Varicella-zoster virus in actively spreading segmental vitiligo skin: Pathological, immunochemical, and ultrastructural findings (a first and preliminary study).

Segmental vitiligo (SV) is a unilateral subtype of vitiligo which is clinically characterized by a cutaneous depigmentation and histologically by a melanocyte loss from the epidermis and hair follicle reservoirs. To date, its pathogenesis remains a mystery. In many cases, this skin depigmentation shares several clinical features and dysfunctions with herpes zoster (HZ). So, for the first time, we examined whether any nucleus and cell fusion associated with a positive immunolabelling of varicella-zoster virus (VZV) and VZV mature virions could be found in SV skin samples as in herpes zoster (HZ). A total of 40 SV samples were used for histological and immunochemical studies. Control samples were obtained from three HZ, and 10 generalized vitiligo lesions. For ultrastructural study, three recent SV and one HZ as controls were recruited. Here, we report that nuclear fusion in epidermal cells were statistically associated with recent SV (p < .001), whereas syncytia formation was associated with long-lasting SV (p = .001). A positive detection of VZV antigen was statistically associated in the epidermis with recent SV and in the dermis with long-lasting SV (p = .001). Finally, the discovery of mature virions in 3/3 recent SV samples provides additional arguments for our viral hypothesis.

Shared histological and immunohistological findings in two patients with generalized vitiligo associated with autoimmune atrophic gastritis.

The prevalence of autoimmune atrophic gastritis (AAG) in vitiligo patients was estimated at about 15%. In both conditions, a release of specific antibodies and an autoimmune destruction of target cells (melanocytes in vitiligo, parietal cells (PC) in AAG) mediated by CD8-T lymphocytes was demonstrated to perform a comparative histological study of vitiligo skin and AAG mucosa. In two patients with concomitant vitiligo and AAG, biopsies from the vitiligo lesions and gastric mucosa from corpus fundus were performed. Sections were immunostained with E-cadherin, Coll IV, CD8, CD20, CD4 antibodies. The skin sections also were stained with HES, HMB45, MITF. Common histological findings were found in both diseases. Adhesivity impairment with down expression of E-cadherin and Coll IV was objectivated. The protruding MITF+melanocytes and the detached PC were surrounded by an infiltrate including CD8 and CD4. CD8 was infiltrating the epidermis in close contact with the remaining melanocytes and the gastric glands around the remaining PC. In both diseases, the autoimmune process could be preceded by a detachment of either melanocytes in vitiligo or PC in AAG possibly in relation to an initial adhesivity impairment of these cells. Common autoimmune mechanisms could be suggested for both diseases.

Tacrolimus (FK506) ointment combined with Nb-UVB could activate both hair follicle (HF) and dermal melanocyte precursors in vitiligo: the first histopathological and clinical study.

Topical Tacrolimus, especially when combined with Nb-UVB, has been proven clinically to be effective in the treatment of vitiligo. However, no histological study has evaluated the repigmentation mechanism of tacrolimus ointment in combination therapy with Nb-UVB. In this study, the histological findings in patients receiving Nb-UVB were compared with those receiving topical tacrolimus combined with Nb-UVB. Twenty patients were recruited and received Nb-UVB treatment. The first ten patients were selected for the combination therapy and instructed to apply tacrolimus 0.1% ointment twice daily on the specified lesion of interest. The remaining ten patients did not receive any other topical treatments. Skin biopsy was performed at baseline from the depigmented area and 2-3 months post-treatment from the repigmented area. Biopsy specimens were stained with haematoxylin-eosin-safran (HES), Fontana Masson, HMB45, Melan A, MITF, SOX10 and Nestin. Clinically, in the combination therapy group, interfollicular repigmentation in addition to the perifollicular and marginal pattern was observed. Histologically, in the combination therapy group, besides the migration of melanocytes from the bulge of the hair follicle seen in the monotherapy group, for the first time, we observed dermal melanocyte precursors located in mid- and superficial dermis.

CDH1 and DDR1 common variants confer risk to vitiligo and autoimmune comorbidities.

