Primary cutaneous posttransplant lymphoproliferative disorders in solid organ transplant recipients: a multicenter European case series.

Primary cutaneous posttransplant lymphoproliferative disorders (PTLD) are rare. This retrospective, multicenter study of 35 cases aimed to better describe this entity. Cases were (re)-classified according to the WHO-EORTC or the WHO 2008 classifications of lymphomas. Median interval between first transplantation and diagnosis was 85 months. Fifty-seven percent of patients had a kidney transplant. Twenty-four cases (68.6%) were classified as primary cutaneous T cell lymphoma (CTCL) and 11 (31.4%) as primary cutaneous B cell PTLD. Mycosis fungoides (MF) was the most common (50%) CTCL subtype. Ten (90.9%) cutaneous B cell PTLD cases were classified as EBV-associated B cell lymphoproliferations (including one plasmablastic lymphoma and one lymphomatoid granulomatosis) and one as diffuse large B cell lymphoma, other, that was EBV-negative. Sixteen (45.7%) patients died after a median follow-up of 19.5 months (11 [68.8%] with CTCL [6 of whom had CD30(+) lymphoproliferative disorders (LPD)] and 5 [31.2%] with cutaneous B cell PTLD. Median survival times for all patients, CTCL and cutaneous B cell PTLD subgroups were 93, 93, and 112 months, respectively. Survival rates for MF were higher than those for CD30(+) LPD. The spectrum of primary CTCL in organ transplant recipients (OTR) is similar to that in the general population. The prognosis of posttransplant primary cutaneous CD30(+) LPD is worse than posttransplant MF and than its counterpart in the immunocompetent population. EBV-associated cutaneous B cell LPD predominates in OTR.

Outcomes from studies of Antineutrophil Cytoplasm Antibody Associated Vasculitis: a systematic review by the European League Against Rheumatism systemic vasculitis task force.

Objectives: We undertook a systematic literature review as a background to the European League Against Rheumatism (EULAR) recommendations for conducting clinical trials in anti-neutrophil cytoplasm antibody associated vasculitis (AAV), and to assess the quality of evidence for outcome measures in AAV. Methods: Using a systematic Medline search, we categorised the identified studies according to diagnoses. Factors affecting remission, relapse, renal function and overall survival were identified. Results: A total of 44 papers were reviewed from 502 identified by our search criteria. There was considerable inconsistency in definitions of end points. Remission rates varied from 30% to 93% in Wegener granulomatosis (WG), 75% to 89% in microscopic polyangiitis (MPA) and 81% to 91% in Churg¿Strauss syndrome (CSS). The 5-year survival for WG, MPA and CSS was 74¿91%, 45¿76% and 60¿97%. Relapse (variably defined) was common in the first 2 years but the frequency varied: 18% to 60% in WG, 8% in MPA, and 35% in CSS. The rate of renal survival in WG varied from 23% at 15 months to 23% at 120 months. Methods used to assess morbidity varied between studies. Ignoring the variations in definitions of the stage of disease, factors influencing remission, relapse, renal and overall survival included immunosuppressive therapy used, type of organ involvement, presence of ANCA, older age and male ender. Conclusions: Factors influencing remission, relapse, renal and overall survival include the type of immunosuppressive therapy used, pattern of organ involvement, presence of ANCA, older age and male gender. Methodological variations between studies highlight the need for a consensus on terminology and definitions for future conduct of clinical studies in AAV.

Parésie trochléaire transitoire comme signe neurologique inaugural d'une panartérite noueuse [Transient trochlear nerve palsy as the presenting neurological sign of panarteritis nodosa]

