Sun exposure and protection habits in transplant athletes: An international survey.

BACKGROUND: Transplant recipients are particularly prone to the development of skin cancer, and overexposure to UV radiation during outdoor activities increases the risk of carcinogenesis. OBJECTIVE: The aim of this study was to analyze sun-related behaviors and knowledge in transplant athletes, examine the frequency of sunburns, and explore associations with a history of skin cancer. MATERIALS AND METHODS: Cross-sectional descriptive study. Participants (n = 170) in the XXI World Transplant Games from >50 countries completed a questionnaire on sun protection habits and knowledge, type of transplant, immunosuppressive therapy, and personal history of skin cancer. RESULTS: The most common transplanted organs were the kidney (n = 79), the liver (n = 33), and the heart (n = 31). Overall, 61.3% of athletes had been doing sport for >15 years and 79.5% spent >1-2 h a day outdoors. Fifteen % of athletes had a history of skin cancer. The prevalence of sunburn in the previous year was 28.9%, higher in athletes aged <50 years (37.2%); without a primary school education (58.3%), not taking cyclosporin (32.6%), and athletes who played basketball (75%). The main sun protection measures used were sunscreen (68.9%) and sunglasses (67.3%). Use of a hat or cap was the only measure significantly associated with a reduced prevalence of sunburn. CONCLUSIONS: Despite high awareness that sun exposure increases the risk of skin cancer, sunburn was common in transplant athletes. Efforts should be made to strengthen multidisciplinary sun protection education strategies and ensure periodic dermatologic follow-up to prevent sun-induced skin cancer in this population.

Moderate to Severe Psoriasis in Pediatric and Young Patients: The BIOBADADERM Registry Experience. / Psoriasis moderada-grave en pacientes pediátricos y jóvenes: experiencia en el registro BIOBADADERM.

Childhood-onset psoriasis generally follows an indolent course but patients with moderate or severe disease may require systemic treatment. The aim of this study was to determine the relative proportion of children and young people aged up to 21 years with moderate to severe psoriasis in the BIOBADADERM registry and to analyze the characteristics of these patients, treatments used, and adverse events. Of the 3946 patients in the registry, 24 were aged 21 years or younger. They had mean age of 16.1 years on starting treatment. When the registry was started, they had a Psoriasis Area and Severity Index of 9.4 and 67% were being treated with a conventional systemic drug. Treatment was discontinued in 14 patients (58%) due to adverse events or a loss or lack of effectiveness. In conclusion, the BIOBADADERM registry shows that young people account for a small proportion of psoriasis patients receiving systemic treatment, and they are more likely to be treated using conventional systemic drugs.

A randomized, intraindividual, non-inferiority, Phase III study comparing daylight photodynamic therapy with BF-200 ALA gel and MAL cream for the treatment of actinic keratosis.

BACKGROUND: The most effective treatment modality for actinic keratosis (AK) is photodynamic therapy (PDT). Major obstacles of PDT are the need of a special illumination device and pain accompanying the illumination. These issues may be overcome by replacing an artificial high-power light source with natural daylight for more extended illumination at lower light doses. OBJECTIVE: To determine whether BF-200 ALA (a nanoemulsion gel containing 7.8% 5-aminolaevulinic acid) is non-inferior to MAL (a cream containing 16% methyl-aminolaevulinate) in the treatment of mild-to-moderate AK with daylight PDT (dPDT). Non-inferiority of the primary efficacy variable (total lesion clearance rate per patient's side 12 weeks after PDT) is established if the mean response for BF-200 ALA is no worse than for MAL, within a statistical margin of Δ = -12.5%. METHODS: The study was performed as an intraindividual comparison with 52 patients in seven centres in Germany and Spain. Each patient received one dPDT. Results include clinical endpoints as well as 1-year follow-up results. RESULTS: Twelve weeks after a single dPDT, 79.8% of the AK lesions treated with BF-200 ALA gel and 76.5% of the lesions treated with MAL cream were completely cleared. The median of differences was 0.0 with a one-sided 97.5% CI of 0.0, establishing non-inferiority (P < 0.0001). Results for secondary efficacy parameters were in line with the primary outcome. Recurrence rates 1 year after the treatment were 19.9% for lesions treated with BF-200 ALA and 31.6% for lesions treated with MAL. Adverse reactions including pain were mostly mild and transient and identical to those previously described for dPDT. CONCLUSION: Daylight PDT of AK with BF-200 ALA is well-tolerated and non-inferior to MAL/dPDT. The study demonstrates a trend towards higher efficacies after 3 months and significantly lower recurrence rates after 1 year follow-up.

