Age-dependent sting recurrence and outcome in immunotherapy-treated children with anaphylaxis to Hymenoptera venom.

BACKGROUND: Data on outcome of insect venom immunotherapy in children are rare. OBJECTIVE: We investigated the rate of sting recurrence and outcome of Hymenoptera venom anaphylaxis in children of different age groups treated with immunotherapy. METHODS: Data from children consecutively referred for anaphylaxis to Hymenoptera venom were collected using a standardized questionnaire. RESULTS: During mean follow-up of 7.7 years after commencement of immunotherapy, 45 of 83 children (56%) were re-stung 108 times by the insect they were allergic to. This corresponds to a rate of 0.23 stings per child and year of follow-up. The younger the subject, the higher was the prevalence of re-stings, with rates of 0.41 in children < 6 years, 0.21 at school age and 0.15 in adolescents (P = 0.001). In contrast, prevalence of systemic allergic reactions to field stings was significantly lower in pre-school (3.4%) and school-age children (4.3%) compared with adolescents (15.6%; P < 0.05). Overall, prevalence of systemic allergic reactions at re-sting was 15.6% in the honey bee venom and 5.9% in the Vespula venom allergic group (P = ns). Younger boys with anaphylaxis to honey bee venom predominated in our cohort (P = 0.019). CONCLUSION AND CLINICAL RELEVANCE: A majority of children with anaphylaxis to Hymenoptera venom (56%) in our cohort were re-stung, equally by honey bees or Vespula species. Younger children were more likely to be re-stung, but less likely to have a systemic reaction. Venom immunotherapy induces long-term protection in most children: 84.4% of subjects with anaphylaxis to honey bee and 94.1% of those to Vespula venom were completely protected at re-stings.

European Academy of Allergy and Clinical Immunology task force report on 'dose-response relationship in allergen-specific immunotherapy'.

BACKGROUND: For a century, allergen-specific immunotherapy (SIT) has proven to be an effective treatment for allergic rhinitis, asthma, and insect sting allergy. However, as allergen doses are frequently adapted to the individual patient, there are few data on dose-response relationship in SIT. Allergen products for SIT are being increasingly required to conform to regulatory requirements for human medicines, which include the need to demonstrate dose-dependent effects. METHODS: This report, produced by a Task Force of the EAACI Immunotherapy Interest Group, evaluates the currently available data on dose-response relationships in SIT and aims to provide recommendations for the design of future studies. RESULTS: Fifteen dose-ranging studies fulfilled the inclusion criteria and twelve reported a dose-response relationship for clinical efficacy. Several studies also reported a dose-response relationship for immunological and safety endpoints. Due to the use of different reference materials and methodologies for the determination of allergen content, variations in study design, and choice of endpoints, no comparisons could be made between studies and, as a consequence, no general dosing recommendations can be made. CONCLUSION: Despite recently introduced guidelines on the standardization of allergen preparations and study design, the Task Force identified a need for universally accepted standards for the measurement of allergen content in SIT preparations, dosing protocols, and selection of clinical endpoints to enable dose-response effects to be compared across studies.

Microduplication of Xp11.23p11.3 with effects on cognition, behavior, and craniofacial development.

We report an ~1.3 Mb tandem duplication at Xp11.23p11.3 in an 11-year-old boy with pleasant personality, hyperactivity, learning and visual-spatial difficulties, relative microcephaly, long face, stellate iris pattern, and periorbital fullness. This clinical presentation is milder and distinct from that of patients with partially overlapping Xp11.22p11.23 duplications which have been described in males and females with intellectual disability, language delay, autistic behaviors, and seizures. The duplicated region harbors three known X-linked mental retardation genes: FTSJ1, ZNF81, and SYN1. Quantitative polymerase chain reaction from whole blood total RNA showed increased expression of three genes located in the duplicated region: EBP, WDR13, and ZNF81. Thus, over-expression of genes in the interval may contribute to the observed phenotype. Many of the features seen in this patient are present in individuals with Williams-Beuren syndrome (WBS). Interestingly, the SYN1 gene within the duplicated interval, as well as the STX1A gene, within the WBS critical region, co-localize to presynaptic active zones, and play important roles in neurotransmitter release.

