RESUMEN

Introduction: Pathogenesis of cutaneous leishmaniases involves parasite growth, persistent inflammation, and likely participation of lipoproteins (LP). The cholesteryl ester transfer protein (CETP), involved in LP remodeling, has been shown to participate in the inflammatory response and the evolution of infectious conditions. Methods: We evaluated the impact of the presence of CETP on infection by Leishmania (L.) amazonensis in an experimental model of cutaneous leishmaniasis using C57BL6/J mice transgenic for human CETP (CETP), having as control their littermates that do not express the protein, wild-type (WT) mice. The progression of the lesion after infection in the footpad was monitored for 12 weeks. Two groups of animals were formed to collect the plantar pad in the 4th and 12th week post-infection. Results: The lesion increased from the 3rd week onwards, in both groups, with a gradual decrease from the 10th week onwards in the CETP group compared to the WT group, showing a reduction in parasitism and an improvement in the healing process, a reduction in CD68+ cells, and an increase in CD163+ and CD206, characterizing a population of M2 macrophages. A reduction in ARG1+ cells and an increase in INOS+ cells were observed. During infection, the LP profile showed an increase in triglycerides in the VLDL fraction in the CETP group at 12 weeks. Gene expression revealed a decrease in the CD36 receptor in the CETP group at 12 weeks, correlating with healing and parasite reduction. In vitro, macrophages derived from bone marrow cells from CETP mice showed lower parasite load at 48 h and, a reduction in arginase activity at 4 h accompanied by increased NO production at 4 and 24 h compared to WT macrophages, corroborating the in vivo findings. Discussion: The data indicate that the presence of CETP plays an important role in resolving Leishmania (L.) amazonensis infection, reducing parasitism, and modulating the inflammatory response in controlling infection and tissue repair.

Asunto(s)

Proteínas de Transferencia de Ésteres de Colesterol , Leishmaniasis Cutánea , Macrófagos , Ratones Endogámicos C57BL , Ratones Transgénicos , Animales , Proteínas de Transferencia de Ésteres de Colesterol/genética , Proteínas de Transferencia de Ésteres de Colesterol/metabolismo , Leishmaniasis Cutánea/inmunología , Leishmaniasis Cutánea/parasitología , Leishmaniasis Cutánea/metabolismo , Ratones , Macrófagos/inmunología , Macrófagos/metabolismo , Macrófagos/parasitología , Humanos , Progresión de la Enfermedad , Modelos Animales de Enfermedad

RESUMEN

Atopic dermatitis (AD) is an inflammatory skin disease with intense pruritus, and chronic skin colonization by Staphylococcus aureus. To understand the inflammatory status in AD, we investigated the inflammasome complex, that activates ASC (Apoptosis-associated speck-like protein containing a CARD), caspase-1 and GSDMD (gasdermin-D), and production of IL-1ß and IL-18. We aimed to evaluate the expression of the inflammasome pathway in the skin of adults with AD. Thirty patients with moderate to severe AD and 20 healthy controls were enrolled in the study. We performed the analysis of the inflammasome components NLRP1, NLRP3, AIM-2, IL-1ß, IL-18, Caspase-1, ASC, GSDMD, and CD68 expression (macrophage marker) by immunohistochemistry and immunofluorescence. The main findings included increased expression of NLRP3, NLRP1 and AIM-2 at dermal level of severe AD; augmented IL-18 and IL-1ß expression at epidermis of moderate and severe patients, and in the dermis of severe AD; augmented expression of ASC, caspase-1 and GSDMD in both epidermis and dermis of moderate and severe AD. We detected positive correlation between caspase-1, GSDMD and IL-1ß (epidermis) and caspase-1 (dermis) and AD severity; NLRP3, AIM-2 and IL-1ß, and NLRP3 with IL-18 in the epidermis; ASC, GSDMD and IL-1ß, and NLRP3, AIM-2, caspase-1, and IL-18 in the dermis. We also evidenced the presence of CD68+ macrophages secreting GSDMD, ASC and IL-1ß in moderate and severe AD. Cutaneous macrophages, early detected in moderate AD, have its role in the disease inflammatory mechanisms. Our study indicates a canonical activation pathway of inflammasomes, reinforced by the chronic status of inflammation in AD. The analysis of the inflammasome complex evidenced an imbalance in its regulation, with increased expression of the evaluated components, which is remarkably in severe AD, emphasizing its relevance as potential disease biomarkers and targets for immunomodulatory interventions.

