Real-world effectiveness of abrocitinib treatment in patients with difficult-to-treat atopic dermatitis.

BACKGROUND: Abrocitinib is a JAK-1 selective inhibitor registered for the treatment of moderate-to-severe atopic dermatitis (AD). Although efficacy and safety have been shown in phase 3 clinical trials, data on real-world patients with a treatment history of advanced systemics are scarce. OBJECTIVES: The objective of the study was to evaluate the effectiveness and safety of abrocitinib treatment in patients with difficult-to-treat AD in daily practice. METHODS: In this prospective observational single-centre study, all AD patients who started abrocitinib treatment in the context of standard care between April 2021 and December 2022 were included. Effectiveness was assessed using clinician- and patient-reported outcome measures. Adverse events were evaluated. RESULTS: Forty-one patients were included. The majority (n = 30; 73.2%) had failed (ineffectiveness) on other targeted therapies, including JAK inhibitors (n = 14, 34%) and biologics (n = 16, 39%). Abrocitinib treatment resulted in a significant decrease in disease severity during a median follow-up period of 25 weeks (IQR 16-34). Median EASI score at baseline decreased from 14.7 (IQR 10.4-25.4) to 4.0 (IQR 1.6-11.4) at last review (p < 0.001). Median NRS itch decreased from 7.0 (IQR 5-8) to 3.0 (IQR 1-2) at last review (p < 0.001). The most frequently reported AEs included gastrointestinal symptoms (27.6%), acne (20.7%) and respiratory tract infections (17.2%). 16 (39%) patients discontinued abrocitinib treatment due to ineffectiveness, AEs or both (41.2%, 41.2% and 11.8%, respectively). CONCLUSION: Abrocitinib can be an effective treatment for patients with moderate-to-severe AD in daily practice, including non-responders to other targeted therapies.

Clinical findings are not helpful in detecting lentigo maligna melanoma in patients with biopsy-proven lentigo maligna.

BACKGROUND: Lentigo maligna (LM) based on biopsy material might be lentigo maligna melanoma (LMM) after excision. OBJECTIVES: Investigate whether clinical and dermoscopic mapping increases the detection rate of LMM when investigating staged excision specimens of biopsy proven LM. METHODS: Patients with biopsy-proven LM planned for staged excision were included. Using clinical inspection and dermoscopy, spots suspicious for LMM were marked. After the excision, needles were placed at the marked spots. Histological examination using vertical sections was done at the needles followed by the standard amount of vertical sections. RESULTS: In 28 of the 58 biopsy-proven LM, there was clinical suspicion of LMM, only 3 of these 28 cases were upgraded into LMM. These three cases showed LMM in other sections, whereas only 1 case showed LMM around the needle. Within the group without clinical suspicion of LMM, 2 cases were LMM. Biopsy-proven LM were in fact LMM in 8.6% of the cases and were found without the clinical guidance of the dermatologist. CONCLUSIONS: 8.6% of the biopsy-proven LM were LMM after complete histological examination. In this study, the dermatologist was not able to increase the detection rate of LMM by using clinical and dermoscopic mapping.

Prevalence of most common skin diseases in Europe: a population-based study.

BACKGROUND: The assessment of the prevalence of diseases is of primary importance in planning health policies. No complete data on the prevalence of skin diseases across European countries are available. OBJECTIVE: To estimate the prevalence of the most frequent skin conditions or diseases in 27 European countries (24 EU countries, plus Norway, Switzerland, and the United Kingdom). METHODS: We conducted a population-based study on representative and extrapolable samples of the general population aged 18 years or more in each of the 27 countries surveyed. