Anisakis simplex as a risk factor for relapsing acute urticaria: a case–control study H Falca ˜o, 1,2 N Lunet, 1 E Neves, 3 I Igle ´sias, 3 H Barros 1 1 Department of Hygiene and Epidemiology of the Porto University Medical School, Portugal; 2 Imunoalergology Unit of the Maria Pia Hospital, Porto, Portugal; 3 Clinical Pathology Department of the Maria Pia Hospital, Porto, Portugal Correspondence to: Dr N Lunet, Servic ¸o de Higiene e Epidemiologia, Faculdade de Medicina da Universidade do Porto, Al Prof Herna ˆni Monteiro, 4200-319 Porto, Portugal; nlunet@med.up.pt Accepted 3 October 2007 ABSTRACT Background: IgE-mediated hypersensitivity reactions to Anisakis simplex have been described after ingestion of fish, suggesting that sensitisation to this parasite may induce acute urticaria and anaphylaxis. Anisakis simplex allergens are highly resistant to heat and freezing, and sensitisation may occur even in populations with low consumption of raw/undercooked fish. This study aimed to quantify the association between sensitisation to A. simplex and relapsing acute urticaria. Methods: This is the first case–control study on this topic. Cases (n = 200) were patients with a clinical diagnosis of relapsing acute urticaria, consecutively approached at the immunoallergology unit of Porto’s largest paediatric hospital. Controls (n = 200) were consecutively selected at the surgery department of the same hospital, from subjects undergoing programmed orthopaedic, maxillofacial or general surgical procedures. Specific IgE measurements (Anisakis and Ascaris) were taken, and skin-prick tests (A simplex, common aero- allergens, fish, and Ascaris) were done. Results: Sensitisation to A simplex (OR 3.86, 95% CI 2.04% to 7.29%), Ascaris (OR 3.37, 95% CI 1.89% to 6.02%), fish (OR 4.62, 95% CI 1.85% to 11.52%), and at least one aeroallergen (OR 4.59, 95% CI 2.99% to 7.05%) were associated with increased risk of acute urticaria. Regarding the sensitisation to A simplex, the aeroallergen sensitisation-adjusted OR was 2.61 (95% CI 1.33% to 5.12%) for the whole sample, and 2.72 (95% CI 0.99% to 7.47%) for those not sensitised to Ascaris or fish. Conclusion: Sensitisation to A simplex increases the risk of relapsing acute urticaria in subjects not sensitised to Ascaris or fish, and this is independent of aeroallergen sensitisation. Anisakis simplex is a parasitic nematode of the Anisakidae family. The life cycle involves larval stages, as intermediate hosts, in fish and cepha- lopods, such as cod, sardine, tuna, mackerel and squid, and an adult stage, during which the worm parasitises the stomach of marine mammals. Humans can became accidental hosts after eating raw or undercooked fish, or seafood that contains the third-stage larvae of A simplex. After inges- tion, larvae can be invasive, penetrating the digestive tract and producing a disease, known as anisakidosis or anisakiasis. 1 However, the A simplex allergens are highly resistant to heat and freezing; though cooking is expected to kill the parasites it may not result in loss of their allergenicity, 2 and sensitisation may occur even in populations with low consumption of raw or undercooked fish, 34 or after the ingestion of other foods contaminated with Anisakis species allergens. 5 Immunoglobulin E-mediated hypersen- sitivity reactions to Anisakis simplex have been described after the ingestion of fish, 6–9 suggesting that sensitisation to this parasite may induce acute urticaria and anaphylaxis. Considering the worldwide increase in fish consumption, and that a large proportion of the commercial fish is infected, 10 A simplex has the potential to become an important determinant of allergic reactions otherwise classified as food allergies. It may be hypothesised that parasitic allergens, and specifically A simplex, are responsible for cases of chronic and relapsing acute urticaria frequently labelled as idiopathic. Therefore, we conducted the first case–control study to quantify the association between sensitisation to A simplex and relapsing acute urticaria. METHODS We performed a hospital-based case–control study in children and adolescents aged 6 to 18 years, comprising 200 cases and 200 controls. Cases were consecutively approached during a visit to the immunoallergology unit of the largest paediatric hospital in Porto. Patients with a clinical diagnosis of acute urticaria, having at least three episodes in the previous two years were eligible. Controls were consecutively selected at the surgery department of the same hospital, among subjects admitted for programmed orthopaedic, maxillofacial, or general surgical procedures. Children undergoing otorhino- laryngologic surgery were not eligible. No refusals were observed. Sample size was estimated for a 95% confidence level and a power of 80%, assuming a 1:1 ratio of controls to cases, and a proportion of participation between 95% and 100%. It allows for the detection of a difference in the prevalence of sensitisation between cases and controls corresponding to an odds ratio (OR) of 3, if the prevalence of exposure among the controls is 5%, or corresponding to an OR of 2, if 20% of the controls are sensitised. The local ethics committee approved this study, and the parents of all participants signed an informed consent form. Skin-prick tests were performed and interpreted by the same experienced allergist (HF) according to standard procedures, 11 using the following allergen extracts: A simplex (2 mg/ml), Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat dander, dog dander, mixed grass, Sebastes marinus, blue fish, and white fish, all from ALK-Abello ´; and Ascaris, whiting, codfish, tuna, salmon, and sardine from BIAL-Aristegui. Research report 634 J Epidemiol Community Health 2008;62:634–637. doi:10.1136/jech.2007.061572