INTRODUCTION: Panarteritis nodosa (PAN) is a systemic vasculitis affecting small and medium-sized arteries. Neuro-ophthalmological complications of PAN are rare but numerous, and may affect the eye, the visual and the oculomotor pathways. Such complications occur mainly in patients previously diagnosed with PAN. OBSERVATION: A 51-year-old woman presented with an isolated right trochlear (IV) palsy, in the setting of headaches and fluctuating fever of unknown etiology. Erythrocyte sedimentation rate was 13 mm and full blood cell count was normal. Previous chest X-ray and blood studies were negative for an infection or inflammation. Orbital and cerebral CT scan was normal. Spontaneous recovery of diplopia ensued over four days. Two days later, paresthesia and sensory paresis of the dorsal portion of the left foot were present. Lumbar puncture revealed 14 leucocytes (76 percent lymphocytes) with elevated proteins, but blood studies and serologies were negative. A diagnosis of undetermined meningo-myelo-radiculoneuritis was made. Because of a possible tick bite six weeks previously the patient was empirically treated with 2 g intravenous ceftriaxone for 3 weeks. Fever rapidly dropped. Six weeks after the onset of diplopia, acute onset of blindness in her right eye, diffuse arthralgias and fever motivated a new hospitalization. There was a central retinal artery occlusion of the right eye. Blood studies now revealed signs of systemic inflammation (ESR 30 mm, CRP 12 mg/L, ANA 1/80, pANCA 1/40, leucocytosis 12.4 G/L, Hb 111 g/L, Ht 33 percent). Biopsy of the left sural nerve revealed arterial fibrinoid necrosis. A diagnosis of PAN was made. CONCLUSIONS: Transient diplopia can be the heralding symptom of a systemic vasculitis such as PAN, giant cell arteritis and Wegener granulomatosis. In this patient the presence of accompanying systemic symptoms raised a suspicion of systemic inflammation, but the absence of serologic and imaging abnormalities precluded a specific diagnosis initially. A few weeks later, the presence of a second ischemic event (retinal) and positive blood studies led to a further diagnostic procedure. Oculomotor and abducens palsies have rarely been reported in association with PAN. We report the first case of trochlear nerve paresis as the inaugural neurological sign of PAN. This case highlights the importance of considering inflammatory systemic disorders in patients with acute diplopia particularly when they are young, lack vascular risk factors or cause, and complain of associated systemic symptoms.

