Prevalence and burden of vitiligo in Africa, the Middle East and Latin America.

Vitiligo is a common chronic autoimmune disorder characterized by skin and hair depigmentation that affects 0.5%-2.0% of the global population. Vitiligo is associated with diminished quality of life (QoL) and psychosocial burden. The burden of vitiligo may vary based on skin tone and cultural differences as well as geographical variations in disease awareness, societal stigma, healthcare systems and treatment options. Data on the burden and management of vitiligo in Africa, the Middle East and Latin America are scarce. Literature searches using terms covering vitiligo in Africa, the Middle East and Latin America were conducted using PubMed to identify relevant publications that focused on disease prevalence and burden, QoL and psychosocial impact and disease management between 2011 and 2021. Most of the reviewed studies were conducted in the Middle East, and most Latin American studies were from Brazil. Most studies involved small patient numbers and may not be generalizable. Reported prevalence of vitiligo ranged from 0.18% to 5.3% in Africa and the Middle East, and from 0.04% to 0.57% in Latin America. In several studies, prevalence was higher among female participants. Generally, non-segmental vitiligo was the dominant clinical variant identified and the age at onset varied widely across studies. Common comorbidities include autoimmune diseases such as Hashimoto's thyroiditis, alopecia areata and diabetes. Few treatment guidelines exist in these regions, with the exceptions of guidelines published by the Brazilian and Argentinian Societies of Dermatology. There is a clear unmet need for large epidemiological studies with uniform methodology to accurately ascertain the true prevalence of vitiligo in Africa, the Middle East and Latin America. Additional data on vitiligo burden and management in Africa and Latin America are also needed, along with local disease management guidelines that consider genetic variation, psychosocial burden and socioeconomic diversity in all 3 regions.

Experimental approaches to assess melanocytes mosaicism in segmental vitiligo.

Vitiligo is an autoimmune disease of the skin that results in localized or disseminated white macules. One common feature of several existing classification protocols is the distribution of the disease into two main subtypes, non-segmental vitiligo (NSV) and segmental vitiligo (SV). SV is characterized by depigmentation spreading within one or more skin segments while NSV is widespread. Several clinical-epidemiological observations suggest that SV has distinct autoimmune pathophysiology compared to NSV. Furthermore, the clinical distribution pattern of SV lesions closely resembles other melanocyte mosaicism diseases. These observations led us to hypothesize that SV is caused by a localized autoimmune reaction targeting epidermal mosaicism melanocytes. Here, we proposed examples of experimental approaches to assess mosaicism in SV patients.

Update on the pathogenesis of vitiligo.

Vitiligo is a complex disease whose pathogenesis results from the interaction of genetic components, metabolic factors linked to cellular oxidative stress, melanocyte adhesion to the epithelium, and immunity (innate and adaptive), which culminate in aggression against melanocytes. In vitiligo, melanocytes are more sensitive to oxidative damage, leading to the increased expression of proinflammatory proteins such as HSP70. The lower expression of epithelial adhesion molecules, such as DDR1 and E-cadherin, facilitates damage to melanocytes and exposure of antigens that favor autoimmunity. Activation of the type 1-IFN pathway perpetuates the direct action of CD8+ cells against melanocytes, facilitated by regulatory T-cell dysfunction. The identification of several genes involved in these processes sets the stage for disease development and maintenance. However, the relationship of vitiligo with environmental factors, psychological stress, comorbidities, and the elements that define individual susceptibility to the disease are a challenge to the integration of theories related to its pathogenesis.

Consensus on the treatment of vitiligo - Brazilian Society of Dermatology.

BACKGROUND: Vitiligo is a muco-cutaneous, autoimmune, localized, or disseminated disease, which manifests through hypochromic or achromic macules, with loss in quality of life. The prevalence of vitiligo in Brazil was determined to be 0.54%. There is no on-label medication for its treatment. To date, no Brazilian consensus on the treatment of vitiligo had been written. OBJECTIVES: The objective of this group of Brazilian dermatologists with experience in the treatment of this disease was to reach a consensus on the clinical and surgical treatment of vitiligo, based on articles with the best scientific evidence. METHODS: Seven dermatologists were invited, and each was assigned two treatment modalities to review. Each treatment (topical, systemic, and phototherapy) was reviewed by three experts. Two experts reviewed the surgical treatment. Subsequently, the coordinator compiled the different versions and drafted a text about each type of treatment. The new version was returned to all experts, who expressed their opinions and made suggestions for clarity. The final text was written by the coordinator and sent to all participants to prepare the final consensus. RESULTS/CONCLUSION: The experts defined the following as standard treatments of vitiligo: the use of topical corticosteroids and calcineurin inhibitors for localized and unstable cases; corticosteroid minipulse in progressive generalized vitiligo; narrowband UVB phototherapy for extensive forms of the disease. Surgical modalities should be indicated for segmental and stable generalized vitiligo. Topical and systemic anti-JAK drugs are being tested, with promising results.

