Browsing by Author "Medenica, Ljiljana (16744100000)"

Aloe-emodin (AE) is a plant-derived hydroxyanthraquinone with several biological activities. It is present in a variety of skin-conditioning agents containing aloe extracts, but its influence on keratinocyte growth was not examined so far. We investigated the influence of AE on human keratinocyte proliferation and apoptosis in vitro. AE significantly inhibited proliferation of cultivated human keratinocytes at 5 μM concentration, as revealed by incorporation of radioactive thymidine. The antiproliferative effect of AE was accompanied with induction of apoptosis, but not necrosis, as demonstrated by flow cytometric analysis and lactate dehy-drogenase release assay. Based on the half maximal inhibitory concentration values, we demonstrated that AE may impair proliferation of keratinocytes at concentrations far below the industry standards for commercial products containing aloe extracts. Therefore, further research of AE effects on the human skin and proper labeling of products are necessary for maximizing benefits from aloe extracts and to avoid undesired responses. © 2018 Society of Cosmetic Chemists. All Rights Reserved.

Aloe-emodin (AE) is a plant-derived hydroxyanthraquinone with several biological activities. It is present in a variety of skin-conditioning agents containing aloe extracts, but its influence on keratinocyte growth was not examined so far. We investigated the influence of AE on human keratinocyte proliferation and apoptosis in vitro. AE significantly inhibited proliferation of cultivated human keratinocytes at 5 μM concentration, as revealed by incorporation of radioactive thymidine. The antiproliferative effect of AE was accompanied with induction of apoptosis, but not necrosis, as demonstrated by flow cytometric analysis and lactate dehy-drogenase release assay. Based on the half maximal inhibitory concentration values, we demonstrated that AE may impair proliferation of keratinocytes at concentrations far below the industry standards for commercial products containing aloe extracts. Therefore, further research of AE effects on the human skin and proper labeling of products are necessary for maximizing benefits from aloe extracts and to avoid undesired responses. © 2018 Society of Cosmetic Chemists. All Rights Reserved.

We report a 47-year-old man with Wilson disease who developed bullous lesions on the trunk and extremities after 20 years of penicillamine treatment. The histologic and immunofluorescence findings were diagnostic of bullous pemphigoid. When penicillamine was replaced by zinc sulfate, the patient's bullous skin lesions improved rapidly. However, after 2 months of zinc sulfate treatment, the patient's skin condition remained improved but his neurologic disease became worse and penicillamine was reinstituted. Bullous lesions recurred within 1 week and the diagnosis of penicillamine-induced bullous pemphigoid was confirmed. This is the first report of penicillamine-induced bullous pemphigoid in a patient with Wilson disease. © 2009 Adis Data Information BV. All rights reserved.

Background: Fitzpatrick skin phototype classification is widely used to assess risk factors for skin cancers. This skin type evaluation is easy to use in clinical practice but is not always applied as initially described, nor practiced in a standardised way. This can have implications on the results of relevant dermato-epidemiological studies. Objectives: To demonstrate, in a large multinational setting, that the phrasing of questions on sun sensitivity can have a strong impact on the perception and reporting of skin phototype, as well as the importance of a standardised procedure for phototype assessment. Materials & methods: Using data collected from 48,258 screenees of the Euromelanoma campaign in six European countries from 2009 to 2011, we analysed the impact of change in the question phrasing on phototype classification in each country. Results: Changing the wording of a question to assess the phototype of a person also significantly influenced the classification of phototypes in different countries (p<0.001 for each country). The difference essentially corresponded to a shift towards a less sun-sensitive skin type when a shorter question that did not include skin colour description was used. The only exception was Portugal where phototype was not patient-assessed and classification shifted towards a more sun-sensitive phototype. Results were statistically significant and highly consistent, irrespective of gender. Conclusions: The phrasing of questions on skin type is important and substantially influences reporting. A standardized procedure to classify phototypes should be used in order to obtain comparable data between studies. © 2017, John Libbey Eurotext. All rights reserved.

The enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence (IIF) have both been used for testing of antibodies to desmogleins 1 and 3 (anti-Dsg1 and anti-Dsg3) and for the serologic diagnosis of pemphigus. IIF values and antibody concentrations and profile do not always correlate with a specific clinical phenotype and with the disease activity. The purpose of the present study was to correlate the clinical phenotype of patients with pemphigus vulgaris (PV) and the disease activity with anti-Dsg1 and anti-Dsg3 antibodies and IIF titers. A total of 72 patients with PV underwent ELISA serum testing for the presence and titers of anti-Dsg1 and anti-Dsg3 and IIF which were correlated with the severity of the disease (evaluated using the Pemphigus Disease Area Index, PDAI), clinical phenotype, and clinical course. In 79.2% patients there was a perfect correlation between the clinical phenotype and antibody profiles; in 20.8% patients, clinical features and antigenic findings were discordant. A statistically significant correlation was found between disease activity and a) anti-Dsg3 and anti-Dsg1 concentrations (Rho=0.679, P<0.001 and Rho=0.363, P=0.02, respectively) and b) IIF titers (Rho=0.426, P<0.01), as well between IIF titers and anti-Dsg3 and anti-Dsg1 antibodies (Rho=0.742, P<0.01 and Rho=0.372, P=0.02, respectively). This study supports the previous observations that the disease severity in most patients with pemphigus correlates with IIF titers, which in turn is determined by the quantities of Dsg1 and Dsg3 antibodies, as well as the previous observation that the clinical phenotype and antibody profile are not always in correlation. © 2017, Croatian Dermatovenerological Society. All rights reserved.

Background: Autoimmune pemphigus is a group of severe blistering diseases. Although corticosteroids have dramatically altered the prognosis of pemphigus, morbidity and mortality resulting from the adverse effects of systemic corticosteroids remain high. Dexamethasone-cyclophosphamide pulse (DCP) therapy was introduced to diminish the adverse effects of prolonged conventional daily dose regimens. Objective: To report our experience with the use of the DCP regimen in patients with autoimmune pemphigus. Methods: In the period 1998-2002, 72 patients with various forms of autoimmune pemphigus treated with DCP therapy were included, of whom 36 patients were previously treated with conventional corticosteroid therapy, and 36 were newly diagnosed patients. Results: Of the 72 patients, 43 completed treatment, while 13 patients did not respond adequately to the treatment and continued with the conventional daily regimen, nine patients were lost to follow-up, and seven patients died. Two of these deaths were probably a consequence of DCP therapy. Conclusion:DCPregimen is a beneficial treatment for patients with pemphigus, sparing the adverse effects of conventional regimens. © 2010 Adis Data Information BV. All rights reserved.

Direct immunofluorescence of peri-lesional skin is the gold standard in the diagnosis of pemphigus. A specific immunofluorescence pattern may also be demonstrated in the outer root sheath of anagen and telogen hair. We demonstrated an intercellular reticular deposition of immunoglobulin G in the outer root sheath of plucked anagen and telogen hair in all pemphigus vulgaris patients with active disease and for the first time in all patients with active pemphigus foliaceus. Moreover, we demonstrated for the first time that plucked hair samples may be kept at -20C for at least 2 weeks before immunofluorescent staining and analysis. © 2013 The Authors. Australasian Journal of Dermatology © 2013 The Australasian College of Dermatologists.

Gianotti-Crosti syndrome (GCS) is a self-limiting, mostly childhood-appearing, cutaneous eruption with characteristic symmetric areal distribution. The original cases, described by Gianotti in 1955, were associated with hepatitis B virus infection, but other viral and bacterial infections, as well as immunizations, have been implied in etiology of this condition. Adult cases are rare and have been reported almost exclusively in women. We present the case of a 20-year-old Caucasian man who had typical clinical presentation: monomorphic pale, pink-to-flesh - colored or erythematous papules and papulovesicles localized symmetrically over the extensor surfaces of the extremities, buttocks and the face; some lesions were detected on knees, elbows and palms, as well. Laboratory tests revealed slight bilirubin and alanine aminotransaminase elevation. Serology tests demonstrated antibodies against Epstein-Barr virus and parvovirus B-19. Histology of skin biopsy specimens revealed a vesicular dermatitis with perivascular lymphocytic infiltrate. Oral and topical corticosteroids and oral antihistamines led to complete resolution of lesions in 3 weeks. GCS is rare in adults, especially men. To the best of our knowledge, this is the fifth male adult case and the first with Parvovirus B-19 and EBV coinfection. © 2016 Edizioni Minerva Medica.

