RESUMEN
Recent studies have demonstrated that thymus-derived naturally occurring CD4(+)Foxp3(+) regulatory T cells (Tregs) in human and mouse may be unstable and dysfunctional in the presence of proinflammatory cytokines. All-trans RA (atRA), the active derivative of vitamin A, has been shown to regulate Treg and T effector cell differentiation. We hypothesize atRA stabilizes human natural Tregs (nTregs) under inflammatory conditions. atRA prevents human nTregs from converting to Th1 and/or Th17 cells and sustains their Foxp3 expression and suppressive function in vitro or in vivo following encounters with IL-1 and IL-6. Interestingly, adoptive transfer of human nTregs pretreated with atRA significantly enhanced their suppressive effects on xenograft-vs.-host diseases (xGVHDs), and atRA- but not rapamycin-pretreated nTregs sustained the functional activity against xGVHD after stimulation with IL-1/IL-6. atRA suppresses IL-1 receptor (IL-1R) up-regulation, accelerates IL-6R down-regulation, and diminishes their signaling events as well as prevents the up-regulation of STIP1 homology and U-Box containing protein 1 on Foxp3(+) cells following IL-1/IL-6 stimulation. atRA also increases histone acetylation on Foxp3 gene promoter and CpG demethylation in the region of Foxp3 locus (i.e., Treg-specific demethylated region). These results strongly implicate that nTregs primed with atRA may represent a novel treatment strategy to control established chronic immune-mediated autoimmune and inflammatory diseases.
Asunto(s)
Inflamación/patología , Linfocitos T Reguladores/efectos de los fármacos , Tretinoina/farmacología , Secuencia de Bases , Citocinas/fisiología , Cartilla de ADN , Citometría de Flujo , Factores de Transcripción Forkhead/metabolismo , Humanos , Inflamación/inmunología , Interleucina-1/fisiología , Interleucina-6/fisiología , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores de Interleucina-1/metabolismo , Receptores de Interleucina-6/metabolismo , Linfocitos T Reguladores/inmunología , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
Dissecting cellulitis of the scalp (DCS) is a rare, primary neutrophilic cicatricial alopecia of unknown etiology. The disease follows a chronic, relapsing, and remitting course which may ultimately lead to scar formation and alopecia. The association of seronegative peripheral and/or axial spondyloarthritis in patients with hidradenitis suppurativa (HS) and acne conglobata (AC) is well established. However, the occurrence of spondyloarthropathy in patients with either isolated or combined DCS is relatively rare and therefore underrecognized by clinicians. We report a patient with DCS with inflammatory peripheral arthritis and asymptomatic radiographic sacroiliitis. Using PubMed, Ovid, and Google scholar, we searched for case reports of inflammatory arthritis in HS, AC, and DCS in the English literature from 1982 to present. We identified 12 patients with DCS who had associated spondyloarthropathy with adequate clinical details for a systematic analysis. We outline key clinical features, radiographic findings, and treatment utilized for these patients. Seronegative axial and peripheral spondyloarthritis may occur in the setting of isolated DCS as well with concomitant HS and AC. The inflammatory arthritis often develops during acute flares of the cutaneous disease. Choosing optimal drug therapy may be challenging. Current options include anti-TNF-α medications, which have been reported to be effective for both the cutaneous lesions and the associated spondyloarthritis. The complex pathophysiology of the conditions that comprise the follicular occlusion triad warrants further research into the potential role of additional biologic agents.