Asunto(s)

Proteínas Adaptadoras de Señalización CARD , Caspasa 1 , Dermatitis Atópica , Inflamasomas , Macrófagos , Proteína con Dominio Pirina 3 de la Familia NLR , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas Adaptadoras de Señalización CARD/metabolismo , Estudios de Casos y Controles , Caspasa 1/metabolismo , Molécula CD68 , Dermatitis Atópica/inmunología , Dermatitis Atópica/metabolismo , Dermatitis Atópica/patología , Proteínas de Unión al ADN , Epidermis/inmunología , Epidermis/metabolismo , Epidermis/patología , Gasderminas , Inflamasomas/metabolismo , Inflamasomas/inmunología , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Macrófagos/metabolismo , Macrófagos/inmunología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteínas NLR/metabolismo , Proteínas de Unión a Fosfato/metabolismo , Índice de Severidad de la Enfermedad , Piel/patología , Piel/inmunología , Piel/metabolismo

RESUMEN

Atopic dermatitis (AD) is a complex, multifactorial skin disease, characterized by pruritus and predominant Th2 inflammation. Innate immune cells may play a role in AD development and are composed of granulocytes, macrophages, innate-like T cells, and innate lymphoid cells. This study investigates the phenotypic and functional profile of circulating CLA+ natural killer (NK) cells and its role in the skin-homing to NK cells infiltrated in adults' skin with AD. We selected 44 AD patients and 27 non-AD volunteers for the study. The results showed increased frequencies of both CLA+CD56bright and CLA+CD56dim NK cell populations in the peripheral blood, mainly in severe AD patients. Upon SEB stimulation, we observed an augmented percentage of CLA+CD56dim NK cells expressing CD107a, IFN-γ, IL-10, and TNF, reinforcing the role of staphylococcal enterotoxins in AD pathogenesis. Additionally, we demonstrated increased dermal expression of both NK cell markers NCAM-1/CD56 and pan-granzyme, corroborating the skin-homing, mostly in severe AD. Further studies are necessary to elucidate the potential role of NK cells in the chronification of the inflammatory process in AD skin, as well as their possible relationship with staphylococcal enterotoxins, and as practicable therapeutic targets.

Asunto(s)

Dermatitis Atópica , Adulto , Humanos , Inmunidad Innata , Antígenos de Diferenciación de Linfocitos T/metabolismo , Células Asesinas Naturales/metabolismo , Enterotoxinas

RESUMEN

Abstract Background: Methotrexate (MTX) is an alternative treatment for patients with moderate/severe atopic dermatitis (AD). Objective: The authors evaluated the effect of MTX on the cutaneous expression of cytokines and chemokines that are involved in the inflammatory response in adult AD patients who received treatment with methotrexate for 24 weeks. Methods: The authors conducted a prospective single-institution cohort study with 12 adults with moderate/severe AD who received oral MTX (15 mg/wk for 24 wks) and 10 non-atopic matched controls. The comparison was made of skin biopsies of lesional and non-lesional skin, pre- and post MTX treatment. The authors analyzed mean epidermal thickness and expression of IL-31, IL-31RA, OSMR, TSLP, Ki67, IL-4 mRNA, IL-6, IL-10, TNF-α, IFN-γ, TARC, and CCL-22. Results: There was a reduction in mean epidermal thickness (p = 0.021), an increase in IL-31RA expression (immunohistochemistry) in the epidermis (p = 0.016) and a decrease in IL-31 gene expression (p = 0.019) on lesional AD skin post-MTX treatment. No significant changes in the cutaneous expression of the other evaluated markers were identified. Study limitations: Small sample size and limited length of follow-up. Conclusions: Treatment with MTX in adults with moderate/severe AD reduced epidermal hyperplasia and changed the cutaneous expression of inflammatory cytokines and receptors that are mainly related to pruritus, including IL-31 and IL-31RA.