Partial repigmentation of vitiligo with tofacitinib, without exposure to ultraviolet radiation.

Vitiligo is a disease that causes macules and achromic and/or hypochromic patches, which can affect from small areas to the entire tegument. Treatment options are few and are generally ineffective. Recently, some case reports have appeared which show positive results with the use of Janus kinase inhibitors associated with phototherapy. This report details the case of a patient with rheumatoid arthritis associated with vitiligo in treatment for two years, whose condition partially improved initially after eight months of oral tofacitinib at a dose of 5mg twice a day, without exposure to ultraviolet radiation and with continuous improvement during these two years of treatment.

Association between three autoimmune diseases: vitiligo, primary biliary cirrhosis, and Sjögren's syndrome.

Although the association of multiple autoimmune diseases has already been widely described, no reports of the association between vitiligo, primary biliary cirrhosis and Sjogren's syndrome were retrieved in the SciELO and PubMed databases. The authors describe the case of a female patient who was diagnosed with primary biliary cirrhosis and Sjogren's syndrome at age 54. At age 58, she developed vitiligo restricted to the face, associated with significant impairment of self-esteem and quality of life. Antinuclear antibody was negative at the onset of the condition, but became positive after phototherapy initiation. In general, the occurrence of multiple autoimmune diseases in the same patient is known as a mosaic of autoimmunity. However, specific mechanisms appear to interconnect primary biliary cirrhosis and Sjogren's syndrome, such as PDC-E2-mediated generalized epithelitis.

Reduced immunohistochemical expression of adhesion molecules in vitiligo skin biopsies.

Because defects in adhesion impairment seem to be involved in the etiopathogenesis of vitiligo, this study aimed to compare the immunohistochemical expression of several adhesion molecules in the epidermis of vitiligo and non lesional vitiligo skin. Sixty-six specimens of lesional and non lesional skin from 33 volunteers with vitiligo were evaluated by immunohistochemistry using anti-beta-catenin, anti-E-cadherin, anti-laminin, anti-beta1 integrin, anti-collagen IV, anti-ICAM-1 and anti-VCAM-1 antibodies. Biopsies of vitiligo skin demonstrated a significant reduction in the expression of laminin and integrin. The average value of the immunohistochemically positive reaction area of the vitiligo specimens was 3053.2µm2, compared with the observed value of 3431.8µm2 in non vitiligo skin (p=0.003) for laminin. The immuno-positive area was 7174.6µm2 (vitiligo) and 8966.7µm2 (non lesional skin) for integrin (p=0.042). A reduction in ICAM-1 and VCAM-1 expression in the basal layer of the epidermis in vitiligo samples was also observed (p=0.001 and p<0.001, respectively). However, no significant differences were observed with respect to the expression of beta-catenin, E-cadherin, and collagen IV between vitiligo and non lesional skin. Our results suggest that an impairment in adhesion exists in vitiligo skin, which is supported by the diminished immunohistochemical expression of laminin, beta1 integrin, ICAM-1 and VCAM-1.

Repigmentation in vitiligo: position paper of the Vitiligo Global Issues Consensus Conference.

The Vitiligo Global Issues Consensus Conference (VGICC), through an international e-Delphi consensus, concluded that 'repigmentation' and 'maintenance of gained repigmentation' are essential core outcome measures in future vitiligo trials. This VGICC position paper addresses these core topics in two sections and includes an atlas depicting vitiligo repigmentation patterns and color match. The first section delineates mechanisms and characteristics of vitiligo repigmentation, and the second section summarizes the outcomes of international meeting discussions and two e-surveys on vitiligo repigmentation, which had been carried out over 3 yr. Treatment is defined as successful if repigmentation exceeds 80% and at least 80% of the gained repigmentation is maintained for over 6 months. No agreement was found on the best outcome measure for assessing target or global repigmentation, therefore highlighting the limitations of e-surveys in addressing clinical measurements. Until there is a clear consensus, existing tools should be selected according to the specific needs of each study. A workshop will be conducted to address the remaining issues so as to achieve a consensus.