Asunto(s)
Acné Vulgar , Espondiloartritis Axial , Hidradenitis Supurativa , Espondiloartritis , Acné Vulgar/tratamiento farmacológico , Alopecia , Celulitis (Flemón) , Hidradenitis Supurativa/complicaciones , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/epidemiología , Humanos , Dermatosis del Cuero Cabelludo , Enfermedades Cutáneas Genéticas , Espondiloartritis/complicaciones , Espondiloartritis/tratamiento farmacológico , Inhibidores del Factor de Necrosis TumoralRESUMEN
BACKGROUND: Leukemic synovitis is a rare complication of adult myeloid leukemias characterized by joint pain and swelling. It is important to recognize this diagnostic challenge as it may be the initial manifestation of leukemia or of relapse. METHODS: A retrospective search of patient files from 2 teaching hospitals identified 4 adult patients who presented with large joint arthritis and concurrent or subsequent leukemic synovitis. All patients presented with inflammatory arthritis of large joints, and leukemic synovitis was identified by the presence of leukemic cells in the synovial fluid or infiltrating the synovial membrane seen at biopsy. RESULTS: A leukemia of monocytic origin-acute myelomonocytic leukemia or chronic myelomonocytic leukemia-was diagnosed in all 4 patients. In 2 cases, leukemic synovitis was the initial manifestation of leukemia. In the third case, it was the first sign of relapse, and in the remaining case, it developed shortly after diagnosis of leukemia. All patients had either osteoarthritis or rheumatoid arthritis. One patient was diagnosed simultaneously with osteoarthritis and leukemia. The remaining patients had a prior history of arthritis. CONCLUSIONS: Adult leukemic synovitis occurs in association with leukemias of monocytic differentiation. Data presented here, and review of isolated case reports, support this association. The finding of large joint arthritis as a comorbidity in these 4 cases raises questions about the role of antecedent arthritis as a predisposing factor in the pathophysiology of leukemic synovitis.
Asunto(s)
Diferenciación Celular , Leucemia Mielomonocítica Aguda/complicaciones , Leucemia Mielomonocítica Aguda/patología , Leucemia Mielomonocítica Crónica/complicaciones , Leucemia Mielomonocítica Crónica/patología , Sinovitis/etiología , Sinovitis/patología , Anciano , Artritis Reumatoide/fisiopatología , Biopsia , Causalidad , Femenino , Humanos , Leucemia Mielomonocítica Aguda/fisiopatología , Leucemia Mielomonocítica Crónica/fisiopatología , Masculino , Persona de Mediana Edad , Osteoartritis/fisiopatología , Estudios Retrospectivos , Líquido Sinovial/citología , Membrana Sinovial/patología , Sinovitis/fisiopatologíaRESUMEN
PURPOSE OF REVIEW: The purpose of this review is to discuss challenges in the diagnosis and treatment of sarcoidosis by rheumatologists. RECENT FINDINGS: Sarcoidosis is a heterogeneous multisystem granulomatous disease. Rheumatologists are faced with multiple challenges in the management of this disease. Features that can have similarities to many rheumatic diseases are being increasingly reported. There are many reports of sarcoidosis coexisting with or mimicking rheumatic diseases such as systemic lupus erythematosus, rheumatoid arthritis, and ankylosing spondylitis. Musculoskeletal features of sarcoidosis can also mimic infection and malignancy. Biomarkers for the diagnosis and monitoring of treatment of response are lacking. Tumor necrosis factor (TNF) inhibition therapy is a viable alternative for immunodulation for various manifestations. However, increased vigilance is needed, as there are also emerging reports of drug-induced sarcoidosis in association with the use of anti-TNFalpha agents and other medications. This article reviews these diagnostic and treatment challenges that rheumatologists face. SUMMARY: Many questions remain to be answered. More studies looking at the reliability of certain serological and radiological biomarkers are needed. Issues concerning the safety of the use of biological response modifiers in inducing sarcoidosis need further study.
