Online prediction tools for melanoma survival: A comparison.

BACKGROUND: Breslow thickness, patient age and ulceration are the three most valuable clinical and pathological predictors of melanoma survival. A readily available reliable online tool that accurately considers these and other predictors could be valuable for clinicians managing melanoma patients. OBJECTIVE: To compare online melanoma survival prediction tools that request user input on clinical and pathological features. METHODS: Search engines were used to identify available predictive nomograms. For each, clinical and pathological predictors were compared. RESULTS: Three tools were identified. The American Joint Committee on Cancer tool inappropriately rated thin tumours as higher risk than intermediate tumours. The University of Louisville tool was found to have six shortcomings: a requirement for sentinel node biopsy, unavailable input of thin melanoma or patients over 70 years of age and less reliable hazard ratio calculations for age, ulceration and tumour thickness. The LifeMath.net tool was found to appropriately consider tumour thickness, ulceration, age, sex, site and tumour subtype in predicting survival. LIMITATIONS: The authors did not have access to the base data used to compile various prediction tools. CONCLUSION: The LifeMath.net prediction tool is the most reliable for clinicians in counselling patients with newly diagnosed primary cutaneous melanoma regarding their survival prospects.

Impact of hidradenitis suppurativa on work loss, indirect costs and income.

BACKGROUND: Hidradenitis suppurativa (HS), a chronic cutaneous disease, can negatively affect work life. OBJECTIVES: This retrospective cohort study evaluates the indirect burden among employed patients with HS in the U.S.A. METHODS: Newly diagnosed and general patients with HS, who were employees (age 18-64 years) from a large claims database (Q1 1999 to Q1 2015), were matched 1 : 5 to controls. Income growth and risk of leaving the workforce were assessed among the newly diagnosed HS and control cohorts in the 5-year study period. Income, work loss days and indirect costs (absenteeism and disability) were assessed among the general HS and control cohorts in the 1-year study period. RESULTS: Newly diagnosed (n = 1003, mean age 39·5 years, 66·3% female) and general patients with HS (n = 1204, mean age 39·9 years, 69·1% female) were matched to 5015 and 6020 controls, respectively. Newly diagnosed patients with HS had significantly slower income growth ($324 per year) and higher risk of leaving the workforce (adjusted hazard ratio 1·65, 95% confidence interval 1·45-1·88) compared with controls (all P < 0·05). General patients with HS had more total days of work loss (18·4 vs. 7·7), higher annual total indirect costs ($2925 vs. $1483) and lower annual income ($54 925 vs. $62 357) than controls (all P < 0·001). CONCLUSIONS: Patients with newly diagnosed HS and general patients with HS experienced a greater indirect burden than matched controls.

Inter-rater agreement and reliability of outcome measurement instruments and staging systems used in hidradenitis suppurativa.

BACKGROUND: Monitoring disease activity over time is a prerequisite for clinical practice and research. Valid and reliable outcome measurement instruments (OMIs) and staging systems provide researchers and clinicians with benchmark tools to assess the primary and secondary outcomes of interventional trials and to guide treatment selection properly. OBJECTIVES: To investigate inter-rater reliability and agreement in instruments currently used in hidradenitis suppurativa (HS), with dermatologists experienced in HS as the rater population of interest. METHODS: In a prospective completely balanced design, 24 patients with HS underwent a physical examination by 12 raters (288 assessments) using nine instruments. The results were analysed using generalized linear mixed models. RESULTS: For the staging systems, the study found good inter-rater reliability for Hurley staging in the axillae and gluteal region, moderate inter-rater reliability for Hurley staging in the groin and for Physician's Global Assessment, and fair inter-rater reliability for refined Hurley staging and the International HS Severity Scoring System. For all the tested OMIs, the observed intervals for limits of agreement were very wide relative to the ranges of the scales. CONCLUSIONS: The very wide intervals for limits of agreement imply that substantial changes are needed in clinical research in order to rule out measurement error. The results illustrate a difficulty, even for experienced HS experts, to agree on the type and number of lesions when evaluating disease severity. The apparent caveats call for global efforts, such as the HIdradenitis SuppuraTiva cORe outcomes set International Collaboration (HISTORIC) to reach consensus on how best to measure physical signs of HS reliably in randomized trials. What's already known about this topic? Without valid and reliable instruments to measure outcomes, researchers and clinicians lack the necessary benchmarks to assess primary and secondary end points of interventional trials properly. Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease. Several outcome measure instruments exist for HS, but their validation is generally incomplete or of relatively low methodological quality. What does this study add? Using a prospective completely balanced design this study examined inter-rater reliability with HS-experienced dermatologists as the rater population of interest. The study did not find very good reliability for any included instrument or lesion counts. This study illustrates the difficulty in finding agreement on the type and number of HS lesions, even among experts. The results question whether physical signs are best measured by a traditional physician lesion count instrument. What are the clinical implications of this work? For staging, Hurley staging and physician global visual analogue scale proved to be acceptable instruments in terms of inter-rater reliability. For the instruments designed to measure changes in health status, our study illustrates how difficult it is, even for experts, to measure the physical signs of HS using a simple rater counting. Consequently, other assessment methods of physicals signs, such as ultrasound evaluation, require consideration.