Characterization of local and systemic immune-modulation in melanoma patients

Le mélanome cutané est un des cancers les plus agressifs et dont l'incidence augmente le plus en Suisse. Une fois métastatique, le pronostic de survie moyenne avec les thérapies actuelles est d'environ huit mois, avec moins de 5% de survie à cinq ans. Les récents progrès effectués dans la compréhension de la biologie de la cellule tumorale mais surtout dans l'importance du système immunitaire dans le contrôle de ce cancer ont permis le développement de nouveaux traitements novateurs et prometteurs. Ces thérapies, appelées immunothérapies, reposent sur la stimulation et l'augmentation de la réponse immunitaire à la tumeur. Alors que les derniers essais cliniques ont démontré l'efficacité de ces traitements chez les patients avec des stades avancés de la maladie, le contrôle de la maladie à long- terme est seulement atteint chez une minorité des patients. La suppression locale et systémique de la réponse immunitaire spécifique anti-tumorale apparaitrait comme une des raisons expliquant la persistance d'un mauvais pronostic clinique chez ces patients. Des études sur les souris ont montré que les vaisseaux lymphatiques joueraient un rôle primordial dans ce processus en induisant une tolérance immune, ce qui permettrait à la tumeur d'échapper au contrôle du système immunitaire et métastatiser plus facilement. Ces excitantes découvertes n'ont pas encore été établi et prouvé chez l'homme. Dans cette thèse, nous montrons pour la première fois que les vaisseaux lymphatiques sont directement impliqués dans la modulation de la réponse immunitaire au niveau local et systémique dans le mélanome chez l'homme. Ces récentes découvertes montrent le potentiel de combiner des thérapies visant le système lymphatique avec les immunothérapies actuellement utilisées afin d'améliorer le pronostic des patients atteint du mélanome. -- Cutaneous melanoma is one of the most invasive and metastatic human cancers and causes 75% of skin cancer mortality. Current therapies such as surgery and chemotherapy fail to control metastatic disease, and relapse occurs frequently due to microscopic residual lesions. It is, thus, essential to develop and optimize novel therapeutic strategies to improve curative responses in these patients. In recent decades, tumor immunologists have revealed the development of spontaneous adaptive immune responses in melanoma patients, leading to the accumulation of highly differentiated tumor-specific T cells at the tumor site. This remains one of the most powerful prognostic markers to date. Immunotherapies that augment the natural function of these tumor-specific T cells have since emerged as highly attractive therapeutic approaches to eliminate melanoma cells. While recent clinical trials have demonstrated great progress in the treatment of advanced stage melanoma, long-term disease control is still only achieved in a minority of patients. Local and systemic immune suppression by the tumor appears to be responsible, in part, for this poor clinical evolution. These facts underscore the need for a better analysis and characterization of immune- related pathways within the tumor microenvironment (TME), as well as at the systemic level. The overall goal of this thesis is, thus, to obtain greater insight into the complexity and heterogeneity of the TME in human melanoma, as well as to investigate immune modulation beyond the TME, which ultimately influences the immune system throughout the whole body. To achieve this, we established two main objectives: to precisely characterize local and systemic immune modulation (i) in untreated melanoma patients and (ii) in patients undergoing peptide vaccination or checkpoint blockade therapy with anti-cytotoxic T- lymphocyte-asisctaed protein-4 (CTLA-4) antibody. In the first and main part of this thesis, we analyzed lymphatic vessels in relation to anti-tumor immune responses in tissues from vaccinated patients using a combination of immunohistochemistry (IHC) techniques, whole slide scanning/analysis, and an automatic quantification system. Strikingly, we found that increased lymphatic vessel density was associated with high expression of immune suppressive molecules, low functionality of tumor-infiltrating CD8+ T cells and decreased cytokine production by tumor-antigen specific CD8+ T cells in the blood. These data revealed a previously unappreciated local and systemic role of lymphangiogenesis in modulating T cell responses in human cancer and support the use of therapies that target lymphatic vessels combined with existing and future T cell based therapies. In the second objective, we describe a metastatic melanoma patient who developed pulmonary sarcoid-like granulomatosis following repetitive vaccination with peptides and CpG. We demonstrated that the onset of this pulmonary autoimmune adverse event was related to the development of a strong and long-lasting tumor-specific CD8+ T cell response. This constitutes the first demonstration that a new generation tumor vaccine can induce the development of autoimmune adverse events. In the third objective, we assessed the use of Fourier Transform Infrared (FTIR) imaging to identify melanoma cells and lymphocyte subpopulations in lymph node (LN) metastasis tissues, thanks to a fruitful collaboration with researchers in Brussels. We demonstrated that the different cell types in metastatic LNs have different infrared spectral features allowing automated identification of these cells. This technic is therefore capable of distinguishing known and novel biological features in human tissues and has, therefore, significant potential as a tool for histopathological diagnosis and biomarker assessment. Finally, in the fourth objective, we investigated the role of colony- stimulating factor-1 (CSF-1) in modulating the anti-tumor response in ipilimumab-treated