Asunto(s)
Sarcoidosis/diagnóstico , Sarcoidosis/terapia , Biomarcadores/análisis , Comorbilidad , Diagnóstico Diferencial , Errores Diagnósticos/prevención & control , Humanos , Factores Inmunológicos/farmacología , Factores Inmunológicos/uso terapéutico , Enfermedades Reumáticas/diagnóstico , Enfermedades Reumáticas/fisiopatología , Reumatología/métodos , Reumatología/tendencias , Sarcoidosis/fisiopatología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
The rheumatic manifestations of sarcoidosis include inflammatory arthritis, periarticular soft tissue swelling, tenosynovitis, dactylitis, bone involvement and myopathy. Two types of arthritis that differ in clinical course and prognosis are recognized. Acute sarcoid arthritis is self-limiting and resolves without permanent sequelae. Chronic sarcoid arthritis although less common can progress to cause joint deformities. There are proliferative and inflammatory changes in the synovium and non-caseating granulomas are seen in half of patients. The pathogenesis of sarcoid arthritis is not well understood, however genetic and environmental factors are important. Drug therapy of sarcoid arthritis with nonsteroidal anti-inflammatory agents, corticosteroids, colchicine, antimalarials and/or immunosuppressive medications is based mainly on open label uncontrolled studies. This review focuses on the current knowledge on the various features of sarcoid arthritis including clinical presentation, course, imaging, and pathology. Recent developments in the usage of anti-tumor necrosis factor therapy for sarcoidosis will be reviewed.
Asunto(s)
Artritis Reumatoide/etiología , Sarcoidosis/complicaciones , Sarcoidosis/inmunología , Enfermedad Aguda , Corticoesteroides/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/patología , Enfermedad Crónica , Ambiente , Predisposición Genética a la Enfermedad , Granuloma/etiología , Humanos , Inmunosupresores/uso terapéutico , Inflamación , Metotrexato/uso terapéutico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
Coronary artery aneurysms are an uncommon manifestation of systemic lupus erythematosus (SLE), with only 14 cases reported previously in the literature. Herein, we report a 29-year-old woman with SLE who developed clinical and serologic evidence of an SLE flare and presented with chest pain and elevated serum troponin-T level. Cardiac computed tomography was performed and demonstrated fusiform aneurysmal enlargement of the proximal and middle portions of the coronary arteries and a beaded appearance of the distal coronary arteries. Extensive intercostal artery aneurysms were also noted. Several areas of abnormal myocardial perfusion were also noted. The patient improved after treatment with steroid pulses and cyclophosphamide. This case report is the first description of the appearance of lupus coronary vasculitis on cardiac computed tomography.
Asunto(s)
Dolor en el Pecho/diagnóstico por imagen , Vasos Coronarios/diagnóstico por imagen , Lupus Eritematoso Sistémico/complicaciones , Radiografía Torácica , Tomografía Computarizada por Rayos X , Vasculitis/diagnóstico por imagen , Adulto , Dolor en el Pecho/etiología , Ciclofosfamida/uso terapéutico , Femenino , Humanos , Inmunosupresores/uso terapéutico , Resultado del Tratamiento , Troponina T/sangre , Vasculitis/tratamiento farmacológicoRESUMEN
This article draws conclusions about pinpointing the actual onset of disease and when interventions should start to occur. The identification of necessary biomarkers will be discussed. We will also examine the incremental consequences of delaying therapy, particularly for 'preclinical' disease. Medical economic analyses can help us balance benefits and avoid some adverse outcomes for patients. To conclude, we will discuss the new roles that need developing for primary care physicians and non-physican providers.
Asunto(s)
Artritis/diagnóstico , Artritis/terapia , Atención a la Salud , Manejo de la Enfermedad , Reumatología/métodos , Artritis/fisiopatología , Progresión de la Enfermedad , Diagnóstico Precoz , Humanos , PronósticoRESUMEN
Soft tissue infections are common and potentially fatal conditions. Infections are a major cause of morbidity and mortality in patients who have rheumatic disease. Patients who have rheumatic diseases may be at increased risk for soft tissue infections because of various factors, including inherent immunologic defects, genetics, and use of immunomodulatory therapy, including biologic agents. Timely diagnosis and management with the institution of antibiotics with or without surgical intervention is imperative for effective resolution of infection. This article provides a review of recent literature on the presentation and clinical course of infectious tenosynovitis, septic bursitis, pyomyositis, and necrotizing fasciitis, especially in relation to patients who have rheumatic disease.
