Mustard: A Priority Food Allergen in Canada

Table 1: Pivotal Clinical Studies (detailed summary in Appendix 2)
Author, Year, Country Study Design Details Subjects Clinical History Symptoms & SignsFootnote 1 (before challenge) Symptoms & SignsFootnote 1 after Challenge Diagnostic TestsFootnote 3 Eliciting Dose Eliciting Allergen Prevalence Comments
1. Double-Blind, Placebo-Controlled Food Challenge (DBPCFC)
a. Randomized

Figueroa et al., 2005 Spain

Prospective Questionnaire & CH

Increasing Dose: 80, 240, 800, 2400, 6480 mg w/ 15 min interval until symptoms appeared or cumulative
max dose of 10g Mus
Followed by an open arm up to 25 g Mus

24/38 (83%) CH w/ Mus

14/38 (37%) excluded because SEV of symptoms or did not agree to enter the food CH

38 SUB

Age: 5/38= 14y

Average: 21.9±8.6y

Sex: 20F:18M

Hx of A in 11% of SUB (exclude from CH)

Hx of atopy in 92% of SUB

Hx of primary Res Sen in 83% of SUB

A: 11%

EIA: 3%

OAS: 47%

U/AE 42%

Positive Rxn 14/24 (58%)

Type of Rxn: OAS 10/14 (71%)
SEV: mild

AE+BA 1/14 (7%)
SEV: mod

A 1/14 (7%) in a SUB w/ out previous Hx of A
SEV: sev

SPT to a panel of aero-allergens and food extracts

IgEto mugwort pollen, mustard, cabagge, broccoli etc.

Mean cumulative dose (until reaction appeared or max dose reached):
891.4
±855.2 mg of Mus sauce equivalent to 124.8
±119.7 mg of Mus

Eliciting dose in most severe cases: 156.8mg of Mus sauce

lowest dose eliciting a reaction was 44.8mg of Mus sauce

Mus sauce

Meta-bisulfite freeFootnote 4

58% of SUB positive for Mus allergy

Cross-Rxn w/ mugwort pollen: 97% SUB

Other food Sen 42% SUB

Sen to Brassicaceae 100% SUB

Assoc. EIA 2% SUB

b. Non-randomized

Morisset et al., 2003 France

Doses 10, 30, 100, 300900 every 20 min with a cumulative dose of 1340 mg

Mus seasoning amount selected based on routine consumption

24 SUB DBPCFC

6 SUB SBPCFC

30 SUB

Ch:28/30
A: 2/30

Age: 3-20 y

Sex: 11F:19M

Hx of Rxn to ingestion of Mus

Screened for Mus allergy by PST and IgE.

U,AE,AD BA, abdominal pain, diarrhea

Positive Rxn 7/30 (23%)

Type of Rxn: SK e.g. pruritus, erythema 5/7 (72%)
SEV: mild

GI /Res e.g.: abdominal pain, diarrhea, sneezing, wheezing 4/7 (57%)
SEV: mod

SPT to Mus seed, Mus flour and metabisulfite-free Mus

Mustard specific IgE

Lowest dose inducing symptoms: 1 Ch 40 mg Mus (0.8mg of protein).

Subject Sen by mustard pollen and rape pollen

Another Ch 440 mg Mus

Mus seasoning (B. juncea seed) containing 34% Mus seed and 6% Mus protein

Metabisulfite-free*

23% SUB positive for Mus allergy

SEV of certain Rxns argues for an informative labelling, Mus often masked allergen in many manufacture sauces

2. Single-Blind, Placebo-Controlled Food Challenge (SBPCFC)
a. Non-randomized

Rancé et al., 2000 & 2001 France

SUB selected for by positive Mus SPT

Compared SUB to 22 controls w/out Hx of food allergy

Increasing doses: 1, 5, 10, 20, 50, 100, 250 and 500 mg Mus

36 Ch

Age: 10 m-15 y
Ave. 5.5y

Sex : 22M:14F

15/30 ch w/ previous hx of food allergy

Family Hx of atopy 81%

8/15 SUB (53.3%) exhibited Rxn to Mus under the age of 3 years

Of the 54 initial clinical features:

AD 52%

U/AE 37%

BA 9%

laryngeal edema + OAS + C 2%

Mustard allergy confirmed in 15/36 (42%)

