Guidelines for clinical trials of frontal fibrosing alopecia: consensus recommendations from the International FFA Cooperative Group (IFFACG).

BACKGROUND: Frontal fibrosing alopecia (FFA) has become one of the most common causes of cicatricial alopecia worldwide. However, there is a lack of clear aetiology and robust clinical trial evidence for the efficacy and safety of agents currently used for treatment. OBJECTIVES: To enable data to be collected worldwide on FFA using common criteria and assessment methods. METHODS: A multicentre, international group of experts in hair loss was convened by email to create consensus recommendations for clinical trials. Consensus was defined at > 90% agreement on each recommended part of these guidelines. RESULTS: Standardized diagnostic criteria, severity rating, staging, and investigator and patient assessment of scalp hair loss and other clinical features of FFA were created. CONCLUSIONS: These guidelines should allow the collection of reliable aggregate data on FFA and advance efforts in both clinical and basic research to close knowledge gaps in this condition.

Association of sunbed use with skin cancer risk factors in Europe: an investigation within the Euromelanoma skin cancer prevention campaign.

INTRODUCTION: Sunbed use has been significantly associated with increased risk of melanoma and non-melanoma skin cancer (NMSC), but its relationship with melanoma's risk factors such as high nevus count, atypical nevi and lentigines is poorly studied. Euromelanoma is a skin cancer prevention campaign conducted all over Europe. It offers a once-a-year screening during which participants' data, including sunbed use and phenotype, are collected via questionnaires. OBJECTIVES: To investigate the association of sunbed use with nevus count, atypical nevi, lentigines and suspicion of skin cancer. METHODS: To ensure reliability of the data, we defined inclusion and exclusion criteria for countries' eligibility for the risk analysis. Multivariate logistic regression models (including age, gender, education, skin type, family history of melanoma, personal history of skin cancer, any sun exposure and any sunscreen use) were used to calculate summary odds ratios (SORs) of each clinical endpoint for ever sunbed use. RESULTS: Overall, 227 888 individuals from 30 countries completed the Euromelanoma questionnaire. After the data quality check, 16 countries were eligible for the multivariate analysis, for a total of 145 980 participants (64.8% females; median age 43 years; 62.3% highly educated; 28.5% skin type I-II; 11.0% ever sunbed use). Ever sunbed use was independently associated with nevus count >50 [SOR = 1.05 (1.01-1.10)], atypical nevi [SOR = 1.04 (1.00-1.09)], lentigines [SOR = 1.16 (1.04-1.29)] and suspicion of melanoma [SOR = 1.13 (1.00-1.27)]. Conversely, no significant association was found between ever sunbed use and suspicion of NMSC [SOR = 1.00 (0.91-1.10)]. CONCLUSIONS: Indoor tanning is significantly associated with well-recognized risk factors for melanoma (including high nevus count, presence of atypical nevi and lentigines) as well as suspicion of melanoma within the Euromelanoma screenees. In order to reduce the prevalence of melanoma risk factors, avoidance/discontinuation of sunbed use should always be encouraged, especially but not exclusively for individuals with high-risk phenotypes.

Sunbed use legislation in Europe: assessment of current status.

BACKGROUND: The use of UV-emitting tanning devices for cosmetic purposes is associated with an increased risk of melanoma and non-melanoma skin cancer. Young women are the most frequent users, therefore, there is an increasing concern about the regulation of sunbed use. OBJECTIVE: The primary objective is to assess the current legislation on sunbed use among European countries. METHODS: We developed a 30-item questionnaire to gather the most relevant information about sunbed use legislation. The questionnaire was sent to Euromelanoma coordinators and to designated coordinators out of the Euromelanoma network. RESULTS: We obtained a response rate of 64%. More than 25% of the countries did not report any specific legislation. Roughly one-third of the countries does not have a restriction for minors. Even in countries with a specific legislation, a lack or insufficient enforcement of age limit was observed in up to 100% of the inspections based on the PROSAFE report from 2012. Self-tanning devices were reported in 50%, and almost 40% of countries do not require supervision of use. Although a warning display is required in 77% of cases, a signed informed consent is not required in 80%. In the vast majority of cases, the number of licensed or closed tanning centres is unknown. CONCLUSIONS: Despite the evidence of its harmful effects, and its frequent use by young people, many of whom are at high risk of skin cancer because of fair skin, a significant number of European countries lack a specific legislation on tanning devices. In order to limit the access of young people to sunbeds, a more strictly enforced regulation is needed, as well as regulation regarding advertisement, and location of tanning centres, in addition to health promotion campaigns that target the vulnerable population of young women seeking its use for improved cosmesis.