Asunto(s)
Bursitis/diagnóstico , Fascitis Necrotizante/diagnóstico , Piomiositis/diagnóstico , Enfermedades Reumáticas/patología , Infecciones de los Tejidos Blandos/diagnóstico , Tenosinovitis/diagnóstico , Antibacterianos/uso terapéutico , Antirreumáticos/efectos adversos , Bursitis/complicaciones , Bursitis/terapia , Fascitis Necrotizante/complicaciones , Fascitis Necrotizante/terapia , Humanos , Huésped Inmunocomprometido , Factores Inmunológicos/efectos adversos , Piomiositis/complicaciones , Piomiositis/terapia , Enfermedades Reumáticas/complicaciones , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades de la Piel/diagnóstico , Enfermedades de la Piel/etiología , Enfermedades de la Piel/terapia , Infecciones de los Tejidos Blandos/etiología , Infecciones de los Tejidos Blandos/terapia , Tenosinovitis/complicaciones , Tenosinovitis/terapia , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
Multiple issues surrounding the publication of clinical trials and the conduct of clinical trials, especially those that are industry-sponsored, have raised doubts regarding the integrity of their results, and of the integrity of the medical profession. An appreciation of the historical and economic changes in the relationship between physicians and industry is crucial to the understanding of these issues. Increasingly, as healthcare professionals and centers in the Asia-Pacific region become involved in corporate-funded multi-center drug trials, these ethical issues similarly come into play. It is imperative for medical leaders to take actions ensuring rights of subjects participating in these clinical trials, and to ensure the integrity of physicians and authors of clinical trials from this region of the world.
Asunto(s)
Ensayos Clínicos como Asunto/normas , Conflicto de Intereses , Industria Farmacéutica/normas , Opinión Pública , Apoyo a la Investigación como Asunto/normas , Asia , Humanos , Islas del Pacífico , ReumatologíaRESUMEN
Serum antibodies reactive with the keratin layer of rat esophagus (AKA) were found in 46 of 80 (57.5%) rheumatoid arthritis (RA) patients. In contrast, AKA were present in only 7 of 82 (9.5%) patients with other types of rheumatic disorders and in 2 of 47 (4.2%) healthy subjects. AKA were not specific for RA, however, because in the former group, AKA were present in 4 of 20 (20%) systemic sclerosis patients and in 3 of 12 (25%) ankylosing spondylitis patients. AKA belong predominantly to the IgG class and are complement fixing. Although found in some RA joint fluids, AKA were not selectively concentrated in the joint fluid. Absorption of RA serum with type I human collagen or with human epidermal keratin did not remove AKA activity. The frequency of AKA in RA patients both negative and positive for DR4 was equal. There was no relationship between the frequency of AKA and the occurrence of other serum autoantibodies such as antibodies to intermediate filaments, smooth muscle, and nuclear antigens. Serum antibody reactive with human stratum corneum found in patients with psoriatic arthritis was shown to be different from AKA. Rabbit antiserum to human keratin did not inhibit the reaction of AKA against the keratin layer of rat esophagus. Autoimmunity to structural proteins including collagen, vimentin intermediate filaments, smooth muscle antigens, and keratin is a characteristic feature of RA.
Asunto(s)
Artritis Reumatoide/historia , Autoanticuerpos/historia , Esófago , Queratinas/historia , Animales , Artritis Reumatoide/epidemiología , Artritis Reumatoide/inmunología , Autoanticuerpos/sangre , Esófago/inmunología , Historia del Siglo XX , Humanos , Queratinas/inmunología , Ratas , Estudios SeroepidemiológicosRESUMEN
PURPOSE OF REVIEW: Anti-tumor necrosis factor-alpha agents have recently been approved and recommended as effective and relatively safe drug therapy for ankylosing spondylitis. In light of this major advance in the management of these patients, recent observations on the pulmonary manifestations of ankylosing spondylitis are reviewed. RECENT FINDINGS: High-resolution computed tomography abnormalities were found to be prevalent (range 50-85%) in ankylosing spondylitis even in patients with early disease, and in those with normal chest radiographs and without respiratory symptoms. The high-resolution computed tomography changes included apical fibrosis, interstitial lung disease, emphysema, bronchietasis and pleural thickening. In general, the high-resolution computed tomography changes were of mild degree, and no correlation was observed between high-resolution computed tomography abnormalities, pulmonary function test variables and indices of ankylosing spondylitis symptoms and disease structural severity. Spontaneous pneumothorax was reported to be a rare complication, but tended to occur in those patients with fibrobullous disease. SUMMARY: The clinical significance of the high-resolution computed tomography abnormalities remains to be determined. Most of the published studies are cross-sectional, and are limited by lack of control subjects matched for age, gender and tobacco use. Studies to correlate high-resolution computed tomography changes with bronchoalveolar lavage and lung biopsies as well as prospective studies on long-term evolution of these findings including those patients receiving anti-tumor necrosis factor-alpha agents are needed.
