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1.
Lakartidningen ; 1162019 Nov 29.
Artigo em Sueco | MEDLINE | ID: mdl-31794046

RESUMO

Although more than 45 years have passed since hypocomplementemic urticarial vasculitis (HUVS) was first described by McDuffie and colleagues at the Mayo clinic, data on epidemiology, disease outcomes, prognosis and clinical features are scarce. Recently, we published the first epidemiological study of HUVS including data on incidence, prevalence, disease outcomes, prognosis and clinical features using data from two separate Swedish regions during a period of 16 years. The estimation of incidence and prevalence rates indicates that HUVS is rare but not always benign. Renal and lung manifestations were severe in some cases, highlighting the need for careful screening and monitoring of this potentially serious condition. It is reasonable to suspect HUVS in patients with unexplained systemic inflammation combined with >6 months of urticaria. Special attention should be paid to patients with recent-onset dyspnea and proteinuria.


Assuntos
Glomerulonefrite Membranoproliferativa/diagnóstico , Urticária/diagnóstico , Vasculite/diagnóstico , Adulto , Complemento C1q/metabolismo , Feminino , Glomerulonefrite Membranoproliferativa/sangue , Glomerulonefrite Membranoproliferativa/epidemiologia , Glomerulonefrite Membranoproliferativa/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Suécia/epidemiologia , Síndrome , Urticária/sangue , Urticária/epidemiologia , Urticária/patologia , Vasculite/sangue , Vasculite/epidemiologia , Vasculite/patologia
4.
J Dtsch Dermatol Ges ; 17(9): 895-904, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31487114

RESUMO

AIMS: The classifications of occluding vasculopathies may present some difficulties. Firstly, classifications may follow different principles, e.g. clinicopathological findings, etiology or pathomechanism. Secondly, authors sometimes do not distinguish between vasculitis and vasculopathy. Thirdly, vasculopathies are often systemic diseases. Organ-specific variations make morphologic findings difficult to compare. Moreover, subtle changes may be recognized in the skin, but be invisible in other organs. Our aim was to use the skin and subcutis as tools and clinicopathological correlation as the basic process for classification. METHODS AND RESULTS: In the first step, we differentiate between small and medium vessel occluding vasculopathies in the skin, and focus in this part on small vessel occluding vasculopathies. In the second step, we differentiate among subtypes of small vessels. In the final step, we differentiate according to the time point of the coagulation/reorganization process and the involved inflammatory cells/stromal features. Applying the same procedure to the various entities and visualizing the findings with bar codes makes the similarities and differences more apparent, both clinically and with histopathology. CONCLUSION: Occluding vasculopathies are often not separate entities, but reaction patterns and epiphenomena. Distinguishing them from vasculitides is crucial because of differences in pathogenesis, therapeutic approach and prognosis.


Assuntos
Algoritmos , Processamento Eletrônico de Dados , Dermatopatias Vasculares/patologia , Vasculite/patologia , Anticoagulantes/efeitos adversos , Constrição Patológica/patologia , Diagnóstico Diferencial , Humanos , Livedo Reticular/classificação , Microvasos/patologia , Necrose/induzido quimicamente , Dermatopatias Bacterianas/patologia
5.
Mayo Clin Proc ; 94(9): 1769-1780, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31486380

