Clinical and serological follow-up studies of endemic pemphigus foliaceus (fogo selvagem) in Western Parana, Brazil (2001-2002)

BACKGROUND: Fogo selvagem (FS) has been described in several regions of Brazil, including the Western regions of the state of Parana. In 1990, Empinotti et al. reported case studies of 213 patients with FS that were collected from 1976 to 1988. The same author (J.C.E.) has observed that the frequency of cases in these regions of Parana has decreased. OBJECTIVES: The purpose of this study was to clinically and serologically evaluate a small group of the patients originally reported in 1990 and compare data with a group of control individuals. These patients were treated at the onset of the disease with systemic steroids. PATIENTS AND METHODS: Patients with FS, their unaffected relatives (n = 80) and genetically unrelated controls (n = 15) were identified during a field study from 1 May 2001 to 30 June 2002. Sera from nine patients with FS and six normal controls that were collected in the 1976-1988 evaluation were available for this study. The sera were tested by indirect immunofluorescence, enzyme-linked immunosorbent assay (ELISA) and immunoprecipitation using recombinant human desmoglein 1 (Dsg1). RESULTS: Only 16 of the originally identified 213 patients with FS were found during the field studies. Thirteen of the 16 patients were in clinical and serological remission; 20% of normal controls (19 of 95) were positive in the Dsg1 ELISA. The majority of these subjects (17 of 19) were genetically related to FS patients. Six normal controls that were positive in the Dsg1 ELISA in the original survey were found to be negative or weakly positive in this evaluation. CONCLUSION: The reduced frequency of positive serological markers of disease in patients and normal controls from Western Parana, as well as the absence of recurrent disease in previously identified patients, suggest that environmental antigenic stimulation of the population at risk may have decreased in recent years.     

Serologic abnormalities in patients with endemic pemphigus foliaceus (Fogo selvagem), their relatives, and normal donors from endemic and non-endemic areas of Brazil

Based on epidemiologic data, a current hypothesis states that Fogo selvagem (FS) may be triggered by environmental factors present in endemic areas of Brazil. Because the appearance of new cases is limited to those areas, we wanted to ascertain if the presence of the pemphigus autoantibodies was restricted to the patients. To further delineate the restriction of the autoantibody response in these patients we also investigated the presence of lupus-associated autoantibodies. Using indirect immunofluorescence (IF) we tested the sera of patients with FS (n = 196), their relatives (n = 138), their cohabitants (n = 13), and normal donors from endemic (n = 38) and non-endemic areas (n = 44) for pemphigus autoantibodies. Antinuclear antibodies (ANA) and anti-nDNA antibodies were determined by indirect IF against Hep-2 cells and Crithidia lucilliae, respectively. Autoantibodies against nRNP, Ro/SSA, La/SSB, and Sm were assayed by double immune diffusion in agarose gels. FS autoantibodies were present in the sera of all patients with active disease (n = 196, 100%, titers greater than 40 to 2560), but were not found in any sera from normal individuals in endemic or non-endemic areas. The titer of the FS autoantibody showed a rough correlation with the extent and activity of the disease. Furthermore, lupus-associated autoantibodies were not present in any of the tested samples. We conclude the FS antiepidermal autoantibodies are specific serologic markers of the disease and are not present in unaffected individual from the endemic areas. As such, they provide an important marker that should be useful in ongoing epidemiologic studies aimed at identifying putative etiologic agent(s).     

