Clinical value of morphine, pholcodine and poppy seed IgE assays in drug-abusers and allergic people.

BACKGROUND: The diagnosis of anaphylactic reactions due to opiates during anaesthesia can be difficult, since in most cases various drugs may have been administered. Detection of specific IgE to poppy seed might be a marker for sensitisation to opiates in allergic people and heroin-abusers. This study assessed the clinical value of morphine, pholcodine and poppy seed skin-prick and IgE determination in people suffering hypersensitivity reactions during anaesthesia or analgesia and drug-abusers with allergic symptoms. METHODS: We selected heroin abusers and patients who suffered severe reactions during anaesthesia and analgesia from a database of 23,873 patients. The diagnostic yield (sensitivity, specificity and predictive value) of prick and IgE tests in determining opiate allergy was analysed. RESULTS: Overall, 149 patients and 200 controls, mean age 32.9 ± 14.7 years, were included. All patients with positive prick to opiates showed positive prick and IgE to poppy seeds, but not to morphine or pholcodine IgE. Among drug-abusers, 13/42 patients (31%) presented opium hypersensitivity confirmed by challenge tests. Among non-drug abusers, sensitisation to opiates was higher in people allergic to tobacco (25%), P<.001. Prick tests and IgE against poppy seed had a good sensitivity (95.6% and 82.6%, respectively) and specificity (98.5% and 100%, respectively) in the diagnosis of opiate allergy. CONCLUSIONS: Opiates may be significant allergens. Drug-abusers and people sensitised to tobacco are at risk. Both the prick and specific IgE tests efficiently detected sensitisation to opiates. The highest levels were related to more-severe clinical profiles.

A randomized placebo-controlled pilot study of Cat saliva 9cH and Histaminum 9cH in cat allergic adults.

BACKGROUND: Cat allergy is an abnormal immune response by the body to cat dander or saliva, leading to the development of a complex of symptoms which can negatively influence health. Cat saliva 9cH and Histaminum 9cH are indicated, according to isopathic principles, for the treatment of cat allergy, however no research has been done to date. AIM: To determine the effect of Cat saliva 9cH and Histaminum 9cH (combined) on cat allergic adults. METHOD: 30 Participants with a positive test result for a cat allergy skin prick test (SPT) were recruited to a double-blind, randomised, placebo controlled clinical trial. Participants took two tablets twice daily for 4 weeks, and attended a follow-up consultation at the end of weeks 2 and 4. The measurement tool used was the SPT, conducted at the beginning and at the end of the study. RESULTS: Cat saliva 9cH and Histaminum 9cH produced a highly statistically significant reduction in the wheal diameter of the cat allergen SPT at the end of week 4. The placebo group showed no statistically significant change. CONCLUSION: The homeopathic medicine reduced the sensitivity reaction of cat allergic adults to cat allergen, according to the SPT. Future studies are warranted to further investigate the effect of Cat saliva and Histaminum and their role as a potential therapeutic option for this condition.

Clinical and immunological effects of a treatment with desentizating low-dose multicomponents in IgE mediated and non IgE mediated food allergies: observational retrospective pilot study.

BACKGROUND: Alimentary allergy has high impact on the quality of life (Qol) of patients and their families: it represents an economic burden for individuals and National Health System. The disease, particularly frequent in pediatric age, recognizes different pathogenetic mechanisms and expresses itself through the production of IgE (IgE mediated form) antibodies or through cell-mediated immunune responses (non IgE mediated forms). The aim of this clinical observational retrospective study is to evaluate the effect of a long-term treatment with Low Dose Medicine (LDM) drugs in pediatric patients affected by IgE and non IgE mediated food allergy. OBJECTIVE: The purpose of the study is to determine the efficacy of the treatment with Allergy Plex (Guna Laboratory, Milan, Italy) to induce clinical and/or immunological tolerance both to IgE mediated and non IgE mediated food allergy; the secondary endpoint is to investigate the treatment tolerability, the reduction of positivity to Skin Prick test and Patch test to food allergens and the decrease on the peripheral blood of the specific IgE to food allergens. The treatment efficacy was measured through a clinical score. METHODS: In this study the immunomodulant activity of Allergy Plex 13, Allergy Plex 7 and Allergy Plex 10 (Guna S.p.A., Milano, Italy) was evaluated. In every patient the state of allergical clinical responses and the immuno-allergological state were evaluated by means of specific parameters letting know the regulatory response to the allergical Th fenotype. RESULTS: Data about Clinical tolerance to food, Symptomatological clinical score, ECP, ACTH, Cortisol; IL-4, IL-10 was collected. There was evidence of improvement of clinical score, reduction of the diameter of cutaneous pomphus obtained through the Prick test and a decrease of IgE specifics values. CONCLUSIONS: The data issued from this study seem to confirm the efficacy of treatment with Allergy Plex in allowing the restoration of immune tolerance and the definite reduction of the clinical score.

