Worldwide expert recommendations for the diagnosis and management of vitiligo: Position statement from the international Vitiligo Task Force-Part 2: Specific treatment recommendations.

BACKGROUND: The treatment of vitiligo can be challenging. Up-to-date agreed consensus recommendations on the use of topical and systemic therapies to facilitate the clinical management of vitiligo are currently lacking. OBJECTIVES: To develop internationally agreed-upon expert-based recommendations for the treatment of vitiligo. METHODS: In this consensus statement, a consortium of 42 international vitiligo experts and four patient representatives participated in different online and live meetings to develop a consensus management strategy for vitiligo. At least two vitiligo experts summarized the evidence for different topics included in the algorithms. A survey was then given to a core group of eight experts to resolve the remaining issues. Subsequently, the recommendations were finalized and validated based on further input from the entire group during two live meetings. RESULTS: The recommendations provided summarize the latest evidence regarding the use of topical therapies (steroids, calcineurin inhibitors and Jak-inhibitors) and systemic therapies, including steroids and other systemic immunomodulating or antioxidant agents. The different modalities of phototherapies (NB-UVB, photochemotherapy, excimer devices and home phototherapy), which are often combined with other therapies, are also summarized. Interventional approaches as well as depigmentation strategies are presented for specific indications. Finally, the status of innovative and targeted therapies under development is discussed. CONCLUSIONS: This international consensus statement culminated in expert-based clinical practice recommendations for the treatment of vitiligo. The development of new therapies is ongoing in vitiligo, and this will likely improve the future management of vitiligo, a disease that still has many unmet needs.

Worldwide expert recommendations for the diagnosis and management of vitiligo: Position statement from the International Vitiligo Task Force Part 1: towards a new management algorithm.

BACKGROUND: The treatment of vitiligo can be challenging and depends on several factors such as the subtype, disease activity, vitiligo extent, and treatment goals. Vitiligo usually requires a long-term approach. To improve the management of vitiligo worldwide, a clear and up-to-date guide based on international consensus with uniform stepwise recommendations is needed. OBJECTIVES: To reach an international consensus on the nomenclature and to develop a management algorithm for the diagnosis, assessment, and treatment of vitiligo. METHODS: In this consensus statement, a consortium of 42 international vitiligo experts and four patient representatives participated in online and live meetings to develop a consensus management strategy for vitiligo. At least two vitiligo experts summarized the evidence of topics included in the algorithms. A survey was utilized to resolve remaining issues among a core group of eight experts. Subsequently, the unanimous recommendations were finalized and validated based on further input from the entire group during two live meetings. RESULTS: The algorithms highlight the importance of shared decision-making. Dermatologists are encouraged to provide patients with detailed explanations of the prognosis and expected therapeutic outcomes based on clinical examination. The treatment goal should be discussed and clearly emphasized to patients given the different approaches for disease stabilization and repigmentation. The evaluation of disease activity remains a cornerstone in the tailor-made approach to vitiligo patients. CONCLUSIONS: These new treatment algorithms are intended to guide clinical decision-making in clinical practice. Promising novel therapies for vitiligo are on the horizon, further highlighting the need for reliable outcome measurement instruments and greater emphasis on shared decision-making.

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.

Thyroid autoimmunity in relation to HLA-DRB1 and HLA-DQB1 polymorphism in nonsegmental vitiligo: a cross-sectional-study.

OBJECTIVES: Nonsegmental vitiligo (NSV) is frequently associated with thyroid autoimmunity (TAI), however, the immunopathogenic mechanisms of such association remain to be investigated. The aims of this work were to estimate the frequency of TAI and to describe the genetic polymorphism in the human leukocyte antigen (HLA)-DRB1 and -DQB1 loci in TAI susceptibility among patients with NSV. PATIENTS AND METHODS: In this cross-sectional study, screening for TAI was performed in 97 Moroccan patients with NSV by measuring antibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TGAb). HLA-DRB1 and -DQB1 were determined with single specific primer-polymerase chain reaction (PCR-SSP) typing methods. RESULTS: TAI was diagnosed in 20 patients with NSV (20.6%). The phenotypic frequency of DQB1*05 (OR = 5.04; P = 0.006; pc = 0.036) was significantly higher in NSV patients with TAI. Genotype DQB1*05/DQB1*06 (OR = 25.33; P = 0.001; pc = 0.003) confer susceptibility to TAI in NSV patients. NSV patients with TAI and early onset vitiligo have an extremely high phenotype frequency of DQB1*05 allele (OR = 14.67; P = 0.001; pc = 0.048) and DQB1*05/DQB1*06 genotype (OR = 26.55; P = 0.01; pc = 0.03). TAI in patients with NSV was (6.2%) associated with onset of clinical thyroid disease based on TSH and free T4. CONCLUSION: Our findings suggest that HLA-DQ polymorphisms influence TAI risk in subjects with NSV, although HLA does not completely explain the co-occurrence of these two diseases.

Paraneoplastic scleroderma in Kaposi's sarcoma: Report of two cases.