Is mitotic rate still useful in the management of patients with thin melanoma?

BACKGROUND: T1 melanoma substaging was recently modified by the American Joint Committee on Cancer (AJCC). Although sentinel lymph node (SLN) positivity is the most important prognostic factor in melanoma, there is a lack of consensus on whether SLN biopsy should be performed in patients with thin melanoma (≤1 mm). OBJECTIVE: The main aim of this study was to investigate predictors of SLN positivity in patients with thin melanoma, with a special emphasis on mitotic rate. A secondary aim was to evaluate survival in this group of patients. MATERIALS AND METHODS: Retrospective multicenter observational study with analysis of age, sex, tumour location, thickness, mitotic rate, regression and microscopic satellites. Predictive factors were identified using a classification and regression tree (CART) approach. Melanoma-specific survival according to SLN status was estimated using Kaplan-Meier curves. RESULTS: We analysed 203 patients with a melanoma ≤1 mm. Using the new AJCC staging criteria, the CART algorithm identified a 7.5% likelihood of SLN positivity in T1a patients. In the case of T1b melanoma, there was a 14.3% likelihood of SLN positivity in patients with a mitotic rate >1 mitosis/mm2 and a 3.2% likelihood in those with ≤1 mitoses/mm2 . None of the patients with T1b disease who had ≤1 mitoses/mm2 and regression had SLN positivity. In T1b patients, 5-year melanoma-specific survival was 98.7% in the SLN-negative group and 75% in the SLN-positive group (P = 0.05). When stratified by mitotic rate, survival was 100% for patients with a mitotic rate of ≤1 mitoses/mm2 and 91.4% for those with >1 mitosis/mm2 (P = 0.022). There were no deaths in the T1a subgroup. CONCLUSIONS: Sentinel lymph node metastasis was less common in patients with T1b melanoma who had a mitotic rate of ≤1 mitoses/mm2 . Performance of SLN biopsy should be carefully considered in this subgroup of patients, particularly considering the good prognosis.

Adverse events associated with discontinuation of the biologics/classic systemic treatments for moderate-to-severe plaque psoriasis: data from the Spanish Biologics Registry, Biobadaderm.

BACKGROUND: Little is known about the adverse events (AEs) that lead to suspension of systemic treatments for psoriasis in clinical practice. OBJECTIVE: The study aimed to investigate AEs associated with discontinuation of systemic therapy in patients with psoriasis in a clinical setting (Biobadaderm). MATERIALS AND METHODS: Multicentre, prospective, cohort study of patients with moderate-to-severe plaque psoriasis receiving systemic therapies from January 2008 to November 2015, in 12 hospitals in Spain. The incidence rate (IR) was used to compare biologics and classic systemic therapies. RESULTS: A total of 4218 courses of treatment were given to 1938 patients. A total of 447 (11%) treatments were discontinued due to AEs. The IR of AE associated with discontinuation of systemic therapies was 13 events/100 patient-years (PY) (95% CI: 12.14-13.93), 9.34 events/100 PY (95% CI: 8.44-10.33) for biologics and 19.67 (95% CI: 17.9-21.6) events/100 PY for classics (P < 0.001). Of 810 discontinuation-related AEs, 117 (14%) were serious. The highest IRs were for cyclosporine [49.18/100 PY (95% CI: 41.91-57.72)] and infliximab [26.52/100 PY (95% CI: 20.98-33.51). Ustekinumab presented the lowest IR (2.6/100 PY (95% CI: 1.83-3.69). LIMITATIONS: Observational study with potential selection bias. CONCLUSION: Biologic therapies are associated with a lower rate of discontinuation-related AEs than are classic therapies in real clinical practice. Ustekinumab showed the lowest incidence.

Comparison of phenotype, comorbidities, therapy and adverse events between psoriatic patients with and without psoriatic arthritis. Biobadaderm registry.

