RESUMO
Atopic dermatitis (AD) is a chronic relapsing inflammatory cutaneous disease that is often associated with other atopic symptoms, such as food allergy, allergic rhinitis and asthma, leading to significant morbidity and healthcare costs. The pathogenesis of AD is complicated and multifactorial. Although the aetiology of AD remains incompletely understood, recent studies have provided further insight into AD pathophysiology, demonstrating that the interaction among genetic predisposition, immune dysfunction and environmental provocation factors contributes to its development. However, the increasing prevalence of AD suggests that environmental factors such as irritation and cutaneous infection play a crucial role in triggering and/or aggravating the disease. Of note, AD skin is susceptible to bacterial, fungal and viral infections, and microorganisms may colonize the skin and aggravate AD symptoms. Overall, understanding the mechanisms by which these risk factors affect the cutaneous immunity of patients with AD is of great importance for developing a precision medicine approach for treatment. This review summarizes recent developments in exogenous factors involved in the pathogenesis of AD, with special emphasis on irritants and microbial infections.
Assuntos
Dermatite Atópica/fisiopatologia , Irritantes/efeitos adversos , Dermatopatias Infecciosas/microbiologia , Pele/microbiologia , Dermatite Atópica/imunologia , Dermatite Atópica/microbiologia , Humanos , Erupção Variceliforme de Kaposi/imunologia , Erupção Variceliforme de Kaposi/fisiopatologia , Microbiota , Molusco Contagioso/imunologia , Molusco Contagioso/fisiopatologia , Dermatopatias Infecciosas/imunologia , Dermatopatias Infecciosas/fisiopatologiaRESUMO
BACKGROUND: Atopic dermatitis (AD) predisposes to viral skin infections, such as eczema herpeticum (EH), and to bacterial skin infections, such as those caused by Staphylococcus aureus (SA) and group A streptococcus (GAS). This study evaluated clinical features of EH and its frequency of codetection with SA or GAS in children hospitalized for presumed AD skin infection. METHODS: We retrospectively reviewed clinical data for children ≤18 years of age admitted to a large hospital system for AD with presumed skin infection from January 2004 to December 2018. Those with an alternate primary diagnosis or missing microbiologic data were excluded. Encounters with herpes simplex virus testing were identified as AD with EH (ADEH+) or without (ADEH-). Encounters with bacterial skin culture growth were identified as SA or GAS. RESULTS: Among 180 AD encounters with suspected skin infection, 133 (74%) were tested for herpes simplex virus. Clinical findings associated with ADEH+ status (n = 61) included fever on admission (59% vs. 32% in ADEH-; P = 0.002), rash on the neck (30% vs. 13%; P = 0.015) and vesicular rash (70% vs. 49%; P = 0.011). Encounters in the ADEH+ group had a longer hospital length of stay compared with encounters in the ADEH- group [median 4 days (interquartile range 3-5 days) vs. 3 days (interquartile range 2-3 days); P < 0.001]. GAS was identified in only 1 ADEH+ encounter (2%) versus 15 ADEH- encounters (26%), P < 0.001. CONCLUSIONS: Providers should maintain a high index of suspicion for EH in children admitted for presumed AD skin infection. GAS was more commonly associated with ADEH- encounters.
Assuntos
Dermatite Atópica/complicações , Erupção Variceliforme de Kaposi/fisiopatologia , Pré-Escolar , Coinfecção/microbiologia , Coinfecção/virologia , Feminino , Infecções por Bactérias Gram-Positivas/microbiologia , Herpesvirus Humano 1/isolamento & purificação , Hospitalização , Humanos , Lactente , Erupção Variceliforme de Kaposi/microbiologia , Erupção Variceliforme de Kaposi/virologia , Masculino , Estudos Retrospectivos , Pele/microbiologia , Pele/virologiaRESUMO
The IL-1 superfamily of cytokines and receptors has been studied extensively. However, the specific roles of IL-1 elements in host immunity to cutaneous viral infection remain elusive. In this study, we applied vaccinia virus (VACV) by scarification to IL-1R1 knockout mice (IL-1R1-/-) and found that these mice developed markedly larger lesions with higher viral genome copies in skin than did wild-type mice. The phenotype of infected IL-1R1-/- mice was similar to eczema vaccinatum, a severe side effect of VACV vaccination that may develop in humans with atopic dermatitis. Interestingly, the impaired cutaneous response of IL-1R1-/- mice did not reflect a systemic immune deficiency, because immunized IL-1R1-/- mice survived subsequent lethal VACV intranasal challenge, or defects of T cell activation or T cell homing to the site of inoculation. Histologic evaluation revealed that VACV infection and replication after scarification were limited to the epidermal layer of wild-type mice, whereas lack of IL-1R1 permitted extension of VACV infection into dermal layers of the skin. We explored the etiology of this discrepancy and determined that IL-1R1-/- mice contained significantly more macrophages and monocyte-derived dendritic cells in the dermis after VACV scarification. These cells were vulnerable to VACV infection and may augment the transmission of virus to adjacent skin, thus leading to larger skin lesions and satellite lesions in IL-1R1-/- mice. These results suggest new therapeutic strategies for treatment of eczema vaccinatum and inform assessment of risks in patients receiving IL-1 blocking Abs for treatment of chronic inflammatory disorders.