Most common reaction: U 14/15 (93%)
SEV: mild

SPT

IgE

1 to 936 mg Mus powder

Mean cumulative dose: 153 mg Mus powder

Mus powder

42% SUB positive for Mus allergy

Symptoms started =3 y of age in 53% of the subjects

67 % SUB were also allergic to other foods- peanuts, eggs & milk

Possible Sen in utero or lactation

Mustard in baby food

Table 2: Non-Pivotal Clinical Studies
Author, Year, Country Study Design Details Subjects Clinical History Symptoms & SignsFootnote 1 (before challenge) Symptoms & SignsFootnote 1 Severity of RxnFootnote 2 after Challenge Diagnostic TestsFootnote 3 Eliciting Dose Eliciting Allergen Prevalence Comments

Niinimaki et al.,1989 Finland

Open study assessing allergy to spices including Mus using SPT and RAST

50 SUB

Age: 1-47y
Ave 16.2y

Sex: 25M:25F

3 Ch: Age 1-1.5y (never ingested Mus; breast-feed for 11m)

Hx allergy to spices & birch pollen 64%

Hx of atopy 96%

Res/OC

Sen

Gastric pain

R

AD 26%

Positive Rxn to SPT 29/50 (58%)

RAST and SPT correlation good

Ch who never ingested Mus had positive SPT Rxn

SPT

RAST

0.648 g Mus dissolved in glycerol & saline to make 5% (w/v) test solution

Commercial powdered Mus

58% SUB positive for Mus by either one or both SPT/RAST

40/50 (80%) SUB positive SPT & RAST to birch pollen

15/50 (30%) SUB positive SPT & RAST to mugwort pollen

Rancé et al., 1994 France

Open study assessing allergy to spices including Mus using SPT and IgE

7/23 SUB had LFC and/or OFC conducted with Mus

83 SUB (Ch) tested for allergy to spices

Age: 15m to 16y

Sex :50M:33F

Hx of pollen and food allergy

Chronic U or recurrent AE/E

Positive SPT for Mus in 23/83 SUB (28%)

6 SUB positive for Mus LFC & 1 SUB positive in OFC

Symptoms specific to Mus :
OAS/ U/ C 11/23 (48%)
SEV: mild

SPT

IgE

Not reported

Commercial extract

39/83 SUB (46%) positive (SPT & IgE) allergy to spices

23/39 SUB (59%) positive allergy to mustard

7/23 SUB (30%)
confirmed by LFC or OFC

ollen allergy existed in 56% of Ch allergic to spices

Niinimaki et al., 1995 Finland

Open study assessing allergy to spices including Mus using SPT, RAST: IgEat 2m and 2.9y intervals

49 SUB

Age: 1 to 51y
ave: 16.5y

Sex: 23M: 26F

Hx allergy to spices & birch pollen

Hx of atopy

Atopic dermatitis w/ Res symptoms 57%

Chronic E

Positive Rxn to Mus specific IgE
22/31 (71%) SUB w/ positive SPT

SPT
RAST: Total IgE
Mus specific IgE

4 mg powdered spice and 50 µL of saline on the skin

Native Mus (Sinapis alba & Brassica nigra)

31/49 (63%) SUB positive SPT

22/31 (71%) SUB positive for Mus allergy

22/49 (45%) SUB positive for Mus allergy

Concomitant Rxn to native spices seen in 19/29 SUB who were tested with all spices

38/46 (83%) positive to birch pollen

Rancé & Dutau, 1997 France

Open allergy study assessing over 25 allergens including Mus using SPT, IgE

LFC and SBPCFC (when LFC negative)

142 SUB (Ch)

Age: 7m to 15y
Ave: 4.5 y

Sex: 95M:47F

Hx of food allergy

Multiple presenting symptoms in 66% Ch
AD 61%
Rash 32%
AE 25%
BA 24%
A 4%

Positive for Mus allergy 23/142 (16%)
16/23 in LCF
7/23 in SBPCFC

Multiple symptoms per Ch.(not specific to Mus)
U 74%
BA 22%
GE 4%
A 2%
SEV: sev

SPT

IgE

1 mg to 5 g for all allergens tested

Further details not provided

extracted from local food

23/202 SUB (11%) positive for Mus allergy

Mus 3rd most common food allergy in study

Rancé & Dutau, 1998 France

Open allergy study assessing foodstuff including Mus using SPT, IgE and open LFC

45 Ch

Age: 3m to 9y
Ave:2.5 y

Sex: 30M: 15F

Family Hx of atopy: 78% SUB

AD: 93%

44% SUB w/ allergy to =3 foods

U 30%
AE 26%
E 20%
BA 10%
A 2%

Positive allergy to mustard
12% SUB

SPT

IgE

Mean dose by OFC 900mg
(1mg to 10gr)

