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Background: The two main tumors treated with Mohs micrographic surgery (MMS) are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). There are no studies analyzing whether MMS is different when treating these two types of tumors., Objective: We aim to compare the characteristics of the patients, the tumors, and MMS, and first-year follow-up of MMS in BCC and SCC., Methods: REGESMOHS is a prospective cohort study of patients treated with MMS. The participating centers are 19 Spanish hospitals where at least one MMS is performed per week. Data on characteristics of the patients, tumors, and surgery were recorded. The follow-up was done with two visits: the first visit within 1 month after surgery and the second one within the first year., Results: From July 2013 to April 2017, a total of 2,669 patients who underwent MMS were included in the registry. Of them, 2,448 (93%) were diagnosed with BCC, and 181 (7%) were diagnosed with SCC. Patients with SCC were older than those with BCC (median age 73 years vs. 68 years) and presented immunosuppression more frequently. The tumor size was significantly larger in the SCC group. Regarding surgery, deeper invasion was more frequent in SCC, resulting in larger defects. Despite this, SCC did not require more stages to get clear margins or more time in the operating room. Incomplete Mohs was more frequent in the SCC group (6%) than in the BCC group (2%). The incidence of perioperative complications was higher when treating SCC. There were more relapses in the first-year follow-up in the SCC group., Conclusion: There are significant differences when comparing MMS in BCC and SCC. Knowledge of these differences can help to prepare the patient and plan the surgery, optimizing results., (© 2018 The International Society of Dermatology.)

Background: Cancer risk following long-term exposure to systemic immunomodulatory therapies in patients with psoriasis is possible., Objectives: To assess a dose-response relationship between cumulative length of exposure to biological therapy and risk of cancer., Methods: Four national studies (a healthcare database from Israel, and prospective cohorts form Italy, Spain and the U.K. and Republic of Ireland) collaborating through Psonet (European Registry of Psoriasis) participated in these nested case-control studies, including nearly 60 000 person-years of observation. 'Cases' were patients who developed an incident cancer. Patients with previous cancers and benign or in situ tumours were excluded. Four cancer-free controls were matched to each case on year of birth, sex, geographic area and registration year. Follow-up for controls was censored at the date of cancer diagnosis for the matched case. Conditional logistic regression was performed by each registry. Results were pooled using random-effects meta-analysis., Results: A total of 728 cases and 2671 controls were identified. After matching, differences between cases and controls were present for the Charlson Comorbidity Index in all three registries, and in the prevalence of previous exposure to psoralen-ultraviolet A and smoking (the British Association of Dermatologists Biologic Interventions Register only). The risk of first cancers was not significantly associated with cumulative exposure to biologics (adjusted odds ratio per year of exposure 1·02, 95% confidence interval 0·92-1·13). Results were similar if squamous and basal cell carcinomas were included in the outcome., Conclusions: Cumulative length of exposure to biological therapies in patients with psoriasis in real-world clinical practice does not appear to be linked to a higher risk of cancer after several years of use., (© 2018 British Association of Dermatologists.)

Background: The elderly population is increasing and more patients in this group undergo Mohs micrographic surgery (MMS). The few publications investigating MMS in elderly people conclude that it is a safe procedure; however, these are single-centre studies without a comparison group., Objective: To compare the characteristics of patients, tumours, MMS and 1-year follow-up in patients younger than 80 years, with patients older than 80 years at the time of surgery., Methods: Data was analysed from REGESMOHS, a prospective cohort study of patients treated with MMS. The participating centres were 19 Spanish hospitals where at least one MMS is performed per week. Data on characteristics of the patient, tumour and surgery were recorded. Follow-up data were collected from two visits; the first within 1 month postsurgery and the second within the first year., Results: From July 2013 to October 2016, 2575 patients that underwent MMS were included in the registry. Of them, 1942 (75.4%) were aged <80 years and 633 (24.6%) were ≥80 years old. In the elderly, the tumour size was significantly higher with a higher proportion of squamous cell carcinoma. Regarding surgery, elderly more commonly had tumours with deeper invasion and required a higher number of Mohs surgery stages, leaving larger defects and requiring more time in the operating room. Despite this, the incidence of postoperative complications was the same in both groups (7%) and there were no significant differences in proportion of relapses in the first-year follow-up., Conclusion: The risk of short-term complications and relapses were similar in elderly and younger groups. MMS is a safe procedure in the elderly., (© 2017 European Academy of Dermatology and Venereology.)

