Academic literature on the topic 'Erythema nodosum, Reversal reaction'

Abstract Background Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae. Erythema Nodosum Leprosum is an acute inflammatory Type III hypersensitivity response during the chronic course of the disease process. This immune response manifests clinically as painful red nodules and systemic symptoms similar to sepsis with neutrophilic leukocytosis. Capsule Thalidomide is the drug of choice for treating this condition. Methods A randomized control study to study the immunological markers involved in the pathogenesis of erythema nododsum leprosum and its successful suppression by Thalidomide should provide newer insight into the pathogenesis of this disease process, provide better diagnostic and therapeutic options and better markers to predict prognosis. Based on the previous studies our aim was to find a correlation with tumor necrosis factor-a, interferon-gamma, and Cd-64 expression on activated circulating neutrophils during Type II lepra reaction and the successful response to capsule Thalidomide. Venous blood samples were collected from all the samples and after 7 days post thalidomide therapy, only in the treated population. All the patients with type II lepra reaction responded to Capsule Thalidomide clinically and all the skin lesions resolved in 7–14 days. Blood samples and skin biopsy was subjected to histopathology, immunofluorescence assay, immunohistochemical staining, quantitative RT–PCR (reverse transcriptase-polymerase chain reaction) and flow cytometry. Results Study found out that Interferon Γand Tumor necrosis factor-Α are sensitive markers in diagnosing erythema nodosum leprosum and Cd-64 expression on activated circulating neutrophils is both a specific and sensitive marker. Cd-64 expression also had a positive correlation with Thalidomide treatment and clinical response. Conclusion Cd-64 expression on circulating neutrophils is a potential early biophysical marker for diagnosing erythema nodosum leprosum and can be used as a tool to assess thalidomide response. InterferonΓ and Tumor necrosis factorΑ are sensitive markers to screen for lepra reactions and this study showed no significant correlation with Thalidomide therapy. Disclosures All authors: No reported disclosures.

Abstract Background Leprosy is a chronic granulomatous disease caused by Mycobacterium leprae. Type II lepra reaction or Erythema Nodosum Leposum is a Type III hypersentivity immune response during the chronic course of the illness. This immune response presents as systemic symptoms and neutrophilic leukocytosis, similar to sepsis. Capsule Thalidomide is considered the drug of choice, when it comes to the treatment of this acute immunological emergency. A rational study into the immunological markers involved in the pathogenesis of erythema nododsum leprosum and its successful suppression by Thalidomide should be helpful in early diagnosis and prompt successful therapy. On the basis of previous studies, our aim was to find a correlation with interferon-γ, tumour necrosis factor-α, and Cd-64 expression on activated circulating neutrophils during Type II lepra reaction and successful response to capsule Thalidomide. Methods This case-controlled study included one group of patients diagnosed to have leprosy and the other group was healthy controlled individuals with matched age, sex, and area of residence. All the patients with type II lepra reaction responded to Capsule Thalidomide clinically, and all the skin lesions resolved in 7–14 days. Blood samples and skin biopsy were subjected to histopathology, immunoflourescence assay, immunohistochemical staining, quantitative RT-PCR (reverse transcriptase-polymerase chain reaction), and flow cytometry. Results Interferon-γ and TNF-α are sensitive markers in diagnosing erythema nodosum leprosum and Cd-64 expression on activated circulating neutrophils is both a specific and sensitive marker in Type II lepra reaction. Cd-64 expression also had a positive correlation with Thalidomide treatment and clinical response. High polymorphonuclear Cd-64 expression was correlated with severity of ENL. Conclusion Cd-64 expression on circulating neutrophils is a potential early biophysical marker for diagnosing erythema nodosum leprosum and can be used as a tool to assess thalidomide response. It is however not a good index to diagnose leprosy infection as it was specific for Type II lepra reaction. Interferon-γ and TNF-α are sensitive markers to screen for lepra reactions and this study showed no significant correlation with Thalidomide therapy. Disclosures All authors: No reported disclosures.

