RESUMEN
Background: Kawasaki disease (KD), an acute febrile illness and systemic vasculitis, is the leading cause of acquired heart disease in children in industrialized countries. KD leads to the development of coronary artery aneurysms (CAA) in affected children, which may persist for months and even years after the acute phase of the disease. There is an unmet need to characterize the immune and pathological mechanisms of the long-term complications of KD. Methods: We examined cardiovascular complications in the Lactobacillus casei cell wall extract (LCWE) mouse model of KD-like vasculitis over 4 months. The long-term immune, pathological, and functional changes occurring in cardiovascular lesions were characterized by histological examination, flow cytometric analysis, immunofluorescent staining of cardiovascular tissues, and transthoracic echocardiogram. Results: CAA and abdominal aorta dilations were detected up to 16 weeks following LCWE injection and initiation of acute vasculitis. We observed alterations in the composition of circulating immune cell profiles, such as increased monocyte frequencies in the acute phase of the disease and higher counts of neutrophils. We determined a positive correlation between circulating neutrophil and inflammatory monocyte counts and the severity of cardiovascular lesions early after LCWE injection. LCWE-induced KD-like vasculitis was associated with myocarditis and myocardial dysfunction, characterized by diminished ejection fraction and left ventricular remodeling, which worsened over time. We observed extensive fibrosis within the inflamed cardiac tissue early in the disease and myocardial fibrosis in later stages. Conclusion: Our findings indicate that increased circulating neutrophil counts in the acute phase are a reliable predictor of cardiovascular inflammation severity in LCWE-injected mice. Furthermore, long-term cardiac complications stemming from inflammatory cell infiltrations in the aortic root and coronary arteries, myocardial dysfunction, and myocardial fibrosis persist over long periods and are still detected up to 16 weeks after LCWE injection.
Asunto(s)
Pared Celular , Modelos Animales de Enfermedad , Fibrosis , Lacticaseibacillus casei , Síndrome Mucocutáneo Linfonodular , Vasculitis , Animales , Ratones , Pared Celular/inmunología , Vasculitis/inmunología , Vasculitis/etiología , Vasculitis/patología , Síndrome Mucocutáneo Linfonodular/inmunología , Síndrome Mucocutáneo Linfonodular/complicaciones , Masculino , Miocarditis/etiología , Miocarditis/patología , Miocarditis/inmunología , Inflamación/inmunologíaRESUMEN
The clinical presentation, disease course, and outcome of SARS-CoV-2 infection in pediatrics differ from the presentation in adults. In a review by Hoang et al., the prevalence of dermatological manifestations was estimated in 0.25% of a total of 2,445 children with confirmed COVID-19. Similarly, the prevalence of skin manifestations was reported in 3% of 100 children in the Parri's study. A systematic review by Shah et al. analyzed 13 studies with 149 children who met eligibility criteria. The acral erythematous maculopapular lesion was the most common, as well as erythema multiforme, varicella rash, and presentations similar to Kawasaki disease. The duration of the skin lesion was one to two weeks in 43%. Skin biopsy of 18 cases complete superficial and deep perivascular and paracrine lymphocytic infiltrate and lymphocytic vasculitis were reported. RT-PCR was positive in 13.8 % of the cases. The serological markers of herpes simplex virus and parvovirus B19 analyzed were negative, except for Mycoplasma pneumoniae in two of 20 cases. The pathophysiological mechanism of skin lesions secondary to SARS-CoV-2 infection has not yet been explained; likely to be a combination of one or more complex mechanisms, direct skin damages induced by the virus, vasculitis-like reactions either indirect or secondary injuries as a consequence of a systemic inflammatory reaction. Publications from years 2019 to 2021 are reviewed in PubMed as the main search source, using key words.