Details not provided

Positive allergy to Mus 12% SUB

None

Rancé and Dutau, 2002 France

Open allergy study assessing foodstuff including Mus documented by DBPCFC in BA patients identified by pulmonary function

163 Ch

Age: 2 to 17 y
Ave. 7.2 y

Sex: 108M:54F

Family Hx atopy 91 %

Hx of = 1 food allergies

BA for ave. 5.5 y

SK 59%;
Res 24%
GI 12%

Asthma induced by food allergens potentially severe.

A 6%

SPT

IgE

Details not provided

Various food extracts

Positive allergy to Mus 7% SUB

Prevalence of asthma induced by food allergen: 10%

Table 3: Other Relevant Studies
Author, Year, Country Study Design Details Subjects Clinical History Symptoms & SignsFootnote 1 (before challenge) Symptoms & SignsFootnote 1 Severity of RxnFootnote 2 after Challenge Diagnostic TestsFootnote 3 Eliciting Dose Eliciting Allergen Prevalence Comments

André et al., 1994 France

Retrospective Analysis 9 y period investigating foodstuff most frequently associated with A Rxn

580 SUB

480 Ad
100 Ch

Age: 1-83 y
mean: 30y

Sex: 290M: 290F

Hx of adverse Rxn to food

60/580 SUB Hx severe Rxn to food
A 52/60
AE 6/60
Broncho-spasm 2/60

Not applicable to study design

SPT

IgE

Details not provided

Mustard

3% of SUB positive for ser Rxn to Mus

An increase in the frequency of sen (1%) to Mus was noted

Rancé et al., 1998 & 1999 a, b France

Prospective prevalence study of food allergy validated by SPT/IgE/ LFC

Ch 544

Age: 0-15

Sex: 343M: 201F

Hx food allergy confirmed by food challenge

Family Hx atopia 71%

AD 275/544 (51%)

U/AE 165/544 (30%)

BA 47/544 (9%)

A 27/544 (5%)

49/544 (9%) positive Rxn to Mus

AD 21/49 (43%)
U/AE 21/49 (43%)
BA 2/49 (4%)
A 1/49 (sev) (2%)
GI 1/49 (2%)
OAS 1/49 (2%)
C 2/49 (4%)

SPT

IgE

0.1-10g for all allergens tested

Dose specific to mustard: not reported

Test substances extracted from local food

49/544 (9%) SUB positive for Mus allergy

Mus 4th most common allergy identified within a population with multiple food allergy

Caballeros et al., 2002 Spain

Cohort

29 SUB
Hx Mus
allergy

Age: 15-58y
mean 27.3±10y

Sex: 10M:19F

Family Hx of atopy

50% SUB allergy to other vegetables

17% allergy to non-vegetables

52% symptoms of pollinosis

Mus allergy confirmed by SPT and IgE

19/29 (65%) SUB systemic Rxn

14/19 (74%) A

AE 16/29

Dyspnea 11/29

U 10/29

OAS 8/29

Most common symptom U & AE.
SEV: mild-sev

SPT

total IgE

Mus specific IgE

Details not provided

Trace amounts reported to elicit Rxn

Mus extract of B. nigra at 1:10 w/v

Not applicable study population 100% positive allergic Rxn to Mus

Mustard seed allergens are resistant to digestion and high temperature

No challenge Study due to risk of sev Rxn

Table 4: Case Reports
Author, Year, Country Cases Clinical History Symptoms & SignsFootnote 1 Severity of RxnFootnote 2 Diagnostic TestsFootnote 3 Eliciting Dose Eliciting Allergen Comments
1. Canadian Reports

Yip and Zimmerman, 1999 Canada

Full Publication

5 children

Sex: 4 M/1 F

Ages:

