Pamphlet for Physicians on M.E.

· Naar Index - Overzicht Bijlages [2007: Zie ME, Canadees medisch rapport, Brits medisch rapport]

Het volgende stuk komt van het internet (waar veel meer te vinden is over M.E. o.a. op het zgn. ME-Net, te bereiken o.a. via "De Digitale Stad", op het zgn. "Gezondheidsplein"). Het is van en voor medici, en dateert uit 1992. Er zou een boel bij op te merken zijn (overwegend als toelichting, niet als kritiek), maar ik merk hier en nu alleen op dat mijn ex en ik sinds resp. 10 en 1 januari 1979 ziek zijn.

Ik laat het stuk ongewijzigd en volledig volgen, afgezien van de noodzakelijke HTML-opmaak.

                  Chronic Fatigue Syndrome

                 A Pamphlet for Physicians

        U.S. Department of Health and Human Services

                   Public Health Service

               National Institutes of Health

                 NIH Publication No. 92-484

                          May 1992

                     Table of Contents

                        Introduction

                        Epidemiology

                   Historical Perspective

                      Clinical Picture

                   Evaluation of Patients

                    Immunologic Features

                 Neuropsychologic Features

                     Etiologic Theories

                     Patient Management

                         Conclusion

                          Appendix

Page 1

                  Chronic Fatigue Syndrome

                        Introduction

Chronic fatigue syndrome (CFS) is an illness characterized

by debilitating fatigue and several flu-like symptoms such

as pharyngitis, adenopathy, low-grade fever, myalgia,

arthralgia, headache, difficulty concentrating, and exercise

intolerance.  These nonspecific symptoms can make the

syndrome difficult to identify.  Profound fatigue -- the

earmark of the disorder -- usually comes on suddenly and

persists or relapses throughout the course of the illness.

But unlike the short-term fatigue and malaise that often

accompanies an acute infection, by definition, CFS symptoms

linger for at least 6 months, and often for years.

Chronic fatigue is a common complaint in primary care

practice.  No evidence exists to suggest that most patients

with chronic fatigue have CFS.  Indeed, CFS is probably an

uncommon cause of chronic fatigue.

When evaluating patients with chronic fatigue of unknown

origin, physicians can use the definition of CFS in the

Appendix as a guide.  This detailed definition was developed

for research use under the leadership of the Centers for

Disease Control.  It was published in Annals of Internal

Medicine in March 1988.  Because the disease is still poorly

understood, however, the outlined criteria should be

considered provisional.

Most investigators studying CFS believe that the syndrome

has many possible causes.  For example, various infectious

agents often trigger the onset of CFS.  Preliminary research

also shows a variety of immunologic disturbances in some

patients.  No single pattern of disturbances appears

consistently, however, and in general, patients are

Page 2

not clinically immunocompromised: they do not develop

opportunistic infections.  In fact, the character,

epidemiology, and prognosis of CFS is quite distinct from

that of major immune deficiency disorders such as AIDS.

Several different latent viruses also appear to be

reactivated in some CFS patients, although reactivation has

not been shown in all patients, and it is not clear that any

of these viruses are causally related to CFS or its

symptoms.  Many patients with CFS also present with anxiety

or depression.  In summary, as with most chronic illness,

CFS has both physical and psychiatric manifestations.

                        Epidemiology

Most cases of CFS are sporadic: the patient does not have a

close contact who has developed a similar illness.

Infrequently, however, close contacts, including family

members, become ill with CFS at about the same time.  During

the past 60 years, several apparent epidemics of this

illness affecting various communities or relatively large

numbers of co-workers have been reported.  Clusters of CFS

cases are unusual, however, and it is not generally thought

that people with CFS need to be isolated in any way.  The

clinical and laboratory findings of sporadic versus epidemic

cases have yet to be compared.

