RESUMEN
Leprosy is a chronic infectious disease caused by the bacillus Mycobacterium leprae. The disease may evolve for inflammatory reactions, reversal reaction (RR) and erythema nodosum leprosum (ENL), the major cause of irreversible neuropathy in leprosy, which occur in 1 in 3 people with leprosy, even with effective treatment of M. leprae. Leprosy remains persistently endemic in our region where it predominantly affects lowest socioeconomic conditions people, as Toxoplasma gondii infection in the municipality studied. Previously, we have shown T. gondii coinfection as a risk marker for leprosy, mainly in its severe form. This present study assessed whether T. gondii infection is also a risk factor for leprosy reactions and the predictive value of immunoglobulin production prior to development of leprosy reactions. Patients with leprosy (n = 180), co-infected or not with T. gondii, had their serum investigated for levels of IgA, IgE, IgG1, IgG2, IgG3 and IgG4 anti-PGL-1 by ELISA prior to development of leprosy reactions. The serologic prevalence for T. gondii infection was 87.7% in leprosy reaction patients reaching 90.9% in those with ENL. The leprosy reaction risk increased in T. gondii seropositive individuals was two-fold ([OR] = 2.366; 95% confidence interval [CI 95%]: 1.024-5.469) higher than those seronegative, and considering the risk of ENL, this increase was even more evident (OR = 6.753; 95% CI: 1.050-72.85) in coinfected individuals. When evaluated the prediction of anti-PGL-1 immunoglobulin levels for development of leprosy reactions in patients coinfected or not with T. gondii, only the increase IgE levels were associated to occurrence of reactional episodes of leprosy, specifically ENL type, in patients coinfected with T. gondii, compared to those not coinfected or no reaction. Thus, the immunomodulation in co-parasitism T. gondii-M. leprae suggest increased levels of IgE as a biomarker for early detection of these acute inflammatory episodes and thereby help prevent permanent neuropathy and disability in leprosy patients.
Asunto(s)
Eritema Nudoso , Inmunoglobulina E , Toxoplasma , Toxoplasmosis , Humanos , Toxoplasmosis/sangre , Toxoplasmosis/complicaciones , Toxoplasmosis/inmunología , Toxoplasmosis/epidemiología , Eritema Nudoso/inmunología , Eritema Nudoso/epidemiología , Eritema Nudoso/sangre , Femenino , Masculino , Adulto , Inmunoglobulina E/sangre , Persona de Mediana Edad , Toxoplasma/inmunología , Coinfección/inmunología , Coinfección/parasitología , Mycobacterium leprae/inmunología , Adulto Joven , Adolescente , Factores de Riesgo , Anciano , Lepra Lepromatosa/inmunología , Lepra Lepromatosa/complicaciones , Lepra Lepromatosa/sangre , Lepra Lepromatosa/epidemiologíaRESUMEN
Introduction: Patients with the multibacillary form of leprosy can develop reactional episodes of acute inflammation, known as erythema nodosum leprosum (ENL), which are characterized by the appearance of painful cutaneous nodules and systemic symptoms. Neutrophils have been recognized to play a role in the pathogenesis of ENL, and recent global transcriptomic analysis revealed neutrophil-related processes as a signature of ENL skin lesions. Methods: In this study, we expanded this analysis to the blood compartment, comparing whole blood transcriptomics of patients with non-reactional lepromatous leprosy at diagnosis (LL, n=7) and patients with ENL before administration of anti-reactional treatment (ENL, n=15). Furthermore, a follow-up study was performed with patients experiencing an ENL episode at the time of diagnosis and after 7 days of thalidomide treatment (THAL, n=10). Validation in an independent cohort (ENL=8; LL=7) was performed by RT-qPCR. Results: An enrichment of neutrophil activation and degranulation-related genes was observed in the ENL group, with the gene for the neutrophil activation marker CD177 being the most enriched gene of ENL episode when compared to its expression in the LL group. A more pro-inflammatory transcriptome was also observed, with increased expression of genes related to innate immunity. Validation in an independent cohort indicated that S100A8 expression could discriminate ENL from LL. Supernatants of blood cells stimulated in vitro with Mycobacterium leprae sonicate showed higher levels of CD177 compared to the level of untreated cells, indicating that the leprosy bacillus can activate neutrophils expressing CD177. Of note, suggestive higher CD177 protein levels were found in the sera of patients with severe/moderate ENL episodes when compared with patients with mild episodes and LL patients, highlighting CD177 as a potential systemic marker of ENL severity that deserves future confirmation. Furthermore, a follow-up study was performed with patients at the time of ENL diagnosis and after 7 days of thalidomide treatment (THAL, n=10). Enrichment of neutrophil pathways was sustained in the transcriptomic profile of patients undergoing treatment; however, important immune targets that might be relevant to the effect of thalidomide at a systemic level, particularly NLRP6 and IL5RA, were revealed. Discussion: In conclusion, our study reinforces the key role played by neutrophils in ENL pathogenesis and shed lights on potential diagnostic candidates and novel therapeutic targets that could benefit patients with leprosy.
