Sublingual immunotherapy with a latex extract in paediatric patients: a double-blind, placebo-controlled study.

BACKGROUND: Natural rubber latex (NRL) allergy remains an important allergic disease triggering urticaria, asthma, angioedema and anaphylaxis. Specific immunotherapy can help to solve problems related to NRL allergy. So far, no controlled clinical trials have been performed in children suffering from NRL allergy. OBJECTIVES: To evaluate the safety and efficacy of sublingual immunotherapy (SLIT) with a commercial NRL extract in children with NRL allergy. RESEARCH DESIGN: Randomized, double-blind, placebo-controlled, 12-month trial. PATIENTS AND METHODS: Twenty-six children (aged 4-15 years) with NRL allergy, who had cutaneous and/or respiratory symptoms, including oral allergy syndrome to fruits containing cross-reactive allergens, were recruited. Twelve children were randomized to SLIT with a commercial NRL extract and eight to placebo (3:2). An additional six children with NRL allergy served as untreated controls. MAIN OUTCOMES MEASURES: A glove use test was utilized to monitor skin and systemic symptoms triggered by NRL exposure at baseline and 3, 6, 9 and 12 months later. Oral allergy symptoms were also monitored. RESULTS: No side effects related to treatments were observed in any patient. A significant improvement of symptom score in treated patients in comparison with baseline values was observed at 3 months (p = 0.01) and consolidated after 1 year of treatment (p = 0.0005). In comparison with placebo, significant improvements were observed starting at 9 months from study start (p = 0.015) and at 12 months (p = 0.005). The number of foods triggering oral allergy symptoms increased in placebo and control subjects, but not in active treated patients (p = 0.05). CONCLUSION: Latex SLIT was safe and efficacious in paediatric patients with NRL allergy.

One- and two-dimensional electrophoretic identification of IgE-binding polypeptides of Lupinus albus and other legume seeds.

The prevalence of food allergies in the world population requires integrated approaches to identify new potential allergens, especially those of plant origin. The aim of this work was the allergen in vitro analysis of Lupinus albus seed proteome, a promising food protein source, and the assessment of IgE cross-reactivities with other more diffused legume species. A combination of one- and two-dimensional gel electrophoresis and immunoblotting analyses with specific IgGs for band identification and lupin-sensitized patients' circulating IgEs for allergenicity studies has been used. Two lupin proteins, namely, conglutin gamma and 11S globulin basic subunits, strongly reacted with all patients' sera. Also, cross-reactivities with the homologous polypeptides of other legume species were observed. Otherwise, no reaction at all was detected with a 2S-type lupin protein. This global electrophoretic approach has allowed the identification of a new potential lupin allergen and confirmed the cross-reactivity among the legume 11S globulin basic subunits.

Injection drug use facilitates hepatitis C virus infection of peripheral blood mononuclear cells.

Infection of peripheral blood mononuclear cells (PBMCs) with hepatitis C virus (HCV) has been demonstrated and has been found to play a role in relapse of HCV disease and vertical transmission of HCV. Injection drug use is thought to impair function of the immune system and induce tolerance to viruses; therefore, HCV infection of PBMCs could be more likely to occur in injection drug users (IDUs) with HCV infection. Of 108 women who tested negative for human immunodeficiency virus type 1 and positive for HCV RNA, 51 had a history of injection drug use and 57 had no known risk factor for HCV infection. HCV infection was found, by nested reverse-transcription polymerase chain reaction analysis, in the PBMCs of 33 IDUs and of 13 non-IDUs (P=.00003). No correlation was found between infection of the PBMCs and HCV genotype or virus load. Route of transmission and viral factors, as well as immunologic dysfunction, may play a role in viral tropism.

Results of a 5-year prospective surveillance study of antibiotic resistance among Salmonella enterica isolates and ceftriaxone therapy among children hospitalized for acute diarrhea.