While the typical patient seeking medical care for CFS is a

white woman in her thirties, patients of all ages (including

the very young and very old), both sexes, many races, and

all socioeconomic groups have been affected.  CDC and

NIAID-sponsored researchers have studies under way to try to

estimate the prevalence of this disorder.

Page 3

                   Historical Perspective

Although interest in this illness has grown tremendously

since the mid-1980's CFS does not appear to be a new

disorder.  It closely resembles neurasthenia or

neurocirculatory asthenia, diagnoses commonly made in the

late 19th and early 20th centuries.  As stated earlier,

small epidemics of a very similar illness (most often called

myalgic encephalomyelitis, or ME) have been described in the

medical literature for at least 60 years.  Furthermore, case

reports describing similar illnesses date back several

centuries.  These sporadic cases of fatigue syndromes have

often been linked to bacterial, viral, or protozoal

infections (for example, brucellosis and influenza).  But

fatigue syndromes also appear outside the setting of an

infectious illness.  Several recent studies indicate that

the rheumatologic disorder called fibrositis or

fibromyalgia, first

...........................................................

     Febricula, Vapors

  ##################

                        Neurasthenia

               #######################

           Da Costa's (Effort) Syndrome

               #################

                       Chronic Brucellosis

                        ############

                            Hypoglycemia

                         ###############

               Myalgic Encephalomyelitis,

                Epidemic Neuromyasthenia

                          ##############

                  Total Allergy Syndrome

                            ############

      Chronic Mononucleosis, Chronic EBV

                          ##############

                     Chronic Candidiasis

                                 #######

              Postviral Fatigue Syndrome

                                  ######

                Chronic Fatigue Syndrome

###

 |_________|_________|_________|________

1800      1850      1900      1950

Timeline graph from 1800 to the present of other

diseases with symptoms very similar to CFS.

Page 4

described in the 19th century, is very similar to CFS.  The

average age of the patient with fibrositis is a bit older,

however, and soft tissue pain is a more prominent symptom in

this illness.

In the early 1980's, several studies indicated that antibody

levels to one virus, Epstein-Barr virus (EBV), were somewhat

higher in patients with CFS than in healthy individuals.  It

is important to put this observation in context.  EBV

infection is extremely common: approximately 90 percent of

American adults have been infected, and they harbor a

lifelong infection thereafter.  In most people the virus

remains dormant.  Antibody studies indicate that EBV may be

reactivated - i.e., replicating itself - more often in

patients with CFS than in healthy individuals.  But the

difference is not striking.  Moreover, as mentioned earlier,

evidence shows that several other viruses may also be

reactivated in CFS.  Therefore, investigators believe that

there is no proof that EBV causes CFS, at least in most

patients.

                      Clinical Picture

A hallmark of CFS is the sudden onset of the illness,

typically with flu-like symptoms.  In contrast to the usual

flu-like illness, however, the symptoms of CFS do not fully

resolve; they persist chronically, or wax and wane

frequently, accompanied by debilitating fatigue and malaise.

In a few cases, CFS seems to follow from a bout of classic

acute infectious mononucleosis rather than from a

nonspecific flu-like illness.  In these cases, EBV - the

cause of most cases of acute mononucleosis - may play a role

in the pathogenesis of CFS.

Clearly some CFS symptoms - headache, myalgia, sleep

disorder, difficulty concentrating - could be secondary

symptoms of a primary affective disorder.  However, other

symptoms such as pharyngitis, fever,

Page 5

adenopathy, and arthralgias suggest a different underlying

process.

Many patients have a history of allergies years before the

onset of CFS, and occasionally allergic symptoms worsen

after these patients become ill.  Allergies are so prevalent

in CFS patients that it is important to differentiate those

symptoms that are allergy-related and thus amenable to

treatment.

The course of CFS varies greatly, with symptoms lasting

anywhere from many months to many years.  Symptoms typical

of CFS are often seen for short periods of time; but these

symptoms must persist for at least 6 months, according to

the current CDC definition, to entertain a diagnosis of CFS.