Case 1: 2.5 y M

Case 2: 2 y M

Case 3: 5 y M

Case 4: 7 y F

Case 5: 3 y M

Case 1: Atopic boy w/ Hx of multiple food allergies since 18 month (sesame seed, fish)

Case 2: Atopic boy w/ Hx of sen to kiwi, peanut

Case 3: boy w/ Hx of BA and multiple food allergies (eggs, sesame, peanuts)

Case 4: Atopic girl w/ E since infancy; BA; Allergy to milk, egg and peanut

Case 5: boy w/ Hx

BA and multiple food allergies

Case 1: 3 episodes of sev Rxn requiring emergency medical treatment
AE and at least one episode of airway obstruction

Case 2: 3 episodes of U immediate after exposure to mustard. No mention of emergency

Case 3: at least one episode of Ax reaction to fast food (mustard and sesame)

Case 4: U and wheezing following ingestion of mustard. No indication of emergency visit

Case 5: vomiting, swelling of the lips
No indication of emergency

SPT positive for several Mus preparations

In 4/5 cases total IgE or mustard specific IgE not reported

Details not provided

Mustard sauce
Salad dressing
Glazed ham

2/5 Cases Severe
2/5 moderate
1/5 mild.

One case due to hidden source of mustard in the glazing of a prepared ham & one case in fast food

Connors et al., 2006 Canada
Abstract

1 female

Age: 50 y

No detailed Hx provided

Hx of A type Rxn to Mus

Symptoms of A after ingestion of Mus

SPT

Details not provided

Fast food Mustard sauce

Very limited info provided

2. International Reports

Paconesi et al., 1980 Italy

1 male

Age: "young"

Hospitalization twice in 1 year. Acute giant U with edema of the glottis after eating pizza

Skin test to Mus antigen extracted from black and white Mus caused intense wheal reaction followed by shock and glottic edema.

SPT

IgE: RAST

Small amount Mus contaminating the pizza

Mustard not used in preparation of the pizza: reaction to cross-contamination with Mus

Meding, 1985 Sweden

1 female

Age: 40 y

Atopy Rxn to Mus

SPT black & white mustard, rape seed & others Cruciferae

Negative SPT for allylisothiocyanate
Positive SPT for Mus, rape seeds

Widstrom and Johansson, 1986 Sweden

1 female

Age: 25 y

Hx of allergy to egg and fish in childhood that cleared.

Acute Rxn to Mus/mayo
U&AE on face & neck

IgE: RAST positive for white & black Mus & rape seed

One episode of possible cross-contamination of fast food

Fast food and mayonnaise

Vidal et al., 1991 Spain

2 females

Age:

Case 1: 47 y

Case 2: 15 y

Case 1: Hx pollen allergy

Case 2: Hx of A and pollen allergy

Case 1: sev U & facial AE w/GI & Res symptoms

Case 2: U, facial & throat edema & chest tightness

Positive STP, Total serum IgE, Specific M IgE

Mayonnaise and Mus on sandwich and in a salad

Monreal et al., 1992 Spain

1 male & 1 female

Age:

Case 1: 17y M

Case 2: 14y F

Case 1: family Hx of atopy, personal Hx of IgE dependent BA, allergy to molds and grasses, reocurrent U/AE since age 5

Case 2: family Hx of atopy, personal Hx of BA

Case 1: Rxn to Mus edema lips/tongue, Dysphagia, Upper Res symptoms Required emergency service

Case 2: 1 hr after physical exercise and ingestion of Mus; edema tongue, lips face, U, upper Res distress Required emergency service

Case 1: STP w/ Mus, aero-allergens positive
Total IgE and specific IgE by RAST positive

Case 2: STP for Mus positive
Total IgE and specific IgE by RAST positive

Both reported as small amount

Both Mustard sauce

Compared Severity of Rxn to Mus allergy w/ penicillin.