The weaker expression of the two main proteins adhering melanocytes to the epidermis basal layer, Epithelial Cadherin (E-cadherin) and Discoidin Domain Receptor Tyrosine kinase 1 (DDR1), has been implicated as one of the aggravating factors in the loss of melanocytes in vitiligo. The present study was designed to assess the association between single nucleotide polymorphisms (SNP) in the genes encoding these proteins, CDH1 and DDR1, and the risk of developing vitiligo. The independent case-control study was conducted on the sample including152 patients with vitiligo and 152 matched controls. A questionnaire was completed for recording demographic and clinical characteristics of vitiligo patients. Venous blood samples were taken from all the subjects. Genotype frequencies were determined for CDHI C/T (rs 10431924) and DDRI A/C (rs 2267641) genes polymorphisms using polymerase chain reaction (PCR) amplification method and Restriction Fragment Length Polymorphism (RFLP) analysis. The CDH1 CC genotype was found to be significantly associated with the risk of developing vitiligo. The results of stratified analysis revealed a correlation between CDH1 CC genotype and late age of onset, clinical type of vitiligo, the absence of autoimmune comorbidities and family history of autoimmune disorders. However, the expression level of CDH1 TT genotype increased significantly in patients with autoimmune comorbidities. There was also a significant relationship between the DDR1 CC genotype and the risk of developing vitiligo. The results of stratified analysis revealed a correlation between DDR1 CC genotype and early age of onset, clinical type of vitiligo and absence of family history of autoimmune disorders. The findings of the study confirm the conjecture previously made in the literature regarding the melanocytes' adhesion deficit as an initial step for pigment loss in vitiligo and emphasize the substantial role of friction and koebner phenomenon in the pathogenesis of vitiligo. Moreover, a probable association can be proposed between the adhesion deficit involved in vitiligo and autoimmune disorders.

Evaluation of using fractional CO2 laser plus NB-UVB versus NB-UVB alone in inducing marginal repigmentation of vitiligo lesions.

Background: Vitiligo is a common depigmenting skin disorder, characterized by patchy loss of skin color and finding effective treatment has remained a challenging issue. Methods: A paired (half-body) randomized clinical trial study was done to compare the efficacy and the safety of narrowband ultraviolet B (NB-UVB) plus fractional CO2 versus NB-UVB alone in stimulation of marginal repigmentation of vitiliginous patches. One side of the body was randomly treated with a fractional CO2 laser and NB-UVB twice weekly, while the other side was exposed only to NB-UVB with the same manner. Results: Thirty patients with the nonsegmental stable vitiligo and mean age of 43 ± 15 years completed a 16-week treatment period with NB-UVB on one side of the body and fractional CO2 laser therapy with NB-UBV on the other side. In addition to the higher rate of response in the combination side compared to the monotherapy side of the body (p < .001), repigmentation was greater in the combination side rather than the NB-UVB monotherapy side (p = .002). In the combination treated side, marginal repigmentation pattern was more frequently seen than perifollicular pattern (p < .001) and more frequently than monotherapy side (p < .001). Conclusion: The fractional CO2 laser combined with NB-UVB seems to be a more effective therapeutic option for treatment than NB-UVB alone for inducing marginal repigmentation.

The first transepidermal transplantation of non-cultured epidermal suspension using a dermarolling system in vitiligo: A sequential histological and clinical study.

The current methods for melanocyte delivery to depigmented skin are invasive and often require sophisticated approaches. Here, we describe a promising simple and minimally invasive technique based on the dermarolling system. The technique involves preparation of a keratinocyte/melanocyte suspension prepared by trypsinization from a non-lesioned part of a patient's scalp skin and transepidermal delivery using a dermaroller equipped with 0.2-mm needles. Dermarolling leads to epidermal microinjuries without, however, causing pain or inflammation. The technique was applied to facial depigmented areas of five patients with stable vitiligo that were resistant to conventional UV/tacrolimus treatment. The efficacy of cell delivery was analysed histologically on punch biopsies, and repigmentation was evaluated photographically and by clinical assessment. We found that the transplanted keratinocytes rapidly degenerated, leading to keratinization, but melanocytes survived and integrated appropriately into the basal layer of the epidermis, leading to excellent repigmentation after 6 months in three cases and mild repigmentation in two cases. Although based on a small number of patients, we anticipate this technique to become a valid addition to the arsenal of therapeutic approaches to repigmentation in depigmenting disorders.

Clinical markers of vitiligo activity.

