Food-induced contact urticaria syndrome (CUS) in atopic dermatitis: reproducibility of repeated and duplicate testing with a skin provocation test, the skin application food test (SAFT)

IgE-mediated contact urticaria syndrome (CUS) is one of the manifestations of allergy in childhood atopic dermatitis (AD). Allergens such as foods and animal products penetrate the skin easily. They can then cause urticarial reactions in sensitized individuals. A provocation test system for foods, called the skin application food test (SAFT), has been developed. Over more than 5 years, a group of 175 patients with AD was built-up and investigated in a prospective follow-up study with SAFT. SAFT was more frequently positive in AD children aged 6–2 years than in older children. In several children of this population (Group 1), we repeated SAFT within a period of 1 year. In another unrelated group of children (Group 2–1), we compared the results of 'original' SAFT and SAFT using square chambers (Van der Bend) or Silver patches. In the 3rd group (Group 2–2) we compared'original' SAFT with SAFT using big Finn Chambers. The agreement between the tests was high: in Group 1, we observed 88 to 93% concordant scores, and in Group 2, the scores were 96% to 100%. Statistically, the K coefficient ranged from 0.71–0.87 in Group 1, and from 0.83–1.00 in Group 2. SAFT is therefore highly reproducible. Agreement was at least 88% between the scores (the lowest K value observed was at least 0.71).     

Identification of a large insertion and two novel point mutations (3671del8 and S1221X) in tuberous sclerosis complex (TSC) patients. Mutations in brief no. 119. Online

Important symptoms of tuberous sclerosis complex (TSC), an autosomal dominant disorder, are hamartomata in several organs, mental retardation and epilepsy. Either one of two loci can be involved (TSC1 and TSC2), of which the TSC2 gene has been cloned. To date, only 35 mutations in the TSC2 gene have been described ranging from large deletions to point mutations. Southern blot analysis using cDNA clones of the TSC2 gene was performed on a cohort of 160 unrelated TSC patients and revealed a 10 kb insertion. The insertion was also present in DNA of the affected father. Both patients showed renal angiomyolipoma, hypomelanotic macules and epilepsy. SSCP analysis of exons 1,2,3,9,12,14,30a and 36 identified two mutations in exon 30a: 3671del8 and S1221X. Symptoms of the sporadic patient with the 3671del8 mutation are cortical tubers, subependymal nodules, facial angiofibroma, ungual fibroma, renal angiomyolipoma, hypomelanotic macules, epilepsy and mental retardation. Clinical symptoms of the patient with the S1221X mutation are facial angiofibroma, ungual fibroma, hypomelanotic macules, epilepsy and mental retardation. His parents were negative for the S1221X mutation, although a germline mosaicism can not be excluded. Besides the previously described polymorphism 1596C->T, two rare variants were observed, a substitution of C->T at position 1294 and at position 1299 C->A.     

Confirmation of the association between high levels of immunoglobulin E food sensitization and eczema in infancy: an international study

Background Studies of Australian infants have reported that more than 80% of those with moderate atopic eczema (AE) have high levels of IgE food sensitization (IgE‐FS) that are commonly associated with IgE food allergy. Objectives To explore the relationship between high levels of IgE‐FS and AE in a large cohort of young children with eczema participating in a multi‐centre, international study. Methods Two thousand one hundred and eighty‐four subjects (mean age 17.6 months, range 11.8–25.4; 1246 males) with active eczema from atopic families from 94 centres in 12 countries were studied. Clinical history, Scoring Atopic Dermatitis index as a measure of eczema severity and CAP‐FEIA measurements for total IgE and IgE antibody levels to cow milk, egg and peanut were entered into a database. If CAP‐FEIA levels exceeded previously reported age‐specific cut‐off levels for 95% positive predictive values (PPVs) for food allergy, subjects were defined as having high‐risk IgE‐FS (HR‐IgE‐FS). Results Serum was available from 2048 patients; 55.5% were atopic. The frequency of HR‐IgE‐FS to milk, egg and/or peanut was the greatest in patients whose eczema developed in the first 3 months of life and the least in those whose eczema developed after 12 months (P<0.0001). In a regression analysis to allow for potential confounding factors, children with HR‐IgE‐FS had the most severe eczema and the youngest age of onset (P<0.001); 64% of infants with severe eczema of onset‐age <3 months had HR‐IgE‐FS. Conclusion Early‐onset severe eczema in infancy was associated with HR‐IgE‐FS. Clinical implications Food allergies should be routinely assessed in infants with moderate or severe eczema. Capsule summary In eczematous infants, the earlier the age of onset, and the greater the severity of eczema, the greater the frequency of associated high levels of IgE‐FS.     

