Santana, ANC. Estudo da trombose microvascular em biópsias pulmonares de pacientes com Granulomatose de Wegener. [tese]. São Paulo: Faculdade de Medicina, Universidade de São Paulo; 2008. A granulomatose de Wegener (GW) é associada com eventos trombo-embólicos. Neste trabalho, quantificamos os trombos em artérias pulmonares de pequeno/médio calibre de pacientes com GW (n:24), comparando com um grupo Controle normal (n:16). O resultado mostrou que a área total das artérias no grupo GW foi similar a do grupo Controle. Já a área do trombo foi significativamente maior no grupo GW em relação ao Controle. Em contrapartida, a área livre do lúmen do vaso foi significativamente menor no grupo GW em comparação ao Controle. Concluindo, este estudo demonstra uma obstrução da microcirculação pulmonar na GW, sugerindo um papel da trombose in situ na fisiopatologia desta doença / Wegeners granulomatosis (GW) is associated with thromboembolic events. In this work, we quantified the thrombus in small/medium-sized pulmonary arteries of patients with GW (n:24) compared to normal controls (n:16). The results showed that the GW and control arteries were similar regarding total area. The thrombus area was significantly increased in GW compared to controls; in contrast, the free lumen area was significantly decreased in GW compared to controls. In summary, this study shows obstruction of microvascular bed in GW, suggesting a possible role of thrombosis in situ in pathophysiology of this vasculitis

Introdução: A arterite de Takayasu (AT) é uma vasculite sistêmica rara caracterizada por oclusão, ectasias, aneurismas e estenose da aorta e seus ramos principais. Consequentemente, pode levar a uma redução no pulso de uma ou mais artérias, diferença nos níveis de pressão sistólica dos membros, presença de sopros (cervicais, cardíacos, axilares e/ou abdominais), além da presença de claudicação vascular (membros e/ou vísceras abdominais) e isquemia periférica, o que por sua vez pode levar a uma maior limitação funcional e consequentemente ao sedentarismo. Esses acometimentos podem, em última análise, levar a uma diminuição da capacidade funcional, da capacidade aeróbia e da força muscular, o que está associado com aumento no risco de mortalidade, assim como já foi demonstrado em outras doenças com manifestações clínicas semelhantes, como a doença arterial periférica (DAP). Nesse sentido, o exercício tem sido apontado como uma estratégia interessante para reduzir esses fatores de risco em pacientes com doenças autoimunes inflamatórias. Entretanto, em pacientes com AT, nenhum estudo até o momento, avaliou a capacidade funcional, a capacidade aeróbia e a força muscular desses pacientes, bem como a segurança da prescrição do exercício por meio da resposta inflamatória a uma sessão aguda de esforço. Da mesma forma, o treinamento aeróbio poderia ser uma potencial estratégia em melhorar essas condições, no entanto, o mesmo ainda foi avaliado nesses pacientes. Objetivos: Avaliar os efeitos agudos e crônicos do exercício físico aeróbio em pacientes com AT em remissão. Métodos: Em um primeiro momento, a capacidade aeróbia, força e função muscular, qualidade de vida, prejuízo de caminhada (WIQ) e função endotelial, foram avaliadas em 11 pacientes com AT e comparados com 10 controles saudáveis (GC) que foram pareados por sexo, idade e IMC. Além disso, foi avaliada e comparada a cinéticas das citocinas (IL1ra, IL-6, IL-10, IL-12p70, TNF-alfa, VEGF e PDGF AA) além dos receptores solúveis de TNF (sTNFRI e sTNFRII) em resposta a uma sessão de exercício aeróbio (~ 60% do VO2 pico). Uma sub-amostra do grupo AT (n = 6) foi submetida a um programa de treinamento aeróbio por 12 semanas (2 vezes por semana, de 30 a 50 minutos, frequência cardíaca (FC) entre os limiares ventilatórios). Antes e depois do treinamento, a sessão de exercício aeróbio agudo foi realizada e as citocinas e os receptores do TNF solúveis foram avaliados como descrito acima. A capacidade aeróbia, força e função muscular, função endotelial, qualidade de vida e o questionário de caminhada foram avaliados. As citocinas e os sTNFRs foram avaliadas por multiplex. Resultados: Pacientes com AT apresentaram uma capacidade cardiorrespiratória, força e função muscular, qualidade