Background: Psoriasis is an immune-mediated disease for which some people have a genetic predisposition. The condition manifests in inflammatory effects on either the skin or joints, or both, and it has a major impact on quality of life. Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. Several randomised controlled trials (RCTs) have compared the efficacy of the different systemic treatments in psoriasis against placebo. However, the relative benefit of these treatments remains unclear due to the limited number of trials comparing them directly head to head, which is why we chose to conduct a network meta-analysis., Objectives: To compare the efficacy and safety of conventional systemic agents (acitretin, ciclosporin, fumaric acid esters, methotrexate), small molecules (apremilast, tofacitinib, ponesimod), anti-TNF alpha (etanercept, infliximab, adalimumab, certolizumab), anti-IL12/23 (ustekinumab), anti-IL17 (secukinumab, ixekizumab, brodalumab), anti-IL23 (guselkumab, tildrakizumab), and other biologics (alefacept, itolizumab) for patients with moderate to severe psoriasis and to provide a ranking of these treatments according to their efficacy and safety., Search Methods: We searched the following databases to December 2016: the Cochrane Skin Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and LILACS. We also searched five trials registers and the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) reports. We checked the reference lists of included and excluded studies for further references to relevant RCTs. We searched the trial results databases of a number of pharmaceutical companies and handsearched the conference proceedings of a number of dermatology meetings., Selection Criteria: Randomised controlled trials (RCTs) of systemic and biological treatments in adults (over 18 years of age) with moderate to severe plaque psoriasis or psoriatic arthritis whose skin had been clinically diagnosed with moderate to severe psoriasis, at any stage of treatment, in comparison to placebo or another active agent., Data Collection and Analysis: Three groups of two review authors independently undertook study selection, data extraction, 'Risk of bias' assessment, and analyses. We synthesised the data using pair-wise and network meta-analysis (NMA) to compare the treatments of interest and rank them according to their effectiveness (as measured by the Psoriasis Area and Severity Index score (PASI) 90) and acceptability (the inverse of serious adverse effects). We assessed the certainty of the body of evidence from the NMA for the two primary outcomes, according to GRADE; we evaluated evidence as either very low, low, moderate, or high. We contacted study authors when data were unclear or missing., Main Results: We included 109 studies in our review (39,882 randomised participants, 68% men, all recruited from a hospital). The overall average age was 44 years; the overall mean PASI score at baseline was 20 (range: 9.5 to 39). Most of these studies were placebo controlled (67%), 23% were head-to-head studies, and 10% were multi-armed studies with both an active comparator and placebo. We have assessed all treatments listed in the objectives (19 in total). In all, 86 trials were multicentric trials (two to 231 centres). All of the trials included in this review were limited to the induction phase (assessment at less than 24 weeks after randomisation); in fact, all trials included in the network meta-analysis were measured between 12 and 16 weeks after randomisation. We assessed the majority of studies (48/109) as being at high risk of bias; 38 were assessed as at an unclear risk, and 23, low risk.Network meta-analysis at class level showed that all of the interventions (conventional systemic agents, small molecules, and biological treatments) were significantly more effective than placebo in terms of reaching PASI 90.In terms of reaching PASI 90, the biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha were significantly more effective than the small molecules and the conventional systemic agents. Small molecules were associated with a higher chance of reaching PASI 90 compared to conventional systemic agents.At drug level, in terms of reaching PASI 90, all of the anti-IL17 agents and guselkumab (an anti-IL23 drug) were significantly more effective than the anti-TNF alpha agents infliximab, adalimumab, and etanercept, but not certolizumab. Ustekinumab was superior to etanercept. No clear difference was shown between infliximab, adalimumab, and etanercept. Only one trial assessed the efficacy of infliximab in this network; thus, these results have to be interpreted with caution. Tofacitinib was significantly superior to methotrexate, and no clear difference was shown between any of the other small molecules versus conventional treatments.Network