RESUMO

OBJECTIVE: To describe the differences in clinical characteristics and outcome between adult- and childhood-onset biopsy-proven IgA vasculitis (IgAV) in North America. PATIENTS AND METHODS: Patients with IgAV diagnosed from January 1, 1997, through December 31, 2016, were retrospectively identified. Data were abstracted from direct medical record review. Kaplan-Meier methods were used to estimate survival rates. RESULTS: A total of 243 patients with IgAV were included (227 [93.4%] white, 141 [58.0%] male); 174 patients were adults (≥21 years), and 69 were younger than 21 years. Compared with patients younger than 21 years, adults at baseline more frequently had ulcerative skin lesions (19 [10.9%] vs 1 [1.4%]; P=.02) and nephrotic-range proteinuria (21 of 96 [21.9%] vs 1 of 38 [2.6%]; P=.007) but less commonly had abdominal pain (59 [33.9%] vs 42 [60.9%]; P<.001), ischemic gastrointestinal tract involvement (18 [10.3%] vs 14 [20.3%]; P=.04), and arthralgias (66 [37.9%] vs 42 [60.8%]; P<.001). During 389 person-years of follow-up, 29 deaths were observed. Five-year survival rates for patients aged younger than 21, 21 to 50, and 51 years or older were 100%, 94%, and 40%, respectively. In comparison to data from the United States life tables for whites, patients 51 years or older at diagnosis had a greater than 7-fold increased risk of mortality (standardized mortality, 7.60 [95% CI, 5.01-11.06]; P<.001). CONCLUSION: IgA vasculitis in adults is associated with more severe skin/kidney involvement and poorer renal outcome. Among adults with IgAV, patients aged 51 years or older at diagnosis have significantly higher mortality (P<.001).


Assuntos
Corticosteroides/uso terapêutico , Glomerulonefrite por IGA/epidemiologia , Imunoglobulina A/imunologia , Vasculite/epidemiologia , Vasculite/patologia , Centros Médicos Acadêmicos , Adulto , Idade de Início , Biópsia por Agulha , Criança , Estudos de Coortes , Bases de Dados Factuais , Feminino , Glomerulonefrite por IGA/tratamento farmacológico , Glomerulonefrite por IGA/patologia , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Prevalência , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , Resultado do Tratamento , Vasculite/imunologia , Vasculite/terapia
6.
EBioMedicine ; 47: 319-328, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31444145

RESUMO

BACKGROUND: The complement and kallikrein-kinin systems (KKS) are activated during vascular inflammation. The aim of this study was to investigate if blockade of the KKS can affect complement activation on the endothelium during inflammation. METHODS: Complement deposition on endothelial microvesicles was assayed in vasculitis patient plasma samples and controls. Plasma was perfused over glomerular endothelial cells and complement deposition assayed by flow cytometry. The effect of the kinin system was assessed using kinin receptor antagonists and C1-inhibitor. The in vivo effect was assessed in kidney sections from mice with nephrotoxic serum-induced glomerulonephritis treated with a kinin receptor antagonist. FINDINGS: Vasculitis patient plasma had significantly more C3- and C9-positive endothelial microvesicles than controls. Perfusion of patient acute-phase plasma samples over glomerular endothelial cells induced the release of significantly more complement-positive microvesicles, in comparison to remission or control plasma. Complement activation on endothelial microvesicles was reduced by kinin B1- and B2-receptor antagonists or by C1-inhibitor (the main inhibitor of the classical pathway and the KKS). Likewise, perfusion of glomerular endothelial cells with C1-inhibitor-depleted plasma induced the release of complement-positive microvesicles, which was significantly reduced by kinin-receptor antagonists or C1-inhibitor. Mice with nephrotoxic serum-induced glomerulonephritis exhibited significantly reduced glomerular C3 deposition when treated with a B1-receptor antagonist. INTERPRETATION: Excessive complement deposition on the endothelium will promote endothelial injury and the release of endothelial microvesicles. This study demonstrates that blockade of the KKS can reduce complement activation and thereby the inflammatory response on the endothelium. FUNDING: Full details are provided in the Acknowledgements/Funding section.


Assuntos
Ativação do Complemento/imunologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Sistema Calicreína-Cinina/efeitos dos fármacos , Vasculite/etiologia , Vasculite/metabolismo , Adulto , Idoso , Animais , Transporte Biológico , Bradicinina/análogos & derivados , Bradicinina/farmacologia , Micropartículas Derivadas de Células/metabolismo , Células Cultivadas , Proteína Inibidora do Complemento C1/metabolismo , Proteínas do Sistema Complemento/imunologia , Proteínas do Sistema Complemento/metabolismo , Modelos Animais de Doenças , Endotélio Vascular/imunologia , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Feminino , Humanos , Imunoglobulina G/imunologia , Masculino , Camundongos , Pessoa de Meia-Idade , Ligação Proteica , Vasculite/patologia
7.
Redox Biol ; 26: 101288, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31419754