de vida e o questionário WIQ prejudicados quando comparados ao grupo controle. Não houve diferença significativa para a função endotelial entre os dois grupos. De forma geral, uma sessão de exercício aeróbio não afeta de forma diferente a cinética de citocinas em pacientes com AT e seus pares saudáveis. O treinamento aeróbio levou a uma melhora da força e função muscular e do questionário WIQ nos pacientes com AT, enquanto a capacidade aeróbia, função endotelial e qualidade de vida permaneceram inalteradas. O programa de treinamento aeróbio não exacerbou as concentrações de citocinas inflamatórias em pacientes com AT; pelo contrário, a citocina pro-inflamatória TNF-alfa foi diminuídatanto em repouso como após uma sessão de exercício aeróbio. Além disso, o treinamento aeróbio aumentou os fatores pró-angiogênicos VEGF (em repouso) e PDGF AA (em repouso e em resposta para a sessão de exercício aeróbico). Conclusões: Pacientes com AT apresentam a capacidade aeróbia, força e função muscular prejudicada comparada a sujeitos saudáveis. Uma sessão de exercício aeróbio não exacerbou a inflamação em pacientes com AT. Além disso, o treinamento aeróbio pode ser uma intervenção bem tolerada, segura e eficiente capaz de induzir efeitos imunomodulatórios e pró-angiogênicos, como também aumentar a força e a função muscular em pacientes com AT / Background: Takayasu arteritis (TA) is a rare systemic vasculitis characterized by occlusion, ectasia, aneurysms and stenosis of the aorta and its main branches. Consequently, it can lead to a reduction in pulse of one or more arteries, a blood pressure difference between arms, bruits presence (neck, heart, axillary and/or abdominal arteries), and the presence of vascular claudication (limbs and/or abdominal arteries) and peripheral ischemia, which in turn can lead to a greater functional limitation and consequently inactivity. These manifestations may cause a decrease in aerobic capacity, muscular strength and muscular function, which is associated with increased risk of mortality, as has been shown in other diseases with similar clinical manifestations, such as peripheral arterial disease (PAD). In this scenario, exercise emerges as a promising therapeutic tool to partially offset these adverse outcomes, similarly as it occurs in many other inflammatory rheumatic diseases. However, in patients with TA, no study to date has evaluated aerobic capacity, muscular strength and function in this patients, as well as the safety of exercise prescription in inflammatory response to an acute session of aerobic exercise. Similarly, aerobic training could be a potential strategy to improve such conditions in these patients, however, until date, no study has evaluated the effects of exercise training program in this patients. Objectives: To evaluate the acute and chronic effects of aerobic exercise in patients with TA in remission. Methods: At first, aerobic capacity, muscle strength and function, quality of life, walking impairment questionnaire (WIQ) and endothelial function were evaluated in 11 patients with TA and compared with 10 healthy controls (HC) that were matched for sex , age and body mass index (BMI). Furthermore, it was evaluated and compared the cytokines kinetics (IL1ra, IL-6, IL-10, IL-12p70, TNF-alfa, VEGF and PDGF) and soluble TNF receptors (sTNFRI and sTNFRII) in response to an acute session of aerobic exercise (~ 60% VO2 peak). A sub-sample from TA group (n=6) underwent a 12-week exercise training program (12 weeks, 2 times a week, 30 to 50 minutes, heart rate (FC) between the ventilatory threshold). Before and after training, the acute session of aerobic exercise was performed and cytokines and soluble TNF receptors were assessed as described above. Muscle strength and function, aerobic capacity, endothelial function, quality of life, and walking impairment scores were evaluated. Cytokines and sTNFRs were assessed by multiplex. Results: TA patients showed impaired aerobic capacity, muscle strength and function, worst quality of life and walking impairment compared to their healthy counterparts. There was no significant difference in endothelial function between the two groups. The acute session of aerobic exercise lead to overall similar responses