Characterization of de novo microdeletions involving 17q11.2q12 identified through chromosomal comparative genomic hybridization.

High-resolution array-comparative genome hybridization (CGH) is a powerful tool for detection of submicroscopic chromosome deletions and duplications. We describe two patients with mild mental retardation (MR) and de novo microdeletions of 17q11.2q12. Although the deletions did not involve the neurofibromatosis type 1 (NF1) gene, they overlap with long-range deletions of the NF1 region which have been encountered in a small group of NF1 patients with more severe MR. Given the overlap of the deletions in our two patients with the large-sized NF1 microdeletions but not with the more frequent and smaller NF1 deletions, we hypothesize that more than one gene in the 17q11.2q12 region may be involved in MR. We discuss candidate genes for MR within this interval that was precisely defined through array-CGH analysis.

Twelve-year follow-up after discontinuation of preseasonal grass pollen immunotherapy in childhood.

BACKGROUND: In a previous controlled study, we demonstrated that preseasonal grass pollen immunotherapy for 3 years was effective in children. Moreover, a significant clinical benefit could still be observed 6 years after discontinuation of specific immunotherapy (SIT). In the current study, we examined the same group of patients again to investigate whether there is a prolonged benefit 12 years after SIT is stopped. METHODS: Twenty-two patients with previous SIT (from 1989 through 1991) or standardized seasonal pharmacotherapy only were prospectively followed during the grass pollen season of 2003. Primary end points were symptom score, medication use, and combined symptom and medication score. In addition, skin prick test reactivity, development of new sensitizations, and prevalence of seasonal asthma were evaluated. RESULTS: Total hay fever symptom score (P < 0.03), use of medication (P < 0.05), and combined symptom and medication score (P < 0.03) remained lower in patients with previous SIT when compared with the control group. Decreased immediate skin response to grass pollen returned 12 years after cessation of SIT. The percentage of new sensitization, however, continued to be significantly smaller in patients with previous SIT (58%) compared with the controls (100%, P < 0.05). There was a tendency for lower prevalence of seasonal asthma in the post-SIT group (P = 0.08). CONCLUSION: This prospective controlled prolonged follow-up study demonstrates the ongoing clinical benefit 12 years after discontinuation of SIT. Furthermore, the reduction in onset of new sensitization, which was found 6 years after discontinuation of SIT, is sustained 6 years later.

Long-term efficacy of preseasonal grass pollen immunotherapy in children.

BACKGROUND: In a previous controlled study we demonstrated that preseasonal grass pollen immunotherapy for three years was effective in children. In the current study we examined the same group of patients to see if there is still a benefit six years after discontinuation of treatment. METHODS: Thirteen of 14 patients with previous specific immunotherapy (SIT) and 10 out of 14 patients of the control group were prospectively followed during the grass pollen season. Outcome measures were seasonal symptom scores for eyes, nose and chest, the use of symptomatic medication and visual analog scale. Objective measures included skin prick test reactivity to seasonal and perennial allergens and conjunctival provocation testing. RESULTS: During the 13 week observation time scores for overall hayfever symptoms (P < 0.004) and individual symptoms for eyes (P < 0.02), nose (P < 0.04) and chest (P < 0.01) as well as combined symptom and medication scores (P < 0.002) remained lower in the group with previous SIT. Only 23% of patients with previous pollen-asthma who had received SIT experienced pollen-associated lower respiratory tract symptoms compared to 70% in the control group (P < 0.05). There was no significant difference in the use of pharmacological treatment during the pollen season except for asthma medication. The average visual analog scale was lower in the post-SIT group (P < 0.05). Six years after cessation of SIT the immediate skin response to grass pollen remained decreased compared to the reaction of the controls (P < 0.01). There was also a tendency for higher allergen concentration to provoke a conjunctival response in the post-SIT group but without reaching statistical significance. Eight years after commencement of SIT, 61% of the initially pollen-monosensitized children had developed new sensitization to perennial allergens compared to 100% in the control group (P < 0.05). CONCLUSIONS: There is still a significant clinical benefit six years after discontinuation of preseasonal grass pollen immunotherapy in childhood. SIT in children with pollen-allergy reduces onset of new sensitization and therefore has the potential to modify the natural course of allergic disease.

