Quality of life measurement in rosacea. 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.

The European Academy of Dermatology and Venereology (EADV) Task Forces (TFs) on Quality of Life (QoL) and Patient-Oriented Outcomes and Acne, Rosacea and Hidradenitis Suppurativa (ARHS) do not recommend the use of any generic instrument as a single method of Health Related (HR) QoL assessment in rosacea, except when comparing quimp (quality of life impairment) in rosacea patients with that in other non-dermatologic skin diseases and/or healthy controls. The EADV TFs on QoL and Patient-Oriented Outcomes and ARHS recommend the use of the dermatology-specific HRQoL instrument the Dermatology Life Quality Index (DLQI) and the rosacea-specific HRQoL instrument RosaQoL in rosacea patients. The DLQI minimal clinically important difference may be used as a marker of clinical efficacy of the treatment and DLQI score banding of 0 or 1 corresponding to no effect on patients' HRQoL could be an important treatment goal. This information may be added to consensuses and guidelines for rosacea.

Unmet clinical needs and burden of disease in hidradenitis suppurativa: real-world experience from EU5 and US.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, inflammatory, debilitating skin disease characterized by painful deep lesions and associated with substantial disease burden. OBJECTIVES: The objective of this study was to describe physician- and patient-reported clinical unmet needs from a real-world perspective. METHODS: This study used data from the Adelphi HS Disease Specific Programme, a point-in-time survey of dermatologists and their patients with HS in Europe and the United States. Dermatologists completed patient record forms (PRFs) for 5-7 consecutively consulting patients with HS; patients or carers of patients also optionally completed a patient/carer self-completion questionnaire (PSC/CSC). Data collection included demographics, symptomatology and impact on quality of life (QoL). RESULTS: Dermatologists (N = 312) completed PRFs for 1787 patients with HS; patient- and carer-reported questionnaires (PSC/CSC) were completed for 33.1% (591/1787) of patients. The mean age was 34.4 ± 12.2 years and 57.6% of patients were female (1029/1787). Physician-judged disease severity at sampling was categorized as mild in 66.0% (1179/1787), moderate in 29.3% (523/1787) and severe in 4.7% (85/1787) of patients. Deterioration or unstable condition over the previous 12 months was described by 17.1% [235/1372] and 12.6% [41/325] of physician- and patient/carer-reported cases, respectively. Despite receiving treatment, high proportions of patients still experienced symptoms at sampling (general pain/discomfort [49.5%, 885/1787]; inflammation/redness of lesions/abscesses [46.1%, 823/1787] and itching [29.9%, 535/1787]); these symptoms were more frequent in patients with moderate or severe disease. Patients reported a mean Dermatology Life Quality Index score of 5.9 ± 5.4 (555/591; mild, 4.1 ± 4.3; moderate, 9.4 ± 5.4; severe, 13.3 ± 5.5) and a mean Hidradenitis Suppurativa Quality of Life score of 11.0 ± 10.6 (518/591; mild, 7.6 ± 8.3; moderate, 17.7 ± 10.0; severe, 31.0 ± 15.4) indicating a substantial impact on QoL. CONCLUSIONS: Patients with HS experienced a high disease burden despite being actively treated by a dermatologist. This study demonstrates that the burden of HS disease is generally poorly managed with a considerable impact observed on patients' QoL.

Evidence for a 'window of opportunity' in hidradenitis suppurativa treated with adalimumab: a retrospective, real-life multicentre cohort study.

