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. Once sensitized, PHO re-exposure will booster IgE antibody levels and IgE by around 100-fold. PHO is monovalent for 2 non-cross-reacting epitopes the quaternary ammonium ion (QAI), the main allergenic epitope of NMBA, and a non-QAI epitope. Thus, PHO most unlikely would initiate an allergic inflammatory response. Consequently, IgE sensitization is not revealed by obvious clinical signs, neither through tests based on IgE-sensitized effector cells. Therefore, it will escape detection if not assayed serologically. However, when subjected to general anesthesia, and thus the IgE-sensitized individual is administered a bivalent NMBA intravenously, the unrecognized presence of serum IgE antibodies to QAI may increase the risk of anaphylaxis 200- to 300-fold. Severe damages to patient's health can result, and mortality rates of 3 to 10% are reported. The Scandinavian experience indicates that the chain of events can efficiently be avoided by stopping PHO exposure: Within 1 year, the prevalence of IgE sensitization to PHO and QAI decreases significantly, and after 2 to 3 years, the numbers of reported anaphylactic reactions decreases equally so

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. Eight-week-old BALB ⁄ c mice were randomly divided into three groups: OVA, OVA 323-339 and saline. On days 0, 7, 14, mice were intraperitoneally injected with 25 lg OVA or OVA 323-339 absorbed on 300 lg Alum, or saline; on days 21–23, all groups were challenged intranasally with either 20 ll of 1% OVA, 1% OVA 323-339 or saline. On day 28, after killing, splenocytes were isolated and cultured under the stimulus of each allergen or medium. Evaluated by hematoxylin ⁄ eosin and major basic protein immunohistochemical stainings, OVA and OVA 323-339 induced similar lung inflammation. Interestingly, significant serum total IgE and OVA-specific IgE were observed in OVA mice when compared to saline control. OVA 323- 339 mice showed higher serum OVA-specific IgE, OVA 323-339-specific IgE, IL-4 and lower IFN-c similar to OVA mice. The proliferative response to OVA was found in cultured splenocytes of both OVA and OVA 323-339 mice, while the similar proliferative response to OVA 323-339 was only observed in the splenocytes of OVA 323-339-sensitized and challenged mice. Although OVA 323-339 induced a Th2-like response in the mouse model as did OVA, OVA 323-339 has clearly limited immunogenic potency to activate OVA-sensitized and challenged mice splenocytes, unlike OVA

High prevalence of immunoglobulin E [IgE] sensitization among sisal [Agave sisalana] processing workers in Tanzania

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. 138 sisal exposed workers and 78 non-exposed controls were skin prick tested (SPT) using dry sisal extract and fresh sisal sap. Sera from a subset of 43 participants were analyzed for total and sisal specific IgE. SPT wheal size, prevalence of positive SPTs and adjusted relative risk (RR) for sisal sensitization were determined and compared between exposed and controls. Prevalences for respiratory symptoms were compared between sensitized and non-sensitized sisal workers. Significantly higher prevalence of positive SPTs to sisal was found among 74 % of sisal workers compared to 17 % among controls. Compared to controls, the RR of sensitization to sisal was 4 times higher (95 % CI; 2.4-6.7) among exposed workers. All exposed workers had elevated IgE levels (>100 kU/l) and 27 % of tested sera had elevated sisal specific IgE. A high prevalence of respiratory symptoms was found in both sensitized and non-sensitized sisal workers. Sisal processing is associated with increased risk of IgE sensitization, but its clinical implication is not obvious