Gastroallergic anisakiasis: immediate ... - Revista seaic

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Gastroallergic anisakiasis The statistical analysis of the characteristics of the three patient groups suggests that they were composed of similar patients. CHALLENGE TESTS AND LATER DIET Over the time of the study no clearly defined cases were seen of patients having had symptoms either with deep-frozen fish (industrial preparations) or with sufficiently cooked fish preparations. It is an axiom in Allergology that, when doubts arise as to a given allergen being the cause of a given reaction, challenge tests with that allergen are proposed, besides the usual in vitro assessments and skin tests. Live parasites were frozen until they became non-infective. Challenge tests were then performed, initially giving from 11 to 20 parasites to a total of 20 out of the 96 patients, with negative results. The challenge tests were thereupon interrupted, and the remainder of the patients were allowed to eat deep-frozen fish or seafoods; the tolerance was repeatedly checked in successive six-monthly visits and up to the time of writing. In a total of 76 patients so investigated, no problem related to the ingestion of deep-frozen fish has been detected until now. Twenty patients were lost to follow-up, as they did not attend the successive review visits. DISCUSSION In 1995, the conditions caused by Anisakis simplex were differentiated into a number of clinical forms according to the digestive tract region involved. Gastric anisakiasis was caused by stage III larvae; in this particular form the larvae reach the submucosa through the action of peptidases, and induce epigastric pain due to the inflammatory reaction of the viscus wall 13-16 . If the parasite(s) were not extracted, the condition progressed to the subacute or chronic anisakiasis form. The larvae might be able to traverse the gastric or intestinal wall; the parenteral invasive form resulting might cause granulomata or abscessification in association to eosinophilia, fever, diarrhoea and abdominal pain. This situation might mimic acute appendicular episodes, but true appendicitis and episodes of intestinal obstruction had also been reported 17-20 . Infrequent cases of polyarthritis 21,22 and still rarer ones of distant organ invasion (lung, liver, spleen and pancreas) 23 had also been described. In these cases of anisakiasis, both the IgE and the eosinophils had been implicated in the aetiopathogenesis of the local lesions caused by the attachment of the parasites 16,24-29 . In the course of a first contact, the parasitic infestation might induce a mild chronic inflammatory reaction in the mucosa. The acute forms would then be due to type I or type III hypersensitivity reactions in the digestive tract in the course of secondary infestations 16,29,30 . Only occasionally had localised maculopapular lesions and generalised urticaria been reported in these patients 13,23,30 . In Europe, and up to 1996, over 100 cases had been reported in the Netherlands (collected between 1995 and 1968) 3,4,11 ; and there had been occasional case reports in France, the United Kingdom and the USA from 1975 onwards 11,20,31,32 . In Spain, some six cases had been reported between 1991 and 1996; cases of anisakiasis were anecdotal at that time 21,33-35 , but from that year onwards the number of reports increased progressively. In 1995 the Spanish allergologists were made aware of Anisakis-induced disease through cases of allergic reactions after the ingestion of presumably well-cooked fish with positive skin tests and specific IgE to Anisakis while the studies were negative for the fish supposedly involved in the reaction 36-41 . The reports of Anisakis simplex sensitisation multiplied, and some confusion arose regarding the value of some positive tests in patients describing no allergic reaction at all, and of course no previous infestation by Anisakis simplex (ca. 13%). For some authors, the basis of Anisakis simplex allergy was to be found in the heatstability of some antigens of the parasite, which would be able to bind to the patients’ IgE and trigger hypersensitivity symptoms upon the ingestion of cooked fish 38-40 . After having observed a number of cases of anaphylaxis associated to Anisakis simplex infestation 42 , a prospective study was initiated at the "La Paz" University Hospital in Madrid. Over a period of 18 months 120 patients were assessed, who had consulted because of allergic symptoms (in many cases life-threatening anaphylaxis or anaphylactic shock); in 96 of them Anisakis simplex was truly implicated in the reactions 43-49 . The associated digestive symptoms were mild or moderate in most patients, and for this reason only 47 patients underwent endoscopy. To our surprise, over those 18 months, and based on the allergic symptoms, 24 patients were detected in whom one or more parasites were removed from their stomachs (almost more parasites found over a period of 18 months than in the whole of the Spanish literature between 1991 233