BACKGROUND: The anti-tumour necrosis factor (TNF)-α adalimumab is the only licenced biologic for moderate-to-severe hidradenitis suppurativa (HS). No predictors of response have been identified so far. OBJECTIVES: To identify clinical parameters predicting response to adalimumab and confirm its efficacy/safety. METHODS: The data of 389 patients with HS treated with adalimumab in 21 Italian centres were reviewed. Sex, age at onset/diagnosis/baseline, body mass index, smoking, phenotype, previous treatments, concomitant antibiotics and 'therapeutic delay', defined as the time from HS onset to adalimumab initiation, were assessed. Response to adalimumab and its impact on quality of life (QoL) were evaluated using the Hidradenitis Suppurativa Clinical Response (HiSCR) and the Dermatology Life Quality Index (DLQI) or the Visual Analogue Scale for pain (VAS pain), respectively. Logistic regression analysis was performed. RESULTS: The therapeutic delay correlated to lack of response to adalimumab at week 16 [odds ratio (OR) 1·92 for therapeutic delay > 10 years; 95% confidence interval (CI) 1·28-2·89; P = 0·0016). HiSCR was achieved in 43·7% and 53·9% patients at week 16 and 52, respectively. Significant reductions in both DLQI and VAS pain were found between week 16 vs. baseline (P < 0·0001 for both) and week 52 vs. baseline (P < 0·0001 for both). Previous immunosuppressants inversely correlated to HiSCR at week 52 (OR = 1·74, 95% CI 1·04-2·91, P = 0·0342). CONCLUSIONS: Inverse correlation between therapeutic delay and clinical response was found, supporting early adalimumab use and providing evidence for a 'window of opportunity' in HS treatment. Adalimumab efficacy and safety were confirmed, along with patients' QoL improvement. Immunosuppressants could negatively influence the response to adalimumab inducing a switch to non-TNF-α-driven pathways.

Comparison of guidelines and consensus articles on the management of patients with acne with oral isotretinoin.

Guidelines and consensus on the management of patients with acne aim to give evidence-based, expert-group recommendations. This review compares current guidelines and consensus articles to provide a compilation of recommendations on the treatment of acne with oral isotretinoin. Ten common, relevant, clinical questions are addressed, based on published recommendations, including the indications of isotretinoin, the proposed daily dose, the cumulative isotretinoin dose and the laboratory monitoring needed. Recommendations on special considerations are also addressed, including the timing of procedures and the question of an association of depression or inflammatory bowel disease with isotretinoin. A major limitation is the use of different classification systems for acne across guidelines. The recommended daily dose ranges from 0.3 to 0.5 mg/kg in the European guidelines to up to 1 mg/kg in the US guidelines. A specific duration of treatment of at least 6 months is only recommended in the European guidelines. All guidelines report the need of strict pregnancy prevention measures. The European, French and US guidelines recommend to monitor for symptoms of depression. Important clinical questions that are inconsistently addressed in guidelines include the age indication, the recommendation for a cumulative dose, the timing of procedures, the association of isotretinoin with IBD, the recommendation for preventing acne flares and for appropriate laboratory monitoring. These topics should be clearly included in the recommendations of guidelines as they are often raised in everyday clinical practice.

Creation of a severity index for hidradenitis suppurativa that includes a validated quality-of-life measure: the HIDRAscore.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, debilitating disease with a considerable effect on patient quality of life. Its clinical severity can be measured using different scoring systems; however, few of them include patient-centred parameters. OBJECTIVE: To create a new scoring system for HS that includes a quality-of-life instrument, the HIDRAdisk. METHODS: This post hoc analysis was carried out within the framework of a multicentre, longitudinal, epidemiologic study conducted over 9 months on quality-of-life aspects of HS. The new severity score was created using as reference a question from the Subject Satisfaction Questionnaire (SSQ) concerning the severity of HS as evaluated by the patient. Associated variables were selected using univariable and multivariable logistic regression models. The discriminant capabilities of the final model and of the final score were evaluated by the area under the receiver operating characteristic curve and the Hosmer-Lemeshow test. RESULTS: The study population included 308 patients with HS of any severity grade. According to the results of the regression models, the variables associated with the reference SSQ measure were number of inflammatory nodules, abscesses and draining fistulas; the HIDRAdisk score; and the number of subumbilical lesions. The HIDRAscore is obtained by the sum of the scores associated with the number of these parameters. Possible scores range from 0 to 10. CONCLUSION: The HIDRAscore is a new scoring system for HS severity which, in addition to the clinical evaluation by the physician, includes a validated patient-reported outcome measure, the HIDRAdisk.

Hidradenitis suppurativa epidemiology: from the first Italian registry in 2009 to the most recent epidemiology updates - Italian Registry Hidradenitis Suppurativa project 2.