RESUMO

Aging is characterized by increased aortic stiffness, an early, independent predictor and cause of cardiovascular disease. Oxidative stress from excess reactive oxygen species (ROS) production increases with age. Mitochondria and NADPH oxidases (NOXs) are two major sources of ROS in cardiovascular system. We showed previously that increased mitochondrial ROS levels over a lifetime induce aortic stiffening in a mouse oxidative stress model. Also, NADPH oxidase 4 (NOX4) expression and ROS levels increase with age in aortas, aortic vascular smooth muscle cells (VSMCs) and mitochondria, and are correlated with age-associated aortic stiffness in hypercholesterolemic mice. The present study investigated whether young mice (4 months-old) with increased mitochondrial NOX4 levels recapitulate vascular aging and age-associated aortic stiffness. We generated transgenic mice with low (Nox4TG605; 2.1-fold higher) and high (Nox4TG618; 4.9-fold higher) mitochondrial NOX4 expression. Young Nox4TG618 mice showed significant increase in aortic stiffness and decrease in phenylephrine-induced aortic contraction, but not Nox4TG605 mice. Increased mitochondrial oxidative stress increased intrinsic VSMC stiffness, induced aortic extracellular matrix remodeling and fibrosis, a leftward shift in stress-strain curves, decreased volume compliance and focal adhesion turnover in Nox4TG618 mice. Nox4TG618 VSMCs phenocopied other features of vascular aging such as increased DNA damage, increased premature and replicative senescence and apoptosis, increased proinflammatory protein expression and decreased respiration. Aortic stiffening in young Nox4TG618 mice was significantly blunted with mitochondrial-targeted catalase overexpression. This demonstration of the role of mitochondrial oxidative stress in aortic stiffness will galvanize search for new mitochondrial-targeted therapeutics for treatment of age-associated vascular dysfunction.


Assuntos
Aorta/metabolismo , Genes Mitocondriais , NADPH Oxidase 4/genética , Rigidez Vascular/genética , Fatores Etários , Animais , Aorta/fisiopatologia , Senescência Celular/genética , Matriz Extracelular/metabolismo , Expressão Gênica , Estudos de Associação Genética , Peróxido de Hidrogênio/metabolismo , Imuno-Histoquímica , Camundongos , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , NADPH Oxidase 4/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Superóxidos/metabolismo , Vasculite/genética , Vasculite/metabolismo , Vasculite/patologia
8.
Dermatol Online J ; 25(7)2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31450279

RESUMO

Angioimmunoblastic T-cell lymphoma (AITL) is a rare form of non-Hodgkin lymphoma often accompanied by autoimmune and paraneoplastic phenomena. Up to 50% of patients with AITL present with skin manifestations. This case series highlights two cases of AITL presenting with unusual cutaneous findings: one with a medium-vessel vasculitis and another with a chronic urticarial eruption. Clinicians should consider AITL in the differential diagnosis of vasculitis or urticaria refractory to standard treatment.


Assuntos
Linfoma Cutâneo de Células T/complicações , Síndromes Paraneoplásicas/patologia , Neoplasias Cutâneas/complicações , Pele/patologia , Urticária/etiologia , Vasculite/etiologia , Evolução Fatal , Feminino , Humanos , Linfadenopatia Imunoblástica/patologia , Linfoma Cutâneo de Células T/patologia , Pessoa de Meia-Idade , Neoplasias Cutâneas/patologia , Urticária/patologia , Vasculite/patologia
10.
BMJ Case Rep ; 12(7)2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31289150

RESUMO

A 3-year-old woman presented with a large ulcerated lesion involving the left upper eyelid and left earlobe with erythematous, swollen, undermined and advancing borders. Culture of the ulcer showed no growth of organisms. Treatment with empiric intravenous and topical antibiotics showed no improvement. Workup revealed an elevated white blood cell count with elevated neutrophil count, elevated erythrocyte sedimentation rate and C reactive protein and positive antinuclear antibody. A skin biopsy showed a neutrophilic dermatitis with vasculitis. The patient was started on oral prednisone, which resulted in halting of the progression of ulceration and clinically decreased skin inflammation. The skin biopsy and positive response to corticosteroids confirmed the diagnosis of pyoderma gangrenosum. Pyoderma gangrenosum is a rare inflammatory skin condition and rarely presents as lesions of the eyelid. Early initiation of immunosuppressive therapy prevents disfigurement. Eyelid reconstruction in these cases may prove to be difficult.


