Re: Check Expiration Dates Mold in Pancake Mix

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An Unusual Case of Anaphylaxis

Mold in Pancake Mix

Allan T. , M.D. ; Kim A. , M.D.

From the Office of the Chief Medical Examiner Department of

Pathology and Laboratory Medicine, Forensic Section Medical

University of South Carolina ton, South Carolina, U.S.A.

THE AMERICAN JOURNAL OF FORENSIC MEDICINE AND PATHOLOGY 2001;22:292-

295

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Anaphylactic reactions involve contact with an antigen that evokes

an immune reaction that is harmful. This type of reaction is a

rapidly developing immunologic reaction termed a type I

hypersensitivity reaction . The antigen complexes with an IgE

antibody that is bound to mast cells and basophils in a previously

sensitized individual. Upon re-exposure, vasoactive and spasmogenic

substances are released that act on vessels and smooth muscle. The

reaction can be local or systemic and may be fatal.

The authors report the death of a 19-year-old white male who had a

history of " multiple allergies, " including pets, molds, and

penicillin. One morning, he and his friends made pancakes with a

packaged mix that had been opened and in the cabinet for

approximately 2 years. The friends stopped eating the pancakes

because they said that they tasted like " rubbing alcohol. " The

decedent continued to eat the pancakes and suddenly became short of

breath. He was taken to a nearby clinic, where he became

unresponsive and died. At autopsy, laryngeal edema and hyperinflated

lungs with mucous plugging were identified. Microscopically, edema

and numerous degranulating mast cells were identified in the larynx.

The smaller airways contained mucus, and findings of chronic asthma

were noted. Serum tryptase was elevated at 14.0 ng/ml. The pancake

mix was analyzed and found to contain a total mold count of 700/g of

mix as follows: Penicillium , Fusarium , Mucor, and Aspergillus .

Witness statements indicate that the decedent ate two pancakes; thus

he consumed an approximate mold count of 21,000. The decedent had a

history of allergies to molds and penicillin, and thus was allergic

to the molds in the pancake mix. The authors present this unusual

case of anaphylaxis and a review of the literature.

Key Words: Anaphylaxis ; Tryptase ; Sudden death

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The differential diagnosis of acute-onset shortness of breath

includes pulmonary embolism, status asthmaticus, acute myocardial

infarction, drug reactions, and anaphylaxis. Systemic anaphylaxis, a

type I hypersensitivity reaction, is an acute allergic reaction that

results from the rapid release of active mediators from tissue mast

cells and peripheral blood basophils (1) . Anaphylactic reactions

can cause variable combinations of symptoms, including cutaneous

urticaria, laryngeal edema, rhinorrhea, conjunctivitis,

bronchospasm, abdominal cramps, nausea, vomiting, diarrhea,

arrhythmias, and hypotension (1,2) . Most reactions are due to

insect stings, foods, immunotherapy injections, or medications.

The prevalence of anaphylaxis is unknown. Unlike many disorders,

there is no requirement to report such reactions to any national

registry (3) . The postmortem diagnosis of anaphylaxis is not an

easy task when the history of events is not witnessed and is further

complicated by the fact that the classic signs, such as laryngeal

edema, pulmonary hyperinflation, and tissue eosinophilia, are

inconstant findings (4) . The use of serum tryptase levels, a

neutral protease released from mast cell secretory granules, has

been helpful in aiding in the diagnosis of anaphylaxis. The

following case report is of an anaphylactic death after the

ingestion of 2-year-old pancake mix with an elevated mold count.

CASE HISTORY

Clinical Course

The decedent was a 19-year-old white male who had a history of

multiple allergies with resultant reactive airway symptoms, which

were usually relieved with an albuterol inhaler. Allergies included

pets (dogs and cats), molds, and penicillin. While home on vacation

from college, he and two friends were eating pancakes made with

pancake mix that had been previously opened and had a date of

expiration 2 years prior. The friends stated that they stopped

eating the pancakes because they tasted like " rubbing alcohol. " The

decedent continued to eat and finished two pancakes. Minutes later,

while watching television, the decedent became short of breath,

which was not relieved by his inhalant. He asked his friends to take

him to a medical clinic not far from the home and was reported to

become slightly cyanotic during the ride. He was able to walk into

the clinic and suddenly collapsed in cardiopulmonary arrest. He

failed to respond to resuscitative efforts and was pronounced dead.

Autopsy Findings

The body was that of an obese, young white male with head and neck

cyanosis without evidence of injuries. Removal of the chest plate

revealed hyperinflated lungs. The right and left mainstem bronchi

contained thick mucus secretions, as did the smaller airways upon

sectioning. The larynx and epiglottis were mildly edematous on gross

examination. The remainder of the organs were in normal anatomic

position and grossly unremarkable.

Microscopic examination of the lungs revealed thickened bronchial

basement membranes, hypertrophy of bronchial muscle smooth muscle,

alveolar capillary hyperemia, and increased size of submucosal

glands, consistent with a history of chronic asthma ( Fig. 1 and

Fig. 2 ). Numerous eosinophils were noted as well ( Fig. 2 ). A

Giemsa stain of the larynx and epiglottis showed increased numbers

of mast cells, many of which were degranulating, within an edematous

submucosa ( Fig. 3, Fig. 4, Fig. 5 and Fig. 6 ).