Evaluation of medical and surgical treatments for hidradenitis suppurativa using real-life data from the Scandinavian registry (HISREG).

BACKGROUND: Hidradenitis suppurativa (HS) substantially affects health-related quality-of-life outcomes. Most treatment options are supported by low quality of evidence without validated outcomes. OBJECTIVE: The aim of this study was to evaluate the efficacy of surgical and medical interventions using physician- and patient-reported outcomes registered in HISREG. METHODS: Data were extracted for all adult patients registered in HISREG between January 2013 and April 2016. Primary endpoints included Dermatology Life Quality Index (DLQI) scores, pain as measured using a numeric rating scale (NRS), Sartorius score and Hurley classification. Minimum clinically important differences (MCIDs) for DLQI and NRS pain were analysed. Secondary endpoints included comparisons among different treatment groups, safety and complications of various treatments. RESULTS: Two hundred and fifty-five patients were included in the study: 31, 188, and 36 patients had Hurley stages I, II and III disease, respectively. Treatment with CO2 lasers was the most common treatment modality. One hundred and forty-nine patients (58.4%) were treated with surgical intervention, 87 (34.1%) received antibiotics and/or anti-inflammatory treatments, and 19 (7.5%) were treated with both surgery and medical intervention. No patients received biologic treatment. In patients with surgical treatments, Sartorius scores were significantly improved compared with baseline (P = 0.001), 83 patients (55%) achieved a DLQI MCID, and 75 patients (49.7%) achieved an NRS pain MCID. In patients with medical treatments, Sartorius scores were not significantly improved compared with baseline (P = 0.582); 25 patients (28%) achieved a DLQI MCID and 28 patients (31%) achieved an NRS pain MCID. In patients treated with surgical and medical combination, 9 (48%) achieved DLQI and NRS pain MCIDs and Sartorius scores were significantly improved. CONCLUSIONS: CO2 laser treatment is more effective than the non-biologic medical treatments in this analysis based on physician- and patient-derived outcomes. The study provides limited evidence for the combination of medical and surgical therapies in patients with HS.

Quality of life measurement in hidradenitis suppurativa: position statement of the European Academy of Dermatology and Venereology task forces on Quality of Life and Patient-Oriented Outcomes and Acne, Rosacea and Hidradenitis Suppurativa.

This paper is organized jointly by the European Academy of Dermatology and Venereology (EADV) Task Force (TF) on Quality of Life (QoL) and Patient-Oriented Outcomes and the EADV TF on acne, rosacea and hidradenitis suppurativa (ARHS). The purpose of this paper was to present current knowledge about QoL assessment in HS, including data on HS-specific health-related (HR) QoL instruments and HRQoL changes in clinical trials, and to make practical recommendations concerning the assessment of QoL in people with HS. HS results in significant quimp that is higher than in most other chronic skin diseases. HS impact in published studies was assessed predominantly (84% of studies) by the Dermatology Life Quality Index (DLQI). There is a lack of high-quality clinical trials in HS patients where HRQoL instruments have been used as outcome measures. One double-blind randomized placebo-controlled trial on infliximab with low number of participants reported significantly better HRQoL improvement in the treatment group than in the placebo group. Well-designed clinical studies in HS patients to compare different treatment methods, including surgical methods and assessing long-term effects, are needed. Because of lack of sufficient validation, the Task Forces are not at present able to recommend existing HS-specific HRQoL instruments for use in clinical studies. The EADV TFs recommend the dermatology-specific DLQI questionnaire for use in HS patients. The EADV TFs encourage the further development, validation and use of other HS-specific, dermatology-specific and generic instruments but such use should be based on the principles presented in the previous publications of the EADV TF on QoL and Patient-Oriented Outcomes.

