A atopia ou dermatite atópica é uma doença inflamatória pruriginosa, crônica e recorrente reconhecida como a segunda alergopatia mais comum, estando aquém apenas da dermatite alérgica à picada de pulgas. Esta doença é caracterizada pela presença exacerbada de prurido corpóreo, infringindo sofrimento ao paciente e desalentando seu proprietário. A busca a uma boa \"qualidade de vida\" está sendo cada vez mais demandada pelos proprietários de animais alergopatas ou portadores de outras doenças crônicas. Por se tratar de uma doença de longo decurso, o tratamento com glicocorticóides pode causar diversos efeitos colaterais, além de doenças mais graves como diabetes melitus e hiperadrenocorticismo iatrogênico. Como alternativa ao tratamento de cães atópicos, a ciclosporina (CsA) acaba tornando-se uma boa opção terapêutica. A CsA inibe as funções das células que iniciam a resposta imunológica (células de Langerhans e linfócitos) e das células que efetuam a resposta alérgica (mastócitos e eosinófilos) e, também, diminui a liberação de histamina e de várias citocinas. Os objetivos do presente estudo incluíram: análise da eficácia da CsA na redução de lesões corpóreas e do prurido com auxílio do CADESI-03 (Olivry et al.,2007) e de duas escalas de prurido corpóreo; detecção de ocorrência de eventuais efeitos adversos (tegumentares ou sistêmicos) decorrentes da terapia imunomodulatória através da realização de hemograma, função renal, função hepática e mensuração da pressão arterial; avaliação e monitoramento da qualidade de vida de 21 animais atópicos tratados com ciclosporina (5 mg/Kg, SID durante 60 dias) com auxílio de uma escala validada para cães. A CsA mostrou-se eficaz no tratamento da dermatite atópica canina pois reduziu as lesões corpóreas em 70% após 60 dias de terapia. Nesse mesmo período ocorreu redução da intensidade do prurido corpóreo em 52,6%, avaliado através da escala numérica verbal; e observou-se redução significativa na escala qualitativa de prurido corpóreo (Hill, 2002; modificada), uma vez que os níveis máximos de prurido (\"três\" e \"quatro\") quase não foram observados após a terapia imunomodulatória. Os efeitos adversos observados foram relacionados a distúrbios gastrintestinais e, ocorreram com maior freqüência nos primeiros 15 dias de tratamento. Alterações laboratoriais não foram observadas. Os animais portadores de dermatite atópica apresentaram melhora no escore de qualidade de vida em 32%. A CsA mostrou-se eficaz no tratamento da dermatite atópica canina. / Atopic dermatitis (AD) is an inflammatory, pruritic and chronic allergic skin disease. It´s recognized as the second most common allergic skin disease of dogs after flea allergy. Pruritus is the predominant sign of canine AD affecting a variety of areas of the body, leading to intense suffering to the animal and its owner. \"Quality of life\" (QL) is being much more requested from owner of animals with allergic skin diseases or with any kind of chronic disease. The long-term use of glucocorticoids therapy can be devastating because of its inumerous adverse effects and secondary diseases like diabetes mellitus and iatrogenic hiperadrenocorticism. Cyclosporine (CsA) has been considered a good therapeutic option in the treatment of canine atopic dermatitis. It inhibits the activation of cells that initiate cutaneous immune response (Langerhans\' cells and lymphocytes) and cells that mediate allergic reactions (mast cell and eosinophils). It also decreases histamine and other citocines release. The objectives of this study included: analysis of the efficacy of CsA in reducing skin lesions and pruritus of 21 atopic dogs using CADESI-03 (Olivry ey al., 2007) and two scales to quantify levels of body itching; detection of any possible adverse effects (dermatologic or systemic) secondary to immunomodulatory therapy, by performing complete blood count, renal and hepatic function and measurement of blood pressure; evaluation and monitoring QL from dogs treated with CsA (5 mg/Kg, SID during 60 days) with a validated scale; This immunomodulatory therapy was considered an effective treatment for atopic dogs because it reduced skin lesions in 70% after 60 days of therapy. During that period there was a reduction of body itching in 52,6% by verbal numeric scale, and there was significant reduction on qualitative scale of body itching (Hill, 2002; modified), since maximum levels of pruritus (\"three\" and \"four\") were hardly observed after immunomodulatory therapy. Gastrointestinal disorders were observed and appeared most often in the first 15 days of therapy. Laboratory abnormalities were not detected. The quality of life of these atopic dogs treated with CsA for 60 days was improved by 32%. CsA was effective and safe in the treatment of canine atopic dermatitis.