Asunto(s)
Eritema Nudoso , Perfilación de la Expresión Génica , Lepra Lepromatosa , Activación Neutrófila , Neutrófilos , Transcriptoma , Humanos , Eritema Nudoso/inmunología , Eritema Nudoso/sangre , Lepra Lepromatosa/inmunología , Lepra Lepromatosa/diagnóstico , Lepra Lepromatosa/sangre , Adulto , Masculino , Neutrófilos/inmunología , Neutrófilos/metabolismo , Femenino , Persona de Mediana Edad , Proteínas Ligadas a GPI/genética , Talidomida , Receptores de Superficie Celular/genética , Leprostáticos/uso terapéutico , Leprostáticos/farmacología , Adulto Joven , Biomarcadores , IsoantígenosRESUMEN
BACKGROUND: Erythema nodosum leprosum (ENL) is a frequent complication of multibacillary leprosy that can result in significant morbidity, including peripheral nerve damage and physical disability. The identification of possible serum markers could be a valuable tool for the early detection of ENL. AIMS: The purpose of this study was to evaluate selected serum mediators involved in the innate and adaptive immune responses to identify possible immunomarkers for ENL. METHODS: The levels of interleukin-2, interleukin-4, interleukin-6, interleukin-10, interleukin-17, interferon-γ, tumor necrosis factor, nitric oxide and anti-phenolic glycolipid-I antibodies were measured in the sera of leprosy patients with ENL [at the beginning of reaction (M0) and 1 month later (M1)], and then compared with the levels of the same markers in patients with untreated multibacillary leprosy without ENL (controls with leprosy: CTRL) and healthy individuals (healthy controls: CTRH). RESULTS: Significantly higher levels of serum interleukin-6 were observed in M0 than in CTRL. In addition, pairwise comparisons showed higher levels of interleukin-6 in M0 compared to M1. Levels of tumor necrosis factor were higher in M0 than in CTRL, with no significant difference between M0 and M1. There were no differences in the levels of interleukin-2, interleukin-4, interleukin-10, interleukin-17 or interferon-γ between groups. The CTRL group had higher levels of nitric oxide compared to M0 and M1. High levels of anti-phenolic glycolipid-I were observed in M0, M1 and CTRL than in CTRH. LIMITATIONS: Three patients were not assessed at M1, decreasing the number of evaluated patients from 14 to 11. CONCLUSION: High-serum levels of interleukin-6 were observed during ENL, primarily in patients with more severe reactions; levels decreased after specific therapy, suggesting a role for this cytokine in pathogenesis and its utility as an ENL biomarker. Further studies should explore whether interleukin-6 could also be used as a predictive marker for ENL or as a specific target for its treatment.
Asunto(s)
Eritema Nudoso/sangre , Interleucina-6/sangre , Lepra/sangre , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Factor de Necrosis Tumoral alfa/sangreRESUMEN
ABSTRACT: Erythema nodosum leprosum (ENL) occurs as an immunological complication of multibacillary leprosy (MBL). The pathogenesis of ENL is long considered to be a T-cell-mediated process. The role of B cells and plasma cells in ENL is not well described in the literature. Therefore, we investigated the B-cell and plasma cell infiltrates in the skin biopsies of biopsy-proven cases of ENL by immunohistochemistry and image morphometry and compared the result with paucibacillary leprosy and MBL. Moreover, we sought a correlation of the B-cell and plasma cell infiltrates with different clinical, hematological, histopathological, and bacteriological parameters as well as the T-cell subsets in the skin biopsies. Our study highlighted a significant reduction in the number of B cells from paucibacillary leprosy to MBL to ENL, although there was no significant variation in the plasma cell infiltrate. The plasma cell infiltrate correlated with absolute neutrophilia in the blood and the presence of eosinophils in the ENL lesions. Both B cells and plasma cells positively correlated with CD4-positive T-helper cells and the CD8-positive cytotoxic T cells. Besides, the B cells also correlated positively with the CD3-positive pan T cells in the biopsy and negatively correlated with the T-regulatory:T-cell ratio. Our results suggested the role of B cells and plasma cells even at the tissue level in the pathobiogenesis of ENL.
