationship with rest and physical
calls for further research. [23] activity, and the degree of limitation of the patient's regu-
lar activities. Furthermore, targeted interrogation will col-
CFS mainly affects young adults from 20 to 40 years, lect the symptoms in the osteomuscular, neurovegetative
although the symptoms also exist in childhood, adoles- and neuropsychological domains. Thus, chronic fatigue
cence and in the elderly [10]. It has a 2-3 times higher should be differentiated from debilitation, exercise intol-
prevalence in women than in men. No evidence exists erance, sleepiness, or loss of motivation and stamina.
showing that any socio-economic group is more affected
than others [5]. The presence of psychiatric disorders (anxiety, depres-
sion) should be included in the personal history as well as
The typical CFS case occurs acutely, and even suddenly, possible non-infectious precipitating factors (organo-
usually in a previously healthy person. Initially, fever, sore phosphorous insecticides, solvents, CO, multiple chemi-
throat, cough, muscular pain and fatigue are the typically cal hypersensitivity, sick building syndrome, situations
predominant symptoms; digestive symptoms such as that disturb sleep, etc.), and prior history of allergies. This
diarrhoea are less common. This initial process resolves information should be included to rule out other alterna-
with intense tiredness as a sequel. The cardinal or key tive diagnoses such as infections, neoplasias, depression
symptom is fatigue, essential for diagnosing the condi- or sleep disorder.
tion. Fatigue in CFS is characterised by not being second-

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Specific exploration is required for the musculoskeletal ria, reducing the symptoms from 11 to 8: these criteria are
system (strength, reflexes and muscular tone), the neuro- based on symptoms, particularly rheumatological and
logical system (looking for any neurological deficit), the neuropsychological symptomatology.
cardiovascular and respiratory systems (anaemia and car-
diac insufficiency), the endocrinological system (thyroid Diagnostic protocol for patients with suspected CFS
gland disorders), the immune system (tender cervical, Figure 1 details the algorithm for CFS diagnosis [28]. Con-
axillary or inguinal lymph nodes) and the gastrointestinal ditions that exclude the diagnosis of CFS are: psychiatric
system. Physical findings are usually unspecific, and a disorders, such as major depression, schizophrenia, eating
large variety of signs can be found, such as pharyngeal disorders (anorexia, bulimia), bipolar disorder, alcohol or
soreness, fever, tender posterior cervical or axillary lymph other substance abuse, in addition to morbid obesity, and
nodes, muscular tenderness on palpation, and, occasion- active medical diseases, either non-treated or without a
ally, rash. completely established resolution.

Currently, there are no specific biological or morphologi- Prognosis

cal markers to establish per se the diagnosis of the CFS, There is an average time of 5 years from the beginning of
and therefore none of the alterations that can be found are the symptoms to the diagnosis of the syndrome, with total
useful for diagnosis. Diagnostic criteria basically arise as a recovery rates between 0% and 37%, and improvement
research requirement, but their limitations for actual clin- between 6% and 63% [29]. Younger patients and those
ical practice must be accepted. without concomitant psychiatric diseases show the best
prognosis, although other studies have estimated that the
The Centres for Disease Control and the CFS International rates for both groups are similar [30].
Study Group proposed in 1994 an international diagnos-
tic criteria (Table 1) [27]. Their main objectives were to Assessment methods
increase the sensitivity of the previous classification, and There is no single tool for the assessment of patients with
to offer a more accurate definition of the condition, in CFS that allows a global appraisal of the clinical manifes-
order to achieve a more consistent clinical diagnosis and tations and the impact of the disease on patients. There
use it as a research tool. The international criteria are are specific questionnaires, according the feature to be
based on the fulfilment of two major criteria (chronic measured, that can provide useful information on specific
fatigue causing incapacity, lasting more than 6 months, issues. A summary of them can be found in the systematic
and the exclusion of associated medical and psychiatric review by Bagnall et al [31]. However, the most useful way
conditions), as well as the concurrence of a series of crite- of collecting information is with interviews and patient

Table 1: Diagnostic criteria for chronic fatigue syndrome

1.-Persistent chronic fatigue (at least 6 months) or intermittent, unexplained chronic fatigue, which relapses, or with a definite start, and is not the
result of recent exertions. Does not improve with rest. Results in a significant reduction in the patient's previous normal activity.

