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BACKGROUND: Anti-desmoglein (Dsg)1 is produced in pemphigus foliaceus (PF), affecting exclusively the skin. Pemphigus vulgaris (PV) shows the production of anti-Dsg3 in the mucosal form, and anti-Dsg1 and 3 in the mucocutaneous form. Anti-Dsg3 autoantibodies have been rarely reported in PF. OBJECTIVES: To determine the factors associated with the production and pathogenicity of anti-Dsg3 in PF. METHODS: Comparative analytical study of three patients groups: 16 PF-anti-Dsg3+, and 42 PF-anti-Dsg3(-) and 22 PV treatment-naïve cases. Serum was used in the anti-Dsg1 and 3 ELISA, and in immunoblotting (IB) with human epidermis extract. The expression of Dsg1 and 3 in paraffin sections was analyzed by immunohistochemistry (IHC). HLA-DRB1 alleles were compiled from a database. RESULTS: In the PF-anti-Dsg3+ group: age range similar to that of the PV group (pâ¯>â¯0.9999); predominance of the generalized form of PF (pâ¯=â¯0.002); anti-Dsg3 titers lower than those of PV (pâ¯<â¯0.0001); IB confirmed Dsg3 identification in one (8.33%) of 12 patients; IHC showed exclusive cytoplasmic internalization of Dsg1; HLA-DRB1 alleles of susceptibility to PF, with the absence of alleles associated with PV, in the five typed patients. STUDY LIMITATIONS: Most of the patients in the PF-anti-Dsg3+ group were undergoing treatment. CONCLUSION: The presence of anti-Dsg3 antibodies in PF was related to older age (comparable to that of PV) and the generalized form of PF. The non-pathogenicity of anti-Dsg3 antibodies in PF can be attributed to the low serum anti-Dsg3 titers, the lack of Dsg3 internalization as detected by IHC, and the absence of PV-associated HLA-DRB1 alleles.
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Autoanticorpos , Desmogleína 1 , Desmogleína 3 , Imuno-Histoquímica , Pênfigo , Humanos , Pênfigo/imunologia , Desmogleína 3/imunologia , Autoanticorpos/imunologia , Autoanticorpos/sangue , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Idoso , Desmogleína 1/imunologia , Ensaio de Imunoadsorção Enzimática , Adulto Jovem , Immunoblotting , Cadeias HLA-DRB1/genética , Cadeias HLA-DRB1/imunologia , Idoso de 80 Anos ou mais , AdolescenteRESUMO
Pemphigus foliaceus (PF) is an autoimmune blistering disorder which affects the superficial layers of the epidermis with rare mucosal involvement. We present the case of a 12-year-old girl with PF involving the eyes and eyelids. A literature review of pediatric nonendemic PF revealed another two cases with ocular manifestations. Eyelid involvement is an uncommon feature of PF that should be properly identified and treated.
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Doenças Palpebrais , Pênfigo , Criança , Feminino , Humanos , Doenças Palpebrais/diagnóstico , Doenças Palpebrais/patologia , Pálpebras/patologia , Pênfigo/diagnóstico , Pênfigo/patologiaRESUMO
Pemphigus, an autoimmune intraepidermal bullous disease group with roughly eight distinct forms, includes pemphigus vulgaris (PV) and pemphigus foliaceus (PF) as its predominant global forms. Despite the increased utilization of global health records and reporting systems, epidemiological data remain limited and poorly categorized. Therefore, this study aimed to conduct a review to track, identify, and characterize cases of PV and PF published and categorized worldwide. A research question was formulated; studies were selected based on the inclusion criteria; and data from these publications were systematically collected, summarized, and presented using narrative descriptions. The search strategy yielded 3,212 articles, of which 95 underwent critical analysis and data extraction. Studies from 52 countries contributed to the dataset, covering various pemphigus variants. Notably, only two countries, Iran (18.87%) and South Korea (11.43%), accounted for approximately a third of the reported PV cases, while Brazil contributed 40.25% of the foliaceus variants cases documented in the literature. These findings offer valuable insights into the global distribution of pemphigus and inform future research and healthcare efforts.
