Pemphigus vulgaris

Abstract: Pemphigus vulgaris is a chronic autoimmune bullous dermatosis that results from the production of autoantibodies against desmogleins 1 and 3. It is the most frequent and most severe form of pemphigus, occurring universally, usually between 40 and 60 years of age. It usually begins with blisters and erosions on the oral mucosa, followed by lesions on other mucous membranes and flaccid blisters on the skin, which can be disseminated. There is a clinical variant, pemphigus vegetans, which is characterized by the presence of vegetating lesions in the large folds of the skin. Clinical suspicion can be confirmed by cytological examination, histopathological examination, and direct and indirect immunofluorescence tests. The treatment is performed with systemic corticosteroids, and immunosuppressive drugs may be associated, among them azathioprine and mycophenolate mofetil. More severe cases may benefit from corticosteroids in the form of intravenous pulse therapy, and recent studies have shown a beneficial effect of rituximab, an anti-CD20 immunobiological drug. It is a chronic disease with mortality around 10%, and septicemia is the main cause of death. Patients need long-term and multidisciplinary follow-up.

Desmoglein 4 gene mutation analysis in a pedigree with autosomal recessive hereditary monilethrix / 中华皮肤科杂志

A 3-year-old female proband presented with patchy follicular keratotic papules on the hairless scalp after birth. At about the age of 2 years, sparse hairs of non-uniform thickness began to grow, but they fell out intermittently and were broken easily. Some eyebrows and eyelashes of different lengths fell out or were broken. Physical examination revealed good condition of nutrition, normal height, weight and intelligence, with no obvious abnormalities in other systems. Skin examination showed sparse and broken hairs with follicular keratotic papules on the vertex and occiput. Teeth, nails, toenails and sweat glands were normal. Dermoscopy, optical microscopy and scanning electron microscopy all showed that affected hairs gave a beaded appearance. Gene sequencing showed that the proband carried heterozygous deletions of exons 2-16 in the desmoglein 4 (DSG4) gene, and a heterozygous mutation c.574T>C (p.S192p) (NM-177986) in the DSG4 gene, which were inherited from her father and mother respectively. None of the above mutations in the DSG4 gene were found in 100 healthy controls. According to the gene sequencing results and clinical phenotype, the patient was finally diagnosed with autosomal recessive hereditary monilethrix, and the c.574T>C mutation and heterozygous deletions of exons 2-16 of the DSG4 gene may contribute to autosomal recessive hereditary monilethrix in the child.

Desmoglein 4 gene mutation analysis in a pedigree with autosomal recessive hereditary monilethrix / 中华皮肤科杂志

A 3-year-old female proband presented with patchy follicular keratotic papules on the hairless scalp after birth.At about the age of 2 years,sparse hairs of non-uniform thickness began to grow,but they fell out intermittently and were broken easily.Some eyebrows and eyelashes of different lengths fell out or were broken.Physical examination revealed good condition of nutrition,normal height,weight and intelligence,with no obvious abnormalities in other systems.Skin examination showed sparse and broken hairs with follicular keratotic papules on the vertex and occiput.Teeth,nails,toenails and sweat glands were normal.Dermoscopy,optical microscopy and scanning electron microscopy all showed that affected hairs gave a beaded appearance.Gene sequencing showed that the proband carried heterozygous deletions of exons 2-16 in the desmoglein 4 (DSG4) gene,and a heterozygous mutation c.574T＞C(p.S192p)(NM-177986) in the DSG4 gene,which were inherited from her father and mother respectively.None of theabove mutations in the DSG4 gene were found in 100 healthy controls.According to the gene sequencing results and clinical phenotype,the patient was finally diagnosed with autosomal recessive hereditary monilethrix,and the c.574T ＞ C mutation and heterozygous deletions of exons 2-16 of the DSG4 gene may contribute to autosomal recessive hereditary monilethrix in the child.