Pregnancy during Ustekinumab Treatment for Severe Psoriasis.

We report the case of a 25-year-old patient who became pregnant during ustekinumab therapy. Treatment was suspended immediately after pregnancy had been confirmed. The patient had an uneventful pregnancy and her child is currently 14 months old, with adequate development to her age. Four reports of pregnancy during ustekinumab treatment have been reported and one resulted in miscarriage.

Polymorphism of the E-cadherin gene CDH1 is associated with susceptibility to vitiligo.

Vitiligo is a depigmenting disorder characterized by loss of functional melanocytes from the epidermis. Experimental data suggest that defective melanocyte adhesion may underlie the pathogenesis of the disease. In particular, association between vitiligo and genetic variants of the DDR1 gene involved in melanocyte adhesion has been recently published. A subsequent, independent study revealed lower expression of DDR1 in vitiligo lesions. Here, we expand this investigation by testing for association between vitiligo and polymorphisms of CDH1, IL1B and NOV (formerly CCN3), genes belonging to the DDR1 adhesion pathway, in two population samples of distinct design. Our results reveal that alleles of marker rs10431924 of the CDH1 gene are associated with vitiligo, especially in the presence of autoimmune comorbidities.

Scientific output of Brazilian dermatologists during the last 25 years in the five highest impact factor journals in dermatology.

BACKGROUND: The qualitative and quantitative scientific output of Brazilian dermatologists in journals of high impact factor is little known. OBJECTIVE: To describe the scientific output of dermatologists from Brazilian institutions in journals of high impact factor. METHODS: The five journals with the highest impact factor in dermatology were analyzed. All articles produced from Brazilian institutions between 1986 and 2010 were compiled and the following aspects were analyzed: position of Brazilian researchers in the list of authors, selected theme, experimental design, studied disease, area of interest and year of publication. RESULTS: Seventy-four articles written with the participation of Brazilian dermatologists have been identified. Upon grouping the articles in five-year periods, an important increase was observed in the Brazilian production from the year 2006 onwards. The dermatologists were placed as second authors in the majority of cases (53.66%). According to the selected theme to be studied, the majority of the articles had a laboratory focus (45.95%). The majority of the articles reported cross-sectional studies or non-controlled clinical trials (both at 17.57%), and pemphigus foliaceus was the most studied disease (29.73%). CONCLUSION: The increase in the number of publications by Brazilian dermatologists over the last years is encouraging, but it is still small in comparison to the total number of articles published in these five periodicals.

Scientific output of Brazilian dermatologists during the last 25 years in the five highest impact factor journals in dermatology / Produção científica de dermatologistas brasileiros nos últimos 25 anos, nos cinco jornais de maior fator de impacto em dermatologia

BACKGROUND: The qualitative and quantitative scientific output of Brazilian dermatologists in journals of high impact factor is little known. OBJECTIVE: To describe the scientific output of dermatologists from Brazilian institutions in journals of high impact factor. METHODS: The five journals with the highest impact factor in dermatology were analyzed. All articles produced from Brazilian institutions between 1986 and 2010 were compiled and the following aspects were analyzed: position of Brazilian researchers in the list of authors, selected theme, experimental design, studied disease, area of interest and year of publication. RESULTS: Seventy-four articles written with the participation of Brazilian dermatologists have been identified. Upon grouping the articles in five-year periods, an important increase was observed in the Brazilian production from the year 2006 onwards. The dermatologists were placed as second authors in the majority of cases (53.66%). According to the selected theme to be studied, the majority of the articles had a laboratory focus (45.95%). The majority of the articles reported cross-sectional studies or non-controlled clinical trials (both at 17.57%), and pemphigus foliaceus was the most studied disease (29.73%). CONCLUSION: The increase in the number of publications by Brazilian dermatologists over the last years is encouraging, but it is still small in comparison to the total number of articles published in these five periodicals.

