Anaphylaxis during anesthesia: results of a 12-year survey at a French pediatric center.

BACKGROUND: Following adverse reactions to anesthesia, tests are carried out to determine the mechanism of the reaction and to identify the agent responsible. No specific data are available in France concerning such skin tests in children. METHODS: Between 1989 and 2001, we assessed hypersensitivity reactions to general anesthesia in 68 children. Thirty underwent more than one operation, for congenital malformations. Immunoglobulin (Ig)E-mediated anaphylaxis was diagnosed on skin tests combined with the clinical history. RESULTS: Grade I, II and III reactions were observed in 20, 27 and 21 children, respectively. IgE-mediated anaphylaxis was diagnosed in 51 children: 31 (60.8%) for neuromuscular blocking agents (NMBA), 14 (27%) for latex, seven (14%) for colloids, five (9%) for opioids and six (12%) for hypnotics. Vecuronium was the NMBA causing the largest number of reactions. Cross reactivity to NMBA available in France was observed in 23 of 30 children (76%), particularly for vecuronium and atracurium or pancuronium. The estimated frequency of IgE mediated anaphylactic reactions was one in 2100 operations. Based on our results, 25 children subsequently received a different anesthetic with no adverse reaction. CONCLUSIONS: As in adults, NMBA, then latex were responsible for most anaphylactic reactions during anesthesia. Our results confirm that skin tests with anesthetic agents are feasible and safe in children and improve the safety of subsequent anesthetic procedures.

Kinetics of plasma cytokine levels in children hyposensitized with wasp venom.

Specific immunotherapy shifts immune responses towards a Th0/Th1 response. Production of chemokines is also decreased early after the initiation of rush venom immunotherapy. We aimed to investigate in vivo whether cytokine plasma levels reflect the shift towards a Th0-Th1 pattern of immune response as seen in vitro in lymphocytes from patients undergoing venom immunotherapy. Therefore, we studied plasma levels of various cytokines before (day 1), during (day 2), and after (day 4) rush immunotherapy in nine wasp-allergic children. The levels of interleukin-5 and IFN-gamma were below the detection threshold. No variations were observed in levels of interleukin-4, interleukin-10, and TNF-alpha. In contrast, mean levels of RANTES transiently increased at day 2, and decreased below the pretreatment levels at day 4. Those alterations were significant in five children with high levels of RANTES at day 1, and reporting severe anaphylaxis. In the four other children, the levels of RANTES were not significantly increased at day 4. These results suggest that RANTES plasma levels are positively correlated with the severity of the reaction to hymenoptera venom, and that a significant decrease in the levels of RANTES occurs only in children with high pretreatment levels. However, the kinetics of RANTES plasma levels correlated neither with the results of allergological tests, nor with the outcome of venom immunotherapy.

Blood histamine levels (BHL) in infants and children with respiratory and non-respiratory diseases.

BACKGROUND: Blood histamine levels are decreased after severe allergic reactions and in various chronic diseases. AIMS: To study blood histamine levels in infants and children with acute infectious and non-infectious, non-allergic, disease. METHODS: Blood histamine levels were investigated by a fluorometric method in infants and children admitted to hospital with bronchiolitis, non-wheezing bronchitis, acute infections of the urinary tract, skin and ear-nose-throat, gastroenteritis, or hyperthermia of unknown aetiology. Results of blood histamine levels and white blood cell counts were compared with those obtained for children recovering from benign non-infectious, non-allergic illnesses. RESULTS: As compared with control children, white blood cell numbers were significantly increased in children with acute infections of the urinary tract, skin and ear-nose-throat, and were significantly decreased in children with gastroenteritis. Blood histamine levels were significantly lower in children with gastroenteritis and hyperthermia than in children with other diseases and control children. It was not possible to correlate blood histamine levels and the number of blood basophils. CONCLUSIONS: BHL are significantly decreased in infants and children with acute gastroenteritis and hyperthermia of unknown aetiology. The mechanisms responsible for the decrease in blood histamine levels in children with gastroenteritis and hyperthermia are discussed.

