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Competing Interests: Conflicts of interest None disclosed.

Autoimmune dermatoses targeting melanocytes have gained attention in human medicine due to their progressive nature and the social impact suffered by affected individuals. In veterinary medicine, vitiligo and the uveodermatological syndrome are the two autoimmune diseases that are known to affect skin melanocytes.In the first part of this article, we will review the signalment, clinical signs, histopathology and the treatment outcome of vitiligo in dogs, cats and horses; where pertinent, we compare the animal diseases to their human homologue. In a similar fashion, the information on the uveodermatological syndrome in dogs is reviewed and, where relevant, it is compared to the Vogt-Koyanagi-Harada (VKH) syndrome in humans.Canine, feline and equine vitiligo have many features that mirror their human counterparts. The most effective treatment and outcome of vitiligo in animals remain unclear. The canine uveodermatological syndrome resembles the incomplete VKH variant in humans; for affected individuals, an immediate diagnosis and aggressive treatment are crucial to prevent the development of blindness.

Background: Aicardi-Goutières syndrome is an early-onset encephalopathy with presumed immune pathogenesis caused by inherited defects in nucleic acid metabolism. It is a model disease to study systemic autoimmunity, and there are many clinical, genetic, and basic science considerations that underline a possible overlap between Aicardi-Goutières syndrome and systemic lupus erythematosus., Results: We describe a 15-year-old girl with Aicardi-Goutières syndrome due to compound heterozygous pathogenic variants in SAMHD1 (sterile alpha motif domain and HD domain-containing protein 1). Over time, she developed multiple autoimmune diseases (vitiligo, alopecia areata, immune thrombocytopenia, positive antithyroglobulin antibodies) without positive antinuclear antibody or features of systemic lupus erythematosus. Her thrombocytopenia was refractory to treatment with corticosteroids and intravenous immunoglobulin but responded to a standard course of rituximab., Conclusion: This is the first report of a multiple autoimmune syndrome in a patient with molecularly proven Aicardi-Goutières syndrome. This study illustrates an emerging pattern of the natural history of Aicardi-Goutières syndrome characterized by early encephalopathic presentation followed by symptoms of systemic autoimmunity., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The skin is the largest organ of the body, at the boundary with the outside environment. Primarily, it provides a physical and chemical barrier against external insults, but it can act also as immune organ because it contains a whole host of immune-competent cells of both the innate and the adaptive immune systems, which cooperate in eliminating invading pathogens following tissue injury. On the other hand, improper skin immune responses lead to autoimmune skin diseases (AISD), such as pemphigus, bullous pemphigoid, vitiligo, and alopecia. Although the interplay among genetic, epigenetic, and environmental factors has been shown to play a major role in AISD etiology and progression, the molecular mechanisms underlying disease development are far from being fully elucidated. In this context, epidemiological studies aimed at defining the association of different AISD with other autoimmune pathologies revealed possible shared molecular mechanism(s) responsible for disease progression. In particular, over the last decades, a number of reports have highlighted a significant association between thyroid diseases (TD), mainly autoimmune ones (AITD), and AISD. Here, we will recapitulate the epidemiology, clinical manifestations, and pathogenesis of the main AISD, and we will summarize the epidemiological evidence showing the associations with TD as well as possible molecular mechanism(s) underlying TD and AISD pathological manifestations.