patients using IHC and in vitro co-cultures, revealing that melanoma cells produce CSF-1 via CTL-derived cytokines when attacked by cytotoxic T lymphocytes (CTLs), resulting in the recruitment of immunosuppressive monocytes. These findings support the combined use of CSF-1R blockade with T cell based immunotherapy for melanoma patients. Taken together, our results reveal the existence of novel mechanisms of immune modulation and thus promote the optimization of combination immunotherapies against melanoma. -- Le mélanome cutané est un des cancers humains les plus invasifs et métastatiques et est responsable de 75% de la mortalité liée aux cancers de la peau. Les thérapies comme la chirurgie et la chimiothérapie ont échoué à contrôler le mélanome métastatique, par ailleurs les rechutes sous ces traitements ont été montrées fréquentes. Il est donc essentiel de développer et d'optimiser de nouvelles stratégies thérapeutiques pour améliorer les réponses thérapeutiques de ces patients. Durant les dernières décennies, les immunologistes spécialisés dans les tumeurs ont démontré qu'un patient atteint du mélanome pouvait développer spontanément une réponse immune adaptative à sa tumeur et que l'accumulation de cellules T spécifiques tumorales au sein même de la tumeur était un des plus puissants facteurs pronostiques. Les immunothérapies qui ont pour but d'augmenter les fonctions naturelles de ces cellules T spécifiques tumorales ont donc émergé comme des approches thérapeutiques très attractives pour éliminer les cellules du mélanome. Alors que les derniers essais cliniques ont démontré un progrès important dans le traitement des formes avancées du mélanome, le contrôle de la maladie à long-terme est seulement atteint chez une minorité des patients. La suppression immune locale et systémique apparaitrait comme une des raisons expliquant la persistance d'un mauvais pronostic clinique chez ces patients. Ces considérations soulignent la nécessité de mieux analyser et caractériser les voies immunitaires non seulement au niveau local dans le microenvironement tumoral mais aussi au niveau systémique dans le sang des patients. Le but de cette thèse est d'obtenir une plus grande connaissance de la complexité et de l'hétérogénéité du microenvironement tumoral dans les mélanomes mais aussi d'investiguer la modulation immunitaire au delà du microenvironement tumoral au niveau systémique. Afin d'atteindre ce but, nous avons établi deux objectifs principaux : caractériser précisément la modulation locale et systémique du système immunitaire (i) chez les patients atteints du mélanome qui n'ont pas reçu de traitement et (ii) chez les patients qui ont été traités soit par des vaccins soit par des thérapies qui bloquent les points de contrôles. Dans la première et majeure partie de cette thèse, nous avons analysé les vaisseaux lymphatiques en relation avec la réponse immunitaire anti-tumorale dans les tissus des patients vaccinés grâce à des techniques d'immunohistochimie et de quantification informatisé et automatique des marquages. Nous avons trouvé qu'une densité élevée de vaisseaux lymphatiques dans la tumeur était associée à une plus grande expression de molécules immunosuppressives ainsi qu'à une diminution de la fonctionnalité des cellules T spécifiques tumoral dans la tumeur et dans le sang des patients. Ces résultats révèlent un rôle jusqu'à là inconnu des vaisseaux lymphatiques dans la modulation directe du système immunitaire au niveau local et systémique dans les cancers de l'homme. Cette recherche apporte finalement des preuves du potentiel de combiner des thérapies visant le système lymphatique avec des autres immunothérapies déjà utilisées en clinique. Dans le second objectif, nous rapportons le cas d'un patient atteint d'un mélanome avec de multiples métastases qui a développé à la suite de plusieurs vaccinations répétées et consécutives avec des peptides et du CpG, un évènement indésirable sous la forme d'une granulomatose pulmonaire sarcoid-like. Nous avons démontré que l'apparition de cet évènement était intimement liée au développement d'une réponse immunitaire durable et spécifique contre les antigènes de la tumeur. Par là- même, nous prouvons pour la première fois que la nouvelle génération de vaccins est aussi capable d'induire des effets indésirables auto-immuns. Pour le troisième objectif, nous avons voulu savoir si l'utilisation de la spectroscopie infrarouge à transformée de Fourier (IRTF) était capable d'identifier les cellules du mélanome ainsi que les différents sous-types cellulaires dans les ganglions métastatiques. Grâce à nos collaborateurs de Bruxelles, nous avons pu établir que les diverses composantes cellulaires des ganglions atteints par des métastases du mélanome présentaient des spectres infrarouges différents et qu'elles pouvaient être identifiées d'une façon automatique. Cette nouvelle technique permettrait donc de distinguer des caractéristiques biologiques connues ou nouvelles dans les tissus humains qui auraient des retombées pratiques importantes dans le diagnostic histopathologique et dans l'évaluation des biomarqueurs. Finalement dans le dernier objectif, nous avons investigué le rôle du facteur de stimulation des colonies (CSF-1) dans la modulation de la réponse immunitaire anti-tumorale chez les patients qui ont été traités par l'Ipilimumab. Nos expériences in vivo au niveau des tissus tumoraux et nos co-cultures in vitro nous ont permis de démontrer que les cytokines secrétées par les cellules T spécifiques anti-tumorales induisaient la sécrétion de CSF-1 dans les cellules du mélanome ce qui résultait en un recrutement de monocytes immunosuppresseurs. Dans son ensemble, cette thèse révèle donc l'existence de nouveaux mécanismes de modulation de la réponse immunitaire anti-tumorale et propose de nouvelles optimisations de combinaison d'immunothérapies contre le mélanome.

