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A 23y/o girl with facial tightness and generalized weakness

A 23y/o girl with facial tightness and generalized weakness. 亞東醫院小兒科 陳萬德 / 溫港生主任. General Data. Name: 彭 x 莉 Age: 23 y/o Sex: Female. 1 st visit. Date: 8/01/2002 Chief complaint:

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A 23y/o girl with facial tightness and generalized weakness

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  1. A 23y/o girl with facial tightness and generalized weakness 亞東醫院小兒科 陳萬德/溫港生主任

  2. General Data • Name: 彭x莉 • Age: 23 y/o • Sex: Female

  3. 1st visit • Date: 8/01/2002 • Chief complaint: • Tingling, numbness, and heat sensation of face, palpitation and generalized weakness recently especially after meals on restaurant • Physical Exam: • Cons: clear • Vital sign: stable • Chest: no tachypnea, clear breathing sound • Heart: RHB without murmur

  4. 1st visit • Past History • Irritable bowel syndrome • No skin allergy, asthma or autoimmune disease • No cardiac vascular disease

  5. 1st visit • Lab: • Total IgE: 8.59 (<250IU/ml) • ECP: <2μg/L • CAP allergen test • Egg white: neg • Milk: neg • Fish: neg • Peanut: neg • Yeast: neg • Shrimp: neg • Treatment: • Home-cocked meal and on elimination diet for 1 week

  6. 2nd visit • 08/08/2002 • Same episode present once in the past week • Possible cause: soy paste intake • Test: • Skin pick test with MSG: negative • MSG sc skin test: 8x9/22x15 mm/mm • PFT: no decreased of FEV1 or FEF25 MSG: monosodium glutamate

  7. 2nd visit • Diagnostic procedure: • Oral challenge with 5mg of MSG and placebo: positive response with flushing of face, weakness and palpitation after one hour • MSG allergy • Treatment: • Loratadine, Vistaril, Prednisolone • Elimination diet

  8. Discussion

  9. Introduction • The Chinese have used certain seaweeds to enhance the flavor of food for 2,000 years. • In 1908, Professor Ikeda of the University of Tokyo isolated MSG from the seaweed. • The Ajinomoto Company was established in Japan; monosodium glutamate, became commercially available.

  10. What is MSG? • The sodium salt of glutamic acid, one of the most abundant amino acid and important components of proteins. • Glutamate occurs naturally in protein-containing foods such as meat, fish, milk and many vegetables. • Glutamate is also produced by the human body and is an essential part of human metabolism. • But only enhances flavors when it appears in its "free" form.

  11. Additive effect of MSG The first evidence of toxicity • The New England Journal of Medicine in 1968 • Robert Ho Man Kwok, M.D. • Title: Chinese-Restaurant Syndrome • Burring, tightness, and numbness in upper arms, thorax, neck, or face, chest pain, dizziness, headache, palpitation, weakness, nausea, and vomiting • Begin shortly after meal and last for less than 4 hours. • Monosodium glutamate may be the cause of the syndrome

  12. Additive effect of GSM Clinical signs and symptoms • Asthma • Headache • Urticaria • Abdominal pain • Atopic dermatitis • Neuropathy • Orofacial granulomatosis • Neuropsychiatric disorders • Arrhythmia

  13. Additive effect of GSM The metabolism and pharmacokinetics of MSG • Transamination to alanine during intestinal obstruction • Excessive glutamate, after deamination, may be utilized in gluconeogenesis • Unless very large bolus dose(>150mg/kg) are administered, concentration of glutamate in portal blood showed only small rise after MSG intake • Further metabolism in the liver • Glutamate is the major excitatory neurotransmitter in central nervous system (minimal peripheral effect)

  14. Additive effect of GSM The evaluation of safety and toxicity • LD50 in rats and mice: 15,000-18000mg/kg respectively • Reproduction and teratogenicity: no evidence

  15. Neurotoxicity • Olney in 1969 • focal necrosis of the hypothalamus in mice (neural and endocrine functions, including weight control) • Continuous excitation of glutaminergic neurons with depletion of ATP • Neonatal was most sensitive • The oral gavage dose: 1000mg/kg • In human: blood level of glutamate do not raise significantly ever after abuse dose up to 10g, and infants are no more risk than adult.

  16. Neurotoxicity • Annals of allergy in 1982 • Neuropathy and Allergic reaction due to MSG

  17. Chinese Restaurant Syndrome • The presence of monosodium glutamate or pyroglutamate may be essential for syndrome

  18. Chinese Restaurant Syndrome Pathogenesis : have not been proven • Ghadimi et al in 1971 • Transient acetylcholinosis • Repression of symptoms after administration of atropine • Without use of control

  19. Chinese Restaurant Syndrome • Kenny and Tidball in 1972 • MSG is may not be the causative agent of CRS • MSG may be initiate immunological events, but not the effective agent for the syndrome. • Glutamate concentrations in blood was significantly difference between MSG trials and placebo group. • No association was found with blood levels and the appearance of symptoms.

