Download 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
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
1st visit

Past History



Irritable bowel syndrome
No skin allergy, asthma or autoimmune disease
No cardiac vascular disease
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
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
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
Discussion
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.
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.
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
Additive effect of GSM
Clinical signs and symptoms









Asthma
Headache
Urticaria
Abdominal pain
Atopic dermatitis
Neuropathy
Orofacial granulomatosis
Neuropsychiatric disorders
Arrhythmia
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)
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
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.
Neurotoxicity


Annals of allergy in 1982
Neuropathy and Allergic reaction due to MSG
Chinese Restaurant Syndrome

The presence of monosodium glutamate or
pyroglutamate may be essential for syndrome
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
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.
Chinese Restaurant Syndrome

Gore in 1980



Smith et al in 1982


Subtle individual variation within the population.
The nature of variation was unknown, may be biochemical
or genetic
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
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
Chinese Restaurant Syndrome
William H et al in 1997
Table I. Rechallenge in 36 subjects
Number (%) responding*
Median no. of symptoms (sum)
Index
Other
Total
Median severity of symptoms (sum)
Sum of severity of index symptoms
Average severity of index symptoms
Sum of severity of other symptoms
Sum of severity of total symptoms
Average severity of total symptoms
MSG (gm)
Placebo
1.25
8 (22)
12 (33)
2.5
21 (58)
5
25(70)
0.000†
0 (23)
0 (22)
0 (45)
1 (41)
0 (26)
1 (67)
2 (64)
1 (57)
3 (121)
2 (76)
1 (49)
4 (125)
0.000‡
0.008‡
0.000‡
0 (35)
0 (22.5)
0 (36)
0 (71)
0 (22.3)
1 (55)
1 (28.2)
0 (41)
1.5 (96)
1 (29.1)
2 (99)
4 (143)
1 (41.5) 1.5 (55.2)
1.5 (84) 1.5 (95)
4.5 (183) 6(238)
1.3 (44.7) 1.6 (56.7)
*Response defined by 2 index symptoms after ingestion of test agent.
†Statistically significant, Cochran test.
‡Statistically significant, Friedman test.
p Value
0.000‡
0.000‡
0.016‡
0.000‡
0.000‡
Chinese Restaurant Syndrome
Table II. Trend or threshold effect with increasing dose of MSG (n = 36)
Placebo vs 1.25 gm
No. of index symptoms
0.129
No. of other symptoms
0.503
No. of total symptoms
0.191
Sum of severity of index symptoms
0.310
Average severity of index symptoms
0.515
Sum of severity of other symptoms
0.598
Sum of severity of total symptoms
0.334
Average severity of total symptoms
0.340
Placebo vs 2.5 gm Placebo vs 5.0 gm
0.000*
0.000*
0.001*
0.021
0.0000*
0.000*
0.003*
0.000*
0.022
0.001*
0.002*
0.003*
0.000*
0.000*
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.
Chinese Restaurant Syndrome

Possible cause


Excitation of central nervous system
Idiosyncratic Intolerance, not allergic (IgE was
not elevated)
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.
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
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
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
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
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
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.
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
Therapy






Supportive treatment
The possibility of life-threatening events, asthma
or arrhythmia
Steroid?
Antihistamine?
Anticholinergic?
Vit B6?
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?
Thanks for your attention