RESUMEN
BACKGROUND: There are two distinctive acral manifestations of COVID-19 embodying disparate clinical phenotypes. One is perniosis occurring in mildly symptomatic patients, typically children and young adults; the second is the thrombotic retiform purpura of critically ill adults with COVID-19. OBJECTIVES: To compare the clinical and pathological profiles of these two different cutaneous manifestations of COVID-19. METHODS: We compared the light microscopic, phenotypic, cytokine and SARS-CoV-2 protein and RNA profiles of COVID-19-associated perniosis with that of thrombotic retiform purpura in critical patients with COVID-19. RESULTS: Biopsies of COVID-19-associated perniosis exhibited vasocentric and eccrinotropic T-cell- and monocyte-derived CD11c+ , CD14+ and CD123+ dendritic cell infiltrates. Both COVID-associated and idiopathic perniosis showed striking expression of the type I interferon-inducible myxovirus resistance protein A (MXA), an established marker for type I interferon signalling in tissue. SARS-CoV-2 RNA, interleukin-6 and caspase 3 were minimally expressed and confined to mononuclear inflammatory cells. The biopsies from livedo/retiform purpura showed pauci-inflammatory vascular thrombosis without any MXA decoration. Blood vessels exhibited extensive complement deposition with endothelial cell localization of SARS-CoV-2 protein, interleukin-6 and caspase 3; SARS-CoV-2 RNA was not seen. CONCLUSIONS: COVID-19-associated perniosis represents a virally triggered exaggerated immune reaction with significant type I interferon signaling. This is important to SARS-CoV-2 eradication and has implications in regards to a more generalized highly inflammatory response. We hypothesize that in the thrombotic retiform purpura of critically ill patients with COVID-19, the vascular thrombosis in the skin and other organ systems is associated with a minimal interferon response. This allows excessive viral replication with release of viral proteins that localize to extrapulmonary endothelium and trigger extensive complement activation.
Asunto(s)
COVID-19/complicaciones , Eritema Pernio/diagnóstico , Livedo Reticularis/diagnóstico , Púrpura/diagnóstico , SARS-CoV-2/inmunología , Adolescente , Factores de Edad , Anciano , Biopsia , COVID-19/diagnóstico , COVID-19/inmunología , COVID-19/virología , Caspasa 3/inmunología , Caspasa 3/metabolismo , Eritema Pernio/inmunología , Eritema Pernio/patología , Diagnóstico Diferencial , Femenino , Pie , Mano , Humanos , Interferón Tipo I/inmunología , Interferón Tipo I/metabolismo , Interleucina-6/inmunología , Interleucina-6/metabolismo , Livedo Reticularis/inmunología , Livedo Reticularis/patología , Livedo Reticularis/virología , Masculino , Persona de Mediana Edad , Proteínas de Resistencia a Mixovirus/análisis , Proteínas de Resistencia a Mixovirus/metabolismo , Púrpura/inmunología , Púrpura/patología , Púrpura/virología , ARN Viral/aislamiento & purificación , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Índice de Severidad de la Enfermedad , Piel/inmunología , Piel/patología , Piel/virología , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/aislamiento & purificaciónRESUMEN
In the United States, there is an epidemic of lung cancer, which causes more deaths annually than any other form of cancer. During 1950-1969, 27 of Louisiana's 64 parishes ranked in the upper 100 US countries for lung cancer mortality. Many of the rural southern parishes in the upper decile for lung cancer were geographically associated with sugarcane production and processing area. In a retrospective case-control study of this excess lung cancer mortality it was found that persons engaged in sugarcane farm-related occupations have a significantly increased risk of mortality due to this disease. To expand this observation, a survey of the environmental exposures of sugarcane workers is being conducted.
Asunto(s)
Carcinógenos , Neoplasias Pulmonares/etiología , Enfermedades Profesionales , Arsenicales/efectos adversos , Benzo(a)pireno/efectos adversos , Relación Dosis-Respuesta a Droga , Humanos , Louisiana , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/epidemiología , Riesgo , FumarRESUMEN
In a study to determine putative occupation-related factors responsible for the excessive mortality due to lung cancer in southern Louisiana, the next-of-kin were interviewed of 284 of 400 persons (71%) randomly sampled from a total of 815 persons who died of lung cancer during 1971 through 1977 and had lived in any of 10 parishes (counties) of southern Louisiana. Of the decedents, 108 (38%) had been employed for at least 6 months as sugarcane farm workers at some time during their lives. Logistic regression analysis indicated this industrial involvement differed significantly (P less than 0.0001) from that of a control group, consisting of persons who had died of any cause other than lung cancer and who were matched for year of death, age, sex race, and parish of residence; only 58 (20%) matched controls had had sugarcane farm employment (odds ratio = 2.4; 95% confidence interval, 2.0-2.9). Employment in other industries or tobacco consumption could not account for the elevated risk of lung cancer mortality associated with sugarcane farming. After adjustment for smoking, the relative risk estimate of lung cancer mortality for sugarcane farm workers was 2.4 (95% confidence limits, 1.7-3.6). The sugarcane farmers who died with lung cancer had worked for longer periods in the sugarcane farm industry than did those sugarcane farmers in whom lung cancer did not develop (P = 0.006). No specific histopathologic cell type was noted to be increased in persons who had been employed in sugarcane farming; however, 2 sugarcane farmers had had mesotheliomas.
Asunto(s)
Neoplasias Pulmonares/mortalidad , Enfermedades Profesionales/mortalidad , Factores de Edad , Agricultura , Femenino , Humanos , Louisiana , Neoplasias Pulmonares/etiología , Masculino , Persona de Mediana Edad , Enfermedades Profesionales/etiología , Grupos Raciales , Riesgo , Factores Sexuales , FumarRESUMEN
In a nationwide survey from January 1978 through September 1979, acute parvovirus-induced myocarditis was identified in 76 of 147 (52%) pups in 19 litters. The affected pups were from 12 states. Birth of all pups registered with the American Kennel Club during this period increased during the spring months, peaking in May, which was correlated in 4 to 8 weeks with the greatest number of cases in the study. Serologic data available for 4 dams, for 6 of their surviving pups, and for 3 contact pups indicated that all had been exposed to parvovirus. In 2 kennels, cases of acute myocarditis were preceded within 2 months by cases of severe gastroenteritis in older litters on the same premises.