Chronic Fatigue Syndrome

A Blessing or a Curse for the Primary Care Physician?

Stephen J. Gluckman, M.D.

Chronic Fatigue Syndrome

• Why have a lecture on it in a conference on infectious diseases?– Often misdiagnosed and mistreated as an

infection

• Incorrect management can be costly and occasionally dangerous

• Fatigue if a very common patient complaint in most of our offices

Case

• A 28 year old housewife who has a previously unremarkable medical history had the acute onset of fever to 103, headaches, myalgias, and a non-productive cough 18 months ago. All of the symptoms resolved over the subsequent 10 days with the exception of profound fatigue which has persisted since that time.

Case (cont.)

• The fatigue waxes and wanes in intensity but is always there. It is worse after physical activity; she had to stop her part time job as a bookkeeper. She states that prior to the onset of her illness she used to go the gym 3 times a week but has had to give that up.

Case (cont.)

• Additional symptoms have included– Intermittent sore throat

– Generalized body aches

– Mental “cloudiness”

– Intermittent “swollen glands”

– Difficultly sleeping

– Blurry vision

– Tingling in her hands and feet

Case (cont.)

• Over this time– Her weight has increased 10 pounds

– Her menses have been normal

– Her hemoglobin has been no lower than 11.8 gm/dl

– Her serum albumin has been normal

Case (cont.)

• She has been evaluated by– Her primary care physician

– A Neurologist

– Two rheumatologists

– An otorhinolaryngologist

– A nutritionist

– A psychotherapist

Case (cont.)

• She has been treated with– Erythromycin twice– Cephalexin twice– Augmentin three times– Ciprofloxacin– Intravenous ceftriaxone– Oral nystatin– Loperamide– High doses of vitamins and a restriction diet

Case (cont.)

• She generally has had transient responses to each of these medications, but her symptoms return within 1-3 days of stopping them

• At times she has been told that she has– Chronic EBV

– Lupus

– Lyme disease

– Yeast

– A nutritional imbalance

– Allergies

CFS

• Is EXHAUSTING for patients and can be for their physicians

• Can be managed successfully by patient and skillful clinicians

• SUCCESSFUL MANAGEMENT IS ACTUALLY VERY REWARDING

Fatigue

• Chronic fatigue syndrome is not the same as chronic fatigue– Chronic fatigue

• 25-30% of patients seeing a primary care provider report fatigue

• Point prevalence about 5%

– CFS

• Incidence is unclear but point prevalence is probably in the range of about 0.1-0.2%

CFS: Revised CDC case definition

1. Clinically evaluated, unexplained persisting or relapsing fatigue that is of new or definite onset; is not the result of ongoing exertion; is not relieved by rest; and results in substantial reduction in previous levels of occupational, education, social, or personal activities.

• PLUS

CFS: Revised CDC case definition

• Four or more of the following symptoms that persist or recur during six or more consecutive months and do not predate the fatigue– Self reported impairment in memory or

concentration– Sore throat– Tender cervical or axillary lymph nodes– Muscle pain– Multiple joint pain without redness or swelling– Headache of a new pattern or severity– Unrefreshing sleep– Post-exertional malaise lasting > 24 hours

CFS: Revised CDC case definition

• Modifications– Excluded

• Patients with psychoses

• Patients with substance abuse

– Included

• Fibromyalgia

• Somatoform disorders

• Generalized anxiety/panic disorder

CFS: Case DefinitionBUT

• It is important to not get overly “hung up” on the CDC case definition when managing a patient– This is an epidemiology/research tool, not a

clinical tool.

CFS

• Complicated and controversial BUT– It is not a new phenomenon

– It is a “real” illness

– We know a great deal about it

• A health care provider can not effectively manage patients with CFS if he or she has doubt about the validity of the patient’s symptoms!

CFS: Epidemiology

• Young to middle age adults• More common in women than men• Fewer cases in minorities • Fewer cases in lower socioeconomic

groups• Usually sporadic and “non-contagious”,

but has occurred in outbreaks• BUT it occurs in all ages, races,

socioeconomic groups

What do we know about prognosis?

• Disability variable

• Often cyclical course

• Most improve

• Few completely recover

• Recovery takes years

• Earlier treatment (symptom management) associated with better prognosis

Chronic Fatigue SyndromeHistorical Perspective

• It is not a new disease

• It is a newly (relatively) named disease

CFS: Historical Perspective

• 1770Febricula

• 1871DaCosta’s (effort) syndrome

• 1880’s Neurasthenia

– Sir William Osler writing in 1895 “in all forms there is a striking lack of accordance between the symptoms of which the patients complain and the objective changes discoverable by the physician”

Principles and Practice of Medicine

CFS: Historical Perspective

• 1934 Myalgic encephalitis• 1930-50’s Chronic brucellosis• 1985 Chronic EBV• 1980-90’s

– CMV– HSV– HHV6– Yeast– Total allergy syndrome– Chemical sensitivity syndrome– Chronic Lyme disease

• 2000’s– XMRV

CFS: EtiologyConsiderations

• Viral– Many viruses have been proposed, but none

have been scientifically linked to CFS

– XMRV

• Endocrine-Metabolic– Variable, mild hormonal abnormalities have

been reported

CFS: Etiology

• Immune Dysfunction (CFIDS)– There is evidence of some immune

differences in patients with CFS, but the significance is unclear

• Diverse

• Modest

• Inconsistently present

• Conflicting

CFS: Etiology

• Autonomic nervous system dysfunction?– Neurally mediated hypotension (Positive tilt

table testing)

• Suggestive studies, but none placebo controlled, blinded, randomized

• No consistent response to treatments for this disorder

CFS: Etiology

• Psychological?– Increased psychopathology in patients with

CFS

– Lack of objective abnormalities despite severe symptoms

– Restricted patient profile

– Responds to placebo

CFS: Organic or Psychological?

