Vitiligo Taïeb, Alain; Picardo, Mauro
The New England journal of medicine,
01/2009, Letnik:
360, Številka:
2
Journal Article
Recenzirano
A healthy 25-year-old brunette woman reports a 12-month history of skin depigmentation. She first noticed patches of skin whitening on her hips, followed by additional depigmented patches on her ...elbows, shins, upper eyelids, and lower chin. A dermatologist recently made a diagnosis of vitiligo and recommended a sunscreen but offered little hope for treatment. How should she be evaluated and treated?
Vitiligo is the most common depigmenting disorder. This article reviews the distinctive clinical features of nonsegmental and segmental vitiligo and discusses treatment and management strategies.
Foreword
This
Journal
feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors' clinical recommendations.
Stage
A healthy 25-year-old brunette woman reports a 12-month history of skin depigmentation. She first noticed patches of skin whitening on her hips; her physician prescribed an imidazole cream for a presumed fungal infection, but there was no improvement. After a vacation at the beach, she noticed additional depigmented patches on her elbows, shins, upper eyelids, and lower chin. A dermatologist made a diagnosis of vitiligo and recommended a sunscreen but offered little hope for treatment. She feels stigmatized by her appearance. How should she be evaluated and treated?
The Clinical Problem
Vitiligo is the most common depigmenting disorder, with . . .
Skin barrier in the neonate Taïeb, Alain
Pediatric dermatology,
March/April 2018, 2018-Mar, 2018-03-00, 20180301, Letnik:
35, Številka:
S1
Journal Article
Recenzirano
Odprti dostop
The purpose of this review is to focus on determinants of skin barrier function in neonates at molecular and cellular levels. The skin barrier is critical in terms of water and gas exchanges during ...fetal life and undergoes rapid changes at birth, followed by a progressive maturation. Consequences of skin barrier disruption can be extremely detrimental or lethal, as shown in severe genetic epidermal defects. In this context, the fine‐tuned rapid adaptation from a liquid to a gaseous milieu is not fully understood. The stratum corneum provides an air‐liquid barrier, tight junctions in the granular layer provide a liquid‐liquid barrier, aquaporins represent a plumbing system for water‐glycerol as well as gas exchanges, and Langerhans cells are central to the immunological barrier. Acid mantle formation is essential for appropriate interaction between the skin and microbial symbionts. Temperature and pH regulate the key enzyme activities responsible for the integrity of the stratum corneum. Skin barrier permeability can be assessed noninvasively and simply with miniaturized devices measuring transepidermal water loss, where water flow is faster in cases of a damaged or functionally premature barrier. New avenues for therapeutic skin barrier research in neonates include a better delineation of the maturation of aquaporins in water balance and gas exchanges from fetal to neonatal life and a better understanding of the role of vernix caseosa, in particular, for the implantation of a healthy microbiote. Practical applications should be derived for caring for infant skin, particularly in fragile zones, such as the diaper area.
Infantile hemangiomas (IHs) are the most-common soft-tissue tumors of infancy. We report the use of propranolol to control the growth phase of IHs.
Propranolol was given to 32 children (21 girls; ...mean age at onset of treatment: 4.2 months) after clinical and ultrasound evaluations. After electrocardiographic and echocardiographic evaluations, propranolol was administered with a starting dose of 2 to 3 mg/kg per day, given in 2 or 3 divided doses. Blood pressure and heart rate were monitored during the first 6 hours of treatment. In the absence of side effects, treatment was continued at home and the child was reevaluated after 10 days of treatment and then every month. Ultrasound measurements were performed after 60 days of treatment.
Immediate effects on color and growth were noted in all cases and were especially dramatic in cases of dyspnea, hemodynamic compromise, or palpebral occlusion. In ulcerated IHs, complete healing occurred in <2 months. Objective clinical and ultrasound evidence of longer-term regression was seen in 2 months. Systemic corticosteroid treatment could be stopped within a few weeks. Treatment was administered for a mean total duration of 6.1 months. Relapses were mild and responded to retreatment. Side effects were limited and mild. One patient discontinued treatment because of wheezing.