BACKGROUND: The spread of resistant Salmonella strains continues to increase worldwide. It is necessary to establish epidemiologic information to determine an appropriate empiric antibiotic regimen (when indicated) in infants and children with suspected Salmonella infections for whom the results of susceptibility tests are not yet available. OBJECTIVES: The aim of the present study was to investigate resistance rates and their modifications among Salmonella enterica strains isolated from Italian children hospitalized for acute diarrhea over 5 years. In addition, when antibiotic treatment was indicated, we assessed the in vivo success of parenteral ceftriaxone therapy. METHODS: This study included children admitted consecutively for acute diarrhea to the Division of Pediatrics and Infectious Diseases, Department of Pediatrics, University of Florence, Italy, from January 1, 1997, to December 31, 2001. S enterica strains were isolated from stool cultures, biochemically identified, and serotyped. These isolates were tested by disk-diffusion assay, using the Kirby-Bauer method, for susceptibilities to ampicillin, ceftriaxone, ciprofloxacin, chloramphenicol, neomycin, tetracycline, and trimethoprim/sulfamethoxazole. The limits used for definition of resistance were those established by the guidelines of the National Committee for Clinical Laboratory Standards. RESULTS: A total of 2003 children (1051 boys, 952 girls; median age, 10.3 years; age range, 1 month-16.8 years) with acute diarrhea were admitted to the study. S enterica strains were isolated using stool cultures from 218 (10.9%) children (108 boys, 110 girls; median age, 3.3 years; age range, 2 months-15.8 years). A total of 148 (67.9%) isolates were resistant to at least 1 antibiotic and 57 (26.1%) were multiresistant. The highest rates of resistance were those to tetracycline (132/218 [60.6%]), ampicillin (102/218 [46.8%]), and chloramphenicol (47/218 [21.6%]). The lowest rate of resistance was to ceftriaxone (4/218 [1.8%]). Overall, the rate of resistance to ciprofloxacin (19/218 [8.7%]) was significantly higher than that for ceftriaxone (P = 0.003). Salmonella typhimurium (119/218 [54.6%]) and Salmonella enteritidis (62/218 [28.4%]) were the most frequently identified serotypes. Ceftriaxone was effective in vivo in all 56 children who required antibiotic therapy. CONCLUSIONS: There was a high prevalence of resistant S enterica strains. Ceftriaxone was used effectively in the treatment of S enterica infection in the population studied.

Undetectable serum IgA and low IgM concentration in children with congenital hypothyroidism.

Some studies suggest thyroid hormones may regulate the human immune system. In order to evaluate the effect of thyroid hormone deficiency on antibody production, we evaluated serum IgA and IgM concentrations in 83 children with congenital hypothyroidism (CH), diagnosed by neonatal screening. Patients were compared to two healthy, age-matched control groups. Patients with permanent CH had a significantly higher frequency of undetectable IgA concentrations (thyroid agenesis, P<10(-5); thyroid ectopy, P=0.013) and lower concentrations of IgA (thyroid agenesis, P<10(-6); thyroid ectopy, P<10(-5); dyshormonogenesis, P=0.0002) and IgM (thyroid agenesis, P=0.0002; thyroid ectopy, P<10(-6); dyshormonogenesis, P=0.0017) compared to control group. No difference was observed between patients with transient hypothyroidism and controls. A significant correlation was observed between serum IgA and IgM concentrations and fT4 levels. IgA and IgM deficiency is correlated with the severity of congenital hypothyroidism and may help to evaluate the duration and severity of thyroid hormone deficiency during prenatal life.

Safety and immunogenicity of measles-mumps-rubella vaccine in children with congenital immunodeficiency (DiGeorge syndrome).

Live attenuated vaccines are usually contraindicated in patients with congenital or acquired immunodeficiency. On the other hand, infections due to wild type virus may be particularly severe in patients with low levels of T cells. The aim of the present study was to evaluate safety and immunogenicity of measles-mumps-rubella (MMR) vaccine in children with congenital T cell defect (DiGeorge anomaly). Fourteen patients were included in the study. No severe adverse reaction was reported. No difference between patients and controls was found in frequency of seroconversion for both measles (92.9% versus 96.3%) and rubella (92.9% versus 100%). No difference in mean titres of anti-measles (1.62+/-0.54 versus 1.89+/-0.49 index) (p=0.13) or anti-rubella (78.1+/-48.0 versus 72.0+/-41.0 UI/ml, p=0.68) antibodies was found between patients and controls. No decrease in CD4 cells was detected after immunization. MMR vaccine is immunogenic and can be safely used in patients with DiGeorge anomaly, so preventing severe complication due to wild virus infection.