Analysis of tissue lesions of the major reactional states of leprosy was undertaken to study the immune mechanisms underlying regulation of cell-mediated immunity and delayed-type hypersensitivity (DTH) in man. In situ hybridization hybridization of reversal reaction biopsy specimens for INF-gamma mRNA expression revealed a 10-fold increase in specific mRNA-containing cells over that observed in unresponsive lepromatous patients. Expression of huHF serine esterase, a marker for T cytotoxic cells, were fourfold increased in reversal reaction and tuberculoid lesions above that detected in unresponsive lepromatous individuals. Immunohistology of reversal reactions confirmed a selective increase of Th and T cytotoxic cells in the cellular immune response. Of interest, the microanatomic location of these serine esterase mRNA-containing cells was identical to the distribution of CD4+ cells. Analysis of erythema nodosum leprosum (ENL) lesions revealed differences in the underlying immune processes in comparison with reversal reaction lesions. Although phenotypic Th cells predominated in ENL lesions, IFN-gamma and serine esterase gene expression were markedly reduced. We suggest that reversal reactions represent a hyperimmune DTH response characterized by a selective increase of CD4+ IFN-gamma producing cells and T cytotoxic cells, which result in the clearing of bacilli and concomitant tissue damage. In contrast, ENL reactions may be viewed as a transient diminution of Ts cells and activity leading to a partial and transient augmentation in cell-mediated immunity, perhaps sufficient to result in antibody and immune complex formation, but insufficient to clear bacilli from lesions.

Microbial agents induce arthritis through mechanisms such as direct infiltration of tissue and by inducing autoimmune phenomena. The mechanisms involved in this last type of arthritis have been investigated. In experimental models of adjuvant and reactive arthritis, the involvement of T cells and in some cases mycobacteria in the development of arthritis have been confirmed. Cross-reactivity between the 65 kD mycobacterial protein and cartilage proteoglycans has been postulated as a possible mechanism. In this study, chronic peripheral arthritis was observed in patients with Hansen's disease, in patients with resolved Hansen's and in those with paucibacillary forms. This arthritis was not related to reactional states (erythema nodosum Ieprosum and reversal reaction), in contrast to several reports in the literature. The mechanisms by which microbes could induce chronic arthritis are discussed herein.

It is well known that reactions are commonplace occurrences during the course of leprosy disease. Stigmatization may even be attributable to reactions which are also responsible for the worsening of neural lesions. A cohort of 162 newly-diagnosed baciloscopically positive patients from the Leprosy Care Outpatient Clinic of the Oswaldo Cruz Foundation (FIOCRUZ) was selected for this study. While 46% of the multibacillary (MB) patients submitted to the 24 fixed-dose multidrug therapy (MDT) regimen suffered reactions during treatment, it was found that all MBs were susceptible and that constant attention and care were required at all times. Fourteen per cent were classified as BB, 52% as BL, and 33% as LL. None of the variables under study, such as, sex, age, clinical form, length of illness, length of dermatological lesions, baciloscopic index (BI), or degree of disability proved to be associate with reaction among the patients studied. Reversal Reaction (RR) occurred in 45%, and Erythema Nodosum Leprosum (ENL) occurred in 55%. Among BB patients who developed reactions (15 patients), 93% presented RR; while among the LL patients who developed reactions (34 patients), 91% presented ENL. Likewise, ENL was very frequent among those with disseminate lesions, while RR was most often observed in patients with segmentary lesions. RR was also most likely to occur during the initial months of treatment. It was demonstrated that the recurrence rate of ENL was significantly higher than that of RR. Neither grade of disability nor BI was shown to be associated with RR and ENL reaction. However, the RR rate was significantly higher among patients showing BI < 3, while ENL predominated among those patients with BI > 3.