meta-analysis also showed that ixekizumab, secukinumab, brodalumab, guselkumab, certolizumab, and ustekinumab outperformed other drugs when compared to placebo in terms of reaching PASI 90: the most effective drug was ixekizumab (risk ratio (RR) 32.45, 95% confidence interval (CI) 23.61 to 44.60; Surface Under the Cumulative Ranking (SUCRA) = 94.3; high-certainty evidence), followed by secukinumab (RR 26.55, 95% CI 20.32 to 34.69; SUCRA = 86.5; high-certainty evidence), brodalumab (RR 25.45, 95% CI 18.74 to 34.57; SUCRA = 84.3; moderate-certainty evidence), guselkumab (RR 21.03, 95% CI 14.56 to 30.38; SUCRA = 77; moderate-certainty evidence), certolizumab (RR 24.58, 95% CI 3.46 to 174.73; SUCRA = 75.7; moderate-certainty evidence), and ustekinumab (RR 19.91, 95% CI 15.11 to 26.23; SUCRA = 72.6; high-certainty evidence).We found no significant difference between all of the interventions and the placebo regarding the risk of serious adverse effects (SAEs): the relative ranking strongly suggested that methotrexate was associated with the best safety profile regarding all of the SAEs (RR 0.23, 95% CI 0.05 to 0.99; SUCRA = 90.7; moderate-certainty evidence), followed by ciclosporin (RR 0.23, 95% CI 0.01 to 5.10; SUCRA = 78.2; very low-certainty evidence), certolizumab (RR 0.49, 95% CI 0.10 to 2.36; SUCRA = 70.9; moderate-certainty evidence), infliximab (RR 0.56, 95% CI 0.10 to 3.00; SUCRA = 64.4; very low-certainty evidence), alefacept (RR 0.72, 95% CI 0.34 to 1.55; SUCRA = 62.6; low-certainty evidence), and fumaric acid esters (RR 0.77, 95% CI 0.30 to 1.99; SUCRA = 57.7; very low-certainty evidence). Major adverse cardiac events, serious infections, or malignancies were reported in both the placebo and intervention groups. Nevertheless, the SAEs analyses were based on a very low number of events with low to very low certainty for just over half of the treatment estimates in total, moderate for the others. Thus, the results have to be considered with caution.Considering both efficacy (PASI 90 outcome) and acceptability (SAEs outcome), highly effective treatments also had more SAEs compared to the other treatments, and ustekinumab, infliximab, and certolizumab appeared to have the better trade-off between efficacy and acceptability.Regarding the other efficacy outcomes, PASI 75 and Physician Global Assessment (PGA) 0/1, the results were very similar to the results for PASI 90.Information on quality of life was often poorly reported and was absent for a third of the interventions., Authors' Conclusions: Our review shows that compared to placebo, the biologics ixekizumab, secukinumab, brodalumab, guselkumab, certolizumab, and ustekinumab are the best choices for achieving PASI 90 in people with moderate to severe psoriasis on the basis of moderate- to high-certainty evidence. At class level, the biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha were significantly more effective than the small molecules and the conventional systemic agents, too. This NMA evidence is limited to induction therapy (outcomes were measured between 12 to 16 weeks after randomisation) and is not sufficiently relevant for a chronic disease. Moreover, low numbers of studies were found for some of the interventions, and the young age (mean age of 44 years) and high level of disease severity (PASI 20 at baseline) may not be typical of patients seen in daily clinical practice.Another major concern is that short-term trials provide scanty and sometimes poorly reported safety data and thus do not provide useful evidence to create a reliable risk profile of treatments. Indeed, we found no significant difference in the assessed interventions and placebo in terms of SAEs. Methotrexate appeared to have the best safety profile, but as the evidence was of very low to moderate quality, we cannot be sure of the ranking. In order to provide long-term information on the safety of the treatments included in this review, it will be necessary to evaluate non-randomised studies and postmarketing reports released from regulatory agencies as well.In terms of future research, randomised trials comparing directly active agents are necessary once high-quality evidence of benefit against placebo is established, including head-to-head trials amongst and between conventional systemic and small molecules, and between biological agents (anti-IL17 versus anti-IL23, anti-IL23 versus anti-IL12/23, anti-TNF alpha versus anti-IL12/23). Future trials should also undertake systematic subgroup analyses (e.g. assessing biological-naïve patients, baseline psoriasis severity, presence of psoriatic arthritis, etc.). Finally, outcome measure harmonisation is needed in psoriasis trials, and researchers should look at the medium- and long-term benefit and safety of the interventions and the comparative safety of different agents.