Assuntos
Pálpebras/patologia , Pioderma Gangrenoso/patologia , Úlcera Cutânea/patologia , Anticorpos Antinucleares/sangue , Biópsia , Pré-Escolar , Dermatite/patologia , Diagnóstico Diferencial , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Neutrófilos/citologia , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Pioderma Gangrenoso/diagnóstico , Pioderma Gangrenoso/tratamento farmacológico , Úlcera Cutânea/diagnóstico , Úlcera Cutânea/tratamento farmacológico , Resultado do Tratamento , Vasculite/patologia
11.
Pediatr Rheumatol Online J ; 17(1): 39, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31291964

RESUMO

BACKGROUND: Deficiency of adenosine deaminase 2 (DADA2) is a rare autosomal recessive autoinflammatory condition. Recognised features include vasculitis predominantly affecting medium sized vessels, livedoid skin rash, central and peripheral nervous system involvement, variable degrees of immunodeficiency, and marrow failure, amongst other clinical presentations. We present the case of a six year old male with DADA2 who presented with acute testicular ischaemia secondary to vasculitis, the first such description in DADA2. CASE PRESENTATION: A six year old male presented acute right-sided testicular pain. His history included transient infantile neutropenia, resolved hepatosplenomegaly, and longstanding livedo racemosa, leading to screening and confirmation of DADA2 caused by homozygous c.139G > C (p.G47R) mutation of ADA2. As his only clinical feature was that of mild livedo racemosa with normal laboratory parameters at diagnosis, he was being actively monitored prior to starting any treatment. At a routine clinic follow-up a 24 h history of testicular pain was noted on systems review. He was afebrile, and his only physical signs were that of moderate livedo racemosa, and tenderness of the right testicle. Laboratory parameters revealed C-reactive protein (CRP) 8 mg/L (reference range [RR] < 20 mg/L); erythrocyte sedimentation rate (ESR) 28 mm/hr. (RR < 10); and serum amyloid A (SAA)5 mg/L (RR < 10). Ultrasound-scan of the scrotum revealed significantly reduced perfusion of the right testes, without torsion. Surgical scrotal exploration confirmed testicular ischaemia without torsion. Histology demonstrated ischaemic seminiferous tubules with intervening haemorrhage and acute inflammatory cells, consistent with vasculitis of the testis as the cause. He was treated with high dose intravenous methyl-prednisolone followed by a weaning course of oral prednisolone, and subcutaneous adalimumab (anti-tumour necrosis factor alpha, anti-TNFα). Repeat ultrasound-scan 3 weeks later revealed good testicular perfusion, with a small area of focal infarction. At last follow-up (11 months post-event) he remained asymptomatic, on treatment with adalimumab. CONCLUSION: The phenotype of DADA2 continues to expand, and we add testicular infarction to the features of DADA2. CRP and SAA cannot be relied on as reliable biomarkers to predict tissue ischaemia and hence who to target for anti-TNFα therapy in DADA2, since these remained steadfastly normal before, during, and after testicular infarction in this case.