RESUMEN

BACKGROUND: Paracoccidioidomycosis is the most prevalent systemic mycosis in Latin America, with a high incidence in Brazil, Colombia and Venezuela, and constitutes a serious public health problem, a frequent cause of morbidity and disability for work. Some mechanisms of cell death are described as important tools in infectious processes. When apoptosis is blocked, RIPK (Receptor-interacting protein kinase) 3 dependent, a caspase-independent form of cell death, can limit the replication and spread of pathogens. Some molecules that mediate necroptosis include RIPK3 and have been extensively studied due to their signalling mechanism and pathological function. RIPK3 activates NLRP1 and NLRP3-mediated inflammasome formation. Caspase-1 has an important role in processing the cytokines ILß and IL18 to their active form. Such molecules are part of the inflammasome characterization, whose caspase-1-dependent activation promotes the death of pyroptotic cells and the secretion of proinflammatory cytokines. Knowledge about the mechanisms of pathogen-mediated cell death can be useful for understanding of the pathogenesis of infections and inflammatory conditions. OBJECTIVE: The objective of this work was to identify the mechanisms of programmed cell death and inflammasome components in human oral mucosal lesions of paracoccidioidomycosis through immunohistochemical methods and identification of RIPK-3, IL1ß, IL18, NLRP-1 and caspase-1. Thirty specimens were included, and a histopathological analysis of the lesions was performed using haematoxylin-eosin staining. RESULTS: Our results on in situ expression of inflammasome elements and programmed cell death showed increased expression of IL-1ß, NLRP-1, caspase-1 and RIPK-3. We suggest that inflammasome complex participate in the immunopathogenesis in paracoccidioidomycosis oral lesions in an interplay with RIPK3.

Asunto(s)

Inflamasomas , Paracoccidioidomicosis , Humanos , Interleucina-18 , Apoptosis/fisiología , Caspasa 1/metabolismo , Citocinas

RESUMEN

BACKGROUND: Methotrexate (MTX) is an alternative treatment for patients with moderate/severe atopic dermatitis (AD). OBJECTIVE: The authors evaluated the effect of MTX on the cutaneous expression of cytokines and chemokines that are involved in the inflammatory response in adult AD patients who received treatment with methotrexate for 24 weeks. METHODS: The authors conducted a prospective single-institution cohort study with 12 adults with moderate/severe AD who received oral MTX (15 mg/wk for 24 wks) and 10 non-atopic matched controls. The comparison was made of skin biopsies of lesional and non-lesional skin, pre- and post MTX treatment. The authors analyzed mean epidermal thickness and expression of IL-31, IL-31RA, OSMR, TSLP, Ki67, IL-4 mRNA, IL-6, IL-10, TNF-α, IFN-γ, TARC, and CCL-22. RESULTS: There was a reduction in mean epidermal thickness (p = 0.021), an increase in IL-31RA expression (immunohistochemistry) in the epidermis (p = 0.016) and a decrease in IL-31 gene expression (p = 0.019) on lesional AD skin post-MTX treatment. No significant changes in the cutaneous expression of the other evaluated markers were identified. STUDY LIMITATIONS: Small sample size and limited length of follow-up. CONCLUSIONS: Treatment with MTX in adults with moderate/severe AD reduced epidermal hyperplasia and changed the cutaneous expression of inflammatory cytokines and receptors that are mainly related to pruritus, including IL-31 and IL-31RA. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03327116.

Asunto(s)

Dermatitis Atópica , Adulto , Humanos , Dermatitis Atópica/tratamiento farmacológico , Metotrexato/uso terapéutico , Estudios de Cohortes , Estudios Prospectivos , Citocinas

Asunto(s)

Criptococosis , Aspergilosis Pulmonar , Humanos , Aspergilosis Pulmonar/complicaciones , Aspergilosis Pulmonar/diagnóstico , Criptococosis/complicaciones , Criptococosis/diagnóstico , Factores de Riesgo

RESUMEN

Sézary syndrome (SS) is a rare and aggressive type of cutaneous T-cell lymphoma, with an abnormal inflammatory response in affected skin. The cytokines IL-1B and IL-18, as key signaling molecules in the immune system, are produced in an inactive form and cleave to the active form by inflammasomes. In this study, we assessed the skin, serum, peripheral mononuclear blood cell (PBMC) and lymph-node samples of SS patients and control groups (healthy donors (HDs) and idiopathic erythroderma (IE) nodes) to investigate the inflammatory markers IL-1B and IL-18 at the protein and transcript expression levels, as potential markers of inflammasome activation. Our findings showed increased IL-1B and decreased IL-18 protein expression in the epidermis of SS patients; however, in the dermis layer, we detected increased IL-18 protein expression. In the lymph nodes of SS patients at advanced stages of the disease (N2/N3), we also detected an enhancement of IL-18 and a downregulation of IL-1B at the protein level. Moreover, the transcriptomic analysis of the SS and IE nodes confirmed the decreased expression of IL1B and NLRP3, whereas the pathway analysis indicated a further downregulation of IL1B-associated genes. Overall, the present findings showed compartmentalized expressions of IL-1B and IL-18 and provided the first evidence of their imbalance in patients with Sézary syndrome.