[New allergens and pediatric allergology]. / Neue Allergene und pädiatrische Allergologie.

The first manifestation of allergies most often occurs in childhood. Prevention of atopic diseases is one of the very important tasks in pediatrics. Exact knowledge of allergens and the role of adjuvant factors in allergic sensitisation is necessary to define measures for allergy prevention aiming at a reduction of the worldwide increasing prevalence of atopic diseases. Indoor allergens and tobacco smoke exposure are risk factors for early sensitisation and asthma. In addition to house dust mites there are other indoor allergens like moulds, pet allergens, cockroaches and many more. Exact diagnosis and identification of the causative allergen allows therapy directing towards allergen avoidance and relieving symptoms without need of any additional pharmaceutical treatment. This cost-saving strategy helps to prevent disease-related long absences from school and work. Exact knowledge of the structure and biology of the etiologic allergens is a prerequisite for this treatment strategy. We review the great contribution of the Allergy Unit in Zurich to the identification and characterisation of environmental allergens.

Pulmonary diseases in children with severe combined immune deficiency and DiGeorge syndrome.

Pulmonary disease is a common presenting feature and complication of T-cell immunodeficiency. We retrospectively reviewed 15 children with severe combined immune deficiency (SCID) and 19 children with DiGeorge syndrome at the time of their first presentation to the Royal Children's Hospital in the 15-year period from 1981 to 1995. In children with SCID, pulmonary disease was a common (67%) presenting feature and the organisms identified were Pneumocystis carinii (PCP) (n = 7), bacteria (n = 4), viruses (n = 3), and a fungus (n = 1). Late pulmonary complications included lower respiratory tract infections, bronchiolitis obliterans, and lymphointerstitial pneumonitis. Pulmonary infections were common (17 occasions) and the organisms identified were bacteria (n = 7), viruses (n = 6), fungi (n = 3), and Mycobacterium tuberculosis (n = 1). Pulmonary complications were responsible for 5 of 9 deaths. PCP was not identified as a late complication in any child, presumably as a result of effective prophylactic therapy. Although pulmonary disease was not a major presenting feature in children with DiGeorge syndrome, pulmonary complications were common. These included recurrent bacterial and viral infections and bronchomalacia, which complicated management and predisposed to morbidity and mortality, even in those without a T-cell defect. We conclude that pulmonary disease is a common manifestation in children with SCID and DiGeorge syndrome.

Inhalant allergy to fresh asparagus.

BACKGROUND: Two patients experienced itching conjunctivitis, running nose, tightness of the throat and coughing during preparation of fresh asparagus. Eating asparagus after cooking did not provoke any allergic symptoms. Both patients were atopic, sensitized additionally to pollens of grasses and trees as well as to onion. OBJECTIVE: To assess the hypersensitivity reactions to fresh and heated asparagus and to investigate any crossreactivities among the allergens. METHODS: Skin-prick tests were performed with commercial allergens and native asparagus and the patients were tested with Pharmacia CAP system for specific IgE antibodies against asparagus, onion, garlic, birch pollen, mugwort pollen and two recombinant birch pollen allergens, Bet v I and profilin. Inhibition of IgE antibody binding to solid phase homologous and unrelated allergens by increasing doses of liquid allergens (inhibitors) was studied. RESULTS: Skin-prick tests with native green and white asparagus were strongly positive, but negative with cooked asparagus. Both patients had measurable levels of IgE antibodies against asparagus (3.0 and 6.2 kU/L respectively) and several other allergens. One patient was highly sensitive to birch and Bet v I. Both were positive to profilin, mugwort and onion. In all cases the antibody uptake could be extensively and specifically inhibited by homologous allergen. The asparagus-specific IgE antibodies of the two patients could only be inhibited by asparagus. No inhibition was obtained after heating of the asparagus extract to 100 degrees C. CONCLUSIONS: The patients were specifically sensitized by asparagus. No immunological crossreactions could be observed. The measurements of IgE antibodies to other allergens were also specific, representing parallel multiple sensitivity. Profilin inhibited profilin-specific IgE binding but did not react with the asparagus-specific IgE antibodies of these patients. The asparagus allergen recognized by the specific IgE antibodies of these patients was thermolabile.