  20. Chinese Restaurant Syndrome • Gore in 1980 • Subtle individual variation within the population. • The nature of variation was unknown, may be biochemical or genetic • Smith et al in 1982 • High sodium intake rather than MSG • Folkers et al in 1984 • Deficiency of Vit B6 was the mechanism of CRS • Failed to explain why patients with Vit B6 deficiency suffered no ill effects when challenged with MSG

  21. Chinese Restaurant Syndrome • Kenny in 1986 • MSG was not unique in producing CRS • Manifestation of esophageal irritation • Chin et al in 1989 • May be caused by histamine in food

  22. Chinese Restaurant Syndrome William H et al in 1997 Table I. Rechallenge in 36 subjects MSG (gm) Placebo 1.25 2.5 5 p Value Number (%) responding* 8 (22) 12 (33) 21 (58) 25(70) 0.000† Median no. of symptoms (sum) Index 0 (23) 1 (41) 2 (64) 2 (76) 0.000‡   Other 0 (22) 0 (26) 1 (57) 1 (49) 0.008‡    Total 0 (45) 1 (67) 3 (121) 4 (125) 0.000‡ Median severity of symptoms (sum) Sum of severity of index symptoms 0 (35) 1 (55) 2 (99) 4 (143) 0.000‡ Average severity of index symptoms 0 (22.5) 1 (28.2) 1 (41.5) 1.5 (55.2) 0.000‡ Sum of severity of other symptoms 0 (36) 0 (41) 1.5 (84) 1.5 (95) 0.016‡    Sum of severity of total symptoms 0 (71) 1.5 (96) 4.5 (183) 6(238) 0.000‡ Average severity of total symptoms 0 (22.3) 1 (29.1) 1.3 (44.7) 1.6 (56.7) 0.000‡ *Response defined by 2 index symptoms after ingestion of test agent. †Statistically significant, Cochran test. ‡Statistically significant, Friedman test.

  23. Chinese Restaurant Syndrome Table II. Trend or threshold effect with increasing dose of MSG (n= 36) Placebo vs 1.25 gm Placebo vs 2.5 gm Placebo vs 5.0 gm No. of index symptoms 0.129 0.000* 0.000* No. of other symptoms 0.503 0.001* 0.021 No. of total symptoms 0.191 0.0000* 0.000* Sum of severity of index symptoms 0.310 0.003* 0.000* Average severity of index symptoms 0.515 0.022 0.001* Sum of severity of other symptoms 0.598 0.002* 0.003* Sum of severity of total symptoms 0.334 0.000* 0.000* Average severity of total symptoms 0.340 0.001* 0.000* Comparisons use Wilcoxon tests to explore paired relationships after significant results to Friedman tests for all dose levels; p< 0.017 considered statistically significant after Bonferroni adjustment. *Statistically significant.

  24. Chinese Restaurant Syndrome • Possible cause • Excitation of central nervous system • Idiosyncratic Intolerance, not allergic (IgE was not elevated)

  25. Chinese Restaurant Syndrome • Moraelli et al in 1970 • 3g of MSG in 150ml beef bouillon to 73 healthy subjects • No differences in symptomatology between control and MSG treated groups • L. Tarasoff et al in 1993 • Failed to demonstrate significant adverse effects from high levels of MSG in the food. • Many of foods can cause sensation and symptoms • Restaurant syndromes can be caused by a wide variety of food components and additives.

  26. Chinese Restaurant Syndrome • Stengink et in 1979 • Levels are greatly decreased when MSG was ingested in a capsule or with protein or carbohydrates as in meal • Tung et al in 1980 • Infants, including premature babies, could metabolize the similar dose as adult

  27. Chinese Restaurant Syndrome The prevalence: have not been a reliable estimate • Kerr et al in 1979 • 43% experienced one or more unpleasant symptoms associated with the consumption of food sometime. • 1.8% with possible CRS, and only 0.19% associated with Chinese food

  28. MSG induced asthma • David et al in 1987 • MSG can provoke asthma, may be severe and life threatening • The reaction is dose dependent, and can be delayed up to 12hrs • 13 of 32 patients with asthma reacted to challenge to MSG • CNS excitation and stimulation of irritant receptor in the lung, leading to bronchospasm • Use bronchodilator during the control period, but not in challenge period, and drug withdraw from challenge period

  29. MSG induced asthma • Manning and Stevenson in 1991 • Can not confirm asthmatic reaction using same protocol • Schwartzstein et al in 1987 • Did not see any decrease in pulmonary function

  30. Glutamate Safety in the Food Supply • FASEB (Federation of American Societies for Experimental Biology) in 1995 • Proposed the term MSG symptom complex instead of Chinese Restaurant Syndrome • An effect of MSG will be seen only when MSG is ingested on an empty stomach and when large dose (>3gm) • FDA classified MSG as a "generally recognized as safe," or GRAS

  31. Glutamate Safety in the Food Supply • The average daily intake of MSG in industrialized countries is 0.3 to 1 gm, but in a highly seasoned restaurant meal as much as 5 gm.

  32. Diagnosis • Clinical diagnosis made from history and awareness that such the clinical entity exits. • Diagnostic test as CBC, electrolytes, or serum glutamate level provide no additional information. • A thorough history and physical examination should be performed on all patients to rule out life-threatening disorder

  33. Therapy • Supportive treatment • The possibility of life-threatening events, asthma or arrhythmia • Steroid? • Antihistamine? • Anticholinergic? • Vit B6?

  34. Summary • Chinese Restaurant Syndrome is indeed existed, but rare(1-2%) • The symptoms are a benign, self-limited process that has an excellent prognosis for rapid recovery • Who is susceptible, how much MSG is needed, whether MSG is the sole etiologic agent?

  35. Thanks for your attention

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