Leprosy, a spectral disease manifested on the basis of host immune responses,is complicated by its reactional stages, namely type I reversal reaction (RR)and type II erythema nodosum leprosum (ENL). These reactional stagesare characterized by uncontrolled and aberrant immune responses. Biomarkersfor reactional stages would aid in early diagnosis, efficient treatment, preventionof neurological complications and prediction of predisposition to reactionalstages. In this study, comparative analysis of the serum proteome of leprosypatients by two-dimensional electrophoresis (2DE) followed by massspectrometry showed differential expression of acute-phase protein α 1-acid glycoprotein (AGP; also known as orosomucoid).AGP levels in untreated ENL cases were significantly higher than in lepromatousleprosy (LL; a non-reactional disease stage) (P=0.0126),RR (P=0.0176) and healthy controls (P=0.0030).These data were confirmed using ELISA. The levels of AGP decreased to normallevels after treatment with multidrug therapy and thalidomide (P=0.0167). In a follow-up study, AGP levels, which were highin the untreated ENL stage, decreased significantly at 5 days (P=0.0084) and 21 days (P=0.0027)post-treatment. A stage-dependent increase in AGP in an LL patient who progressedinto the ENL stage was also shown. Glycosylation analysis by 2DE showed differentialexpression of acidic glycoforms of AGP in untreated ENL cases. Changes inAGP concentration and differential expression of isoforms correlated withthe inflammatory condition in ENL and also with the treatment regimen. Thus,initial validation of AGP as an ENL-specific biomarker and treatment indicatorwas shown in this study.

A hanseníase é geralmente agravada pelo aparecimento de reações, que são quadros inflamatórios de difícil tratamento e a principal causa de seqüelas. Nossa hipótese é de que deficiência e/ou perda da função das células T reguladoras (Tregs) podem estar envolvidas no desenvolvimento das reações. Além da avaliação da frequência das Tregs circulantes em pacientes com reação tipo 1 (R1) e reação tipo 2 (R2), também foi avaliada a frequência in situ de FoxP3, IL-17, IL-6 e TGFbeta. Pacientes com R2 apresentaram expressiva diminuição na frequência das Tregs circulantes e in situ em comparação com pacientes com R1 e com os controles. Paralelamente a diminuição das Tregs nas R2 foi observado aumento da expressão de IL-17 in situ e diminuição da expressão de TGFbeta. Biópsias obtidas de pacientes com R1 e R2 antes do episódio reacional mostraram números de células FoxP3+ e IL-17+ similares entre os dois grupos. Entretanto, nas biópsias obtidas durante a reação foi observado diminuição de Tregs e aumento de células IL-17+ em pacientes com R2, enquanto que pacientes com R1 apresentaram o oposto: aumento de Tregs e diminuição de células IL-17+. Além disso, foi observada diminuição da expansão das Tregs frente ao estímulo in vitro com Mycobacterium leprae e uma tendência a baixa expressão de FoxP3 e da molécula imunossupressora CTLA-4 em Tregs de pacientes com R2. Nossos resultados sugerem que nas R2, a diminuição na frequência de Tregs possa estar favorecendo o desenvolvimento de uma resposta Th17, a qual é característica deste tipo de reação. Adicionalmente, com a finalidade de obter um número suficiente de Tregs para realização de ensaios funcionais com estas células, uma vez que se trata de uma subpopulação com baixa freqüência no sangue periférico ( < 10%), foram estabelecidos e avaliados três protocolos distintos para expansão in vitro de Tregs: protocolo Rapamicina, protocolo TGFbeta e protocolo Vitamina D3. Todos os protocolos foram capazes de induzir expansão de Tregs viáveis nos grupos estudados (paucibacilares e multibacilares sem reação, R1 e R2). Em todos os grupos estudados as Tregs expandidas apresentaram capacidade de suprimir a proliferação de linfócitos TCD4+ e TCD8+. Apesar dos três protocolos testados apresentarem capacidade de expandir Tregs in vitro, selecionamos para ensaios futuros os protocolos Rapamicina e TGFbeta por apresentarem melhor custo-benefício. A expansão in vitro será utilizada para estudos funcionais das Tregs buscando melhor entendimento do envolvimento desta subpopulação na patogenia das reações hansênicas
Leprosy is frequently complicated by the appearance of reactions that are difficult to treat and are the main cause of sequelae. We speculated that disturbances in regulatory T-cells (Tregs) could play a role in leprosy reactions. We determined the frequency of circulating Tregs in patients with type 1 reaction (T1R) and type 2 reaction (T2R). The in situ frequency of FoxP3 and interleukin (IL)-17, IL-6, and transforming growth factor beta (TGF)-beta expressing cells was also determined. T2R patients showed markedly lower number of circulating and in situ Tregs than T1R patients and controls. This decrease was paralleled by increased in situ IL-17 expression but decreased TGF-beta expression. Biopsies from T1R and T2R patients before the reaction episodes showed similar number of forkhead box protein P3 + (FoxP3+) and IL-17+ cells. However, in biopsies taken during the reaction, T2R patients showed a decrease in Tregs and increase in IL-17+ cells, whereas T1R patients showed the opposite: Tregs increased but IL17+ cells decreased. We also found decreased expansion of Tregs upon in vitro stimulation with Mycobacterium leprae and a trend for lower expression of FoxP3 and the immunosuppressive molecule CTLA-4 in T2R Tregs. Our results provide some evidence to the hypothesis that, in T2R, downmodulation of Tregs may favor the development of T-helper-17 responses that characterize this reaction. In addition, aiming to provide sufficient number of Tregs to perform functional assays with these cells, as they correspond to a subtle subpopulation among the peripheral blood mononuclear cells ( < 10%), we established and analyzed three different protocols for in vitro Tregs: a Rapamycin protocol, a TGFbeta protocol and a Vitamina D3 protocol. All three protocols were able to induce the expansion of viable in the four types of patients of the study (paucibacillary and multibacillary patients without reaction, and R1 and R2 patients). In these four groups the tregs were able to suppress the proliferative response of TCD4+ e TCD8+ lymphocytes. Although the three protocols resulted in expansion of Tregs, we selected two of them, Rapamycin and TGFbeta for further assays since they showed better cost-benefit. The in vitro expansion will be used to perform functional assays of the Tregs aiming at a better understanding of the involvement of this subpopulation in the pathogenesis of the leprosy reaction episodes