La presentación clínica, curso de la enfermedad y resultado de la infección por SARS-CoV-2 en pediatría difieren de los observados en adultos. En una revisión de Hoang et al. se estimó que la prevalencia de las manifestaciones dermatológicas fue de 0.25 % de un total de 2445 niños con COVID-19 confirmada. Según Parri, se documentó 3 % en 100 niños. En la revisión sistemática de Shah et al.se analizaron 13 estudios que incluyeron 149 niños que cumplieron con los criterios de elegibilidad. La lesión maculopapular eritematosa acral fue la más común, también el eritema multiforme, el exantema de la varicela y las presentaciones similares a enfermedad de Kawasaki. La duración de las lesiones cutáneas fue de una a dos semanas en 43 %. La biopsia de piel de 18 casos reveló infiltrado linfocítico perivascular, infiltrado paracrino superficial y profundo y vasculitis linfocítica. La RT-PCR fue positiva en 13.8 %. Los marcadores serológicos analizados de virus de herpes simple y parvovirus B19 fueron negativos, y fueron positivos para Mycoplasma pneumoniae en dos de 20 casos. El mecanismo fisiopatológico de las lesiones en piel secundarias a infección por SARS-CoV-2 aún no se ha podido explicar; es probable que se trate de la combinación de uno o más mecanismos complejos, daños cutáneos directos inducidos por el virus, reacciones vasculíticas o lesiones indirectas o secundarias como consecuencia de una reacción inflamatoria sistemática. Se revisaron las publicaciones de 2019 a 2021 en PubMed como fuente principal de búsqueda, para lo cual se utilizaron palabras clave.
Asunto(s)
COVID-19 , Enfermedades de la Piel , Vasculitis , Adulto , Humanos , Niño , SARS-CoV-2 , COVID-19/complicaciones , Piel , Inflamación/complicaciones , Vasculitis/complicaciones , Vasculitis/patologíaRESUMEN
Peripheral ulcerative keratitis (PUK) is a progressive peripheral thinning of the corneal stroma caused by proinflammatory mediators' release from corneal limbal vasculitis. The clinical presentation is an epithelial defect with a crescent-shaped stromal inflammation. Its exact pathophysiologic mechanisms of PUK remain partially understood, but the overall understanding of the fundamental processes that mediate and effect corneal immunity has continued to expand over the past 25 years. The unique anatomical and physiological characteristics of the periphery in relation to collagen bundles and peripheral corneal vascular arch contribute to the occurrence of this type of ulcer in this region, in addition to the concentration of complement and immunoglobulins. There is a relevant participation of the adjacent conjunctiva. Both cell-mediated immunity and humoral immunity are implicated in the pathogenesis of PUK, and the postulated mechanisms are autoimmune reactions to corneal antigens, deposition of circulating immune complexes and hypersensitivity reactions to foreign antigens. These immunocomplexes are deposited in limbic vessels resulting in the activation of the classical pathway of the complement system and, consequently, in the chemotaxis of inflammatory cells and in the release of several pro-inflammatory cytokines, which allow the production and release of matrix metalloproteinases. The release of inflammatory cytokines by infiltrating cells may induce keratocyte activation, which could then generate more release of a variety of cytokines, such as the neutrophil calgranulin C, thus facilitating an autoimmune response to the protein and precipitating an antibody- and cell-mediated hyperimmune reaction in the peripheral cornea.
