Pholcodine, perioperative anaphylaxis, and the European Medicines Agency: finally the decision to remove pholcodine from the market in the European Union.

Two recent case-control studies, both published in the British Journal of Anaesthesia, have shown that intake of pholcodine-containing cough medicines during the year preceding general anaesthesia significantly increased the risk of anaphylaxis caused by neuromuscular blocking agents. Both a French multicentre study and a single-centre study from Western Australia offer strong support to the pholcodine hypothesis for IgE-sensitisation to neuromuscular blocking agents. The European Medicines Agency, criticised for not taking preventive action at its first assessment of pholcodine in 2011, finally recommended a stop to sales of all pholcodine-containing medicines throughout the EU on December 1, 2022.

Six years without pholcodine; Norwegians are significantly less IgE-sensitized and clinically more tolerant to neuromuscular blocking agents.

Background: As a strong inducer of IgE antibodies to substituted ammonium ion epitopes (QAI), pholcodine (PHO) is a postulated cause of allergic anaphylaxis to neuromuscular blocking agents (NMBAs). Three years after withdrawal of PHO in Norway, a significant reduction in IgE sensitization and anaphylaxis reporting was seen.

Objective: Six-year follow-up study on the effects of PHO withdrawal on IgE sensitization and anaphylaxis reporting.

Functional Gastrointestinal Symptoms Are Associated with Higher Serum Total IgE Levels, but Less Atopic Sensitization.

Background: The relation of gastrointestinal (GI) complaints to IgE-mediated allergy is not well understood. Increased numbers of "IgE-armed" mast cells have been observed in duodenal mucosa of patients with functional GI complaints.

Aims: To explore whether total IgE and atopic sensitization were associated with functional GI complaints.

Pholcodine consumption and immunoglobulin E-sensitization in atopics from Australia, Korea, and Japan.

Background: Accumulating data indicates that pholcodine (PHO)-consuming countries have higher sero-prevalences of immunoglobulin E (IgE)-antibodies to PHO and suxamethonium (SUX) and increased frequencies of IgE-mediated anaphylaxis to neuromuscular blocking agents (NMBAs) than nonconsuming. Withdrawing PHO-containing cough syrups resulted in a significant decrease of cases with anaphylaxis in Scandinavia. Nevertheless, the European Medicines Agency in 2011 advised to continue the unrestricted use throughout the European Union.

An extended study of seroprevalence of anti-Anisakis simplex IgE antibodies in Norwegian blood donors.

During the last decade, cases of the fish parasite Anisakis simplex infection and allergy in human have increased in countries with high fish consumption. Our aim was to perform an extended seroprevalence study of anti-IgE antibodies against this parasite in Norway, one of the high fish-consuming countries. At the Department of Immunology and Transfusion Medicine and the Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway, two main groups of anonymized serum samples were collected; the first (n = 993) from recently recruited blood donors (designated 'BDO') and the second (n = 414) from patient with total IgE levels ≥1000 kU/l (designated 'IGE+').

The Pholcodine Case. Cough Medicines, IgE-Sensitization, and Anaphylaxis: A Devious Connection.

: The Scandinavian data on pholcodine (PHO) strongly indicates that there is a biological chain from PHO exposure through IgE-sensitization to IgE-mediated anaphylaxis to neuromuscular blocking agents (NMBA). PHO is probably one of the strongest inducer of an IgE antibody response known. Of individuals taking PHO in cough medicines, over-the-counter accessibility to large populations, as many as 20 to 25% may become IgE sensitized.

IgE sensitization to the fish parasite Anisakis simplex in a Norwegian population: a pilot study.

The reports on fish parasite Anisakis simplex allergy have increased in countries with high fish consumption in the last decade. In Norway, a high consumption country, the prevalence of immunoglobulin E (IgE) sensitization to A. simplex was still unknown.

Perceived food hypersensitivity: a review of 10 years of interdisciplinary research at a reference center.

Perceived food hypersensitivity is a prevalent, but poorly understood condition. In this review article, we summarize narratively recent literature including results of our 10 years' interdisciplinary research program dealing with such patients. The patients (more than 400) included in our studies were all adults referred to a university hospital because of gastrointestinal complaints self-attributed to food hypersensitivity.

Clinical characteristics of patients with drug hypersensitivity in Norway: a single-centre study.

Background: Drug hypersensitivity reactions (DHRs) represent an important public health problem. Knowledge of their clinical characteristics will provide improved diagnostic approaches to this topic.

Objectives: The aim of the present study was to describe the clinical characteristics of patients with suspected DHRs.