Assuntos
Adenosina Desaminase/deficiência , Infarto/patologia , Peptídeos e Proteínas de Sinalização Intercelular/deficiência , Doenças Testiculares/patologia , Vasculite/patologia , Adenosina Desaminase/genética , Criança , Doenças Hereditárias Autoinflamatórias/complicações , Doenças Hereditárias Autoinflamatórias/genética , Humanos , Infarto/diagnóstico por imagem , Infarto/etiologia , Peptídeos e Proteínas de Sinalização Intercelular/genética , Isquemia/diagnóstico por imagem , Isquemia/etiologia , Isquemia/patologia , Masculino , Doenças Testiculares/diagnóstico por imagem , Doenças Testiculares/etiologia , Testículo/irrigação sanguínea , Testículo/diagnóstico por imagem , Testículo/patologia , Vasculite/diagnóstico por imagem , Vasculite/etiologia
12.
Arkh Patol ; 81(3): 37-44, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31317929

RESUMO

Panniculitis is a heterogeneous group of diseases that are characterized by a subcutaneous adipose tissue (SAT) lesion and frequently occur with involvement of the musculoskeletal system and viscera in the process. This is a chronic multiple organ disease. The gold standard for its diagnosis is noted to be a morphological study. The paper presents the current classification of panniculitis. OBJECTIVE: To study the morphological features of idiopathic lobular panniculitis (ILP) in accordance with the nature of the course and clinical forms of the disease. SUBJECT AND METHODS: Biopsy specimens were studied in 62 patients with various clinical forms of ILP. Biopsy and surgical materials were investigated by light optical morphological methods. The results were statistically processed using a statistical analysis software Statistica Version 10 package for Windows ('StatSoft Inc.', USA). The differences were considered statistically significant at an error level of p<0.05. Methods, such as Pearson's c2 test (analysis of contingency tables), Student's t-test, Z-test for comparison of proportions, nonparametric tests, such as Mann-Whitney U-test, Kruskal-Wallis test, were used to assess the results. RESULTS: The nature of the morphological parameters of the disease corresponded to the course of ILP. The acute course of the disease was characterized by the predominance of liponecrosis and inflammation concurrent with productive-destructive vasculitis. In the chronic course, there was a preponderance of lymphohistiocytic infiltrate with gigantic macrophages (lipophages) and granuloma-like structures. The above morphological changes were characteristic of the phagocytic morphological stage of node formation. The fibroplastic stage of panniculitis was absent in this study. The morphological features of the disease were shown depending on the form of idiopathic lobular panniculitis, which may be of diagnostic value in the differential diagnosis of panniculitis. CONCLUSION: The pathologist must first of all pay attention to the preferential localization of pathological changes (in the SAT septa or slices), the presence or absence of vasculitis and the nature of the infiltrate. The skin in panniculitis is typically intact or has minimal changes following the pattern seen in reactive ones. Panniculitis shows an undulatory course, and therefore all signs of this disease are present in biopsy specimens; however, morphological signs of the acute inflammatory, lipophagic or fibroplastic stage of the disease predominate depending on the stage and activity of the process.


Assuntos
Paniculite , Vasculite , Biópsia , Granuloma , Humanos , Paniculite/diagnóstico , Paniculite/patologia , Pele/patologia , Vasculite/diagnóstico , Vasculite/patologia
13.
Chin Med J (Engl) ; 132(14): 1723-1732, 2019 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-31283654

RESUMO

OBJECTIVE: Cryoglobulinemia often causes systemic vasculitis, thereby damaging to skin and internal organs including kidneys, even life-threatening. This review aimed to introduce the advances in understanding, detection, and treatment of this disease in recent years, with a particular concern to clinical practice. DATA SOURCES: All the data in this review were from the English or Chinese literature in the PubMed and China National Knowledge Infrastructure databases as of March 2019. STUDY SELECTION: This review selected important original articles, meaningful reviews, and some reports on cryoglobulinemia published in recent years and in history, as well as the guidelines for treatment of underlying diseases which lead to cryoglobulinemia. RESULTS: Diagnosis of cryoglobulinemia relies on serum cryoglobulin test, in which to ensure that the blood sample temperature is not less than 37°C in the entire pre-analysis phase is the key to avoid false negative results. Cryoglobulinemic vasculitis (Cryo Vas), including cryoglobulinemic glomerulonephritis (Cryo GN), usually occurs in types II and III mixed cryoglobulinemia, and can also be seen in type I cryoglobulinemia caused by monoclonal IgG3 or IgG1. Skin purpura, positive serum rheumatoid factor, and decreased serum levels of C4 and C3 are important clues for prompting types II and III Cryo Vas. Renal biopsy is an important means for diagnosis of Cryo GN, while membranous proliferative GN is the most common pathological type of Cryo GN. In recent years, great advances have been made in the treatment of Cryo Vas and its underlying diseases, and this review has briefly introduced these advances. CONCLUSIONS: Laboratory examinations of serum cryoglobulins urgently need standardization. The recent advances in the diagnosis and treatment of Cryo Vas and GN need to be popularized among the clinicians in related disciplines.


