Chewing-Gum Preservative Induced Toxidermic Vasculitis

This paper reports the case of a young female patient who presented with a cutaneous urticarial disseminated eruption. Drug-induced side effects were eliminated, and the only recent dietary change was the regular use of chewing-gums containing chlorophylla (E140), menthol and BHT (butylhydroxytoluene). Immunohistological analysis of a cutaneous lesion revealed signs of vasculitis. Within 1 week after stopping chewing gum, the eruption subsided. Oral provocation tests at 4-day intervals confirmed the responsibility of BHT by the reinduction of the cutaneous signs after a few hours.     

Surimi and native codfish contain a common allergen identified as a 63-kDa protein

We have compared the allergenicity of codfish and surimi (prepared from codfish) by skin testing, specific IgE-RIA, and leukocyte histamine release (LHR) in six fish-allergic patients. Prick tests were positive for codfish and, to a lesser extent, surimi. The percentages of labeled anti-IgE bound to surimi-Sepharose were 1.55 ± 0.19% and 3-6% with control and patient sera, respectively. Inhibition of the surimi protein-Sepharose IgE-RIA was greatest (80%) at protein concentrations of 13.4 and 408.5 μg/ml for codfish and surimi extract, respectively. The allergenic protein was isolated by gel filtration and subjected to SDS-PAGE. The eluate from codfish contained several proteins ranging from 13 to 63 kDa, while the eluate from surimi contained a single 63-kDa protein. It was concluded that surimi contained a single allergenic protein.
Mata E, Favier C, Moneret-Vautrin DA, Nicolas JP, Han Ching L, Guéant JL. Surimi and native codfish contain a common allergen identified as a 63-kDa protein.     

Hyperglobulinemia E syndrome with recurrent infections (Job's syndrome)

INTRODUCTION: To provide definition and nosology of hyperimmunoglobulinemia E previously termed Job's syndrome or Buckleys' syndrome in the literature. Generalization of IgE dosages makes it more commonly diagnosed, though sometimes diagnosis may not be accurate. CURRENT KNOWLEDGE AND KEY POINTS: The clinical picture is dominated by recurring cutaneous and visceral bacterial infections, particularly infections due to staphylococci, and severe generalized eczema, which may be associated with osteoporosis. Biochemistry includes a high level of total and specific IgE and immunological abnormalities dominated by frequent absence of immune antibodies to staphylococci and disorders of neutrophil chemotaxis. Current pathogenic studies show dysregulation of TH1 and TH2 lymphocytes in favor of TH2 activation with depressed TH1 activation, leading to an imbalance in cytokine synthesis. FUTURE PROSPECTS AND PROJECTS: New therapeutical possibilities with alpha and gamma interferon.     

Prospective study of mustard allergy: first study with double-blind placebo-controlled food challenge trials (24 cases)

BACKGROUND: Mustard allergy accounts for 1.1% of food allergies in children. However, double-blind placebo-controlled food challenge trials (DB PCFCs) have not yet been proposed. OBJECTIVE: To carry out DB PCFCs to determine the real frequency of mustard allergy in patients sensitized to mustard. METHODS: A prospective study was conducted in 30 subjects aged 3-20 years presenting positive prick tests to ground mustard seeds (Brassica nigra), mustard flour (B. juncea), metabisulfite-free strong mustard seasoning (B. juncea) and a commercialized allergenic extract (B. nigra). Twenty-seven subjects were screened for mustard-specific immunoglobulin E (IgE). PCFCs were carried out either DB or single blind (SB) with up to 1340 mg of metabisulfite-free seasoning. RESULTS: The mean diameter of the wheal induced by prick tests with the allergenic extract was lower (n.s.) than that induced by the native mustard products: 5.8 mm (1.5-15) vs 6.9 mm (0.5-18) for B. nigra ground seeds, 7.8 mm (1-20) for B. juncea flour and 9.7 mm (3-20) for the strong mustard seasoning. The diameter of the wheal induced by the allergenic extract was significantly different from that induced by the mustard seasoning (P < 0.005). The mean of mustard specific-IgE values was 8.7 KU/l (0.35-72.4). Seven of 30 food challenges were considered positive. Mean prick test results in the positive and negative PCFC subgroups were 5.5 mm vs 5.9 mm for the commercialized extract, 10.9 mm vs 5.8 mm for B. nigra ground seeds (P < 0.01), 9.9 mm vs 7.1 mm for B. juncea flour (n.s. P > 0.25) and 11.5 mm vs 9.1 mm for the metabisulfite-free mustard seasoning (n.s. P > 0.1). Mean specific IgE values determined by CAP system radioallergosorbent test (Phadebas Pharmacia) were higher but not significantly so (P > 0.25) in the subgroup with mustard allergy (12.3 K/l vs 7.6 KU/l). CONCLUSIONS: About 23.3% of the sensitized subjects were allergic to a routine dose of mustard. Positive prick tests and the presence of specific IgE were not predictive. SB PCFC or DB PCFC is required before recommending avoidance diets.     