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Doenças Autoimunes , Pênfigo , Humanos , BrasilRESUMO
Introduction: Primarily driven by autoreactive B cells, pemphigus foliaceus (PF) is an uncommon autoimmune blistering skin disease of sporadic occurrence worldwide. However, PF reaches a prevalence of 3% in the endemic areas of Brazil, the highest ever registered for any autoimmune disease, which indicates environmental factors influencing the immune response in susceptible individuals. We aimed to provide insights into the immune repertoire of patients with PF living in the endemic region of the disease, compared to healthy individuals from the endemic region and a non-endemic area. Methods: We characterized the B-cell repertoire in i) nontreated patients (n=5); ii) patients under immunosuppressive treatment (n=5); iii) patients in remission without treatment (n=6); and two control groups iv) from the endemic (n=6) and v) non-endemic areas in Brazil (n=4). We used total RNA extracted from peripheral blood mononuclear cells and performed a comprehensive characterization of the variable region of immunoglobulin heavy chain (IGH) in IgG and IgM using next-generation sequencing. Results: Compared to individuals from a different area, we observed remarkably lower clonotype diversity in the B-cell immune repertoire of patients and controls from the endemic area (p < 0.02), suggesting that the immune repertoire in the endemic area is under geographically specific and intense environmental pressure. Moreover, we observed longer CDR3 sequences in patients, and we identified differential disease-specific usage of IGHV segments, including increased IGHV3-30 and decreased IGHV3-23 in patients with active disease (p < 0.04). Finally, our robust network analysis discovered clusters of CDR3 sequences uniquely observed in patients with PF. Discussion: Our results indicate that environmental factors, in addition to disease state, impact the characteristics of the repertoire. Our findings can be applied to further investigation of the environmental factors that trigger pemphigus and expand the knowledge for identifying new targeted and more effective therapies.
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Pênfigo , Humanos , Leucócitos Mononucleares , Vesícula , ImunoglobulinasRESUMO
Background: Endemic pemphigus foliaceus and endemic pemphigus vulgaris are autoimmune dermatologic disorders endemic to the Peruvian Amazon. Objective: To determine the ultrastructural skin alterations of three healthy subjects with anti DSG-1 antibodies in areas endemic to pemphigus foliaceus and pemphigus vulgaris in the Peruvian Amazon. Patients and methods: Case series carried out from data of three clinically healthy subjects positive to anti DSG-1 antibodies, from Peru. This study consists of a sub-analysis of data gathered in a previous study. Results: Ultrastructural results are presented from the skin biopsies of three clinically healthy patients positive to anti-desmoglein 1 (DSG-1) antibodies. High Resolution Optical Microscopy (HROM) showed the absence of acantholysis. Transmission Electron Microscopy (TEM) showed the widening of intercellular space between keratinocytes, the presence of vacuoles in intercellular space with granular material and cytoplasmic vacuolization, loss of desmosome structure, loss of normal distribution among tonofilaments and lateral separation among cells in the stratum basale. Conclusion: According to our results, healthy subjects that present anti-desmoglein 1 antibodies can develop ultrastructural alterations that are visible through transmission electron microscopy but not through conventional optical microscopy.
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Pemphigus foliaceus (PF) is an autoimmune skin blistering disease characterized by antidesmoglein-1 IgG production, with an endemic form (EPF) in Brazil. Genetic and epigenetic factors have been associated with EPF, but its etiology is still not fully understood. To evaluate the genetic association of histone (de)acetylation-related genes with EPF susceptibility, we evaluated 785 polymorphisms from 144 genes, for 227 EPF patients and 194 controls. Carriers of HDAC4_rs4852054*A were more susceptible (OR = 1.79, p = 0.0038), whereas those with GSE1_rs13339618*A (OR = 0.57, p = 0.0011) and homozygotes for PHF21A_rs4756055*A (OR = 0.39, p = 0.0006) were less susceptible to EPF. These variants were not associated with sporadic PF (SPF) in German samples of 75 SPF patients and 150 controls, possibly reflecting differences in SPF and EPF pathophysiology. We further evaluated the expression of histone (de)acetylation-related genes in CD4+ T lymphocytes, using RNAseq. In these cells, we found a higher expression of KAT2B, PHF20, and ZEB2 and lower expression of KAT14 and JAD1 in patients with active EPF without treatment compared to controls from endemic regions. The encoded proteins cause epigenetic modifications related to immune cell differentiation and cell death, possibly affecting the immune response in patients with PF.