Prevalence of anti-desmoglein-3 antibodies in endemic regions of Fogo selvagem in Brazil

Fogo selvagem (FS), the endemic form of pemphigus foliaceus (PF), is an autoimmune blistering disease characterized by autoantibodies against desmoglein 1. The Terena reservation of Limao Verde in Mato Grosso do Sul, Brazil, is a previously identified focus of disease. Autoantibodies against desmoglein 3 (Dsg3) have also been detected in sera from patients with FS. In an effort to further characterize the serological, geographical, and clinical epidemiology of the disease, we sought to determine the prevalence of anti-Dsg3 autoantibodies in sera from normal subjects living outside of and in an endemic area using an ELISA. Anti-Dsg3 antibodies were detected in 53 of 146 normal subjects from Limao Verde (36%), and in eight of 140 normal subjects from surrounding areas (6%). A significant trend was observed in the proportion of positive tests relative to distance from the endemic area (P < 0.001). Our seroepidemiological observations support the concept that the likely environmental trigger of the antibody response in FS is located in this endemic area, and that the population at risk to develop FS may also be at risk to develop an endemic form of pemphigus vulgaris as reported by our co-investigators from Brasilia.     

Pregnant women with endemic pemphigus foliaceus (Fogo Selvagem) give birth to disease-free babies.

Endemic pemphigus foliaceus (PF), also known as Fogo Selvagem (FS), is an organ-specific autoimmune disease mediated by autoantibodies. These autoantibodies are disease specific, predominantly restricted to the IgG4 subclass, and pathogenic, as demonstrated by passive transfer studies. In contrast to pemphigus vulgaris, neonatal skin disease does not appear to occur in babies born to mothers with non-endemic PF or FS. In the present study we have examined 19 mother/neonate pairs where the mother had documented FS. Mothers and neonates were examined soon after delivery and tested by immunofluorescent (IF) techniques for FS autoantibodies either in circulation (mothers' sera or babies' cord blood) or bound to the neonatal epidermis. All neonates included in this study were born with normal skin. Twelve biopsies from 17 neonates showed negative direct IF using both FITC-antihuman IgG or monoclonal anti-IgG subclass antibodies. In five biopsies the epidermal ICS of the babies showed weak staining. In 10 of the 19 cord sera tested, FS IgG autoantibodies were undetectable; in nine, these autoantibodies were present in low titers (less than 1:40). The sera of the mothers showed higher titers of FS autoantibodies, and IgG4 was the predominant IgG subclass autoantibodies. It appears that human placenta may modulate the expression of disease in the newborn by operating as a "biologic immunoadsorbent" of pathogenic autoantibodies.     

Pmphigus in Mali: a study of 30 cases

Summary Pemphigus has been largely studied in developed countries (North America and Europe) and in Brazil. In these geographical settings, pemphigus presents two very different epidemiological and clinical patterns. Little is known about pemphigus in other regions of the world, particularly in Africa. We report here a study of 30 cases of pemphigus observed in Bamako, Mali. Our data suggest that pemphigus in this area presents a distinctive pattern. Our cases of pemphigus were diagnosed on the basis of clinical, histological and direct immunofluorescence studies. We estimated the annual incidence in the Bamako region to be 0.29 cases per 100,000 inhabitants. There was no endemic focus in Mali. The disease was observed mainly in women (24 of 30; 80%), especially those older than 40 years (mean age, 46.7 years), and in the Fulani ethnic group (10 of 30; 33%). Our study group was composed of 25 cases of pemphigus foliaceus (PF) (83%), four cases of pemphigus vulgaris and one case of pemphigus vegetans. Pustules with hypopyon were observed in 11 patients (37%). A diffuse verrucous change in the skin was noted in four cases of erythrodermic PF. In 16 patients with PF, localized verrucous lesions mimicking seborrhoeic keratoses were observed when oral corticosteroid treatment was decreased. Histopathological examination demonstrated eosinophilic spongiosis in 50% of patients.
These data suggest that pemphigus in Mali differs from the two main known patterns of the disease; the North American/European one, and the Brazilian pattern, with which it shares the predominance of superficial forms but otherwise differs in many features.     