Background: Anti-tumor necrosis factor (TNF) therapy in psoriasis has been associated with an increased risk of serious infections compared with nonbiologic systemic therapies., Objective: We sought to quantify the risk of: (1) serious infections (leading to hospitalization, sequelae, or death); and (2) "any infection," bacterial cutaneous infections, and granulomatous infections among patients receiving anti-TNF therapy compared with nonbiologics (acitretin, methotrexate, cyclosporine)., Methods: We used prospective meta-analysis to combine data from the Psocare registry (Italy), Biobadaderm registry (Spain), and Clalit Health Services database (Israel), including 17,739 patients and 23,357.5 person-years of follow-up., Results: For serious infections, age, gender, and Charlson morbidity index adjusted hazard ratio of exposure to anti-TNFs compared with nonbiologics was 0.98 (95% confidence interval 0.80-1.19), for bacterial cutaneous infections it was 1.00 (95% confidence interval 0.62-1.61), and for granulomatous infections it was 1.23 (95% confidence interval 0.82-1.84). Using methotrexate as comparator and comparing first year of exposure with later exposure did not modify the results. For any infectious episode, risks and relative risks were heterogeneous among registries, probably because of different definitions of outcome., Limitations: There was lack of power to describe risk of single drugs., Conclusion: In current clinical practice, treatment with anti-TNF drugs was not associated with a higher risk of serious infections than treatment with nonbiologic systemic therapy., (Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.)

Introduction: Biologic medications increase dramatically the burden of a chronic and high prevalent disease like psoriasis. The objective of the study was to quantify the use of dose reduction or dose escalation strategies, not reflected in the drug summary of product characteristics, in clinical practice., Methods: An observational, cross-sectional study of a subset of patients from the Spanish Registry for Systemic Treatments in Psoriasis (BIOBADADERM) treated for over six consecutive months with the same biologic agent., Results: The study included 637 patients. At the cut-off date, the initial dose had been reduced in 223 patients (35%; 95% CI: 31.3-38.9%) and escalated in 46 (7.2%; 95% CI: 5.3-9.5%). When compared with the patients treated with standard doses, the patients on reduced doses had a lower PASI score at the cut-off date (a mean 2.6 versus 1; -1.6 points) and exhibited greater improvement in PASI since the start of biologic therapy (mean reduction over baseline 75% versus 87%). By contrast, the patients receiving an escalated dose had higher PASI scores (2.6 versus 8.0) and showed less improvement in PASI (75% versus 46.8%)., Conclusion: Off-label doses of biologic agents for psoriasis are frequent in clinical practice. This information is especially relevant for pharmacoeconomic models.