Allergy to beta-lactam antibiotics in children.

BACKGROUND: Skin tests with soluble beta-lactams can be used to diagnose immediate and delayed hypersensitivity (HS) reactions to beta-lactam antibiotics. Very few studies have been performed with children with suspected beta-lactam allergy. In these studies, immediate HS to beta-lactams was diagnosed by skin tests in 4.9% to 40% of children. The diagnostic and predictive values of immediate responses in skin tests are good, because very few children with negative skin test results have positive oral challenge (OC) test results. Delayed responses in skin tests (intradermal and patch tests) have been reported in adult patients and children suffering with urticaria, angioedema, and maculopapular rashes during treatments with beta-lactam antibiotics. However, the diagnostic and predictive values of late responses are unknown. Semi-late responses in skin tests with beta-lactams have never been studied in adults or children. OBJECTIVES: The aims of this study were to confirm or rule out the diagnosis of allergy to beta-lactams in children with histories of adverse reactions to these antibiotics, to determine whether allergic children were sensitized to one or several classes of beta-lactams, and to evaluate the frequency and diagnostic value of immediate, accelerated, and delayed responses in skin tests with beta-lactam antibiotics in children. METHODS: We studied 325 children with suspected beta-lactam allergy. Skin tests (prick and intradermal) were performed with soluble forms of the suspected (or very similar) beta-lactams and with one or several beta-lactams from other classes. The reaction was assessed after 20 minutes (immediate), 8 hours (accelerated), and 48 to 72 hours (delayed). OCs with the suspected beta-lactams were performed in patients with negative skin test results, except those with severe serum sickness-like reactions and potentially harmful toxidermias. RESULTS: Skin tests and OCs led to the diagnosis of beta-lactam allergy in 24 (7.4%) and 15 (4.6%) of the children, respectively. Thus, only 12% of the children were diagnosed as allergic to beta-lactams by means of skin tests and OC. HS to beta-lactams was suspected from clinical history in 30 (9.2%) children reporting serum sickness-like reactions and potentially harmful toxidermias. In a few children, we diagnosed food allergy and intolerance to excipients or nonsteroidal antiinflammatory drugs. No cause was found in the other children. Based on skin tests and OC, the prevalences of immunoglobulin E-dependent and of semi-late or delayed sensitizations to beta-lactam assessed were similar (6.8% vs 5.2%, respectively). Most immunoglobulin E-dependent sensitizations were diagnosed by means of skin tests (86.4%). In contrast, most semi-late and delayed sensitizations were diagnosed by OC (70.6%). The likelihood of beta-lactam allergy was significantly higher for anaphylaxis (42.9% vs 8.3% in other reactions) and immediate reactions (25% vs 10% in accelerated and delayed reactions). Of the children diagnosed as allergic to beta-lactam by means of skin tests, OC, and clinical history, 11.7% were sensitized to several classes of beta-lactams. The risk was significantly higher in children with anaphylaxis (26. 7% vs 7.5% of the children with other reactions) and in children reporting immediate reactions (33.3% vs 8.5% of the children with accelerated and delayed reactions). Finally, age, sex, personal history of atopy, number of reactions to beta-lactams, and number of reactions to other drugs were not significant risk factors for beta-lactam allergy. CONCLUSION: The skin tests were safe, and the immediate reaction to skin tests successfully diagnosed allergy to beta-lactam antibiotics in children reporting reactions suggestive of immediate HS. In contrast, most accelerated and delayed reactions were diagnosed by OC. Thus, our results suggest that the diagnostic and predictive values of skin tests for nonimmediate HS to beta-lactams in children are low. (ABSTRACT TRU

[An unusual foreign body. Report of a case of subcutaneous emphysema during an asthma attack]. / Un corps étranger hors du commun. À propos d'un cas d'emphysème sous-cutané lors d'une crise d'asthme.