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The long search for the environmental trigger of the endemic pemphigus foliaceus (EPF, fogo selvagem) has not yet resulted in any tangible findings. Here, we searched for genetic associations and the differential expression of host genes involved in early viral infections and innate antiviral defense. Genetic variants could alter the structure, expression sites, or levels of the gene products, impacting their functions. By analyzing 3063 variants of 166 candidate genes in 227 EPF patients and 194 controls, we found 12 variants within 11 genes associated with differential susceptibility (p < 0.005) to EPF. The products of genes TRIM5, TPCN2, EIF4E, EIF4E3, NUP37, NUP50, NUP88, TPR, USP15, IRF8, and JAK1 are involved in different mechanisms of viral control, for example, the regulation of viral entry into the host cell or recognition of viral nucleic acids and proteins. Only two of nine variants were also associated in an independent German cohort of sporadic PF (75 patients, 150 controls), aligning with our hypothesis that antiviral host genes play a major role in EPF due to a specific virus−human interaction in the endemic region. Moreover, CCL5, P4HB, and APOBEC3G mRNA levels were increased (p < 0.001) in CD4+ T lymphocytes of EPF patients. Because there is limited or no evidence that these genes are involved in autoimmunity, their crucial role in antiviral responses and the associations that we observed support the hypothesis of a viral trigger for EPF, presumably a still unnoticed flavivirus. This work opens new frontiers in searching for the trigger of EPF, with the potential to advance translational research that aims for disease prevention and treatment.
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Pênfigo , RNA Mensageiro , Humanos , Pênfigo/epidemiologia , Pênfigo/genética , Pênfigo/virologia , RNA Mensageiro/genéticaRESUMO
BACKGROUND: A new variant of endemic pemphigus foliaceus is present in El Bagre, Colombia, and surrounding municipalities (El Bagre-EPF) that affects the skin and in some presentations affects other organs with autoantibodies directed against cell junctions. METHODS: We studied 200 El Bagre-EPF patient perilesional skin biopsies, as well as 200 skin biopsies from normal controls in the endemic area. RESULTS: We observed blister extrusions of sebaceous glands or entire pilosebaceous units via the isthmus in 23% of the patients and not in the controls. CONCLUSIONS: The extrusion of hair follicular unit contents is consistent with our previous pathologic findings of autoreactivity to these units, and their observed clinical decrease in patients affected by El Bagre-EPF.
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Pênfigo , Autoanticorpos , Vesícula/epidemiologia , Colômbia/epidemiologia , Doenças Endêmicas , Humanos , Pênfigo/patologia , América do SulRESUMO
Abstract Background: Pemphigus foliaceus is exceedingly rare around the world, except within the few regions where it occurs as an endemic variant. Various factors can trigger immune mechanisms that induce pemphigus foliaceus or worsen its course. Objective: To determine the demographic and clinical characteristics of the patients with pemphigus foliaceus in a large series from a non-endemic country, investigate the triggering factors, and seasonal patterns. Methods: The data of the patients diagnosed with pemphigus foliaceus in the study's center between 1989-2018 were retrospectively analyzed. Results: Sixty-eight patients (mean age, 45.7 ± 14.5 years) were included in the study. The number of onsets reached its peak in spring-summer (p = 0.008). A total of 117 relapses occurred in 42 patients and were most common in spring-summer (not significant). Specific trigger factors were detected in 45 relapses. In the other 72 relapses, the peak was observed in spring-summer (p = 0.005). There were no significant differences in the demographic and clinical variables investigated between relapsed and non-relapsed patients. Study limitations: Retrospective design. Conclusions: Triggering factors could not be identified in more than half of the relapses in the study's series. The subgroup of relapses (without identified causes), as well as the onsets of the disease, showed a significant seasonal variation with a peak in spring-summer; however, the seasonal variable did not justify the total group of relapses. Although the seasonal variation may be caused by a combination of factors, UV radiation should be considered a trigger factor for the peaks in spring-summer, particularly in Turkey.