2.-Exclusion of other diseases that may cause chronic fatigue.

Four of the following minor criteria (signs or symptoms) must be present concurrently for six months or longer, after the onset of fatigue:

Minor criteria 1-Recently impaired memory or concentration.

(Signs and symptoms)

2.-Odynophagia

3.-Painful axilar or cervical adenophatias

4.-Myalgias

5.-polyartralgias without phlogosis

6.-Headache with a new pattern or seriousness.

7.-sleep which does not improve by resting.

8.-Discomfort post effort > 24 hs.

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FA T IGUE

-
Medical history: History-taking and physical examination
Basic Complementary Tests

Less than six months: Acute

or self-limited fatigue.
Chronic fatigue and relapses Prolonged fatigue.
(physical and mental) during six NO Periodic health evaluation.
months or more. During all the lifetime:
Depression, other causes.
yes

Daily tasks, style and quality of Idiophatic chronic asthenia.

life significantly affected. NO Periodic health evaluations.
NO

yes

Is there any exclusion causes?

Medical history and directed
physical examination. Medical or psychiatric disease.
Selective complementary tests yes NO
Rule out CFS
(immunological, serological,
endocrinological, electrophysi-
ological, image techniques,
biopsy)

NO

There are four or more of this eight minor

criteria:
1- Memory and concentration disturb
2- Odynophagia
3- Painful axilar or cervical adenophatias
4- Myalgias NO Idiophatic chronic asthenia.
5- Articular pain without phlogosis
6- Headache with a new pattern or
seriousness.
7- Sleep that no improvement with rest.
8- Discomfort post effort > 24 hs.

yes

CHRONIC FATIGUE
SYNDROME

Figure 1 protocol for patients with suspected CFS

Diagnostic
Diagnostic protocol for patients with suspected CFS.

diaries. Interview can include patient self-records, ques- Self-records and scales are excellent references and help
tionnaires and scales for functional assessment, such as the therapist to assess the patient's daily activities, general
"Karnofsky Performance Scale, Medical Outcomes Study functioning and the degree of disability.
Short-Form General Health Survey" (SF-36®) [32] and
Sickness Impact Profile (SIP) [33]. Interviews should be The scale is useful for the patient because they can fill in a
repeated periodically in time. hierarchy/severity scale their symptoms during the initial