Asunto(s)
Úlcera de la Córnea/inmunología , Inmunidad Celular/fisiología , Inmunidad Humoral/fisiología , Autoinmunidad , Sustancia Propia/patología , Úlcera de la Córnea/diagnóstico , Úlcera de la Córnea/fisiopatología , Humanos , Limbo de la Córnea/patología , Vasculitis/patologíaRESUMEN
BACKGROUND: Vasculitic peripheral neuropathy (VPN) is caused by vessel inflammation leading to peripheral nerve injury of acute-to-subacute onset. When VPN occurs in the context of systemic disease it is classified as Systemic Vasculitic Neuropathy (SVN) and as Non-Systemic Vasculitic Neuropathy (NSVN) when restricted to the nerves. OBJECTIVE: This study aimed to compare the clinical characteristics, biopsy findings and disease outcome in patients with VPN. METHODS: Clinical records of adult patients with VPN diagnosed at our institution between June-2002 and June-2019 were retrospectively reviewed. Demographic characteristics, clinical manifestations, nerve conduction studies, nerve biopsies, treatment and clinical evolution were analyzed in all patients with at least 6 months follow-up. RESULTS: Twenty-five patients with VPN were included (SVN, nâ=â10; NSVN, nâ=â15). No significant differences in demographic or clinical features were found between groups. The median delay between symptom onset and nerve biopsy was significantly longer in NSVN patients (10 vs 5.5 months, pâ=â0.009). Erythrocyte sedimentation rate (ESR) values over 20âmm/h were significantly more common in SVN patients (100% vs. 60%, pâ=â0.024). Nerve biopsies showed active lesions more frequently in treatment-naive patients compared to those who had received at least 2 weeks of corticosteroids (92% vs 38%; pâ=â0.03), with a higher proportion of definite VPN cases (92 vs 46%; pâ=â0.04). CONCLUSIONS: Although the clinical manifestations are similar, ESR is an important tool to help distinguish between both conditions. Early nerve biopsy in untreated patients increases diagnostic accuracy, avoiding misdiagnosis.
Asunto(s)
Enfermedades del Sistema Nervioso Periférico/diagnóstico , Enfermedades del Sistema Nervioso Periférico/etiología , Vasculitis/complicaciones , Vasculitis/diagnóstico , Adulto , Edad de Inicio , Biopsia , Sedimentación Sanguínea , Estudios de Seguimiento , Humanos , Enfermedades del Sistema Nervioso Periférico/sangre , Enfermedades del Sistema Nervioso Periférico/patología , Estudios Retrospectivos , Vasculitis/sangre , Vasculitis/patologíaRESUMEN
Abstract The term vasculitis refers to the inflammation of vessel walls. It may range in severity from a self-limited disorder in one single organ to a life-threatening disease due to multiple organ failure. It has many causes, although they result in only a few histological patterns of vascular inflammation. Vessels of any type and in any organ can be affected, a fact that results in a broad variety of signs and symptoms. Different vasculitides with indistinguishable clinical presentations have quite different prognosis and treatments. This condition presents many challenges to physicians in terms of classification, diagnosis, appropriate laboratory workup, and treatment. Moreover, it compels a careful follow-up. This article reviews the Chapel-Hill 2012 classification, etiology, recent insights in pathophysiology, some important dermatological clues for the diagnosis and summarizes treatment of some of these complex vasculitis syndromes.
Asunto(s)
Humanos , Masculino , Femenino , Vasculitis/diagnóstico , Vasculitis/patología , Enfermedades Cutáneas Vasculares/diagnóstico , Enfermedades Cutáneas Vasculares/patología , Síndrome , Vasculitis/clasificación , Enfermedades Cutáneas Vasculares/clasificación , NecrosisRESUMEN
The term vasculitis refers to the inflammation of vessel walls. It may range in severity from a self-limited disorder in one single organ to a life-threatening disease due to multiple organ failure. It has many causes, although they result in only a few histological patterns of vascular inflammation. Vessels of any type and in any organ can be affected, a fact that results in a broad variety of signs and symptoms. Different vasculitides with indistinguishable clinical presentations have quite different prognosis and treatments. This condition presents many challenges to physicians in terms of classification, diagnosis, appropriate laboratory workup, and treatment. Moreover, it compels a careful follow-up. This article reviews the Chapel-Hill 2012 classification, etiology, recent insights in pathophysiology, some important dermatological clues for the diagnosis and summarizes treatment of some of these complex vasculitis syndromes.