Pneumomediastinum is an uncommon complication after an asthma attack. The essential clinical sign is the presence of subcutaneous emphysema. In the great majority of cases, the treatment of pneumomediastinum corresponds to that of asthma, with resorption over several days. The situation is very different when the development of pneumomediastinum and subcutaneous emphysema is secondary to an aspiration syndrome.

[Allergic children]. / L'enfant allergique.

Epidemiologic data have shown an increased prevalence (and severity) of atopy related diseases (asthma, eczema and allergic rhinitis) during the post 15-20 years. Atopic respiratory diseases such as allergic rhinitis and asthma represent the effects of an immunological response to allergens, mediated through immunoglobulins E. Development of a clinically significant atopic reaction depends on environmental exposure. The majority of allergic children display positive skin tests to house dust mites, animal danders or pollens. Immediate hypersensitivity to food allergens starts early in life and is most often associated with atopic dermatitis. Allergic reactions to peanuts are generally acute and severe, with an increasing frequency. Parents must be aware of their child's problem and preventive measures must be undertaken very early in life, first at home and later also at school. Family history remains the best predictor of atopy in newborn babies.

IL-7 drives donor T cell proliferation and can costimulate cytokine secretion after MHC-matched allogeneic bone marrow transplantation.

Transplantation of MHC-matched, allogeneic B10.D2 bone marrow plus T cells into BALB/c recipients ultimately results in chronic graft-vs-host disease (GVHD) and mortality 8 to 12 wk post-transplant. We have identified IL-7-specific mRNA in the spleens of BALB/c bone marrow transplantation (BMT) recipients during the first week post-transplant. The response by T cells from B10.D2-->BALB/c BMT recipients to stimulation with IL-7 in vitro during the early period after transplant was then examined. The findings indicated that within the first week post-transplant, spleen cells removed from recipients injected with allogeneic, but not syngeneic, T cells proliferated vigorously to rIL-7. Both IL-2-dependent and -independent components were identified. Depletion of responding cells before culture with anti-Thy-1.2 Ab virtually eliminated this response. We conclude that transplant of allogeneic T cells is required for the observed IL-7 response, and moreover, such cells proliferate after exposure to this cytokine in vitro. To determine whether IL-7 could have a functional effect on donor T cells, the production of IFN-gamma by T cells from allogeneic BMT recipients stimulated with anti-T cell receptor (i.e., anti-V beta) Ab was examined. IL-7 was demonstrated to enhance IFN-gamma production by donor T cells postallogeneic BMT. These results suggest that a cytokine presumably produced in the host for the physiologic function of hematologic reconstitution is playing an additional role during the early events after allogeneic BMT mediated via the expansion and augmented cytokine production by donor T cells.

Endogenous superantigens in allogeneic bone marrow transplant recipients rapidly and selectively expand donor T cells which can produce IFN-gamma.

Despite the existence of many non-MHC disparities between MHC matched but non-MHC mismatched donors and recipients, graft-versus-host disease (GVHD) is not clinically apparent following a significant number of allogeneic bone marrow transplants (BMT) in experimental animals. The present studies examined V beta TcR expression and IFN-gamma production by donor T cells in a BMT model involving an MHC matched, allogeneic donor-recipient combination which included a unidirectional superantigen disparity (Mls). B10.D2-->BALB/c, but not BALB/c-->B10.D2 recipients develop GVHD and mortality ensues 8-12 weeks post-transplant. During the first 2 weeks post-transplant of B10.D2-->BALB/c, approximately 50% of all Thy1.2+ spleen and lymph node cells were found to express T cell receptors utilizing V beta 3. A similar rapid and selective expansion of V beta 3+ TcR bearing donor T cells was detected in two other H-2 matched superantigen disparate donor-recipient BMT combinations. An increased percentage of V beta 3+ T cells was noted among both the CD4+ and CD8+ populations. Thus, in these donor/recipient combinations, all TcR families were not equally expanded early following transplant. At 4-10 days post-transplant, IFN-gamma specific mRNA was readily detected in the spleens of B10.D2-->BALB/cBMT recipients containing large numbers of V beta 3+ T cells. Moreover, V beta 3+ donor T cells from these recipients contained IFN-gamma mRNA. Specific stimulation in vitro with immobilized anti-TcR moAbs demonstrated that V beta 3+ T cells secreted a large amount of the total IFN-gamma levels detected. The ability of endogenous superantigens to activate large numbers of T cells which can produce cytokines after BMT indicates that when present, such antigenic differences may contribute to events occurring during initial graft-versus-host reactions. Such antigens could therefore participate in the events influencing whether GVHD develops following BMT between certain donors and recipients.