Can we evaluate electrodermal testing?

Electrodermal testing (ED testing) is an acupuncture-based approach and was developed to refine homeopathic prescriptions. It is currently being used to advise patients about their "allergies". The evidence for its use in "allergy testing" is limited and often misrepresented. This article addresses the research and clinical issues involved in investigating the reliability and validity of various ED testing machines.

[Anaphylactic shock caused by pancuronium and vecuronium]. / Choc anaphylactique au pancuronium et au vécuronium.

A case is reported of anaphylactic shock due to vecuronium occurring in a patient who had already had such a shock, due then to pancuronium, during a previous general anaesthesia. The need for a full immuno-allergological investigation, the occasional efficiency of the anti-histamine premedication, and crossed allergies between muscle relaxants are stressed. It is noted that an anaphylactic shock can be seen on first using a new molecule, as the patient can have been sensitized to it by other muscle relaxants. This case was the first to be described of an anaphylactic shock due to vecuronium bromide.

[Severe anaphylactic reactions after administration of rocuronium]. / Accidents anaphylactiques graves après administration de rocuronium.

The authors report four cases of severe anaphylactic reactions (grade III or IV) to rocuronium bromide. In three of them, it was the first contact with a muscle relaxant. In three patients the reaction was mediated by IgE anti-bodies. A cross-reactivity with other muscle relaxants was existing in two cases (suxamethonium, vecuronium and atracurium in one patient, suxamethonium, vecuronium and pancuronium in the other.

Histaminoid responses to atracurium, vecuronium and tubocurarine.

Sixty patients scheduled for elective surgery underwent intradermal testing with 0.1 ml of the following solutions diluted in 0.9% saline: vecuronium and tubocurarine (1 in 1,000), atracurium (1 in 1,000 and 1 in 10,000), thiopentone (1 in 100) and also a 0.9% saline control. Thirty minutes later, an area of erythema of greater than 1.5 cm, or a wheal exceeding 1.0 cm in diameter, was recorded as a positive reaction. The patients then randomly received equipotent doses of atracurium, vecuronium or tubocurarine during a standardized anaesthetic induction. Any cutaneous reaction and the percentage fall in systolic pressure three minutes after administration of the relaxant were recorded. In 51 patients plasma IgE levels were measured. The incidence of positive cutaneous reactions to intradermal and intravenous relaxants was significantly different with each agent (p less than 0.01). The percentage fall in systolic pressure after tubocurarine was significantly different relative to the other two agents (p less than 0.01). This was regarded as reflecting potency in releasing histamine and placed the relaxants in the same order: tubocurarine, atracurium and vecuronium. The response to intradermal administration was no guide to the subsequent response after intravenous administration of the three relaxants. IgE levels below 15 IU X ml-1 occurred significantly more often in females and were associated with a significantly higher incidence of cutaneous reactions after intradermal atracurium (1 in 1,000 and 1 in 10,000) (p less than 0.05 and 0.001 respectively) and tubocurarine (1 in 1,000). With these two agents, generalized flushing after intravenous administration was also more common in this group, relative to the normal/high IgE group.

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.

Pancuronium allergy: a case report.

A case of anaphylactic shock to pancuronium bromide is described in which a type I immunological reaction occurred. A 33-yr-old male anaesthetist, with no family or personal history of allergy, collapsed soon after induction of anaesthesia. The drugs used included fentanyl, droperidol, thiopentone and pancuronium. Diffuse erythema occurred, with probable cardiac arrest. The patient was treated with cardiac massage, sympathomimetics and cortisone, and made a complete recovery. Examination (skin tests, passive transfer according to Prausnitz and Küstner, in vitro lymphocyte transformation test, total IgE assay) revealed that the allergic reaction was to pancuronium bromide.

Cutaneous sensitivity to atracurium and vecuronium in patients suffering anaphylactoid reactions to neuromuscular blockers.