M. a C. López Serrano, et al and that time). The very typical "boquerón en vinagre" (vinegar-marinated anchovies) and in some cases presumably well-cooked fresh hake were the sources of most infestations. The latency period of the allergic symptoms was quite variable, ranging between a few minutes and over 24 hours. The average latency for the digestive symptoms was similar, although they tended to occur slightly earlier. No endoscopy was performed when the digestive symptoms had already subsided at the time of seeing the patient. The total serum IgE and the specific IgE were found to be significantly increased one month after the index contact 45,47,48 . The statistical analyses suggested that the study population was formed by similar patients, in whom in some cases the parasite became attached to the gastric mucosa for a time sufficient for triggering the allergic reaction; however, its trend to then detach and be expelled does not allow it to be detected in time at endoscopy. The authors termed this particular condition gastroallergic anisakiasis" 42-51 , differentiating it from gastric anisakiasis, as the hypersensitivity symptoms after contact with the parasite were more intense and severe than the gastric ones. However, in the course of the study period and also in a review of previous suggestive cases from our Hospital no cases were detected in which symptoms had arisen after consuming industrially deep-frozen or sufficiently cooked fish. In the light of this observation, it would appear that in most cases the live parasite had been the antigen source, and furthermore, that the parasite required attachment to the submucosa in order to elicit the hypersensitivity reaction. At this point in time, true allergy to heat-stable proteins of Anisakis simplex appeared to be less frequent than previously supposed, and it was thought that the IgE-mediated response corresponded, in most of the sensitised patients, to previous contacts with the live parasite (transient infestation either in the luminal form or clinically asymptomatic). Adhering to the diagnostic procedure usually applied in Allergology whenever there is doubt about a given antigen as the cause of a given reaction, the next step in these patients with gastroallergic anisakiasis was challenge testing with non-infective frozen parasites 50 . Tolerance was confirmed in a number of patients, and from then onwards the remainder of the patients were allowed to eat deep-frozen fish, with no untoward problems arising. The immunologic and inflammatory response to the parasite may explain most of the clinical symptoms and signs in anisakiasis. The parasite avails itself of proteases in order to achieve attachment to the gastrointestinal mucosa. It is quite possible that local factors such as preexisting mucosal lesions, changes in gastrointestinal motility or changes in the environmental pH may influence not only the parasite’s ability to become attached but also the duration of such attachment end even the possibility –rather more remote, but already reported– of transmucosal penetration. Once attached to the submucosa, the secretion of proteins by the parasite sets in motion the defensive response of the rich gastrointestinal lymphoid tissue. The type of anti-parasite response in this case is predominantly Th2. Thus, the expression pattern of cytokines such as IL-4 and IL-5 leads to chemotactic attraction of eosinophils and to intestinal lymphoid tissue hyperplasia and also to a stimulation to IgE production, with the subsequent increase of the total and parasite-specific IgE levels 16,24-29,48 . Other immunoglobulins are also produced and may in some cases lead to immune-complex-mediated responses. The symptomatology of anisakiasis would be mediated mainly by this inflammatory response and in some cases by the penetration of the parasite. If the response is maintained only in the local gastric environment, acute gastric anisakiasis will ensue. Further to this, the already initiated immune response may induce distant hypersensitivity symptoms mediated by IgE –and therefore allergic–, which seem to be rather frequent: gastro-allergic anisakiasis. Immune complexes might explain the articular manifestations sometimes observed but, in the light of the published reports, are rather infrequent. Subacute or chronic anisakiasis is usually seen at the intestinal level, and the inflammation (even though the parasite may have already been expelled with the faeces) may induce mucosal changes leading even to an acute abdomen. If the parasite still remains within the digestive tract wall, or even achieves its penetration, surgery will be required in most of these cases. In very rare cases, penetration of the parasite leads to its apparition in exceptional locations such as the lung, the liver, the spleen or the pancreas. In the cases of subacute or chronic anisakiasis, distant hypersensitivity manifestations are infrequent. The previous history of fish or seafood ingestion, the clinical manifestations, the endoscopic and radiologic examination, the response to the skin tests and the serial measurements of the specific IgE Anisakis simplex antibodies are important clues for the diagnosis. Cases may exist of true Anisakis simplex allergy but, in the light of the results of this prospective study, they 234
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Gastroallergic anisakiasis: immediate ... - Revista seaic

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