• Does it matter if the origin is physical or psychological? Not much– If it is organic we do not have a diagnostic test

or specific treatment

– If it is psychological it does not make it less real or less valid.

CFS PathophysiologyWhat’s Hot?

• XMRV – Not found in subsequent studies

– Do not treat with medications for HIV

• Genetic– CFS has been linked to genes involved in the immune

and stress responses

– These findings suggest that patients with CFS have a biologically determined difficulty managing stressors

CFS

• How can we diagnose something without a diagnostic test?– There is a characteristic history

– There is a characteristic physical examination

– There are characteristic test results

CFS: Characteristic History

• Sudden onset of fatigue often associated with a typical infection such as a URI or mononucleosis

• After resolution of the initial disease the patient is left with chronic fatigue and several additional symptoms

• Physical activity exacerbates the symptoms

CFS: Characteristic History

• Pre-CFS history of the patient is NOT one

of multiple somatic complaints.

– They are not hypochondriacs. They have

been highly functioning individuals who are

“struck down” with the disease

CFS: Characteristic Examination

• Normal examination

– Including Mini Mental Status Exam (MMSE)

CFS: Characteristic Clinical Features

• Specific points to emphasize– Though patients often complain of fever, very

few have significantly elevated temperatures

• “I run low temperatures normally”

– Joints may ache, but there is no objective evidence of joint disease

– Though muscles fatigue easily, strength is normal as is EMG and muscle biopsy

– Lymphadynia is common, lymphadenopathy is rare

CFS: Characteristic Laboratory Results

• Normal– CBC

– Chemistry screen

– TSH

– Sedimentation rate

– Other tests?: ONLY WITH CLINICAL INDICATION

CFS: Diagnosis

• DO NOT ROUTINELY DO:– Serology for

• CMV

• EBV

• Toxoplasmosis

• Lyme disease

• ANA

– Expensive neuroimaging

– Tilt table testing

CFS: Diagnosis

• If the patient has a typical story, negative physical examination, and negative screening tests we can make the diagnosis.

CFSConcepts To Remember For Successful

Management• Patients with CFS are partially or completely

disabled.

• Their outward healthy appearance belies an internal sense of ill health.

• It is common for friends, relatives, employers, and physicians to believe they are malingering or their symptoms are not “real”.

• This results in anger, frustration, and a need to justify their illness

CFS: Specific steps in Management

1. Give the patient enough time and do a thorough evaluation

2. Reassure the patient that the symptoms are real3. Discuss problem of patient having to deal with the

validity of his/her disease4. Do not underestimate the benefits of trust, support,

and reassurance that you can provide

CFS: Specific steps in Management

5. Explain to the patient that this is not a new disease – we know a lot about it

– Review the history of CFS in detail6. Avoid the debate over psychogenic v organic

origin7. Review treatment options

CFSSo what are the treatment options?

1. Tell the patient that there is no cure for CFS, but there are treatments that help

2. “Re-frame” expectations – the patient has a disability and should have appropriate expectations

3. Encourage graded exercise– Inactivity contributes to deconditioning and

depression

4. Suggest Cognitive Behavioral Therapy5. Treat depression aggressively

CFS: Treatment Options (cont.)6. Treat insomnia aggressively7. Treat other “treatable” conditions

– Do not assume that every symptom is CFS related– Caution patients about this

8. Options for fibromyalgia- Physical therapy- Duloxetine (Cymbalta®)

- 30-60 mg per day- Amitriptyline (Elavil®)

- 12.5-50 mg per day- Pregabalin (Lyrica®)

- 150-450 mg per day- Topiramate (Topamax®)

- 25-200 mg per day

CFS: Treatment Options (cont.)

9. Orthostatic intolerance- clonidine 0.1 mg nightly

- midodrine

10. Fatigue- methylphenidate (Ritalin LA®)

- modafinil (Provigil®)

11. Reassure about prognosis

CFS: Treatment Options (cont.)

12. See at regular intervals

13. Caution about unproven, dangerous or expensive treatments

14. Offer CDC pamphlet, website and hotline– 404-639-1338

CFS: ManagementUnproven and Disproved Therapies

• Ampligen

• Essential fatty acids

• Magnesium

• Bovine liver extract

• Acyclovir

• Folic acid

• B12

• Interferon

• Exclusion diets

• IVIG

• Removal of dental fillings

• IL 2

• Cimetidine

• Ranitidine

• Evening primrose

• Many antibiotics

• Corticosteroids

CFS: Management

• Accept the fact that you will not be able to

successfully manage all patients with CFS

but avoid the temptation to give

unnecessary treatments.

Questions?