Introduction Iatrogenic Kaposi’s sarcoma (KS) represents a multifocal, angioproliferative tumor that develops in patients undergoing immunosuppressive treatment and is considered to be induced by activation of latent human herpes virus type 8 (HHV8) infection. The aim of this report is to present a patient with iatrogenic KS due to immunosuppressive treatment. Case outline We present a 69-year-old male non-HIV patient, previously treated for anti-aquaporin-4 antibody negative recurrent longitudinal extensive transverse myelitis with prednisolone and azathioprine for one year. The patient developed bluish and violet plaques and nodules on his face, trunk, and extremities. Skin biopsy findings (histopathology and immunohistochemical detection of CD31 expression and anti-HHV8 antibodies in the spindle cells) confirmed the diagnosis of KS. The reduction of immunosuppression and topical treatment with imiquimod resulted in a partial but significant regression of skin lesions, but the patient had another relapse of myelitis following the cessation of azathioprine and a reduction in the dose of prednisolone. Conclusion To the best of our knowledge, this is the first case of an inflammatory and demyelinating central nervous system disease treated with corticosteroids and azathioprine that was associated with iatrogenic KS. The efficient treatment of both conditions is highly challenging and can be troublesome in specific cases. © 2018, Serbia Medical Society. All rights reserved.

Background and objectives: While most previous surveys on the clinico-epidemiological features of autoimmune bullous diseases (AIBDs) have predominantly focused on a single disease entity or just one disease group, there have been only few studies examining the incidence of various AIBDs. In the present study, we set out to determine the spectrum of AIBDs, to estimate the incidence of the most common AIBDs, and to examine their temporal trends in Central Serbia over a period of 20 years. Methods: We retrospectively recruited 1,161 new AIBD cases diagnosed in Central Serbia during the period from January 1991 to December 2010. The diagnosis was based on strict clinical, histological, and immunohistological evaluation. Results: The incidence rates were: 4.35 per million population/year (pmp/year) for pemphigus, 4.47 pmp/year for pemphigoid, 1.42 pmp/year for dermatitis herpetiformis (DH), 0.25 pmp/year for linear IgA disease, and 0.08 pmp/year for epidermolysis bullosa acquisita. In the period observed, age-adjusted incidence rates significantly increased for pemphigus and particularly for pemphigoid, whereas they decreased, albeit not significantly, for DH. Conclusions: For the first time, our study evaluates the incidence rates of the entire spectrum of AIBDs in Serbia, and examines their temporal trends over a 20-year period. To the best of our knowledge, our finding of similar incidence rates for pemphigus and pemphigoid has previously not been reported. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Objective: We studied the relation between the presence or absence of urethral discharge, urethral pathogens, and polymorhonuclear (PMN) counts on Gram stained urethral smears in men with symptomatic urethritis. Methods: The study population was composed of 630 sexually active heterosexual men (aged 18-45 years) who had urethral symptoms and signs (discharge, dysuria or urethral discomfort). Participants were divided into two groups: the first (n=320) was comprised of men with urethral discharge confirmed on examination, while the other (n=310) was composed of patients with urethral symptoms but without discharge. Urethral swabs for Gram stained smears and microbiological analyses (N. gonorrhoeae, C. trachomatis, T. vaginalis and U. urealyticum) were taken from all study participants. Polymorphonuclear leukocytes (PMN) on Gram-stained urethral smears were counted in 5 oil immersion x1000 PMN per high power fields (phpf). Urethritis was defined as the presence of ≥5 PMN/hpf. Results: N. gonorrhoeae was isolated only in men with urethritis accompanied by discharge. The prevalence of T. vaginalis, C. trachomatis and U. urealyticum was significantly higher (F=8.854, P<0.01) in urethral swabs of urethritis patients with discharge compared to patients with no discharge. The most common urethral pathogen in both groups of patients was T. vaginalis (31.56% and 26.45%, respectively). One or more microorganisms were isolated in 258 (81%) subjects with urethritis with discharge, and in 166 (53.5%) urethritis patients without discharge. There was a positive correlation between the significant number of PMN in Gram stained urethral smears and positive microbiological findings in men with urethritis both with and without urethral discharge (Spearman's coefficients p=0.986 and p=0.993, respectively; P<0.01). Conclusions: The study found a relatively high prevalence of T. vaginalis among our men with urethritis irrespective of the presence or absence of urethral discharge, and showed that taking into account both discharge found on examination, and relevant PMN counts on Gram stained urethral smears fails to detect only 4.2% of oligosymptomatic urethritis patients who are infected with one of the strict urethral pathogens.