Assuntos
Proteína Antagonista do Receptor de Interleucina 1/deficiência , Proteína Antagonista do Receptor de Interleucina 1/imunologia , Dermatopatias Infecciosas/imunologia , Pele/patologia , Vaccinia virus/imunologia , Vacínia/imunologia , Administração Cutânea , Animais , Linfócitos T CD8-Positivos/imunologia , Proteína Antagonista do Receptor de Interleucina 1/genética , Erupção Variceliforme de Kaposi/imunologia , Erupção Variceliforme de Kaposi/fisiopatologia , Erupção Variceliforme de Kaposi/terapia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pele/anatomia & histologia , Pele/imunologia , Pele/virologia , Vacinação , Vaccinia virus/fisiologia , Replicação ViralAssuntos
Encefalite por Herpes Simples/complicações , Encefalite por Herpes Simples/fisiopatologia , Erupção Variceliforme de Kaposi/etiologia , Erupção Variceliforme de Kaposi/fisiopatologia , Adulto , Líquido Cefalorraquidiano/microbiologia , Dermatite Atópica , Humanos , Masculino , Punção Espinal , Tomografia Computadorizada por Raios X/métodosAssuntos
Citocinas/genética , Dermatite Atópica/genética , Erupção Variceliforme de Kaposi/genética , Receptores de Citocinas/genética , Receptores de Interleucina-7/genética , Citocinas/imunologia , Citocinas/metabolismo , Análise Mutacional de DNA , Dermatite Atópica/imunologia , Dermatite Atópica/fisiopatologia , Frequência do Gene , Estudos de Associação Genética , Variação Genética , Humanos , Erupção Variceliforme de Kaposi/imunologia , Erupção Variceliforme de Kaposi/fisiopatologia , Polimorfismo de Nucleotídeo Único , Grupos Raciais , Receptores de Citocinas/metabolismo , Receptores de Interleucina-7/metabolismo , Linfopoietina do Estroma do TimoAssuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/normas , Coleta de Dados/estatística & dados numéricos , Interpretação Estatística de Dados , Erupção Variceliforme de Kaposi/etiologia , Vacina Antivariólica/efeitos adversos , Humanos , Imunização/efeitos adversos , Erupção Variceliforme de Kaposi/epidemiologia , Erupção Variceliforme de Kaposi/fisiopatologia , Segurança , Vacina Antivariólica/administração & dosagem , Terminologia como Assunto , Vaccinia virusRESUMO
BACKGROUND: Kaposi's varicelliform eruption (KVE) is characterized by disseminated cutaneous eruptions usually caused by infection with herpes simplex virus (HSV). Kaposi's varicelliform eruption is commonly observed among patients with atopic dermatitis (AD). Why AD patients are prone to HSV infections is still an enigma. Recent findings suggest that an increased number of IL-4-secreting cells can be cloned from lesions of AD. Because IL-4 is a known Th1 cell inhibitor, theoretically, by inhibiting the Th1 cells, it could downregulate the immune response against HSV. In this study, we have evaluated the role of IL-4 on HSV replication. METHODS: Peripheral blood mononuclear cells (PBMC) from 10 HSV seronegative and five seropositive healthy individuals were stimulated with PHA, recall antigen (tetanus toxoid), and HSV antigen in combination with IL-4 and anti-IL-4. Supernatants were assessed for interferon (IFN) gamma, IL-4 by enzyme-linked immunosorbent assay (ELISA), and for anti-HSV effect. Anti-HSV effect was assessed by measuring inhibition of the cytopathic effect (CPE) of HSV on a Vero cell line. RESULTS: Both seropositive and seronegative groups showed significant inhibition of IFN-gamma secretion with addition of IL-4 (P < .001, Wilcoxon rank sum test) and this effect could be neutralized by anti-IL-4. There was a direct relationship between the IFN-gamma concentration and the HSV cytopathic effect and an inverse relationship between IL-4 concentration and HSV CPE: CONCLUSIONS: This study provides evidence that IL-4 can enhance HSV infection. Therefore, it is conceivable that patients with conditions of increased activity of IL-4, as in AD, would be prone to extensive forms of HSV infection.