Fortunately, CFS is not a progressive disease: usually the

symptoms are most severe in the first year of illness.

Systematic studies are under way to better define the

prognosis.

                   Evaluation of Patients

The patient with the complaint of chronic fatigue that is

interfering with his or her life must be taken seriously.

CFS symptoms overlap with those of many well-recognized

illnesses.  For example, Lyme borreliosis, mild systemic

lupus erythmatosus (SLE), and early or mild multiple

sclerosis (MS) are among the numerous disorders that

resemble CFS.  A history of potential tick exposure, the

typical Lyme rash (erythema chronicum migrans), and

antibodies to the Lyme spirochete suggest the diagnosis of

Lyme borreliosis. In both SLE and MS, debilitating chronic

fatigue can be more prominent than rheumatologic or

neurologic symptoms.  Psychiatric illnesses that most

resemble CFS include major depressive episode, panic

disorder, generalized anxiety disorder, and somatization

disorder.  It remains unresolved whether

Page 6

prior or current depressive episodes should exclude a

diagnosis of CFS.

Although infectious agents can trigger the syndrome, the

diagnosis of CFS currently is one of exclusion.  The

Appendix lists several illnesses that must be considered and

"ruled out" when first evaluating a patient with chronic

fatigue.  This list is a useful guide but should not be

thought of as exhaustive.

The patient's medical history -- particularly his or her

potential epidemiologic exposures -- and physical

examination will help determine the need for various

laboratory tests.  A reasonable initial laboratory workup

would include a urinalysis, complete blood count and

differential count, chemistry panel, thyroid function test

(a TSH test may be sufficient), erythrocyte sedimentation

rate, anti-nuclear antibodies, and rheumatoid factor.

Significantly abnormal results on any of these tests should

prompt consideration of alternative diagnoses.  It is

prudent for physicians today to also consider the

possibility of infection with the human immunodeficiency

virus.  Subsequent workup should be guided by the clinical

picture and may necessitate a chest X-ray, an

electrocardiogram, an Ig level, a tuberculin skin test, and

serum cortisol determinations, among other tests.

                    Immunologic Features

Many different immunologic findings have been described in

patients with CFS, but no single immunologic disturbance has

yet been identified as typical of the syndrome.  Those

disturbances observed include depressed natural killer (NK)

cell activity, elevated viral antibody titers, and

circulating immune complexes.  These findings indicate

general differences between patient populations

Page 7

and control groups, but none is specific for CFS or abnormal

in all CFS patients.  Immunologic changes like these are

often associated with infections and other stressful

processes.

                 Neuropsychologic Features

As mentioned earlier, many patients with CFS also meet

diagnostic criteria for depression or anxiety disorders at

presentation.  It remains unclear whether a higher than

normal frequency of psychiatric disorders in this patient

group also exists in the years prior to the onset of CFS.

On the other hand, psychiatric evaluations fail to identify

any psychiatric disorders in some patients.  Because subtle

psychiatric problems can be difficult to recognize, a

consult with a psychiatrist or psychologist may benefit the

evaluation of some patients.

Many people with CFS have neurologic symptoms, including

paresthesias, disequilibrium, and visual blurring.  A few

patients who are otherwise identical to the larger group

have had more dramatic acute and transient neurologic

events, such as primary seizures, periods of severe visual

impairment, and periods of paresis.  These few patients show

no evidence of any well-recognized neurologic disorder such

as MS.  Patients with these more dramatic symptoms warrant a

more intensive neurologic workup.

One study found that people with CFS have a subtle

deficiency of the steroid hormone cortisol.  Because

cortisol is a potent suppressor of immune responses, this

finding provides an alternative explanation for some of the

immune findings in the syndrome.