Asunto(s)
Linfocitos B/patología , Eritema Nudoso/patología , Lepra Lepromatosa/patología , Células Plasmáticas/patología , Adolescente , Adulto , Anciano , Antígenos CD20/metabolismo , Linfocitos B/metabolismo , Recuento de Células Sanguíneas , Niño , Preescolar , Eosinófilos/patología , Eritema Nudoso/sangre , Eritema Nudoso/inmunología , Femenino , Humanos , Inmunohistoquímica , Lactante , Lepra Lepromatosa/sangre , Lepra Lepromatosa/inmunología , Lepra Paucibacilar/inmunología , Lepra Paucibacilar/patología , Masculino , Persona de Mediana Edad , Neutrófilos , Células Plasmáticas/metabolismo , Sindecano-1/metabolismo , Linfocitos T Citotóxicos/patología , Linfocitos T Colaboradores-Inductores/patología , Linfocitos T Reguladores/patología , Adulto JovenRESUMEN
We report a 50-year-old Caucasian woman who presented with recurrent erythema nodosum, leg swelling, malaise, weight loss and abdominal pain associated with an IgM lambda paraprotein. She was treated with six courses of an anti-CD20 monoclonal antibody and bendamustine chemotherapy over 6 months with a good clinical response.
Asunto(s)
Dolor Abdominal , Clorhidrato de Bendamustina/administración & dosificación , Eritema Nudoso , Inmunoglobulina M/análisis , Linfocitosis , Rituximab/administración & dosificación , Síndrome de Schnitzler/diagnóstico , Dolor Abdominal/diagnóstico , Dolor Abdominal/etiología , Antineoplásicos/administración & dosificación , Diagnóstico Diferencial , Eritema Nudoso/sangre , Eritema Nudoso/diagnóstico , Eritema Nudoso/fisiopatología , Eritema Nudoso/terapia , Femenino , Humanos , Linfocitosis/diagnóstico , Linfocitosis/etiología , Persona de Mediana Edad , Paraproteínas/análisis , Manejo de Atención al Paciente/métodos , Resultado del Tratamiento , Pérdida de PesoRESUMEN
BACKGROUND: Leprosy is a treatable infectious disease caused by Mycobacterium leprae. However, there is additional morbidity from leprosy-associated pathologic immune reactions, reversal reaction (RR) and erythema nodosum leprosum (ENL), which occur in 1 in 3 people with leprosy, even with effective treatment of M. leprae. There is currently no predictive marker in use to indicate which people with leprosy will develop these debilitating immune reactions. Our peripheral blood mononuclear cell (PBMC) transcriptome analysis revealed that activation of the classical complement pathway is common to both RR and ENL. Additionally, differential expression of immunoglobulin receptors and B cell receptors during RR and ENL support a role for the antibody-mediated immune response during both RR and ENL. In this study, we investigated B-cell immunophenotypes, total and M. leprae-specific antibodies, and complement levels in leprosy patients with and without RR or ENL. The objective was to determine the role of these immune mediators in pathogenesis and assess their potential as biomarkers of risk for immune reactions in people with leprosy. METHODOLOGY/FINDINGS: We followed newly diagnosed leprosy cases (n = 96) for two years for development of RR or ENL. They were compared with active RR (n = 35), active ENL (n = 29), and healthy household contacts (n = 14). People with leprosy who subsequently developed ENL had increased IgM, IgG1, and C3d-associated immune complexes with decreased complement 4 (C4) at leprosy diagnosis. People who developed RR also had decreased C4 at leprosy diagnosis. Additionally, elevated anti-M. leprae antibody levels were associated with subsequent RR or ENL. CONCLUSIONS: Differential co-receptor expression and immunoglobulin levels before and during immune reactions intimate a central role for humoral immunity in RR and ENL. Decreased C4 and elevated anti-M. leprae antibodies in people with new diagnosis of leprosy may be risk factors for subsequent development of leprosy immune reactions.