Agregación de autoinmunidad en familias extremas con Síndrome de Sjogren: una aproximación a la medicina personalizada

Objetivo: investigar la agregación de autoinmunidad en familiares en primer grado (FPG) de probandos con Síndrome de Sjogren (SS) con poliautoinmunidad y autoinmunidad familiar. Metodología: estudio de corte transversal en el cual se incluyeron 14 familias de mujeres con SS. Se realizó un análisis genético a través del cálculo de riesgos relativos para cada enfermedad autoinmune (EAI). La agregación familiar se calculó para los FPG, teniendo en cuenta la prevalencia de la enfermedad en cada familia y en la población general. Resultados: Se analizaron un total de 112 individuos, con una media de edad de 51.7 años ± 12.9. Veintidós individuos de los FPG tuvieron al menos una EAI (28.2%). La prevalencia de poliautoinmunidad fue del 93% y 6.4% en probandos y FPG, respectivamente. Se observaron valores que soportaron la agregación familiar para varias EAIs, entre ellas púrpura trombocitopénica idiopática, granulomatosis con poliangeiitis, síndrome antifosfolipídico, lupus eritematoso sistémico y artritis reumatoide. Discusión: estos resultados indican que las EAIs se agregan entre familias con SS, sugiriendo un origen común entre ellas. La elección de fenotipos clínicamente relevantes representa una nueva aproximación a la medicina personalizada en autoinmunidad.

Evidencia actual sobre características demográficas en mastitis granulomatosa idiopática

Introducción: La mastitis granulomatosa idiopática es una enfermedad crónica benigna, rara y de etiología desconocida; tiende a confundirse con otras enfermedades debido a síntomas similares. Este estudio pretende identificar y cuantificar las características demográficas, los antecedentes ginecoobstétricos relevantes y las manifestaciones clínicas prediagnósticas de esta enfermedad Metodología: Se realizó una revisión sistemática con análisis agrupado de datos tipo meta análisis. Se utilizó una estrategia de búsqueda en PubMed. Todos los estudios relacionados con la definición, manifestaciones clínicas, diagnóstico, tratamiento y pronóstico de la mastitis granulomatosa idiopática fueron elegibles. Las variables de interés fueron edad, país, antecedente de contracepción hormonal, tiempo de evolución, tiempo desde el último embarazo, diagnóstico inicial, y manifestaciones clínicas previas a la consulta. No hubo restricción en fechas de publicación. Resultados: Fueron incluidas 641 mujeres con diagnóstico de MGI reportadas en 68 publicaciones que cumplieron los criterios de selección. La edad media fue 35.9 años, 14.1% de ellas estaba embarazada o lactando, el antecedente de consumo de anticonceptivos hormonales fue 21% y el tiempo promedio desde el último parto fue de 3.9 años. La afectación ocurre principalmente en mama izquierda y en cuadrante superoexterno. El cáncer de mama y el absceso mamario son diagnósticos diferenciales en la consulta. Discusión: El diagnóstico de MGI es un reto para el ginecólogo desde la consulta inicial. Debido a que sus manifestaciones clínicas no son específicas, su diagnóstico parece apuntar a la necesidad de un proceso de descarte de otras patologías más frecuentes e incluso de peor pronóstico. Palabras clave mastitis granulomatosa idiopática