BACKGROUND: The incidence of hidradenitis suppurativa (HS) is still not fully established with only a few studies reporting its estimates. Prevalence estimates range from 5:10 000 to 4:100. These extremely large variations could be explained by a combination of factors, including different selection procedures, different diagnostic criteria, and variations in the sex and age distribution of the examined samples. OBJECTIVES: To analyze variations between two consecutive Italian Registries on HS. METHODS: Data obtained from the second Italian Registry on HS, named 'Italian Registry Hidradenitis Suppurativa (IRHIS) Project 2', are compared to the previous first Italian registry on HS. RESULTS: Data on 944 patients are reported. The more relevant aspects that characterize IRHIS 2 project, in comparison with the previous first Italian Registry on HS, are as follows: (i) the total number of patients, about fourfold higher; (ii) a more uniform national geographic distribution of the patient population; (iii) a larger number of dermatology units involved; (iv) a larger number of items considered in the data collection; (v) 6 years of difference between the onset of the two registries (2009-2013 vs. 2015-2019). Comparing data of the two registries, there are no statistically significant differences in terms of age at the time of the visit, gender, BMI, smoking habits, age at onset and age at first diagnosis by physician. Interestingly, the mean Sartorius score in the IRHIS project 2 (58.8) was significantly lower compared to the first Italian Registry (78.4). CONCLUSIONS: The importance of the registries, at both national and international levels, in collecting useful real-life data is confirmed by these two Italian projects.

The evolution of healthy skin to acne lesions: a longitudinal, in vivo evaluation with reflectance confocal microscopy and optical coherence tomography.

BACKGROUND: Comedogenesis is defined as the process of the development of a new comedo, which is of great importance for the understanding of acne. OBJECTIVE: To evaluate the formation and evolution of acne lesions from clinically unaffected skin of patients with mild-moderate acne to characterize the morphological changes and natural resolution by means of in vivo reflectance confocal microscopy (RCM) and dynamic optical coherence tomography (D-OCT). METHODS: Ten patients with mild-moderate acne, not assuming any topical or systemic therapy, comprised between 12 and 30 years of age, were recruited. A target area of 4 × 4 mm of the face, without acne lesions at baseline, was selected. A set of standardized clinical pictures, RCM and D-OCT images were acquired weekly for 6 weeks and evaluated. RESULTS: Seventy full sets of clinical, RCM and D-OCT images were analysed. The appearance of acne lesion is preceded by an increase of large bright follicles in the area corresponding to infundibular keratinization, followed by increment of inflammation parameter, such as increased of small bright cells upon RCM and vascular network upon D-OCT, which return to normal after the resolution of acute inflammation. CONCLUSION: Acne skin dynamics is complex and seems characterized by the early increase in the number of dysmorphic pilosebaceous units and the hyperkeratinization of the acroinfundibulum of the pilosebaceous duct prior to the occurrence of inflammatory events around the follicle. The processes of hyperkeratinization and inflammatory phenomena may generate a pathologic vicious cycle, which characterizes acne through progressive worsening and a self-sustainment mechanism.

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.

HIDRAdisk: validation of an innovative visual tool to assess the burden of hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, relapsing, inflammatory skin disease characterized by painful inflamed nodules, recurrent abscesses and fistulas located in apocrine gland-bearing body sites. The negative impact of HS on patient's quality of life (QoL) has been reported to be greater than other dermatologic conditions as psoriasis and atopic eczema, and its improvement is an important goal in disease management. Nowadays, there are no specific validated QoL instruments available for HS and generic dermatologic questionnaires are used. OBJECTIVE: The objective of this study was to demonstrate the validity, reliability and responsiveness of HIDRAdisk, a new innovative tool designed for rapid assessment of HS burden and, at the same time, an intuitive graphic visualization of the measurement outcome. METHODS: A multicentre, longitudinal, observational study was conducted to validate the HIDRAdisk compared with other validated questionnaires [Skindex-16, Dermatology Life Quality Index (DLQI), Work Productivity and Activity Impairment-General Health (WPAI:GH)] and to evaluate its correlation with disease severity in Italian patients with any degree of HS severity, as measured by Hurley stage and HS Physician Global Assessment (HS-PGA). RESULTS: A total of 140 patients (59% women; mean age 34.9 ± 11.0 years) were enrolled in 27 dermatologic centres. HIDRAdisk showed a strong correlation with Skindex-16 and DLQI, and a good one with WPAI:GH (correlation coefficient: 0.7568, 0.6651 and 0.5947, respectively) and a statistically significant correlation with both Hurley stage and HS-PGA. Very good internal consistency (Cronbach coefficient >0.80; intraclass correlation coefficient >0.6), with correlation between the 10 items, good test-retest reliability (Spearman correlation coefficient, 0.8331; P < 0.0001) and responsiveness to changes were demonstrated. CONCLUSION: Our study shows that HIDRAdisk, a short and innovative visual HS QoL instrument, has been psychometrically validated in Italian language and it may help improve the management of HS once implemented in routine clinical practice.