Asunto(s)
Enfermedades Cutáneas Vasculares/diagnóstico , Enfermedades Cutáneas Vasculares/patología , Vasculitis/diagnóstico , Vasculitis/patología , Femenino , Humanos , Masculino , Necrosis , Enfermedades Cutáneas Vasculares/clasificación , Síndrome , Vasculitis/clasificaciónAsunto(s)
Livedo Reticularis/patología , Sarcoidosis/patología , Enfermedades de la Piel/patología , Eritema/patología , Femenino , Granuloma/patología , Humanos , Persona de Mediana Edad , Sarcoidosis Pulmonar/diagnóstico por imagen , Sarcoidosis Pulmonar/patología , Tomografía Computarizada por Rayos X , Vasculitis/patologíaRESUMEN
The panniculitides remain as one of the most challenging areas for clinicians, as they comprise a heterogeneous group of inflammatory diseases involving the subcutaneous fat with potentially-shared clinical and histopathological features. Clinically, most panniculitides present as red edematous nodules or plaques. Therefore, in addition to a detailed clinical history, a large scalpel biopsy of a recent-stage lesion with adequate representation of the subcutaneous tissue is essential to specific diagnosis and appropriate clinical management. Herein we review the panniculitides of particular interest to the rheumatologist.
Asunto(s)
Paniculitis/patología , Reumatólogos , Síndrome de Behçet/patología , Biopsia/métodos , Eritema Indurado/patología , Eritema Nudoso/patología , Etanercept/efectos adversos , Humanos , Inmunosupresores/efectos adversos , Infecciones/patología , Paniculitis/clasificación , Paniculitis de Lupus Eritematoso/patología , Poliarteritis Nudosa/patología , Grasa Subcutánea/patología , Tejido Subcutáneo/patología , Vasculitis/patologíaAsunto(s)
Humanos , Femenino , Persona de Mediana Edad , Sarcoidosis/patología , Enfermedades de la Piel/patología , Livedo Reticularis/patología , Vasculitis/patología , Tomografía Computarizada por Rayos X , Sarcoidosis Pulmonar/patología , Sarcoidosis Pulmonar/diagnóstico por imagen , Eritema/patología , Granuloma/patologíaAsunto(s)
Sarcoidosis/diagnóstico por imagen , Accidente Cerebrovascular/diagnóstico por imagen , Vasculitis/diagnóstico por imagen , Adulto , Imagen de Difusión por Resonancia Magnética/métodos , Humanos , Imagenología Tridimensional , Masculino , Sarcoidosis/patología , Accidente Cerebrovascular/patología , Vasculitis/patologíaRESUMEN
A free-ranging, male, yearling Guadalupe fur seal ( Arctocephalus philippii townsendi) died due to multifocal verminous vasculitis with thrombosis and several embolic infarcts in liver, kidney, and brain. Nematodes extracted from lung blood vessels were identified as Parafilaroides decorus, a parasite normally found in alveoli of California sea lions ( Zalophus californianus).
Asunto(s)
Lobos Marinos/parasitología , Enfermedades Pulmonares Parasitarias/veterinaria , Nematodos/aislamiento & purificación , Infecciones por Nematodos/veterinaria , Trombosis/veterinaria , Vasculitis/veterinaria , Animales , Enfermedades Pulmonares Parasitarias/parasitología , Enfermedades Pulmonares Parasitarias/patología , Masculino , Nematodos/clasificación , Infecciones por Nematodos/complicaciones , Infecciones por Nematodos/patología , Trombosis/parasitología , Trombosis/patología , Vasculitis/parasitología , Vasculitis/patologíaRESUMEN
Deferasirox is an iron chelator agent used in the treatment of diseases with iron overload, such as thalassemia and myelodysplastic syndrome. Although the majority of adverse reactions of deferasirox involve gastrointestinal symptoms and increase in serum creatinine and transaminases, skin rashes, such as maculopapular and urticarial eruptions, have also been reported. This study reports a case of myelodysplastic syndrome with urticarial vasculitis due to deferasirox therapy. Drug eruption was been confirmed by means of a challenge test, together with histopathological and clinical findings. To the best of our knowledge, we report the first case of deferasirox-induced urticarial vasculitis. Physicians should be aware of the possibility of urticarial vasculitis on deferasirox therapy and the fact that the discontinuation of the drug generally results in improvement.