Long eyelashes in a case series of 93 children with vernal keratoconjunctivitis.

OBJECTIVE: Vernal keratoconjunctivitis (VKC) is a chronic conjunctivitis that affects children mainly in temperate areas, with exacerbations in spring and summer. Eyelashes provide natural protection for the eyes from sunshine, wind, and foreign bodies. These factors induce a worsening of signs and symptoms in VKC, whereas mechanical protection of the eyes produces relief. The aim of this study was to evaluate eyelash length in a large series of VKC patients and in age- and gender-matched healthy subjects. METHODS: Upper eyelash length was measured in 93 VKC patients (mean age: 8.7 years; range: 4-18 years) with a digital caliper. History, clinical form, type of presentation, degree of severity, and drug therapy were evaluated. Skin tests and serum-specific immunoglobulin E for common allergens, serum-total immunoglobulin E, peripheral blood eosinophil counts, and serum eosinophil cationic protein were determined. Two age- and gender-matched control subjects for each VKC patient underwent the same eyelash measurement. RESULTS: The upper eyelashes were significantly longer in VKC patients than in control subjects (mean +/- SD: 8.9 +/- 1.17 mm vs 7.9 +/- 1.07 mm). In healthy subjects, a negative correlation was found between eyelash length and age. With multivariate analysis, unlike control subjects, the eyelash length in VKC patients did not correlate with age, was positively correlated with the degree of severity of VKC, and was negatively correlated with the use of topical cyclosporine. CONCLUSIONS: Patients with VKC had longer eyelashes than healthy matched subjects. The ocular inflammation, by unknown chemical mediators, was likely responsible for the excessive eyelash growth. The finding may represent a defensive mechanism against physical agents that might have a crucial role in the etiopathogenesis of this disease.

Anaphylaxis: a 7-year follow-up survey of 46 children.

BACKGROUND: Little is known about the frequency of and the features associated with recurrent anaphylaxis in pediatric populations. During 1994 to 1996, we enrolled 76 children affected by anaphylaxis in a prospective study to analyze their clinical and allergic features. OBJECTIVE: To undertake a follow-up study of these children to ascertain how many experienced a recurrence of anaphylaxis. METHODS: After a mean interval of 7 years, a pediatric allergist conducted a telephone interview of patients who had been enrolled in our 1994-1996 study. RESULTS: A telephone interview was successfully completed in 46 (61%) of the 76 patients who had been enrolled in our 1994-1996 study. Of these 46 patients, 14 (30%) had experienced a recurrence of anaphylaxis. Children with atopic dermatitis either during 1994 to 1996 (64% vs 34%; P = .04) or at the time of the current study (43% vs 16%; P = .03) and those with urticaria-angioedema at the time of the current study (93% vs 31%; P = .0002) were found to be at a significantly higher risk for recurrent anaphylaxis. Furthermore, those children who were sensitive to at least 1 food allergen during 1994 to 1996 were more likely to have experienced a recurrence of anaphylaxis (93% vs 56%; P < .04). CONCLUSIONS: This study suggests that patients may have a greater risk of recurrence of anaphylaxis if they have atopic dermatitis, urticaria-angioedema, or at least 1 positive result of skin prick tests to food allergens.

Efficacy and safety of cyclosporine eyedrops in vernal keratoconjunctivitis.