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Humanos , Neoplasias Cutâneas/diagnóstico por imagem , Acantoma/diagnóstico por imagem , DermoscopiaRESUMO
BACKGROUND: Pemphigus foliaceus is exceedingly rare around the world, except within the few regions where it occurs as an endemic variant. Various factors can trigger immune mechanisms that induce pemphigus foliaceus or worsen its course. OBJECTIVE: To determine the demographic and clinical characteristics of the patients with pemphigus foliaceus in a large series from a non-endemic country, investigate the triggering factors, and seasonal patterns. METHODS: The data of the patients diagnosed with pemphigus foliaceus in the study's center between 1989-2018 were retrospectively analyzed. RESULTS: Sixty-eight patients (mean age, 45.7 ± 14.5 years) were included in the study. The number of onsets reached its peak in spring-summer (p = 0.008). A total of 117 relapses occurred in 42 patients and were most common in spring-summer (not significant). Specific trigger factors were detected in 45 relapses. In the other 72 relapses, the peak was observed in spring-summer (p = 0.005). There were no significant differences in the demographic and clinical variables investigated between relapsed and non-relapsed patients. STUDY LIMITATIONS: Retrospective design. CONCLUSIONS: Triggering factors could not be identified in more than half of the relapses in the study's series. The subgroup of relapses (without identified causes), as well as the onsets of the disease, showed a significant seasonal variation with a peak in spring-summer; however, the seasonal variable did not justify the total group of relapses. Although the seasonal variation may be caused by a combination of factors, UV radiation should be considered a trigger factor for the peaks in spring-summer, particularly in Turkey.
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Pênfigo , Adulto , Humanos , Pessoa de Meia-Idade , Pênfigo/epidemiologia , Recidiva , Estudos Retrospectivos , Estações do Ano , Turquia/epidemiologiaRESUMO
Pemphigus foliaceus (PF) is an autoimmune blistering disease of the skin, clinically characterized by erosions and, histopathologically, by acantholysis. PF is endemic in the Brazilian Central-Western region. Numerous single nucleotide polymorphisms (SNPs) have been shown to affect the susceptibility for PF, including SNPs at long non-coding RNA (lncRNA) genes, which are known to participate in many physiological and pathogenic processes, such as autoimmunity. Here, we investigated whether the genetic variation of immune-related lncRNA genes affects the risk for endemic and sporadic forms of PF. We analysed 692 novel SNPs for PF from 135 immune-related lncRNA genes in 227 endemic PF patients and 194 controls. The SNPs were genotyped by Illumina microarray and analysed by applying logistic regression at additive model, with correction for sex and population structure. Six associated SNPs were also evaluated in an independent German cohort of 76 sporadic PF patients and 150 controls. Further, we measured the expression levels of two associated lncRNA genes (LINC-PINT and LY86-AS1) by quantitative PCR, stratified by genotypes, in peripheral blood mononuclear cells of healthy subjects. We found 27 SNPs in 11 lncRNA genes associated with endemic PF (p < .05 without overlapping with protein-coding genes). Among them, the LINC-PINT SNP rs10228040*A (OR = 1.47, p = .012) was also associated with increased susceptibility for sporadic PF (OR = 2.28, p = .002). Moreover, the A+ carriers of LY86-AS1*rs12192707 mark lowest LY86-AS1 RNA levels, which might be associated with a decreasing autoimmune response. Our results suggest a critical role of lncRNA variants in immunopathogenesis of both PF endemic and sporadic forms.