Blistering mucocutaneous disease of oral cavity Pemphigus vulgaris 8 year study in Nalgonda population

Background: Autoimmune disorders are conditions in which autoantibodies are directed against a single organ or tissue resulting in localized tissue damage. Pemphigus includes a group of autoimmune blistering diseases of skin and mucous membranes characterized by intra dermal blisters and immunologically by finding of circulating immunoglobulin G antibody directed against the cell surface of keratinocytes. Objectives: To analyze age distribution of Pemphigus vulgaris, prevalence among males and females, predominant oral site and clinical presentation. Materials and methods: A retrospective study of 31 cases of Pemphigus vulgaris obtained over a period of 8 years from January 2008 to September 2015 in the Department of Oral Pathology, Kamineni Institute of Dental Sciences was designed. Clinical details of age, sex, intraoral distribution and oral presentation were noted. P Pavan, T Madhusudan Rao, Pavan G Kulkarni, SRK Nandan, Shyam Prasad Reddy, M Keerthi. Blistering mucocutaneous disease of oral cavity Pemphigus vulgaris – 8 year study in Nalgonda population. IAIM, 2017; 4(1): 58-63. Page 59 Results: Age distribution of Pemphigus vulgaris was 30 – 70 years with a mean age of 49.12 years. Mean age of presentation in males was 45.5 years and in females 46.76 years. Females are more commonly affected than males with a ratio of 2:1. Most commonly affected sites were buccal mucosa, lips and palate, tongue, floor of mouth and skin. Erosions and encrustations were the most common clinical presentation. Conclusion: Pemphigus vulgaris is a fatal disease if left untreated. The skin and the mucosa are majorly involved and oral mucosa is often affected first. The study elucidates the characterization of Pemphigus vulgaris so that early diagnosis can be made. As oral lesions precede, oral health care professionals can play a major role in early diagnosis and managing oral lesions.

Pénfigo vulgar oral: reporte de un caso clínico / Oral penphigus vulgaris: report of a clinical case

El pénfigo vulgar es el tipo más común de un grupo padecimientos crónicos autoinmunes identificados por la presencia de lesiones ampulosas situadas en las mucosas y piel. El pénfigo vulgar oral (PVO) se caracteriza por la presencia de ampollas localizadas en las encías, paladar blando, carrillos, pero cualquier sitio de la cavidad oral puede ser afectado. Estas lesiones se presentan primero en la cavidad oral y meses después en la piel, por lo que su diagnóstico temprano y oportuno es vital para el pronóstico. El propósito de este trabajo es presentar esta condición clínica en una persona adulta mayor.

Pemphigus vulgaris is the most common of a group of chronic autoim-mune conditions characterized by the presence of mucosal and dermal blisters. In the case of oral pemphigus vulgaris (OPV), these are typi-cally found on the gums, soft palate, and cheeks, though anywhere in the oral cavity can be affected. These lesions appear first in the oral cavity and then, months later, on the skin. Therefore, early diagnosis is crucial for prognosis. The aim of this paper is to present a case report of this condition in an older adul.

Fluctuations in anti-desmoglein antibody levels and their relationship with disease activity in patients with pemphigus / 中华皮肤科杂志

Objective To investigate the relationship between disease severity and enzyme-linked immunosorbent assay (ELISA) index values of anti-desmoglein (Dsg) 1 and-Dsg3 antibodies in 56 patients with pemphigus,and to characterize fluctuations in anti-Dsg1 and-Dsg3 antibodies in different forms of pemphigus.Methods Fifty-six patients with pemphigus (including 36 cases of pemphigus vulgaris (PV) and 20 cases of pemphigus foliaceus (PF)) were enrolled in this study.Blood samples were obtained from these patients before treatment and at the following four time points:when the condition was relieved and the taper of glucocorticoids began,the dose of glucocorticoids was tapered to half of their initial dose,the maintenance treatment started,and when the duration of maintenance treatment reached two years.ELISA was performed to determine the levels of anti-Dsg1 and-Dsg3 antibodies in these serum samples.Spearman correlation analysis was carried out to assess the relationship between disease severity and ELISA index values,and independent sample's t test to compare the levels of anti-Dsg antibodies among these time points.Results The severity of pemphigus was correlated with anti-Dsg antibody ELISA index values.Both anti-Dsg1 and anti-Dsg3 ELISA index values were significantly reduced at the remission of pemphigus compared with those before treatment (all P ＜ 0.01).At the end of the two-year maintenance treatment,10 (50％) patients with PF and 7 (19.4％) patients with PV became negative for anti-Dsg1 ELISA,whereas only 1 (2.7％) patient with PV became negative for anti-Dsg3 ELISA.Conclusions Anti-Dsg antibody ELISA index value is correlated with disease severity in patients with pemphigus,which may serve as a useful marker for assessing disease severity and activity as well as evaluating therapeutic efficacy.