Hidradenitis suppurativa/acne inversa: a practical framework for treatment optimization - systematic review and recommendations from the HS ALLIANCE working group.

Hidradenitis suppurativa (HS)/acne inversa is a debilitating chronic disease that remains poorly understood and difficult to manage. Clinical practice is variable, and there is a need for international, evidence-based and easily applicable consensus on HS management. We report here the findings of a systematic literature review, which were subsequently used as a basis for the development of international consensus recommendations for the management of patients with HS. A systematic literature review was performed for each of nine clinical questions in HS (defined by an expert steering committee), covering comorbidity assessment, therapy (medical, surgical and combinations) and response to treatment. Included articles underwent data extraction and were graded according to the Oxford Centre for Evidence-based Medicine criteria. Evidence-based recommendations were then drafted, refined and voted upon, using a modified Delphi process. Overall, 5310 articles were screened, 171 articles were analysed, and 65 were used to derive recommendations. These articles included six randomized controlled trials plus cohort studies and case series. The highest level of evidence concerned dosing recommendations for topical clindamycin in mild disease (with systemic tetracyclines for more frequent/widespread lesions) and biologic therapy (especially adalimumab) as second-line agents (following conventional therapy failure). Good-quality evidence was available for the hidradenitis suppurativa clinical response (HiSCR) as a dichotomous outcome measure in inflammatory areas under treatment. Lower-level evidence supported recommendations for topical triclosan and oral zinc in mild-to-moderate HS, systemic clindamycin and rifampicin in moderate HS and intravenous ertapenem in selected patients with more severe disease. Intralesional or systemic steroids may also be considered. Local surgical excision is suggested for mild-to-moderate HS, with wide excision for more extensive disease. Despite a paucity of good-quality data on management decisions in HS, this systematic review has enabled the development of robust and easily applicable clinical recommendations for international physicians based on graded evidence.

Quality of life measurement in acne. Position Paper of the European Academy of Dermatology and Venereology Task Forces on Quality of Life and Patient Oriented Outcomes and Acne, Rosacea and Hidradenitis Suppurativa.

Acne causes profound negative psychological and social effects on the quality of life (QoL) of patients. The European Dermatology Forum S3-Guideline for the Treatment of Acne recommended adopting a QoL measure as an integral part of acne management. Because of constantly growing interest in health-related QoL assessment in acne and because of the high impact of acne on patients' lives, the European Academy of Dermatology and Venereology Task Force on QoL and Patient Oriented Outcomes and the Task Force on Acne, Rosacea and Hidradenitis Suppurativa have documented the QoL instruments that have been used in acne patients, with information on validation, purposes of their usage, description of common limitations and mistakes in their usage and overall recommendations.

Development and validation of the International Hidradenitis Suppurativa Severity Score System (IHS4), a novel dynamic scoring system to assess HS severity.

