A. AlonsoA. Moreno-AncilloA. DaschnerM.C. Lo pez-Serrano

Authors' af®liations:

A. Alonso, A. Moreno-Ancillo, A. Daschner,

M.C. Lo pez-Serrano, Section of Allergy, ``La Paz''

General University Hospital, P8 de la Castellana

261, 28046 Madrid, Spain

Correspondence to:

Dr Alvaro Moreno-Ancillo

SeccioÂn de Alergia

Hospital General Universitario ``La Paz''

Paseo de la Castellana 261

28046 Madrid

Spain

Date:

Accepted for publication 18 December 1998

To cite this article:

Alonso A., Moreno-Ancillo A., Daschner A., Lo pez-

Serrano M.C. Dietary assessment in ®ve cases of allergic

reactions due to gastroallergic anisakiasis.

Allergy 1999, 54, 517±520.

Copyright # Munksgaard 1999

ISSN 0105-4538

Short communication

Dietary assessment in ®vecases of allergic reactions dueto gastroallergic anisakiasis

Anisakis simplex is a nematode of the Anisakidae family,

Ascaridoidea superfamily, Ascaridida order, that in its adult

Key words: allergy; Anisakis simplex; Anisakis simplex allergy;

challenge; gastroallergic anisakiasis; seafood.

Background: Anisakis simplex can cause allergic reactions in

sensitized patients. Some of these reactions are related to acute

parasitism, as is shown in gastroallergic anisakiasis (anisakiasis

with digestive and predominantly allergic symptoms). At

present, a nonseafood diet is recommended for all patients

with any kind of A. simplex allergy. We wished to con®rm the

clinical suspicion that patients with allergic symptoms after

ingestion of raw or undercooked seafood who are sensitized to

A. simplex, and diagnosed with gastroallergic anisakiasis, can

tolerate the ingestion of seafood when the parasites are dead

and noninfective.

Methods: We included patients diagnosed with gastroallergic

anisakiasis (positive skin prick test or/and serum speci®c IgE to

A. simplex, with one or more parasites found by gastroscopy in

the stomach). Patients included in the study gave written,

informed consent. Specimens of A. simplex about 2 cm long

were selected, placed in capsules, and frozen at ±208C for more

than 48 h to make them noninfective. We administered 11

specimens to every patient at the hospital. If they tolerated the

larvae, they were told to eat well-frozen seafood (±208C at least

48 h). After 6 months, the patients were re-evaluated.

Results: Five patients accepted the challenge with noninfective

A. simplex larvae. All tolerated the noninfective larvae. After

eating deep-frozen seafood for 6 months, no patient suffered a

reaction.

Conclusions: In gastroallergic anisakiasis, the antigens of the live

parasite probably cause the allergic symptoms. Patients with this

disease can tolerate deep-frozen seafood, in which the parasites

are dead.

517

stage parasitizes sea mammals. The common intermediary

host species are cod®sh, hake, sardine, anchovy, salmon, red

mullet, tuna, mackerel, horse mackerel, and squid (1). In

these intermediary hosts, the larvae enter the third stage.

The ingestion of third-stage Anisakidae larvae in raw or

undercooked seafood may cause the human disease known

as anisakiasis or anisakidosis (2±10). After ingestion, A.

simplex larvae can attach themselves to gastric mucosa

(acute anisakiasis), or penetrate the host stomach or

intestinal wall (chronic anisakiasis). In the latter form, the

invasion causes abscesses or eosinophilic granulomas. This

form is rare, and can mimic appendicitis, gastroduodenal

ulcer, eosinophilic colitis, in¯ammatory bowel disease, and

intestinal obstruction (2±6). Some rare cases of anisakiasis

affecting the lung, spleen, pancreas, and liver have been

reported (4). Because of the national eating habits, anisa-

kiasis is common in Japan (2, 4±9). In Europe, several cases

have been reported over the years (3, 10±18).

The larvae of A. simplex cannot survive a temperature

higher than 608C for 10 min, or lower than ±208C for 48 h

(19). However, the ingestion of safely cooked sea ®sh,

without viable larvae, has been reported to cause allergy

(20±24). In such cases, the allergy to the parasite is avoided

by a seafood-free diet.

It is believed that allergic reaction plays a role in the

pathogenesis of anisakiasis (7±9). We have described a form

of anisakiasis with severe allergic symptoms (17). This

gastroallergic form includes allergic and gastric symptoms

after contact with live parasites, which disappear after

removal of the worms by gastroscopy. However, purely

gastrointestinal anisakiasis has marked digestive symptoms

without allergic symptoms.

Until now, allergists recommended a seafood-free diet for

both kinds of patients, i.e., those with A. simplex allergy and

those with gastroallergic anisakiasis; however, many of the

patients with gastroallergic anisakiasis went on eating

seafood, mainly well cooked or frozen, without problems.

After considering this fact and our patients with gastro-

allergic anisakiasis who suffered allergic reactions only after

ingesting live parasites, we decided to determine the correct

diet for these patients by performing food challenge with the

seafood involved in their reactions and with noninfective

larvae of A. simplex.

Material and methods

Patients

We selected patients diagnosed with gastroallergic anisa-

kiasis (allergic symptoms, such as urticaria, bronchospasm,

angioedema, or anaphylaxis; and digestive symptoms, such

as epigastric pain and, in some cases, nausea, vomiting

and diarrhea) less than 24 h after the ingestion of raw

or undercooked seafood, with detection of one or more

A. simplex larvae in gastric mucosa by ®beroptic gastro-

scopy (Fig. 1). All patients were sensitized to A. simplex.

Skin testing was performed with A. simplex extract (I.P.I.