Behçet’s syndrome is an inflammatory disorder of unknown aetiology that involves arteries and veins of all sizes. Most cases are from the countries around the Mediterranean basin, the Middle East, and East Asia, with the highest prevalence in Turkey. It typically presents in the second and third decades with recurrent oral ulcers (98% of cases), genital ulcers (85%), acneiform lesions (85%), pathergy reaction (60% in some countries), erythema nodosum (50%), uveitis (50%), arthritis (50%), thrombophlebitis (30%), and less commonly with arterial occlusion/aneurysm, central nervous system involvement, or gastrointestinal lesions. A relapsing/remitting course is usual. Disease is more severe and mortality is higher in men. The diagnosis is clinical, laboratory findings are non-specific, and there is no specific diagnostic test for Behçet’s syndrome.

Behçet’s syndrome is an inflammatory disorder of unknown aetiology that involves arteries and veins of all sizes. Most cases are from the countries around the Mediterranean basin, the Middle East and east Asia, with the highest prevalence in Turkey. Clinical features—the disease typically presents in the second and third decades with recurrent oral ulcers (98% of cases), genital ulcers (85%), acneiform lesions (85%), pathergy reaction (60% in some countries), erythema nodosum (50%), uveitis (50%), arthritis (50%), thrombophlebitis (30%), and less commonly with arterial occlusion/aneurysm, central nervous system involvement or gastrointestinal lesions. A relapsing/remitting course is usual. Disease is more severe and mortality is higher in men. The diagnosis is clinical, laboratory findings are nonspecific and there is no specific diagnostic test for Behçet’s syndrome....