Atopic Manifestations: Dermatitis, Allergic Rhinitis and Asthma in Patients With Hypogammaglobulinemia

Background: Most of the hypogammaglobulinemic patients have a clinical history in favor of allergic respiratory disease. Nevertheless, in these patients the importance and prevalence of atopic disorders have not been completely explained. Objectives: This study was aimed to evaluate atopic manifestations (dermatitis, allergic rhinitis and asthma) and pulmonary function in patients with hypogammaglobulinemia. Patients and Methods: We used the international study of asthma and allergies in childhood (ISAAC) questionnaire in forty-five patients diagnosed with hypogammaglobulinemia and spirometry was done in 41 patients older than 5 years. Results: Spirometry results were normal in 21 (51%), and showed obstructive in 15 (37%) and restrictive pattern in 5 (12%) of the 41 patients who were evaluated. By the end of the study, asthma was diagnosed in nine (20%) patients and other atopies (rhinitis and dermatitis) identified in 10 (22%), and four (9%), respectively. Conclusions: Atopic conditions should be investigated in the hypogammaglobulinemic patients and the prevalence in these patients may be higher than in normal population. Also, it is recommended to perform a pulmonary function test as a routine procedure in patients with hypogammaglobulinemia and atopy should be assessed in these patients.

Allergological evaluation of a dog population in a veterinary immuno-allergology consultation: What correlates in a canine model

Introduction: Allergic dermatitis (AD) is the most common canine pruritic condition in veterinary dermatology. Allergic dermatitis to flea bites presents the highest prevalence, followed by atopic dermatitis and food AD. This study aimed to identify possible correlation between data from clinical signs, intradermal tests (IDT) and specific IgE levels, which are used in dog AD assessment. Methods: Fifty five dogs from the Veterinary Hospital of the University of Évora (Portugal) and Rof Codina University Hospital (Lugo, Spain) outpatient consultations were studied by means of clinical inquiry, IDT and specific IgE determination. Thirty five of the patients belonged to predisposed breeds, 30 were females and 25 males. Forty one (74%) were indoor. Results: In 82% of cases first clinical signs appeared before the age of 3 years and 24% even before 1 year old. In 70% of the individuals clinical signs included itching, which was generalized in 66%, with 78% of paw licking and chewing. Clinical profile showed seasonal worsening in 64% of cases. From the 69.1% of dogs already presenting with dermatitis, 50% also presented external otitis and 28.9% self-inflicted alopecia. "Intense itching" was found in 10.5%, "medium itching" in 81.6% and “mild itching” in 5.26% of the patients. Prevalence of positive IDT was 37.3 % to Lep d, 29.41% to Der f, 27.5% to Der p, 25.5% to Dac g and 21.6% to Malassezia sp. From the 37 dogs submitted to food IDT, 40.5% revealed positive to beef, 27% to chicken, 27% to porc and 5.4% to lamb. Specific IgE > 150 EAU was found in 84% of dogs to indoor allergen sources and in 68% to pollens. A negative correlation was found between an outdoor life and the intensity (p = 0.033) and precocity (p = 0.026) of clinical signs. Sensitization to pollens was found positively correlated with the seasonality of clinical signs (p = 0.001) and the positivity for Dac g (p = 0.007). The prevalence of chronic otitis correlated positively with alopecia and reactivity to Lep d (p = 0.008), Plantago lanceolata (p = 0.026) and Platanus acerifolia (p = 0.017). There was no correlation between the results of ITD and specific IgE. Conclusion: We can conclude that correlation between different clinical signs and positive testing for some allergenic sources may occur, as well as between sensitization to pollens and the beginning, the intensity and the seasonality of dog patient clinical signs.

Towards global consensus on outcome measures for atopic eczema research: results of the HOME II meeting

The use of nonstandardized and inadequately validated outcome measures in atopic eczema trials is a major obstacle to practising evidence-based dermatology. The Harmonising Outcome Measures for Eczema (HOME) initiative is an international multiprofessional group dedicated to atopic eczema outcomes research. In June 2011, the HOME initiative conducted a consensus study involving 43 individuals from 10 countries, representing different stakeholders (patients, clinicians, methodologists, pharmaceutical industry) to determine core outcome domains for atopic eczema trials, to define quality criteria for atopic eczema outcome measures and to prioritize topics for atopic eczema outcomes research. Delegates were given evidence-based information, followed by structured group discussion and anonymous consensus voting. Consensus was achieved to include clinical signs, symptoms, long-term control of flares and quality of life into the core set of outcome domains for atopic eczema trials. The HOME initiative strongly recommends including and reporting these core outcome domains as primary or secondary endpoints in all future atopic eczema trials. Measures of these core outcome domains need to be valid, sensitive to change and feasible. Prioritized topics of the HOME initiative are the identification/development of the most appropriate instruments for the four core outcome domains. HOME is open to anyone with an interest in atopic eczema outcomes research.