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visit, and then, approximately every 6 months. This scale included, there was no significant difference between the
categorizes both the severity of the symptom and the two groups. [41]
aggravating factors.
Cognitive therapy as a therapeutic modality for CFS com-
Daily activity/functional capacity scale is also a useful prises a series of techniques, based on the principles of
tool. In this case the patient is asked to make a diary of all behaviour modification and the cognitive theory, aimed
their daily activities and periods of rest for a week. at strengthening the modification of thoughts and behav-
iour related to the patient's symptoms and distress [42].
Symptoms assessment Most protocols developed for this treatment modality are
The easiest way to measure pain in the locomotive appara- based on three key factors: programmed physical exercise,
tus is with an Analogical Visual Scale (AVS), especially control and coping with disease-associated stress, and
when trying to assess the pain that a patient has experi- cognitive restructuring [43].
enced during a given period of time [34].
Regarding to prescription of appropriate exercise sched-
To assess fatigue, one of the most used tools is the Multi- ules, there is no consensus for patients with CFS. How-
dimensional Fatigue Inventory [35], a 20-item question- ever, it has been demonstrated that gradual exercise
naire that measures global, physical and mental fatigue, programmes are beneficial for some patients, improving
and decrease in activity and motivation. both their physical work and the psychological and cogni-
tive aspects. The main objective of the exercise pro-
When the patients have difficulties for carrying out physi- gramme is the progressive prevention of physical
cal exercise it is important to quantify the degree of deterioration and optimizing the functional capacity,
impairment. The most objective methods are based on looking for an improvement of the patient's quality of life
determining the aerobic capacity of patients, usually with [44].
spiro-ergometric tests, expired gases/heart rate are meas-
ured, and work load quantified. Other alternative meth- Many pharmacological therapies have been used for treat-
ods that offer semi-quantitative measures, and are often ing CFS. However, there are very few publications on ran-
used, are the 6-minute running test [36], measuring the domised clinical trials with drugs, and the quality of the
strength of certain muscular groups, and the degree of available studies is not good [45-47]. On the other hand,
mobility of the column or the peripheral joints. since the course of CFS is highly fluctuating, with alternat-
ing periods of improvement and deterioration, it has been
The assessment of disability is complex due to the fact that recommended that any therapeutic modality should com-
the clinical diagnostic criteria have not been validated in ply with several requirements to consider the study as
the medical-legal framework, to the lack of any objective methodologically adequate.
proof of existence as well the lack or low medical-legal
performance of validated instruments to quantify the dis- Ampligen, an antiviral agent, has been used recently in the
ability associated with CFS. There is a big barrier for fulfill- treatment of this disease [48-50]. This agent is a stimula-
ing two major conditions in the assessment of the tor of interferon production, which reduces the levels of
disability, namely objective evidence of the impairment RNasaL. Available results from clinical trials show modest
and the absence of data corroborating the severity of the improvements, but results need to be verified. The FDA
pain [37]. currently considers Ampligen an experimental therapy,
and has not approved it for general use [51], although an
Treatment open clinical trial is being carried out with this drug.
The therapeutic approach to CFS is complex and requires
a combination of different therapeutic modalities. In Chronic fatigue syndrome in paediatric patients
recent decades, many therapies for CFS have been exam- It can be stated that CFS is rare in childhood and adoles-
ined, but the only one that has demonstrated a significant cence: only 0.06% to 0.32% of children from 5 to 15 years
efficacy in patients diagnosed with CFS, together with of age fulfil the US Centers for Disease Control and Pre-
gradual physical exercise, is cognitive behaviour therapy, vention (CDC) criteria for CFS [51].
which has been intensely developed in recent years [38-
40]. A 2008 Cochrane review found that 40% of patients Although the CDC criteria is mostly followed [27], differ-
reported improvements in fatigue after cognitive behav- ent research groups accept that, although fatigue for at