BACKGROUND: A validated tool for the dynamic severity assessment of hidradenitis suppurativa/acne inversa (HS) is lacking. OBJECTIVES: To develop and validate a novel dynamic scoring system to assess the severity of HS. METHODS: A Delphi voting procedure was conducted among the members of the European Hidradenitis Suppurativa Foundation (EHSF) to achieve consensus towards an initial HS Severity Score System (HS4). Strengths and weaknesses of HS4 were examined by a multicentre prospective study. Multivariate logistic regression, discriminant analysis and receiver operating characteristic curves, as well as examination for correlation (Spearman's rho) and agreement (Cohen's kappa) with existing scores, were engaged to recognize the variables for a new International HS4 (IHS4) that was established by a second Delphi round. RESULTS: Consensus HS4 was based on number of skin lesions, number of skin areas involved and Dermatology Life Quality Index (DLQI), and was evaluated by a sample of 236 patients from 11 centres. Subsequently, a multivariate regression model calculated adjusted odds ratios for several clinical signs. Nodules, abscesses and draining tunnels resulted as the scoring variables. Three candidate scores were presented to the second Delphi round. The resulting IHS4 score is arrived at by the number of nodules (multiplied by 1) plus the number of abscesses (multiplied by 2) plus the number of draining tunnels (multiplied by 4). A total score of 3 or less signifies mild, 4-10 signifies moderate and 11 or higher signifies severe disease. Cohen's kappa was fair (κ = 0·32) compared with Hurley classification, and moderate (κ = 0·49) compared with Expert Opinion. Correlation was good (ρ > 0·6) with Hurley classification, Expert Opinion, Physician's Global Assessment and Modified Sartorius score, and moderate for DLQI (ρ = 0·36). CONCLUSIONS: The novel IHS4 is a validated tool to dynamically assess HS severity and can be used both in real-life and the clinical trials setting.

Cardiovascular disease risk factors in patients with hidradenitis suppurativa: a systematic review and meta-analysis of observational studies.

Hidradenitis suppurativa (HS) is a chronic, inflammatory, debilitating skin disease. The aim of the study was to systematically review the literature and critically answer the question: In patients with HS, do cardiovascular risk factors appear at a significantly higher rate compared with controls? The main search was conducted in Medline, Embase and the Cochrane Central Register. Studies eligible for inclusion were of case-control, cross-sectional and cohort design, and included comparison of any cardiovascular risk factor(s) in patients with HS with those of control groups. An I(2) value > 50% was considered to show substantial heterogeneity. In this case, DerSimonian and Laird random-effect models were considered to compute pooled odds ratios (OR). Otherwise, a fixed-effects model was suitable. Nine studies, with 6174 patients with HS and 24 993 controls, were included. Significant association of HS with obesity [OR 3·45, 95% confidence interval (CI) 2·20-5·38, P < 0·001], central obesity (OR 2·97, 95% CI 1·41-6·25, P = 0·004), active smoking (OR 4·34, 95% CI 2·48-7·60, P < 0·001), history of smoking (OR 6·34, 95% CI 2·41-16·68, P < 0·001), hypertriglyceridemia (OR 1·67, 95% CI 1·14-2·47, P = 0·009), low high-density lipoprotein (HDL) (OR 2·48, 95% CI 1·49-4·16, P < 0·001), diabetes (OR 2·85, 95% CI 1·34-6·08, P = 0·007) and metabolic syndrome (OR 2·22, 95% CI 1·62-3·06, P < 0·001) was detected. Associations were significant both in population and hospital patients with HS, with hospital HS groups having uniformly higher ORs than the population HS groups. Causality could not be assessed. Heterogeneity was substantial in all analyses. This systematic review indicated that cardiovascular risk factors appear at a significantly higher rate in patients with HS compared with controls. The need for screening of patients with HS for modifiable cardiovascular risks is emphasized.

Applicability of dermoscopy for evaluation of patients' response to nonablative therapies for the treatment of superficial basal cell carcinoma.

BACKGROUND: Applicability of dermoscopy in evaluation of outcome and monitoring of superficial basal cell carcinoma (sBCC) after nonablative therapies has not been sufficiently assessed. OBJECTIVES: Certain dermoscopic criteria, namely pigmented structures, ulceration and arborizing vessels, have been suggested to predict the presence of residual disease [residual disease-associated dermoscopic criteria (RDADC)]. We aimed to assess this hypothesis. PATIENTS AND METHODS: Lesions exhibiting RDADC 3 months after treatment were biopsied and in the case of histopathological confirmation were excised. Lesions characterized by white/red structureless areas, superficial fine telangiectasias, or lacking any dermoscopic criterion, were monitored for 12 months. RESULTS: At the 3-month evaluation, one or more of the RDADC were detected in 25/98 (25·5%) sBCCs, in which histology confirmed tumour persistence. In 45 (61·6%) of the 73 remaining lesions, dermoscopy showed white/red structureless areas and/or superficial fine telangiectasias. Twenty-eight lacked any dermoscopic criterion of sBCC. The two latter groups entered follow-up. In total, disease recurred in 13 (17·8%) of the 73 lesions. CONCLUSIONS: RDADC accurately predict residual disease. Absence of dermoscopic criteria of sBCC safely predicts complete histopathological clearance. Detection of white/red structureless areas and/or superficial fine telangiectasias warrants close monitoring to recognize early recurrence.