IgE-sensitization to the cough suppressant pholcodine and the effects of its withdrawal from the Norwegian market.

Background: IgE-mediated anaphylaxis to neuromuscular blocking agents (NMBA), frequent in Norway, was proposed to be caused by exposure to pholcodine (PHO) carrying the allergenic quarternary ammonium ion epitope. Consequently, the PHO-containing drug was withdrawn from the market in March 2007.

Objective: Describe the effects of withdrawal of PHO on IgE, IgE-antibodies and reported frequencies of anaphylaxis to NMBAs.

Comparison between ovalbumin and ovalbumin peptide 323-339 responses in allergic mice: humoral and cellular aspects.

Ovalbumin (OVA) is widely used in allergy research. OVA peptide 323-339 has been reported to be responsible for 25-35% of isolated BALB/c mouse T-cell response to intact OVA. An investigation of whether OVA and OVA 323-339 molecules can induce equivalent in vivo and in vitro immune responses was conducted.

[Anaphylaxis during anaesthesia].

Background: Anaphylaxis is a serious life-threatening generalized or systemic hypersensitivity reaction. The aim of this paper is to provide knowledge on how to diagnose, treat and follow up patients with suspected anaphylaxis during general and local anaesthesia.

Material And Methods: The article is based on literature identified through a non-systematic search in PubMed, the Scandinavian Guidelines on anaphylaxis during anaesthesia and on own research.

Indications of 'atopic bowel' in patients with self-reported food hypersensitivity.

Background: An association between atopic disease and gastrointestinal complaints has been suggested.

Aim: To explore the association between atopic disease, gastrointestinal symptoms, and possible gastrointestinal manifestations of atopic disease in patients with self-reported food hypersensitivity.

Methods: Symptoms, skin prick tests, serum markers of allergy and intestinal permeability were recorded in 71 adult patients.

Anxiety and depression in patients with self-reported food hypersensitivity.

Objective: Self-reported food hypersensitivity (SFH) is common. Psychological factors are assumed to be associated. We assessed anxiety and depression in SFH patients, using both questionnaires and interview.

Suspected allergy to local anaesthetics: follow-up in 135 cases.

Background: Local anaesthetics (LA) are generally considered safe with respect to allergy. However, various clinical reactions steadily occur. Even though most reactions are manifestations of reflexes to perceptive stimuli, uncertainty often remains regarding a possible allergic mechanism.

National pholcodine consumption and prevalence of IgE-sensitization: a multicentre study.

Background: The aim of this study was to test, on a multinational level, the pholcodine (PHO) hypothesis, i.e. that the consumption of PHO-containing cough mixtures could cause higher prevalence of IgE antibodies to PHO, morphine (MOR) and suxamethonium (SUX).

Effects of industrial processing on the immunogenicity of commonly ingested fish species.

Background: Food-processing techniques may induce changes in fish protein immunogenicity. Allergens from >100 fish species have been identified, but little is known on the effects of processing on fish protein immunogenicity.

Methods: IgE binding of sera of patients allergic to fresh and processed (smoked, salted/sugar-cured, canned, lye-treated and fermented) cod, haddock, salmon, trout, tuna, mackerel and herring and of hydrolysates based on salmon and whiting was investigated using immunoblot and inhibition ELISA.

The pholcodine story.

Anaphylactic reactions to neuromuscular blocking agents during general anesthesia constitute a major cause of concern and a great source of debate among anesthesiologists. The authors' recent investigations, taking the striking differences of incidence between Norway and Sweden as the point of departure, have provided valuable insights into the pathogenetic mechanisms and the highly uneven geographical distribution of these rare, but dramatic and notoriously unpredictable, events. Eventually, a cough syrup containing pholcodine emerged as the most likely suspect.

Occupational allergy to Artemia fish fry feed in aquaculture.

Background: Artemia (brine shrimp) is used as feed for fish fry and shrimp in aquaculture. Two employees in a Norwegian aquaculture research farm reported having chest symptoms when working in an Artemia hatch room.

Aims: To determine the presence and prevalence of Artemia sensitization at the farm and the extent of any Artemia-related respiratory and hand skin symptoms and to identify the allergens involved.

High prevalence of immunoglobulin E (IgE) sensitization among sisal (Agave sisalana) processing workers in Tanzania.

Purpose: Allergic sensitization among workers exposed to sisal is scarcely documented. We examined whether sisal processing is associated with IgE sensitization and its relationship to the prevalence of respiratory symptoms among Tanzanian processors.

Methods: 138 sisal exposed workers and 78 non-exposed controls were skin prick tested (SPT) using dry sisal extract and fresh sisal sap.