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Antígenos de Superfície/genética , Pênfigo/genética , Polimorfismo de Nucleotídeo Único/genética , RNA Longo não Codificante/genética , Antígenos de Superfície/imunologia , Predisposição Genética para Doença , Humanos , Pênfigo/imunologia , Polimorfismo de Nucleotídeo Único/imunologia , RNA Longo não Codificante/imunologiaRESUMO
Pemphigus foliaceus (PF) is an autoimmune blistering skin disease characterized by the presence of pathogenic autoantibodies against desmoglein 1, a component of intercellular desmosome junctions. PF occurs sporadically across the globe and is endemic in some Brazilian regions. Because PF is a B-cell-mediated disease, we aimed to study the impact of variants within genes encoding molecules involved in the different steps of B-cell development and antibody production on the susceptibility of endemic PF. We analysed 3,336 single nucleotide polymorphisms (SNPs) from 167 candidate genes genotyped with Illumina microarray in a cohort of 227 PF patients and 193 controls. After quality control and exclusion of non-informative and redundant SNPs, 607 variants in 149 genes remained in the logistic regression analysis, in which sex and ancestry were included as covariates. Our results revealed 10 SNPs within or nearby 11 genes that were associated with susceptibility to endemic PF (OR >1.56; p < 0.005): rs6657275*G (TGFB2); rs1818545*A (RAG1/RAG2/IFTAP);rs10781530*A (PAXX), rs10870140*G and rs10781522*A (TRAF2); rs535068*A (TNFRSF1B); rs324011*A (STAT6);rs6432018*C (YWHAQ); rs17149161*C (YWHAG); and rs2070729*C (IRF1). Interestingly, these SNPs have been previously associated with differential gene expression, mostly in peripheral blood, in publicly available databases. For the first time, we show that polymorphisms in genes involved in B-cell development and antibody production confer differential susceptibility to endemic PF, and therefore are candidates for possible functional studies to understand immunoglobulin gene rearrangement and its impact on diseases.
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Formação de Anticorpos/genética , Formação de Anticorpos/imunologia , Linfócitos B/imunologia , Pênfigo/genética , Pênfigo/imunologia , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/genética , Autoanticorpos/imunologia , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Brasil , Estudos de Casos e Controles , Criança , Estudos de Coortes , Feminino , Expressão Gênica/genética , Expressão Gênica/imunologia , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/imunologia , Adulto JovemRESUMO
Pemphigus foliaceus is an autoimmune disease that is sporadic around the world but endemic in Brazil, where it is known as fogo selvagem (FS). Characterized by autoantibodies against the desmosomal cadherin desmoglein 1, FS causes painful erosions, and crusts that may be widespread. The recognition of antigens, including exposed sugar moieties, activates the complement system. Complement receptor 1 (CR1, CD35), which is responsible for the Knops blood group on erythrocytes (York and McCoy antigens), is also expressed by antigen-presenting cells. This regulates the complement system by removing opsonized antigens, blocking the final steps of the complement cascade. Membrane-bound CR1 also fosters antigen presentation to B cells, whereas soluble CR1 has anti-inflammatory properties. CR1 gene polymorphisms have been associated with susceptibility to complex diseases. In order to investigate the association of CR1 polymorphisms with FS susceptibility, we developed a multiplex sequence-specific assay to haplotype eleven polymorphisms in up to 367 FS patients and 242 controls from an endemic area and 289 from a non-endemic area. We also measured soluble CR1 (sCR1) in the serum of 53 FS patients and 27 controls and mRNA levels in the peripheral blood mononuclear cells of 63 genotyped controls. The haplotypes CR1*3B2B (with the York antigen-encoded by p.1408Met) and CR1*3A2A (with p.1208Arg) were associated with protection against FS (OR = 0.57, P = 0.027, and OR = 0.46, P = 0.014, respectively). In contrast, the CR1*1 haplotype (with the McCoy antigen - encoded by p.1590Glu) was associated with FS susceptibility (OR = 4.97, P < 0.001). Heterozygote rs12034383*A/G individuals presented higher mRNA expression than homozygotes with the G allele (P = 0.04). The lowest sCR1 levels occurred in patients with active disease before treatment (P = 0.036). Patients in remission had higher levels of sCR1 than did healthy controls (P = 0.013). Among those under treatment, patients with localized lesions also presented higher sCR1 levels than those with generalized lesions (P = 0.0073). In conclusion, the Knops blood group seems to modulate susceptibility to the disease. Furthermore, corticosteroid treatment might increase sCR1 serum levels, and higher levels may play an anti-inflammatory role in patients with FS, limiting the distribution of lesions. Based on these results, we suggest CR1 as a potential new therapeutic target for the treatment of FS.