Anti-neutrophil cytoplasmic antibodies (ANCA) in the clinical forms of leprosy

Anti-neutrophil cytoplasmic antibodies (ANCA) are autoantibodies against enzymes present in primary granules of neutrophils and lysosomes of monocytes detected in systemic vasculitis and in other diseases, including infections, ANCA are markers of active Wegener granulomatosis, which presents some anatomo-pathologic and immune response features similar to those of leprosy. Thus, we raised the hypothesis that ANCA may be present in leprosy as markers specifically linked to the presence of vasculitis. The aim of this study was to determine the presence of ANCA in leprosy and its correlation with the clinical forms of the disease. Sera from 60 normal individuals and from 59 patients with different clinical forms of leprosy were studied. The patients were also allocated into reactional and nonreactional groups. By indirect immunofluorescence, ANCA were positive, an atypical pattern A-ANCA, in 28.8% of the patient sera. A-ANCA predominated, although not significantly (p >0,05), in the reactional groups (37.9% vs 20.0%), and in those at the lepromatous pole (41.6% vs 20.0%). There was no correlation between ANCA positivity and either disease duration, disease activity, or therapeutic regimen (p >0.05), An interesting finding was the correlation between ANCA and gender: 94.1% of ANCA-positive patients were males (p <0.01), a feature that so far has not been reported in ANCA-related diseases and for which there is no explanation at the moment. By ELISA, the sera of the lepromatous leprosy patients did not show activity against either PR3, MPO, HLE, the most common ANCA antigens. Because A-ANCA are nonspecific, this finding requires further investigation for the determination of the responsible antigen(s), in conclusion, A-ANCA are present in 28.8% of leprosy patients but are not related to vasculitis in the erythema nodosum leprosum reaction and are not a marker of a specific clinical form.

Nasal T-cell lymphoma presenting as midline lethal granuloma. Characterization of three cases by clinical markers of lymphomas

The authors report on three cases of so-called midline granuloma submitted to clinicopathologic and immunophenotype studies. The histopathologic features detected were necrosis, vasculitis and an atypical lymphohistiocytic infiltrate. Immunophenotype studies using monoclonal antibodies showed evidence leading to the diagnosis of nasal T cell lymphoma or lymphomatoid granulomatosis. Two of the patients with the presence of progressive or large cells died within 24 months, indicating that the size of the atypical lymphoid cells may be of prognostic significance.

Effect of dietary supplementation with vitamin E and stocking density on macrophage recruitment and giant cell formation in the teleost fish, Piaractus mesopotamicus

The effect of dietary supplementation with 0, 100 and 450 mg of vitamin E (DL-α tocopheryl acetate)/kg of a dry diet on the kinetics of macrophage recruitment and giant cell formation in the pacu, maintained at different stocking densities (5 kg/m3 and 20 kg/m3), was investigated by insertion of round glass coverslips into the subcutaneous connective tissue. After a feeding period of 18 weeks, the coverslips were implanted and later removed for examination at 2, 7 and 15 days post-implantation. Fish fed diets supplemented with 450 mg of vitamin E showed an increase (P<0.05) in the accumulation of macrophages, foreign body giant cells and Langhans type cells. The kinetics of macrophage recruitment and giant cell formation on the glass coverslips appeared to be strongly influenced by vitamin E supplementation, since fish fed a basal diet and held at high stocking densities showed low numbers of adhering cells on the coverslips, and high concentrations of plasma corticosteroids. On the other hand, fish given a diet supplemented with 450 mg of vitamin E did not show a similar difference in plasma cortisol concentrations related to stocking density. The effect of cortisol concentrations on carbohydrate metabolism, analysed by assessment of plasma glycaemia, was not clear. Blood glucose concentrations did not vary substantially with the different treatments examined. These results suggest that vitamin E may contribute to the efficiency of the fish's inflammatory response by increasing macrophage recruitment and giant cell formation in the foreign body granulomatous reaction. Vitamin E appeared to act on the stress response of pacus by preventing a stress-related immunosuppression. © 2005 Elsevier Ltd. All rights reserved.