Vitiligo is an idiopathic systemic autoimmune disease affecting skin, hair and oral mucosa. This genetic yet acquired disease characterized by melanin loss is a cause of morbidity across all races. Though thyroid disturbance has been recognized as a key trigger of this pathology, an array of other factors plays critical role in its manifestation. Multiple hormones (corticotropin-releasing hormone, adrenocorticotropic hormone, α-melanocyte-stimulating hormone, melatonin, calcitriol, testosterone, estrogen), genes (Human leukocyte antigen (HLA), Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), Forkhead box D3 (FOXD3), Cluster of differentiation 117 (CD117), Estrogen receptor (ESR) 1, Cyclooxygenase-2 (COX2), Vitiligo-associated protein 1 (VIT1)), and lifestyle choices (stress, diet, cosmetic products, and medications) have been suspected as drivers of this disorder. The pathological mechanisms have been understood in recent times, with the aid of genomic studies; however a universally-effective therapy is yet to be achieved. This review discusses these under-investigated facets of vitiligo onset and progression; hence, it is expected to enrich vitiligo research., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background: It is known that the association with Down syndrome (DS) can affect the phenotypic expression of autoimmune thyroid diseases (AITDs), whilst is unknown whether the clustering of extra-thyroidal autoimmune diseases (ETADs) may also be atypical in DS children., Methods: The aim of this study was to investigate the clustering of ETADs in 832 children with AITDs divided in two groups with or without DS (A and B, respectively) and in four subgroups of patients aged either <6 or ≥6 years., Results: The rate of children with ETADs was significantly higher in Group A; in particular, alopecia areata (p=0.00001) and vitiligo (p=0.00001) were found more often in Group A irrespective of age, whilst the distribution of T1 diabetes mellitus was not different in the two groups. Celiac disease prevalence was significantly higher in DS patients only in the older subgroup., Conclusions: The association with DS may be able to modify the clustering of ETADs in the children with AITDs by favoring the aggregation of some specific diseases such as alopecia areata and vitiligo.

It has long been appreciated in science that correlation does not imply causation. However, with any logical fallacy, simply spotting that the reasoning behind an argument is faulty does not imply that the resulting conclusion is false. Thus, I begin the tricky business of exploring the basis upon which researchers and clinicians are often tempted to conclude that two medical conditions (here alopecia areata and vitiligo), with some striking resemblances, are in fact related. This is relevant, particularly if assumptions of shared aetiology (and to some extent shared pathomechanism) encourage a common strategy to finding a treatment or cure., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Inducible heat-shock protein 70 (HSP70i) is a protein regulated by stress that protects cells from undergoing apoptosis. Such proteins are marvellously well conserved throughout evolution, which has placed them in the spotlight for helping to understand the intriguing relationship between infection and immunity. In the presence of stress proteins, dendritic cells (DCs) will sense this alarm signal and respond by recruiting immune cells of different plumage to fit the occasion. In times of stress, melanocytes will secrete antigen-bound HSP70i to act as an alarm signal in activating DCs that comes equipped with an address of origin to drive the autoimmune response in vitiligo. Here we pose that if the autoimmune response is funnelled through HSP70i, then blocking the stress protein from activating DCs can lend new treatment opportunities for vitiligo., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The pathogenesis of vitiligo is complex and not well understood. Genes play a role in all aspects of vitiligo pathogenesis, and studies are ongoing to identify these genes and understand their biology. There is a body of interlocking, compelling evidence supporting an autoimmune basis for most or all cases of generalized vitiligo. The development of an autoimmune disease generally involves three components; the immune system, environmental triggers and other exogenous precipitating factors, and the target tissue. In vitiligo, precipitating factors could induce melanocyte damage in genetically susceptible individuals and consequent cell death, loss of tolerance, and induction of melanocyte-directed autoimmunity. Future research will more precisely define the multiple biological events that regulate development of vitiligo.

Objective: To characterize the epidemiology and genetics of vitiligo and associated autoimmune diseases in a population isolate in Romania in which there is a high frequency of these diseases., Design: Prospective and retrospective ascertainment of all patients and extended families with these disorders in the study community., Setting: A geographically isolated community in the mountains of northern Romania. Patients Fifty-one affected individuals and their close relatives from 35 nuclear families in an extended kindred that effectively constitutes the entire community population., Main Outcome Measures: Demographic, phenotypic, and genetic aspects of vitiligo and other autoimmune diseases in the extended kindred., Results: The frequencies of vitiligo and several other autoimmune diseases, including autoimmune thyroid disease, adult-onset autoimmune diabetes mellitus, and rheumatoid arthritis, are greatly elevated. The age of vitiligo onset in this village is relatively delayed, suggesting that the causes of vitiligo in this community may be somewhat atypical. Genetic segregation analysis is most consistent with a single major locus recessive model, although incomplete penetrance and heritability suggest that other genes and nongenetic factors likely influence occurrence of disease in homozygotes., Conclusions: The high frequency of vitiligo and other autoimmune diseases in this isolated inbred community and an unusual aspect of the vitiligo phenotype suggest that susceptibility to these disorders in this "special population" may be unusual, likely involving a major recessive gene. Whereas disease susceptibility seems to involve a major genetic component, actual onset of vitiligo in genetically susceptible individuals seems to require exposure to environmental triggers.