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Pênfigo/sangue , Pênfigo/etiologia , Polimorfismo Genético , Receptores de Complemento 3b/sangue , Receptores de Complemento 3b/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Biomarcadores , Estudos de Casos e Controles , Suscetibilidade a Doenças , Feminino , Loci Gênicos , Predisposição Genética para Doença , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Pênfigo/diagnóstico , Filogenia , RNA Mensageiro/genética , Adulto JovemRESUMO
BACKGROUND: El Bagre endemic pemphigus foliaceus (El Bagre-EPF) is a new variant of endemic pemphigus foliaceus present in the El Bagre area of Colombia, South America. Here, we investigate the presence of complement/C5-b9 in lesional skin of patients and matched controls from the endemic area. We also aim to compare the patient's autoantibody levels using indirect immunofluorescent titers (IIF) and correlate with the lesional presence of complement/C5b-9. METHODS: A case-control study was carried out by testing for the presence of complement/C5b-9 in lesional skin in 43 patients affected by El Bagre-EPF, as well as 43 matched, healthy controls from the endemic area. Skin biopsies were obtained and evaluated via hematoxylin and eosin staining, and immunohistochemistry. RESULTS: The presence of complement/C5b-9 was observed in all cases of the patients affected by El Bagre-EPF and was not observed in the controls from the endemic area (P < 0.001). The patients' autoantibody titers utilizing IIF for IgG and IgM showed correlation between higher autoantibody titers and stronger intensity of staining with complement/C5-b9 staining (P < 0.001). CONCLUSION: Patients affected by El Bagre-EPF have lesional deposition of complement/C5b, which correlates with disease severity and previously established serologies.
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Proteínas do Sistema Complemento/imunologia , Pênfigo/imunologia , Pênfigo/patologia , Autoanticorpos/imunologia , Biópsia , Estudos de Casos e Controles , Colômbia/epidemiologia , Feminino , Humanos , Imuno-Histoquímica/instrumentação , Masculino , Pênfigo/epidemiologia , Índice de Gravidade de Doença , Pele/patologia , Dermatopatias/epidemiologia , Dermatopatias/imunologia , Dermatopatias/patologiaRESUMO
Fogo Selvagem (FS) is a rare autoimmune disease characterized by acantholysis and inflammation of the epidermis. It was evidenced in this disease the increase of proinflammatory cytokines levels which can be influenced by physical activities. Kinesiotherapy, as physiotherapeutic interventions, was associated improvement levels of the quality of live, mainly the pain. Understanding the impact of such methodology in immunology of the FS, may constitute an alternative and effective approach. We compare the levels of serum cytokines and chemokines between nine patients with FS submitted to kinesiotherapy for 12 weeks and ten patients not submitted to kinesiotherapy. The kinesiotherapy was composed by self-stretching followed by a resistance training for upper and lower limbs. The protocol was carried out in three sections of eight to ten repetitions with 70% of the maximum load measured by test maximum of ten repetitions. After strengthening period patients performed a passive stretching. The training sessions lasted 50 min and were performed 3 times a week at least 12 weeks. Cytokines and chemokines were assessed in plasma using enzyme-linked immunosorbent assay and/or cytometric bead array. Patients with FS were being kinesiotherapy presented minors levels of interferon-γ, interleukin (IL)-17, IL-22, and IL-15 when compared to those not submitted to kinesiotherapy. No differences were observed for the detection of the chemokines chemokine ligand (CCL)-2, CCL-3, CCL-5, CCL-11, C-X-C motif chemokine 8 (CXCL-8), and CXCL-10. These results suggest that kinesiotherapy had a positive impact on inflammatory markers that are associated with disease worsening in FS.