on cytokine kinetics in TA and HC groups. The exercise training program improved muscle strength and function, whereas aerobic capacity, quality of life, and endothelial function parameters remained generally unchanged. The exercise training program did not exacerbate inflammatory cytokines in TA patients; on the contrary, the pro-inflammatory cytokine TNF-alfa was diminished both at resting and following the acute session of aerobic exercise. In addition, the exercise training program increased the pro-angiogenic factors VEGF (at resting) and PDGF AA (at resting and in response to the acute session of aerobic exercise). Conclusions: Patients with TA has an impaired aerobic capacity, muscle strength and function compared to healthy subjects. An acute session of aerobic exercise does not exacerbate inflammation in these patients. Furthermore, exercise could be a well-tolerable, safe and efficient intervention able to induce immunomodulatory and pro-angiogenic effects as well as to increase muscle strength and function in TA patients

Disertacijos tema: Odos kraujagyslių ir jungiamojo audinio pažeidimai sergant sistemine skleroze. Disertacijos tikslas buvo nustatyti kraujagyslių pažeidimo ir fibrozės vystymosi eiliškumą, ištiriant kraujagyslių pakitimus odoje ir jungiamajame audinyje sergantiems sistemine skleroze , su šiai patologijai būdinga kraujagyslių atrezija, bei palyginant su kitomis būklėmis, kurių metu kraujagyslių atrezijos nėra (sistemine raudonaja vilklige), bei su būklėmis, kurioms būdingas kraujagyslių funkcinis nestabilumas (Reino sindromas). Tai retrospektyvus tyrimas. Analizuota po 20 kiekvienos iš minėtų ligų sergančių ligonių ir kontrolinės grupės odos biopsijų. Be rutininių histocheminių dažymų, naudata eilė imunohistocheminių žymenų ir elektroninis mikroskopinis tyrimas. Nustatyta, kad sergantiems sistemine skleroze odoje ankščiau, negu išreikšta fibrozė pasireiškia kraujagyslių endotelio pažeidimai ir padidėjęs kraujagyslių sienelės pralaidumas. Nustatyta, kad kraujagyslių endotelio augimo veiksnio VEGF-A ir jo receptoriaus FLT-1, ir ypač HSP-47 (terminio šoko baltymo, kolagenams specifinio šaperono skatinančio fibrozę), bei eNOS (endotelio azoto sintazės) gausi ekspresija yra ankstyvos sisteminės sklerozės stadijos endotelio pakenkimo imunohistocheminiai žymenys. Taip pat nustatyta, kad ankstyvosios sisteminės sklerozės stadijos patogenezėje odoje vyrauja smulkių kraujagyslių pažeidimai. Rekomenduota naudoti odos biopsiją kaip pagalbinį diagnostinį metodą diferencijuojant tarp... [toliau žr. visą tekstą] / Dissertation topic: the damage to dermal blood vessels and connective tissue during systemic sclerosis. The aim of this dissertation was to determine the sequence in the development of vascular damage and fibrosis by studying vascular changes in the skin and connective tissue of systemic sclerosis patients with vascular atresia characteristic of this pathology and by comparing it with other conditions, where there is no vascular atresia (systemic lupus erythematosus), and with conditions, which are characterised by vascular function instability (Raynaud’s phenomenon). This was a retrospective study, which analysed 60 patients with the aforementioned diseases, 20 with each disease, and a control group of 20 skin biopsies. In addition to routine histochemical stains, a series of immunohistochemical signs and electron microscopic examination were used. It was determined that damage to the vascular endothelium and increased permeability of the vascular walls appear earlier than expressed fibrosis in the skin of systemic sclerosis patients and that the abundant expression of vascular endothelial growth factor (VEGF)-A and its receptor FLT-1 and especially HSP-47 (heat shock protein, a collagen-specific chaperone that induces fibrosis) and eNOS endothelial (nitric oxide synthase) are immunohistochemical signs of endothelial injury in the early stage of systemic sclerosis. It was determined that in the pathogenesis of the early stage of systemic sclerosis, damage to the small blood... [to full text]

