On the nature of sarcoidosis.

More than 140 years since its recognition as a clinical entity, sarcoidosis remains enigmatic. Its classification as a disease vs. a syndrome is uncertain. Its etiology remains undefined. The "immune paradox" (delayed type hypersensitivity anergy in a setting of exuberant systemic granulomatous response) resists explanation. Its relationship to the Kveim test is poorly understood. Its prognostic determinants and treatment indications are among the unsolved or disputed problems. Immunological investigations generated the thesis that the characterizing systemic granuloma arise as a fallback reaction to inefficient cellular immune processing, due most often to impaired myeloid dendritic cell function of unknown cause. The concept that sarcoidosis represents a (genetically conditioned) default to a more primitive immunological response provides a unifying explanation for its development in persons with a variety of antigenic exposures and in individuals with cellular immune deficiencies. It furnishes a coherent explanation for the apparent paradox that individuals exhibiting the most intense cellular response experience the most favorable outcomes and for the adverse effect of corticosteroid-suppression in recent onset sarcoidosis.

Sarcoidose: o que interessa na prática médica? / Sarcoidosis: what matters in medical practice?

Os autores, baseados na vivência clínica em Pneumologia e em revisão bibliográfica, repassam os principais tópicos às dificuldades no diagnóstico de sarcoidose. Abordam critérios para o diagnóstico, resultantes da somação de vários fatores, dando ênfase ao quadro clínico compatível, confirmação histopatológica, teste de Kveim-Siltzbach positivo e resposta clínico-radiográfica eficaz à corticoterapia sistêmica. Ilustram o tema em pauta com apresentação de três casos, os quais se revelaram por demais exuberantes pelos seus elementos apresentados com os sintomas respiratórios dominando toda a cena

The authors, based on the clinical practice in Pneumology and in review of literature, revise the main topics of the difficulties in the diagnosis of sarcoidosis. They approach criteria for the diagnosis, resultants of the addition of several factors, giving emphasis to the compatible clinical picture, histopathologic confirmation, positive Kveim-Siltzbach's test and clinical radiographic answer effective to the systemic corticotherapy. They illustrate the topic under discussion with presentation of three cases, which were revealed for too much exuberant for your elements presented with the breathing symptoms dominating the whole scene

Valor actual del test de Kveim en el diagnóstico de la sarcoidosis / Current value of the kveim test in the diagnosis of sarcoidosis

Introducción. La sarcoidosis es una enfermedad multisistémica para cuyo diagnóstico es preciso demostrar granulomas en uno o más órganos. El test de Kveim-Siltzbach puede ser útil para casos en los que no se puede demostrar inflamación granulomatosa en órganos afectados. En los últimos años su uso se ha restringido debido a la dificultad para obtenerlo y algunos autores lo han desaconsejado por el riesgo de transmisión de enfermedades infecciosas como la encefalopatía espongiforme bovina. Pretendemos analizar el valor actual del test Kveim-Siltzbach en los pacientes con especiales dificultades diagnósticas.Métodos. Se ha practicado el test de Kveim-Siltzbach a 20 pacientes remitidos al Servicio de Medicina Interna del Hospital de Bellvitge de Barcelona con sospecha de sarcoidosis en los que el diagnóstico no pudo ser confirmado mediante otros métodos. Las reacciones positivas se clasificaron en tres categorías según la cantidad de granulomas y la presencia de necrosis. Los pacientes fueron controlados durante un mínimo de 2 años.Resultados. El test de Kveim-Siltzbach fue positivo en 10 casos (ligeramente en 4 casos, moderadamente en cuatro e intensamente positivo en dos). En nueve de ellos el diagnóstico de sarcoidosis se confirmó mediante otros procedimientos. Únicamente en un paciente con test positivo el diagnóstico de sarcoidosis no pudo confirmarse por otros métodos.Conclusiones. El test de Kveim-Siltzbach sigue siendo útil como procedimiento diagnóstico en pacientes con especiales dificultades en la demostración histológica de granulomas (AU)

[The Kveim-Siltzbach test in sarcoidosis]. / La prueba de Kveim-Siltzbach en la sarcoidosis.