Re-evaluation of the risk for major adverse cardiovascular events in patients treated with anti-IL-12/23 biological agents for chronic plaque psoriasis: a meta-analysis of randomized controlled trials.

OBJECTIVE: To detect a detrimental or beneficial effect of anti-IL-12/23 biological agents (ustekinumab and briakinumab) for the treatment of chronic plaque psoriasis on major adverse cardiovascular events (MACEs). DESIGN: Systematic review and meta-analysis MEDLINE, EMBASE, the Cochrane Skin Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, SciVerse Scopus and ongoing trial registries were searched from inception until December 2011. Search strategy, eligibility criteria, data and statistical analysis methods were defined prior to the literature search. Randomized, placebo-controlled, double-blind, monotherapy studies with safety data for MACEs of IL-12/23 antibodies in adults were eligible for inclusion. Studies of psoriatic arthritis were excluded. Information from each study was extracted independently by two reviewers, using a standardized data extraction form. The primary outcome measure was the number of MACEs during the placebo-controlled phase of treatment. RESULTS: MACEs include myocardial infarction, cerebrovascular accident or cardiovascular death. No statistical heterogeneity across the studies using the I(2) statistic (I(2) = 0) was found. We employed Peto one-step method to determine odds ratios and quantify a possible detrimental or beneficial association of IL-12/23 antibodies treatment with MACEs. We found a possible higher risk of MACEs in those patients treated with IL-12/23 antibodies compared with those at placebo (OR = 4.23, 95% CI: 1.07-16.75, P = 0.04). This study is unaffected by non-reporting of outcomes with no events. CONCLUSION: Compared with placebo, there was a significant difference in the rate of MACEs observed in patients receiving anti-IL-12/23 biological agents.

Dermoscopy of early stage mycosis fungoides.

BACKGROUND: Early stage mycosis fungoides (MF) is difficult to be clinically differentiated from chronic dermatitis (CD) in a high proportion of patients. Dermoscopy is a rapid, cheep, non-invasive and widely used method for the evaluation of skin tumours and, recently, of inflammatory skin diseases, as well. OBJECTIVE: To describe the dermoscopic pattern of early stage MF and compare it with the dermoscopic features observed in CD. METHODS: This was a retrospective study. Dermoscopic images of lesions that were clinically equivocal between MF and CD were evaluated for the presence of predefined morphologic criteria. Diagnosis had been histopathologically and immunohistochemically confirmed in all cases. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for predefined dermoscopic criteria in relation to the diagnosis of mycosis fungoides. RESULTS: A total of 67 dermoscopic images were selected for dermoscopic evaluation. Mycosis fungoides lesions exhibited a characteristic dermoscopic pattern consisting of fine short linear vessels (sensitivity 93.7%, specificity 97.1%) and orange-yellowish patchy areas (sensitivity 90.6%, specificity 99.7%). A characteristic vascular structure resembling spermatozoa was also found to be highly specific for the diagnosis of mycosis fungoides. CD was typified by a different dermoscopic pattern, usually consisting of dotted vessels. CONCLUSIONS: These observations provide a first indication that early stage MF exhibits a characteristic dermoscopic pattern which is different from CD. Prospective studies with long term follow-up are needed to determine the value of these dermoscopic criteria in the differentiation between the two entities in the daily routine.

Accuracy of dermoscopic criteria for the diagnosis of psoriasis, dermatitis, lichen planus and pityriasis rosea.