No oral Challenge due to Severity of Rxn

Malet et al., 1993 Spain

2 males

Age:

Case 1: 31 y

Case 2: 32 y

Case 1: Hypersensitivity to pollen, seasonal R

Case 2: No reported Hx of other allergies, Contact Hypersensitivity to Mus since age 10

Case 1: AE of face, U, Dyspnea, after oral & nasal exposure to Mus

Case 2: U, AE, pruritus, BA after accidental ingestion of Mus, requiring hospital treatment

Case 1: SPT, total IgE high, Specific IgE by RAST positive to Mus seed

Case 2: SPT, total IgE high, specific IgE by RAST to Mus seed

At least one case of accidental contact to mustard or even the smell of mustard elicited Rxn

Mustard sauce or seed

Minimal quantities elicited a dermo- Res Rxn sev enough in one case to require hospitalization

Jorro et al., 1995 Spain

2 male & 1 female

Age:

Case 1: 43y M

Case 2: 17y F

Case 3: 19y M

Case 1: Hx of sev Rxn to Mus & AE to shellfish

Case 2: Hx of BA, R, U

Case 3: Hx of R

All 3 cases very severe A requiring urgent hospital service

Case 1&2: pruritus, edema of face/tongue, upper Res distress

Case 3: upper Res distress, U

All cases positive SPT & IgE to Mus

Case 1& 3: Mus sauce

Case 2: Mus in salad

No oral challenge to Mus due to sev of Rxn

Oral challenge to others Cruciferae negative

Valero et al., 1995 Spain

3 male & 2 female

Age:

Case 1: 34y F

Case 2: 31y M

Case 3: 25y M

Case 4: 52y F

Case 5: 33y M

4 cases w/ Hx of Aero-allergy
3 cases w/ Hx of food allergies
2 cases w/ Hx of reaction when present in areas where Mus was manipulated

SPT on 86 patients with Hx of atopy

U, AE, R, Dyspnea, Bronchial spasm
All cases w/ SK symptoms
4/5 cases w/ Res symptoms
All requiring hospital emergency service

All 5 cases positive to Mus by SPT & IgE

18.4% of the 86 subjects tested by SPT were positive to Mus

Mus sauce

The two cases described earlier in Malet et al., (1993) appear to be included in this case report

Kanny et al., 1995 France

1 female

Age: 38 y

Hx allergy to mustard.
Hx of exposure to Mus powder in pharmacy where she worked

Oral pruritus Facial edema, U Dyspnea, fainting 20 min after eating Chicken dip
Severe reaction requiring emergency medical attention

Positive SPT/ IgE: RAST

Estimated Concentration of Mustard in the dip: 0.15 mg/100mg

Chicken dip Hidden source of Mus allergen

Mus is the most allergenic of the commonly used spices, it is able to induce sev A in very small amounts

Frémont et al., 1996 France

1 female

Age: 22 m

Family Hx atopy
Hx of Celiac Disease & allergy to milk at age 11 month

Failure to thrive
Diarrhea
Vomiting
Coughing fits
AEl

SPT/IgE positive for Mus, although the culprit food in this case was not Mus

Milk proteins in flour

Emphasis on Hidden allergens
Case demonstrates Sen to Mus in young baby

Asero et al., 2002 Italy

1 male

Age: 54 y

Hx of A Rxn after ingestion of sunflower seed in bread

STP positive to Sunflower seeds and Mus
IgE specifc positive
Cross-reactivity of Mus and sunflower seeds

Sunflower seeds in bread

Objective of the report was to demonstrate the Cross-reactivity of Sunflower seeds and Mus

Lingelbach et al., 2003 Germany

1 female

Age: 40 y

Hx of food and pollen allergies
11 years Hx of EIA

At least two episodes of EIA requiring emergency medical assistance.

STP, Specific IgE (RAST)

Fast food

EIA associated to Mus in food

Patient Rejected Oral challenge

Aygencel et al., 2007 Turkey

1 female

Age: 53 y

AE of tongue and oropharynx, Requiring hospital Emergency assistance

Wild mustard: raw leaves of Brassica (Sinapis) Arvensis in salad

Abbreviations:

Ad:
adult
CH:
challenge
Ch:
children
DBPCFC:
double-blind ,placebo-controlled food challenge
F:
female
Hx:
history
LFC:
labial food challenge
M:
male
max:
maximum
min:
minute
mod:
moderate
Mus:
mustard
OC:
occupational
OFC:
oral food challenge
Res:
respiratory
Rxn:
reaction
Sen:
Sensitization
SEV:
severity
sev:
severe
SBPCFC:
single-blind, placebo-controlled food challenge
SUB:
subjects
w/:
with
( y)
years old

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