Using an ordinal measure of cutaneous sensitivity to intradermal injections of atracurium and vecuronium, 40 nonreacting subjects were compared with a group of 24 patients previously suffering life-threatening anaphylactoid reactions to other muscle relaxants. Enhanced cutaneous sensitivity to vecuronium was found in three, and to atracurium in two of the previously reacting group. With the exception of those showing abnormal reactivity, no significant difference was found in the distribution of cutaneous sensitivity in the control and reacting group. A concentration of vecuronium 8.75 times that of atracurium was required to produce an equivalent intradermal wheal response.

Intradermal histamine releasing effect caused by Org-NC 45. A comparison with pancuronium, metocurine and d-tubocurarine.

Histamine release caused by Org-NC 45, pancuronium, metocurine and d-tubocurarine was determined by measuring the diameter of the redness and skin induration following the intradermal injection of these drugs. d-Tubocurarine and metocurine caused the largest diameter of redness and induration, followed by pancuronium. Org-NC 45 caused the smallest reaction. We conclude that Org-NC 45 may be the drug of choice in patients with asthma and allergic reactions.

Opiate-sensitivity: clinical characteristics and the role of skin prick testing.

BACKGROUND: The value of skin prick testing in opiate-sensitive individuals is uncertain as opiates cause non-specific weals by direct degranulation of mast cells. OBJECTIVE: To define whether skin prick test (SPT) responses to opiates in opiate-sensitive individuals are different to those seen in the normal population and to describe the clinical characteristics of this group of subjects. METHODS: The SPT responses of eight opiate-sensitive subjects to morphine 10 mg/mL, pethidine (meperidine) 50 mg/mL and papaveretum 15.4 mg/mL at four different concentrations (undiluted, 1/10, 1/50 and 1/100) were compared with the responses of 100 (32 atopic) non-opiate-sensitive control subjects. Four of the opiate-sensitive subjects had a clinical history of asthma, rhinitis or urticaria on occupational exposure to morphine. One subject developed urticaria with codeine, one developed urticaria and asthma with morphine and diamorphine and two subjects reacted to intravenous papaveretum with anaphylaxis or urticaria. Five out of the eight cases had opiate sensitivity confirmed by single-blind placebo-controlled oral challenge. RESULTS: Skin prick tests to all three opiates were not significantly different when the eight opiate-sensitive subjects were compared with either the entire normal control group or the subgroup of 47 definite opiate-tolerant controls that had previously received opiates for clinical indications. Furthermore, there were no significant differences in size of opiate SPT responses between atopic and non-atopic control subjects. In the control subjects, there was a positive correlation in SPT weal size between the three opiates. CONCLUSION: Skin prick testing is not useful in the diagnosis of opiate sensitivity and placebo-controlled challenge should be considered.

Use of ultramolecular potencies of allergen to treat asthmatic people allergic to house dust mite: double blind randomised controlled clinical trial.

OBJECTIVE: To evaluate the efficacy of homoeopathic immunotherapy on lung function and respiratory symptoms in asthmatic people allergic to house dust mite. DESIGN: Double blind randomised controlled trial. SETTING: 38 general practices in Hampshire and Dorset. PARTICIPANTS: 242 people with asthma and positive results to skin prick test for house dust mite; 202 completed clinic based assessments, and 186 completed diary based assessments. INTERVENTION: After a four week baseline assessment, participants were randomised to receive oral homoeopathic immunotherapy or placebo and then assessed over 16 weeks with three clinic visits and diary assessments every other week. OUTCOME MEASURE: Clinic based assessments: forced expiratory volume in one second (FEV(1)), quality of life, and mood. DIARY BASED ASSESSMENTS: morning and evening peak expiratory flow, visual analogue scale of severity of asthma, quality of life, and daily mood. RESULTS: There was no difference in most outcomes between placebo and homoeopathic immunotherapy. There was a different pattern of change over the trial for three of the diary assessments: morning peak expiratory flow (P=0.025), visual analogue scale (P=0.017), and mood (P=0.035). At week three there was significant deterioration for visual analogue scale (P=0.047) and mood (P=0.013) in the homoeopathic immunotherapy group compared with the placebo group. Any improvement in participants' asthma was independent of belief in complementary medicine. CONCLUSION: Homoeopathic immunotherapy is not effective in the treatment of patients with asthma. The different patterns of change between homoeopathic immunotherapy and placebo over the course of the study are unexplained.

Validation of a flow cytometric assay detecting in vitro basophil activation for the diagnosis of muscle relaxant allergy.