Background: The current standard in the serologic diagnosis of autoimmune bullous diseases (AIBD) is a multistep procedure sequentially applying different assays. In contrast, the BIOCHIP Mosaic technology combines multiple substrates for parallel analysis by indirect immunofluorescence. Methods: Sera from 749 consecutive, prospectively recruited patients with direct immunofluorescence–positive AIBD from 13 international study centers were analyzed independently and blinded by using (1) a BIOCHIP Mosaic including primate esophagus, salt-split skin, rat bladder, monkey liver, monkey liver with serosa, recombinant BP180 NC16A, and gliadin GAF3X, as well as HEK293 cells expressing recombinant desmoglein 1, desmoglein 3, type VII collagen, and BP230 C-terminus and (2) the conventional multistep approach of the Department of Dermatology, University of Lübeck. Results: In 731 of 749 sera (97.6%), specific autoantibodies could be detected with the BIOCHIP Mosaic, similar to the conventional procedure (725 cases, 96.8%). The Cohen κ for both serologic approaches ranged from 0.84 to 1.00. In 6.5% of sera, differences between the 2 approaches occurred and were mainly attributed to autoantigen fragments not present on the BIOCHIP Mosaic. Limitations: Laminin 332 and laminin γ1 are not represented on the BIOCHIP Mosaic. Conclusions: The BIOCHIP Mosaic is a standardized time- and serum-saving approach that further facilitates the serologic diagnosis of AIBD. © 2020 American Academy of Dermatology, Inc.

Kindler syndrome (OMIM 173650) is an autosomal recessive condition characterized by skin blistering, skin atrophy, photosensitivity, colonic infammation and mucosal stenosis. Fewer than 100 cases have been described in the literature. First reported in 1954, the molecular basis of Kindler syndrome was elucidated in 2003 with the discovery of FERMT1 (KIND1) loss-of-function mutations in affected individuals. The FERMT1 gene encodes kindlin-1 (also known as fer-mitin family homologue 1), a 77 kDa protein that localizes at focal adhesions, where it plays an important role in integrin signalling. In the current study, we describe five novel and three recurrent loss-of-function FERMT1 mutations in eight individuals with Kindler syndrome, and provide an overview of genotype-phe-notype correlation in this disorder.© 2011 The Authors.

Chronic venous disease (CVD) has been reported to substantially affect patients' quality of life (QoL). To evaluate the impact of CVD on patient-reported QoL in a patient series in Serbia, a cross-sectional study of 570 CVD patients, classified according to the CEAP clinical classification into classes (C) 1-6, was performed in a Belgrade outpatient clinic. QoL was assessed by the general short-form (SF)-36 questionnaire, and additionally by a brief CVD-specific questionnaire. The SF-36 scores for all QoL dimensions showed a progressive reduction from C1 to C6. Class 5 and 6 patients scored the lowest across all dimensions, with significant (p < 0.05) reductions in physical functioning, role-physical, general health, vitality and mental health. The score for bodily pain decreased from C1 to C4, but increased in C5 and C6 as compared to C4 patients. Interestingly, despite an increasing rate of aesthetic concerns as the disease progresses, no variations were found in the social functioning and emotional role scores across the groups. There were no age or gender differences in any QoL item across the classes. The data presented show that QoL of CVD patients decreases, particularly after the appearance of skin changes, and suggest that even patients in the early stages consider CVD a disease and not merely a cosmetic problem.