Preliminary research indicates that some patients with CFS

demonstrate punctate areas of high signal in the

sub-cortical white matter on magnetic resonance imaging

scans of the brain.  Studies are under way to

Page 8

determine if these abnormalities are found more frequently

in people with CFS than in healthy individuals.  For many

patients, the cognitive impairment they experience is one of

the most disconcerting symptoms.  It is usually

characterized as an inability to concentrate, unusual

absent-mindedness, and difficulty with word finding.  CFS

patients do not exhibit gross dementia.  Neuropsychological

testing is being conducted to better define the presence,

nature, and severity of cognitive impairment in patients

with CFS.

                     Etiologic Theories

Several theories have been postulated as to the etiology of

CFS.  Most investigators currently believe that no single

etiologic agent will prove to be the cause of all cases.

Many investigators believe that the illness involves a

constant antigenic challenge to the immune system and, as a

consequence, a constant immunologic response to that

challenge.  One popular theory, which has experimental

support, suggests that elevated levels of cytokines (e.g.,

interleukin-1, interleukin-2, various interferons) are

generated by an immune system that is doing battle against

antigens that it perceives to be foreign.  The flu-like

symptoms associated with many common infections are known to

be caused by cytokines.  Moreover, when these cytokines are

administered for therapeutic purposes, such as the use of

interleukin-2 or interferon in cancer therapy, many flu-like

symptoms occur.

Preliminary evidence suggests that several latent viruses

may be actively replicating more often in CFS patients than

in healthy control subjects.  Antibody levels are higher in

patients (indirect evidence of active infection); viral

antigen is found more commonly; or there is direct evidence

that the

Page 9

virus is replicating in cells that it commonly infects, such

as lymphocytes.  Thus far, those viruses that show some

evidence of more frequent active infection are several

members of the herpesvirus family -- EBV, cytomegalovirus,

herpes simplex viruses 1 and 2, and human herpesvirus 6 --

and of the enterovirus family -- coxsackievirus and

echovirus.

If subsequent studies confirm that several viruses are

active more often in people with CFS than in healthy

individuals, it will then need to be determined if this

activity is a primary or secondary event.  Because the viral

agents thus far identified typically infect people in

childhood, and since most patients with CFS are young

adults, most investigators believe reactivation of these

viruses is probably secondary to some immunologic

disturbance.  If viral activation is indeed a secondary

event, it will need to be determined if it is merely an

epiphenomenon, having nothing to do with the reason the

patient feels sick, or whether the viral activation - even

if secondary -- contributes to the symptoms.

                     Patient Management

CFS is debilitating in all patients, disabling in some, but

apparently not progressive or fatal.  The debility and

disability stem from a combination of symptoms such as

fatigue, arthralgias, or cognitive impairment, and in some

patients from associated depression.  The patients need both

symptomatic treatment and emotional support.  It should be

noted, however, that some patients get better all by

themselves.

It is vitally important for the physician to be the

patient's advocate.  In the absence of any proven

treatments, empiric therapies should be tried.  At the same

time, patients need to be kept from using exotic, untested

remedies that may hurt them.  Physicians also need to be on

the lookout for other medical

Page 10

problems, and to avoid the danger of interpreting every new

sign or symptom as a manifestation of CFS.

For many patients, it is important to slow the pace of their

lives and to avoid situations that are physically or

psychologically stressful.  Counseling for both the patient

and his or her family benefits their adjustment to this

chronic illness.  It is important for them to realize that

no definitive diagnostic or therapeutic approaches exist.

Neither has a specific nutritional program proved

beneficial, though a balanced diet and rest enhance

well-being.  Some patients benefit from a graduated program

of exercise.  At a minimum, patients should be encouraged to

maintain physical conditioning -- in some cases through a

sustained program of physical therapy -- at whatever level

of activity they can manage.  Abrupt resumption of vigorous

exercise should be avoided, however, because this can

exacerbate symptoms.