Dissertation topic: the damage to dermal blood vessels and connective tissue during systemic sclerosis. The aim of this dissertation was to determine the sequence in the development of vascular damage and fibrosis by studying vascular changes in the skin and connective tissue of systemic sclerosis patients with vascular atresia characteristic of this pathology and by comparing it with other conditions, where there is no vascular atresia (systemic lupus erythematosus), and with conditions, which are characterised by vascular function instability (Raynaud’s phenomenon). This was a retrospective study, which analysed 60 patients with the aforementioned diseases, 20 with each disease, and a control group of 20 skin biopsies. In addition to routine histochemical stains, a series of immunohistochemical signs and electron microscopic examination were used. It was determined that damage to the vascular endothelium and increased permeability of the vascular walls appear earlier than expressed fibrosis in the skin of systemic sclerosis patients and that the abundant expression of vascular endothelial growth factor (VEGF)-A and its receptor FLT-1 and especially HSP-47 (heat shock protein, a collagen-specific chaperone that induces fibrosis) and eNOS endothelial nitric oxide synthase are immunohistochemical signs of endothelial injury in the early stage of systemic sclerosis. It was determined that in the pathogenesis of the early stage of systemic sclerosis, damage to the small blood... [to full text] / Disertacijos tema: Odos kraujagyslių ir jungiamojo audinio pažeidimai sergant sistemine skleroze. Disertacijos tikslas buvo nustatyti kraujagyslių pažeidimo ir fibrozės vystymosi eiliškumą, ištiriant kraujagyslių pakitimus odoje ir jungiamajame audinyje sergantiems sistemine skleroze , su šiai patologijai būdinga kraujagyslių atrezija, bei palyginant su kitomis būklėmis, kurių metu kraujagyslių atrezijos nėra (sistemine raudonaja vilklige), bei su būklėmis, kurioms būdingas kraujagyslių funkcinis nestabilumas (Reino sindromas). Tai retrospektyvus tyrimas, analizuota po 20 kiekvienos iš minėtų ligų sergančių ligonių ir kontrolinės grupės odos biopsijų. Be rutinių histocheminių dažymų naudata eilė imunohistocheminių žymenų ir elektroninės mikroskopijos tyrimas. Nustatyta, kad sergantiems sistemine skleroze odoje ankščiau, negu išreikšta fibrozė pasireiškia kraujagyslių endotelio pažeidimai ir padidėjęs kraujagyslių sienelės pralaidumas, kad kraujagyslių endotelio augimo veiksnio VEGF-A ir jo receptoriaus FLT-1, ir ypač HSP-47 (terminio šoko baltymo, kolagenams specifinio šaperono skatinančio fibrozę), bei eNOS (endotelio azoto sintazės) gausi ekspresija yra ankstyvos sisteminės sklerozės stadijos endotelio pakenkimo imunohistocheminiai žymenys. Nustatyta, kad ankstyvosios sisteminės sklerozės stadijos patogenezėje odoje vyrauja smulkių kraujagyslių pažeidimai ir į tą tikslinga atsižvelgti skiriant patogeneze pagristą sisteminės sklerozės gydymą Rekomenduota naudoti odos... [toliau žr. visą tekstą]

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Les vascularites des gros vaisseaux comprennent principalement la maladie de Takayasu et l'artérite à cellules géantes. Elles sont caractérisées par des lésions inflammatoires artérielles, associées à une néo-vascularisation adventitielle importante, une désorganisation architecturale de la paroi artérielle et des lésions fibrotiques, affectant l’aorte et ses principales branches. Ces maladies sont caractérisées par des réponses lymphocytaires Th1 et Th17 excessives et dérégulées. Actuellement, les mécanismes régulant la différenciation lymphocytaire, la réponse endothéliale et l’homéostasie tissulaire en contexte d’inflammation artérielle chronique ne sont pas suffisamment connus. Dans la 1ère partie de nos travaux, nous avons étudié le rôle de l’IL-33, cytokine sécrétée par les cellules endothéliales en cas de nécrose tissulaire, surexprimée dans les vascularites des gros vaisseaux et impliquée dans la régulation de la réponse immune. Nous avons mis en évidence le rôle immunomodulateur de l’IL-33 dans les vascularites des gros vaisseaux. Cette cytokine favorise en effet directement une différenciation Th2 et une augmentation des lymphocytes T régulateurs (Treg). L’IL-33 exerce également son action immunorégulatrice par le biais des mastocytes qui favorisent également une augmentation majeure des Treg en présence