Asunto(s)
Benzoatos/efectos adversos , Erupciones por Medicamentos/etiología , Quelantes del Hierro/efectos adversos , Síndromes Mielodisplásicos/tratamiento farmacológico , Triazoles/efectos adversos , Urticaria/inducido químicamente , Vasculitis/inducido químicamente , Anciano , Biopsia , Deferasirox , Erupciones por Medicamentos/patología , Femenino , Humanos , Urticaria/patología , Vasculitis/patologíaRESUMEN
Interleukin-1ß (IL-1ß) is a highly inflammatory cytokine that significantly contributes to both acute and chronic inflammatory diseases. The secretion of IL-1ß requires a unique protease, caspase-1, which is activated by various protein platforms called inflammasomes. Data suggests a key role for mitochondrial reactive oxygen species for inflammasome activation. Flavonoids constitute a group of naturally occurring polyphenolic molecules with many biological activities, including antioxidant effects. In this study, we investigated the effect of three flavonoids, quercetin (QUC), naringenin, and silymarim on inflammasome activation. We found that QUC inhibits IL-1ß secretion by both the NLRP3 and AIM2 inflammasome in a dose dependent manner, but not the NLRC4 inflammasome. QUC inhibition of the inflammasome was still observed in Atg16l1 knockout macrophages, indicating that QUC's effect was autophagy independent. Since QUC inhibited both NLRP3 and AIM2 inflammasomes but not NLRC4, we assessed ASC speck formation. QUC reduced ASC speck formation and ASC oligomerization compared with controls. Additionally, QUC inhibited IL-1ß in Cryopyrin-Associated Periodic Syndromes (CAPS) macrophages, where NLRP3 inflammasome is constitutively activated. In conclusion, QUC inhibits both the NLRP3 and AIM2 inflammasome by preventing ASC oligomerization and may be a potential therapeutic candidate for Kawasaki disease vasculitis and other IL-1 mediated inflammatory diseases.
Asunto(s)
Antiinflamatorios/farmacología , Proteínas Adaptadoras de Señalización CARD/metabolismo , Inflamasomas/antagonistas & inhibidores , Interleucina-1beta/metabolismo , Multimerización de Proteína/efectos de los fármacos , Quercetina/farmacología , Vasculitis/etiología , Vasculitis/metabolismo , Animales , Aneurisma de la Aorta/patología , Proteínas Reguladoras de la Apoptosis/metabolismo , Autofagia , Proteínas Adaptadoras de Señalización CARD/química , Proteínas de Unión al Calcio/metabolismo , Vasos Coronarios/patología , Proteínas de Unión al ADN/antagonistas & inhibidores , Modelos Animales de Enfermedad , Ratones , Síndrome Mucocutáneo Linfonodular/etiología , Síndrome Mucocutáneo Linfonodular/metabolismo , Síndrome Mucocutáneo Linfonodular/patología , Síndrome Mucocutáneo Linfonodular/prevención & control , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Vasculitis/patología , Vasculitis/prevención & controlRESUMEN
Abstract Deferasirox is an iron chelator agent used in the treatment of diseases with iron overload, such as thalassemia and myelodysplastic syndrome. Although the majority of adverse reactions of deferasirox involve gastrointestinal symptoms and increase in serum creatinine and transaminases, skin rashes, such as maculopapular and urticarial eruptions, have also been reported. This study reports a case of myelodysplastic syndrome with urticarial vasculitis due to deferasirox therapy. Drug eruption was been confirmed by means of a challenge test, together with histopathological and clinical findings. To the best of our knowledge, we report the first case of deferasirox-induced urticarial vasculitis. Physicians should be aware of the possibility of urticarial vasculitis on deferasirox therapy and the fact that the discontinuation of the drug generally results in improvement.