FUNDAMENTOS: A produção científica da dermatologia brasileira, qualitativa e quantitativamente, é pouco conhecida. OBJETIVO: Avaliar a produção científica dos dermatologistas vinculados a instituições brasileiras. MÉTODOS: Foram analisados os cinco jornais de maior fator de impacto em dermatologia. Compilados os trabalhos vinculados a instituições brasileiras de 1986 a 2010 e analisados: posição dos pesquisadores Brasileiros na lista de autores, objeto temático, delineamento, doença estudada, área de interesse da investigação e ano de publicação. RESULTADOS: Foram contabilizados setenta e quatro trabalhos realizados por dermatologistas de instituições brasileiras. Agrupando os trabalhos de cinco em cinco anos, um aumento importante foi observado na produção brasileira de 2006 em diante. Os dermatologistas foram classificados como investigadores secundários na maioria dos casos (53,66%). Segundo o objeto temático estudado, a maioria dos artigos era de enfoque laboratorial (45,95%). Em relação ao delineamento, constatou-se que os trabalhos na maioria eram transversais ou ensaios clínicos não controlados (ambos com 17,57%). Os trabalhos de investigação também foram tabulados conforme a doença estudada, e a mais estudada foi pênfigo foliáceo (29,73%). CONCLUSÃO: O aumento do número de publicações nos últimos anos é alentador, mas ainda pequeno comparado ao número de artigos publicados nesses periódicos.

A pattern of association between clinical form of vitiligo and disease-related variables in a Brazilian population.

BACKGROUND: Vitiligo classification systems are often based exclusively on the number and distribution of the white patches. To what extend these classification protocols reflect possible different pathophysiological basis for vitiligo or carry any prognostic value is currently unknown. OBJECTIVE: To investigate patterns of association between type of vitiligo and common disease-related variables, in order to advance on the understanding of the exact nature of different clinical forms of disease, as well as to identify features with prognostic value for clinical progression of early diagnosed vitiligo. MATERIALS AND METHODS: This is a cross-sectional study of a population sample from south of Brazil composed of 586 independent vitiligo-affected individuals. Different strategies of case-control analysis were employed to test for association between the three most common vitiligo clinical types and age of onset, family history of vitiligo, occurrence of Köebner phenomenon (KP) and presence of autoimmune co-morbidity. RESULTS: Individuals affected by segmental vitiligo showed lower average age of onset (16 years) when compared with vulgaris (23.9 years) and acrofacial cases (29 years) (p<0.001). The distribution of occurrence of KP, family history of vitiligo and co-occurrence of autoimmune disease followed a gradient pattern, with high, intermediate and low chance of occurrence of all three variables observed for vulgaris, acrofacial and segmental vitiligo, respectively (p<0.001 for overall distribution). CONCLUSION: Results indicate a uniform pattern of association between vitiligo clinical forms and KP, positive vitiligo family history and occurrence of co-morbidity autoimmune. The impact of the observed pattern of association over disease prognosis and classification is discussed.

Genetic variants of the DDR1 gene are associated with vitiligo in two independent Brazilian population samples.

Vitiligo is a chronic disease characterized by macules devoid of melanin and identifiable melanocytes. Adhesion of melanocytes to the basement membrane by integrin CCN3 is mediated through collagen IV receptor DDR1. We hypothesize that genetic variants of the DDR1 gene are associated with the occurrence of vitiligo. To test this hypothesis, we genotyped 10 DDR1 tag single-nucleotide polymorphisms (SNPs) in 212 trios composed of an affected child and both parents. Associated markers were then genotyped in 134 independent, unrelated individuals with vitiligo and 134 unrelated controls. Allele T of tag SNP rs4618569 was associated with an increased risk for vitiligo in the family trios (P=0.002, odds ratio (OR)=5.27; 95% confidence interval (CI)=1.59-17.40), whereas allele C of tag SNP rs2267641 was associated with an increased risk for vitiligo in both family-based and case-control populations (P=0.01, OR=3.47; 95% CI=1.22-9.17; P=0.04, OR=6.00; 95% CI=1.73-52.33, respectively). The best evidence for association in the trios was obtained for a haplotype composed of risk alleles of markers rs4618569 and rs2267641 (P=0.0006). There was an age-dependent enrichment of rs4618569 T allele and rs2267641 C allele in early-onset affected individuals. In conclusion, we propose DDR1 as a susceptibility gene for vitiligo, possibly implicating a defective cell adhesion in vitiligo pathogenesis.