Simultaneous occurrence of herpetiform pemphigus and endemic pemphigus foliaceus (fogo selvagem)

A 32–year-old woman from Franco da Rocha, one of the last endemic areas of pemphigus foliaceus (fogo selvagem, FS) in the state of Sao Paulo, Brazil,'² developed generalized FS based on clinical (see Fig. 1), histologic and immunologic criteria.³ She had subcorneal vesicles with acantholytic cells histologically, circulating intercellular immunoglobulin G (IgG) autoantibodies at a titer of 640, and deposits of IgG in epidermal intercellular spaces. Her sister also had FS. The course of the disease was chronic with periods of remission and relapses. Six years later, she developed pruritic erythematous edematous plaques with overlying vesicles and blisters in a herpetiform pattern on the abdomen and forearm (Fig. 2) that resembled lesions of dermatitis herpetiformis. The lesions disappeared with prednisone 40 mg/day. Five years later, while affected with typical lesions of FS, she developed intensely pruritic erythematous urticarial edematous plaques (Fig. 3), some of which were covered with vesicles typical of herpetiform pemphigus (HP) (Fig. 4). Histologically these lesions showed epidermal spongiosis, with eosinophilic exocytosis and acantholysis (Fig. 5). Direct immunofluorescence (DIF) was positive for granular intercellular deposits of IgG and C3 in the epidermis (Fig. 6). IgA Studies were negative. Circulating Intercellular IgG autoantibodies were present at a titer of 80. By immunoblotting, the sera reacted to a 160 kD antigen which co-migrated with desmoglein–1 detected by monoclonal antibody (AE 23) (kindly provided by Dr. Tung-Tien Sun, New York University Medical Center, New York) and by pemphigus foliaceus sera (Fig. 7). Thus, after 12 years of FS, the patient developed a mixed bullous disease with concomitant clinical and laboratory features typical of HP and FS.     

107例天疱疮回顾性研究

通过回顾性分析107例天疱疮住院病例临床资料，研究其病情受控前的各项指标，发现病情的轻重是影响皮质类固醇（下称激素）初始量、激素减量前时间、减量前激素总量、最大控制量和激素总量等指标的重要因素；加用免疫抑制可减少激素用量；红斑型大疱疮和疱疹样天疱疮病情轻，容易控制。对其中的55例进行了随访，发现患者的死亡率与年龄、天疱疮类型和有无应用免疫抑制剂有关，缓解率与病情轻重、住院间最大控制量和天疱类型相关。     

Antigenic specificity of fogo selvagem autoantibodies is similar to North American pemphigus foliaceus and distinct from pemphigus vulgaris autoantibodies

Fogo selvagem (FS) is clinically, histologically, and immunopathologically similar to sporadic pemphigus foliaceus (PF, as seen in North America and Europe), although the epidemiology of these 2 diseases differs markedly. It has been proposed that FS is identical to PF but, for some reason, occurs in an endemic focus in central Brazil. If this hypothesis is correct, the autoantibodies in FS and PF should have similar antigenic specificities. We studied sera from 13 patients with FS from central Brazil, and compared them with 20 sera from patients with PF from the United States. All these sera had circulating antibodies that bound the cell surface of epithelial cells in identical patterns by indirect immunofluorescence on monkey esophagus or normal human skin. In immunoprecipitation studies none of the 13 FS sera precipitated the pemphigus vulgaris (PV) antigen from radiolabeled extracts of cultured human keratinocytes. This is similar to the findings with PF sera of which 19 of 20 sera did not react with PV antigen, but in sharp contrast to the results with PV sera which, as previously reported, all immunoprecipitate the PV antigen. Immunoblotting performed on extracts of normal human epidermis demonstrated that 7 of 20 PF sera specifically and intensely bound an approximately 160 kD polypeptide, previously identified as desmoglein I, a desmosomal glycoprotein. Similarly, 3 of 13 FS sera specifically bound a 160 kD polypeptide. Thirteen normal sera from North America, 8 normal and disease control sera from central Brazil, 11 PV sera, and 12 bullous pemphigoid sera did not specifically bind this polypeptide. Two-dimensional gel electrophoresis confirmed that the 160 kD polypeptides identified by the subgroup of PF and FS sera were identical. These studies demonstrate that, although the exact molecular specificities of the majority of PF and FS sera remain to be determined, FS autoantibodies do not bind the PV antigen and a subgroup of FS autoantibodies have molecular specificity identical to that of a subgroup of PF autoantibodies.     