Prevalence and determinants of sunbed use in thirty European countries: data from the Euromelanoma skin cancer prevention campaign.

BACKGROUND: Although considered as a first-group carcinogen, indoor tanning is a common practice in Europe. Euromelanoma is a pan-European skin cancer prevention campaign. OBJECTIVES: To compare several European countries in terms of the prevalence and determinants of sunbed use. METHODS: Participants in the Euromelanoma campaigns filled in questionnaires containing demographics and risk factors, including type/duration of sunbed use. Multivariate analyses adjusted for age, gender, education, skin type and year of survey were employed to assess factors independently associated with sunbed use in each country. RESULTS: In total, 227 888 individuals (67.4% females, median age 44, 63.4% highly educated, 71.9% skin types III-VI) from 30 countries participated. Overall, the prevalence of sunbed ever use was 10.6% (≤19-year-olds: 5.9%; 20 to 35-year-olds: 17.0%; >35-year-olds: 8.3%). Females displayed a higher prevalence than males in all countries. Balkan countries displayed the highest female/male ratios (≥4). Sunbed use was significantly more prevalent among skin type III-VI (14/30 countries) and highly educated participants (11/30 countries). Significant correlations were found between sunbed use prevalence and countries' latitude (P < 0.001) and sunshine (P = 0.002); Italy and Spain represented exceptions towards excessive exposure. Very different prevalence rates were found for Spain (19.3%) and Portugal (2.0%). Scandinavian countries ranked highest in sunbed use among ≤19-year-olds, Baltic countries among 20 to 35-year-olds. CONCLUSIONS: Sunbed use prevalence was higher in northern, sun-deprived countries, with the exception of Italy and Spain. The main determinants of sunbed use were age (young adults) and gender (females), whereas education and skin type had a less relevant effect. Geographic particularities were found in four regions: Iberian (prevalence ten times higher in Spain than Portugal), Balkan (prevalence disproportionately higher among women), Baltic (highest prevalence among young adults) and Scandinavian (highest prevalence among adolescents). These data have public health relevance for future interventions aimed at reducing sunbed use in Europe.

"Retronychia--clinical and pathophysiological aspects".

Retronychia represents proximal ingrowth of the nail that occurs when the nail embeds backwards into the proximal nail fold. It is suspected when there is a persistent paronychia, particularly in the setting of trauma. Important clinical criteria for diagnosis are inflammation of the proximal nail fold, granulation tissue emerging from under the nail fold, thickening of the proximal portion of the nail plate and interruption of nail growth. The condition is rarely diagnosed and often misinterpreted, and is therefore unnecessarily treated with systemic antibiotics and antifungals. Avulsion of the nail confirms the diagnosis and it is the curative treatment. Conservative treatment with an adhesive technique is a valid option in early cases. We report 20 cases of retronychia diagnosed in our department between 2010 and 2013.

Evidence- and consensus-based (S3) Guidelines for the Treatment of Actinic Keratosis - International League of Dermatological Societies in cooperation with the European Dermatology Forum - Short version.