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are rare autoimmune blistering diseases with presumed T-cell–dependent pathology. Activation of naïve T cells is dependent on antigen recognition, subsequent signaling through the T-cell receptor complex (signal 1), and various other interactions of T cells with antigen presenting cells that may be collectively designated as signal 2, which is unconditionally required for T-cell activation both in response to infection and to autoantigens. Among the best described interactions contributing to signal 2 are those mediated by B7 family molecules, such as CD80 and CD86 with their ligands; CD28, providing activation signals; and cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4), conferring inhibition. Single nucleotide polymorphisms (SNPs) within genes encoding those molecules may alter the signaling process. It is not known whether functional genetic polymorphisms within genes encoding the aforementioned proteins may increase risk for developing PV and PF and, if so, whether they might serve as biomarkers for susceptibility to these diseases. To address those questions, we examined functional single nucleotide polymorphisms within CD86 (rs1129055) and CTLA4 (rs733618 and rs5742909) genes in 61 pemphigus patients and 486 healthy controls. We found statistically significant differences in allele and genotype frequencies between PV patients and controls for rs1129055, as well as for rs5742909 among PV and PF patients. Namely, the rs1129055 A allele was significantly more common in PV patients compared with controls (35.4% versus 25.7%, respectively; P = .040), whereas the rs5742909 T allele was significantly more common in PF compared with PV patients (19.2% versus 5.2%, respectively; P = .035). The frequency of the rs5742909 T allele did not, however, differ significantly in PF or in PV compared with controls (10.5%; P = .187 and P = .100, respectively). We report a novel association of SNPs within CD86 and CTLA4 genes with pemphigus. The CD86 rs1129055 A allele appears to confer susceptibility to PV but not to PF. © 2016 Elsevier Inc. All rights reserved. © 2016 Elsevier Inc.

We report three adolescents with pemphigus vulgaris whose disease started at the age of 13, 15 and 14 years, respectively. The course of the disease and the treatment approaches were reviewed. Pemphigus vulgaris during childhood and adolescence is a very rare disease in this part of Europe. Among 410 pemphigus vulgaris patients that we treated during the 20-year period, only three patients (0.73%) were under the age of 18 years. According to our experience, the course of pemphigus vulgaris in patients before the age of 18 years is comparable with the course of pemphigus vulgaris in adults. © 2010 The Authors. Australasian Journal of Dermatology © 2010 The Australasian College of Dermatologists.

Background Serologic diagnosis of autoimmune blistering disease (AIBD) usually follows a sophisticated multistep algorithm. Objective We sought validation of a multivariant enzyme-linked immunosorbent assay (ELISA) in the routine diagnosis of AIBD. Methods The multivariant ELISA comprising 6 recombinant immunodominant forms of major AIBD target antigens, ie, desmoglein 1, desmoglein 3, envoplakin, BP180, BP230, and type VII collagen was applied in: (1) a cohort of well-characterized AIBD (n = 173) and control sera (n = 130), (2) a prospective multicenter study with 204 sera from patients with newly diagnosed AIBD with positive direct immunofluorescence microscopy, and (3) a prospective monocenter study with 292 consecutive sera from patients with clinical suspicion of AIBD in comparison with the conventional multistep diagnostic algorithm. Results Concordant results in the multivariant ELISA compared with direct immunofluorescence microscopy were seen in 94% of patients with pemphigus and 71% of patients with pemphigoid (Cohen κ value, 0.95 and 0.66) and with the conventional multistep diagnostic approach in 91% of patients with pemphigus and 88% of patients with bullous pemphigoid and 93% of autoantibody-negative sera (Cohen κ, 0.95, 0.84, and 0.78). Limitations IgA autoantibodies and less common target antigens were not analyzed. Conclusions The multivariant ELISA is a practical, highly standardized, and widely available novel diagnostic tool for the routine diagnosis of AIBD. © 2016 American Academy of Dermatology, Inc.