Environmental risk factors in endemic pemphigus foliaceus (Fogo selvagem). "The Cooperative Group on Fogo Selvagem Research".

Endemic pemphigus foliaceus or Fogo selvagem (FS) is an epidermal organ-specific autoimmune disease mediated by autoantibodies. Individuals at risk are peasants who live and work on farms located in the interior of certain endemic states of Brazil. This case-control study compares a group of 52 FS patients with 52 patients suffering from other dermatoses admitted and followed at the hospital for pemphigus (Hospital do Penfigo) in the city of Goiania, state of Goias. Patients and controls matched 1:1 by age, sex, and occupation were examined by two dermatologists at the time of admission and asked to respond to a prepared questionnaire. This questionnaire concerned current and past (1 and 5 years) exposure to environmental risk factors. The following risk factors were assessed: black fly bites, presence of rodents at home, exposure to cereal dust, exposure to fumes or dust released by tree and shrub removal, and exposure to insecticides. Relative risks were estimated from tabulated data by the odds ratio and tested for significance by the chi-square test. The 95% confidence interval for the odds ratio was also calculated for each of the risk factors. The only risk factor showing an odds ratio significantly different from one was exposure to simuliidae bites (odds ratio 4.7, p less than 0.001). This study reinforces the hypothesis that chronic exposure to black fly antigens may precipitate IgG4 antibody formation in predisposed individuals. These antibodies in turn may cross-react with epidermal antigens and cause acantholysis and the clinical expression of the disease known as FS.     

Broad histopathologic patterns of non‐glabrous skin and glabrous skin from patients with a new variant of endemic pemphigus foliaceus‐part 1

A prospective, controlled epidemiologic survey performed in El Bagre, Colombia revealed a new variant of endemic pemphigus disease, occurring in a gold mining region. The disease resembled Senear‐Usher syndrome, and occurred in an endemic fashion. The aim of this study is to describe the most frequent histopathologic patterns in non‐glabrous skin and in glabrous skin observed in these patients, and their clinical correlation. The study was performed on non‐glabrous skin biopsies of 30 patients from the dominantly clinical affected areas (either on the chest, arms or face). Simultaneously, biopsies from the palms were obtained in 10 randomly chosen patients of the 30 total patients. The specimens were examined following hematoxylin and eosin (H&E) staining. The most common blisters observed were subcorneal, although in some cases intraspinous and subepidermal blisters were visualized. Our results showed a very heterogeneous pattern of histopathologic patterns in non‐glabrous skin, which seemed to correlate with the clinical features. The most common pattern was typical pemphigus foliaceus‐like, with some lupus erythematosus‐like features. A non‐specific, chronic dermatitis pattern prevailed in the clinically controlled patients taking daily corticosteroids. In the patients who have had the most severe and relapsing pemphigus, early sclerodermatous changes and scleredermoid alterations prevailed in their reticular dermis. In addition to the scleredermoid alterations, the reticular dermis showed a paucity of appendageal structures. On the contrary, in the palms, a similar pattern was seen in all cases, including thickening of the stratum corneum, hypergranulosis, edema in the papillary and reticular dermis and a dermal perivascular lymphocytic infiltrate. The direct immunofluorescence of the glabrous vs. the non‐glabrous skin also showed some differences. We conclude that the histopathologic features of this new variant of endemic pemphigus are complex, therefore, classical histopathologic features previously described for superficial, endemic pemphigus cannot be used alone to diagnose this disease. Howard MS, Yepes MM, Maldonado‐Estrada JG, Villa‐Robles E, Jaramillo A, Botero JH, Patiño PJ, Hashimoto T, Abreu‐Velez AM. Broad histopathologic patterns of non‐glabrous skin and glabrous skin from patients with a new variant of endemic pemphigus foliaceus‐part 1.     