BACKGROUND: Current modalities of understanding disease state (active/stable) are limited when considering treatment of vitiligo. OBJECTIVE: We sought to develop a rapid, accurate, and noninvasive assessment of vitiligo state. METHODS: In daylight and Wood's light examinations, 2 common clinical types of vitiligo were identified as amelanotic with sharply demarcated borders and hypomelanotic with poorly defined borders. Photographs were taken at the time of examination and a skin biopsy at the edge of a vitiligo lesion was performed. One year after the initial visit, the vitiligo was classified as stable if no new lesions had appeared, and as active if the number, size, or both of existing vitiligo lesions were increased. Skin biopsy specimens from 71 patients were stained and immunostained for melanocytes, CD8+ T lymphocytes, and E-cadherin. RESULTS: The active lesions were associated with hypomelanotic appearance with poorly defined borders (P < .001), and histologically with an infiltration of CD8+ T lymphocytes in the epidermis and dermis (P = .017), with a strong expression of E-cadherin (P = .044). LIMITATION: The fact that this was a single-center study and that activity was sometimes site-dependent are limitations. CONCLUSION: The hypomelanotic with poorly defined borders type could be a good indicator of the actual activity of a vitiligo lesion.

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.

[Crossroads, 50 years of child care]. / La croisée des chemins, 50 ans de soins aux enfants.

INTRODUCTION: Through a journey in time, we propose to revisit the birth of the first mental health care settings for children with mental disorders affiliated with Université de Montréal, Quebec, Canada. METHODS: The main centers of child psychiatry affiliated with the Université de Montréal are presented with the outstanding figures of the time. RESULTS: Philosophical transitions and therapeutic paradigms are also briefly discussed. The creation of subspecialty clinics and training approved by the Royal College of Psychiatry of Child and Adolescent marked the contemporary era. CONCLUSION: The contribution to training medical students, residents and researchers in the field of Child and Adolescent Psychiatry reflects the important milestones since the foundation of the Université de Montréal Department of Psychiatry. So much achieved in half a century.

Altered E-Cadherin Levels and Distribution in Melanocytes Precede Clinical Manifestations of Vitiligo.

Vitiligo is the most common depigmenting disorder resulting from the loss of melanocytes from the basal epidermal layer. The pathogenesis of the disease is likely multifactorial and involves autoimmune causes, as well as oxidative and mechanical stress. It is important to identify early events in vitiligo to clarify pathogenesis, improve diagnosis, and inform therapy. Here, we show that E-cadherin (Ecad), which mediates the adhesion between melanocytes and keratinocytes in the epidermis, is absent from or discontinuously distributed across melanocyte membranes of vitiligo patients long before clinical lesions appear. This abnormality is associated with the detachment of the melanocytes from the basal to the suprabasal layers in the epidermis. Using human epidermal reconstructed skin and mouse models with normal or defective Ecad expression in melanocytes, we demonstrated that Ecad is required for melanocyte adhesiveness to the basal layer under oxidative and mechanical stress, establishing a link between silent/preclinical, cell-autonomous defects in vitiligo melanocytes and known environmental stressors accelerating disease expression. Our results implicate a primary predisposing skin defect affecting melanocyte adhesiveness that, under stress conditions, leads to disappearance of melanocytes and clinical vitiligo. Melanocyte adhesiveness is thus a potential target for therapy aiming at disease stabilization.

Whose Rights Count? Negotiating Practice, Policy, and Legal Dilemmas Regarding Infant-Parent Contact When Infants are in Out-of-Home Care.

This article takes a human rights perspective with a view to articulating the infant's perspective when the infant has been subjected to abuse, neglect, or both and is reliant on the state to ensure his or her health and well-being. When a young child is removed from parental care, important and often difficult decisions have to be made about subsequent contact between child and parent. We consider a number of dilemmas which may arise for practitioners when they are assisting child welfare decision makers in relation to contact, and acknowledge the limited empirical follow-up studies of the impact of child welfare practice and legal decisions on infant outcomes. We draw on the significant and substantive evidence base about infant emotional and cognitive development and infant-parent attachment relationships as well as infant mental health to illuminate the infant's subjective experience in these practice dilemmas. We describe innovations in practice from various countries, which seek to shed light on the challenges often associated with contact.

[Brunschvicg, bachelard and the internal logic of scientific discourse]. / Bachelard et Brunschvicg la Logique Interne du Discours Scientifique Bachelard und Brunschvicg die Innere Logik des Wissenschaftlichen Diskurses Bachelard y Brunschvicg la Lógica Interna del Discurso Científico.

Bachelard is seen as sharing with Brunschvicg an "internalist" epistemology of mathematics and exact sciences. Brunschvicg's notion of constructive idealism concurs with Bachelard's surrationalism. Both philosophers defended the idea of an internal logic of scientific discourse which discloses the dialectics inherent in the dynamics of reason. The aim of philosophy is then to emphasize the genesis and progress of rationality in the historical development of science.

Non-cultured epidermal suspension in vitiligo: from laboratory to clinic.