Dermatophagoides farinae-specific immunotherapy in atopic dogs with hypersensitivity to multiple allergens: a randomised, double blind, placebo-controlled study

A randomised, placebo-controlled, double blind study was conducted on 25 dogs that had atopic dermatitis, together with skin test reactivity and elevated serum IgE to Dermatophagoides farinae (Df) and at least one additional allergen. Dogs were treated with either a Df-restricted immunotherapy solution (n=14) or a placebo (n=11) and evaluated 6 weeks and 3, 5, 7 and 9 months after the initiation of treatment using a clinical scoring system (SASSAD) and pruritus analogue scale scores. The Df-restricted solution and the placebo had an equal effect on both pruritus and the skin manifestations (P>0.05). The results of this study indicate that in dogs with atopic dermatitis based on hypersensitivity to environmental allergens in addition to D. farinae, Df-restricted immunotherapy is insufficient to control the disease. Consequently, a solution for allergen-specific immunotherapy should remain customised.

Two Loci on Chromosome 5 Are Associated with Serum IgE Levels in Labrador Retrievers

Crosslinking of immunoglobulin E antibodies (IgE) bound at the surface of mast cells and subsequent mediator release is considered the most important trigger for allergic reactions. Therefore, the genetic control of IgE levels is studied in the context of allergic diseases, such as asthma, atopic rhinitis, or atopic dermatitis (AD). We performed genome-wide association studies in 161 Labrador Retrievers with regard to total and allergen-specific immunoglobulin E (IgE) levels. We identified a genome-wide significant association on CFA 5 with the antigen-specific IgE responsiveness to Acarus siro. We detected a second genome-wide significant association with respect to the antigen-specific IgE responsiveness to Tyrophagus putrescentiae at a different locus on chromosome 5. A. siro and T. putrescentiae both belong to the family Acaridae and represent so-called storage or forage mites. These forage mites are discussed as major allergen sources in canine AD. No obvious candidate gene for the regulation of IgE levels is located under the two association signals. Therefore our studies offer a chance of identifying a novel mechanism controlling the host's IgE response.

Randomised controlled trial of short bursts of a potent topical corticosteroid versus prolonged use of a mild preparation for children with mild or moderate atopic eczema

Objective To determine whether a three day burst of a potent corticosteroid is more effective than a mild preparation used for seven days in children with mild or moderate atopic eczema. Design Randomised, double blind, parallel group study of 18 weeks' duration. Setting 13 general practices and a teaching hospital in the Nottingham area. Participants 174 children with mild or moderate atopic eczema recruited from general practices and 33 from a hospital outpatient clinic. Interventions 0.1% betamethasone valerate applied for three days followed by the base ointment for four days versus 1% hydrocortisone applied for seven days. Main outcome measures Primary outcomes were total number of scratch­free days and number of relapses. Secondary outcomes were median duration of relapses, number of undisturbed nights, disease severity (six area, six sign atopic dermatitis severity scale), scores on two quality of life measures (children's life quality index and dermatitis family impact questionnaire), and number of patients in whom treatment failed in each arm. Results No differences were found between the two groups. This was consistent for all outcomes. The median number of scratch­free days was 118.0 for the mild group and 117.5 for the potent group (difference 0.5, 95% confidence interval - 2.0 to 4.0, P = 0.53). The median number of relapses for both groups was 1.0. Both groups showed clinically important improvements in disease severity and quality of life compared with baseline. Conclusion A short burst of a potent topical corticosteroid is just as effective as prolonged use of a milder preparation for controlling mild or moderate atopic eczema in children.