Newly generated IgE antibodies to Dermatophagoides pteronyssinus in children are directed against components distinct from Der p I and Der p II

The specificity of newly generated IgE antibodies (Abs) to the house dust mite, Dermatophagoides pteronyssinus, in longitudinal serum samples from 18 young children with an increased risk for IgE-mediated allergy was studied. The first IgE Ab response to house dust mite was detected early in life (mean age, 32 months; range, 11 to 60 months). For 83% of the children, more than half of the newly generated IgE Ab response to house dust mite was directed against components distinct from the major allergens, Der p I (Pl) and Der p II (DpX). These results suggest that the early IgE Ab response to house dust mite is induced by components distinct from the major allergens, Der p I and Der p II.     

Educational paper: neonatal skin lesions

Although most skin lesions in neonates are transient or benign, they may also be the presenting symptom of a life-threatening disease such as herpes neonatorum. In the present review, we present a short overview of neonatal skin lesions and a practical table to guide the general paediatrician in the diagnosis and management of neonatal skin lesions. Recent reviews are cited for further reading.     

P50 Suppression and Its Neural Generators in Antipsychotic-Na?ve First-Episode Schizophrenia Before and After 6 Months of Quetiapine Treatment

Background: Numerous studies have demonstrated sensory gating deficits in schizophrenia. However, only a few longitudinal studies report on the effects of antipsychotic treatment on sensory gating deficits and their results are inconsistent. In the present study, P50 suppression and its neural generators were investigated in antipsychotic-naïve first-episode patients with schizophrenia before and after 6 months of treatment with quetiapine. Methods: Thirty-four antipsychotic-naïve first-episode schizophrenia patients and age and gender matched healthy controls were tested in an auditory sensory gating paradigm at baseline and after 6 months. During this period, the patients were treated with quetiapine, while controls received no treatment. Sixteen patients completed the study. Results: Patients showed significant reduced P50 suppression compared with controls at baseline but not at follow-up. Furthermore, a significant positive correlation between baseline P50 suppression and dose of quetiapine at follow-up was found. P50 suppression in patients receiving above median dosages of quetiapine increased significantly from baseline to follow-up. At baseline, a frontocentral source was significantly more active in patients than in controls at the time of the testing stimulus. Conclusions: The present findings suggest that P50 suppression deficits are already present at an early stage of schizophrenia. Furthermore, particularly those patients with more severe gating deficits appeared to need higher dosages of quetiapine, although their clinical symptoms did not seem to indicate this. Quetiapine treatment significantly improved these gating deficits. Furthermore, a frontocentral source in the brain appeared to be involved in the deficient P50 gating of the patients.     

Effects of Dopamine D2/D3 Blockade on Human Sensory and Sensorimotor Gating in Initially Antipsychotic-Naive,First-Episode Schizophrenia Patients

It has been suggested that psychophysiological measures of sensory and sensorimotor gating, P50 gating and prepulse inhibition of the startle reflex (PPI), underlie core features of schizophrenia and are linked to dopaminergic pathways in the striatum and prefrontal cortex. In the present study, the effects of a potent D2/D3 receptor antagonist, amisulpride, were investigated on PPI and P50 gating in a large sample of antipsychotic-naive, first-episode patients with schizophrenia. A total of 52 initially antipsychotic-naive, first-episode schizophrenia patients were assessed for their P50 gating, PPI, and habituation/sensitization abilities at baseline and after 2 and 6 weeks of treatment with flexible doses of amisulpride. In addition, 47 matched healthy controls were assessed at baseline and after 6 weeks. At baseline, the patients showed significantly reduced PPI, yet normal levels of P50 gating, habituation, and sensitization. Treatment with amisulpride showed no effects on these measures, either at 2 or 6 weeks of follow-up. This is the first study investigating the effects of monotherapy with a relatively selective dopamine D2/D3 receptor antagonist (amisulpride) on sensory and sensorimotor gating deficits in a longitudinal study of a large group of initially antipsychotic-naive, first-episode patients with schizophrenia. Our finding that amisulpride effectively reduced symptom severity in our patients without reducing their PPI deficits indicates that increased activity of dopamine D2 receptors may be involved in symptomatology of patients with schizophrenia, but not in their sensorimotor gating deficits.