Kaposi's sarcoma (KS) is a proliferative and multifocal disease with a double vascular and fibroblastic cell component, of mucocutaneous and visceral expression. It is a multifocal tumoral process, hyperplastic in nature without metastatic potential, induced by the human herpes virus 8 (HHV8). Paraneoplastic syndromes (PS) in KS are rare, with only a small number of cases reported and we have found no previous descriptions of a paraneoplastic scleroderma in KS in the literature. We report the cases of two patients with this atypical PS.

Surgical management of deep dermatophytosis in a patient with CARD9 deficiency.

Deep dermatophytosis is a dermal infection caused by Dermatophytes. It can cause deeper dermal dermatophytosis, Majocchi's granuloma, dermatophytic pseudomycetoma or a widespread infection. CARD9 deficiency is a known risk factor in the Mediterranean region, first reported in 1964 in Morocco. We report a case of 23-year-old man with a scarring alopecia who presented with subcutaneous abscesses topped off with a large ringworm infection. Mycotic analysis revealed a Trichophyton Rubrum deep dermatophytosis. The molecular study revealed a CARD9 mutation confirming dermatophytosis with parotid and lymph nodes involvement. The patient underwent successful drainage surgery of the abscesses alongside medical treatment including antifungal agents and he was discharged after an uneventful postoperative course.

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.

Subcutaneous phaeohyphomycosis caused by Aureobasidium Pullulans in an immunocompetent carpenter.

Phaeohyphomycosis refers to uncommon infections due to a large group of heterogeneous organisms called "dematiaceous fungi". Here, we report a rare case of subcutaneous phaeohyphomycosis in an immunocompetent carpenter, presenting as multiple verrucous and confluent papulo-nodules of the right leg, and likely due to traumatic inoculation. The pathogenic fungal species was identified as Aureobasidium pullulans, according to macroscopic and microscopic morphological characteristics of the colonies. Surgical excision of the entire lesion and adjunctive antifungal therapy was curative.

[Sneddon-Wilkinson disease: a case report]. / Maladie de Sneddon-Wilkinson: à propos d'un cas.

Sneddon-Wilkinson disease is a benign amicrobial pustulosis belonging to the spectrum of neutrophilic dermatoses. It is characterized by evident stereotypic clinical features, including, in most cases, pustular lesions of the trunk and prominent skin folds. This pustulosis may be associated with other diseases (IgA monoclonal gammopathy, rheumatoid arthritis, neoplasms or other neutrophilic dermatoses) and therefore requires regular follow-up. This disease has a relapsing-remitting course. First line therapy is dapsone. We here report the case of a 49-year-old patient with amicrobial pustulosis (Sneddon-Wilkinson disease).

A polymorphous cutaneous tuberculosis.

Cutaneous tuberculosis is uncommon, comprising 1%-2% of all extrapulmonary manifestations. It has a wide clinical spectrum. The clinical presentation depends on the route of the infection, the pathogenicity of the bacteria, and the immune status of the host. Association of multiple forms in a same patient is uncommon. We report a case of disseminated tuberculosis with polymorphous cutaneous lesions in an immunocompetent woman, combining scrofuloderma, gummas, and sporotrichoid lesions, along with tuberculous adenitis and bone tuberculosis.

Toe necrosis: report of uncommon aetiology.

Toe necrosis has many aetiologies. The most common one is ischaemia. In fact, both direct and indirect toe necrosis, as well as related lower limb gangrene, could be secondary to mechanical trauma, infections, pharmacological sensitivity, cancer, blue toe syndrome and other granulomatous diseases. We report a case of toes necrosis caused by an uncommon aetiology.

[Predisposition to infection in patients with pemphigus. Retrospective study of 141 cases]. / Prédisposition aux infections des malades ayant un pemphigus Etude rétrospective de 141 cas.

INTRODUCTION: The relation between pemphigus and infection is complex. The aim of this work was to determine the frequency and impact of infection as well as the factors associated with it among our patients with pemphigus. METHODS: This retrospective case series examined records of patients with pemphigus admitted to the dermatology unit of Ibn Sina University Hospital of Rabat between 1989 and 2004. We compared the patients with and without infections as well as the patients with and without severe bacterial infections according to patient profile and outcome. The principal outcome measure was death and the secondary measure, duration of hospitalization. RESULTS: Of the 141 patients with pemphigus included in our study, 68% developed an infection. Infections were bacterial in 52% of cases, fungal in 50%, herpetic in 19% and parasitic in 1.5%. They were associated with diabetes mellitus and immunosuppressive drugs. Severe bacterial infection was frequent in patients with diabetes and rare in those treated with corticosteroids or with pemphigus foliaceous. Death occurred significantly more often among infected subjects (p=0.01), especially those with severe bacterial infections (p<0.001). Hospitalization was slightly longer among patients with infections (p=0.01) but shorter in cases of severe bacterial infections (p=0.004). DISCUSSION: Our study confirms the predisposition to all types of infection among patients with pemphigus, as well as the undeniable role its treatment plays in promoting infection. Severe bacterial infections were most often contracted before hospitalization. The literature reports a wide variety of infections, with pemphigus-herpes documented most often. Prevention and management require hygienic measures as well as early diagnosis and treatment of pemphigus and infections. Preventive treatment may be considered, but studies are needed to define the patients who might benefit from it.

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.

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.