Short-term efficacy of ultrasonically nebulized hypertonic saline in cystic fibrosis.

Progressive lung disease in patients with cystic fibrosis (CF) is caused by thick secretions, which cause airway obstruction and subsequent colonization and infection by inhaled pathogenic microorganisms. Recently, recombinant human DNase has been shown to reduce the viscoelasticity of sputum in patients with cystic fibrosis and to improve lung function. Ultrasonically nebulized hypertonic saline (HS) has been demonstrated to enhance mucociliary clearance and sputum expectoration by rehydrating airway secretions, and may therefore provide a low cost alternative. We studied the changes in pulmonary function and symptoms in a group of patients with CF who have moderate to severe lung disease. The patients were evaluated following 2 weeks of treatment with HS in an open-label study. Subjects were randomly allocated to receive 10 ml of either 0.9% NaCl (IS) or 6% NaCl (HS). Twice daily, prior to physiotherapy, treatments were delivered by a portable ultrasonic nebulizer. To prevent bronchoconstriction, 600 mg of salbutamol was administered prior to the nebulized solutions. A symptom score was recorded and spirometry was performed on day 0 before therapy was started, on day 14 (the last day of therapy), and on day 28 (14 days after the last treatment with either IS or HS). Fifty-two patients (32 males), with a mean age of 16.2 (range 7-36) years completed the study. There was no difference in baseline characteristics between the two groups. Following 2 weeks of treatment, there was a significant improvement from baseline in FEV1 of 15.0 +/- 16.0% (mean +/- SD) in patients treated with HS, compared with a change of 2.8 +/- 13% in those on IS therapy (P = 0.004). Furthermore, there was a subjective improvement in the effectiveness of chest physiotherapy as reported by those using HS (P = 0.02). The treatment was well tolerated. We conclude that in patients with CF, ultrasonically nebulized hypertonic saline improves lung function in a way similar to that reported for human recombinant DNase when inhaled over a 2 week period. Nebulized saline also enhances the perception of effectiveness of chest physiotherapy.

[Silk waste--a further allergen in the bedroom]. / "Wildseide"--ein weiteres Allergen im Schlafzimmer.

From 1978 until 1993 we diagnosed 167 cases of inhalative allergy to silk-filled bed quilts. The patients experienced asthma attacks predominantly during the night. Occupational exposure to silk materials was found in six cases. The mean age at first manifestation of symptoms (31 years, range 8 to 58) was relatively high, indicating an aggressive inhalation allergen. Beside a case of occupational asthma in a silk filature, we present two patients with nightly respiratory symptoms: an 8-year-old boy, whose asthma immediately disappeared during his holidays away from home, and a 48-year-old woman diagnosed only eight years after the beginning of an asthma unresponsive to therapy. Elimination of the silk-waste-containing bed quilts led to complete recovery of respiratory symptoms. Prick and intracutaneous skin testing as well as scratch tests using material of silk-filled quilts and the RAST (Pharmacia k 73) to silk waste turned out to be sensitive diagnostic parameters. Many of these bed quilts filled with silk-waste are still used today. Beside the house-dust mites they are a further cause of nightly attacks and should also be considered in allergic work-up.