BACKGROUND: Actinic keratosis (AK) is a frequent health condition attributable to chronic exposure to ultraviolet radiation. Several treatment options are available and evidence based guidelines are missing. OBJECTIVES: The goal of these evidence- and consensus-based guidelines was the development of treatment recommendations appropriate for different subgroups of patients presenting with AK. A secondary aim of these guidelines was the implementation of knowledge relating to the clinical background of AK, including consensus-based recommendations for the histopathological definition, diagnosis and the assessment of patients. METHODS: The guidelines development followed a pre-defined and structured process. For the underlying systematic literature review of interventions for AK, the methodology suggested by the Cochrane Handbook for Systematic Reviews of Interventions, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was adapted. All recommendations were consented during a consensus conference using a formal consensus methodology. Strength of recommendations was expressed based on the GRADE approach. If expert opinion without external evidence was incorporated into the reasoning for making a certain recommendation, the rationale was provided. The Guidelines underwent open public review and approval by the commissioning societies. RESULTS: Various interventions for the treatment of AK have been assessed for their efficacy. The consenting procedure led to a treatment algorithm as shown in the guidelines document. Based on expert consensus, the present guidelines present recommendations on the classification of patients, diagnosis and histopathological definition of AK. Details on the methods and results of the systematic literature review and guideline development process have been published separately. CONCLUSIONS: International guidelines are intended to be adapted to national or regional circumstances (regulatory approval, availability and reimbursement of treatments).

Spanish-Portuguese consensus statement on use of daylight-mediated photodynamic therapy with methyl aminolevulinate in the treatment of actinic keratosis.

INTRODUCTION: Daylight-mediated photodynamic therapy (PDT) is a new type of PDT that is as effective as conventional PDT in grade 1 and 2 actinic keratosis but with fewer adverse effects, resulting in greater efficiency. The climatic conditions in the Iberian Peninsula require an appropriately adapted consensus protocol. OBJECTIVE: We describe a protocol for the treatment of grade 1 and 2 actinic keratosis with daylight-mediated PDT and methyl aminolevulinate (MAL) adapted to the epidemiological and clinical characteristics of Spanish and Portuguese patients and the climatic conditions of both countries. METHODS: Twelve dermatologists from different parts of Spain and Portugal with experience in the treatment of actinic keratosis with PDT convened to draft a consensus statement for daylight-mediated PDT with MAL in these countries. Based on a literature review and their own clinical experience, the group developed a recommended protocol. RESULTS: According to the recommendations adopted, patients with multiple grade 1 and 2 lesions, particularly those at risk of developing cancer, are candidates for this type of therapy. Daylight-mediated PDT can be administered throughout the year, although it is not indicated at temperatures below 10°C or at excessively high temperatures. Likewise, therapy should not be administered when it is raining, snowing, or foggy. The procedure is simple, requiring application of a sunscreen with a protection factor of at least 30 based exclusively on organic filters, appropriate preparation of the lesions, application of MAL without occlusion, and activation in daylight for 2hours. CONCLUSION: This consensus statement represents a practical and detailed guideline to achieve maximum effectiveness of daylight-mediated PDT with MAL in Spain and Portugal with minimal adverse effects.

Euromelanoma: a dermatology-led European campaign against nonmelanoma skin cancer and cutaneous melanoma. Past, present and future.

Euromelanoma is a dermatologist-led skin cancer prevention programme conducting an annual screening and public education campaign in over 20 European countries. Within its 10-year history, Euromelanoma has screened over 260,000 individuals across Europe, detecting a significant number of cutaneous melanomas and nonmelanoma skin cancers, identifying high-risk individuals for further surveillance and promoting awareness on the suspicious features of melanoma and the hazardous effects of ultraviolet exposure. In this review article, we summarize the history of the Euromelanoma campaign, present its organizational structure and discuss the results of the campaign in individual countries and on a European scale. Euromelanoma has had a significant impact on melanoma prevention and early diagnosis in participating countries and, despite many challenges, has positively influenced public health attitudes towards regular mole examination and the implementation of preventive measures against skin cancer.