BACKGROUND: Medical treatments are ineffective in many patients and surgical methods have therefore been developed. OBJECTIVE: A review of autologous non-cultured melanocyte grafting techniques is proposed to obtain a successful repigmentation of vitiligo macules. METHODS: Initially in 1992, we had developed a simplified grafting method which was carried out in the following two steps: production of blisters on the depigmented lesions by freezing with liquid nitrogen and injection in each blister of a non-cultured suspension of epidermal cells. The cellular suspension was obtained from samples of skin of the hair scalp after trypsinization. This very simple technique could be used at the dermatologist's clinic. Since 1998 (Olsson MJ, Juhlin L), quite comparable but improved and more sophisticated techniques have been proposed for the surgical treatment of vitiligo. These techniques require a laboratory set up to perform the melanocyte transplantation. The donor zone was usually taken on the gluteal region. The time of trypsinization was reduced to 60 minutes at 37°C and the centrifuged cellular suspension added with hyaluronic acid (Van Geel) was directly applied on a dermabraded or laser abraded vitiligo lesions. RESULTS: Whatever the technique chosen, repigmentation was evident within 25 to 30 days. Coalescence of the pigmented areas was spontaneously observed or obtained after UVB radiation. It is obvious that the complete repigmentation occurred more rapidly with the recent techniques compared with the initial method, but the efficiency was quite similar. CONCLUSION: The use of non-cultured epidermal suspension appears to be an effective, safe, and simple method for treating patients with achromic areas lacking melanocytes.

Segmental vitiligo associated with generalized vitiligo (mixed vitiligo): a retrospective case series of 19 patients.

BACKGROUND: Mixed vitiligo (MV), the association of segmental vitiligo (SV) and nonsegmental vitiligo, has been rarely reported. OBJECTIVE: The aim of this study was to delineate the clinical spectrum of MV through a case series of patients with typical SV associated with patchy bilateral vitiligo. METHODS: This was a cross-sectional evaluation in the setting of a prospective observational study conducted in the vitiligo clinic of the department of dermatology in Bordeaux, France. RESULTS: Nineteen patients with MV were identified. Four were male and 15 were female. Most patients had an onset of SV before the age of 18 years (18 of 19). In all patients, SV preceded nonsegmental vitiligo with a delay ranging from 6 months to more than 24 months. LIMITATIONS: This study was cross-sectional and based on a single-center experience. CONCLUSION: MV is not yet part of a conventional classification. However, this entity may have been neglected until now and should be included in the classification of vitiligo in addition to SV and nonsegmental vitiligo. Moreover, MV may be essential to the understanding of the pathogenesis of vitiligo as a primary skin disorder.

Koebner's phenomenon in vitiligo: European position paper.

Koebner's phenomenon (KP) has been observed in a number of skin diseases, including vitiligo. Its clinical significance in vitiligo with respect to disease activity and course is still debatable, while its relevance for surgical techniques has been demonstrated in some reports. We present a literature review on the currently known facts about KP in vitiligo, including details of clinical, experimental, and histopathological changes. The consensus view is that there are still no methods to define and assess KP in vitiligo. A new classification is proposed to allow an evaluation of KP in daily practice or in experimental studies. However, many unanswered questions still remain after redefining KP in patients with vitiligo. Active research focusing on KP in vitiligo may not only provide unexpected clues in the pathogenesis of vitiligo but also help to tailor novel therapies against this chronic and often psychologically devastating skin disease.

Child analysis in a changing world. In the face of a paradigm shift from the mind to the brain: Can we meet the challenge?

Child analysts and child therapists are now practicing in a new environment where an increased emphasis is made on identifying the symptoms and finding the shortest possible way to get rid of them, from the knowledge of brain functioning. From that perspective, the history of the symptom, of the child who owns it, and of the family in which this child is being raised are not emphasized as strongly. Searching for a specific meaning of such symptoms seems to be of no more interest. How can such a heavy trend be met? Major changes also have occurred within the psychoanalytic milieu. Advances from the observational world, from Spitz (1945) to Bowlby's (1987) attachment theory, provide essential knowledge to the field of early child-parent interactions. Longitudinal research in recent decades has shown close ties between early development and future outcomes. Such new knowledge is inspiring child analysis with very young children as well as with severely disturbed, older children. Early intervention with disadvantaged populations is showing the importance of the nonspecific aspects of the therapeutic relationship as a factor of change. In light of recent neurobiologic research on the influence of a specific environment-attachment experiences-on early development of the brain, it is now possible to speak of the social brain (Cozolino, 2006).