d’IL-33, probablement grâce à la sécrétion d’IL-2, essentielle à la survie et l’expansion des Treg et la sécrétion d’indoléamine 2,3 dioxygénase (IDO). L’IL-33 et les mastocytes ont également un rôle paradoxal en contexte inflammatoire, en favorisant les processus de néo-angiogenèse, d’activation endothéliale et d’augmentation de la perméabilité vasculaire, phénomènes participant au recrutement de cellules inflammatoires sur le site lésionnel. L’axe IL-33/ST2 et les mastocytes, via leurs actions pro-Th2, immunorégulatrice, et pro-angiogénique, sont également associés aux processus de réparation tissulaire, qui pourraient s’avérer délétères en cas d’inflammation persistante, en raison du développement de lésions de fibrose. Si l’IL-33 ne semble pas être directement responsable d’une activation ou d’une prolifération fibroblastique au niveau artériel, les mastocytes activés par du sérum de patients ayant une vascularite des gros vaisseaux conduisent en revanche à des modifications du phénotype fibroblastique et induisent une augmentation de production de collagène de type 1 et de fibronectine.Dans la 2ème partie de nos travaux, nous avons mis en évidence des profils de différenciation distincts des lymphocytes T CD4+ dans la maladie de Takayasu et l’artérite à cellules géantes. Nous avons démontré une augmentation des lymphocytes T folliculaires helper (Tfh) circulants dans la maladie de Takayasu. L’augmentation des Tfhc chez les patients ayant une maladie de Takayasu est associée à une augmentation des lymphocytes B circulants et à la présence d’organes lymphoïdes ectopiques aortiques. Les Tfhc des patients Takayasu gardent les propriétés fonctionnelles des lymphocytes Tfh tissulaires, puisqu’ils favorisent la prolifération des lymphocytes B ainsi que leur différenciation en cellules mémoires. Nos résultats suggèrent donc l’implication d’une coopération lymphocytaire B et T centrale dans la physiopathologie de la maladie de Takayasu, qui pourrait être associée à la présence de lymphocytes B auto-réactifs sécrétant des auto-anticorps. / Large vessel vasculitis (LVV) mainly include Takayasu arteritis (TA) and giant cell arteritis (GCA), which are characterized by arterial inflammatory lesions, associated with adventitial neo-angiogenesis and fibrotic lesions. They predominantly involve aorta and its major branches. These diseases are related to unbalanced Th1 and Th17 immune responses. The mechanisms regulating lymphocyte differentiation, endothelial response and tissue homeostasis in arterial inflammatory diseases are not sufficiently known. First, we have studied the role of IL-33, which is a cytokine secreted by endothelial cells in response to tissue necrosis and is involved in the regulation of immune response. We demonstrated the immunomodulatory impact of IL-33 and mast cells in LVV. IL-33 had a direct immunomodulatory impact by increasing Th2 and regulatory T cells in PBMC. IL-33 and MC further enhanced Th2 and regulatory responses by inducing a 6.1 fold increased proportion of Tregs through increased indoleamine 2 3-dioxygenase (IDO) and IL-2 secretion. IL-33 and mast cells also had a paradoxical impact in LVV, by promoting angiogenesis, endothelial activation and vascular permeability. IL-33 and mast cells, through Th2 and regulatory responses and angiogenesis, were associated with tissue repair and arterial fibrosis. Although IL-33 did not appear to directly lead to arterial fibroblast activation and proliferation, mast cells activated by LVV serum induced increased production of type 1 collagen and fibronectin by arterial fibroblasts. In the second part of our work, we have demonstrated distinct differentiation profiles of CD4 + T cells in TA and GCA. We demonstrated an increase in circulating T follicular helper lymphocytes (cTfh), defined as CXCR5+ CD4+ T cells, in TA. The increase of cTfh was associated with an increase in circulating B lymphocytes and the presence of tertiary lymphoid organs in TA aorta. CXCR5+ CD4+ T cells of TA patients helped B cells to differentiate into memory cells, to proliferate and to secrete type G immunoglobulins. Our data provide evidence of the key coordinated role of Tfh and B cells in tertiary lymphoid structures in TA and suggest an antigenic trigger.