Dermoscopy of scalp tumours: a multi-centre study conducted by the international dermoscopy society.

BACKGROUND: Little is known about the dermoscopic features of scalp tumours. Objective To determine the dermoscopic features of scalp tumours. METHODS: Retrospective analysis of dermoscopic images of histopathologically diagnosed scalp tumours from International Dermoscopy Society members. RESULTS: A total of 323 tumours of the scalp from 315 patients (mean age: 52 years; range 3-88 years) were analysed. Scalp nevi were significantly associated with young age (<30 years) and exhibited a globular or network pattern with central or perifollicular hypopigmentation. Melanoma and non-melanoma skin cancer were associated with male gender, androgenetic alopecia, age >65 years and sun damage. Atypical network and regression were predictive for thin (≤1 mm) melanomas, whereas advanced melanomas (tumour thickness > 1 mm) revealed blue white veil, unspecific patterns and irregular black blotches or dots. CONCLUSIONS: The data collected provide a new knowledge regarding the clinical and dermoscopy features of pigmented scalp tumours.

The Euromelanoma skin cancer prevention campaign in Europe: characteristics and results of 2009 and 2010.

BACKGROUND: Euromelanoma is a skin cancer education and prevention campaign that started in 1999 in Belgium as 'Melanoma day'. Since 2000, it is active in a large and growing number of European countries under the name Euromelanoma. OBJECTIVE: To evaluate results of Euromelanoma in 2009 and 2010 in 20 countries, describing characteristics of screenees, rates of clinically suspicious lesions for skin cancer and detection rates of melanomas. METHODS: Euromelanoma questionnaires were used by 20 countries providing their data in a standardized database (Belgium, Croatia, Cyprus, Czech Republic, FYRO Macedonia, Germany, Greece, Hungary, Italy, Lithuania, Luxembourg, Malta, Moldavia, Portugal, Serbia, Slovenia, Spain, Sweden, Switzerland and Ukraine). RESULTS: In total, 59,858 subjects were screened in 20 countries. Most screenees were female (64%), median ages were 43 (female) and 46 (male) and 33% had phototype I or II. The suspicion rates ranged from 1.1% to 19.4% for melanoma (average 2.8%), from 0.0% to 10.7% for basal cell carcinoma (average 3.1%) and from 0.0% to 1.8% for squamous cell carcinoma (average 0.4%). The overall positive predictive value of countries where (estimation of) positive predictive value could be determined was 13.0%, melanoma detection rates varied from 0.1% to 1.9%. Dermoscopy was used in 78% of examinations with clinically suspected melanoma; full body skin examination was performed in 72% of the screenees. CONCLUSION: Although the population screened during Euromelanoma was relatively young, high rates of clinically suspected melanoma were found. The efficacy of Euromelanoma could be improved by targeting high-risk populations and by better use of dermoscopy and full body skin examination.

Skin cancer healthcare impact: A nation-wide assessment of an administrative database.

BACKGROUND: Skin cancer is an important health concern, with an increasing incidence worldwide. OBJECTIVE: To assess the clinical and economic burden of melanoma (MM) and non-melanoma skin cancer (NMSC) at public hospitals in mainland Portugal. METHODS: We used an administrative database containing a registration of all hospitalizations and ambulatory episodes occurred in Portuguese public hospitals between 2011 and 2015. We assessed all episodes with associated diagnoses of MM or NMSC regarding neoplasm location, metastases occurrence, length of stay, in-hospital mortality and hospital costs. RESULTS: We assessed 15,913 MM and 72,602 NMSC episodes. 14.3% of MM episodes presented with metastases, compared to 1.9% of NMSC episodes. Patients' median age was lower for MM (66 years) than NMSC (76 years). The trunk was the most common location for MM (32.5%), followed by the lower limbs (26.5%). NMSC presented with higher length of stay than MM (median 5 versus 4 days; p < 0.001), but with lower in-hospital mortality (7.3% versus 11.9%; p < 0.001). MM episodes had higher average hospital costs than NMSC episodes (1197.7 versus 1113.5 €; p < 0.001). Overall, NMSC episodes amounted a total of 80.8 million € in hospital costs versus 19.1 million € for MM episodes. CONCLUSION: Skin neoplasms have substantial impact on healthcare services. NMSC is an important contributor to this burden. NMSC underreporting should be tackled and it should not be downplayed in skin cancer preventative strategies.