Asunto(s)
Anticuerpos Antibacterianos/sangre , Complemento C3d/análisis , Complemento C4/análisis , Eritema Nudoso/epidemiología , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Lepra Lepromatosa/epidemiología , Mycobacterium leprae/inmunología , Adulto , Anciano , Anticuerpos Antibacterianos/inmunología , Linfocitos B/inmunología , Complemento C3d/inmunología , Complemento C4/inmunología , Eritema Nudoso/sangre , Eritema Nudoso/inmunología , Femenino , Perfilación de la Expresión Génica , Humanos , Inmunidad Activa/inmunología , Inmunoglobulina G/inmunología , Inmunoglobulina M/inmunología , Lepra Lepromatosa/sangre , Lepra Lepromatosa/inmunología , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
BACKGROUND: Erythema nodosum leprosum (ENL) is a systemic inflammatory complication occurring mainly in patients with lepromatous leprosy (LL) and borderline lepromatous leprosy (BL). Prednisolone is widely used for treatment of ENL reactions. However, it has been reported that prolonged treatment with prednisolone increases the risk for prednisolone-induced complications such as osteoporosis, diabetes, cataract and arteriosclerosis. It has been speculated that perhaps these complications result from lipid profile alterations by prednisolone. The effects of extended prednisolone treatment on lipid profiles in ENL patients have not been studied in leprosy patients with ENL reactions. Therefore, in this study we conducted a case-control study to investigate the changes in lipid profiles and serological responses in Ethiopian patients with ENL reaction after prednisolone treatment. METHODS: A prospective matched case-control study was employed to recruit 30 patients with ENL and 30 non-reactional LL patient controls at ALERT Hospital, Ethiopia. Blood samples were obtained from each patient with ENL reaction before and after prednisolone treatment as well as from LL controls. The serological host responses to PGL-1, LAM and Ag85 M. leprae antigens were measured by ELISA. Total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL) and low density lipoprotein (LDL) were measured by spectrophotometric method. RESULTS: The host antibody response to M. leprae PGL-1, LAM and Ag85 antigens were significantly reduced in patients with ENL reactions compared to LL controls after treatment. Comparison between patients with acute and chronic ENL showed that host-response to PGL-1 was significantly reduced in chronic ENL after prednisolone treatment. Untreated patients with ENL reactions had low lipid concentration compared to LL controls. However, after treatment, both groups had comparable lipid profiles except for LDL, which was significantly higher in patients with ENL reaction. Comparison within the ENL group before and after treatment showed that prednisolone significantly increased LDL and HDL levels in ENL patients and this was more prominent in chronic ENL than in acute patients with ENL. CONCLUSION: The significantly increased prednisolone-induced LDL and TG levels, particularly in patients with chronic ENL reactions, is a concern in the use of prednisolone for extended periods in ENL patients. The findings highlight the importance of monitoring lipid profiles during treatment of patients to minimize the long-term risk of prednisolone-induced complications.
Asunto(s)
Eritema Nudoso/sangre , Eritema Nudoso/tratamiento farmacológico , Lepra Lepromatosa/complicaciones , Prednisolona/administración & dosificación , Adolescente , Adulto , Estudios de Casos y Controles , Colesterol/sangre , Eritema Nudoso/etiología , Eritema Nudoso/inmunología , Femenino , Humanos , Lepra Lepromatosa/microbiología , Lipoproteínas HDL/sangre , Lipoproteínas LDL/sangre , Masculino , Persona de Mediana Edad , Mycobacterium leprae/fisiología , Prednisolona/efectos adversos , Estudios Prospectivos , Triglicéridos/sangre , Adulto JovenRESUMEN
The disease leprosy is caused by Mycobacterium leprae. The disease displays a spectrum of clinical manifestations relating to the stage of the infection and the pathogen-specific immune response. The most frequent M. leprae-specific hypersensitivity reactions are erythema nodosum leprosum (ENL) and type-1 (reversal) reaction (T1R). Omega-3 and omega-6 fatty acid-derived lipid mediators are involved in the regulation of these M. leprae-specific inflammatory and immune responses. Studies on lipid mediators showed their presence during different manifestations of leprosy-before and after multidrug therapy (MDT) and during T1R. This review aims to compare the lipid mediators at different stages of the disease. This review also presents new data on the significance of lipid mediators (cysteinyl leukotrienes and leukotriene B4, prostaglandin E2 and D2, lipoxin A4 and resolvin D1) on ENL.