No description available.

L’acide mycophénolique (MPA) est un immunosuppresseur très prometteur dans le traitement des maladies auto-immunes (MAI) telles que le lupus érythémateux disséminé (LED) et les vascularites à ANCA, et disponible sous deux formes pharmaceutiques : le mycophénolate mofétil (MMF) et le mycophénolate sodique (EC-MPS). Les études menées chez les patients transplantés recommandent le dosage plasmatique et le suivi pharmacocinétique (PK) du MPA, dans un objectif d’optimisation thérapeutique. A ce jour, ce suivi est encore inexistant dans les MAI, et les données de corrélation concentrations-efficacité thérapeutique, sur lesquelles se base l’optimisation, demeurent toujours rares dans ce domaine. Les travaux présentés dans cette thèse s’inscrivent dans l’étude des corrélations PK/pharmacodynamie (PD) du MPA dans les MAI. Ces travaux ont permis de proposer des schémas et des outils d’optimisation des traitements à base de MPA pour ces patients. Pour cela, les concentrations plasmatiques du MPA et de son métabolite 7-O-glucuronide (MPAG) ont été déterminées pour 53 patients présentant de manifestations extra-rénales de MAI à l’aide d’une méthode de chromatographie couplée à la spectrométrie de masse. Les paramètres PK ont été estimés pour MMF et EC-MPS dans les deux groupes de MAI. D’après ces travaux, l’optimisation du MMF chez les patients atteints de MAI peut reposer sur le suivi de la concentration à 12 h (C12) en MPA. Un seuil de 3 mg/L est proposé afin de maintenir la rémission dans le LED, mais reste à définir dans les vascularites. Pour EC-MPS, une stratégie de prélèvements limités basée sur la mesure de la concentration maximale et la C12 est nécessaire pour estimer l’aire sous la courbe des concentrations entre 0 et 12 h du MPA. / Mycophenolic acid (MPA), the active form of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), is an immunosuppressant increasingly used in the treatment of autoimmune diseases such as systemic lupus erythematosus (SLE) and ANCA-associated vasculitis. In transplant recipients, therapeutic drug monitoring (TDM) of MPA is widely used to prevent acute organ rejection. However, MPA TDM is currently not available in autoimmune diseases, as data on the pharmacokinetic (PK)/pharmacodynamic (PD) relationships are very sparse in this indication. Our aim was to study the possible PK/PD relationships of MPA in patients with non-renal manifestations of SLE or ANCA-associated vasculitis. An assay based on liquid chromatography coupled with mass spectrometry was applied to the PK study of MPA and its major glucuronide metabolite (MPAG) in 53 SLE and vasculitis patients receiving either MMF or EC-MPS. According to our results, in SLE patients with non-renal manifestations, TDM based on the measurement of MPA 12-h trough concentration (C12) would allow optimizing therapies with MMF. A 3-mg/L efficacy threshold could be proposed to prevent clinical flares under MMF maintenance therapy. For EC-MPS, a limited sampling strategy including MPA maximum concentration and C12 is necessary to estimate the area under the curve between 0 and 12-h of MPA.

