Medically Unexplained Symptoms

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Medically Unexplained Symptoms

• Mark Feldman, MD
• July 5, 2006

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Case 1

• 36 year old woman presented with atypical facial
  pain admitted to Teaching Service. Physical
  examination was normal.
• Past history depression, anxiety and Mollarets
  meningitis.
• Meds Trazodone, venlafaxine, chlorazepate
  valacyclovir
• Started on gabapentin (Neurontin) with no pain
  relief.
• Switched to carbamazepine (Tegretol) with no pain
  relief.
• A few weeks later, she developed a severe
  generalized pruritic maculopapular rash,
  granulomatous hepatitis, and eosinophilia
  (35), treated with prednisone and hydroxyzine.
  She then developed CNS vasculitis with multiple
  strokes (carbamazepine hypersensitivity syndrome
  CHS with CNS vasculitis).

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Case 2

• 53 year old woman referred for chronic upper and
  lower abdominal pain and constipation.
• Past history of anxiety, depression, stress,
  perineal pain, fibro-myalgia, nonulcer dyspepsia,
  and hysterectomy/oophorectomy.
• Recent flare of pain led to laparoscopic
  appendectomy, with no pain relief (and no
  abnormality of the appendix on path exam).
• Common bile duct was slightly dilated (10 mm) on
  ultrasound history of cholecystectomy 20 years
  ago for upper abdominal pain. GI was consulted
  and an ERCP was attempted, complicated by acute
  pancreatitis requiring hospitalization.
• Physical exam and lab studies at this time were
  normal.
• Abdominal pain and constipation improved with the
  5-HT4 agonist tegaserod (Zelnorm). Her dyspepsia
  did not improve and was treated with a PPI with
  minimal relief. She is being seen by at least 3
  gastroenterologists currently.

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Case 3

• 22 year old woman (daughter of a physician)
  referred because of flushing, abdominal cramps,
  and loose stools after eating. She is unable to
  attend school or work due to her GI symptoms.
• Negative or normal colonoscopy X2 stool fat
  urine 5-HIAA, sprue panel, EGD, CT, octreoscan,
  EUS, etc.
• Past medical history of obesity, PCOS with
  normal ovarian sonogram, asthma, multiple food
  sensitivities/allergies, chronic headaches,
  myalgia and arthralgia compatible with FM,
  multiple knee surgeries, possible Sjögrens
  syndrome. Taking 23 medications from numerous
  specialists such as an allergist/pulmonologist
  and endocrinologist, including prednisone and
  octreotide.
• Exam (with parents present) morbidly obese and
  Cushingoid with buffalo hump and hundreds of red
  and purple striae, but otherwise well-appearing.
  Exam was otherwise normal and laboratory studies
  were all normal.

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Summary of Cases
Demographics Symptoms Complication
Case 1 36 year old woman Atypical facial pain CHS, strokes
Case 2 53 year old woman Upper/lower abdominal pain ERCP-induced pancreatitis
Case 3 23 year old woman Abdominal pain, flushing, loose stools Cushings syndrome
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Working definitions

• Symptom a patients subjective experience of a
  change in his/her body
• Disease an objective, observable abnormality in
  the body
• When we can find no objective change to explain
  the patients subjective experience, we term the
  symptoms medically unexplained or functional.

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Synonyms for todays topic

• Medically unexplained symptoms
• Somatization
• Somatoform disorder
• Functional Somatic Syndromes

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Functional somatic syndromes, classified by
subspecialty

• Gastroenterology
• Gynecology
• Rheumatology
• Cardiology
• Infectious Disease
• Neurology
• Dentistry
• ENT
• Allergy

• IBS, nonulcer dyspepsia
• PMS, chronic pelvic pain
• Fibromyalgia
• Atypical or non-cardiac CP
• Chronic fatigue syndrome (CFS)
• Tension headache
• TMJ syndrome / atypical facial pain
• Globus syndrome
• Multiple chemical sensitivity

Adapted from Wessely S, Nimnuan C, Sharpe M.
Lancet 354 936-9, 1999
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Characteristics of the various Functional Somatic
Syndromes

• They are extremely common.
• They are frequently persistent (i.e., chronic).
• Conventional medical therapy is fairly
  ineffective.
• They are associated with
• Considerable distress (IBS gt IBD in inpatients)
• Considerable disability (CFS gt CHF in
  outpatients)
• Unnecessary expenditures of medical revenues
• Unnecessary exposure to medical risks
• Case 1. Anticonvulsant drugs
• Case 2. ERCP
• Case 3. Glucocorticoids

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Frequency of Functional Somatic Syndromes

• Primary care consultations (UK)
  20
• New referral as medical outpatients (UK) 35
• Medical outpatient visits (Denmark)
  25

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Functional Somatic Syndromes One or Many ?