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Pemphigus foliaceus (PF) is an autoimmune disease of the skin and is the most common form of pemphigus in domestic animals. This work reports a case of pemphigus foliaceus in a Santa Inês hair sheep. The ewe presented with multifocal bilateral crusted alopecic dermatitis affecting the chest, abdomen, and pelvic and thoracic limbs. Parakeratotic hyperkeratosis and acanthosis, in addition to subcorneal pustules, were observed histologically, and acantholytic cells and neutrophils were observed within the pustules. In the superficial and deep dermal tissues, there was intense eosinophilic infiltration and the presence of rare macrophages. These microscopic findings were characteristic of PF, and treatment with dexamethasone was ineffective. This disease is rare in sheep, and this is the first case report to be published in Brazil.(AU)
Pênfigo foliáceo (PF) é uma doença autoimune da pele e é a forma mais comum de pênfigo em animaisdomésticos. Este trabalho relata um caso de pênfigo foliáceo em uma ovelha Santa Inês. A ovelhaapresentava dermatite alopécica crostosa bilateral e assimétrica no tórax, abdômen, e membros pélvicose torácicos. Hiperceratose paraqueratótica e acantose, além de pústulas subcorneais, foram observadoshistologicamente, e células acantolíticas e neutrófilos foram observadas dentro das pústulas. Naderme superficial e profunda, havia intenso infiltrado de eosinófilos e raros macrófagos. Os achadosmicroscópicos são característicos de PF, e o tratamento com dexametasona foi ineficiente. Esta doençaé rara em ovinos e este é o primeiro relato de caso a ser publicado no Brasil.(AU)
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Animais , Feminino , Pênfigo/veterinária , Ovinos , Alopecia/veterinária , Doenças Autoimunes/veterinária , Imuno-Histoquímica/veterinária , Dermatopatias/veterináriaRESUMO
Pemphigus foliaceus (PF) is a blistering autoimmune skin disease rare in most of the world but endemic in certain regions of Brazil. PF is characterized by the detachment of epidermal cells and the presence of autoantibodies against desmoglein 1. In previous studies, we have shown that genetic polymorphisms and variable expression levels of certain leucocyte receptor complex (LRC) genes were associated with PF. However, the role of the LRC on PF susceptibility remained to be investigated. Here, we analysed 527 tag single nucleotide polymorphisms (SNPs) distributed within the 1·5â Mb LRC. After quality control, a total of 176 SNPs were analysed in 229 patients with PF and 194 controls. Three SNPs were associated with differential susceptibility to PF. The intergenic variant rs465169 [odds ratio (OR)â =â 1·50; Pâ =â 0·004] is located in a region that might regulate several immune-related genes, including VSTM1, LILRB1/2, LAIR1/2, LILRA3/4 and LENG8. The rs35336528 (ORâ =â 3·44; Pâ =â 0·009) and rs1865097 (ORâ =â 0·57; Pâ =â 0·005) SNPs in LENG8 and FCAR genes, respectively, were also associated with PF. Moreover, we found four haplotypes with SNPs within the KIR3DL2/3, LAIR2 and LILRB1 genes associated with PF (Pâ <â 0·05), which corroborate previously reported associations. Thus, our results confirm the importance of the LRC for differential susceptibility to PF and reveal new markers that might influence expression levels of several LRC genes, as well as candidates for further functional studies.
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DNA Intergênico/genética , Genótipo , Leucócitos/fisiologia , Pênfigo/genética , Receptores Imunológicos/genética , Autoanticorpos/metabolismo , Brasil , Desmogleína 1/imunologia , Regulação da Expressão Gênica , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único , Análise Serial de TecidosRESUMO
Pemphigus foliaceus (PF) is an autoimmune disease of the skin and is the most common form of pemphigus in domestic animals. This work reports a case of pemphigus foliaceus in a Santa Inês hair sheep. The ewe presented with multifocal bilateral crusted alopecic dermatitis affecting the chest, abdomen, and pelvic and thoracic limbs. Parakeratotic hyperkeratosis and acanthosis, in addition to subcorneal pustules, were observed histologically, and acantholytic cells and neutrophils were observed within the pustules. In the superficial and deep dermal tissues, there was intense eosinophilic infiltration and the presence of rare macrophages. These microscopic findings were characteristic of PF, and treatment with dexamethasone was ineffective. This disease is rare in sheep, and this is the first case report to be published in Brazil.
Pemphigus foliaceus (PF) is an autoimmune disease of the skin and is the most common form of pemphigus in domestic animals. This work reports a case of pemphigus foliaceus in a Santa Inês hair sheep. The ewe presented with multifocal bilateral crusted alopecic dermatitis affecting the chest, abdomen, and pelvic and thoracic limbs. Parakeratotic hyperkeratosis and acanthosis, in addition to ballooning degeneration of keratinocytes and subcorneal pustules, were observed histologically, and acantholytic cells and neutrophils were observed within the pustules. In the superficial and deep dermal tissues, there was intense eosinophilic infiltration and the presence of rare macrophages. These microscopic findings were characteristic of PF, and treatment with dexamethasone was ineffective. This disease is rare in sheep, and this is the first case report to be published in Brazil.
