The severe cutaneous adverse reaction epidermal necrolysis (EN) which includes toxic epidermal necrolysis and the milder Stevens-Johnson syndrome is characterized by epidermal loss due to massive... Show moreThe severe cutaneous adverse reaction epidermal necrolysis (EN) which includes toxic epidermal necrolysis and the milder Stevens-Johnson syndrome is characterized by epidermal loss due to massive keratinocyte apoptosis and/or necroptosis. EN is often caused by a drug mediating a specific TCR-HLA interaction via the (pro)hapten, pharmacological interaction or altered peptide loading mechanism involving a self-peptide presented by keratinocytes. (Memory) CD8 + T cells are activated and exhibit cytotoxicity against keratinocytes via the perforin/granzyme B and granulysin pathway and Fas/FasL interaction. Alternatively drug-induced annexin release by CD14 + monocytes can induce formyl peptide receptor 1 death of keratinocytes by necroptosis. Subsequent keratinocyte death stimulates local inflammation, activating other immune cells producing pro-inflammatory molecules and downregulating regulatory T cells. Widespread epidermal necrolysis and inflammation can induce life-threatening systemic effects, leading to high mortality rates. Research into genetic susceptibility aims to identify risk factors for eventual prevention of EN. Specific HLA class I alleles show the strongest association with EN, but risk variants have also been identified in genes involved in drug metabolism, cellular drug uptake, peptide presentation and function of CD8 + T cells and other immune cells involved in cytotoxic responses. After the acute phase of EN, long-term symptoms can remain or arise mainly affecting the skin and eyes. Mucosal sequelae are characterized by occlusions and strictures due to adherence of denuded surfaces and fibrosis following mucosal inflammation. In addition, systemic pathology can cause acute and chronic hepatic and renal symptoms. EN has a large psychological impact and strongly affects health-related quality of life among EN survivors. Show less
Rijsbergen, M.; Niemeyer-van der Kolk, T.; Rijneveld, R.; Pinckaers, J.H.F.M.; Meshcheriakov, I.; Bavinck, J.N.B.; ... ; Rissmann, R. 2020
BackgroundAssessment of treatment effects in clinical trials requires valid information on treatment adherence, adverse events and symptoms. Paper-based diaries are often inconvenient and have... Show moreBackgroundAssessment of treatment effects in clinical trials requires valid information on treatment adherence, adverse events and symptoms. Paper-based diaries are often inconvenient and have limited reliability, particularly for outpatient trials.ObjectivesTo investigate the utility of an electronic diary (e-diary) application for patients with skin diseases in outpatient clinical trials.MethodsAn e-diary application was developed and technically validated. Treatment adherence was defined as topical administration by the patient, and patient-reported outcomes, i.e. pain and itch, were evaluated by the e-diary in six clinical trials on newly tested topical drugs. Additionally, the proportion of patients capturing the applied topical drug by camera and filling in the pain and itch scores was defined as e-diary adherence, and patients' perception of usefulness and acceptability of the e-diary were evaluated.ResultsTreatment adherence rates of the included 256 patients were high (median 98%, range 97-99%). E-diary adherence was also high with a median of 93% (range 87-97%) for capturing the applied drug by camera, and 89% (range 87-96%) and 94% (range 87-96%) for entering respectively the itch and pain score. Daily symptom scores provided good insights into the disease burden, and patients rated the e-diary as good to excellent with respect to user acceptability.ConclusionsThe results suggest that the e-diary is an excellent way to ensure proper treatment administration, indicated by both the high user acceptability scores and high treatment adherence. Moreover, the e-diary may also be valuable for frequent and reliable monitoring of patient-reported outcomes in daily clinical practice. Show less
Rijsbergen, M.; Niemeyer-van der Kolk, T.; Rijneveld, R.; Pinckaers, J.H.F.M.; Meshcheriakov, I.; Bavinck, J.N.B.; ... ; Rissmann, R. 2020