Assuntos
Crioglobulinemia/sangue , Glomerulonefrite/sangue , Animais , Complemento C3 , Complemento C4 , Crioglobulinemia/metabolismo , Crioglobulinemia/patologia , Crioglobulinas/metabolismo , Glomerulonefrite/metabolismo , Glomerulonefrite/patologia , Humanos , Vasculite/sangue , Vasculite/metabolismo , Vasculite/patologia
14.
Ceska Gynekol ; 84(2): 149-153, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31238686

RESUMO

OBJECTIVE: To review contemporary knowledge of isolated vasculitis in urology and gynaecology. DESIGN: A review. SETTING: Department of Obstetrics and Gynaecology, University Hospital Hradec Kralove. METHODS: To present own experience and an overview of recent literature. CONCLUSION: Vascular system inflammation is a very important and broadly studied medical condition. It can affect either veins or arteries. In pelvic veins it can significantly increase the risk of thromboembolic complications, while in the case of arteries; the clinical significance is still unknown. We still do not know what does the histopathological proven isolated vasculitis in this area mean. Is it just a local finding, or should we look for systemic vasculitis? Unlike most of non-symptomatic gynecological vasculitis, urological cases are often accompanied by severe symptoms depending on the anatomical location of the process. This work presents a basic overview and includes our experience with this issue. Our thesis does not include the vasculitis in pregnancy.


Assuntos
Doenças dos Genitais Femininos/patologia , Ginecologia , Pelve/irrigação sanguínea , Urologia , Vasculite/patologia , Feminino , Humanos , Gravidez
15.
Nat Commun ; 10(1): 2247, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-31113953

RESUMO

Complement promotes vascular inflammation in transplant organ rejection and connective tissue diseases. Here we identify ZFYVE21 as a complement-induced Rab5 effector that induces non-canonical NF-κB in endothelial cells (EC). In response to membrane attack complexes (MAC), ZFYVE21 is post-translationally stabilized on MAC+Rab5+ endosomes in a Rab5- and PI(3)P-dependent manner. ZFYVE21 promotes SMURF2-mediated polyubiquitinylation and proteasome-dependent degradation of endosome-associated PTEN to induce vesicular enrichment of PI(3,4,5)P3 and sequential recruitment of activated Akt and NF-κB-inducing kinase (NIK). Pharmacologic alteration of cellular phosphoinositide content with miltefosine reduces ZFYVE21 induction, EC activation, and allograft vasculopathy in a humanized mouse model. ZFYVE21 induction distinctly occurs in response to MAC and is detected in human renal and synovial tissues. Our data identifies ZFYVE21 as a Rab5 effector, defines a Rab5-ZFYVE21-SMURF2-pAkt axis by which it mediates EC activation, and demonstrates a role for this pathway in complement-mediated conditions.


Assuntos
Proteínas de Transporte/metabolismo , Endossomos/metabolismo , Rejeição de Enxerto/patologia , NF-kappa B/metabolismo , Vasculite/patologia , Aloenxertos/patologia , Animais , Linhagem Celular , Complexo de Ataque à Membrana do Sistema Complemento/metabolismo , Vasos Coronários/patologia , Vasos Coronários/transplante , Modelos Animais de Doenças , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Membrana , Camundongos , Camundongos SCID , Fosfatos de Fosfatidilinositol/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Proteínas rab5 de Ligação ao GTP/metabolismo
16.
Intern Med ; 58(17): 2451-2458, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31118402