Comparative effects of pimecrolimus cream vehicle and three commercially available moisturizers on skin hydration and transepidermal water loss

Background: Hydration and integrity of the horny layer is essential to normal skin function. Objective: Comparison of the hydrating properties of three moisturizers with pimecrolimus cream vehicle. Methods: Four test preparations (high-quality skin cream, cold cream emulsion, emollient oil, pimecrolimus cream vehicle) were applied to four different regions of the forearms and legs. Transepidermal water loss (TEWL) was assessed by evaporimetry at baseline, and 3 and 6 hours after arm application, and electrical capacitance was assessed by corneometry at baseline, and 1, 2, 3 and 6 hours after leg application. Results: Corneometry assessment - in terms of efficacy in moisturizing the skin, test preparations were ranked (best to worst): high-quality skin cream (45.9 arbitrary units versus 75.3; p < 0.001) > pimecrolimus vehicle cream (46.6 versus 61.5; p < 0.001) > emollient oil (43.5 versus 54.8; p = 0.006) > cold cream emulsion (44.8 versus 49.9; p = 0.738). Untreated skin (control) had a mean capacitance of 44.8 units at baseline and 48.5 units at endpoint. Evaporimetry (assessment of TEWL) revealed no significant differences between control and any test preparation at any timepoint. Conclusions: Pimecrolimus cream vehicle has skin hydration properties comparable with highly effective commercially available products. No test preparation had a significant effect on TEWL.

Food Allergy and Anaphylaxis in Infants and Preschool-Age Children

Food allergy (FA) prevalence data in infants and preschool-age children are sparse, and proposed risk factors lack confirmation. In this study, 19 children’s day care centers (DCC) from 2 main Portuguese cities were selected after stratification and cluster analysis. An ISAAC’s (International Study of Asthma and Allergies in Childhood) derived health questionnaire was applied to a sample of children attending DCCs. Outcomes were FA parental report and anaphylaxis. Logistic regression was used to explore potential risk factors for reported FA. From the 2228 distributed questionnaires, 1217 were included in the analysis (54.6%). Children’s median age was 3.5 years, and 10.8% were described as ever having had FA. Current FA was reported in 5.7%. Three (0.2%) reports compatible with anaphylaxis were identified. Reported parental history of FA, personal history of atopic dermatitis, and preterm birth increased the odds for reported current FA. A high prevalence of parental-perceived FA in preschool-age children was identified. Risk factor identification may enhance better prevention.

Update in clinical allergy and immunology.

In the recent years, a tremendous body of studies has addressed a broad variety of distinct topics in clinical allergy and immunology. In this update, we discuss selected recent data that provide clinically and pathogenetically relevant insights or identify potential novel targets and strategies for therapy. The role of the microbiome in shaping allergic immune responses and molecular, as well as cellular mechanisms of disease, is discussed separately and in the context of atopic dermatitis, as an allergic model disease. Besides summarizing novel evidence, this update highlights current areas of uncertainties and debates that, as we hope, shall stimulate scientific discussions and research activities in the field.

The pro-allergic influences of helminth parasites

Parasitic infection is highly allergenic, and the present paper illustrates how parasites might disrupt the regulation of IgE synthesis, resulting in heightened Th-2 responses. The study of parasites, and dysregulation of the IgE ntwork, could in turn provide information relating to the aetiology of allergic diseases such as asthma and atopic dermatitis.

The Role of Skin Opioid Receptor System in Itch

Opioid receptors are key players in induction of chronic itch. This could be confirmed using opiate receptor knockout mice experiments and clinical studies on patients with chronic itch. We have induced a dry skin dermatitis as a model for chronic itching on -(MOR) and -(KOR) opioid receptor knockout (KO) mice. MOR KO mice scratched significantly less than wild type (WT). Additionally the epidermal hypertrophy caused by chronic dermatitis and the amount of epidermal nerve endings in MOR KO mice were significantly decreased than in WT mice. KOR KO mice showed similar scratching behavior as MOR KO mice; however the changes were less significant. In addition, we performed a double blind, placebo controlled, cross over study using topically applied opioid receptor antagonist, Naltrexone, on patients with pruritus in atopic dermatitis. The results revealed significant effects of the topical application of Naltrexone in patients with chronic pruritus (45% improvement of pruritus by VAS compared to placebo, n=24), but not in patients with acute pruritus (7%, n=15). These studies establish the clinical relevance of MOR system and the peripheral, epidermal nerve endings in chronic pruritus and warrant further research and therapeutic potential for such research.