Symptomatic treatment can be quite helpful.  Non-steroidal

anti-inflammatory drugs may benefit the myalgias,

arthralgias, headaches, or fever associated with the

illness.  Nonsedating antihistamines may help relieve any

prominent allergic symptoms.

Very few randomized, controlled clinical drug trials for CFS

have been conducted.  One such trial found the antiviral

drug acyclovir to be no better than a placebo treatment.  In

fact, more than 40 percent of patients on placebo reported

improvement.

Several empiric therapies have been tried for CFS.  Some

investigators have administered intramuscular or intravenous

gammaglobulin, particularly to those patients who, unlike

most patients with CFS, have low levels of immunoglobulins.

There are conflicting claims regarding the efficacy of this

form of therapy -- one trial found some benefit, the other

none.

Page 11

Several empiric therapies have been tried for CFS.  Because

well-designed clinical trials have demonstrated the benefit

of low doses of tricyclic antidepressant drugs in

fibromyalgia (an illness similar to CFS), tricyclics are

widely prescribed for CFS patients.  Anecdotal experience

with tricyclics has generally been positive.  Some

investigators believe that the tricyclics act by improving

the quality of sleep.  Other types of antidepressants have

also been tried with some success.  CFS patients often

report that antidepressants exacerbate their fatigue,

however, especially when given in therapeutic doses.  It may

be necessary to escalate doses very slowly and urge patience

in detecting benefit, or to try the more activating

antidepressants such as desipramine, fluoxetine, and MAO

inhibitors.

In brief, no strict recipe for treating CFS exists, and

sometimes several different treatment approaches may have to

be tried before the patient reports benefit.  Both the

physician and the patient need to be open to reasonable

treatment alternatives and appreciate the difficulty in

assessing their benefit in CFS.

                         Conclusion

A great deal of controversy and speculation surrounds CFS:

Is it a single disorder or a heterogeneous mix of problems?

What is its relationship to infections, the immune system,

and mood disturbances?  How can it best be treated?  These

and many more issues fuel the continuing broad debate, often

leaving patients and their physicians frustrated.  For now,

physicians don't have all the answers.  But in treating

people with CFS, they can draw on practices that have always

made medicine a valued art: exclude alternative problems,

ameliorate symptoms, and offer guidance with compassion.

Page 12

                          Appendix

               Research Case Criteria for the

                 Chronic Fatigue Syndrome*

A case of chronic fatigue syndrome must fulfill major

criteria 1 and 2 and the following minor criteria: 6 or more

of the 11 symptom criteria and 2 or more of the 3 physical

criteria; or 8 or more of the 11 symptom criteria.

Major Criteria

1.     New onset of persistent or relapsing, debilitating

fatigue or easy fatigability in a person who has no previous

history of similar symptoms, that does not resolve with

bedrest, and that is severe enough to reduce or impair

average daily activity below 50% of the patient's premorbid

activity level for a period of at least 6 months.

2.     Other clinical conditions that may produce similar

symptoms must be excluded by thorough evaluation, based on

history, physical examination, and appropriate laboratory

findings.  These conditions include malignancy; autoimmune

disease; localized infection (such as occult abscess);

chronic or subacute bacterial disease (such as endocarditis,

Lyme disease, or tuberculosis), fungal disease (such as

histoplasmosis, blastomycosis, or coccidioidomycosis), and

parasitic disease (such as toxoplasmosis, amebiasis,

giardiasis, or helminthic infestation); disease related to

human immunodeficiency virus (HIV) infection; chronic

psychiatric disease, either newly diagnosed by history (such

as endogenous depression; hysterical personality disorder;

anxiety neurosis; schizophrenia; or chronic use of major

tranquilizers, lithium, or antidepressive medications);

chronic inflammatory disease (such

*From Holmes GP, et al.  Chronic fatigue syndrome: a working

case definition.  Ann. Intern. Med. 1988;108:387-9.