Adenopatia cervical tuberculosa em crianças: aspectos epidemiológicos, clínicos e laboratoriais

A tuberculose constitui um sério problema de saúde pública, sendo o M. tuberculosis o principal agente da doença no Brasil. Entre as formas extra pulmonares, a ganglionar periférica é uma das mais freqüentes na infância, apesar de pouco estudada. Com o objetivo de avaliar a incidência e conhecer os aspectos epidemiológicos, clínicos e laboratoriais da tuberculose ganglionar foram atendidas no ambulatório do Hospital Ofir Loiola, no período de janeiro de 1995 a dezembro de 1996, 73 crianças entre 0-14 anos, de ambos os sexos, portadoras de linfadenopatia cervical. A amostra foi dividida em dois grupos: o primeiro constituído por 61 crianças com adenopatias de outras etiologias e o segundo formado de 12 pacientes com etiologia tuberculosa. Nesse período, para as adenopatias tuberculosas, a taxa anual de incidência na área metropolitana de Belém, por 100 mil habitantes, foi de 1,03 e para o grupo de outras etiologias a incidência foi de 4,27 e 6,15 para os anos de 1995 e 1996, respectivamente. Verificou-se que a maioria das adenopatias na infância foram inespecíficas (64,4%), entretanto, quando consideradas somente as de etiologia conhecida, o risco relativo de ser tuberculose foi de 1,17. A análise comparativa entre os dois grupos não revelou diferença estatisticamente significativa no que tange à faixa etária, sexo, estado nutricional, apresentação clínica inicial, cadeias ganglionares comprometidas e características dos linfonodos. Em ambos foi observado maior incidência em pré-escolares e no sexo masculino. O comprometimento do estado nutricional pode ter contribuído para o aumento da morbidade em 41,7% dos casos de tuberculose. A presença de massa cervical constitui a queixa principal nos dois grupos embora durante o exame tenha sido constatado comprometimento ganglionar generalizado em 75,1% das crianças com adenopatia tuberculosa. Quanto à duração dos sintomas, os casos de adenopatia tuberculosa foram atendidos a partir do primeiro mês de doença e tiveram como manifestação clínica abscesso frio em 25% dos casos. A fonte de infecção foi identificada em 1/3 dos pacientes. A reação tuberculínica com leitura >10mm foi positiva em 63,6% das crianças tuberculosas. Entre os exames bacteriológicos realizados, a cultura constituiu o elemento fundamental para o diagnóstico de tuberculose, obtendo-se 100% de positividade nos exames realizados; a baciloscopia foi de menor importância. O exame histopatológico com lesão granulomatosa compatível com tuberculose foi observado em 88,9% dos casos. O comprometimento pulmonar associado esteve presente em 27, 3% das crianças tuberculosas. A resposta à terapêutica com esquema padronizado pelo Ministério da Saúde foi satisfatória, não tendo sido observados efeitos colaterais aos medicamentos utilizados.

Ciclosporina A no eritema nodoso hansênico com manifestações sistêmicas: avaliação clínica, laboratorial e histopatológica

O ENH é séria intercorrência aguda ou subaguda que acomete pacientes das formas dimorfa-virchowiana e virchowiana da classificação de Ridley e Jopling. Neste estudo, foi utilizada uma droga imunorreguladora, a ciclosporina A, com o propósito de avaliar a eficácia nesta reação, cujo tratamento depende de medicamentos como a talidomida, que tem contra-indicações formais e corticóides, que provocam dependência, entre outros danos. Foram selecionados dez doentes de ENH com sintomas sistêmicos; todos haviam passado por vários episódios desta reação e faziam uso contínuo e prolongado de prednisona em doses elevadas e ocasionalmente, de talidomida. Os pacientes tomaram ciclosporina A em doses de 3-5 mg/kg/dia durante um período de 90 dias. Realizaram exames laboratoriais nos dias zero, 150 e 600 de uso da ciclosporina A e também o histopatológico das lesões de ENH (antes do tratamento e com 60 dias). Os exames laboratoriais solicitados foram: hemograma e leucograma; TGO; TGP: uréia e creatinina. Detectou-se leucocitose em graus entre moderado e elevado em 70% dos casos, mas evoluiu para leucocitose leve até o término do acompanhamento na mesma percentagem dos doentes. O exame bioquímico não mostrou alterações significantes, com exceção da elevação da TGO em um caso, da TGP em outro, além de dois pacientes que mostraram aumento da uréia e creatinina, mas que posteriormente, normalizaram sem precisar de medidas adicionais. Os achados histológicos encontrados no primeiro exame foram representados em 40% dos doentes, por dermatite granulomatosa e em 30%, por dermatite nodular. Na segunda análise, houve mudança para dermatite perivascular superficial e profunda em 50% dos casos e para paniculite septal em 20%; isto denota melhora histológica compatível com a melhora dos sintomas verificada nos primeiros quinze dias de terapêutica. A ação da ciclosporina A se revelou benéfica, principalmente na sintomatologia sistêmica, com exceção dos casos que se acompanhavam de neurite; desta forma, a ciclosporina A pode ser uma opção para a melhoria clínica das reações hansênicas tipo 11.