Role of Notch signaling in the skin and cornea

Résumé : La voie de signalisation Notch est essentielle pour la différentiation de l'épiderme lors du développement embryonnaire de la peau. Il a été démontré que l'inactivation de Notch1 dans la peau de souris conduit à une hyperplasie de l'épiderme ainsi qu'à la formation subséquente de carcinomes basocellulaires ainsi que de plaques cornéennes. L'inactivation de Notch1 dans la cornée combinée à des lésions mécaniques démontre que les cellules progénitrices de la cornée se différentient en un épithélium hyperplasique et kératinisé comme la peau. Ce changement de destinée cellulaire conduit à une cécité cornéenne et implique des processus non-autonomes aux cellules épithéliales, caractérisés par la sécrétion de FGF-2 par l'épithélium Notch1-/- suivi d'une vascularisation et d'un remaniement du stroma sous-jacent. La déficience en vitamine A est connu comme cause de lésions cornéennes humaines (xérophtalmie sévère). En accord, nous avons trouvé que la signalisation Notch1 était liée au métabolisme de la vitamine A par la régulation de l'expression de CRBP1, nécessaire pour générer un pool de rétinol intracellulaire. La perte de Notch1 dans l'épiderme, l'autre récepteur de la famille présent dans la peau marine, ne conduit pas à un phénotype manifeste. Cependant, l'inactivation dans l'épiderme de Notch1 et Notch2 ensemble, ou de RBP-J, induit une dermatite atopique (DA) sévère chez les souris. De même, les patients souffrants de DA mais pas ceux souffrant de psoriasis ou de lichen plan, ont une réduction marquée de l'expression des récepteurs Notch dans la peau. La perte de Notch dans les keratinocytes conduit à une activation de la voie NF-κB, ce qui ensuite induit la production de TSLP, une cytokine profondément impliquée dans la pathogenèse de la DA. Nous démontrons génétiquement que TSLP est responsable de la DA ainsi que du développent d'un syndrome myéloprolifératif non-autonome aux cellules induit par le G-CSF. Cependant, ces souris avec une inactivation dans l'épiderme de Notch1 et Notch2 et aussi incapables de répondre au TSLP développent des tumeurs invasive sévères caractérisées par une haute activité de signalisation ß-catenin. TSLPR est identifié comme un potentiel suppresseur de tumeur non-autonome aux cellules tumorales; la transplantation de cellules hématopoïétiques TSLPR-/- dans des souris déficientes pour Notch est suffisant pour causer des tumeurs. Summary : The Notch pathway is essential for proper epidermal differentiation during embryonic skin development. It has previously been demonstrated that Notch1 inactivation in marine skin results in epidermal hyperplasia and subsequent formation of basal cell carcinoma-like (BCC-like) tumors as well as corneal plaques. Inducible ablation of Notch1 in the cornea combined with mechanical wounding show that Notch1 deficient corneal progenitor cells differentiate into a hyperplasic, keratinized, skin-like epithelium. This cell fate switch leads to corneal blindness and involves cell non-autonomous processes, characterized by secretion of FGF-2 through Notch1-/- epithelium followed by vascularisation and remodelling of the underlying stroma. Vitamin A deficiency is known to induce a similar corneal defect in humans (severe xerophthalmia). Accordingly, we found that Notch1 signaling is linked to vitamin A metabolism by regulating the expression of CRBP1, required to generate a pool of intracellular retinol. Epidermal loss of Notch2, the other Notch receptor present in marine skin, doesn't lead to any overt phenotypes. However, postnatal epidermis-specific inactivation of both Notch1 and Notch2, or of RBP-J, induces the development of a severe form of atopic dermatitis (AD) in mice. Likewise, patients suffering from AD, but not psoriasis or lichen planas, have a marked reduction of Notch receptor expression in the skin. Loss of Notch in keratinocytes leads to an activation of NF-κB signaling which in turn induces the production of Thymic stromal lymphopoietin (TSLP), a cytokine deeply implicated in the pathogenesis of AD. We genetically demonstrate that TSLP is responsible for AD as well as the development of a cell non-autonomous G-CSF induced myeloproliferative disorder (MPD) in mice. However, these mice with conditional epidermal inactivation of Notch1 and Notch2 as well as incapable to respond to TSLP develop severe invasive tumors characterized by high ß-catenin signaling activity. TSLPR is identified as a potential cell non-autonomous tumor suppressor; transplantation of TSLPR-/- hematopoietic cells into epidermal Notch deficient mice is sufficient to cause tumors.

Validation of a new tool to assess health-related quality of life in psoriasis: the PSO-LIFE questionnaire.