BACKGROUND: There are a limited number of studies comparing psoriasis patients without psoriatic arthritis (PsA) to those with arthritis. Previous results are controversial. OBJECTIVES: To perform a comparative analysis of the phenotype, baseline comorbidities, therapeutic profile and incidence of adverse events (particularly overall adverse events, infections and infestations, malignancies and psychiatric disorders) among psoriatic patients with/without PsA. METHODS: All the patients on the Biobadaderm registry, a prospective inception cohort of psoriasis patients on systemic therapy, were included. Patients were divided into two groups: those with psoriasis without arthritis at the time of entry into the cohort (Pso group) and those with psoriasis and psoriatic arthritis (PsA group) at entry. Patients were followed until the censorship date (last visit in a lost-to-follow-up patient, or 10 November 2015, whichever occurred first). We excluded all the patients who developed any kind of signs and/or symptoms of joint involvement during the follow-up. A descriptive analysis was performed. We estimated incidence ratios (IRR) of adverse events during systemic treatment using a mixed-effects Poisson regression. RESULTS: We included 2120 patients: 1871 (88%) patients with psoriasis without arthritis and 249 (12%) with psoriasis and PsA. The follow-up time was 5020 patients-year in the Pso group and 762 patients-year in the PsA group. Patients with PsA had more comorbidities, particularly hypertension and liver disease; used a higher number of systemic therapies, particularly anti-TNFα drugs and combination therapy; and presented more adverse events (IRR adjusted = 1.29; 95% CI: [1.05-1.58]), particularly serious adverse events (IRR adjusted = 1.51; 95% CI: [1.01-2.26]) and infections/infestations (IRR adjusted = 1.88; 95% CI: [1.27-2.79]), independently of the associated comorbidities and present/past therapies. CONCLUSIONS: Given the differences between patients with psoriasis alone or with psoriasis associated with PsA, patients with psoriasis and PsA should be followed and managed more closely and with specific attention.

Management of Biologic Therapy in Moderate to Severe Psoriasis in Surgical Patients: Data From the Spanish Biobadaderm Registry. / Manejo de los tratamientos biológicos en pacientes con psoriasis moderada-grave sometidos a intervenciones quirúrgicas en el registro español Biobadaderm.

BACKGROUND AND OBJECTIVE: We now have considerable experience in the use of biologic agents to treat psoriasis, but doubts about management arise in certain clinical settings. Surgery is one of them. Although treatment guidelines advise that biologics be suspended before major surgery, data about actual clinical practices and associated complications are lacking. We aimed to analyze current practice in the clinical management of these cases. METHODS: Retrospective study of cases in the Biobadaderm database. We analyzed the management of biologic therapy in patients with psoriasis who underwent surgical procedures. RESULTS: Forty-eight of the 2113 patients registered in Biobadaderm underwent surgery. The largest percentage of procedures (31%) involved skin lesions. Biologic treatment was interrupted in 42% of the cases. No postsurgical complications were significantly related to treatment interruption. Likewise we detected no associations between treatment interruption and other variables, such as sex, age, or duration or severity of psoriasis. CONCLUSION: Continuity of biologic treatment and the risk of postsurgical complications were not associated in this study, although conclusions are limited by the small sample size.

Survival of classic and biological systemic drugs in psoriasis: results of the BIOBADADERM registry and critical analysis.

BACKGROUND: Few reported studies compare drug survival in moderate-to-severe psoriasis vulgaris. OBJECTIVES: To describe and compare drug survival of systemic drugs, including biologic agents (infliximab, etanercept, adalimumab and ustekinumab) and classical drugs (acitretin, ciclosporin and methotrexate) in moderate-to-severe psoriasis. METHODS: This was a multicenter, prospective, cohort study of patients receiving systemic therapies between 2008 and 2013 in 12 hospitals in Spain. Baseline data and drug discontinuation were collected. Drug survival is presented using Kaplan-Meier survival curves. We compared adjusted risk ratios of serious adverse events (AEs) with results of survival analysis for AEs. RESULTS: A total of 1956 patients were included for analysis (1240 exposed to biologics during follow-up and 1076 to classic therapies). Median follow-up time was 3.3 years (0.0-5.1 years). There were 2209 discontinuations out of 3640 therapy cycles started. The main reason for discontinuation was lack of efficacy (36.4%) and remission (27.2%). Biologics showed a higher drug survival than classics and the pattern of survival results for all outcomes (positive or negative) were very similar. Adjusted risk ratios of serious AEs did not agree with results of survival analysis. LIMITATIONS: A limitation is that this is an observational study with potential selection bias. CONCLUSION: Survival as a proxy measure of drug safety in psoriasis is inadequate.

Risk of adverse events in psoriasis patients receiving classic systemic drugs and biologics in a 5-year observational study of clinical practice: 2008-2013 results of the Biobadaderm registry.

