Guidelines for the management of vitiligo: the European Dermatology Forum consensus.

The aetiopathogenic mechanisms of vitiligo are still poorly understood, and this has held back progress in diagnosis and treatment. Up until now, treatment guidelines have existed at national levels, but no common European viewpoint has emerged. This guideline for the treatment of segmental and nonsegmental vitiligo has been developed by the members of the Vitiligo European Task Force and other colleagues. It summarizes evidence-based and expert-based recommendations (S1 level).

Epitopes, avidity and IgG subclasses of tyrosine hydroxylase autoantibodies in vitiligo and alopecia areata patients.

BACKGROUND: We previously detected antibodies against tyrosine hydroxylase (TH) in 23% of patients with nonsegmental vitiligo and in 19% of patients with alopecia areata (AA). OBJECTIVES: To identify TH epitopes recognized by TH antibodies in patients with vitiligo and AA. METHODS: Recombinant plasmids containing defined fragments of TH cDNA were constructed. The cloned TH cDNA fragments were subsequently translated in vitro to produce a series of [(35) S]-labelled TH protein fragments which were then used in radioimmunoassays to analyse the immunoreactivity of sera from 18 TH antibody-positive patients with vitiligo and so initially define TH epitope domains. Further localization of TH epitopes was investigated by antibody absorption experiments using synthetic TH peptides and nonradiolabelled, in vitro-expressed TH protein fragments. Antibody binding to identified epitopes was confirmed in TH peptide enzyme-linked immunosorbent assays. RESULTS: Analysis of the results obtained indicated the presence of two major antibody-binding sites on TH between amino acids 1 and 14 (epitope 1-14) and between amino acids 61 and 80 (epitope 61-80). Of 18 patients with vitiligo and six with AA, 17 (94%) and five (83%), respectively, had antibodies against epitope 1-14. In addition, 11/18 (61%) vitiligo and 2/6 (33%) AA patient sera displayed immunoreactivity against epitope 61-80. CONCLUSIONS: Two major binding sites for human TH antibodies are located at the N-terminus of the protein. The humoral immune response to TH in vitiligo and AA is heterogeneous in nature in that patients may have antibodies to more than one TH epitope. TH antibodies from patients with vitiligo or AA can recognize identical epitopes.

Risk management in dermatology: an analysis of data available from several British-based reporting systems.

BACKGROUND: The elimination or reduction of risk is a prime requirement of all healthcare workers. The matter has come to the fore in dermatological practice recently with the widespread use of effective drugs that have significant side-effects (e.g. retinoids, cytotoxic drugs, biologics), the increase in skin surgery, especially for skin cancer, and the extensive use of phototherapies. OBJECTIVES: To examine the available database from different agencies to which adverse events may be reported over at least a 5-year time frame, categorize the risks, look forward to where as yet unidentified risks might exist, and draw conclusions to improve the safety of dermatological practice. This work came about through a request from the National Patient Safety Agency [to the Joint Specialty Committee of the British Association of Dermatologists (BAD) and Royal College of Physicians] for information on risks to patients receiving treatment or investigation for skin disease. METHODS: Organizations in the U.K. that receive information about adverse events, whether caused by drugs or procedures in dermatological treatments, were approached for information about reported events over a 5-year (or, in one case, 10-year) time frame up to 2009. Data were received from the National Patient Safety Agency, the Medicines and Healthcare Products Regulatory Agency, the National Health Service Litigation Authority, the Medical Protection Society and the Medical Defence Union. In addition, the results of a survey conducted in 2010 by the BAD of its members concerning potential critical incident reporting were included. The received information was analysed according to category of event and conclusions drawn about how best to manage the risks that were identified. RESULTS: Adverse events were divided into the following categories, listed in order of the number of reports received: drug side-effects (biologics and retinoids), phototherapy dosage, drug monitoring (including initial screening), pregnancy prevention programmes, skin cancer follow-up (including acting on reports), dermatopathological reporting and conduct of dermatological surgery (including management of complications, equipment problems, use of lasers, cosmetic procedures and cryotherapy). Critical incidents reported by BAD members often concerned follow-up failures, e.g. of patients receiving systemic drugs or of those with skin cancer. CONCLUSIONS: Several of the reported adverse events concern systemic failures. Recommendations for risk reduction include the following points: better systems for drug monitoring (including regularity of attendance, provision of sufficient follow-up appointments, acting on results and adequacy of pregnancy prevention programmes); staff training and record keeping for phototherapy; acting on skin cancer multidisciplinary team meeting outcomes (including provision of sufficient follow-up appointments); and adequate training of staff in dermatological surgery including cryotherapy. Regular monitoring of the occurrence of such reports is needed to ensure safe practice and to identify early areas of new risk.

Future research into the treatment of vitiligo: where should our priorities lie? Results of the vitiligo priority setting partnership.