Pharmaceutical, Madrid, Spain) sea ®shes, cephalopods, and

other seafood involved in the reaction. Serum speci®c IgE

was determined against the implicated seafood and

A. simplex by the CAP System (Pharmacia Diagnostics,

Uppsala, Sweden). All patients showed positive SPT and

serum speci®c IgE to A. simplex and were negative to any

seafood (Table 1).

Five patients gave written, informed consent to carry out

the challenge.

Methods

We performed two types of food challenge. The ®rst

challenge was performed with 11 noninfective A. simplex

larvae which had been frozen at ±208C for 48 h, and the

second challenge with the seafood involved in their

reactions, after freezing at ±208C for 48 h. The challenges

were performed single-blind vs placebo (Table 1).

We obtained the larvae from anchovy, hake, and blue

whiting. We selected worms about 2 cm long. They were

identi®ed as A. simplex larvae by the microbiology service of

our hospital, who listed the following characteristics for

identi®cation: three bilibed lips, one dorsal and two

Figure 1. Third-stage larval A. simplex attached to gastric mucosa.

Alonso et al . Dietary assessment in gastroallergic anisakiasis

518 | Allergy 54, 1999 / 517±520

ventrolateral; a boring tooth projecting anteroventrally,

ventral to the mouth; a simple digestive tube; distinctive

Y-shaped lateral chords; and no lateral alae extending from

the cuticle. Then we separated the larvae, and introduced

them into capsules, where they were frozen for 48 h at

±208C. The patients swallowed capsules with one, four, and

six larvae, with a 1-h interval, and they remained at the

hospital for 6 h after the last administration. If no symptom

appeared, they were told that they could eat deep-frozen

seafood until the next visit. If there was no allergic reaction,

the challenged patients were seen again after 6 months.

Results

Five patients were included in the study. Their characteristics

are shown in Table 1. All of them tolerated both challenges

without any allergic or gastric symptom. After 6 months, no

reaction had been reported, and all of them had eaten seafood

at least once a week, according to our recommendation; that

is, deep-frozen. Skin prick testing and serum speci®c IgE were

still positive in all patients after 6 months.

Discussion

Gastroallergic anisakiasis is a form of acute anisakiasis,

with allergic and gastric symptoms, that has usually been

misdiagnosed. In large series of patients, Japanese authors

ascribed marked importance to the local allergic reaction in

gastric mucosa (5±9), but the only therapy for acute

anisakiasis is endoscopic removal of the larvae. The

treatment of chronic anisakiasis (gastric or intestinal) is

surgery. No drugs have been able to destroy the larvae.

In A. simplex allergy, most allergists recommend a

nonseafood diet, because it is impossible to know whether

a piece of ®sh contains the parasite or not. The thermo-

stability of some A. simplex allergens has previously been

con®rmed, and this explains the allergic manifestations

after ingestion of cooked or frozen seafood (20±24).

In gastroallergic anisakiasis, allergic symptoms after the

attachments of live worms are manifestations of allergy to

antigens of the live parasite. Gastroscopy and clinical ®ndings

showed that these patients become sensitized to the Anisakis

allergens in response to being parasitized (8, 9, 17).

The challenge with A. simplex or infected seafood to

assess the true clinical implication of a positive skin prick

test or serum speci®c IgE has been considered unethical.

However, since the sea ®sh of all ®shing grounds are infested

by nematodes (25), many people ingest larvae every day. In

Spain, the incidence of infected ®sh is 37.7% of samples in

the Madrid markets (26). Hake is the most parasitized North

Sea ®sh, with an infection rate of 45% in the north of Spain

(25), and an intensity (parasites per ®sh) of 12±63 in studies

from Spain and Italy (19, 25, 27).

On the other hand, we had patients diagnosed with

gastroallergic anisakiasis who did not follow a correct diet,

but allergic episodes appeared again only after they ate raw

or undercooked food. In addition, although heated or deep-

frozen seafood can cause allergic reactions due to the

sensitization to thermostable antigens of A. simplex, in

gastroallergic anisakiasis, the patients are probably sensi-

tized to other A. simplex antigens, such as the secretor

antigens. All these facts were investigated in the present

work by performing a challenge with noninfective deep-

frozen parasites. A food challenge with noninfective

A. simplex is an ethical solution in those patients who

have been diagnosed with gastroallergic anisakiasis.

The results of these challenges and the evolution of the

challenged patients after 6 months support our thesis. No

patient suffered any reaction to noninfective larvae. Those

patients with gastroallergic anisakiasis had allergic reac-

tions only after ingestion of the live parasite, a fact which is

very important for a correct dietary assessment.

Further in vitro investigations are needed to determine the

immunologic basis of these clinical ®ndings.

Table 1. Characteristics of challenged patients

Name Age(years)

Sex Seafood SPT IgE-As Gastroscopy Aschallenge

Seafoodchallenge

VIsit at 6months

MDH 58 F Anchovy + 100 ku/l 1 As larva Negative Negative No problems

FYM 59 M Hake + 86.9 ku/l 1 As larva Negative Negative No problems

SHR 46 M Hake + 12.2 ku/l 2 As larvae Negative Negative No problems

EFS 27 F Anchovy + 2.16 ku/l 1 As larva Negative Negative No problems

ARM 19 F Anchovy + 2.84 ku/l 1 As larva Negative Negative No problems

As: Anisakis simplex; SPT: skin prick test. Anchovy was taken raw in vinegar sauce. Hake was taken undercooked.

Alonso et al . Dietary assessment in gastroallergic anisakiasis

Allergy 54, 1999 / 517±520 | 519

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