Asunto(s)
Humanos , Femenino , Anciano , Triazoles/efectos adversos , Urticaria/inducido químicamente , Vasculitis/inducido químicamente , Benzoatos/efectos adversos , Síndromes Mielodisplásicos/tratamiento farmacológico , Quelantes del Hierro/efectos adversos , Erupciones por Medicamentos/etiología , Urticaria/patología , Vasculitis/patología , Biopsia , Erupciones por Medicamentos/patologíaRESUMEN
ANCA mediated vasculitis mainly occur between the fourth and fifth decade of life; therefore, it is very uncommon to see pregnant patients with the disease. Vasculitis may affect significantly the course of pregnancy; in turn pregnancy can change the course of vasculitis. We report a 20 years old woman with ANCA-mediated renal vasculitis lasting 10 years who consulted with a pregnancy of 15 weeks. She was in remission and had amenorrhea attributed to ovarian toxicity due to cyclophosphamide. Pregnancy had an uneventful course with spontaneous delivery at the 37th week, giving birth to a healthy newborn. Proteinuria increased during the course of pregnancy with a mild deterioration of kidney function. During the year after delivery, she had nephrotic proteinuria and a worsening of renal function.
Asunto(s)
Humanos , Femenino , Embarazo , Adulto Joven , Complicaciones del Embarazo/patología , Vasculitis/patología , Anticuerpos Anticitoplasma de Neutrófilos , Enfermedades Renales/patología , Complicaciones del Embarazo/etiología , Complicaciones del Embarazo/sangre , Proteinuria , Factores de Tiempo , Vasculitis/etiología , Vasculitis/sangre , Biopsia , Resultado del Embarazo , Edad Gestacional , Tasa de Filtración Glomerular , Enfermedades Renales/etiología , Enfermedades Renales/sangreAsunto(s)
Lupus Eritematoso Sistémico/patología , Vasculitis/patología , Adulto , Femenino , HumanosRESUMEN
ANCA mediated vasculitis mainly occur between the fourth and fifth decade of life; therefore, it is very uncommon to see pregnant patients with the disease. Vasculitis may affect significantly the course of pregnancy; in turn pregnancy can change the course of vasculitis. We report a 20 years old woman with ANCA-mediated renal vasculitis lasting 10 years who consulted with a pregnancy of 15 weeks. She was in remission and had amenorrhea attributed to ovarian toxicity due to cyclophosphamide. Pregnancy had an uneventful course with spontaneous delivery at the 37th week, giving birth to a healthy newborn. Proteinuria increased during the course of pregnancy with a mild deterioration of kidney function. During the year after delivery, she had nephrotic proteinuria and a worsening of renal function.
Asunto(s)
Anticuerpos Anticitoplasma de Neutrófilos , Enfermedades Renales/patología , Complicaciones del Embarazo/patología , Vasculitis/patología , Biopsia , Femenino , Edad Gestacional , Tasa de Filtración Glomerular , Humanos , Enfermedades Renales/sangre , Enfermedades Renales/etiología , Embarazo , Complicaciones del Embarazo/sangre , Complicaciones del Embarazo/etiología , Resultado del Embarazo , Proteinuria , Factores de Tiempo , Vasculitis/sangre , Vasculitis/etiología , Adulto JovenRESUMEN
The different clinical forms of leprosy are mainly related to the variety of immunological responses to the infection. Several forms of lepromatous leprosy are recognized, including macular, nodular, and diffuse. Lucio's phenomenon is a rare but distinctive skin eruption seen in patients with diffuse lepromatous leprosy. The diffuse lesions of Lucio's phenomenon have a predilection for the extremities, can include nodules, and heal with atrophic stellate scars; histologically, a necrotizing vasculitis accompanied by a nonspecific inflammatory reaction may be seen. Because of its rarity and similarity with some manifestations of the rheumatic disease and other causes of vasculitis, Lucio's phenomenon may not be easily recognized, especially in non-endemic countries, which leads to confusing diagnosis and loss of time for treatment. We report five patients with vasculitis caused by Lucio's phenomenon.