Cetirizine for seasonal allergic rhinitis in children aged 2-6 years. A double-blind comparison with placebo.

A total of 107 children of both sexes between 2 and 6 years of age with pollen-induced seasonal allergic rhinitis (SAR) were entered in a multicentre study of double-blind parallel group design in which the effects of 5 mg cetirizine, given as drops from a solution containing 10 mg/ml once daily each evening for two weeks, were compared with those of identical placebo. Sneezing, rhinorrhea, nasal obstruction and nasal and ocular pruritus were the symptoms evaluated by means of symptom scores by investigators and, on daily record cards, by parents. Investigators also made a global evaluation at the end of treatment. Cetirizine was more active than placebo for each symptom evaluated both by parents and investigators. There were significant by more (p = 0.002) days during which symptoms were absent or mild, in the cetirizine than in the placebo group. When the maximum symptom scores rated by investigators at each visit were compared, the difference in favour of cetirizine at the end of treatment was statistically significant (p = 0.04). Global evaluation by investigators of changes in symptoms at the end of the study showed an improvement in both groups which was significantly greater with cetirizine, providing excellent or good improvement in 34/54 patients compared with 25/53 patients on placebo (p = 0.039). Tolerance was good. Three patients on cetirizine and none on placebo experienced mild somnolence.

[Vaccinations of children allergic to eggs with vaccine prepared with egg]. / Vaccinations des enfants allergiques à l'oeuf par un vaccin préparé sur oeuf.

BACKGROUND: The mumps, influenza, yellow fever and measles vaccines are grown in chick-embryos. Because allergic reactions to these vaccines have occasionally been reported in children who have suffered anaphylaxis from egg ingestion, it has been claimed that these children should not receive such vaccines. PATIENTS AND METHODS: 17 egg-allergic children aged 1 year 1 month to 7 years 10 months (mean 2 years 4 months) were studied. All had developed an allergic reaction less than one hour after egg ingestion. Allergy was confirmed by skin testing (prick skin test) and detection of IgE antibodies to egg (RAST). RESULTS: Seven children were immunized normally by their general practitioner, who was not aware of their allergy; 8 children having negative prick skin and intradermal tests with the vaccine were also immunized normally while 2 children who had positive intradermal test with the vaccine received divided doses following a protocol established for this study. None of these 17 egg-allergic children developed local and/or general reactions. Reintroduction of egg (yolk then white) was tested on the day of immunization in 4 children: only one developed facial edema. CONCLUSION: This protocol permits these vaccines to be safely given to egg-allergic children.

[The asthmatic child]. / L'enfant asthmatique.

Asthma is the most frequent chronic pediatric disease. Management is based on assessment of severity and should normalize lifestyle as well as pulmonary function. Mild asthma is treated with intermittent beta-2-agonists. Moderate asthma should receive non-steroids prophylactic anti-inflammatory drugs. Immunotherapy should be considered. Severe asthma requires inhaled steroids. At each stage inhaled medications should be preferred. Therefore inhalation delivery system must be adapted for children of different ages and degree of dyspnea. The importance of environment control is well recognized. Establishing a partnership with the child and its family and with the medical staff and with the child's school is always necessary.

Dissociation of symptom scores and bronchial hyperreactivity: study in asthmatic children on long-term treatment with inhaled beclomethasone dipropionate.