• Potential Splitters
• Specialists
• Specialty Societies
• Support/Help Groups
• local chapters
• Internet sites
• Researchers

• Potential Lumpers
• Primary care providers
• Epidemiologists
• Researchers
• Mental health professionals
• Enlightened specialists

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A case for Lumping

• Argument 1
• There is a great deal of overlap in case
  definitions of specific syndromes.
• Of 12 specific syndromes analyzed by Wessely et
  al, the definition of the syndrome included
• Bloating/feeling of abdominal distention in 8
• Headache in 8
• Fatigue in 6
• Abdominal pain features in 6

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Fibromylagia (Arthritis Foundation)

• Pain (tender points)
• Fatigue
• Sleep disturbances
• Depression
• Anxiety
• Brain fog (fibro fog)
• Migraine headaches

• Abdominal pain, bloating, alternating diarrhea
  and constipation (IBS)
• TMJ disorder
• Skin color changes
• Tingling limbs
• Restless legs syndrome

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Chronic fatigue syndrome (CDC)

• Primary Symptoms (n8)
• Cognitive dysfunction
• Post-exertion malaise
• after physical or mental exertion
• Unrefreshing sleep
• Joint pain
• Persistent muscle pain
• New headaches
• Tender cervical/axillary lymph nodes
• Sore throat

• Other common symptoms
• Irritable bowel syndrome
• Abdominal pain, diarrhea
• Nausea, bloating
• Chills and night sweats
• Brain fog
• Chest pain
• Shortness of breath/chronic cough
• Multiple food/chemical allergies/sensitivities
• Psychological problems
• Depression, anxiety, mood swings, irritability
• Jaw (facial) pain
• Weight loss or gain

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Multiple Chemical Sensitivity Syndrome. Common
Symptoms

• Fatigue
• Difficulty concentrating
• Depressed mood
• Memory loss
• Weakness

• Headaches
• Heat intolerance
• Arthralgia
• Numerous GI symptoms
• Respiratory/mucosal irritation

Magill and Suruda. American Family Physician,
Sept. 1, 1996.
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A case for Lumping

• Argument 2
• Patients with one functional syndrome frequently
  meet diagnostic criteria for other syndromes (if
  queried!). Wessely et al
• CFS linked to/overlaps with FM, tension
  headache, multiple chemical sensitivity, food
  allergy, PMS, and IBS.
• IBS linked to NUD, CFS, hyperventilation, FM,
  tension headache, atypical facial pain,
  non-cardiac CP, chronic pelvic pain. and PMS.

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A case for Lumping

• Argument 3
• Patients with different symptoms (functional
  syndromes) share non-symptom features
• Gender female predominance of non-gynecologic
  FSSs, such as IBS, CFS, TMJ dysfunction, atypical
  facial pain, globus syndrome, tension headaches.
• Association of FFSs with emotional disorders
  correlated with current and past anxiety and
  depression. Examples IBS, multiple chemical
  sensitivity, CFS
• Pathophysiology Little known, but FSSs may
  share a common pathophysiology (altered
  functioning of the CNS) rather than be caused by
  disorders in specific organ systems
• IBS Colon ? CNS
• NUD/Bloating Stomach ? CNS
• FM and CFS Muscle ? CNS
• Facial pain TMJ, etc. ? CNS

? Role of 5-HT neurons
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A case for Lumping

• Argument 3, contd
• History of childhood mistreatment and/or abuse,
  especially sexual abuse pelvic pain, PMS, IBS,
  tension headache, FM, CFS
• Difficulties in the doctor-patient relationship
• Unsatisfactory for the doctor
• Unsatisfactory for the patient
• headache, non-cardiac chest pain, FM, CFS

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A case for Lumping

• Argument 4
• All functional syndromes respond to
  similar therapies.
• General approaches
• Take patients complaints seriously.
• Explain the physiology of the symptoms.
• Limit investigations.
• Emphasize rehabilitation at the expense of cure.
• Antidepressant drugs (tricyclic, SSRI off
  label)
• Accepted for PMS, atypical facial pain,
  non-cardiac chest pain
• Role in FM, CFS, and IBS less clear, but evolving
• Psychological therapies (e.g., cognitive
  behavioral therapy)
• Effective in CFS, PMS, IBS, and in nearly all
  pain syndromes

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Rome III. Psychosocial aspects of the functional
GI disorders. Levy et al. Gastroenterology 130
1447-58, 2006.

• The committee reached consensus in finding
  considerable evidence supporting the association
  between psychological distress, childhood trauma
  and recent environmental stress, and several of
  the FGIDs but noted that this association is not
  specific to FGIDs.
• there is now increasing evidence that a number
  of psychological treatments and antidepressants
  are helpful in reducing symptoms and other
  consequences of the FGIDs in children and adults.

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Multiple Chemical Sensitivity (MCS) Syndrome

• Several theories have been advanced to explain
  the cause of MCS, including allergy, toxic
  effects and neurobiologic sensitization. There is
  insufficient scientific evidence to confirm a
  relationship between any of these possible causes
  and symptoms.
• Patients with MCS have high rates of depression,
  anxiety and somatoform disorders, but it is
  unclear if a causal relationship or merely an
  association exists between MCS and psychiatric
  problems. Physicians should compassionately
  evaluate and care for patients who have this
  distressing condition, while avoiding the use of
  unproven, expensive or potentially harmful tests
  and treatments. The first goal of management is
  to establish an effective physician-patient
  relationship. The patient's efforts to return to
  work and to a normal social life should be
  encouraged and supported.

Magill and Suruda. Amer Fam Physician, September,
1998
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Functional Somatic Syndromes New or Old Concept ?

• Psychosomatic Syndromes
• Psychosomatic Affections
• Multiple Visceral Neuroses
• Syndrome Shift

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Implications

• For sub-specialists
• Elicit symptoms outside of your area of specialty
  (look at the big picture)
• Ask about childhood/sexual abuse
• Minimize excessive testing if symptoms fit a
  functional disorder
• Consider more general and safer therapies
• For primary care physicians
• Look at the company your patients symptoms keep
• Minimize referrals to sub-specialists if patient
  has evidence of multiple functional somatic
  syndromes
• Seek co-existing anxiety and/or depression and
  treat accordingly
• Ask about childhood/sexual abuse
• Be willing to consider off-label antidepressants
  for symptoms
• Be prepared to refer difficult/refractory cases
  to a mental health professional