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FIG. 1. Hematoxylin and eosin–stained section of lung showing mucus

plugging, numerous eosinophils, thickened basement membrane, and

increased smooth muscle, consistent with a history of asthma (10×).

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FIG. 2. Hematoxylin and eosin–stained section of lung at higher

power (40×) showing the thickened basement membrane and the numerous

eosinophils.

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FIG. 3. Section of larynx (hematoxylin and eosin) shows edema and a

mast cell infiltration (10×).

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FIG. 4. Section of larynx stained with Giemsa. Note the numerous

mononuclear cells infiltrating the lamina propria (10×).

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FIG. 5. Larynx stained with Giemsa depicting the marked infiltration

of mast cells (20×).

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FIG. 6. Giemsa stain highlights the degranulating mast cells in the

larynx (40×).

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Toxicologic examination revealed a negative blood alcohol and a

negative urine drug screen. The serum tryptase level was elevated at

14.0 ng/ml (normal value reported as < 11.4 ng/ml).

The pancake mix was sent to the South Carolina Department of Health

and Environmental Control for examination. The total mold count was

700/g of mix with the breakdown as follows: Penicillium species

100/g, Fusarium species 200/g, Mucor 100/g, Aspergillus flavus group

200/g, and Aspergillus niger group 100/g. According to the

nutritional labeling on the box, one pancake would contain 15 g of

mix if the directions for preparation were followed. The decedent

reportedly consumed two pancakes, ingesting approximately 30 g of

mix for a possible total mold count of 21,000.

With the reported history of events, the decedent's history of

multiple allergies, an elevated tryptase level, and an elevated mold

count in the pancake mix, the cause of death was determined to be

anaphylaxis due to an allergic reaction to molds.

DISCUSSION

Anaphylaxis is a rapidly developing immunologic reaction occurring

within minutes after the combination of antigen and antibody bound

to mast cells and/or basophils in individuals previously sensitized

(5) . Mast cells are found predominately near blood vessels and

nerves and in subepithelial sites. Their cytoplasm contains membrane-

bound granules that possess a variety of biologically active

metabolites. IgE antibodies bind to mast cell surfaces by plasma

membrane–bound Fc receptors, and activation of mast cells occurs

when the bound IgE antibodies are crosslinked by binding to

multivalent allergen (1) .

Anaphylaxis is an uncommon but well-recognized cause of sudden

death, resulting from respiratory or cardiac arrest in severe

reactions (2) . Death is usually attributed to airway obstruction

secondary to laryngeal edema, bronchospasm, or mucus plugging.

Cardiac arrest can occur with or without respiratory difficulty as

the result of either direct effects of the mediators of anaphylaxis

on the heart or shock resulting from peripheral vasodilation (2) .

Previous studies of fatal cases of anaphylaxis revealed that

symptoms developed within 20 minutes in 86% of the cases, and death

occurred within 30 minutes in 33% of the cases and within 1 hour in

50% of cases (6) . Respiratory distress and circulatory overload

were the presenting symptoms in 37% and 33%, respectively, and skin

symptoms were the presenting symptom in only 7% of the cases (6) .

It is important to realize that the absence of cutaneous symptoms

does not rule out anaphylaxis. The symptoms of anaphylaxis are

generally related to the gastrointestinal, respiratory, cutaneous,

and cardiovascular systems (7) . The sequence, timing, and severity

of symptoms vary from one individual to the next (7) . In the

current case study, the victim, who lacked cutaneous symptoms, began

to experience respiratory difficulty minutes after the ingestion of

several pancakes and died within 1 hour.

The classic postmortem findings of anaphylaxis, such as laryngeal

edema, pulmonary hyperinflation, and tissue eosinophilia, are

subjective and inconstant (4) . A recent study showed that 23 of the

56 anaphylactic deaths studied had no macroscopic postmortem

findings of anaphylaxis (2) . Thus, it may be speculated that

anaphylaxis can be an unrecognized cause of death in individuals

dying unexpectedly (8) . In cases in which there is no macroscopic

evidence of anaphylaxis, laboratory testing is a useful adjunct for

elucidating the etiology. The investigation of possible anaphylactic

deaths can be facilitated by the measurement of serum tryptase

levels (8) . Tryptase, a neutral protease released from mast cell

secretory granules when these cells degranulate, is found almost

exclusively in tissue mast cells, thus making it a specific marker

for systemic mast cell events (8,9) . Serum tryptase elevation in

postmortem sera has been shown to reflect antemortem mast cell

activation, which is compatible with an anaphylactic reaction

(9,10) . Elevated tryptase levels have been obtained up to 24 hours

post mortem (10) . The individual in this case report had an

elevated tryptase level of 14 ng/ml (reference range, <11.4 ng/ml)

at 5 hours post mortem, indicating a systemic mast cell event.