BACKGROUND: Vitiligo is the most frequent depigmentation disorder of the skin and is cosmetically and psychologically devastating. A recently updated Cochrane systematic review 'Interventions for vitiligo' showed that the research evidence for treatment of vitiligo is poor, making it difficult to make firm recommendations for clinical practice. OBJECTIVES: To stimulate and steer future research in the field of vitiligo treatment, by identifying the 10 most important research areas for patients and clinicians. METHODS: A vitiligo priority setting partnership was established including patients, healthcare professionals and researchers with an interest in vitiligo. Vitiligo treatment uncertainties were gathered from patients and clinicians, and then prioritized in a transparent process, using a methodology advocated by the James Lind Alliance. RESULTS: In total, 660 treatment uncertainties were submitted by 461 participants. These were reduced to a list of the 23 most popular topics through an online/paper voting process. The 23 were then prioritized at a face-to-face workshop in London. The final list of the top 10 treatment uncertainties included interventions such as systemic immunosuppressants, topical treatments, light therapy, melanocyte-stimulating hormone analogues, gene therapy, and the impact of psychological interventions on the quality of life of patients with vitiligo. CONCLUSIONS: The top 10 research areas for the treatment of vitiligo provide guidance for researchers and funding bodies, to ensure that future research answers questions that are important both to clinicians and to patients.

Guideline for the diagnosis and management of vitiligo.

This detailed and user-friendly guideline for the diagnosis and management of vitiligo in children and adults aims to give high quality clinical advice, based on the best available evidence and expert consensus, taking into account patient choice and clinical expertise. The guideline was devised by a structured process and is intended for use by dermatologists and as a resource for interested parties including patients. Recommendations and levels of evidence have been graded according to the method developed by the Scottish Inter-Collegiate Guidelines Network. Where evidence was lacking, research recommendations were made. The types of vitiligo, process of diagnosis in primary and secondary care, and investigation of vitiligo were assessed. Treatments considered include offering no treatment other than camouflage cosmetics and sunscreens, the use of topical potent or highly potent corticosteroids, of vitamin D analogues, and of topical calcineurin inhibitors, and depigmentation with p-(benzyloxy)phenol. The use of systemic treatment, e.g. corticosteroids, ciclosporin and other immunosuppressive agents was analyzed. Phototherapy was considered, including narrowband ultraviolet B (UVB), psoralen with ultraviolet A (UVA), and khellin with UVA or UVB, along with combinations of topical preparations and various forms of UV. Surgical treatments that were assessed include full-thickness and split skin grafting, mini (punch) grafts, autologous epidermal cell suspensions, and autologous skin equivalents. The effectiveness of cognitive therapy and psychological treatments was considered. Therapeutic algorithms using grades of recommendation and levels of evidence have been produced for children and for adults with vitiligo.

The prevention of nickel contact dermatitis. A review of the use of binding agents and barrier creams.

Chelating agents and other substances can be used to bind nickel or reduce its penetration through the skin, and hence to reduce the symptoms in subjects with nickel sensitivity. Topical usage is mostly described but, in some studies, chelating agents have been given systemically. The most effective ligand for nickel so far described is 5-chloro-7-iodoquinolin-8-ol. Although normally regarded as safe, its usage in some situations may be limited by concerns about its toxicity. Other ligands with demonstrable effect include ethylenediaminetetraacetic acid in various forms, diphenylglyoxime and dimethylglyoxime. Cation exchange resins can effectively bind nickel and work both in vitro and in vivo. Propylene glycol, petrolatum and lanolin reduce the absorption of nickel through the skin. Corticosteroids and cyclosporin work in nickel dermatitis by suppressing the immunological reaction rather than through an effect on nickel. Studies of the oral administration of ligands such as tetraethylthiuram disulphide have given conflicting results but the use of these agents is limited by hepatoxicity in any case. Some compounds offer potential for use in the prophylaxis of nickel dermatitis. Further work is required to develop the existing agents and to look at the use of novel combinations, such as that of a cation exchanger with a ligand.

Light cautery and EMLA in the treatment of chloracne lesions.

We report six patients with chloracne, unresponsive to conventional therapy, whose lesions were cleared by treatment with EMLA (eutectic mixture of lignocaine [lidocaine] 25 mg/g and prilocaine 25 mg/g) topical anaesthesia and light cautery. To the best of our knowledge, this form of treatment for chloracne has not previously been reported.

Plasma 5-S-cysteinyldopa as an index of melanogenesis.

Plasma 5-S-cysteinyldopa (5-S-CD) concentration measured in healthy volunteers in Edinburgh, Scotland (latitude 56 degrees N) showed only minor changes during the day. However, when measurements were performed over a 12-month period a significant rise in 5-S-CD concentration was found. Skin pigmentation and hair colour were not related to plasma 5-S-CD levels. Patients with psoriasis treated with ultraviolet-B or photochemotherapy (PUVA) developed an almost two fold increase in their plasma 5-S-CD level within the first five treatments, before pigmentation developed, subsequent increments of up to four times the pretreatment level being found in the PUVA group. Dithranol treatment caused an increase in plasma 5-S-CD in some psoriatic patients, suggesting a possible association between skin erythema and elevated 5-S-CD levels. The value of plasma 5-S-CD in the follow-up of patients with malignant melanoma does not seem to be invalidated by unavoidable exposure of the subjects to sunlight in a temperate climate such as that of South East Scotland.

Neonatal lupus erythematosus in four successive siblings born to a mother with discoid lupus erythematosus.

A young woman with inactive discoid lupus erythematosus (LE) gave birth in three successive pregnancies to four male infants who showed cutaneous, and in one case cardiac, signs of neonatal LE. The mother had Ro and La antibodies although the anti-nuclear factor (ANF) was not consistently detectable. Three of the infants received phototherapy for neonatal jaundice. Maternal discoid LE may give rise to neonatal LE, and successive siblings can be affected.