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. METHODS: From 650 acute consecutive reports (2005-2013) to the Norwegian Network for Anaphylaxis under Anaesthesia (NARA), total number of reports on suspected anaphylactic reactions, number of reactions where NMBAs were administered, number of reactions where serum IgE antibodies (≥0.35 kUA /l) to suxamethonium (SUX) and PHO were present at time of reaction and anaphylaxis severity grades were retrieved. In addition, NMBA sales and prevalence of IgE sensitization to PHO and SUX among 'allergics' were monitored. RESULTS: From baseline period P0 (PHO on the market) through the first (P1) and second (P2), three-year periods after withdrawal, significant falls in total reports (P < 0.001) and reports with IgE antibodies to PHO (P = 0.008) and SUX (P = 0.001) at time of reaction were found. Total NMBA sales in P2 were 83% of P0, and SUX and rocuronium (ROC) together made up 86% of sales throughout the study. Five NMBA-related anaphylactic deaths occurred during P0 and P1 and, however, none during P2. Prevalence of IgE sensitization to SUX in 'allergics' fell to 0% at 4 and 5 years after withdrawal. CONCLUSIONS: Six years after PHO withdrawal, the Norwegian population has become significantly less IgE-sensitized and clinically more tolerant to NMBAs.

Intravenous fluorescein as a cause of immunoglobulin E-mediated anaphylactic shock.

We report a patient with severe anaphylactic shock immediately after injection of i.v. fluorescein. The patient recovered without sequela. Immunoglobulin E (IgE) mechanism was highly suggestive with significant increase in serum tryptase, positive basophil allergen threshold sensitivity (CD-sens) and histamine release tests towards fluorescein. This is, to our knowledge, the first report where CD-sens has been used to aid in diagnosing an IgE-mediated anaphylactic shock caused by fluorescein.

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. METHODS: Three hundred sera from supposedly allergic patients sampled yearly through 2006 to 2010 were analysed for IgE antibodies to PHO, suxamethonium (SUX) and morphine (MOR). Furthermore, IgE and preliminary reports from the Norwegian Network for Anaphylaxis under Anaesthesia (NARA) were monitored. RESULTS: PHO exposure was associated with IgE sensitization to PHO, MOR and SUX. However, after withdrawal, within 1 year, antibody prevalences to PHO and SUX fell significantly from 11.0% to 5.0% and from 3.7% to 0.7%, respectively. At 3 years, SUX had fallen to 0.3%, PHO to 2.7% and MOR to 1.3%. By 2 years, the prevalence of elevated IgE was significantly reduced. After 3 years, the incidence of reported suspected anaesthetic anaphylaxis fell significantly, both the total number, the reactions related to NMBAs and those with IgE antibodies to SUX. CONCLUSIONS: Withdrawing of PHO lowered significantly within 1-2 years levels of IgE and IgE antibodies to PHO, MOR and SUX, and, within 3 years, the frequency of NMBA suspected anaphylaxis. The results strengthen the PHO hypothesis considerably and equally the need to question the existence of cough depressants containing PHO.