Asunto(s)
Ácidos Grasos Omega-3/sangre , Ácidos Grasos Omega-6/sangre , Lepra/sangre , Animales , Quimioterapia Combinada , Eritema Nudoso/sangre , Eritema Nudoso/tratamiento farmacológico , Humanos , Leprostáticos/farmacología , Lepra/tratamiento farmacológico , Mycobacterium leprae/efectos de los fármacosRESUMEN
Complement C1q is a soluble protein capable of initiating components of the classical pathway in host defence system. In earlier qualitative studies, C1q has been implicated in the pathogenesis of Erythema Nodosum Leprosum (ENL). However, little is known about the role of this complement in ENL reaction. In the present study we described the protein level of C1q production and its gene expression in the peripheral blood and skin biopsies in patients with ENL reaction and lepromatous leprosy (LL) patient controls before and after treatment. Thirty untreated patients with ENL reaction and 30 non-reactional LL patient controls were recruited at ALERT Hospital, Ethiopia. Peripheral blood and skin biopsies were obtained from each patient before and after treatment. The level of circulating C1q in the plasma was determined by enzyme-linked immunosorbent assay. The mRNA expression of the three C1q components, C1qA, C1qB, and C1qC in the peripheral blood and skin biopsies was determined by qPCR. Circulating C1q in the peripheral blood of untreated ENL patients was significantly decreased compared to LL patient controls. Untreated ENL patients had increased C1q gene expression in the peripheral blood compared to LL controls. Similarly, C1qA and C1qC gene expression were substantially increased in the skin biopsies of untreated ENL patients compared to LL controls. However, after treatment none of these genes show significant difference in both groups. In conclusion, while circulating C1q is inversely correlated with active ENL reactions, its gene expression is directly correlated with ENL. The decreased circulating C1q may suggest the utilization of C1q in immune-complex formation in these patients. Therefore, C1q could be a potential diagnostic marker for active ENL reactions as well as for monitoring ENL treatment.
Asunto(s)
Complemento C1q/genética , Eritema Nudoso/sangre , Lepra Lepromatosa/sangre , Adolescente , Adulto , Estudios de Casos y Controles , Complemento C1q/metabolismo , Citocinas/sangre , Eritema Nudoso/genética , Etiopía , Femenino , Regulación de la Expresión Génica , Humanos , Lepra Lepromatosa/genética , Masculino , Persona de Mediana Edad , ARN Mensajero/genética , Piel/patología , Adulto JovenRESUMEN
BACKGROUND: Leprosy is a chronic dermato-neurological disease caused by Mycobacterium leprae infection. In 2016, more than 200,000 new cases of leprosy were detected around the world, representing the most frequent cause of infectious irreversible deformities and disabilities. PRINCIPAL FINDINGS: In the present work, we demonstrate a consistent procoagulant profile on 40 reactional and non-reactional multibacillary leprosy patients. A retrospective analysis in search of signs of coagulation abnormalities among 638 leprosy patients identified 35 leprosy patients (5.48%) which displayed a characteristic lipid-like clot formed between blood clot and serum during serum harvesting, herein named 'leprosum clot'. Most of these patients (n = 16, 45.7%) belonged to the lepromatous leprosy pole of the disease. In addition, formation of the leprosum clot was directly correlated with increased plasma levels of soluble tissue factor and von Willebrand factor. High performance thin layer chromatography demonstrated a high content of neutral lipids in the leprosum clot, and proteomic analysis demonstrated that the leprosum clot presented in these patients is highly enriched in fibrin. Remarkably, differential 2D-proteomics analysis between leprosum clots and control clots identified two proteins present only in leprosy patients clots: complement component 3 and 4 and inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP). In agreement with those observations we demonstrated that M. leprae induces hepatocytes release of IHRP in vitro. CONCLUSIONS: We demonstrated that leprosy MB patients develop a procoagulant status due to high levels of plasmatic fibrinogen, anti-cardiolipin antibodies, von Willebrand factor and soluble tissue factor. We propose that some of these components, fibrinogen for example, presents potential as predictive biomarkers of leprosy reactions, generating tools for earlier diagnosis and treatment of these events.