BACKGROUND: Biobadaderm is the Spanish registry of psoriasis patients receiving systemic treatment in clinical practice. OBJECTIVE: To compare the safety of biologics and classic systemic treatment. METHODS: Prospective cohort of patients receiving biologics and classic systemic therapies between 2008 and 2013 in 12 hospitals are included. We registered demographic data, diagnoses, comorbidities, treatments and adverse events (AE). We obtained raw relative risks (RR) for specific AE. Multivariate analysis consisted of Cox models adjusting for age, gender, chronic hepatic disease and previous cancer. RESULTS: A total of 1030 patients received biologics (2061 AE in 3681 person-years), 926 patients classic systemic drugs (1015 AE in 1517 person-years). Ninety-three per cent of AE in both groups were non-serious, 6% serious and 0.003% fatal. The age- and gender-adjusted hazard ratio of AE was lower in the biologics group [hazard ratio 0.6 (95% CI: 0.5-0.7)].We found no differences in rates of serious and mortal AE. Some system organ class AE rates differed between both groups. As limitations: Prescription bias might affect the incidence of AE in both groups. Association of drug and AE was based on timing: associations might not be causal. CONCLUSION: Patients receiving biologics had lower risk of AE. We did not find differences in the risk of serious or fatal AE.

Safety of classic and biologic systemic therapies for the treatment of psoriasis in elderly: an observational study from national BIOBADADERM registry.

BACKGROUND: Psoriasis patients over 65 years-old (elderly) constitute a growing group, underrepresented in clinical trials, and likely to be more prone to adverse events. OBJECTIVE: To describe safety of systemic psoriasis therapy in patients over 65 years-old compared to younger patients. METHODS: Patients registered in Biobadaderm, a Spanish national registry of psoriasis patients treated with systemic therapy, were grouped in elderly (≥ 65 years old) and younger patients. Rates of adverse events were described by severity and type, and the risks compared in both groups, taking into account exposure to classic or biologic drugs, using Cox regression. RESULTS: 175 (9.8%) of 1793 patients were elderly. Overall risk of adverse events was not higher in elderly (drug group adjusted HR 1.09 (95%CI: 0.93-1.3)). Serious adverse events were more common in elderly (drug group adjusted HR 3.2 (95%CI: 2.0-5.1)). Age adjusted HR of all adverse events was lower for patients exposed to biologics compared to classic drugs in the whole sample (HR 0.7 (95%CI: 0.6-0.7)). Age did not seem to modify the effect of therapy (biologic vs. classic) in the risk of adverse events (likelihood ratio test for interaction, p = 0.12 for all adverse events, p = 0-09 for serious adverse events). CONCLUSIONS: Serious adverse events are more common in elderly patients, although they may be related to other variants that are associated with this age group and not due to the treatment itself. Use of biologics was associated with lower risk of adverse events in the whole group. We found no differences in this association between young and elderly. These results are reassuring, although uncontrolled confounding could not be excluded as an explanation for these findings, and the power of the study to detect differences was low.

Predictors of sentinel lymph node status in cutaneous melanoma: a classification and regression tree analysis.

OBJECTIVE: The main aim of this study was to identify predictors of sentinel lymph node (SN) metastasis in cutaneous melanoma. PATIENTS AND METHODS: This was a retrospective cohort study of 818 patients in 2 tertiary-level hospitals. The primary outcome variable was SN involvement. Independent predictors were identified using multiple logistic regression and a classification and regression tree (CART) analysis. RESULTS: Ulceration, tumor thickness, and a high mitotic rate (≥6 mitoses/mm(2)) were independently associated with SN metastasis in the multiple regression analysis. The most important predictor in the CART analysis was Breslow thickness. Absence of an inflammatory infiltrate, patient age, and tumor location were predictive of SN metastasis in patients with tumors thicker than 2mm. In the case of thinner melanomas, the predictors were mitotic rate (>6 mitoses/mm(2)), presence of ulceration, and tumor thickness. Patient age, mitotic rate, and tumor thickness and location were predictive of survival. CONCLUSIONS: A high mitotic rate predicts a higher risk of SN involvement and worse survival. CART analysis improves the prediction of regional metastasis, resulting in better clinical management of melanoma patients. It may also help select suitable candidates for inclusion in clinical trials.

Does the treatment ladder for systemic therapy in moderate to severe psoriasis only go up? The percentage of patients with severe psoriasis on biologics increases over time.

BACKGROUND: With the advent of biologic drugs in the management of moderate to severe psoriasis, there may have been a shift in therapeutic approach from rotational strategies to a unidirectional progression from topical treatments to the highest rung of the therapeutic ladder. We studied the frequency of switching from classic to biologic therapy and vice versa in a cohort of patients with psoriasis over a period of up to 5 years. METHODS: Patients are included in the BIOBADADERM prospective registry when they are first prescribed any specific conventional or biologic systemic treatment. The data for each patient refer to the follow-up period from the time they entered the cohort until October 2013. To describe the pattern of switches from classic to biologic therapy and vice versa, we used the data in the registry on the first day of every 365-day period following the date each patient was included in the cohort. RESULTS: In total, 47.3% of the patients (926/1956) were prescribed a classic systemic drug and 52.7% (1030/1956) a biologic agent on entry into the study. Of the 741 patients who accumulated 5 years of follow-up, 21.9% (155) were receiving nonbiologic drugs and 78.1% (553) were on biologic therapy on the first day of their 5th year of follow-up. CONCLUSIONS: The proportion of patients receiving biologic therapy increased with longer follow-up.