<p>Morbidity of asthma has increased over the world. The reasons for this increase have remained unclear. Studies in children have reported considerable East-West difference in the prevalence of atopy and respiratory allergies.</p><p>The aim of this thesis was to compare the prevalence and risk factors of respi-ratory symptoms, atopic sensitisation and bronchial hyperresponsiveness (BHR) in young adults in Estonia and Sweden. </p><p>Following the protocol of the European Community Respiratory Health Survey (ECRHS), two random population samples, 3000 from Tartu, Estonia, and 3600 from Uppsala, Sweden were investigated with postal questionnaires. Random sub samples and subjects with asthma-like complaints were subsequently interviewed, BHR was tested and serum samples analysed for total and specific IgE and eosinophil cationic protein (ECP). In a separate study two methacholine challenge methods, using either Spira Elektro2 or Mefar MB3 as dosimeters, were compared on 28 mild to moderate asthma patients.</p><p>Symptoms of asthma and hay fever were less common in Esto-nia than in Sweden, while respiratory symptoms in general were more common in Estonia. The prevalence of BHR was high and the prevalence of atopy and the levels of serum ECP were low in Tartu. The differences between the two centres in the prevalence of atopy and allergic rhinitis diminished with age, indicating a probable cohort effect. Current smoking was a dominant risk factor for BHR and for all respiratory symptoms, except attacks of asthma, both in Tartu and Uppsala. There was some difference between risk factors for BHR and atopy between Tartu and Uppsala, mostly of social and environmental origin. The low prevalence of hay fever and asthma in Tartu seemed to be partly explained by a lack of awareness of atopy and allergic diseases in the Estonian society. The estimated cumulative dose causing a 20% fall in FEV₁ was smaller and the decline of FEV₁ /log(dose) curve steeper, using the Spira, compared to the Mefar protocol.</p>

<p>Immunoglobulin E (IgE) occurs exclusively in mammals and is one of five immunoglobulin (Ig) classes found in man. Unlike other isotypes, IgE is best known for its pathological effects, whereas its physiological role remains somewhat elusive. </p><p>To trace the emergence of IgE and other post-switch isotypes we have studied Ig expression in two monotreme species, the duck-billed platypus (<i>Ornithorhynchus anatinus</i>) and the short-beaked echidna (<i>Tachyglossus aculeatus</i>), leading to the cloning of IgE, two IgG isotypes in platypus and echidna IgE. The presence of IgE and the conservation of the overall structure in all extant mammalian lineages indicates an early appearance in mammalian evolution and a selective advantage of structural maintenance. Furthermore, both of the two highly divergent platypus γ-chains have three constant domains. Hence, the major evolutionary changes that gave rise to the IgE and IgG isotypes of present day mammals occurred before the separation of monotremes from the marsupial and placental lineages, estimated to have occurred 150-170 million years ago.</p><p>As the central mediator in atopic allergy, IgE is a prime target in the development of preventive treatments. This thesis describes an active immunization strategy that has the potential to reduce IgE to a clinically significant extent. The active vaccine component is a chimeric IgE molecule, Cε2-Cε3-Cε4. The receptor-binding target domain, Cε3, is derived from the recipient species, whereas the flanking domains, acting both as structural support and to break T-cell tolerance, are derived from an evolutionarily distant mammal. Vaccination of ovalbumin-sensitized rats resulted in a substantial reduction in total IgE in three out of four strains, accompanied by a significant reduction in skin-reactivity upon allergen challenge. No cross-linking activity was observed and the response to vaccination was reversible with time. The apparent safety and efficacy of the vaccine suggest that active immunization against IgE has the potential to become a therapeutic method for humans. </p><p>Furthermore, the cloning and expression of the pig (<i>Sus scrufa</i>) ε-chain will facilitate the development of sensitive and specific assays for pig IgE, thus increasing the possibilities of using the pig model in future studies of IgE-mediated reactions.</p>

Morbidity of asthma has increased over the world. The reasons for this increase have remained unclear. Studies in children have reported considerable East-West difference in the prevalence of atopy and respiratory allergies. The aim of this thesis was to compare the prevalence and risk factors of respi-ratory symptoms, atopic sensitisation and bronchial hyperresponsiveness (BHR) in young adults in Estonia and Sweden. Following the protocol of the European Community Respiratory Health Survey (ECRHS), two random population samples, 3000 from Tartu, Estonia, and 3600 from Uppsala, Sweden were investigated with postal questionnaires. Random sub samples and subjects with asthma-like complaints were subsequently interviewed, BHR was tested and serum samples analysed for total and specific IgE and eosinophil cationic protein (ECP). In a separate study two methacholine challenge methods, using either Spira Elektro2 or Mefar MB3 as dosimeters, were compared on 28 mild to moderate asthma patients. Symptoms of asthma and hay fever were less common in Esto-nia than in Sweden, while respiratory symptoms in general were more common in Estonia. The prevalence of BHR was high and the prevalence of atopy and the levels of serum ECP were low in Tartu. The differences between the two centres in the prevalence of atopy and allergic rhinitis diminished with age, indicating a probable cohort effect. Current smoking was a dominant risk factor for BHR and for all respiratory symptoms, except attacks of asthma, both in Tartu and Uppsala. There was some difference between risk factors for BHR and atopy between Tartu and Uppsala, mostly of social and environmental origin. The low prevalence of hay fever and asthma in Tartu seemed to be partly explained by a lack of awareness of atopy and allergic diseases in the Estonian society. The estimated cumulative dose causing a 20% fall in FEV1 was smaller and the decline of FEV1 /log(dose) curve steeper, using the Spira, compared to the Mefar protocol.

