CHRONIC FATIGUE SYNDROME

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CHRONIC FATIGUE SYNDROME

• By Sumeeta Kantak
• Dept of Medicine
• Dr. James Baraniuk
• Dept of Allergy, Immunology

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1994 CDC Definition

• Clinically evaluated, unexplained, persistent, or
  relapsing fatigue that is
• Of new or definite onset
• Not a result of ongoing exertion
• Not alleviated by rest
• Results in a substantial reduction in previous
  levels of occupational, social, or personal
  activity
• Four or more of the following symptoms that
  persist or recur during 6 or more consecutive
  months of illness and that do not predate the
  fatigue
• Self-reported impairment of short-term memory or
  concentration
• Sore throat
• Tender lymph nodes
• Muscle pain
• Multijoint pain without swelling or redness
• Headaches of a new type, pattern, or severity
• Unrefreshing and/or interrupted sleep
• Postexertion malaise (a feeling of general
  discomfort or uneasiness) lasting more than 24
  hours

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Exclusion Criteria

• Active, unresolved or suspected disease that is
  likely to cause fatigue (anemia, hypothyroidism,
  Lupus or other inflammatory conditions, cancer,
  seizures, cardiopulmonary disease, HIV or known
  chronic infectious process, etc.)
• Psychotic, melancholic, or bipolar depression
  (but not uncomplicated major depression)
• Psychotic disorders
• Dementia
• Anorexia or bulimia nervosa
• Alcohol or other substance misuse
• Severe obesity

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Oxford Canada

• Severe disabling fatigue of at least a 6-month
  duration that
• Affects both physical and mental functioning
• Is present for more than 50 of the time
• Other symptoms, particularly myalgia and sleep
  and mood disturbances, may be present.
• Same exclusion criteria

• 1. Fatigue gt 6 mo
• 2. Post exertional fatigue
• 3. Arthralgia/myalgia
• 4. sleep disturbance
• 5. neurologic/cognitive dysfunction
• 6. 2 of autonomic, neuroendocrine, or immune
  manifestations

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Clinical Presentation

• High functioning individual
• Stressor (viral illness?)
• Prolonged immobilization (virus, trauma)
• Feel like theyve been hit by a truck
• Normal physical exam

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Epidemiology

• Prevalence (0.23 to 2.6)
• Approx. 1 million Americans
• Only 20 diagnosed
• Onset median 36.5 yrs
• Peak prevalence ages 40-59 yrs
• Female to male 41
• Hispanics, AA, Native Americans
• 20,000 per year annual earnings
• 9.1 billion in lost productivity

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Laboratory Testing

• Routine tests
• CBC with differential
• Chem 20
• ESR
• TSH
• Optional tests include
• ANA, RF
• Urinalysis
• Adrenal tests (a.m. and p.m. cortisol levels)
• Lyme titers and HIV serology
• Specific tests that support but do not confirm
• CMV, EBV, human herpes virus 6, and
  coxsackievirus
• Immune system tests, including low natural killer
  (NK) cell counts, elevated interferon alpha,
  tumor necrosis-alpha, interleukins 1 and 2,
  T-cell activation, altered T4/T8 cell ratios, low
  T-cell suppressor cell (T8) count, fluctuating B-
  and T-cell counts, antinuclear antibodies,
  immunoglobin deficiency, antithyroid antibodies
• Tilt table testing
• Exercise testing may show decreased cortisol
  levels after exercise, decreased cerebral blood
  flow after exercise, inefficient glucose
  utilization, and erratic breathing patterns

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Treatment

• Cognitive Behavioral Therapy
• Graded exercise
• Supportive therapy
• Dietary agents
• Antidepressants?
• Immunotherapy?
• Steroids?

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Limitations

• What is fatigue?
• What causes CFS?
• Minor criteria
  studies?
• Basis for
  choosing treatment?

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Pilot Study CSF Proteonomics

• Pooled CFS and PGI samples had 20 CSF proteins
  undetectable in controls
• Pooled CFS, FM, and PGI had 10 CSF proteins
  undetectable in controls
• All 3 had similar responses on symptom inventory,
  quality of life, and nociceptive measurements
• CRH elevations in CSF of CFS patients compared to
  controls

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LONG TERM ASSAY OF MECHANISMS AND PREDICTORS FOR
CFS LAMP4CFS study

• Objectify fatigue
• Pain dysregulation
• Autonomic dysfunction
• Subjective/objective measures to identify CFS
  patients, psychometric and physiologic measures
  of pain, esp. CSF neuropeptides, autonomic indices

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FATIGUE

• Goal Determine objective criteria to correlate
  and predict subjective facets of fatigue
• Plan Use self-reported questionnaires (CFS score
  from subjective MFI, SF-36, STPI, CSQ, MHHQ,
  depression) and pedography/actigraphy for
  objective measurements

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PAIN DYSREGULATION

• Goal determine range of pain, identify
  psychometric/physiologic covariates
• Plan Assess subjective (Beck depression
  inventory, SF36, McGill Pain questionairre) and
  objective (random staircase testing, dolorimetry,
  tender points, CFS neuropeptides assoc with pain)

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AUTONOMIC DYSFUNCTION

• Goal determine which autonomic indices are
  covariates of CFS
• Plan assess heart rate variability and
  orthostatics during handgrip and daily activities

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Longitudinal Study

• Subjects 50 women/men gt 18 yrs meeting CFS
  criteria, 50 FM, 50 controls over 2 year period
• Exclusion criteria (physical impairment, other
  CFS exclusions, chronic infections, pregnancy)
• Screening blinded by P.I., GCRC RNP

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• Core Study Questionnaires (pain, sleep, fatigue,
  activity, psychometric status)
• Actigraphy, pedography
• Capsaicin skin testing
• Genetic Testing
• Orthostatics, Holter monitoring,heart rate
  variability
• Pain testing (tender points, dolorimetry)
• Lumbar puncture at 0, 6, and 24 months for CSF
  neuropeptide measurements
• Exercise capacity (6 minute walk test)

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Questions
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