Body mass index in patients with moderate-to-severe psoriasis in Spain and its impact as an independent risk factor for therapy withdrawal: results of the Biobadaderm Registry.

BACKGROUND: There are few data on the prevalence of obesity in the general psoriasis population and on the real impact of obesity on the management of psoriasis patients in the clinical setting. OBJECTIVES: To evaluate the prevalence of overweight and obesity in patients with moderate-to-severe psoriasis compared to the general population and to assess the relationship between Body Mass Index (BMI) and the risk of discontinuing treatment. METHODS: Patients registered on Biobadaderm, a prospective registry, were grouped according the different categories of BMI and compared to the general Spanish population. Drug survival was analysed considering only drug withdrawal due to lack of effectiveness, remission and adverse events. RESULTS: A total of 1162 moderate-to-severe psoriasis patients on systemic conventional or biological treatment were recruited. The prevalence of obesity was found to be significantly higher in psoriasis patients than in the general Spanish population (P < 0.001). In multivariate analysis a 5-unit increase in BMI, similar to a change in BMI category from normal weight to overweight and from overweight to obesity, was associated with a 12% increased risk of discontinuing therapy due to lack of effectiveness (HR 1.12, 95% CI: 1.01-1.24) and with a 17% increased risk of having an adverse event (HR 1.17, 95% CI: 1.02-1.36), both independently of the drug used. CONCLUSIONS: Patients with moderate-to-severe psoriasis had a higher prevalence of obesity than the general population. Increased BMI was associated with an increased risk of treatment discontinuation due to lack of effectiveness and a higher risk of adverse events.

Interstitial granulomatous dermatitis and arthritis revealing oesophageal carcinoma.

Interstitial granulomatous dermatitis and arthritis (IGDA) is an uncommon clinicopathological condition that may occur in association with a number of systemic disorders. We present a novel case of IGDA in association with oesophageal squamous cell carcinoma (SCC). A 67-year-old man with a 3-month history of arthritis presented with several erythematous indurated plaques on his lateral trunk and arms. An oesophagogastroduodenoscopy showed an irregular mass 20 mm in size in the proximal third of the oesophagus, and on histopathological examination of a biopsy, the mass was identified as a poorly differentiated SCC. Histopathological examination of a skin biopsy found features consistent with interstitial granulomatous dermatitis. The combination of clinicopathological correlation and laboratory findings led to the diagnosis of IGDA. This association has not been previously described, to our knowledge.

Latent tuberculosis infection and active tuberculosis in patients with psoriasis: a study on the incidence of tuberculosis and the prevalence of latent tuberculosis disease in patients with moderate-severe psoriasis in Spain. BIOBADADERM registry.

INTRODUCTION: The incidence of tuberculosis (TB) or the prevalence of latent tuberculosis infection (LTBI) in psoriasis patients has not been described in the Spanish population. We carried out a study with the objectives: (i) To describe the incidence of TB in patients with psoriasis on systemic treatment in the Spanish population; (ii) To determine the prevalence of LTBI in patients who are candidates for biological treatment; and (iii) To investigate the level of compliance with current recommendations for LTBI and TB screening. METHODS: Data were obtained from BIOBADADERM (Spanish registry for systemic biological and non-biological treatments in psoriasis). An analysis was performed of the exposed cohort to determine the prevalence of LTBI and to describe compliance with the screening guidelines. RESULTS: A total of 1425 patients were registered in BIOBADADERM. They included 793 (56%) patients exposed to biological treatment and 632 (44%) treated with conventional systemic drug. Overall follow-up was 3720 person-years. Of the 793, 20.5% (163) were diagnosed with LTBI before starting biological treatment. The rate of active TB for the exposed cohort was 145 cases × 100,000 patient-years (95% CI 54-389). No case of TB was found in the control group. Screening for LTBI was performed in 83% of the exposed sample. CONCLUSION: Patients with psoriasis who are exposed to biological treatment appear to be at greater risk for tuberculosis. In Spain, up to 20% of patients with psoriasis who are candidates for biological therapy have LTBI. There continues to be a significant percentage of errors in compliance with clinical guidelines.