Immunoglobulin E (IgE) occurs exclusively in mammals and is one of five immunoglobulin (Ig) classes found in man. Unlike other isotypes, IgE is best known for its pathological effects, whereas its physiological role remains somewhat elusive. To trace the emergence of IgE and other post-switch isotypes we have studied Ig expression in two monotreme species, the duck-billed platypus (Ornithorhynchus anatinus) and the short-beaked echidna (Tachyglossus aculeatus), leading to the cloning of IgE, two IgG isotypes in platypus and echidna IgE. The presence of IgE and the conservation of the overall structure in all extant mammalian lineages indicates an early appearance in mammalian evolution and a selective advantage of structural maintenance. Furthermore, both of the two highly divergent platypus γ-chains have three constant domains. Hence, the major evolutionary changes that gave rise to the IgE and IgG isotypes of present day mammals occurred before the separation of monotremes from the marsupial and placental lineages, estimated to have occurred 150-170 million years ago. As the central mediator in atopic allergy, IgE is a prime target in the development of preventive treatments. This thesis describes an active immunization strategy that has the potential to reduce IgE to a clinically significant extent. The active vaccine component is a chimeric IgE molecule, Cε2-Cε3-Cε4. The receptor-binding target domain, Cε3, is derived from the recipient species, whereas the flanking domains, acting both as structural support and to break T-cell tolerance, are derived from an evolutionarily distant mammal. Vaccination of ovalbumin-sensitized rats resulted in a substantial reduction in total IgE in three out of four strains, accompanied by a significant reduction in skin-reactivity upon allergen challenge. No cross-linking activity was observed and the response to vaccination was reversible with time. The apparent safety and efficacy of the vaccine suggest that active immunization against IgE has the potential to become a therapeutic method for humans. Furthermore, the cloning and expression of the pig (Sus scrufa) ε-chain will facilitate the development of sensitive and specific assays for pig IgE, thus increasing the possibilities of using the pig model in future studies of IgE-mediated reactions.

Background The prevalence of atopic disease among children in the formerly socialist countries in Europe, with a life style similar to that prevailing in Western Europe 30–40 years ago, is low, whereas there has been a pronounced increase in industrialized countries over the last decades. The environment during infancy influences the risk of developing allergy for many years, perhaps even for life. Objective To investigate the development of allergen-specific cytokine responses during the first 2 years of life in two geographically adjacent countries with marked differences in living conditions and incidence of atopic diseases, i.e. Estonia and Sweden. Methods The development of immune responses to food (β-lactoglobulin (BLG) and ovalbumin (OVA)) and inhalant (cat and birch) allergens was studied from birth up to the age of 2 years in 30 Estonian and 76 Swedish infants. Clinical investigation and skin prick tests were performed and blood samples were obtained at birth and at 3, 6, 12 and 24 months. Results The levels of IL-5, IL-10 and IL-13 secreted by peripheral blood mononuclear cells stimulated with BLG, OVA and cat allergen in Estonian and Swedish infants declined during the first 3 months of life. All cytokines then progressively increased in the Swedish infants, indicating the replacement of non-specifically responding immature cord blood T cells with specific T memory cells, which are primed postnatally. The resurgence of allergen-specific responses in the Estonian infants was less marked. These differences were particularly notable for birch-specific T cell responses, which correlated with development of atopic disease in the Swedish children. Conclusions The development of specific T cell memory to food and inhalant allergens during the first 2 years of life differs between infants living in Sweden and Estonia, and mirrors the disparate patterns of expression of allergic disease which subsequently develops in the respective populations.