RESUMO

Objectives To investigate the sensitivity and specificity of a temporal artery biopsy (TAB) in the diagnosis of giant cell arteritis (GCA) in a single-center retrospective cohort in Japan. Methods A retrospective chart review was performed on consecutive patients who visited our hospital between April 2009 and October 2018 and underwent a TAB. The sensitivity and specificity were calculated for the three pathological standards for a TAB, predetermined according to the pathological criterion of the 1990 American College of Rheumatology (ACR) criteria: A) vasculitis characterized by predominant mononuclear cell infiltration; B) vasculitis with granulomatous inflammation; and C) vasculitis with multinucleated giant cells. We also analyzed the clinical parameters predicting the diagnosis of GCA and the impact of a diagnostic delay of ≥3 months on cardiovascular complications of GCA. Results Our study population was 16 cases in the GCA group and 13 in the non-GCA group. The sensitivity and specificity for Standard A of a TAB were 81% and 85%, respectively, while those for stricter Standards B or C were identical, at 75% and 100%, respectively. These pathological standards, but not any other parameters, significantly predicted the diagnosis. A diagnostic delay tended to cause cardiovascular complications (p=0.057). Conclusion The sensitivity and specificity of the pathological standards of a TAB were favorable in our cohort and were the only predictors for the diagnosis of GCA. Considering the possible impact of a diagnostic delay on cardiovascular complications, the early recognition and prompt initiation of glucocorticoid therapy is needed, even in Japan, where GCA is uncommon.


Assuntos
Doenças Cardiovasculares/etiologia , Arterite de Células Gigantes/complicações , Arterite de Células Gigantes/diagnóstico , Artérias Temporais/patologia , Idoso , Idoso de 80 Anos ou mais , Biópsia , Doenças Cardiovasculares/patologia , Estudos de Coortes , Diagnóstico Tardio/efeitos adversos , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Vasculite/patologia
18.
J Am Podiatr Med Assoc ; 109(2): 150-154, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31135196

RESUMO

BACKGROUND: Since 2006 there have been increased reports of severe agranulocytosis and vasculitis associated with levamisole use. Historically, levamisole was an immunomodulatory agent used in various cancer treatments in the United States. Currently the drug is used as an antihelminthic veterinary medication, but it is also used as an additive in freebase cocaine. There are multiple reports of levamisole-induced vasculitis in the head and neck but limited reported cases in the lower extremities. This article describes a 60-year-old woman who presented to the emergency department with multiple painful lower-extremity ulcerations. RESULTS: Radiographs, laboratory studies, and punch biopsy were performed. Physical examination findings and laboratory results were negative for signs of infection. Treatment included local wound care and education on cocaine cessation, and the patient was transferred to a skilled nursing facility. Her continued use of cocaine, however, prevented her ulcers from healing. CONCLUSIONS: Local wound care and cocaine cessation is the optimal treatment for levamisole-induced lesions. With the increase in the number of patients with levamisole-induced vasculitis, podiatric physicians and surgeons would benefit from the immediate identification of these ulcerations, as their appearance alone can be distinct and pathognomonic. Early identification of levamisole-induced ulcers is important for favorable treatment outcomes. A complete medical and social history is necessary for physicians to treat these lesions with local wound care and provide therapy for patients with addictions.


Assuntos
Adjuvantes Imunológicos/efeitos adversos , Transtornos Relacionados ao Uso de Cocaína/complicações , Levamisol/efeitos adversos , Extremidade Inferior , Vasculite/induzido quimicamente , Feminino , Humanos , Pessoa de Meia-Idade , Vasculite/patologia , Vasculite/terapia
19.
Orphanet J Rare Dis ; 14(1): 110, 2019 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-31096996