Introduction Chronic venous disease has been shown to have a significant impact on patients' quality of life (QoL). Objective The aim of this study was to estimate the impact of chronic venous insufficiency (CVI) on QoL in patients with terminal stages of HVI, classified according to the CEAP clinical classification into classes C5 (healed ulcers) and C6 (active ulcers), on admission and after applied therapy. Methods A cross-sectional study performed between October 2007 and June 2008 in a Belgrade outpatient clinic involved a total of 82 patients with venous ulcers (38 C5 and 44 C6) examined at the beginning of therapy. Of these, 14 C5 and 15 C6 patients in remission were re-examined after therapy from November 2007 to January 2010. QoL was assessed using a standard short-form (SF-36) questionnaire, and additionally by a brief CVD questionnaire specific for chronic venous disease. Results At the beginning of therapy the SF-36 scores showed significant (p<0.05) reductions in all QoL domains of C5 and C6 patients regarding physical, general health, and vitality in C5 and C6 patients. After therapy QoL was significantly improved in both classes of patients, but remained unchanged in the domain of emotional functioning suggesting the patients' fear and worry of HVI progression. Conclusion In patients with terminal stages of CVI QoL was decreased at the beginning of therapy, but with the remission of the disease and ulcer healing it was significantly improved. This indicates the significance of prevention and timely treatment, and the need for patients' education about the chronic nature of the disease.

Dystrophic epidermolysis bullosa (DEB) and aplasia cutis congenita (ACC), also known as congenital localized absence of skin (CLAS) are rare clinical entities. Aplasia cutis congenita presented in conjunction with simplex, junctional, or dystrophic types of epidermolysis bullosa (EB) is classified as type-6 ACC. This association was initially described and referred in the literature as Bart syndrome. We describe two cases of recessive DEB (RDEB), one with the major Hallopeau-Siemens (RDEB-HS) subtype and one case with the minor RDEB inversa (RDEB-I) subtype associated with ACC localized on the lower extremities. Full clinical history and transmission electron microscopic findings are presented for both cases. To date, only five cases of RDEB presenting with ACC have been reported in the literature. Detailed descriptions of the association of RDEB and ACC in the literature are scarce. It seems that this condition is probably more common in clinical practice than described in the literature. Our findings confirm that the term, Bart syndrome, should not be considered as a separate entity or clinical variant of dominant dystrophic EB as it was initially described. Congenital localized absence of skin may be associated with any of the three major types of EB (simplex, junctional, or dystrophic). © 2008 Dermatology Online Journal.

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening diseases that are most frequently caused by drugs. Objectives: The purpose of this study was to summarize 20 years of experience with SJS and TEN in the largest dermatology clinic in Serbia. Methods: The study included 38 patients treated during the period 1993-2012. The patients were classified into three groups according to whether they were diagnosed with SJS, a condition representing an overlap of SJS and TEN (SJS/TEN), or TEN. Patients with TEN were also divided into three groups according to the modality of therapy: supportive therapy (ST) only (n = 3); ST plus systemic corticosteroids (SC) (n = 8); and ST plus SC plus IV immunoglobulins (IVIG) (n = 6). Results: The study population included 13 SJS patients, eight SJS/TEN patients, and 17 TEN patients. The disease had started at a mean ± standard deviation (SD) of 7.1 ± 3.5 days after the commencement of treatment with the offending drug. The disease resulted in three lethal outcomes, all of which occurred in TEN patients. However, the predicted mortality for the whole group was 5.6 in 38 patients, whereas that for the TEN group was 3.97 in 17 patients. The differences between actual and predicted rates of mortality were not significant. Among the three groups of TEN patients, there were no significant differences in the commencement of re-epithelialization or the duration of hospitalization. Conclusions: In the present study, nonsteroidal anti-inflammatory and anti-infective drugs were the most frequent causative agents (eight patients in each group). In the group of SJS and SJS/TEN patients treated with ST and SC, the mortality rate was 0%. In TEN patients, the mortality rate was 17.6% (three of 17 patients). There were no significant differences in mortality rate among the three TEN treatment groups, but the results may have been biased by the small number of patients. © 2014 The International Society of Dermatology.