Severe Multi-Resistant Pemphigus vulgaris: prolonged remission with a single cycle of Rituximab / Penfigo vulgar grave Multirresistente: controle prolongado com um unico ciclo de Rituximabe

Pemphigus vulgaris is an autoimmune bullous disease whose therapy is based on systemic corticosteroids, with or without immunosuppressants. Rituximab is a chimeric monoclonal antibody of the IgG class, directed at a specific CD20 B cell surface antigen, used in pemphigus vulgaris empirically since 2002, with success in 90% of the cases and long periods of remission. Male patient, 33 years old, diagnosed with pemphigus vulgaris, confirmed by histopathology and direct immunofluorescence. He was treated for seven months with numerous treatments, including immunosuppressive drugs, with an unsatisfactory response, until he had complete remission with the use of rituximab. During a 34-month follow-up period, the patient presented a slight clinical relapse, which was successfully controlled with prednisone in a daily dose of 120mg, soon reduced to 20mg.

Pênfigo Vulgar é uma doença bolhosa auto-imune, cuja terapêutica é baseada em corticoesteróides sistêmicos, associados ou não a imunossupressores. Rituximabe é um anticorpo monoclonal quimérico da classe IgG direcionado a um antígeno CD20 de superfície celular específico da célula B, usado em pênfigo vulgar desde 2002, com sucesso em 90% e longos períodos de remissão. Paciente masculino, 33 anos, diagnóstico de pênfigo vulgar, confirmado por histopatologia e imunofluorescência direta. Durante 7 meses, recebeu inúmeros tratamentos com imunossupressores, apresentando resposta insatisfatória e progressão da doença, até que logo após a introdução de rituximabe teve completa remissão. Durante um acompanhamento de 34 meses, apresentou leve recidiva clínica, controlada com prednisona 120mg/dia, rapidamente reduzida e em uso atual de Prednisona 20mg/dia.

Pénfigo vulgar tipo cutáneo: Caso clínico / Cutaneous pemphigus vulgaris: A case report

Pemphigus is an autoimmune bullous disease that involves skin and mucous membranes caused by autoantibodies against antigens on the surface of keratinocytes. We report a 30-year-old mole presenting with a five months history of pruriginous alopecic and crusted lesions in the scalp, that extended posteriorly to the trunk and limbs. Mucous membranes were not involved. A skin biopsy was performed, showing extensive loss of epidermis and acantholysis. Immuno fluorescence waspositivefor C3 and intercellular and epidermic IgG. With the presumptive diagnosis of pemphigus vulgaris (PV) without mucous involvement, thepatient was treated with prednisone, observing an excellent clinical response. There are only few cases published in the literature of PV without mucous involvement. Some authors refer to this subtype of PV as "Cutaneous pemphigus vulgaris".