Asunto(s)
Trastornos de la Coagulación Sanguínea/microbiología , Eritema Nudoso/sangre , Lepra Lepromatosa/sangre , Piel/microbiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Brasil , Niño , Electroforesis en Gel Bidimensional , Electroforesis en Gel de Poliacrilamida , Eritema Nudoso/complicaciones , Femenino , Humanos , Lepra Lepromatosa/complicaciones , Modelos Lineales , Masculino , Espectrometría de Masas , Persona de Mediana Edad , Mycobacterium leprae/aislamiento & purificación , Estudios Prospectivos , Proteómica/métodos , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Erythema nodosum leprosum is an immune-mediated complication of leprosy which causes significant morbidity. Biomarkers in the pathogenesis of erythema nodosum leprosum are not yet fully determined. AIM: To determine macrophage migration inhibitory factor levels in the sera of leprosy patients with erythema nodosum leprosum and to correlate the same with clinical parameters. METHODS: This cross-sectional study included 37 consecutive leprosy patients with active erythema nodosum leprosum and 31 age- and sex-matched controls. Detailed clinical history and examination findings were recorded including the severity and frequency of erythema nodosum leprosum. Slit skin smears and histopathologic examination were done in all patients at baseline. Serum macrophage migration inhibitory factor levels were determined using an enzyme-linked immunosorbent assay. RESULTS: Most of our patients were males (78.4%) and suffering from lepromatous leprosy (27, 73%) with a mean initial bacillary index of 3.38 ± 1.36. Recurrent and chronic patterns of erythema nodosum leprosum were seen in 15 (40.5%) and 6 (16.3%) patients, respectively. Most (86.5%) of our patients presented with moderate to severe erythema nodosum leprosum. The mean serum macrophage migration inhibitory factor level was 21.86 ± 18.7 ng/ml among patients while it was 11.78 ± 8.4 ng/ml in the control group (P < 0.01). There were no statistically significant correlations of macrophage migration inhibitory factor levels with erythema nodosum leprosum frequency or severity. LIMITATION: Serum macrophage migration inhibitory factor levels in leprosy patients with no erythema nodosum leprosum and in patients with other inflammatory and autoimmune conditions were not assessed. Hence, this study falls short of providing the predictive value and specificity of higher macrophage migration inhibitory factor concentrations in serum as a biomarker of erythema nodosum leprosum. CONCLUSION: Macrophage migration inhibitory factor levels are elevated in erythema nodosum leprosum patients as compared to controls. A larger sample size and macrophage migration inhibitory factor gene polymorphism analysis will be needed to elucidate the role of this pro-inflammatory cytokine in erythema nodosum leprosum.
Asunto(s)
Eritema Nudoso/sangre , Eritema Nudoso/diagnóstico , Oxidorreductasas Intramoleculares/sangre , Lepra/sangre , Lepra/diagnóstico , Factores Inhibidores de la Migración de Macrófagos/sangre , Adulto , Biomarcadores/sangre , Estudios Transversales , Eritema Nudoso/epidemiología , Femenino , Humanos , Lepra/epidemiología , Masculino , Persona de Mediana EdadRESUMEN
Hemostatic illnesses are frequently associated with acute and chronic infections. In the present work we demonstrated that leprosy patients developed hemostatic abnormalities, like the formation of an atypical lipid clot mass during sera harvesting, a phenomenon previously observed and never unraveled. We characterize the nature of the "leprosum clot", formed during a protrombotic state developed by some patients. During the proteomic analysis of the leprosum clot we discovered a set of potential serum biomarkers to leprosy reactional episodes diagnosis, which at this moment is based only in clinical features. Taking together, our data suggest that leprosy patients are suffering from a procoagulant status, being beneficiated by the introduction of routine coagulation tests during their treatment, which will aloud physicians to prevent some of the acute clinical symptoms related with superficial vein thrombosis such as cyanosis and tissue necrosis observed during severe cases of leprosy reactional episodes. (AU)
Asunto(s)
Humanos , Masculino , Femenino , Niño , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Adulto Joven , Piel/microbiología , Espectrometría de Masas , Trastornos de la Coagulación Sanguínea/microbiología , Biomarcadores/sangre , Electroforesis en Gel Bidimensional , Lepra Lepromatosa/complicaciones , Lepra Lepromatosa/sangre , Modelos Lineales , Proteómica/métodos , Electroforesis en Gel de Poliacrilamida , Eritema Nudoso/complicaciones , Eritema Nudoso/sangre , Mycobacterium leprae/aislamiento & purificación , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
Mycobacterium tuberculosis is very rarely found in erythema induratum of Bazin; recently, we found an unusual case with positive acid-fast bacilli and polymerase chain reaction for detecting M. tuberculosis in both skin lesions of the extremities and the site of Mantoux test.