Background: The ichthyoses comprise a group of inherited disorders of keratinization. Because of the need for lifelong treatment, it is important that therapies are beneficial, safe, and well tolerated., Objectives: We sought to review the evidence on existing treatments for the congenital ichthyoses, excluding ichthyosis vulgaris., Method: We undertook a systematic review using the methodology of the Cochrane Collaboration. Articles published in MEDLINE, EMBASE, and CENTRAL and registered clinical trials were screened. Randomized controlled trials involving patients with the inherited ichthyoses, either syndromic or nonsyndromic but excluding ichthyosis vulgaris, were considered., Results: Six trials met the inclusion criteria. Topical treatments including 5% urea, 20% propylene glycol alone or in combination with 5% lactic acid, calcipotriol ointment, and liarozole 5% cream showed therapeutic benefit. Oral liarozole, a retinoic acid metabolism blocking agent, showed no advantage over oral acitretin., Limitations: Most studies were performed on a small sample of patients and lacked methodological and reporting quality. The small number of trials and the nearly constant positive results make publication bias likely. The absence of standardization of outcome measures precluded the comparison of studies., Conclusions: Topical treatments including emollients, calcipotriol ointment, and liarozole cream seem to have therapeutic benefit and a good safety profile, although the use of topical calcipotriol is limited by a maximum weekly dose of 100 g. The advantage of oral liarozole over acitretin is uncertain. Multicenter trials comparing oral and topical interventions and evaluation of long-term outcomes are needed., (Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Background and Objective: Systematic reviews are one of the most important sources of information for evidence-based medicine. However, there is a general impression that these reviews rarely report results that provide sufficient evidence to change clinical practice. The aim of this study was to determine the percentage of Cochrane Skin Group reviews reporting results with the potential to guide clinical decision-making., Material and Methods: We performed a bibliometric analysis of all the systematic reviews published by the Cochrane Skin Group up to 16 August, 2012. We retrieved 55 reviews, which were analyzed and graded independently by 2 investigators into 3 categories: 0 (insufficient evidence to support or reject the use of an intervention), 1 (insufficient evidence to support or reject the use of an intervention but sufficient evidence to support recommendations or suggestions), and 2 (sufficient evidence to support or reject the use of an intervention)., Results: Our analysis showed that 25.5% (14/55) of the studies did not provide sufficient evidence to support or reject the use of the interventions studied, 45.5% (25/25) provided sufficient but not strong evidence to support recommendations or suggestions, and 29.1% (16/55) provided strong evidence to support or reject the use of 1 or more of the interventions studied., Conclusions: Most of the systematic reviews published by the Cochrane Skin Group provide useful information to improve clinical practice. Clinicians should read these reviews and reconsider their current practice., (Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.)

Background: Previous reports on the prevalence of autosomal recessive congenital ichthyosis (ARCI) were based on single source data, such as lists of members in a patient association. These sources are likely to be incomplete., Objectives: We sought to describe the prevalence of ARCI., Methods: We obtained data from 3 incomplete sources (dermatology departments, a genetic testing laboratory, and the Spanish ichthyosis association) and combined them using the capture-recapture method., Results: We identified 144 living patients with ARCI. Of these, 62.5% had classic lamellar ichthyosis and 30.6% had congenital ichthyosiform erythroderma. The age distribution included fewer elderly patients than expected. The prevalence of ARCI in patients younger than 10 years, the best estimate as less subject to bias, was 16.2 cases per million inhabitants (95% confidence interval 13.3-23.0). According to the capture-recapture model, 71% of the patients were not being followed up in reference units, 92% did not have a genetic diagnosis, and 78% were not members of the ichthyosis association., Limitations: The prevalence of ARCI in Spain and findings related to the Spanish health care system might not be generalizable to other countries., Conclusions: The prevalence of ARCI is higher than previously reported. Many patients are not being followed up in reference units, do not have a genetic diagnosis, and are not members of a patient association, indicating room for improvement in their care. Data suggesting a reduced number of older patients might imply a shorter life expectancy and this requires further study., (Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Objective: To describe the use of systemic therapy for psoriasis (biologic and nonbiologic [classic] drugs) in patients not adequately represented in randomized controlled trials (RCTs) and the risk of serious adverse events (SAEs) in these patients., Design: A registry inception cohort was used., Setting: Thirteen dermatology departments in Spain participated., Patients: A consecutive sample of patients treated with biologics and a systematic sample of patients treated with classic systemic therapy were evaluated. A total of 1042 patients (2179 person-years) were included., Exposure: Inadequate representation in trials was defined as the presence of any of the following factors: elderly age (>70 years); type of psoriasis other than chronic plaque psoriasis; history of infection caused by hepatitis B, hepatitis C, or human immunodeficiency virus; history of cancer (excluding nonmelanoma skin cancer); and chronic renal or hepatic disease., Main Outcome Measures: Serious adverse events as defined by the International Conference on Harmonization were evaluated., Results: In all, 29.8% of patients receiving systemic therapy for psoriasis would not have been eligible for RCTs. These individuals had an increased risk of SAEs (incidence rate ratio, 2.7; 95% CI, 1.5-4.7). Patients exposed to biologics had an adjusted increased risk of SAEs (incidence rate ratio, 2.3; 95% CI, 1.1-4.8) that was similar in patients eligible and ineligible for RCTs., Conclusions: Patients ineligible for RCTs are an important proportion (30%) of those receiving systemic therapy for psoriasis. These patients have a higher risk of SAEs and should be closely monitored. Patients exposed to biologics (whether these patients are eligible for RCTs or ineligible) are susceptible to the same increase in risk of SAEs, but biologics add to a higher baseline risk in patients who are ineligible for RCTs. The risk-benefit ratio in ineligible patients receiving biologics might be different from the ratio in eligible patients.

Background: Large disease registries are the preferred method to assess long-term treatment safety. If psoriasis registries collaborate in a network, their power to assess safety is increased., Objective: To identify heterogeneity in psoriasis registries and methodological challenges for synthesising the data they provide., Methods: We surveyed the registries in PSONET and identified and addressed the challenges to collaborative analysis for the network in several round table meetings., Results: Eight out of 10 registries had a prospective comparator cohort with similar disease characteristics but not on biologics. Registries differed in the coding and validation or follow-up of adverse events and in the way they sampled their population. Fifteen challenges to registries collaborating were identified in the areas of operational governance, structural conduct, bias and analysis., Conclusions: Participation in PSONET, a network of psoriasis registries, helps identify and solve common issues, enhancing the individual registries, and provides larger sets of more powerful safety data in a diverse population. Challenges to interpreting data collectively include heterogeneity in sampling, variable penetration of biologics and compatibility of different datasets., (Copyright © 2012 S. Karger AG, Basel.)

Background: Suspected toenail onychomycosis is a frequent problem. Clinical diagnosis has been considered inadequate., Objectives: To assess the diagnostic accuracy of clinical findings for detecting fungi in toenails, and to develop and validate a clinical diagnostic rule aimed at improving dermatologists' diagnosis of onychomycosis., Methods: A cross-sectional diagnostic study was performed including a total of 277 patients seen by 12 dermatologists. The gold standard was the presence of dermatophytes on culture or a positive nail plate biopsy. For each sign we described prevalence, sensitivity, specificity, positive and negative predictive values, and likelihood ratios for positive and negative results. We developed a diagnostic clinical rule and validated it in a subsample., Results: Helpful findings to predict the presence of fungi are: previous diagnosis of fungal disease; abnormal plantar desquamation (affecting > 25% of the sole); onychomycosis considered the most probable diagnosis by a dermatologist; and presence of interdigital tinea. When dermatologists considered onychomycosis the most probable diagnosis and plantar desquamation was present (13% of patients), the positive predictive value for presence of fungi was 81%. When both signs were absent (34% of patients), the positive predictive value for absence of fungi was 71%. In other situations, clinical diagnosis might not give enough information to decide on therapy., Conclusions: In 13% of the patients (a large number in absolute terms), when dermatologists consider onychomycosis the most probable diagnosis and plantar desquamation is present, therapy should be started without any further test, as clinical diagnosis is at least as accurate as laboratory tests. In other situations, an optimal management strategy should be defined., (© 2010 The Authors. BJD © 2010 British Association of Dermatologists.)