Rates of antibiotic resistance/sensitivity in bacterial cultures of hidradenitis suppurativa patients.

BACKGROUND: Antibiotic (AB) treatment is one of the first steps in the management of hidradenitis suppurativa (HS). Bacteria, in HS patients, may play a double role, as triggering factors of inflammatory reactions and/or agents of infection. OBJECTIVES: The aims of this study are as follows: (i) to assess prevalence and AB resistance of bacterial growths in HS patients (ii) assessment of the clinical relevance of obtained data in guiding the selection of the most effective AB therapy. METHODS: Purulent material from 137 skin lesions of HS patients was collected with swabs. Bacterial flora and AB sensitivity were determined using microbiological cultures for aerobic and anaerobic bacteria. RESULTS: A total of 114 samples resulted positive for bacteria. Sample was collected from the axillae, groin and perianal areas. A total of 163 single bacterial growths were observed; 55% were Gram-positive and 44% were Gram-negative. Among them, 18.4% were anaerobic. The most frequent bacterial families included enterobacteriaceae (30.7%), Staphylococcus (25.2%) and Streptococcus (14.1%). The most frequent genus or species were proteus spp. (13.5%) and Escherichia coli (9.8%). The prevalence of AB resistance observed was clindamycin 65.7%, rifampicin 69.3%, penicillin 70.0%, ciprofloxacin 74%, tetracycline 84.7% and erythromycin 89.0%. A limitation of the study is represented the short culture period adopted which may have impaired the isolation of anaerobes. CONCLUSIONS: Bacterial growth in HS patients has shown a high level of resistance to ABs, including rifampicin, clindamycin and tetracyclines, cited as an empiric choice in HS therapeutic guidelines. A targeted and specific AB therapy, driven by microbiological evaluations with prolonged culture periods, seems more appropriate than empiric, generic, non-specific, therapeutic approaches. Current knowledge regarding HS bacterial AB resistance should be considered in the update of current therapeutic guidelines for HS.

Validation of a visual-aided questionnaire for the self-assessment of hidradenitits suppurativa.

BACKGROUND: Hidradenitis Suppurativa (HS) is a chronic, highly debilitating disease. Few questionnaires have been developed to identify potential HS cases based on simple questions. A visual representation may help in characterising these lesions. OBJECTIVE: To develop and validate a visually assisted questionnaire for HS detection. METHODS: This was an observational diagnostic study on a series of patients with a first diagnosis of HS and a corresponding series of age and gender-matched controls consecutively observed in two Italian centres. The questionnaire was developed based on a critical appraisal of the relevant literature and on expert consensus. Measures of accuracy and reproducibility were assessed. RESULTS: 57 patients with HS and 57 controls were included in the study (mean age 32.9 ± 12.3 years). Based on at least one affirmative answer to the proposed questionnaire items, the accuracy was 95.6%, with a sensitivity of 98.2% and a specificity of 93.0%. Reproducibility was almost perfect on all the tested items (Cohen's kappa ≥ 0.85). LIMITATIONS: The questionnaire was tested only in experimental conditions. CONCLUSION: The questionnaire could be a useful tool for HS screening in the general population. Further studies are needed to confirm its performance in a real-world setting.