Treatment of severe refractory pemphigus vulgaris with rituximab

Pemphigus vulgaris is a potentially fatal autoimmune bullous disease. High doses of immunosuppressive drugs are used in managing severe cases of pemphigus. Rituximab, an anti-CD20 monoclonal antibody, has proven to be effective in patients with refractory pemphigus vulgaris and pemphigus foliaceus. We review cases of pemphigus vulgaris and pemphigus foliaceus not associated with lymphoma that were treated with rituximab, and we report a new case of severe refractory pemphigus vulgaris successfully treated with rituximab.     

[开放获取] 米诺环素单药或联合小剂量糖皮质激素治疗红斑型天疱疮15例和疱疹样天疱疮9例疗效和安全性回顾分析

【摘要】 目的 探讨米诺环素单药或联合小剂量糖皮质激素（简称激素）治疗红斑型天疱疮（PE）和疱疹样天疱疮（PH）的疗效和安全性及对免疫指标的影响。方法 回顾性纳入2011年6月至2021年6月于北京大学第一医院皮肤科初诊、初治方案为米诺环素单独或联合小剂量激素且随访至少6个月的PE和PH患者。收集基线及不同随访时间点患者病情、自身抗体水平变化，分析疾病严重程度、诊断、自身抗体变化趋势及与疗效间的关系。采用Kaplan-Meier方法分析完全缓解情况，用卡方检验分析不同严重度和疗法下PF患者的疗效。结果 共纳入24例汉族患者，包括15例PE和9例PH，男女比例为1.4∶1，中位年龄68.8岁，中位病程为22.1个月，平均随访时间为21.8个月。24例均获得疾病控制，疾病控制时间M（Q1，Q3）为15.9（12，20.1）周。完全缓解23例 （95.8%），完全缓解时间8.7（6.4， 10）个月。米诺环素单药治疗1年完全缓解率（11/13）与联合小剂量激素疗法（9/11）差异无统计学意义（χ2 = 0.16，P = 0.692）。随访期间复发2例（8.7%），皆处于疾病控制状态，1例调整剂量后于第38周达完全缓解，另1例换用利妥昔单抗，半年后达到完全缓解。轻中度患者间疗效差异无统计学意义（χ2 = 0.28，P = 0.599）。3例发生药物相关不良反应，1例为背部体癣，2例为全身皮肤及牙龈部位色素沉着。结论 米诺环素单药或联合小剂量激素治疗轻中度PE或PH疗效显著，且无严重药物相关不良反应，但该方案的长期疗效、不良反应及患者预后需未来进一步扩大样本量，进行多中心、前瞻性研究。     

Drug-induced versus drug-triggered pemphigus

112 cases of induced pemphigus were reviewed. The causative drugs were divided into three groups according to their chemical structure, and the clinical, prognostic and laboratory characteristics were analyzed and compared. Our literature screening indicates that the biological progress and clinical course of the disease depend upon the type of the inducing/triggering drug in the majority of patients. Patients with penicillamine-induced pemphigus or with pemphigus induced by SH drugs (drugs containing a sulfhydryl radical) showed spontaneous recovery in 39.4 and 52.6%, respectively, once the drug was discontinued. Patients whose pemphigus was induced by other drugs showed spontaneous recovery in only 15% of the cases. These results indicate that in patients with pemphigus induced by penicillamine (or SH drugs), the drug plays a major role in the pathogenesis of the disease, as compared to patients with pemphigus induced by other drugs. It seems that penicillamine (and SH drugs) actually induces pemphigus in most of the cases, whereas other drugs only trigger the disease in patients with a previous predisposition.     