BACKGROUND Several questionnaires have been used to measure health related quality of life (HRQoL) in patients with psoriasis, few have been adapted for use in Spain; none of them was developed specifically for the Spanish population. The purpose of the study was to validate and assess the sensitivity to change of a new questionnaire to measure HRQOL in patients with psoriasis (PSO-LIFE). METHODS Observational, prospective, multicenter study performed in centers around Spain. Patients with active or inactive psoriasis completed the PSO-LIFE together with other Dermatology Quality of Life Index (DLQI) and Psoriasis Disability Index (PDI). A control group of patients with urticaria or atopic dermatitis was also included. Internal consistency and test-retest reliability of the PSO-LIFE were assessed by calculating Cronbach's alpha and Intraclass Correlation Coefficient (ICC). Validity was assessed by examining factorial structure, the capacity to discriminate between groups, and correlations with other measures. Sensitivity to change was measured using effect sizes. RESULTS The final sample included for analysis consisted of 304 patients and 56 controls. Mean (SD) age of psoriasis patients was 45.3 (14.5) years compared to 38.8 (14) years for controls (p < 0.01). Cronbach's alpha for the PSO-LIFE was 0.95 and test-retest reliability using the ICC was 0.98. Factor analysis showed the questionnaire to be unidimensional. Mean (SD) PSO-LIFE scores differed between patients with psoriasis and controls (64.9 [22.5] vs 69.4 [17.3]; p < 0.05), between those with active and inactive disease (57.4 [20.4] vs 76.4 [20.6]; p < 0.01), and between those with visible and non-visible lesions (63.0 [21.9] vs. 74.8 [23.9]; p < 0.01). The correlation between PSO-LIFE and PASI scores was moderate (r = -0.43) while correlations with DLQI and PDI dimensions ranged from moderate to high (between 0.4 and 0.8). Effect size on the PSO-LIFE in patients reporting 'much improved' health status at study completion was 1.01 (large effect size). CONCLUSIONS The present results provide substantial support for the reliability, validity, and responsiveness of the PSO-LIFE questionnaire in the population for which it was designed.

Efecte de la nutrició precoç en el desenvolupament de sibilàncies

Objectiu: provar que, enfront de l’aparició de sibilàncies, l’alletament matern es comporta com a un factor protector i l’alletament artificial com a un factor inductor. Material i mètodes: assaig clínic controlat, randomitzat, a doble cec amb grup control i seguiment de 8 anys, de la submostra espanyola, en el seu 5è any de seguiment, del treball multicèntric europeu EU CHILDHOOD OBESITY PROGRAMME (QLK1-2001-00389). La població es va dividir en 3 grups: nadons alimentats amb lactància artificial amb baix contingut proteic, nadons alimentats amb lactància artificial amb alt contingut proteic i un grup control de nadons alimentats amb llet materna. Per avaluar l’aparició de sibilàncies i la seva evolució en el temps es van realitzar entrevistes als pares a mesura que la població assolia els 6 anys de vida sobre qüestions referides als 3 i als 6 anys i s’havien de realitzar entrevistes als 8 anys de vida sobre qüestions referdies a aquesta mateixa edat. Per comprovar la repercussió en la funció pulmonar i valorar la base atòpica, es tenia previst realitzar, als 8 anys, espirometria, prik test amb aeroalergens, determinació de IgE sèrica total i quantificació dels eosinòfils en sang perifèrica. S’han valorat possibles factors de confusió com antecedents familiars de malalties de base al•lèrgica, nivell socioeconòmic familiar, factors, ambient epidemiològic i s’ha estudiat altra morbiditat associada com episodis de febre, vòmits, diarrea, dermatitis atòpica, refredat de vies respiratòries altes i prescripció mèdica d’antibiòtics. Resultats: només un 20’8% van rebre alletament matern. No s’han trobat diferències estadísticament significatives entre la història d’episodis de sibilàncies i el tipus d’alletament rebut. Tampoc s’han trobat diferències estadísticament significatives entre l’alimentació rebuda i la història de dermatitis atòpica. La llet artificial es va associar, amb significació estadística, a una major prescripció d’antibiòtics i una major incidència de patir diarrees i, sense significació estadística, es va associar a un augment del risc de patir RVA. La lactància materna es va associar amb significació estadística a una menor prescripció d’antibiòtics. La presència de germans grans i un baix nivell d’educació de la mare van contribuir a augmentar la morbiditat durant el primer any de vida. El consum d’alcohol durant l’embaràs es va associar a més episodis de vòmits i el consum de tabac a més episodis de diarrea. Conclusions: l’alletament artificial no predisposa a patir més episodis de sibilàncies ni de dermatitis atòpica. La lactància materna exclusiva durant almenys 3 mesos disminueix el risc de diarrees en els primers 6 mesos de vida i retarda l’aparició d’infeccions aparentment bacterianes que requereixen tractament antibiòtic. L’alletament matern exclusiu durant un mínim de tres mesos no comporta una substancial disminució de la morbiditat durant els primers 12 mesos de vida.