Which acne treatment has the best influence on health-related quality of life? Literature review by the European Academy of Dermatology and Venereology Task Force on Quality of Life and Patient Oriented Outcomes.

According to results of a recent literature search performed by the European Academy of Dermatology and Venereology (EADV) Task Forces (TF) on Quality of Life and Patient Oriented Outcomes (QoL and PO) and Acne, Rosacea and Hidradenitis Suppurativa (ARHS), most of the publications where health-related (HR) QoL of acne patients was studied were clinical trials. Members of the EADV TF on QoL and PO decided to detect which acne treatment has the best influence on HRQoL of acne patients. A new literature search was organized to find publications on acne treatment where the HRQoL of patients was assessed as an outcome measure. From 186 papers with HRQoL assessment, 37 papers were included for further analysis. Our results revealed that oral isotretinoin had the best influence on HRQoL of acne patients. Several other treatment methods also showed good effects on the HRQoL of acne patients. Oral isotretinoin and norethindrone acetate/ethinyl estradiol, topical clindamycin phosphate/benzoyl peroxide and adapalene/benzoyl peroxide showed significantly better effect on HRQoL than placebo. There is limited number of the high-quality studies on acne treatment where HRQoL was assessed. Dermatology-specific and acne-specific instruments showed much better sensitivity to successful therapeutic intervention than generic HRQoL instruments. The most frequently used HRQoL instrument was the Dermatology Life Quality Index questionnaire.

Validation of 3D skin imaging for objective repeatable quantification of severity of atrophic acne scarring.

BACKGROUND: One major sequelae of acne is atrophic scarring, yet objective tools to assess scars are lacking. Neither depth nor volume of atrophic scars is readily evaluable clinically and standard 2D photography is significantly affected by lighting and shadows. The aim of our study was to define and evaluate parameters of 3D imaging that can be used to assess severity of atrophic acne scarring. METHODS: Single center study of 31 patients with acne scarring. A target area of 3 × 3 cm was defined on the face. The global severity of atrophic acne scarring in the target area was evaluated by 5 dermatologists and scars were counted and categorized by size (scars < 2 mm, 2-4 mm, and > 4 mm in diameter). Three dimensional images of the target area were acquired with the LifeViz Micro® system and analysis was performed using MountainsMaps® software. An algorithm was developed to quantify the scar volume loss: shape removal step, with an order 5 polynomial, and to calculate the Valley void volume 80% (Vvv 80%) defined in the ISO-25178 standard for 3D surface texture. RESULTS: Correlation coefficient of the Vvv parameter to mean global severity at the target area rating was 0.77. The volume of scars evaluated with the Vvv parameter was mainly impacted by scars > 2 mm. The evaluations demonstrated good repeatability (with an intra-class correlation coefficient ICC = 0.98). CONCLUSIONS: We demonstrate convergent validation to clinical assessment and repeatability of 3D skin imaging in atrophic acne scarring. Image analysis is straightforward and can be integrated into an automated workflow.

The influence of exposome on acne.

BACKGROUND: Acne vulgaris is one of the main reasons for dermatological consultations. Severity and response to treatment may be impacted by various external factors or exposome. AIM: To assess the impact of environmental factors on acne and to provide a comprehensive overview of the acne exposome. METHODS: Two consensus meetings of five European dermatologists and a comprehensive literature search on exposome factors triggering acne served as a basis for this review. RESULTS: Acne exposome was defined as the sum of all environmental factors influencing the occurrence, duration and severity of acne. Exposome factors impact on the response and the frequency of relapse to treatments by interacting with the skin barrier, sebaceous gland, innate immunity and cutaneous microbiota. They may be classified into the following six main categories: nutrition, psychological and lifestyle factors, occupational factors including cosmetics, as well as pollutants, medication and climatic factors. Moreover, practical considerations for the dermatologist's clinical practice are proposed. CONCLUSION: Exposome factors including nutrition, medication, occupational factors, pollutants, climatic factors, and psychosocial and lifestyle factors may impact on the course and severity of acne and on treatment efficacy. Identifying and reducing the impact of exposome is important for an adequate acne disease management.