Page 13

as sarcoidosis, Wegener's granulomatosis, or chronic

hepatitis); neuromuscular disease (such as multiple

sclerosis or myasthenia gravis); endocrine disease (such as

hypothyroidism, Addison disease, Cushing syndrome, or

diabetes mellitus); drug dependency or abuse (such as

alcohol, controlled prescription drugs, or illicit drugs);

side effects of chronic medication or other toxic agent

(such as chemical solvent, pesticide, or heavy metal); or

other known or defined chronic pulmonary, cardiac,

gastrointestinal, hepatic, renal, or hematologic disease.

Specific laboratory tests or clinical measurements are not

required to satisfy the definition of the chronic fatigue

syndrome, but the recommended evaluation includes serial

weight measurements (weight change of more than 10% in the

absence of dieting suggests other diagnoses); serial morning

and afternoon temperature measurements; complete blood count

and differential; serum electrolytes; glucose; creatinine,

blood urea nitrogen; calcium, phosphorous; total bilirubin,

alkaline phosphatase, serum aspartate aminotransferase;

creatine phosphokinase or aldolase; urinalysis;

posteroanterior and lateral chest roentgenograms; detailed

personal and family psychiatric history; erythrocyte

sedimentation rate; antinuclear antibody;

thyroid-stimulating hormone level; HIV antibody measurement;

and intermediate-strength purified protein derivative (PPD)

skin test with controls.

If any of the results from these tests are abnormal, the

physician should search for other conditions that may cause

such a result.  If no such conditions are detected by a

reasonable evaluation, this criterion is satisfied.

Page 14

Minor criteria

Symptom criteria

To fulfill a symptom criterion, a symptom must have begun at

or after the time of onset of increased fatigability, and

must have persisted or recurred over a period of at least 6

months (individual symptoms may or may not have occurred

simultaneously).  Symptoms include:

1.  Mild fever -- oral temperature between 37.6 degrees C

and 38.6 degrees C, if measured by the patient -- or chills.

(Note: oral temperatures of greater than 38.6 degrees C are

less compatible with chronic fatigue syndrome and should

prompt studies for other causes of illness.)

2.  Sore throat.

3.  Painful lymph nodes in the anterior or posterior

cervical and axillary distribution.

4.  Unexplained generalized muscle weakness.

5.  Muscle discomfort or myalgia.

6.  Prolonged (24 hours or greater) generalized fatigue

after levels of exercise that would have been easily

tolerated in the patient's premorbid state.

7.  Generalized headaches (of a type, severity, or pattern

that is different from headaches the patient may have had in

the premorbid state).

8.  Migratory arthralgia without joint swelling or redness.

9.  Neuropsychologic complaints (one or more of the

following: photophobia, transient visual scotomata,

forgetfulness, excessive irritability, confusion, difficulty

thinking, inability to concentrate, depression).

10. Sleep disturbance (hypersomnia or insomnia).

11. Description of the main symptom complex as initially

developing over a few hours to a few days (this is not a

true symptom, but may be considered as equivalent to the

above symptoms in meeting the requirements of the case

definition).

Page 15

Physical Criteria

Physical criteria must be documented by a physician on at

least two occasions, at least 1 month apart.

1.  Low-grade fever - oral temperature between 37.6 degrees

C and 38.6 degrees C, or rectal temperature between 37.8

degrees C and 38.8 degrees C.  (See note under Symptom

Criterion 1.)

2.  Nonexudative pharyngitis.

3.  Palpable or tender anterior or posterior cervical

axillary lymph nodes.  (Note: lymph nodes greater than 2 cm

in diameter suggest other causes. Further evaluation is

warranted.)

To receive a CFS information packet, contact:

Office of Communications

National Institute of Allergy and

  Infectious Diseases

Building 31, Room 7A32

9000 Rockville Pike

Bethesda, MD 20892

(301) 496-5717

National Institute of Allergy

and Infectious Diseases

NIH Publication No. 92-484

May 1992

Colofon:
Zie inleiding

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