BACKGROUND: Anaphylactic reactions during anesthesia are mainly the result of muscle-relaxant (MR) drugs. Skin tests, serologic detection of specific IgE, and in vitro leukocyte histamine release are used to investigate MR allergy. OBJECTIVE: We describe a new assay that is based on the detection by flow cytometry of the altered expression of plasma membrane molecules of MR-activated basophils. METHODS: For this assay, which we have named the BASIC assay, basophils are incubated in vitro with MR, after which they are fixed and then triple labeled with fluorescein-conjugated anti-CD63, tandem dye R-phycoerythrin-cyanin 5.1 conjugated anti-CD45, and R-phycoerythrin conjugated anti-IgE. The resulting B asophils' A ltered S urface I mmunofluorescence is detected by flow C ytometry (BASIC). RESULTS: Forty-one patients who had an allergic reaction during general anesthesia and 23 control subjects without such a history were studied. All included subjects' basophils were tested in the BASIC assay with at least 4 MR: suxamethonium, gallamine, vecuronium, and pancuronium. After reaction of the basophils of the MR-allergic patients with MRs, increased surface expression of CD63 and CD45 and decreased expression of IgE were detected. Increased expression of CD63 was observed most frequently and it was stronger than the alteration of the 2 other markers. Cross-reactivity between MRs commonly occurred. MRs diluted 10(-1) activate the basophils of the control subjects, suggesting that at relatively high concentrations MRs are also nonspecific basophil activators. CONCLUSION: In the diagnosis of MR allergy, the BASIC assay has a good specificity but a low sensitivity, and it correlates strongly with skin test results. It is currently appraised for the diagnosis of anaphylactic reaction induced by other classes of drugs.

Prevalence of muscle relaxant sensitivity in a general population: implications for a preoperative screening.

BACKGROUND: Muscle relaxants (MR) are responsible for 59% of peroperative anaphylactic reactions. A major issue would be to determine whether a systematic preoperative screening in the general population should be recommended. OBJECTIVE: The purpose of the study was to evaluate the prevalence of muscle relaxant sensitivity in a sample of the general population and to assess the role of possible risk factors. METHODS: Two hundred and fifty-eight subjects, aged 20-40 years, visiting a health care centre for a check-up were evaluated. Protocol included a questionnaire (occupation, symptoms of atopy, previous surgery, history of drug allergy), skin-prick tests to four commercial muscle relaxants and measurement of specific IgE against quaternary ammonium ions. Atopy was evaluated by skin-prick tests to common inhalant allergens and by a Phadiatop test. RESULTS: Of the study group, 9.3% had either a positive skin test to one or more muscle relaxant or a presence of specific IgE to quaternary ammonium ions. No risk factor was identified in the studied group. CONCLUSION: Since the rate of MR sensitivity is much higher than the anticipated rate of peroperative reactions due to allergy, a systematic preoperative screening for MR allergy should not be recommended for adults in a general population.

Anaphylaxis to muscle relaxants: cross-sensitivity studied by radioimmunoassays compared to intradermal tests in 34 cases.

Thirty-four patients (31 female and three male patients) with a previous anaphylactoid shock to muscle relaxants were investigated. The seric antimyorelaxant IgE was detected by radioimmunoassay (RIA), and the results were compared to intradermal test (IDR) reactions to dilutions of the commercial drugs. The RIA was carried out with a Sepharose-myorelaxant solid phase and anti-IgE 125I-labeled IgG. The results corresponded to the percentage of labeled anti-IgE bound on the solid phase. The RIA with Sepharose-alcuronium and Sepharose-choline was estimated positive from determination with normal sera (n = 12) when bound IgE was greater than 1.0% and 1.5%, respectively. The RIA and IDR were positive in 43.5% and 75%, respectively, of the cases, with a concordance of 66%. One test at least was positive in 79.4% of the cases. No correlation was found between IgE seric levels and the RIA nor between the cutaneous sensitivity and the RIA. Cross-reactivity with Sepharose-choline and Sepharose-alcuronium was observed in 50%, and it was demonstrated by IDR in only 34.2%. The RIA demonstrated the specificity of IgE to quaternary ammonium compounds as myorelaxant drugs. The positive IDR revealed the bridging of mast cell-bound specific IgE, depending on structural conditions, such as the flexibility of the molecules or the variable specificity of the antibodies, restricted to quaternary ammonium ions or enlarged to a broader part of the incriminated molecules.