Asunto(s)

Interleucina-18 , Síndrome de Sézary , Neoplasias Cutáneas , Humanos , Dermatitis Exfoliativa/metabolismo , Inflamasomas/metabolismo , Interleucina-18/genética , Interleucina-18/metabolismo , Leucocitos Mononucleares/metabolismo , Síndrome de Sézary/metabolismo , Piel/metabolismo , Neoplasias Cutáneas/metabolismo

RESUMEN

Obesity is increasing in incidence worldwide, especially in women, which can affect the outcome of pregnancy. During this period, viral infections represent a risk to the mother, the placental unit, and the fetus. The Zika virus (ZIKV) outbreak in Brazil has been the cause of congenital Zika syndrome (CZS), with devastating consequences such as microcephaly in newborns. Herein, we analyzed the impact of maternal overweight/obesity on the antiviral factors' expression in the placental tissue of Zika-infected mothers. We accessed placentas from women with and without obesity from 34 public health units (São Paulo) and from Zika-infected mothers with and without obesity from the Clinical Cohort Study of ZIKV pregnant women (Rio de Janeiro, Brazil). We first verified that obesity, without infection, did not alter the constitutive transcriptional expression of antiviral factors or IFN type I/III expression. Interestingly, obesity, when associated with ZIKV infection, showed a decreased transcriptional expression of RIG-I and IFIH1 (MDA-5 protein precursor gene). At the protein level, we also verified a decreased RIG-I and IRF-3 expression in the decidual placenta from the Zika-infected obese group, regardless of microcephaly. This finding shows, for the first time, that obesity associated with ZIKV infection leads to an impaired type I IFN downstream signaling pathway in the maternal-fetal interface.

Asunto(s)

Interferón Tipo I , Microcefalia , Infección por el Virus Zika , Virus Zika , Recién Nacido , Embarazo , Femenino , Humanos , Antivirales , Mujeres Embarazadas , Infección por el Virus Zika/complicaciones , Estudios de Cohortes , Brasil/epidemiología , Placenta , Obesidad

RESUMEN

Chromoblastomycosis (CBM) is a chronic, progressive fungal disease of the skin and subcutaneous tissue caused by a group of dematiaceous fungi. Verrucous lesions present parasite-rich granulomas and predominance of a Th2 patterns of cytokines. The inflammasome constitutes a macromolecular protein complex that play a role in the activation of caspase 1 that cleaves pro-IL1ß and pro-IL18, essential mediators of inflammation, and also activates pyroptosis. We intended to explore the presence and a possible role of inflammasome elements in cutaneous human lesions in CBM, considering the expression of IL1ß, IL18, caspase 1, NLRP1, and also RIPK3, a key downstream component of necroptosis signaling. 35 skin biopsies of cutaneous lesions of verrucous form of CBM and 10 biopsies from normal skin were selected. The diagnosis was based on histological and clinical analysis. An immunohistochemical protocol was performed. The histopathological analysis evidenced epidermis with hyperkeratosis, irregular acanthosis, and micro abscesses. The dermis presented suppurative granulomas and inflammatory infiltrate composed by giant cells, macrophages, epithelioid cells, lymphocytes, and some eosinophils. Positive cells were distributed in the inflammatory infiltrate, with an increased number of cells expressing caspase 1, IL1ß and IL18. Cells expressing RIPK3 and NLRP1 were less frequent. The intense presence of caspase 1, IL1ß and IL18, allied to NLRP1 expression, suggest that inflammasome and pyroptosis could play a role in the immune response against fungal agents of CBM. Our results, allied to data from literature, could suggest that inflammasome-mediated response and pyroptosis could be a target to be explored to decrease CBM lesions.