An international collaborative case-control study of severe cutaneous adverse reactions (SCAR). Design and methods.

A multicenter international case-control study has been designed to elucidate the etiology of Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN). Although these diseases occur rarely, the morbidity is high and the mortality for TEN is of the order of 30%. These serious dermatologic conditions have often been linked to exposure to drugs. Infective and autoimmune diseases, as well as other non-drug risk factors, have also been postulated to be of importance in increasing the risk. The design and methods are described, with particular attention to the unique challenges for an epidemiologic study of these conditions.

Cutaneous T-cell recruitment in toxic epidermal necrolysis. Further evidence of CD8+ lymphocyte involvement.

BACKGROUND: Toxic epidermal necrolysis (TEN) is a life-threatening disease with severe mucocutaneous shedding. Although it is widely accepted that immune mechanisms are at play, the pathophysiology of TEN is still unknown. We studied the blister fluid inflammatory cells in three drug-related cases to further define the suspected T-cell involvement in TEN. OBSERVATIONS: A peripheral blood lymphopenia, especially of CD4+ T lymphocytes, was associated with a high lymphocytic cellularity of the blister fluid. In two cases, immunophenotyping of blister fluid lymphocytes showed a predominance of the CD8 phenotype. Furthermore, using two-color flow cytometry in one patient, we could show the predominance of CD8+ CD29+ lymphocytes and CD45RA- negative cells. CONCLUSIONS: Our findings point to a cutaneous recruitment of antigen-primed and cytotoxic T cells in TEN, further supporting the involvement of CD8+ lymphocytes in TEN pathogenesis and its immune mediation.

Ocular involvement in toxic epidermal necrolysis.

Toxic epidermal necrolysis (TEN) or Lyell's syndrome is an acute life-threatening disease often triggered by an adverse drug reaction and/or infection. It is characterized by an extensive epidermal loss and severe mucosal involvement. Its pathophysiology is unresolved, but several studies support the hypothesis of an immune mediation. The authors review the ocular involvement of ten drug-induced TEN cases observed in the last four years (eight females and two males; mean age=47). An epidermal loss ranging from 24 to 95% of body surface area was associated with ocular (10/10), oral (9/10), genital (6/10) and anal (4/10) involvement. Ocular findings in the acute phase were: bilateral mucopurulent conjunctivitis (9/10), with inflammatory membranes (3/10), punctate epithelial keratitis (6/10) and corneal ulcers (3/10). Skin palpebral detachment occurred in seven cases, all with extensive and severe systemic disease. In the chronic phase of the disease the authors observed keratoconjunctivitis sicca (4/7), symblepharon (3/7), entropion with trichiasis (2/7) and corneal neovascularization (2/7). HLA B44 (B12) was observed in four of eight studied patients. In conclusion, ocular involvement is frequent in TEN patients and, in those who survive, it significantly contributes to the morbidity of the disease.

Gangrene of the fingertips after bleomycin and methotrexate.

The increased use of cytostatic drugs, which are sometimes used in combination chemotherapy, may result in new and unusual cutaneous side effects. We describe a 57-year-old man with acral erythrocyanosis progressing to acute digital ischemia and gangrene that developed after combined chemotherapy (bleomycin and methotrexate) used to treat a metastatic squamous cell carcinoma of the hypopharynx. A leukocytoclastic vasculitis was found in both the acute phase and in the amputated fingertips. This supports the well-reported potential of bleomycin to trigger acral vascular toxicity.