BackgroundAssessment of treatment effects in clinical trials requires valid information on treatment adherence, adverse events and symptoms. Paper-based diaries are often inconvenient and have... Show moreBackgroundAssessment of treatment effects in clinical trials requires valid information on treatment adherence, adverse events and symptoms. Paper-based diaries are often inconvenient and have limited reliability, particularly for outpatient trials.ObjectivesTo investigate the utility of an electronic diary (e-diary) application for patients with skin diseases in outpatient clinical trials.MethodsAn e-diary application was developed and technically validated. Treatment adherence was defined as topical administration by the patient, and patient-reported outcomes, i.e. pain and itch, were evaluated by the e-diary in six clinical trials on newly tested topical drugs. Additionally, the proportion of patients capturing the applied topical drug by camera and filling in the pain and itch scores was defined as e-diary adherence, and patients' perception of usefulness and acceptability of the e-diary were evaluated.ResultsTreatment adherence rates of the included 256 patients were high (median 98%, range 97-99%). E-diary adherence was also high with a median of 93% (range 87-97%) for capturing the applied drug by camera, and 89% (range 87-96%) and 94% (range 87-96%) for entering respectively the itch and pain score. Daily symptom scores provided good insights into the disease burden, and patients rated the e-diary as good to excellent with respect to user acceptability.ConclusionsThe results suggest that the e-diary is an excellent way to ensure proper treatment administration, indicated by both the high user acceptability scores and high treatment adherence. Moreover, the e-diary may also be valuable for frequent and reliable monitoring of patient-reported outcomes in daily clinical practice. Show less
Background The quantification of human papilloma virus (HPV)-induced skin lesions is essential for the clinical assessment of the course of disease and the response to treatment. However, clinical... Show moreBackground The quantification of human papilloma virus (HPV)-induced skin lesions is essential for the clinical assessment of the course of disease and the response to treatment. However, clinical assessments that measure dimensions of lesions using a caliper do not provide complete insight into three-dimensional (3D) lesions, and its inter-rater variability is often poor. Objective The aim of this study was to validate a stereophotogrammetric 3D camera system for the quantification of HPV-induced lesions. Methods The camera system was validated for accuracy, precision and interoperator and inter-rater variability. Subsequently, 3D photographs were quantified and compared to caliper measurements for clinical validation by Bland-Altman modelling, based on data from 80 patients with cutaneous warts (CW), 24 with anogenital warts (AGW) patients and 12 with high-grade squamous intraepithelial lesions of the vulva (vulvar HSIL) with a total lesion count of 220 CW, 74 AGW and 31 vulvar HSIL. Results Technical validation showed excellent accuracy [coefficients of variation (CV) <= 0.68%] and reproducibility (CVs <= 2%), a good to excellent agreement between operators (CVs <= 8.7%) and a good to excellent agreement between different raters for all three lesion types (ICCs >= 0.86). When comparing 3D with caliper measurements, excellent biases were found for diameter of AGW (long diameter 5%), good biases were found for diameter of AGW (short diameter 10%) and height of CW (8%), and acceptable biases were found for the diameter of CW (11%) and vulvar HSIL (short diameter 14%, long diameter 16%). An unfavourable difference between these methods (bias 25%) was found for the assessment of height of AGWs. Conclusion Stereophotogrammetric 3D imaging is an accurate and reliable method for the clinical visualization and quantification of HPV-induced skin lesions. Show less
Rijsbergen, M.; Pagan, L.; Niemeyer-van der Kolk, T.; Rijneveld, R.; Hogendoorn, G.; Lemoine, C.; ... ; Rissmann, R. 2019
Background The quantification of human papilloma virus (HPV)-induced skin lesions is essential for the clinical assessment of the course of disease and the response to treatment. However, clinical... Show moreBackground The quantification of human papilloma virus (HPV)-induced skin lesions is essential for the clinical assessment of the course of disease and the response to treatment. However, clinical assessments that measure dimensions of lesions using a caliper do not provide complete insight into three-dimensional (3D) lesions, and its inter-rater variability is often poor. Objective The aim of this study was to validate a stereophotogrammetric 3D camera system for the quantification of HPV-induced lesions. Methods The camera system was validated for accuracy, precision and interoperator and inter-rater variability. Subsequently, 3D photographs were quantified and compared to caliper measurements for clinical validation by Bland-Altman modelling, based on data from 80 patients with cutaneous warts (CW), 24 with anogenital warts (AGW) patients and 12 with high-grade squamous intraepithelial lesions of the vulva (vulvar HSIL) with a total lesion count of 220 CW, 74 AGW and 31 vulvar HSIL. Results Technical validation showed excellent accuracy [coefficients of variation (CV) <= 0.68%] and