Asunto(s)
Antituberculosos/uso terapéutico , Eritema Indurado/microbiología , Eritema Nudoso/diagnóstico , Glucocorticoides/uso terapéutico , Mycobacterium tuberculosis/aislamiento & purificación , Piel/microbiología , Anciano , Biopsia , Eritema Indurado/sangre , Eritema Indurado/diagnóstico , Eritema Indurado/tratamiento farmacológico , Eritema Nudoso/sangre , Eritema Nudoso/tratamiento farmacológico , Femenino , Humanos , Reacción en Cadena de la Polimerasa , Prednisona/uso terapéutico , Radiografía , Recurrencia , Estaciones del Año , Piel/patología , Insuficiencia del Tratamiento , Prueba de TuberculinaRESUMEN
Erythema nodosum (EN) represents an acute, erythematous nodular eruption that is generally found on the lower aspects of the legs. Despite the variety of triggering factors, the clinical findings of EN are classic. It is often hard to determine which patients have an underlying systemic disorder. The aim of this study was to investigate clinical and laboratory parameters in patients with EN, especially those with an underlying systemic disorder. A total of 43 patients diagnosed with EN at an adult and children's hospital were retrospectively reviewed for triggering factors, any underlying systemic diseases, clinical features, laboratory parameters, treatment modalities, and disease outcome. The mean age of the patients was 40.91±15.57 years (minimum 7 years, maximum 71 years). Patients with an underlying systemic disorder were grouped as complicated EN (CEN), patients without an underlying disorder were grouped as non-complicated EN (NCEN). Patients with EN more frequently presented with more nonpretibial localizations than patients with NCEN (P=.023). Platelet levels in patients with CEN were significantly higher than in patients with NCEN (P=.036). Erythrocyte sedimentation rate, C-reactive protein, and procalcitonin levels did not differ among the two groups (P>.05). Hospitalization shortened the active disease duration (P=.046). EN lesions present on the nonpretibial area, which may be a clue for systemic associations of the disease. The presence of elevated platelet levels may indicate systemic inflammatory and infectious diseases in patients with EN. Procalcitonin, which is a marker for systemic infection, was not helpful in detecting chronic infections such as tuberculosis or systemic fungal infections in patients.
Asunto(s)
Eritema Nudoso , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Sedimentación Sanguínea , Proteína C-Reactiva/análisis , Calcitonina/sangre , Niño , Eritema Nudoso/sangre , Eritema Nudoso/complicaciones , Eritema Nudoso/diagnóstico , Humanos , Persona de Mediana Edad , Recuento de Plaquetas , Estudios Retrospectivos , Adulto JovenAsunto(s)
Artralgia/diagnóstico , Eritema Nudoso/diagnóstico , Factor Estimulante de Colonias de Granulocitos/sangre , Mastitis Granulomatosa/diagnóstico , Complicaciones del Embarazo/diagnóstico , Adulto , Artralgia/sangre , Artralgia/complicaciones , Eritema Nudoso/sangre , Eritema Nudoso/complicaciones , Femenino , Mastitis Granulomatosa/sangre , Mastitis Granulomatosa/complicaciones , Humanos , Periodo Posparto/sangre , Embarazo , Complicaciones del Embarazo/sangreAsunto(s)
Antiinflamatorios no Esteroideos/administración & dosificación , Eritema Nudoso , Exantema , Pierna/patología , Sarcoidosis , Diagnóstico Diferencial , Eritema Nudoso/sangre , Eritema Nudoso/diagnóstico , Eritema Nudoso/tratamiento farmacológico , Eritema Nudoso/etiología , Eritema Nudoso/fisiopatología , Exantema/diagnóstico , Exantema/etiología , Exantema/fisiopatología , Exantema/terapia , Femenino , Humanos , Persona de Mediana Edad , Radiografía Torácica/métodos , Sarcoidosis/complicaciones , Sarcoidosis/diagnóstico , Piel/patología , Resultado del TratamientoRESUMEN