ioural therapy compared with 26% in usual care at the least 6 months is required to establish the diagnosis,
end of treatment. At follow-up, 1-7 months after treat- shorter periods of debilitating fatigue should be consid-
ment ended, when people who had dropped out were ered in adolescents or school-aged children [52]. Since the
adjective debilitating is the disease's main feature, it is

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highly likely that shorter periods of 3 months, or even 4- In epidemiological studies including children and adoles-
6 weeks, should be considered when associated with cents, prevalence of 8.7 cases per 100,000 with fatigue,
absenteeism. This factor is so important that the primary and 2.7 per 100,000 people with CFS are found according
care paediatrician or general practitioner (GP) should sus- to a study published by Jordan et al [55]. It must be
pect CFS whenever it is present, although the clinical pic- assumed that, since there are no accurate and realistic cri-
ture does not fulfil more stringent criteria. teria for the diagnosis of CFS in adolescents and children,
there are no accurate epidemiological data either.
The Australian Clinical Guide, sponsored by the Royal
Australasian Collage of Physicians, includes issues such as When analysing the psychological aspects in adolescents
the definition of fatigue, its assessment, particular charac- who fulfil the CFS diagnostic criteria, more than 1/3 have
teristics when the condition affects children and adoles- psychiatric diagnoses at the same time, particularly
cents, and its associated symptoms. But the guide goes depression, and less often, generalized anxiety disorder
beyond major and minor inclusion or exclusion criteria [56]. A prospective, community-based study in the UK
[5]. In contrast with the CDC criteria, this guide empha- found an incidence of 0.5%for CFS in 11 to 15-year-old
sizes as a key issue the patient feeling symptomatically ill adolescents, using the CDC criteria, and identified anxi-
after a minimum physical or mental effort. In addition, it ety/depression, conduct disorder, older age and female
offers clear explanations for neurological and neuroendo- gender as risk factors for the development of CFS [57].
crine disorders, as well as the autonomic and immune Several studies show that adolescents with CFS internalize
manifestations of CFS. somatic symptoms more intensely and are more disabled
than other adolescents diagnosed with chronic diseases
The obsessive tendency to rigidly classify children and with bad prognosis, such as cancer, cystic fibrosis, or juve-
adolescents with highly stringent criteria is inappropriate, nile idiopathic arthritis [58].
even though such criteria are internationally accepted.
Table 2 summarizes the differences noted in CFS between Prognosis
adults and children. Twenty percent of patients in Bell's study [53] continue to
consider themselves ill with limitations or disability even
Children and adolescent patients, although they do not 13 years after the onset of the syndrome; although 8% of
strictly fulfil the CDC criteria, will benefit from an early children find their outcome satisfactory. Although is diffi-
intervention, with a substantially more adequate thera- cult to differentiate children with CFS from those who are
peutic response [53]. This fact urges primary care paedia- just chronically tired according to the duration of symp-
tricians and GPs to make a presumptive CFS diagnosis toms, in this study there is no correlation between the
resulting in early intervention. Nevertheless, Davies et al degree of recovery and age of diagnosis, sex, or clinical fea-
assessed the clinical presentation of CFS in children tures at presentation. The educational impact of the dis-
younger than 12-year-old, based on the Royal College of ease is closely related to the outcome; 23% of patients
Paediatrics and Child Health criteria (less stricter criteria miss school from 1 to 6 months, 8.6% from 6 to 12
compared to CDC adult criteria) and found that these months, 5.7% from 1 to 2 years, and 8% do not recover at
children were very disabled, with mean school attendance all after 13 years of follow-up. A follow-up study involving
of just over 40%. But, when compared to adolescent 28 patients, aged 7 to 17 years, highlights the need for
patients, clinical assessment was very similar. In addition, early recognition and diagnosis of chronic fatigue syn-
younger patients (24/26) also fullfilled the CDC criteria drome in young people and the importance of continuing
[54]. paediatric support to reduce symptom persistence in the
sensitive recovery period. Maintaining school attendance