Developing a provisional definition of flare in patients with established gout

Objective Various nonvalidated criteria for disease flare have been used in studies of gout. Our objective was to develop empirical definitions for a gout flare from patient-reported features. Methods Possible elements for flare criteria were previously reported. Data were collected from 210 gout patients at 8 international sites to evaluate potential gout flare criteria against the gold standard of an expert rheumatologist definition. Flare definitions based on the presence of the number of criteria independently associated with the flare and classification and regression tree approaches were developed. Results The mean +/- SD age of the study participants was 56.2 +/- 15 years, 207 of them (98%) were men, and 54 of them (26%) had flares of gout. The presence of any patient-reported warm joint, any patient-reported swollen joint, patient-reported pain at rest score of >3 (010 scale), and patient-reported flare were independently associated with the study gold standard. The greatest discriminating power was noted for the presence of 3 or more of the above 4 criteria (sensitivity 91% and specificity 82%). Requiring all 4 criteria provided the highest specificity (96%) and positive predictive value (85%). A classification tree identified pain at rest with a score of >3, followed by patient self-reported flare, as the rule associated with the gold standard (sensitivity 83% and specificity 90%). Conclusion We propose definitions for a disease flare based on self-reported items in patients previously diagnosed as having gout. Patient-reported flare, joint pain at rest, warm joints, and swollen joints were most strongly associated with presence of a gout flare. These provisional definitions will next be validated in clinical trials.

Comprometimento da árvore respiratória na granulomatose de Wegener

INTRODUÇÃO: A granulomatose de Wegener (GW) é uma forma de vasculite sistêmica que envolve primariamente as vias aéreas superiores e inferiores e os rins. As manifestações mais frequentes nas vias aéreas são estenose subglótica e inflamações, estenoses da traqueia e dos brônquios. A visualização endoscópica das vias aéreas é a melhor ferramenta para avaliação, diagnóstico e manejo dessas alterações. OBJETIVOS: Descrever as alterações endoscópicas encontradas na mucosa das vias aéreas de um grupo de pacientes com GW submetido à broncoscopia no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP) e relatar as intervenções terapêuticas broncoscópicas utilizadas em alguns casos. MÉTODOS: Foram estudados 15 pacientes com diagnóstico de GW provenientes do Ambulatório de Vasculites da Disciplina de Pneumologia do HC-FMUSP, encaminhados para a realização de broncoscopia no serviço de Endoscopia Respiratória do HC-FMUSP no período de 2003 a 2007. RESULTADOS: Dos 15 pacientes avaliados, 11 eram mulheres (73,33%) com idade média de 34 ± 11,5 anos. Foram encontradas alterações das vias aéreas em 80% dos pacientes, e o achado endoscópico mais frequente foi estenose subglótica (n = 6). Realizou-se broncoscopia terapêutica em três pacientes com estenose subglótica e em outros três com estenose brônquica, todos apresentando bons resultados. CONCLUSÃO: A broncoscopia permite diagnóstico, acompanhamento e tratamento das lesões de vias aéreas na GW, constituindo-se um recurso terapêutico pouco invasivo em casos selecionados.