RESUMO
Pemphigus foliaceus (PF) is an autoimmune disease of the skin and is the most common form of pemphigus in domestic animals. This work reports a case of pemphigus foliaceus in a Santa Inês hair sheep. The ewe presented with multifocal bilateral crusted alopecic dermatitis affecting the chest, abdomen, and pelvic and thoracic limbs. Parakeratotic hyperkeratosis and acanthosis, in addition to subcorneal pustules, were observed histologically, and acantholytic cells and neutrophils were observed within the pustules. In the superficial and deep dermal tissues, there was intense eosinophilic infiltration and the presence of rare macrophages. These microscopic findings were characteristic of PF, and treatment with dexamethasone was ineffective. This disease is rare in sheep, and this is the first case report to be published in Brazil.
Pemphigus foliaceus (PF) is an autoimmune disease of the skin and is the most common form of pemphigus in domestic animals. This work reports a case of pemphigus foliaceus in a Santa Inês hair sheep. The ewe presented with multifocal bilateral crusted alopecic dermatitis affecting the chest, abdomen, and pelvic and thoracic limbs. Parakeratotic hyperkeratosis and acanthosis, in addition to ballooning degeneration of keratinocytes and subcorneal pustules, were observed histologically, and acantholytic cells and neutrophils were observed within the pustules. In the superficial and deep dermal tissues, there was intense eosinophilic infiltration and the presence of rare macrophages. These microscopic findings were characteristic of PF, and treatment with dexamethasone was ineffective. This disease is rare in sheep, and this is the first case report to be published in Brazil.
RESUMO
Pemphigus foliaceus (PF) is the most common autoimmune skin disease in dogs. It is characterized by pustules, erosions, and crusts which occur due to the presence of autoantibodies that target intercellular adhesion. Histopathological examination is considered the gold standard pattern in the diagnosis, but may sometimes be inconclusive, especially when the characteristic findings are not identified. New diagnostic tests are continuously being developed and immunofluorescence assays, could be a valuable alternative diagnostic tool. This study aimed to evaluate the applicability of direct and indirect immunofluorescence (DIF and IIF) tests for the diagnosis of canine PF. Twenty eight dogs were divided into two groups: Group I with 14 dogs with PF and Group II (control) with 14 dogs with Superficial pyoderma (differential diagnoses of PF). All animals were submitted to skin biopsy to histopathological and DIF. Blood samples were collected to assess IIF. Comparing the DIF results against the histopathology test, there was an agreement of 75% (9/12) with a Kappa index of 0.77 (P<0.001). Considering IIF, the agreement was 100% (14/14), with a Kappa index of 1.0 (P<0.001). We conclude that DIF and IIF are highly effective and were useful and effective complementary examination tests for an improvement in the diagnosis of canine PF.(AU)
O pênfigo foliáceo (PF) é considerado uma das doenças tegumentares autoimunes mais frequentes em cães. Clinicamente, caracteriza-se pela presença de pústulas, erosões e crostas. O exame histopatológico é considerado o teste diagnóstico de eleição, porém pode se mostrar inconclusivo, sobretudo quando os achados característicos da doença não são observados. Novas ferramentas diagnósticas têm sido desenvolvidas e os testes de imunofluorecência são uma valiosa alternativa. Este estudo teve como objetivo avaliar a aplicabilidade das reações de imunofluorescência direta (IFD) e indireta (IFI) para o diagnóstico do PF canino. Vinte e oito cães foram divididos em dois grupos: grupo I com 14 cães com PF e grupo II (controle) com 14 cães com piodermite superficial (um dos principais diagnósticos diferenciais do PF). Todos os animais foram submetidos à biópsia cutânea, seguida de exame histopatológico e IFD. Amostras de sangue foram coletadas para realização da IFI. Comparando-se os valores de IFD com o histopatológico, obtiveram-se valores de concordância de 75% (9/12), com índice Kappa de 0,77 (P<0,001). Já na IFI, a concordância foi de 100% (14/14), com índice Kappa de 1,0 (P<0,001). Concluiu-se, então, que a IFD e a IFI apresentaram excelentes resultados e podem ser consideradas novas alternativas diagnósticas do PF canino.(AU)