Exposure to a strong T-helper 2 (Th2)-like environment during fetal development may promote allergy development. Increased cord blood (CB) levels of the Th2-associated chemokine CCL22 were associated with allergy development during the first 2 y of life. The aim of the present study was to determine whether CB Th1- and Th2-associated chemokine levels are associated with allergy development during the first 6 y of life, allowing assessment of respiratory allergic symptoms usually developing in this period. The CB levels of cytokines, chemokines, and total IgE were determined in 56 children of 20 women with allergic symptoms and 36 women without allergic symptoms. Total IgE and allergen-specific IgE antibody levels were quantified at 6, 12, 24 mo, and 6 y of age. Increased CB CCL22 levels were associated with development of allergic sensitization and asthma and increased CCL17 levels with development of allergic symptoms, including asthma. Sensitized children with allergic symptoms showed higher CB CCL17 and CCL22 levels and higher ratios between these Th2-associated chemokines and the Th1-associated chemokine CXCL10 than nonsensitized children without allergic symptoms. A pronounced Th2 deviation at birth, reflected by increased CB CCL17 and CCL22 levels, and increased CCL22/CXCL10 and CCL17/CXCL10 ratios might promote allergy development later in life.

Background: Birch pollen is an important outdoor allergen able to aggravate symptoms in atopic dermatitis (AD). Specific immunotherapy (SIT), an established procedure for allergic airway diseases, might also represent an attractive therapeutic option for the causal treatment of allergen-triggered cutaneous symptoms in these patients. Studies with house dust mite SIT have already shown beneficial effects in AD patients, whereas the safety and efficacy of SIT with birch pollen extract in AD patients have not been studied so far. The aim of this study was to evaluate for the first time the safety and efficacy of SIT with a depigmented polymerized birch pollen extract in AD patients. Methods: Fifty-five adult patients with moderate-to-severe AD and clinically relevant sensitization to birch pollen received SIT for 12 weeks. SIT was continued during birch pollen season. The assessment of safety, the total SCORAD value, and the Dermatology Life Quality Index (DLQI) were evaluated. Results: The median total SCORAD value was reduced by 34% (p < 0.001) during the course of treatment and the mean DLQI improved by 49% (p < 0.001) despite strong simultaneous birch pollen exposure. Eight patients (14.5%) developed systemic reactions and 19 patients (34.5%) developed local reactions which were of mild intensity in most cases. No patient discontinued the study prematurely due to adverse drug reactions. Coseasonal treatment was well tolerated. Conclusion: SIT with a depigmented polymerized birch pollen extract leads to significant improvement of the SCORAD value and the DLQI in patients suffering from moderate-to-severe AD sensitized to birch pollen. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Diss. (sammanfattning) Linköping : Univ., 2002. / Härtill 5 uppsatser.

Teste intradérmico avalia reação de hipersensibilidade a diversos agentes que possam apresentar poder reacional alérgico e são comumente utilizados para complementar o diagnóstico da dermatite atópica canina (DAC). Ainda não existe consenso sobre as concentrações de histamina e extratos alergênicos a serem utilizadas. Para determinar a concentração ideal de histamina, como controle positivo, e do limiar irritativo de extratos alergênicos em teste intradérmico é necessário que diversas concentrações sejam avaliadas em uma população bem numerosa de cães hígidos. O objetivo desta pesquisa foi avaliar em 160 cães sadios submetidos a teste intradérmico, quais seriam as concentrações de histamina e de extratos alergênicos consideradas ideais. A solução contendo 0,1 mg/mL de histamina foi considerada como parâmetro ideal, provocando reações cutâneas com diâmetro médio, mediana e desvio padrão, de 15,18 mm, 14,97 mm e 2,07 mm, respectivamente. A partir do estabelecimento da concentração de histamina, foram determinadas as concentrações ótimas dos extratos alergênicos, expressas em PNU/mL: 1.000 para Dermatophagoides pteronyssinus, 500 para D. farinae, 125 para Blomia tropicalis e 2.000 para Malassezia pachydermatis. Futuros estudos devem ser conduzidos em cães atópicos para verificação da acurácia dos testes intradérmicos realizados com essas concentrações. / Intradermal testing evaluates hipersensitivity reaction to different agents that can present allergic reactivity power. It is commonly used to complement canine atopic dermatitis diagnosis. There is still no consensus about histamine concentrations and allergen extracts to be used. The determination of the histamine ideal concentration as positive control and the irritant threshold of allergen extracts for intradermal testing, requires evaluation of different concentrations on a large population of healthy dogs. The purpose of this research was to evaluate the ideal histamine and allergen extracts concentrations on 160 healthy dogs submitted to intradermal testing. A histamine solution 0,1 mg/mL was considered the ideal parameter. It caused cutaneous reactions with average diameter, median measure and standard deviation of 15.18 mm, 14.97 mm and 2.07 mm, respectively. From the histamine concentration establishment, the optimum allergen extracts concentrations were determined, expressed by PNU/mL: 1.000 for Dermatophagoides pteronyssinus, 500 for D. farinae, 125 for Blomia tropicalis and 2.000 for Malassezia pachydermatis. Future studies have to be conducted on atopic dogs to verify the accuracy of the intradermal testing with these concentrations.