Propranolol administered orally at 2 to 3 mg/kg per day has a consistent, rapid, therapeutic effect, leading to considerable shortening of the natural course of IHs, with good clinical tolerance.
Vitiligo is an acquired chronic depigmenting disorder of the skin, with an estimated prevalence of 0.5% of the general population, characterized by the development of white macules resulting from a ...loss of epidermal melanocytes. The nomenclature has been revised after an extensive international work within the vitiligo global issues consensus conference, and vitiligo (formerly non-segmental vitiligo) is now a consensus umbrella term for all forms of generalized vitiligo. Two other subsets of vitiligo are segmental vitiligo and unclassified/undetermined vitiligo, which corresponds to focal disease and rare variants. A series of hypopigmented disorders may masquerade as vitiligo, and some of them need to be ruled out by specific procedures including a skin biopsy. Multiple mechanisms are involved in melanocyte disappearance, namely genetic predisposition, environmental triggers, metabolic abnormalities, impaired renewal, and altered inflammatory and immune responses. The auto-immune/inflammatory theory is the leading hypothesis because (1) vitiligo is often associated with autoimmune diseases; (2) most vitiligo susceptibility loci identified through genome-wide association studies encode immunomodulatory proteins; and (3) prominent immune cell infiltrates are found in the perilesional margin of actively depigmenting skin. However, other studies support melanocyte intrinsic abnormalities with poor adaptation of melanocytes to stressors leading to melanocyte instability in the basal layer, and release of danger signals important for the activation of the immune system. Recent progress in the understanding of immune pathomechanisms opens interesting perspectives for innovative treatment strategies. The proof of concept in humans of targeting of the IFNγ /Th1 pathway is much awaited. The interplay between oxidative stress and altered immune responses suggests that additional strategies aiming at limiting type I interferon activation pathway as background stabilizing therapies could be an interesting approach in vitiligo. This review covers classification and clinical aspects, pathophysiology with emphasis on immunopathogenesis, and promising therapeutic approaches.
Summary
From a therapeutic standpoint, vitiligo is still regarded by many physicians as a simple problem of regenerative medicine, with the main aim to repopulate the depigmented skin with functional ...melanocytes from the margins of the lesions or from intact progenitors in hair follicles. However, recent research in vitiligo suggests that various local triggers alert the skin immune innate system and may precede adaptive immune responses targeting melanocytes. This scenario is close to that of other common skin inflammatory disorders like psoriasis and atopic, and suggests to target as a priority this clinically silent inflammatory component of he disease. This perspective highlights possible targets for intervention.
The clinical assessment of vitiligo involves an estimation of the affected body surface area. The most commonly used method is the “palm of hand 1% rule” as integrated in the Vitiligo Area Scoring ...Index. However, this method can be challenging and time consuming. In this study, we introduce a global Vitiligo Extent Score (VES). In the first part of the study, this measurement instrument was developed and subsequently optimized during a pilot scoring session. In a subsequent stage, the inter- and intrarater reliability of the instrument were tested. Live scoring showed an excellent interrater reliability for the VES (intraclass correlation VES: 0.924 vs. Vitiligo Area Scoring Index: 0.846). Subsequent scoring on pictures was comparable with the live evaluation and demonstrated an excellent intrarater reliability. A high intraclass correlation for the VES (intraclass correlation VES: 0.923 vs. Vitiligo Area Scoring Index: 0.757) was also found in an additional subgroup of patients with extensive vitiligo. Moreover, user-friendliness and timing were scored very favorably. In conclusion, this measurement instrument allows us to monitor accurately and easily the affected body surface area in a standardized way. Moreover, our results provide evidence that the VES can be proposed as a promising tool to measure the vitiligo extent in clinical trials and in daily practice.