RESUMO

Linear scleroderma "en coup de sabre" (LSES) variant is a cephalic subtype of localized scleroderma that can be associated with extracutaneous stigmata, such as epilepsy, dementia syndromes, as well as focal central nervous system neurologic deficits. While the pathophysiology of cutaneous linear scleroderma includes endothelial cell injury and up regulation of pro-fibrogenic pathways, the basis of LSES-associated neurologic complications is largely unknown. We report a patient with a history of LSES who developed intractable epilepsy and cognitive decline. Magnetic resonance imaging (MRI) of the brain exhibited numerous persistently enhancing brain lesions. Due to progressive neurologic deterioration over a period of 7 years, despite interventional therapy, a brain biopsy was performed. Neuropathologic analysis exhibited acute and chronic cortical ischemia associated with a small vessel lymphocytic vasculitis. Direct immunofluorescent studies showed C5b-9 and IgG deposition on endothelium while indirect immunofluorescent studies demonstrated reactivity of the patient's serum with the microvasculature of the patient's own brain tissue and generic human umbilical vein endothelial cells indicative of anti-endothelial cell antibodies. Therapy focusing on damaged endothelium was implemented. The interleukin-6 (IL-6) receptor inhibitor tocilizumab was used and the patient improved dramatically, likely reflecting the drug's effect on the replenishment of endothelial progenitor cells.


Assuntos
Esclerodermia Localizada/tratamento farmacológico , Esclerodermia Localizada/patologia , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Cognição/efeitos dos fármacos , Progressão da Doença , Epilepsia/diagnóstico por imagem , Epilepsia/tratamento farmacológico , Epilepsia/patologia , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Imuno-Histoquímica , Imagem por Ressonância Magnética , Poliendocrinopatias Autoimunes/diagnóstico por imagem , Poliendocrinopatias Autoimunes/tratamento farmacológico , Poliendocrinopatias Autoimunes/patologia , Receptores de Interleucina-6/antagonistas & inibidores , Esclerodermia Localizada/diagnóstico por imagem , Vasculite/diagnóstico por imagem , Vasculite/tratamento farmacológico , Vasculite/patologia
20.
Histopathology ; 75(5): 683-693, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31136006

RESUMO

AIMS: IgA vasculitis (IgAV) is a common small-vessel systemic vasculitisthat is histologically characterised by granulocyte infiltration and IgA deposition in vessel walls. Information on microRNA (miRNA) involvement inIgAVis limited. The aim of this study was to analyse the association between histopathological changes and expression profiles of 14 miRNAs in the affected skin of 70 adult patients with IgAV. METHODS AND RESULTS: miRNA expression analysis was performed by quantitative real-time polymerase chain reaction and evaluation of histopathological changes by light and immunofluorescence microscopy on formalin-fixed paraffin-embedded skin excision samples. In IgAV-affected skin, granulocyte infiltration was significantly associated with vessel fibrinoid necrosis. Of the analysed miRNAs, four showed two-fold increased expression (let-7d, let-7f, miR-21-5p, and miR-203-3p), five showed five-fold increased expression (let-7b, miR-17-5p, miR-155-5p, miR-423-5p, and miR-451a), and threeshowed 15-fold increased expression (let-7a, miR-21-3p, miR-223-3p), as compared with controls (all P < 0.001). miR-146a-5p and miR-148b-3p showed three-fold decreased expression (P = 0.981 and P < 0.001). The expression of miR-223-3p also showed a significant positive association with granulocyte infiltration and fibrinoid necrosis. CONCLUSIONS: Altered miRNA expression, especially of miRNA-223-3p, may be associated with the skin inflammatory state in IgAV. The majority of aberrantly expressed miRNAs in IgAV-affected skin are known to influence the nuclear factor-κB signalling pathway, which is crucial for activation of key proinflammatory genes, including those encoding tumour necrosis factor-α, interleukin (IL)-6, and IL-8. Furthermore, miR-146a-5p and miR-148b-3p, which are negative regulators of inflammatory gene expression, showed decreased expression and could contribute to the exaggerated inflammation. Further investigation of miRNA expression in the affected tissues could improve our knowledge of IgAV pathogenesis, and possibly help to identify novel biomarkers in body fluids.


Assuntos
MicroRNAs/metabolismo , Pele/patologia , Vasculite/patologia , Adulto , Perfilação da Expressão Gênica , Histocitoquímica , Humanos , Vasculite/metabolismo
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