Comparison of desmoglein ELISA and indirect immunofluorescence using two substrates (monkey oesophagus and normal human skin) in the diagnosis of pemphigus

A prospective study was performed to assess the usefulness of desmoglein enzyme-linked immunosorbent assay testing compared with indirect immunofluorescence in the diagnosis of new cases of pemphigus, as well as to compare the relative sensitivities of monkey oesophagus and normal human skin as substrates for indirect immunofluorescence. These tests were performed on the sera of 29 consecutive new cases of pemphigus diagnosed over a 2-year period based on clinical, histological and direct immunofluorescence findings. Desmoglein enzyme-linked immunosorbent assay was positive in all patients whereas indirect immunofluorescence was positive in only 25 of 29 patients. All four patients with negative indirect immunofluorescence had positive antinuclear antibodies or cytoplasmic fluorescence that could have masked the anti-intercellular antibodies. Desmoglein enzyme-linked immunosorbent assay appeared to reflect the disease activity better than indirect immunofluorescence in a few patients who had active disease of recent onset. Monkey oesophagus was found to be superior or equal to human skin as a substrate for indirect immunofluorescence in both pemphigus vulgaris and foliaceus.     

Grading criteria for disease severity by pemphigus disease area index

Pemphigus is a group of autoimmune blistering diseases that affect the skin and mucous membranes. A reliable and accurate disease severity tool to assess pemphigus severity is crucial for managing pemphigus and for clinical trials. The purpose of this study was to compare the pemphigus disease area index activity score (PDAI), the Japanese pemphigus disease severity score (JPDSS) and the physician's subjective impression, and also to find appropriate severity grading cut‐offs for the PDAI. We also evaluated the correlation between PDAI activity score and the JPDSS. Thirty‐seven pemphigus patients and 110 assessments were analyzed in this study. The optimal points of pemphigus disease severity score in PDAI were: mild (0–8), moderate (9–24) and severe (≥25). In mild or moderate cases, the JPDSS was well correlated with the PDAI, but in severe cases the JPDSS reached a plateau at a PDAI score of approximately 30. The PDAI evaluates disease severity more accurately than the JPDSS, particularly in severe cases. The PDAI is not only a useful tool to measure the extent of cutaneous lesions, but also an excellent scoring system for evaluating pemphigus disease severity.     

The incidence of pemphigus in the southern region of Saudi Arabia

BACKGROUND: This is the first epidemiologic study of pemphigus in the southern region of Saudi Arabia. METHODS: Data were collected from patient records in the outpatient and inpatient departments of Asir Central Hospital during the period 1990-99. The diagnosis of pemphigus was based on the clinical, histopathologic, and direct immunofluorescence patterns which were consistent with pemphigus. RESULTS: The results showed that the mean incidence of the disease in the general population was 0.16/100 000; the mean incidence of the disease in the population above 20 years of age was 0.27/100 000. The prevalence of the disease at the end of the study period was 1.56/100 000 for the total population, and 2.7/100 000 for the population above 20 years of age. The male to female ratio was 2.2 : 1. The age of onset of the disease ranged from 23 to 67 years, except for one case at an age of 9 years, giving an average of 43.1 +/- 13.4 years and a median of 40 years. Pemphigus vulgaris was the most commonly encountered type, followed by pemphigus erythematosus (94.7% and 5.3%, respectively). Mucosal involvement occurred in 84.2% of cases. No association with neoplasia was found in the current study. CONCLUSIONS: Pemphigus in the southern region of Saudi Arabia is as common as in other parts of the world, but with higher mucosal involvement.     

Epidemiology of pemphigus in Macedonia: a 15-year retrospective study (1990-2004)