The pathobiology of vitiligo has been hotly disputed for as long as one remembers, and has been a magnet for endless speculation. Evidently, the different schools of thought--ranging, e.g. from the concept that vitiligo essentially is a free-radical disorder to that of vitiligo being a primary autoimmune disease--imply very different consequences for the best therapeutic strategies that one should adopt. As a more effective therapy for this common, often disfiguring pigmentary disorder is direly needed, we must strive harder to settle the pathogenesis debate definitively--on the basis of sound experimental evidence, rather than by a war of dogmatic theories. Recognizing, however, that it is theories which tend to guide our experimental designs and choice of study parameters, the various pathogenesis theories on the market deserve to be critically, yet unemotionally re-evaluated. This Controversies feature invites you to do so, and to ask yourself: is there something important or worthwhile exploring in other pathogenesis scenarios than those already favoured by you that may help you improve your own study design, next time you have a fresh look at vitiligo? Vitiligo provides a superb model for the study of many fundamental problems in skin biology and pathology. Therefore, even if it later turns out that, as far as your own vitiligo pathogenesis concept is concerned, you have barked-up the wrong tree most of the time, chances are that you shall anyway have generated priceless new insights into skin function along the way.

Aim: To investigate the prevalence and clinical characteristics of vitiligo after allogeneic hematopoietic cell transplantation (AHCT)., Methods: The development of vitiligo was analyzed among 421 patients who underwent AHCT in Ibni Sina Hospital (University of Ankara) between 1988 and 2004., Results: Among 421 patients, we describe 6 with generalized vitiligo occurring after AHCT for chronic myelogenous leukemia. Five of them had severe chronic graft-versus-host disease (GVHD). Vitiligo was accompanied by alopecia areata and acquired ichthyosis in 2 patients with GVHD., Conclusion: Melanocyte destruction caused by the autoimmune reactions triggered by chronic GVHD as well as a genetic predisposition might have played a role in the development of vitiligo in our patients. These data support the hypothesis that vitiligo is an autoimmune entity., (Copyright 2008 S. Karger AG, Basel.)

Generalized vitiligo is an acquired disorder in which patches of depigmented skin, overlying hair and oral mucosa result from progressive autoimmune loss of melanocytes from the involved areas. Perhaps the most common pigmentary disorder, vitiligo results from a complex interaction of environmental, genetic and immunologic factors that ultimately contribute to melanocyte destruction, resulting in the characteristic depigmented lesions. In the past few years, studies of the genetic epidemiology of generalized vitiligo have led to the recognition that vitiligo is part of a broader, genetically determined, autoimmune and autoinflammatory diathesis. Attempts to identify genes involved in vitiligo susceptibility have involved gene expression studies, allelic association studies of candidate genes and genome-wide linkage analyses to discover new genes, and these studies have begun to shed light on the mechanisms of vitiligo pathogenesis. It is anticipated that the discovery of biological pathways of vitiligo pathogenesis will provide novel therapeutic and prophylactic targets for future approaches to the treatment and prevention of vitiligo and its associated autoimmune diseases.

Vitiligo is an autoimmune condition in which T cells recognize and destroy melanocytes. We present a case of a 20-year-old male who developed generalized vitiligo 4 years after allogeneic bone marrow transplantation (BMT) for Fanconi anemia. Although other autoimmune conditions have been well characterized as post-BMT complications, vitiligo is very rare. We review the 9 previously reported cases of post-BMT vitiligo.

A major concern for cancer vaccines targeting self-tumor antigens is the risk of autoimmune sequelae. Although antitumor immunity correlates with autoimmune disease in some preclinical models, the mechanism(s) linking antitumor immunity and subsequent autoimmune pathology remain(s) to be determined. In the current study, we demonstrated that intradermal (i.d.) immunization with a recombinant adenovirus (Ad) expressing the murine melanoma antigen tyrosinase-related protein 2 (AdmTrp-2) results in a moderate level of tumor protection against the B16F10 murine melanoma without any vitiligo. Similar immunization with an Ad encoding human Trp-2 (AdhTrp-2) resulted in 50-fold greater protective immunity and produced vitiligo in all of the mice, suggesting that the development of autoimmunity may reflect the potency of the vaccine. Interestingly, delivery of AdhTrp-2 by i.m. injection generated protective immunity comparable with that seen in mice that received the vaccine by the i.d. route, but none of the recipients in the i.m. group developed vitiligo. The cellular and humoral responses in the i.m. immunized mice were greater than in the i.d. group; therefore, the lack of vitiligo was not caused by reduced efficacy of the vaccine. These results led us to hypothesize that vaccine-induced vitiligo was associated with local inflammatory responses. Mice immunized i.m. with AdhTrp-2 did develop vitiligo when they subsequently were injected i.d. with either a control Ad vector or complete Freund's adjuvant, suggesting that vitiligo is initiated by some form of trauma within the skin. Our data demonstrated that autoimmune pathology is not an unavoidable outcome of effective cancer vaccines directed against self-tumor antigens.