Asunto(s)
Fibrosis Pulmonar/diagnóstico por imagen , Fibrosis Pulmonar/etiología , Espondilitis Anquilosante/complicaciones , Tomografía Computarizada por Rayos X , Antirreumáticos/uso terapéutico , Humanos , Espondilitis Anquilosante/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
PURPOSE OF REVIEW: Microscopic polyangiitis is a systemic necrotizing vasculitis that affects small vessels, resulting in a wide spectrum of organ involvement including the kidneys and the lungs. This paper reviews recent insights and observations into the pathogenesis, clinical manifestations, and treatment of pulmonary involvement in microscopic polyangiitis. RECENT FINDINGS: The spectrum of clinical presentations ranges from antecedent interstitial fibrosis to frank hemoptysis secondary to capillaritis. Computerized tomography imaging reveals a variety of pulmonary findings, including ground-glass attenuation, consolidation, thickening of bronchovascular bundles, and honeycombing. Antineutrophil cytoplasmic antibodies are important in diagnosis as well as in the pathogenesis and prognosis of microscopic polyangiitis. There is more evidence to support the various therapeutic modalities currently used in pulmonary manifestations of microscopic polyangiitis, including induction therapy with cyclophosphamide, the use of other novel pharmacologic agents such as the tumor necrosis factor-alpha blockers and rituximab, and nonpharmacologic modalities such as plasmapheresis and ventilatory management. SUMMARY: The pulmonary manifestations of microscopic polyangiitis are diverse and often difficult to manage; however, as our understanding and experience grows so does our ability to successfully diagnose and treat these patients.
Asunto(s)
Enfermedades Pulmonares/etiología , Vasculitis/complicaciones , Anticuerpos Anticitoplasma de Neutrófilos/análisis , Antirreumáticos/uso terapéutico , Ciclofosfamida/uso terapéutico , Quimioterapia Combinada , Glucocorticoides/uso terapéutico , Humanos , Enfermedades Pulmonares/diagnóstico , Enfermedades Pulmonares/patología , Pronóstico , Vasculitis/diagnóstico , Vasculitis/patologíaRESUMEN
Metastatic spread of malignancy to the joints is rare and only a few cases of solid tumors have been reported. We describe a patient with inflammatory arthritis of the knee and ankle secondary to metastatic gastric adenocarcinoma to the joints and bone diagnosed by synovianalysis. Arthritis secondary to metastatic cancer is a poor prognostic sign. The diagnosis is based on a strong clinical suspicion, magnetic resonance imaging, and joint fluid cytology or synovial biopsy.
Asunto(s)
Adenocarcinoma/secundario , Artritis Reumatoide/patología , Neoplasias Óseas/secundario , Articulación de la Rodilla/patología , Neoplasias Gástricas/patología , Adenocarcinoma/complicaciones , Artritis Reumatoide/etiología , Exudados y Transudados , Resultado Fatal , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Cuidados Paliativos , Radiografía , Neoplasias Gástricas/complicaciones , Líquido Sinovial/citologíaAsunto(s)
Poliarteritis Nudosa/complicaciones , Poliarteritis Nudosa/patología , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/patología , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética , Poliarteritis Nudosa/diagnóstico , Hemorragia Subaracnoidea/líquido cefalorraquídeo , Vértebras Torácicas/patología , Vasculitis del Sistema Nervioso Central/complicacionesRESUMEN
We read with interest the article the dramatic response to dapsone therapy...