The aim of the study was to evaluate the effects of inhaled steroids (IS) on the improvement of clinical asthma symptoms and on the decrease in bronchial hyperreactivity (BHR). Twenty-four children with severe asthma were given 1,000 micrograms beclomethasone dipropionate (BDP) daily and compared with ten asthmatic control children. The study included the evaluation of daily clinical score, of exercise induced asthma, of bronchial obstruction (forced expiratory volume in 1 sec, FEV1), and of BHR at months 0, 1, 2-3, and 4-5 (M0, M1, M2-3, and M4-5). BHR was assessed by standardized inhaled carbachol provocation measuring plethysmographic specific airway resistance (SRaw). The carbachol dose causing a 40% decrease in specific conductance (SGaw) was determined (PD40 SGaw). Clinical scores decreased at M1 (P less than 0.01) and throughout the study. FEV1 increased at M1 (P less than 0.05), M2-3 (P less than 0.01), and M4-5 (P less than 0.05) compared to M0. PD40 SGaw only increased significantly at M1 and M2-3. No individual correlation was found between clinical scores and PD40 SGaw at any testing, or between the decrease of clinical scores and the decrease of BHR. We conclude that bronchoconstrictive challenge tests do not adequately assess the clinical efficacy of IS. In clinical practice non-specific BHR should be preferentially measured for diagnosing atypical forms of asthma.

Modifications in tissue histamine levels in mice treated with chronic epicutaneous application of phorbol-12-myristate-13-acetate.

Chronic epicutaneous application of phorbol-12-myristate-13-acetate (PMA) on the right flank of C 57 BL/6 mice induces an inflammatory reaction and a selective increase in skin histamine level at the site of treatment. Tissue histamine levels were not increased at other sites such as contralateral skin, stomach rumen and skeletal muscle, and were decreased in stomach fundus and dorsal skin. These results are in agreement with the hypothesis that mast cells play a significant role in cutaneous inflammation induced by PMA.

Clinical trials on pediatric lower-respiratory-tract infection: results and comments with cefetamet pivoxil.

A total of 30 pediatric patients suffering from lower-respiratory-tract infections were admitted to a three-arm, open, randomized study comparing two different doses of cefetamet pivoxil (either 10 or 20 mg/kg b.i.d.; groups A and B, respectively) with the standard cefaclor treatment (10 mg/kg t.i.d.; group C) for 7-12 days. The 30 cases were randomly assigned to the three treatment arms which were comparable with regard to demographics as well as to diagnosis on admission and concomitant medication. The children ranged from 1.08 to 12 years in age, and comprised 18 males and 12 females, with a weight range of 11-42 kg. As is to be expected in these patients, bacteriology was mostly not assessable. The overall clinical outcome was cure in 9, 8 and 9 cases, respectively, and improvement in 1, 2 and 0 cases, respectively. In the cefaclor group 1 patient failed to respond. Signs and symptoms of disease improved significantly in the three treatment groups; there were no intergroup differences. Vital signs (morning and evening temperature and pulse rate) improved in parallel. Radiological results had improved by the end of treatment in 9/10 patients in group A, in 10/10 patients in group B, and in 9/10 evaluable patients in group C. Mild to moderate nausea or vomiting were each reported in 1 patient in group A. Platelet increase was reported as a mild adverse event in 2 patients in each of the cefetamet pivoxil groups and in 4 patients given cefaclor.(ABSTRACT TRUNCATED AT 250 WORDS)

[Mucoviscidosis and allergic bronchopulmonary aspergillosis]. / Mucoviscidose et aspergillose bronchopulmonaire allergique.

Allergic bronchopulmonary aspergillosis (ABPA) is a severe disease inducing bronchopulmonary anatomic lesions which complicate those already present in patients with cystic fibrosis. The frequency of this association is estimated between 0.6 and 10% according to American studies. Diagnosis of ABPA is difficult, as findings such as sibilant rales, pulmonary infiltrates, bronchiectasies, anti-aspergillus precipitins may be present as single features in patients with cystic fibrosis. Thus it is important to ascertain the diagnosis as oral corticosteroid treatment is the only one able to prevent evolution towards bronchiectasies and pulmonary fibrosis.