Asunto(s)

Cromoblastomicosis , Inflamasomas , Humanos , Inflamasomas/metabolismo , Cromoblastomicosis/patología , Caspasa 1/metabolismo , Interleucina-18/metabolismo , Apoptosis

RESUMEN

Leprosy, a disease caused by Mycobacterium leprae, has polymorphic neurocutaneous manifestations strongly correlated with the host immune response. Peripheral neural damage can lead to sensory and motor losses, as well as deformities of the hands and feet. Both innate and acquired immune responses are involved, but the disease has been classically described along a Th1/Th2 spectrum, where the Th1 pole corresponds to the more limited presentations and the Th2 to the multibacillary ones. The aim of this review is to discuss this dichotomy in light of the current knowledge of the cytokines, T helper subpopulations, and regulatory T cells involved in each presentation of leprosy. The text will also address leprosy reactions related to increased inflammatory activity in both limited and multibacillary presentations, leading to exacerbation of chronic signs and symptoms and/or the development of new ones. Despite the efforts of many research groups around the world, there is no standardized serological test/biological marker for diagnosis so far, even in endemic areas, which could contribute to the eradication of leprosy.

Asunto(s)

Lepra , Citocinas , Humanos , Lepra/patología , Mycobacterium leprae , Linfocitos T Reguladores

RESUMEN

Leprosy is a disease caused by Mycobacterium leprae (ML) with diverse clinical manifestations, which are strongly correlated with the host's immune response. Skin lesions may be accompanied by peripheral neural damage, leading to sensory and motor losses, as well as deformities of the hands and feet. Both innate and acquired immune responses are involved, but the disease has been classically described along a Th1/Th2 spectrum, where the Th1 pole corresponds to the most limited presentations and the Th2 to the most disseminated ones. We discuss this dichotomy in the light of current knowledge of cytokines, Th subpopulations and regulatory T cells taking part in each leprosy presentation. Leprosy reactions are associated with an increase in inflammatory activity both in limited and disseminated presentations, leading to a worsening of previous symptoms or the development of new symptoms. Despite the efforts of many research groups around the world, there is still no adequate serological test for diagnosis in endemic areas, hindering the eradication of leprosy in these regions.

Asunto(s)

Lepra , Inmunidad Adaptativa , Citocinas , Humanos , Lepra/diagnóstico , Lepra/patología , Mycobacterium leprae/fisiología , Linfocitos T Reguladores

RESUMEN

Abstract Leprosy, a disease caused by Mycobacterium leprae, has polymorphic neurocutaneous manifestations strongly correlated with the host immune response. Peripheral neural damage can lead to sensory and motor losses, as well as deformities of the hands and feet. Both innate and acquired immune responses are involved, but the disease has been classically described along a Th1/Th2 spectrum, where the Th1 pole corresponds to the more limited presentations and the Th2 to the multibacillary ones. The aim of this review is to discuss this dichotomy in light of the current knowledge of the cytokines, T helper subpopulations, and regulatory T cells involved in each presentation of leprosy. The text will also address leprosy reactions related to increased inflammatory activity in both limited and multibacillary presentations, leading to exacerbation of chronic signs and symptoms and/or the development of new ones. Despite the efforts of many research groups around the world, there is no standardized serological test/biological marker for diagnosis so far, even in endemic areas, which could contribute to the eradication of leprosy.

RESUMEN

This study presents a single center experience with livedoid vasculopathy (LV). A rare disease that can lead to severe quality of life impairment. Characterize clinical data of LV patients at the Dermatology Division at the University of São Paulo. A retrospective and transversal study was conducted, from 1 January 2005 to 31 December 2019. About 75 patients diagnosed as LV and confirmed by skin biopsy were included. Epidemiology, clinical appearance, histopathology data, and treatment history were observed. There were 78.66% Caucasian women, with a mean age of 39.9 years. Frequent cutaneous manifestations were ulcers, atrophic blanche-like scars, hyperpigmentation, purpuras, telangiectasias, and livedo racemosa. Pain, pruritus, and hypoesthesia were the main symptoms. After treatment, almost 40% of cases relapsed during spring and summer months. About 66% of cases had thrombophilia factors associated, such as high levels of lipoprotein(a). Frequent treatments included acetylsalicylic acid, pentoxifylline, and diosmin with hesperidin. Not being a prospective study. This research provides useful data on Latin American LV patients, indicating multifactorial conditions involved in LV pathogenesis. An extensive work-up including autoimmune laboratory tests, thrombophilia factors, and other conditions associated with venous stasis should be part of LV investigation and controlled to improve treatment response.