Background: Toenail disorders are frequent, especially onychomycosis. The interobserver variability of nail signs needs to be known before these signs can be confidently applied for diagnosis., Objectives: To describe observer agreement in toenail findings as described by dermatologists in standard clinical practice, focusing on signs that could be useful for diagnosis of onychomycosis., Methods: Prospective cross-sectional study in five dermatology departments. Eighty-six patients with abnormal toenails that could have onychomycosis as a differential diagnosis were independently examined by a pair of dermatologists using a predefined questionnaire, to describe the presence of 10 findings on previous history and 14 physical signs., Results: Agreement was fine for previous history findings: it was very good (kappa > 0.81) for previous diagnosis of diabetes, smoking and use of public dressing rooms or swimming pools. Agreement was good (kappa 0.61-0.80) for immune suppression (drugs or cancer), previous diagnosis of fungal disease and worsening in the last year. It was moderate (kappa 0.41-0.60) for previous diagnosis of arterial disease, trauma induced by work or sports, and distal vs. proximal or lateral vs. central start of the lesion. Agreement was worse for physical signs: we found good agreement for the presence of the same disease in fingernails, abnormal plantar desquamation, deformity causing nail trauma, and subungual hyperkeratosis. It was moderate for the presence of nail destruction, tinea interdigitalis, onycholysis, and the type of material obtained by subungual curettage (dust vs. hard). Agreement was fair (kappa 0.21-0.40) for the presence of longitudinal or transverse striae, trachyonychia, pachyonychia, and change in colour of the nail plate. Pitting was too infrequent to allow for kappa calculation. Chance expected agreement was between 51% and 84% for all signs except pitting., Conclusions: Agreement is adequate for most signs. It is low for the presence of longitudinal or transverse striae, trachyonychia, and change in colour of the nail plate. Pitting is rare in toenails.

A 76-year-old woman presented with a 1-year history of back pain and sudden onset of plantar keratoderma. Her serum carbohydrate antigen (CA 19.9) levels were elevated. Endoscopic radial sonographic examination led to the diagnosis of pancreatic adenocarcinoma, in a stage not detectable with helical CT yet amenable to surgical therapy. Cutaneous lesions disappeared after distal pancreatectomy., ((c) 2007 Wiley Periodicals, Inc.)

Background: Withdrawal of the drug(s) that cause severe cutaneous adverse reactions is usually recommended without proof that it alters the course of those reactions., Objective: To determine whether the timing of causative drug withdrawal is related to the prognosis of patients with toxic epidermal necrolysis (TEN) or Stevens-Johnson syndrome (SJS)., Design: A 10-year observational study (January 1, 1987, through October 30, 1997) of patients admitted to a dermatological intensive care unit, using binary logistic regression analysis., Setting: A single referral unit in a university hospital., Patients: Consecutive sample of 203 patients with TEN or SJS. Exclusion criteria included causative drug undetermined, lack of information on disease evolution, the date of causative drug(s) withdrawal, or the date when the first definite sign of TEN or SJS appeared., Main Outcome Measure: Death before hospital discharge., Results: One hundred thirteen patients were included; 74 had TEN and 39 had SJS; 20 died. The drug causing TEN or SJS was withdrawn early in 64 patients and late (after the first definite sign of TEN or SJS) in 49 patients. After adjustment for confounding variables (age, maximum extent of detachment, admission year, human immunodeficiency virus status), our model showed that the earlier the causative drug was withdrawn, the better the prognosis (odds ratio, 0.69 for each day; 95% confidence interval, 0.53-0.89). Patients exposed to causative drugs with long half-lives had an increased risk of dying (odds ratio, 4.9; 95% confidence interval, 1.3-18.9). The variables did not interact., Conclusions: Prompt withdrawal of drug(s) that are suspected to cause SJS or TEN may decrease mortality. Prompt withdrawal of causative drugs should be a priority when blisters or erosions appear in the course of a drug eruption.