BACKGROUND: The Kveim-Siltzbach test has been widely used in the diagnosis of sarcoidosis. This reactive is currently available in the authors' hospitals. Previous experience with this test in the same centers was reviewed to know its diagnostic usefulness. The present is the first series described in Spain. METHODS: From 1977 to 1988 the Kveim-Siltzbach test was performed in 79 patients diagnosed or suspected of having sarcoidosis. The study was carried out as cooperation of the validation process of sarcoid spleen suspensions (lots K12, K12 1/2, K32, K41, K42, K42 1/2 and K50 of the Colindale antigen) prepared in the Standards Laboratory for Serological Reagents in the Royal Brompton Hospital in London. RESULTS: The results of test positivity were determined following the criteria established by Siltzbach. The global sensitivity of the Kveim-Siltzbach test was 78% (CI 95% = 67.8-86.9). Positivity ranged from 84% in subacute sarcoidosis to 61% in chronic sarcoidosis (p = 0.08). Likewise, it was higher in patients with radiologic stage I (84%) and II (81%) with respect to stage III (62%) or the cases with exclusive extrathoracic sarcoidosis (stage 0) (57%) (p = 0.11). No association was found between the Kveim-Siltzbach test positivity and the elevation in serum values of the angiotensin-converting enzyme (p = 0.575). CONCLUSIONS: In the present study the Kveim-Siltzbach test showed high sensitivity in the diagnosis of sarcoidosis. This fact, together with the high specificity observed in other studies, makes the test a very useful tool for the non-invasive diagnosis of sarcoidosis.

Selection of oligoclonal V beta-specific T cells in the intradermal response to Kveim-Siltzbach reagent in individuals with sarcoidosis.

Sarcoidosis is a multiorgan granulomatous disorder of unknown etiology characterized by noncaseating granulomas in involved tissues. A positive Kveim-Siltzbach reaction is a granulomatous response to an intradermal injection of a suspension of sarcoid tissue extract in individuals with sarcoidosis. The protracted time course and granulomatous features of this reaction have a striking resemblance to the Mitsuda reaction in tuberculous leprosy, which suggests that the Kveim-Siltzbach reaction is a response to an unknown Ag(s). To evaluate whether this reaction is Ag-driven, an analysis of the TCR V beta repertoire in 15 Kveim-Siltzbach reaction sites was performed using a PCR technique and primers specific for 20 V beta gene families. Results of this analysis demonstrated a pattern of V beta expression dominated by expression of V beta 2, V beta 3, V beta 6, or V beta 8 to levels > 20% of total V beta gene expression in nine of 15 individuals. Analysis of paired biopsy and blood specimens revealed a preferential expression of specific V beta genes, such as V beta 3, V beta 5, and V beta 8, at sites of Kveim-Siltzbach reactions to levels four to seven times that of the corresponding peripheral blood. Sequence analysis demonstrated that preferential expression of specific V beta genes at Kveim-Siltzbach reaction sites is oligoclonal. Furthermore, the dominant V beta 8 sequence present at one of the reaction sites contained a sequence motif in the variable-diversity-joining junctional region previously identified in sarcoid lung and blood T cell populations. These results suggest that the Kveim-Siltzbach reaction is characterized by a limited TCR beta-chain repertoire consistent with an Ag-driven T cell immune response.

Kveim-Siltzbach test revisited.

The Kveim-Siltzbach (KS) skin test has been in use worldwide for fifty years. It is a safe, simple and specific out-patient technique to confirm the diagnosis of sarcoidosis and to provide evidence of activity of the disease. It is most helpful in delineating sarcoidosis as a cause of erythema nodosum, uveitis, liver granulomas, hypercalciuria and meningitis. It is the patient's preference when he is confronted with the choice between a skin test or alternatively bronchoscopy, lung biopsy or aspiration liver biopsy. It also creates considerable academic interest for it reflects granuloma formation vividly when viewed by modern immunopathology techniques. Its disadvantage is that it takes a month to provide a result; a critical month in which systemic steroids are avoided for this would suppress the test. The immunopathology of the KS test is similar to spontaneous sarcoid granuloma formation, and evolution of the KS granuloma may provide clues to the cause of sarcoidosis and other granulomatous disorders.