II. Epidemiology

  1. Rare Condition associated with an unknown contaminant L-Tryptophan supplements from a single Tokyo manufacturer
    1. However case reports continue with L-Tryptophan and 5-Hydroxytryptophan (5-HTP) supplement use
  2. Ultimately >1500 confirmed cases (actual numbers estimated at 5,000-10,000) and resulted in 37 deaths
  3. Gender: Women were most often affected
  4. U.S. had most reported cases, but

III. History

  1. First described in 1989 in New Mexico and Minnesota
  2. Associated with L-Tryptophan and 5-Hydroxytryptophan (5-HTP) supplement use
  3. Resulted in a U.S. recall of L-Tryptophan supplements in 1989

IV. Associated Conditions

V. Pathophysiology

  1. Linked to L-Tryptophan and 5-Hydroxytryptophan (5-HTP) usage
  2. Suspected cause is an unknown contaminant in the supplements

VI. Symptoms

  1. Myalgias (Uniformly present)
    1. Rapid onset with persistent pain
    2. Severe and incapacitating pain (limits Activities of Daily Living)
    3. Associated with Muscle spasms (esp. calves, Abdomen)
    4. Associated with perceived weakness
    5. Exacerbated by movement
  2. Arthralgias (73%)
  3. Pruritus
  4. Non-productive cough with Dyspnea (59%)
  5. Neuropathy (27%)
    1. Paresthesia or Hypesthesia (e.g. Burning Sensation)

VII. Signs

  1. Rash (60%)
  2. Peripheral Edema (59%)
    1. Cutaneous Non-Pitting Edema
  3. Periorbital edema (28%)
  4. Fever (36%)
  5. Alopecia (28%)
  6. Hepatomegaly (5%)
  7. Thickened skin (32%)

VIII. Labs

  1. Complete Blood Count (CBC)
    1. Elevated Peripheral Eosinophil Count
    2. Leukocytosis (85%)
  2. Aldolase increase (46%)
  3. Creatine Kinase increase (10%)
  4. Erythrocyte Sedimentation Rate (ESR) increased (33%)
  5. Liver Function Test (LFT) abnormality (43%)
  6. Antinuclear Antibody (ANA) frequently positive
    1. Speckled pattern most common

IX. Radiology: Chest XRay findings

  1. Infiltrates (17%)
  2. Pleural Effusions (12%)

XI. Diagnosis: Criteria from CDC Cases

  1. Peripheral Eosinophil Count >1000 cells/mm
  2. Severe myalgias that interfere with daily activity
  3. Exclude other diagnoses
    1. Infection
    2. Neoplastic Disease
    3. Other diagnosis responsible

XII. Management

  1. General Therapies
    1. Systemic Corticosteroids
      1. Not uniformly effective
      2. Unlikely effective if no response by 4-6 weeks
      3. Predictors of response
        1. Edema
        2. Eosinophilia
      4. High doses are required initially
    2. Other experimental therapies
      1. Methotrexate
      2. Vitamin B6
      3. Cyclosporine
      4. Cyclophosphamide
      5. Plasmapheresis
  2. Myalgias and Muscle spasms (very difficult to treat)
    1. Quinine sulfate
    2. Tricyclic Antidepressants
    3. Methocarbamol
    4. Cyclobenzaprine
    5. Dantrolene
    6. Baclofen
    7. Benzodiazepines
    8. Narcotics Analgesics may be needed
    9. Chronic Pain Management

XIII. Resources

XIV. Reference

  1. Freundlich in Kelley (1993), Textbook Rheumatology, Saunders, Philadelphia, p. 1150-7
  2. Hertzman (1995) J Rheumatol 22(1):161-3 [PubMed]
  3. Swygart (1990) JAMA 264:1698-1703 [PubMed]

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