Interleukin (IL)-13 plays a key role in type 2 inflammation and is an emerging pathogenic mediator in atopic dermatitis (AD).
We investigated the efficacy and safety of lebrikizumab, an IL-13 ...monoclonal antibody, as an add-on to topical corticosteroid (TCS) treatment.
A randomized, placebo-controlled, double-blind, phase 2 study. Adults with moderate-to-severe AD were required to use TCS twice daily and then randomized (1:1:1:1) to lebrikizumab 125 mg single dose, lebrikizumab 250 mg single dose, lebrikizumab 125 mg every 4 weeks for 12 weeks, or placebo every 4 weeks for 12 weeks, after a 2-week TCS run-in. The primary endpoint was percentage of patients achieving Eczema Area and Severity Index (EASI)-50 at week 12.
In total, 209 patients received the study drug. At week 12, significantly more patients achieved EASI-50 with lebrikizumab 125 mg every 4 weeks (82.4%; P = .026) than placebo every 4 weeks (62.3%); patients receiving a single dose of lebrikizumab showed no statistically significant improvements in EASI-50 compared with placebo. Adverse events were similar between groups (66.7% all lebrikizumab vs 66.0% placebo) and mostly mild or moderate.
Protocol-mandated twice daily TCS treatment limits our understanding of the efficacy of lebrikizumab as a monotherapy. The short study duration did not enable long-term efficacy or safety evaluations.
When combined with TCS, lebrikizumab 125 mg taken every 4 weeks led to a significant improvement and was well tolerated in patients with moderate-to-severe AD.
Propranolol for Severe Hemangiomas of Infancy Taïeb, Alain; Thambo, Jean-Benoît; Léauté-Labrèze, Christine ...
The New England journal of medicine,
06/2008, Letnik:
358, Številka:
24
Journal Article
Recenzirano
Odprti dostop
Despite their self-limited course, infantile capillary hemangiomas can impair vital or sensory functions or cause disfigurement. These authors have observed in 11 children that propranolol can ...inhibit the growth of these hemangiomas.
To the Editor:
Despite their self-limited course, infantile capillary hemangiomas can impair vital or sensory functions or cause disfigurement. Corticosteroids are the first line of treatment for problematic infantile capillary hemangiomas
1
,
2
; other options include interferon alfa
3
and vincristine.
1
We have observed that propranolol can inhibit the growth of these hemangiomas. Our preliminary data from 11 children are summarized in Table 1 in the Supplementary Appendix, available with the full text of this letter at www.nejm.org.
The first child had a nasal capillary hemangioma. Despite corticosteroid treatment, the lesion was stabilized but obstructive hypertrophic myocardiopathy developed, so the patient was . . .
The risk of relapse after successful repigmentation in vitiligo is estimated to 40% within the first year. It has been shown in atopic dermatitis that continuous low-level use of topical ...corticosteroids and calcineurin inhibitors in previously affected skin can prevent new flares. We hypothesized that a twice-weekly application of 0.1% tacrolimus ointment might be effective for maintaining repigmentation in therapeutically repigmented lesions of vitiligo patients. After randomization, sixteen patients with 31 patches were assigned to the placebo group and 19 patients with 41 patches were assigned to the tacrolimus group. In the intention-to-treat analysis, 48.4% of lesions showed depigmentation in the placebo group, whereas 26.8% did in the tacrolimus group (P=0.059). The intention-to-treat results did not remain significant after adjustment for within-patient clustering, odds ratio (OR) 2.55; 95% confidence interval (CI; 0.65–9.97); P=0.1765. The per-protocol analysis (n=56) showed that 40% of lesions had some depigmentation in the placebo group, whereas only 9.7% did in the tacrolimus group (P=0.0075). The per-protocol results remained significant after adjustment for within-patient clustering: OR 6.22; 95% CI (1.48–26.12); P=0.0299. Our study shows that twice-weekly application of 0.1% tacrolimus ointment is effective in preventing the depigmentation of vitiligo patches that have been previously successfully repigmented.
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