BACKGROUND: Pemphigus is an autoimmune blistering skin disease mediated by auto-antibodies directed against desmoglein proteins. There are only a few epidemiological studies on pemphigus. Our objective was to determine the epidemiological features of pemphigus in Macedonia, and to compare the results with those reported elsewhere. METHODS: Diagnosis in all cases was confirmed by histopathology and direct immunofluorescence. Binomial distribution testing and Fisher's exact-test at the 0.01 level of significance were used to determine if particular demographic groups were over-/ under-represented among the pemphigus patients. RESULTS: One hundred and thirty-three new pemphigus cases were diagnosed in Macedonia from 1990-2004. The average annual incidence was 0.44/100,000 inhabitants (SD = 0.17). The incidence doubled to 0.89 in 2001 during the local armed unrest. The disease did not affect either gender to a greater extent. The average annual incidence was 0.51 for ethnic Macedonians. Roma (Gypsies) had a statistically significantly higher incidence of pemphigus at 2.4 cases/100,000 individuals. Ethnic Albanians had statistically significantly lower incidence of 0.1 cases/100,000 individuals. The most common variant was pemphigus vulgaris (77.4%). CONCLUSIONS: The annual incidence for pemphigus in Macedonia is 0.44 cases/100,000 inhabitants. Most common form was pemphigus vulgaris. An epidemiological peak occurred in 2001 during the local armed conflict. Macedonian Roma had a sixfold higher incidence of pemphigus compared with the overall population; ethnic Albanians had a fourfold lower incidence.     

Desmoplakin I and II in acantholytic dermatoses: preservation in pemphigus vulgaris and pemphigus erythematosus and dissolution in Hailey-Hailey's disease and Darier's disease

Desmoplakin I and II are important components of the attachment plaque of the desmosome which mediates cell to cell adhesion, in epithelial cells. In this study we used well-characterized antibody against desmoplakin I and II immunohistochemically and immunoelectron microscopically on two cases of pemphigus vulgaris and one case of pemphigus erythematosus and two cases each of Hailey-Hailey's disease and Darier's disease. In the normal human epidermis the desmosomes were demonstrated in a dotted pattern along cell periphery. In pemphigus vulgaris and pemphigus erythematosus acantholytic cells and the perilesional cells exhibited normal dotted pattern along the cell periphery. In Hailey-Hailey's disease and Darier's disease, the dotted pattern is lost in acantholysed and perilesional areas and anti-desmoplakin I + II positive proteins were observed diffusely in the cytoplasm. Immunoelectron microscopical findings correspond to these light microscopical observations. It is concluded that in autoimmune acantholytic disease such as pemphigus vulgaris and pemphigus erythematosus, desmoplakins are intact even in acantholytic cells, whereas in genodermatoses such as vulgaris and pemphigus erythematosus, desmoplakins are intact even in acantholytic cells, whereas in genodermatoses such as Hailey-Hailey's disease and Darier's disease primary or secondary abnormalities abnormalities of desmosomes may be involved in their pathogenesis.     

UVB-induced acantholysis in endemic Pemphigus foliaceus (Fogo selvagem) and Pemphigus vulgaris

BACKGROUND: The autoantibody-mediated disease in fogo selvagem (FS) is aggravated by sunlight exposure. OBJECTIVE: The aim of this study was to test whether UVB exposure of uninvolved skin of patients with FS (n = 21) enhances epidermal acantholysis and in vivo binding of FS autoantibodies as compared with a control group (n = 4). Another control group included 8 patients with pemphigus vulgaris (PV). RESULTS: Exposure of uninvolved skin of FS to UVB induces acantholysis (15/21 patients) with in vivo binding of IgG and C3 to the epidermal intercellular spaces (17/21 patients). Similar results were found in PV (6/8 patients). The test was negative in the control group. CONCLUSION: Sunlight exposure is harmful in the clinical course of patients with FS and those with PV. Protection from sunlight should be part of the treatment of these patients.     

Advances in pemphigus therapy

The pemphigus variants represent a group of potentially life-threatening autoimmune mucocutaneous blistering diseases. Though systemic corticosteroids have dramatically reduced the rate of disease mortality, current therapeutic options are limited by their toxicity profiles. Advancements in our understanding of the molecular mechanisms involved in the pathogenesis of pemphigus have translated into the development of novel therapies. However, few treatments have been subject to randomized controlled trials to firmly establish therapeutic efficacy. Herein, we focus on the new and emerging therapies in the management of pemphigus.