BACKGROUND: Dermoscopy is useful in evaluating skin tumours, but its applicability extends also to the field of inflammatory skin disorders. Plaque psoriasis (PP), dermatitis, lichen planus (LP) and pityriasis rosea (PR) are common inflammatory skin diseases, but little is currently known about their dermoscopic features. OBJECTIVES: To determine and compare the dermoscopic patterns associated with PP, dermatitis, LP and PR and to assess the validity of certain dermoscopic criteria in the diagnosis of PP. METHODS: Patients with PP, dermatitis, LP and PR were prospectively enrolled. The single most recently developed lesion was examined dermoscopically and histopathologically. Variables included vascular morphology, vascular arrangement, background colour, scale colour, scale distribution and presence of Wickham striae. Univariate and adjusted odds ratios were calculated. Discriminant functions were used to plot receiver-operator characteristic curves. RESULTS: Eighty-three patients with PP and 86 patients with either dermatitis, LP or PR were included in the study. Dotted vessels in a regular arrangement over a light red background and white scales were highly predictive for the diagnosis of PP, whereas dermatitis more commonly showed yellow scales and dotted vessels in a patchy arrangement. PR was characterized by yellowish background, dotted vessels and peripheral scales; whitish lines (Wickham striae) were seen exclusively in LP. CONCLUSIONS: PP, LP, PR and dermatitis show specific dermoscopic patterns that may aid their clinical diagnosis. Certain combinations of dermoscopic features can reliably predict the diagnosis of PP.

Selenomethionine treatment in patients with autoimmune thyroiditis: a prospective, quasi-randomised trial.

AIMS: To test whether selenium administration affects autoantibodies to thyroid peroxidase (anti-TPO) and thyroglobulin (anti-TG) titres in chronic autoimmune (Hashimoto's - HT) thyroiditis. METHODS: A prospective, open-label, quasi-randomised study in 86 HT patients (n = 86) assigned to either selenomethionine (Seme) 200µg daily for 3 months (Se3, n = 15) or 6 months (Se6, n = 46) or placebo (Control, n = 25). Serum Se, anti-TPO, anti-TG and thyroid hormones were measured in all patients at baseline, 3 and 6 months. A subgroup of 18 patients (twelve on Se6 and six controls) were subjected in thyroid fine-needle biopsy at baseline and 6 months to detect changes in lymphocyte infiltration. RESULTS: No significant difference in anti-TPO levels was recorded after 3 (p = 0.88) or 6 months (p = 0.62) on Seme. Anti-TG levels decreased both at 3 months (p = 0.001) and 6 months (p = 0.001). No significant changes in thyroid stimulating hormone, free thyroxine and free triiodothyronine levels or in the lymphocytes' number in thyroid cytology specimens were detected. Age, gender, duration of disease, baseline anti-TPO levels and per cent change in Se levels could not predict the response of anti-TPO levels to Seme administration. CONCLUSION: Our data suggest that Seme administration in pharmacological doses for a period of 6 months seems to have no significant effect on serum thyroid auto-antibodies' levels or lymphocyte infiltration of the thyroid gland.

Investigation of cytokine levels and their association with SCORAD index in adults with acute atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease with increasing frequency over the last decades, especially in adults. Cytokines orchestrate atopic skin inflammation. Objectives The aim of this study was to compare serum levels of cytokines in adult patients with acute AD (AD1) with other groups of AD patients and controls and investigate the possible association between such cytokines and disease severity. METHODS: We measured cytokine levels using flow cytometry in 21 adult patients with acute AD, 12 adults with chronic AD, 10 children with acute AD and 10 healthy adults. RESULTS: Flow cytometry analysis of cytokines revealed that interleukin 10 (IL-10), IL-6, interferon γ (IFN-γ) and IL-4 levels were significantly decreased in AD1 group compared with controls, whereas IL-2 and tumour necrosis factor (TNF) did not differ. Comparison of AD1 group with adults chronic phase group showed that IgE, eosinophil and IL-2 levels remained unaltered, whereas IL-10, IL-6, IFN-γ, IL-4 and TNF were significantly decreased. SCORAD and IgE levels were significantly increased, IL-10, IL-6 and IFN-γ were decreased and TNF, IL-2, IL-4 and eosinophil levels remained unchanged in AD1 group compared with children acute phase group. Within AD1 group correlation analysis revealed that IgE and TNF levels were significantly associated with AD severity. Coefficient of determination analysis revealed that TNF and IgE levels could explain 49.14% and 35.28% of the variance of SCORAD. CONCLUSIONS: These data indicate that serum IgE and TNF levels correlate with AD severity and that serum cytokines are downregulated in AD1 group. Further studies are clearly needed to elucidate cytokines' role in adults with AD.