Immunotherapy with an oral bacterial extract (OM-85 BV) for upper respiratory infections.

The efficacy of Broncho-Vaxom/Imocur (OM-85 BV), an orally administered lyophilized bacterial extract, for recurrent respiratory and ear, nose and throat (ENT) infections was evaluated in 116 children aged 6 months to 19 years by comparing its activity in 61 children with that of a placebo in 55 children. The study was randomized, double-blind, and comprised a 90-day treatment period followed by a 90-day follow-up period without test drugs. Over the 180 days, 39.5% of patients taking OM-85 BV remained free from infection compared with 16.5% on placebo (p less than 0.01). 44% on OM-85 BV did not need antibiotics compared with 23.5% on placebo (p less than 0.05). These differences were even greater in the subgroup of children aged 6 years and less (34 vs. 3.5% for the absence of infections, p less than 0.01 and 37 vs. 10% for the need of antibiotics, p less than 0.05). Tolerance to OM-85 BV was excellent, and laboratory investigations showed no abnormalities attributable to this product. This work confirms that the immunomodulator OM-85 BV is an effective immunotherapy for recurrent respiratory and ENT infections in children.

Scavengers of free radical oxygen affect the generation of low molecular weight DNA in stimulated lymphocytes from patients with systemic lupus erythematosus.

Factors that potentially affect the generation of excess low molecular weight DNA (LMW-DNA) in cultured phytohemagglutinin (PHA)-stimulated lymphocytes of patients with systemic lupus erythematosus (SLE) were studied because this species of DNA is consistently found and this DNA may play a role in the pathogenesis of the disease. Superoxide dismutase (SOD; 0.05 mg/mL), a scavenger of free radical oxygen, decrease LMW-DNA formation in lymphocytes by 22%. Co-cultivation with cysteamine, a second scavenger of free radical oxygen and a sulfhydryl radioprotective agent, resulted in a 32% decrease in the generation of excess LMW-DNA at a concentration of 0.5 x 10(-3) mol/L and largely prevented its formation at 1.0 x 10(-3) mol/L. Other free radical scavengers (catalase, mannitol, vitamins C and E), cyclooxygenase inhibitors (ibuprofen and aspirin), a xanthine oxidase inhibitor (allopurinol), and an iron chelator (desferoxamine) did not affect excess LMW-DNA formation. Glutathione (1 x 10(-3) mol/L) had no effect and cysteine was toxic. Because scavengers of free radicals might be useful in the therapy of lupus, a trial of cysteamine (30 to 60 mg/kg/d) was administered to six acutely ill patients with SLE. A therapeutic benefit was not demonstrated, and some patients had exacerbation of disease. Lymphocyte cell growth from control and lupus subjects was stimulated when cysteamine, 1 x 10(-5) to 1 x 10(-4) mol/L was added to the media, but inhibited at concentrations of 2 x 10(-4) mol/L or greater. These studies suggest that the autooxidation and toxicity of high-dose cysteamine preclude its therapeutic use as a free radical scavenger.

[Consensus conference. The management of asthma in children]. / Conférence de consensus. Prise en charge de l'asthme de l'enfant.

At this international consensus conference, a number of conclusions concerning the diagnosis and management of childhood asthma were reached. The following practical definition was given to asthma: intermittent wheezing and/or cough in a clinical situation where asthma is likely and less common diseases have been outruled. A thorough clinical history is essential to the diagnosis of asthma. Additional tests are used only to confirm the clinical impression and to provide objective evidence supporting therapeutic recommendations. Multidisciplinary management includes an evaluation of psychosocial factors and patient information. Drugs should be selected according to the severity of the condition: beta-2-agonists for intermittent mild wheezing; cromolyn sodium for moderate to severe asthma; xanthines, ipratropium bromide, and oral corticosteroids in more persistent and severe forms. The child and parents should be told that a normal, physically active life is quite possible if the disease is correctly controlled. The reward for correct management of asthma is resumption, in nearly every case, of a normal life including active participation in sports.