A Aspergilose Broncopulmonar alérgica (ABPA) é uma doença complexa,desencadeada por uma reação de hipersensibilidade ao Aspergillus fumigatus, que apresenta vários estágios, sendo que no estágio mais grave, os pacientes apresentam bronquiectasias. O diagnóstico da doença é difícil e o maior problema é a falta de antígenos padronizados necessários para a determinação de anticorpos específicos. O objetivo do presente estudo é avaliar se os testes cutâneos com os análogos de Asp f 1 podem auxiliar no diagnóstico e no estadiamento da ABPA. Três grupos de pacientes classificados por testes sorológicos foram obtidos a saber 20 ABPA (16BQ+; 4BQ-), 25 possíveis -ABPA (14BQ+;11BQ-) e 24 asmáticos sem ABPA (11BQ+;13BQ-). Fizeram parte do estudo 10 pessoas sem asma . Todos foram submetidos a testes intradérmicos com três antígenos a-sarcina, mitogilina e estrictocina.Houve uma intensa reação a todos os antígenos e as reações produzidas foram semelhantes para os três antígenos. As reações de leitura tardia positivas à mitogilina foram biopsiadas. As biopsias de 2 (12,5%) dos pacientes BQ+ do grupo ABPA e 5 do grupo ABPA possível com BQ+ (35,6%) mostraram vasculite por depósito de imunocomplexos. 11 pacientes do terceiro grupo não apresentaram vasculite. O quarto grupo não apresentou reação tardia. Todos os pacientes com reação positiva apresentaram BQ+. alfa-sarcina, a mitogilina e a restrictocina diferenciaram pacientes com ABPA por testes intradérmicos e podem ser aplicados no diagnóstico da doença. A maior incidência de bronquiectasias foi encontrada no primeiro grupo (80%) e no segundo (56%). No terceiro grupo nenhum caso foi encontrado em 23 pacientes com asma e teste ID positivo ao aspergillus fumigatus todos os pacientes com vasculite tinham bronquiectasia. Há possibilidade de que as lesões produzidas nos pulmões sejam produzidas por vasculite. / Allergic Bronchopulmonary Aspergillosis (ABPA) is a complex disease, triggered by a hypersensitivity reaction to Aspergillus fumigatus. The disease diagnosis is difficult, and a major problem is the lack of standardized allergens for the determination of specific antibodies. The aim of the present study is to evaluate if intradermal (ID) tests with analogs of Asp f 1 can aid in the diagnosis and stage assessment of abpa. Three groups of patients classified by serological tests were obtained. 20 ABPA (16BQ+; 4BQ-), 25 possible-ABPA (14BQ+; 11BQ-), 24 asthmatic-ABPAfree (11BQ+; 13BQ-) and 10 asthma-free people were submitted to id tests with three antigens: mitogillin, a-sarcin and restrictocin. There was intense reaction to all three antigens and the response was similar. The positive reactions to mitogillin were biopsied. The skin biopsies of two (12,5%) bq+ patients of the first group and 5 BQ+ (35,6%) patients of the second one showed vasculitis by immune complexes (IC) deposition. 11 patients of the third group had negative biopsies. The fourth group didn\'t have late-reaction. All patients with positive reaction were BQ+. By ID test, alfa-sarcin, mitogillin and restrictocin could differentiate patients with abpa and can be applicable in disease diagnosis. The higher incidence of bronchiectasis was found in the first (80%) and second (56%) groups. In the third group, IC wasn\'t found in 23 asthma patients and id test was positive to A. fumigatus. All patients with vasculitis by IC had bronchiectasis. Therefore, the results indicate that this kind of pulmonary lesion is caused by vasculitis.

Diese Arbeit beschreibt die Farb-Duplex-Sonographie bei Vaskulitiden, insbesondere bei der Arteriitis temporalis (AT), bei der Takayasu-Arteriitis und bei Vaskulitis-Overlap-Syndromen. Dabei wird die erstmals von uns beschriebene charakteristische echoarme Wandschwellung der Temporalarterien (Halo-Phänomen) bei akuter AT erläutert. Dieser Befund wird durch ein Arterienwandödem erklärt und verschwindet unter Therapie mit Kortikosteroiden innerhalb von durchschnittlich 16 Tagen. Zusätzlich lassen sich Stenosen und akute Verschlüsse der Temporalarterien in der Akutphase der Erkrankung darstellen. An den ersten 30 konsekutiven Patienten mit akuter AT führten wir eine kontrollierte, prospektive Studie durch. Diese ergab, dass das Halo-Phänomen bei 73 %, Stenosen und/oder Verschlüsse bei 80 %, und alle drei pathologischen Befunde bei 93 % der Patienten