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a critical immunoregulatory molecule (expressed on activated T cells and a subset of regulatory T cells) capable of down-regulating T cell activation. Blockade of CTLA-4 has been shown in animal models to improve the effectiveness of cancer immunotherapy. We thus treated 14 patients with metastatic melanoma by using serial i.v. administration of a fully human anti-CTLA-4 antibody (MDX-010) in conjunction with s.c. vaccination with two modified HLA-A*0201-restricted peptides from the gp100 melanoma-associated antigen, gp100:209-217(210M) and gp100:280-288(288V). This blockade of CTLA-4 induced grade III/IV autoimmune manifestations in six patients (43%), including dermatitis, enterocolitis, hepatitis, and hypophysitis, and mediated objective cancer regression in three patients (21%; two complete and one partial responses). This study establishes CTLA-4 as an important molecule regulating tolerance to "self" antigens in humans and suggests a role for CTLA-4 blockade in breaking tolerance to human cancer antigens for cancer immunotherapy.

Vitiligo is an autoimmune disease caused by T-lymphocyte-mediated destruction of melanocytes. We describe two patients with generalized vitiligo caused iatrogenically after donor lymphocyte infusion (DLI) for leukaemia relapse over 3 years after bone marrow transplantation (BMT). Neither the sibling donor nor the recipient had vitiligo or other autoimmune diseases, and vitiligo did not occur after the first BMT. DLI was accompanied by skin graft-versus-host disease in both cases, which was controlled with immunosuppression. However, over several months, progressive generalized and persistent skin depigmentation occurred in both patients. Peripheral blood molecular studies showed the complete disappearance of host haematolymphopoiesis. The specific destruction of melanocytes in both patients was therefore probably mediated by new alloreactive lymphocytes infused from the donors.

In patients infected with human immunodeficiency virus (HIV) the development of autoimmune diseases, while not life threatening, is an interesting phenomenon that may result from immune dysfunction or from B cell infection by HIV, Epstein-Barr virus, or other unknown viruses. Vitiligo and alopecia areata are among the autoimmune diseases that have been reported in 11 patients infected with HIV. We describe a 47-year-old man who had vitiligo and alopecia areata approximately 2 years after testing positive for HIV antibodies.

The authors studied the association between vitiligo and autoimmune thyroid disease. Vitiligo was found in 20 of 293 patients with autoimmune thyroid disease (6.83%), 2 out of 227 patients with nonautoimmune thyroid disease (0.88%), and 3 out of 386 control group (0.78%). These results showed that vitiligo is closely associated with autoimmune thyroid disease (chi 2 = 24.33, p < 0.0001), but not with nonautoimmune thyroid disease. Prevalence of vitiligo in nonautoimmune thyroid disease was not different from that in control. Vitiligo in autoimmune thyroid disease was most frequently found on dorsum hands and forearms, and usually preceded the onset of thyroid disease. Four out of twenty patients with vitiligo associated autoimmune thyroid disease had another presumed autoimmune disease, that is, alopecia areata, alopecia totalis, and rheumatoid arthritis. These findings suggested that autoimmunity plays an important role in the pathogenesis of vitiligo.

Persistent viral infections have been postulated to be trigger factors for the development of autoimmune disease. We report the development of vitiligo in four patients with human immunodeficiency virus (HIV)-related conditions and in one patient with hepatitis who later developed both psoriasis and acquired immunodeficiency syndrome (AIDS). Other common features were hepatitis and multiple other viral infections. Ribavirin was associated with repigmentation in one patient. Vitiligo may be an example of an autoimmune disease triggered by viral infection in a genetically predisposed host.