No correlation between wine intolerance and histamine content of wine

BACKGROUND: Histamine is thought to be the main cause of adverse reactions to wines. OBJECTIVE: The purpose of this study was to test the hypothesis that the level of histamine in wine affects the tolerance to wine in 16 subjects with wine intolerance. METHODS: We performed a study to examine the effects of wine histamine content in 16 adults with wine intolerance. Each subject underwent 2 double-blind provocation tests with wine: 1 with a wine poor in histamine (0.4 mg/L), and 1 with a wine rich in histamine (13.8 mg/L). Blood was collected for histamine and methylhistamine RIAs at 0, 10, 30, and 45 minutes after ingestion of the wine. Methylhistamine and methylimidazolacetic acid (gas chromatography and mass spectrometry) were measured in urine 5 hours before and 5 hours after ingestion. RESULTS: No significant differences in the occurrence of adverse reactions were noted after ingestion of either of the wines (McNemar test). At 10 minutes, a significant increase was observed in plasma histamine with histamine-poor wine. No significant changes (Wilcoxon test) were observed in the methylhistamine and methylimidazolacetic acid levels after ingestion of either histamine-poor or histamine-rich wine. CONCLUSION: This study demonstrates that there is no correlation between the histamine content of wine and wine intolerance. The increase of plasma histamine levels at 10 minutes with histamine-poor wine suggested the role of a histamine-releasing substance. The role of acetaldehyde is discussed.     

Histamine release “in vivo” and “in vitro” induced by hypnotics in normal and atopic patients

The in vitro test of histamine release induced in the leukocytes of atopic subjects selected according to specific criteria would seem to be much more accurate to study the histamine releasing characteristics of intravenous agents than the in vivo study in patients who have to be anaesthetised. Moreover, different concentrations of the test drug may be used, and thus the threshold for histamine release may be compared. It is the test which we recommend for investigating new drugs. However, it is lengthy and expensive; it can therefore not be recommended as a routine preoperative investigation.     

Severe complications related to metabisulfites

Metabisulfite intolerance is encountered in 8 p. 100 of cases of extrinsic asthma and in 20 p. 100 of cases of the "aspirin triad" with nasosinusal polyposis, asthma and aspirin sensitivity. The possibility that anaphylactoid shock or acute severe asthma leading to status asthmaticus, might be related to sulfite sensitivity must be well known. Two case reports are set out. The first observation is that of a 35-year-old woman suffering from intrinsic asthma with alcohol intolerance, who developed status asthmaticus a few minutes after intravenous administration of Doxycycline associated with a metabisulfite preservative. The other 33-year-old patient presented with an acute bronchospasm in the course of a fiberoscopy using Lidocaine associated by mishap with epinephrine, as local anesthetic. The authors point to the miscellaneous drugs containing sulfites, that are employed in asthmatics by different routes, i.e. parenteral, oral, inhalational and other local treatments. Heavy metabisulfite intake may also arise from daily alcohol consumption. Sulfite intolerance could contribute to the persistence of chronic inflammatory processes in bronchial asthma and therefore should be systematically investigated.     