BACKGROUND: Corticosteroids have been the only effective topically administered treatment for severe vernal keratoconjunctivitis (VKC), but their prolonged use is often associated with complications. Topical cyclosporine therapy has been used in the past decade, but few controlled trials have been conducted, and conflicting results have been reported. OBJECTIVE: This study sought to evaluate the efficacy and safety of ocular administration of cyclosporine in VKC. METHODS: Twenty-four children with severe VKC were treated with cyclosporine 2% eyedrops. The treatment began in spring and lasted 4 months. One eye was treated with cyclosporine (Cs-eye); the fellow eye received the vehicle as placebo (Pl-Cs-eye) during the first 2 weeks in a double-blind, placebo-controlled trial and thereafter was treated with cyclosporine (open trial). Patients were instructed to protect their eyes against sunlight. Ocular symptoms and signs were scored at entry and at 2 weeks, 4 weeks, and 4 months after the beginning of treatment. All children underwent biochemical and immunologic evaluations. RESULTS: Compared with baseline, scores for ocular signs and symptoms at 2 weeks decreased significantly in the Cs-eyes (P < 0.001), and signs improved in the Pl-Cs-eyes (P = 0.001). A significant difference was noted between Cs-eyes and Pl-Cs-eyes at 2 weeks for both subjective (P < 0.005) and objective (P < 0.001) scores. At 4 weeks, scores for signs (P < 0.001) and symptoms (P = 0.01) were reduced in the Pl-Cs-eyes, with no further improvement in the Cs-eyes. At 4 months, clinical scores had declined further, and serum eosinophil cationic protein levels were significantly lower than at entry (P = 0.009). Most patients reported mild burning sensation and tearing after administration of cyclosporine. Four patients (17%) required an additional brief period of topical corticosteroid therapy. CONCLUSIONS: Cyclosporine eyedrops were effective and safe for treating severe VKC, without causing major side effects. Most of the therapeutic effect was achieved after 2 weeks. The initial therapeutic effect was maintained during the next 3 months, with a further slow decrease in the symptoms.

Maternal drug use is a preeminent risk factor for mother-to-child hepatitis C virus transmission: results from a multicenter study of 1372 mother-infant pairs.

This prospective multicenter study evaluated separately the significance of maternal injection drug use (IDU) and human immunodeficiency virus type 1 (HIV-1) coinfection in vertical transmission of hepatitis C virus (HCV). In all, 1372 consecutive, unselected HCV antibody-positive mothers and their infants were studied. Maternal HIV-1 coinfection (crude odds ratios [OR], 1.41; 95% confidence interval [CI], 1.16-1.66; P =.007) and IDU (OR, 1.58; 95% CI, 1.37-1.78; P <.00001) were linked to mother-to-child HCV transmission in unadjusted analysis when all anti-HCV-positive mothers were evaluated. When only HCV RNA-positive mothers were evaluated, maternal IDU, but not maternal HIV-1 coinfection, was significantly associated with mother-to-child HCV transmission. Multivariable analysis confirmed the link between maternal IDU and HCV transmission (adjusted OR [AOR], 1.51; 95% CI, 1.19-1.92; P =.0006), but no association was found with HIV-1 coinfection (AOR, 0.98; 95% CI, 0.73-1.33; P =.93). IDU, but not HIV-1 coinfection, seems to be a preeminent risk factor for vertical HCV transmission.

Coseasonal sublingual immunotherapy reduces the development of asthma in children with allergic rhinoconjunctivitis.

BACKGROUND: We wondered whether short-term coseasonal sublingual immunotherapy (SLIT) can reduce the development of asthma in children with hay fever in an open randomized study. OBJECTIVE: We sought to determine whether SLIT is as effective as subcutaneous immunotherapy in reducing hay fever symptoms and the development of asthma in children with hay fever. METHODS: One hundred thirteen children aged 5 to 14 years (mean age, 7.7 years) with hay fever limited to grass pollen and no other clinically important allergies were randomized in an open study involving 6 Italian pediatric allergy centers to receive specific SLIT for 3 years or standard symptomatic therapy. All of the subjects had hay fever symptoms, but at the time of study entry, none reported seasonal asthma with more than 3 episodes per season. Symptomatic treatment was limited to cetirizine, loratadine, nasal budesonide, and salbutamol on demand. The hay fever and asthma symptoms were quantified clinically. RESULTS: The actively treated children used less medication in the second and third years of therapy, and their symptom scores tended to be lower. From the second year of immunotherapy, subjective evaluation of overall allergy symptoms was favorable in the actively treated children. Development of asthma after 3 years was 3.8 times more frequent (95% confidence limits, 1.5-10.0) in the control subjects. CONCLUSIONS: Three years of coseasonal SLIT improves seasonal allergic rhinitis symptoms and reduces the development of seasonal asthma in children with hay fever.