reproducibility (CVs <= 2%), a good to excellent agreement between operators (CVs <= 8.7%) and a good to excellent agreement between different raters for all three lesion types (ICCs >= 0.86). When comparing 3D with caliper measurements, excellent biases were found for diameter of AGW (long diameter 5%), good biases were found for diameter of AGW (short diameter 10%) and height of CW (8%), and acceptable biases were found for the diameter of CW (11%) and vulvar HSIL (short diameter 14%, long diameter 16%). An unfavourable difference between these methods (bias 25%) was found for the assessment of height of AGWs. Conclusion Stereophotogrammetric 3D imaging is an accurate and reliable method for the clinical visualization and quantification of HPV-induced skin lesions. Show less
Background Organ transplant recipients (OTR) have a higher risk of developing cutaneous squamous cell carcinoma (cSCC) compared to the immunocompetent population. Immunosuppression is often stated... Show moreBackground Organ transplant recipients (OTR) have a higher risk of developing cutaneous squamous cell carcinoma (cSCC) compared to the immunocompetent population. Immunosuppression is often stated as a risk factor for metastasis. However, evidence for this is scarce.Objectives To investigate the cSCC metastasis risk in OTR and the immunocompetent population by systematically reviewing the literature.Methods A systematic review of the literature was performed up to January 2018 using: Medline; Embase; Web of Science and ISI Science Citation Index. Studies assessing cSCC metastasis risk in ORT or immunocompetent cohorts were considered. A pooled risk estimate for metastasis was calculated for the immunocompetent population and OTR separately.Results The pooled metastasis risk estimate for OTR was, respectively, 7.3% (95% CI 6.2-8.4) for cSCC on total body, and 11.0% (95% CI 7.7-14.8) for cSCC of the head neck area. For the immunocompetent population reported risk estimate analysis showed a pooled metastatic risk of 3.1% (95% CI 2.8-3.4) in total body cSCC and of 8.5% (95% CI 7.3-9.8) in cSCC of the head and neck area. Pooled risk estimate per single cSCC in OTR was 1.3% (95% CI 1.0-1.7) in total body cSCC and 4.0% (95% CI 2.7-5.5) in cSCC of the head and neck area. In the immunocompetent population, these pooled risk estimates were, respectively, 2.4% (95% CI 2.1-2.6) and 6.7% (95% CI 5.7-7.8).Conclusions Organ transplant recipients show a higher overall risk of cSCC metastasis compared to the immunocompetent population. Metastasis risks per single cSCC were substantially lower in both groups. However, due to heterogeneity and differences between studies, comparisons are difficult. Comprehensive follow-up studies with defined cohorts are necessary to adequately asses the risk for cSCC metastasis. Show less
Background Prurigo is defined by the presence of chronic pruritus and multiple localized or generalized pruriginouslesions.Objective The aim of this study was to assess the psychological burden of... Show moreBackground Prurigo is defined by the presence of chronic pruritus and multiple localized or generalized pruriginouslesions.Objective The aim of this study was to assess the psychological burden of prurigo in patients of European countries.Methods In this multicentre European study, 3635 general dermatology outpatients and 1359 controls were included.Socio-demographic data and answers to questionnaires (regarding quality of life, general health, anxiety and depressionand suicidal ideation) were collected.Results There were 27 patients with prurigo; of these, 63% were men, and the mean age was 58.6 years. Amongpatients with prurigo, 10 of 27 (37%) suffered from anxiety and 8 of 27 (29%) from depression. Suicidal ideation wasreported in 5 of 27 (19%) patients, and for four of these five patients, suicidal ideation was related to their skin disease.These frequencies were higher in the 10 commonest dermatological diseases (including psoriasis, atopic dermatitis andleg ulcers). The impact on quality of life was severe, with a mean Dermatologic Life Quality Index (DLQI) of 12.4, with anextreme impact on quality of life for 23% of patients and a very large impact for 27% of patients.Conclusion The psychological comorbidities of prurigo are common, greater than those of other skin diseases, andtheir impact on quality of life is significant. Thus, it is important to study this condition and to find new treatments. Show less
Kester, M.S. van; Langeveld, T.J.C.; Bouwsma, H.; Rees, J.B. van; Holman, E.R.; Teng, Y.K.O.; Zuuren, E.J. van 2018
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... Show moreAccording 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. Show less
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... Show moreAcne 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. Show less