Skin reactions to intradermal neuromuscular blocking agent injections: a randomized multicenter trial in healthy volunteers

BACKGROUND: Numerous reports confirm the performance of intradermal tests for the diagnosis of anaphylaxis during anesthesia; however, there is controversy over their diagnostic value regarding the newer neuromuscular blocking agents (NMBAs). METHODS: One hundred eleven healthy volunteers were randomly assigned to receive intradermal injections of two NMBAs, at five increasing concentrations. A concentration was considered as a reactive concentration when it led to a positive reaction in more than 5% of the subjects. These concentrations were compared with the maximal concentration recommended for the diagnosis of sensitization to NMBAs. RESULTS: The maximal nonreactive concentrations were 10 m for suxamethonium; 10 m for pancuronium, vecuronium, rocuronium, and cisatracurium; and 10 m for atracurium and mivacurium. Except for mivacurium, these nonreactive concentrations were close to the maximal concentrations used for the diagnosis of sensitization against NMBAs. For mivacurium, the nonreactive concentrations were higher than the maximal concentration currently recommended in clinical practice. CONCLUSION: The aminosteroidal NMBAs pancuronium, vecuronium, and rocuronium and the benzylisoquinoline cisatracurium have a similar potency to induce a nonspecific skin reactivity. If the criteria for positivity and the maximal concentrations of the commercially available compounds recommended by French practice guidelines are used, the risk of false-positive results is limited, and only minor modifications of these recommendations could be suggested. A slight reduction in the maximal concentration used for rocuronium from 1:100 to 1:200 and an increase from 1:1,000 to 1:200 for mivacurium can be proposed.     

Downregulation of membrane complement inhibitors CD55 and CD59 by siRNA sensitises uterine serous carcinoma overexpressing Her2/neu to complement and antibody-dependent cell cytotoxicity in vitro: implications for trastuzumab-based immunotherapy

Background:

We evaluated the expression of CD46, CD55 and CD59 membrane-bound complement-regulatory proteins (mCRPs) in primary uterine serous carcinoma (USC) and the ability of small interfering RNA (siRNA) against these mCRPs to sensitise USC to complement-dependent cytotoxicity (CDC) and antibody (trastuzumab)-dependent cellular cytotoxicity (ADCC) in vitro.

Methods:

Membrane-bound complement-regulatory proteins expression was evaluated using real-time PCR (RT–PCR) and flow cytometry, whereas Her2/neu expression and c-erbB2 gene amplification were assessed using immunohistochemistry, flow cytometry and fluorescent in-situ hybridisation. The biological effect of siRNA-mediated knockdown of mCRPs on HER2/neu-overexpressing USC cell lines was evaluated in CDC and ADCC 4-h chromium-release assays.

Results:

High expression of mCRPs was found in USC cell lines when compared with normal endometrial cells (P<0.05). RT–PCR and FACS analyses demonstrated that anti-mCRP siRNAs were effective in reducing CD46, CD55 and CD59 expression on USC (P<0.05). Baseline complement-dependent cytotoxicity (CDC) against USC cell lines was low (mean±s.e.m.=6.8±0.9%) but significantly increased upon CD55 and CD59 knockdown (11.6±0.8% and 10.7±0.9%, respectively, P<0.05). Importantly, in the absence of complement, both CD55 and CD59, but not CD46, knockdowns significantly augmented ADCC against USC overexpressing Her2/neu.

Conclusion:

Uterine serous carcinoma express high levels of the mCRPs CD46, CD55 and CD59. Small interfering RNA inhibition of CD55 and CD59, but not CD46, sensitises USC to both CDC and ADCC in vitro, and if specifically targeted to tumour cells, may significantly increase trastuzumab-mediated therapeutic effect in vivo.