Elevated tryptase levels have been identified in specimens from

individuals who have died from nonanaphylactic causes, so an

elevated postmortem level cannot be used to establish the cause of

death as anaphylaxis without additional supportive findings or

information (9) . The diagnosis of anaphylaxis in this case report

was not made on an elevated tryptase level alone but by using the

autopsy findings and case history in conjunction with laboratory

results. The tryptase test does remain useful in evaluating

unexplained deaths, when other clinical information suggests an

anaphylactic reaction.

Most anaphylactic reactions are due to insect stings, food

allergies, or pharmaceuticals. We present an unusual case of

anaphylaxis to molds in pancake mix in an individual with a history

of mold allergies. It was determined that the decedent was not

allergic to eggs, which are a component of the pancake mix. In this

case, the clinical history, macroscopic findings, microscopic

findings, elevated tryptase level, and an identifiable allergen were

used in conjunction to make the postmortem diagnosis of an

anaphylactic reaction. It is important in cases of suspected

anaphylaxis to obtain the substance in question and have it tested

to possibly determine the suspected allergen that caused the

reaction. In the current case, it was determined that the excess

mold in the outdated pancake mix was the probable allergen. The

luxury of having all these findings are not present in many cases of

anaphylactic deaths, showing the importance of using gross findings,

microscopic findings, medical history, event history, and laboratory

testing in the evaluation of possible anaphylaxis.

REFERENCES

Yunginger JW. Anaphylaxis. Ann Allergy 1992; 69: 87– 96.

Pumphrey SH, ISD. Postmortem findings after fatal

anaphylactic reactions. J Clin Pathol 2000; 53: 273– 6.

Burks W, Bannon GA, Sicherer S, et al. Peanut-induced anaphylactic

reactions. Int Arch Allergy Immunol 1999; 119: 165– 72.

Weeden VW. Anaphylactic deaths [letter]. J Forensic Sci 1988; 33:

1108– 10.

Cotran RS, Kumar V, T. Robbin's pathologic basis of disease.

6th ed. Philadelphia: W.B. Saunders, 1999.

Delage C, Irey NS. Anaphylactic deaths: a clinicopathologic study of

43 cases. J Forensic Sci 1972; 17: 525– 40.

Sampson HA. Fatal food-induced anaphylaxis. Allergy 1998; 53 (suppl

46): 125– 30.

Schwartz HJ, Yunginger JW, Schwartz LB. Is unrecognized anaphylaxis

a cause of sudden unexpected death? Clin Exp Allergy 1995; 25: 866–

70.

Randal B, Butts J, Halsey JF. Elevated postmortem tryptase in the

absence of anaphylaxis. J Forensic Sci 1995; 40: 208– 11.

Yunginger JW, RN, Squillace DL, et al. Laboratory

investigation of death due to anaphylaxis. J Forensic Sci 1991; 36:

857– 65.

Address correspondence and reprint requests to Kim A. , M.D.,

3 Huguenot Avenue, ton, SC 29407, U.S.A.; email:

collinsk@....

Am J Forensic Med Pathol 2001 September;22(3):292-295

>

> I thought this was important enough to pass along to

> those of you who may not have seen it.

>

> 4/14/06

>

> PANCAKES MADE FROM OLD MIX CAUSE ACUTE ALLERGIC

> REACTION

>

> DEAR ABBY: I recently made a batch of pancakes for my

> healthy 14-year-old son, using a mix that was in our

> pantry. He said that they tasted " funny, " but ate them

> anyway. About 10 minutes later, he began having

> difficulty breathing and his lips began turning

> purple. I gave him his allergy pill, had him sit on

> the sofa and told him to relax. He was wheezing while

> inhaling and exhaling.

>

> My husband, a volunteer firefighter and EMT, heated up

> some water, and we had my son lean over the water so

> the steam could clear his chest and sinuses. Soon, his

> breathing became more regular and his lips returned to

> a more normal color.

>

> We checked the date on the box of pancake mix and, to

> my dismay, found it was very outdated. As a reference

> librarian at an academic institution, I have the

> ability to search through many research databases. I

> did just that, and found an article the next day that

> mentioned a 19-year-old male DYING after eating

> pancakes made with outdated mix. Apparently, the mold

> that forms in old pancake mix can be toxic!

>

> When we told our friends about my son's close call, we

> were surprised at the number of people who mentioned

> that they should check their own pancake mix since

> they don't use it often, or they had purchased it some

> time ago. With so many people shopping at

> warehouse-type stores and buying large sizes of

> pancake mix, I hope your readers will take the time to

> check the expiration date on their boxes. -- SUE IN

> WYANTSKILL, N.Y.

>

> DEAR SUE: Thank you for the warning. I certainly was

> not aware that pancake mix could turn moldy and cause

> an allergic reaction in someone with an allergy to

> mold -- but it's logical. I wonder if the same holds

> true for cake mix, brownie mix and cookie mix. If so,

> then a warning should be placed on the box for people

> like me.

>

> We hear so often about discarding prescription and

> over-the-counter medications after their expiration

> dates, but I don't recall warnings about packaged

> items in the pantry. Heads up, folks!

>

>

> __________________________________________________

>