BACKGROUND: Pyoderma gangrenosum (PG) and erythema nodosum (EN) are the most common cutaneous manifestations of inflammatory bowel disease (IBD) but little is known regarding their etiopathogenesis. METHODS: We performed a case-control study comparing characteristics between IBD patients with a documented episode of PG (PG+) and/or EN (EN+) with those without PG (PG-) and EN (EN-). Data on clinical features were obtained by chart review. IBD-related serology was determined using enzyme-linked immunosorbent assay and genome-wide data generated using Illumina technology. Standard statistical tests for association were used. RESULTS: We identified a total of 92 cases of PG and 103 cases of EN with genetic and clinical characteristics, of which 64 PG and 55 EN cases were available for serological analyses. Fewer male subjects were identified in the PG(+) (odds ratio 0.6, P = 0.009) and EN(+) groups (odds ratio 0.31, P = 0 < 0.0001). Colonic disease, previous IBD-related surgery, and noncutaneous extra-intestinal manifestations were more common among both PG(+) and EN(+) patients compared with controls. PG(+) was associated with anti-nuclear cytoplasmic antibody seropositivity (P = 0.03) and higher anti-nuclear cytoplasmic antibody level (P = 0.02) in Crohn's disease. Genetic associations with PG included known IBD loci (IL8RA [P = 0.00003] and PRDM1 [0.03]) as well as with USP15 (4.8 × 10) and TIMP3 (5.6 ×10). Genetic associations with EN included known IBD susceptibility genes (PTGER4 [P = 8.8 × 10], ITGAL [0.03]) as well as SOCS5 (9.64 × 10), CD207 (3.14 × 10), ITGB3 (7.56 × 10), and rs6828740 (4q26) (P < 5.0 × 10). Multivariable models using clinical, serologic, and genetic parameters predicted PG (area under the curve = 0.8) and EN (area under the curve = 0.97). CONCLUSION: Cutaneous manifestations in IBD are associated with distinctive genetic characteristics and with the similar clinical characteristics, including the development of other extra-intestinal manifestations suggesting shared and distinct etiologies.
Asunto(s)
Anticuerpos Antinucleares/sangre , Biomarcadores/análisis , ADN/genética , Eritema Nudoso/etiología , Enfermedades Inflamatorias del Intestino/complicaciones , Piodermia Gangrenosa/etiología , Adulto , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Eritema Nudoso/sangre , Eritema Nudoso/patología , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Enfermedades Inflamatorias del Intestino/sangre , Enfermedades Inflamatorias del Intestino/genética , Masculino , Oportunidad Relativa , Reacción en Cadena de la Polimerasa , Pronóstico , Piodermia Gangrenosa/sangre , Piodermia Gangrenosa/patologíaRESUMEN
Fixed erythema--a kind of clinical and histopathologic reaction, fixed drug eruption. The purpose of the study--the study of characteristics of the cytokine profile in patients with erythema and the dynamics of the basal levels of proinflammatory and antiinflammatory cytokines during immunotherapy. All 41 patients with fixed erythema at baseline and after treatment was carried out determination of levels of pro-, anti-inflammatory and regulatory cytokines in the serum by ELISA using test systems "Biosource" (Austria). In patients with fixed erythema Immunovac treatment increased serum IFN-gamma (p < 0.05), IL-1beta (p > 0.05), IL-6. While Kagocel led to an increase in IFN-gamma (p < 0.05), IL-1beta, IL-6 and reduction of TGF-beta (p < 0.05). At the same time in patients with fixed erythema basic therapy contributed to the significant increase in TGF-â and decrease in IL-10. Immunovac-VP-4 had the highest activity for the induction of IFN-gamma. Inclusion in the range of therapeutic and prophylactic measures in patients with fixed erythema immunomodulators promotes activation links innate and adaptive immunity triggers mechanisms, thus increasing the antiviral response in patients with erythema.