Table 2: Adult/Children CFS differences

Age Fatigue Symptoms Psychiatric profile Prevalence Sex Triggering factor

% M/F

Adult >6 Odynophagia Post-anxiety disorders 0.006-2.5 2-3/1 Flu

20-40 months Painful adenophatias Depression Cold
Myalgias cephalea Serious disease

Child >3-6 Episodic tension cephalea Sadness 0.06-0.32 2.5/1 Traumatism

5-15 months Recurrent abdominal pain Hyperactivity (initial phase) Sport failure
Tachycardia Fatigue Mild disease
Orthostatic hypotension

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by close liaison between health and education services included with other chronic processes among the highest
both before and after diagnosis and treatment is also vital healthcare and socioeconomic burdens.
if long-term morbidity is to be reduced. It should be noted
that 15 patients experienced difficulties when returning to Healthcare management
school [59]. In another study including 42 children diag- Management of CFS should start with a correct and ade-
nosed with CFS with 1 to 4 years of follow-up after the ini- quate diagnosis and patient care; primary care healthcare
tial medical intervention, 43% considered themselves professionals should obtain a careful medical history and
cured, 52% improved and 5% showed no changes in their a complete physical examination. This context gives the
condition [60]. best thruway to the healthcare system due to its easy
access, and its knowledge and close relationship with peo-
The best predictor for good outcome is still the amount of ple.
school time lost during the first 4 years of the disease.
Teachers, primary care doctors, paediatricians, psycho- Primary care staff should be appropriately trained, and
therapists and social workers, should be aware of this to capable of explaining the problem, as well as the available
achieve the best results and meet the best life expectations therapeutic options to the patients [5].
for children suffering from this syndrome.
After the initial diagnostic suspicion, and although the
Treatment burden of patients' follow-up can be perfectly accom-
In adolescents, cognitive behaviour therapy combined plished in the primary care context, it is recommended
with other group therapies that promote treatment com- that patients are referred to a second level of specialised
pliance and sharing experiences or thoughts with other care for confirmation of the diagnosis and treatment guid-
adolescents is very useful, even when they do not have ance. Since in CFS medical specialities are involved in care
identical pathologies. It must be noted that there is very and treatment (rheumatology, internal medicine, psychi-
limited evidence on cognitive therapy in adolescents. atry, etc.), such specialists should also receive adequate
Some non-controlled studies suggest that this therapy training. Cooperation and coordination between primary
reduces fatigue in young people [58,61] with early inter- and specialised care is basic for the correct management of
vention. CFS. Occasionally, the intervention of the physiotherapist
or psychologist in the treatment is also necessary, and ade-
When assessing therapies, it must be remembered that quate training should also be offered to these healthcare
exercise temporarily worsens the symptoms and the times professionals.
for rest, naps, leisure time, or outdoors activities should
be established jointly with the adolescent. In addition to a timely and appropriate diagnosis, patients
with CFS usually require individualized management pro-
In this chronic situation, reassurance for both adolescents grams, as well as long-term follow-up. Although health-
and parents is the key factor that will determine the suc- care professionals are mostly responsible for the latter, the
cess of the therapeutic interventions, strengthening the collaboration of the patient's relatives and friends is also
self-confidence and increasing the adherence to the pre- essential. It is therefore necessary to train them, with the
scribed therapies started, and avoiding the organic versus objective of reducing the patient's anxiety and strengthen-
psychiatric debate. ing the very valuable therapeutic alliance [5]. All this can
considerably improve the prognosis of the condition. The
Chronic fatigue syndrome in healthcare particular social context of each patient and the functional
Healthcare cost associated to CFS repercussion should also be recognized and assessed [65].
It is difficult to estimate the costs imposed by CFS on
healthcare. There are few studies evaluating the use of Finally, as CFS is not well known, the contribution of
healthcare resources by these patients [62,63]. enough funds for research is also necessary, and the regu-
lated identification and management of patients or the
Although many people suffering CFS continue to work creation of adequate records by the healthcare system
despite of their illness for economic reasons and social would be a very useful intervention.
prestige, this represents an annual global loss of produc-
tivity of approximately n6,900 million, or what is the Legal aspects
same n15,200 per patient and year. These figures are com- Giving advice to a person with CFS in medical-legal mat-
parable to the losses caused by other diseases, such as ters can be very complex and should be done by a quali-
digestive system-related conditions or infectious and par- fied, experienced specialist. The notion of "permanent"
asitic diseases [1,64], suggesting that the CFS can be disability is problematic, as many people with CFS gradu-
ally improve. In patients seriously disabled, who have

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BMC Psychiatry 2009, 9(Suppl 1):S1 http://www.biomedcentral.com/1471-244X/9/S1/S1

been unable to work for more than five years, the proba- As mentioned above, CFS is disabling in some patients. In
bility of significant improvement in 10 years is less than these cases, all the support measures recognised in current
10-20%. This can be considered "permanent disability" in legislation should be applied. The most important issues
medical-legal terms [5]. to overcome are the difficulties of access to employment,
timetable flexibility and ergonomic assessments in order
As explained above, CFS is a highly disabling condition in to adapt the work post.
some patients, frequently requiring legal support for man-
aging possible social aids, handicaps or even disabilities. Competing interests
Ancillary personnel or social workers in healthcare centres The authors declare that they have no competing interests.
and city councils should provide information and advice
to the patients when they need it. It will also be necessary Acknowledgements
for the administrators to adapt the help to each case and The authors wish to express our gratitude to Dr. Jesús Ramírez Díaz-Ber-
the training of their personnel to become familiar with the nardo for the trust he placed, as the Director of the Instituto de Investi-
CFS, avoiding excessive litigation when looking for social gación de Enfermedades Raras (Rare Diseases Research Institute), in
assembling interdisciplinary work teams. We thank the Presidents of scien-
aids.
tific societies and associations of affected people for their support, and
those who suffer from this syndrome.
Educational aspects
A good interdisciplinary team for the diagnosis and treat- We are also grateful to the Instituto de Salud Carlos III and the Public
ment of CFS, together with personalised care will enhance Health and Health Administration Chair of the Universidad Europea de
the patient's improvement. The person suffering the dis- Madrid for their sponsorship. Without each of their contributions, this pub-
ease wants to know what can be done to improve and lication would not have been possible.
adapt to the upcoming changes.
This article has been published as BMC Psychiatry Volume 9 Supplement 1,
2009: Chronic fatigue syndrome: aetiology, diagnosis and treatment, and is
Patient education should always be supported by the available online at http://www.biomedcentral.com/1471-244X/9?issue=S1.
healthcare sector, and may be grouped in two different
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