Pénfigo: análisis clínico y serológico en 26 pacientes / Pemphigus: clinical and serological analysis in 26 patients

En la actualidad, para diagnosticar pénfigo, es necesaria una clínica con ampollas y erosiones, histopatología con acantólisis y detección de anticuerpos en la piel afectada (inmunofluorescencia directa) o en sangre circulante (inmunofluorescencia indirecta). Objetivos: Los objetivos del trabajo son comparar la sensibilidad y especificidad de estas dos últimas técnicas y demostrar si existe relación de los niveles de ELISA frente a desmogleínas con elgrado de afectación cutáneo-mucoso. Material y métodos: Se obtuvieron 117 determinaciones en 26 pacientes con pénfigo y 29 determinaciones en pacientes con otras enfermedades ampollosas como grupo control. Medimos anticuerpos antisustancia intercelular por inmunofluorescencia indirecta y anticuerpos antidesmogleína 1 y 3 por ELISA. También se midieron las cifras de anticuerpos antes y después de terapias como las inmunoglobulinas intravenosas y plasmaféresis. Resultados: La determinación de anticuerpos por ELISA frentea desmogleínas 1 y 3 es más sensible que la inmunofluorescencia indirecta. No encontramos diferencias en cuanto a especificidad. Los niveles de anticuerpos son paralelos a la actividad clínica. Estos niveles no descienden inmediatamente tras la terapia con inmunoglobulinas intravenosas.

Nowadays diagnostic criteria of pemphigus include:clinical presentation with blisters and erosions, acantholisison the conventional histopathological examinationand detection of antibodies on affected skin (directimmunofluorescence) or serum (indirect immunofluorescence). Objective: The aims of this study are to compare sensibility and specificity between the ELISA method and the indirect immunofluorescence test (IIF)and to investigate a possible correlation between desmoglein titers (detected by ELISA) and clinical severity. Materials and methods: 26 patients with pemphigus were included in the study. The control group included 29patients with other bullous diseases. In every patient, antiintercellular substance antibodies were detected by the indirect immunofluorescence test while anti-desmoglein1 and 3 antibodies were titered by ELISA. In addition, titers of antibodies were measured before and aftertherapy with intravenous immunoglobulins and plasmapheresis. 117 determinations were obtained frompatients with pemphigus and 29 from the control group.Results: ELISA detection of antibodies against desmoglein1 and desmoglein 3 is a more sensitive method than the indirect immunofluorescence test. No difference inspecificity has been found. There is a positive correlation between titers of antibodies and clinical activity. Intravenous immunoglobulin therapy does not induceimmediate tapering of antibody titers.

Significado do epitope spreading na patogênese dos pênfigos vulgar e foliáceo / Significance of epitope spreading in the pathogenesis of pemphigus vulgaris and foliaceus

Os pênfigos são dermatoses bolhosas auto-imunes, em que há a produção de auto-anticorpos direcionados contra moléculas de adesão dos epitélios, levando à perda da coesão celular. A produção de auto-anticorpos ocorre quando os pacientes desenvolvem um desequilíbrio da resposta imune (quebra da tolerância imunológica), passando a reconhecer antígenos próprios. A resposta é geralmente direcionada contra um único epítopo alvo; entretanto, como conseqüência da resposta inflamatória do processo primário e do extenso dano tecidual ocasionado, pode haver exposição de componentes protéicos ocultos, levando à produção de diferentes auto-anticorpos. Assim, é possível que surja uma nova doença cutânea auto-imune, em decorrência do fenômeno intra ou intermolecular de epitope spreading. São revistos os principais conceitos desse fenômeno e sua ocorrência nas dermatoses bolhosas auto-imunes, com ênfase nos pênfigos, grupo de dermatoses bolhosas autoimunes mais prevalente no Brasil.

Pemphigus comprises autoimmune blistering skin diseases in which autoantibodies directed against antigens (epithelial adhesion molecules) are found, leading to loss of cell cohesion. The production of autoantibodies occurs due to an immune imbalance (break of immune tolerance) driving to recognition of self- antigens. The response is usually directed against an exclusive target epitope; however, due to the inflammatory response and to the extensive tissue damage, it is possible that the exposure of hidden protein components leads to distinct autoantibody production. Hence, a new autoimmune disease may occur in consequence of an intra- or intermolecular epitope spreading phenomenon. The authors review the main concepts of this phenomenon, and its occurrence in autoimmune blistering diseases, with emphasis on pemphigus, the most prevalent disease of this group in our country.