mit der klinischen Diagnose einer akuten AT nachweisbar waren. Die Sensitivität gegenüber der Temporalarterien-Histologie betrug jeweils 76 %, 86 % und 95 %. Die Spezifität des Halo-Phänomens betrug 100 % und von Stenosen/Verschlüssen 93 % gegenüber der klinischen Diagnose. Inzwischen hat der Autor dieser Arbeit 742 Untersuchungen an 630 Patienten durchgeführt. Davon hatten 80 Patienten eine akute AT und 104 weitere Patienten eine akute Polymyalgia rheumatica (PMR). Sensitivität und Spezifität sind vergleichbar mit den Ergebnissen der zuvor genannten kontrollierten Studie. Dabei liegt die Sensitivität der Sonographie sogar über derjenigen der Histologie, da längere Gefäßabschnitte untersucht werden. Bei eindeutigem klinischen und sonographischen Befund erscheint es möglich, auf die Biopsie zu verzichten. Außerdem wird der sonographische Befund der peripheren Riesenzellarteriits an der A. brachialis dargestellt. Zusätzlich fanden wir bei 10 von 33 konsekutiven Patienten mit akuter AT entzündliche Veränderungen an vielen anderen Arterien. Diese Befunde belegen, dass die akute AT stärker generalisiert ist, als bisher angenommen. Selbst bei einer Wegener`schen Granulomatose kann es zum Befall großer Gefäße, wie der Arteria carotis interna kommen, der sich sonographisch darstellen lässt, wie ein weiterer Patient zeigt. Die PMR kann gemeinsam mit der AT vorkommen. Umgekehrt war bei 7 von 102 Patienten mit PMR ohne klinische Zeichen einer AT die Sonographie der Temporalarterien wegweisend für die Diagnose einer begleitenden AT. Bei der Takayasu-Arteriitis finden sich ebenfalls charakteristische, allerdings hellere Wandschwellungen. Drei Patientinnen werden beschrieben, bei denen die Sonographie bereits im prästenotischen Frühstadium für die Diagnose wegweisend war. Die Duplex-Sonographie ist eine faszinierende Methode, wenn sie bei Patienten mit Verdacht auf eine Vaskulitis großer Gefäße angewandt wird, weil es mit ihr schnell, nicht-invasiv und mit vorhandener Technik gelingt, eine Diagnose zu stellen. / Color Duplex sonography is an excellent tool in the diagnosis of vasculitides, particularly for giant cell arteritis (GCA), for Takayasu`s artertis, and for vasculitis overlap syndromes. We described a characteristic dark wall-swelling of the temporal arteries (halo) in acute GCA that is due to an edema. It resolves within about 16 days with corticosteroid therapy. Additionally stenoses and occlusions of the temporal arteries are found in acute disease. A prospective, controlled study was performed on 30 patients with acute GCA. Sensitivity was 73 % (halo), 80 % (stenoses and/or occlusions), and 93 % (at least one of the three findings) for the clinical diagnosis, and 76 %, 86 %, and 95 % for positive histology. Specificity for the clinical diagnosis was 100 % (halo) and 93 % (stenoses, occlusions). Until now the author has performed 742 investigations in 630 patients including 80 patients with acute GCA and 104 more patients with acute polymyalgia rheumatica (PMR). Sensitivity and specificity are comparable to the results of the study. Sensitivity of sonography is even superior to that of histology because a longer segment of the artery can be investigated. In cases with typical clinical and ultrasound findings biopsy may not be necessary any more. Additionally we described the ultrasound image of large-vessel GCA in the brachial artery. In 10 of 33 consecutive patients with acute GCA we found inflammatory changes in many arteries other than the temporal arteries. Thus a generalized vasculitis occurs more frequently in GCA than assumed up to now. Even in Wegener`s granulomatosis large vessels like the internal carotid artery may be involved. We described the ultrasound image of one patient. In 102 patients with PMR and no clinical symptoms of GCA sonography of the temporal arteries delineated typical findings of GCA. In Takayasu`s arteritis sonography also shows a characteristic wall swelling which is brighter than in GCA. We described three patients in which sonography aided in establishing the diagnosis already in the early prestenotic stage of the disease. Duplex sonography is a fascinating method that can be used in the diagnosis of patients with suspected large vessel vasculitis like GCA and Takayasu`s arteritis. It is fast, non-invasive, and the equipment is widely available.