Asunto(s)

Livedo Reticularis , Calidad de Vida , Adulto , Brasil/epidemiología , Femenino , Humanos , Livedo Reticularis/diagnóstico , Livedo Reticularis/tratamiento farmacológico , Livedo Reticularis/epidemiología , Estudios Prospectivos , Estudios Retrospectivos

RESUMEN

Lacaziosis is a cutaneous mycosis caused by the fungus Lacazia loboi, described in different countries of Latin America and prevalent in the Amazon region. The ineffective immune response against the agent seems to be related to a Th2 pattern of cytokines. There are few reports exploring elements of the humoral response in these lesions. Our aim was to investigate some elements focusing on B cells, plasma cells and local expression of IgG and IgM antibodies. Forty skin biopsies of lower limbs were selected. The diagnosis of lacaziosis was based on direct mycological examination and histological analysis. The visualization of fungal cells was improved by using Gridley's staining. An immunohistochemical protocol was performed to detect the expression of B cells, plasma cells, IgG and IgM. A double staining was performed to explore the presence of yeasts in the cytoplasm of keratinocytes, using an anti-AE1 AE3 antibody over Gridley's staining. The inflammatory infiltrate consisted of macrophages, multinucleated giant cells, lymphocytes, and fibrosis. Fungal cells were frequent in the stratum corneum and in both, the dermis and, in 50% of the specimens, also in the epidermis. Cells expressing IgG were more abundant when compared to cells expressing IgM. B cells and the presence of IgG might indicate that the humoral response promotes a Th2 immune response resulting in an anti-inflammatory phenotype. Our results lead us to suggest a possible role of B cells and immunoglobulins in the mechanisms of lacaziosis pathogenesis.

Asunto(s)

Dermatomicosis , Lacazia/aislamiento & purificación , Lobomicosis/diagnóstico , Biopsia , Humanos , Inmunoquímica , Piel

RESUMEN

Abstract Vasculitis is a group of several clinical conditions in which the main histopathological finding is fibrinoid necrosis in the walls of blood vessels. This article assesses the main dermatological aspects relevant to the clinical and laboratory diagnosis of small- and medium-vessel cutaneous and systemic vasculitis syndromes. The most important aspects of treatment are also discussed.

Asunto(s)

Humanos , Vasculitis , Piel

RESUMEN

Vasculitis is a group of several clinical conditions in which the main histopathological finding is fibrinoid necrosis in the walls of blood vessels. This article assesses the main dermatological aspects relevant to the clinical and laboratory diagnosis of small- and medium-vessel cutaneous and systemic vasculitis syndromes. The most important aspects of treatment are also discussed.

Asunto(s)

Vasculitis , Humanos , Piel

RESUMEN

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 , Necrosis

RESUMEN

Lacaziosis is a cutaneous chronic mycosis caused by Lacazia loboi. Macrophages are important cells in the host immune response in fungal infections. The macrophage population exhibits strong plasticity that varies according to the stimuli in the microenvironment of lesions M1 profile promotes a Th1 pattern of cytokines and a microbicidal function and M2 is related to Th2 cytokines and immunomodulatory response. We investigated the population of M1 and M2 polarized macrophages in human cutaneous lesions. A total of 27 biopsies from human lesions were submitted to an immunohistochemistry protocol using antibodies to detect M1 and M2 macrophages (Arginase-1, CD163, iNOS, RBP-J and cMAF). We could observe high number of cells expressing Arginase1, CD163 and c-MAF that correspond to elements of the M2 profile of macrophage, over iNOS and RBP-J (elements of the M1 profile). The results suggest a predominant phenotype of M2 macrophages, which have an immunomodulatory role and probably contributing to chronicity of Lacaziosis.

Asunto(s)

Lacazia/inmunología , Lobomicosis/patología , Macrófagos/inmunología , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Arginasa/metabolismo , Biopsia , Plasticidad de la Célula/inmunología , Epidermis/inmunología , Epidermis/metabolismo , Epidermis/patología , Humanos , Proteína de Unión a la Señal Recombinante J de las Inmunoglobulinas/metabolismo , Inmunohistoquímica , Lobomicosis/inmunología , Óxido Nítrico Sintasa de Tipo II/metabolismo , Proteínas Proto-Oncogénicas c-maf/metabolismo , Receptores de Superficie Celular/metabolismo

RESUMEN

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/clasificación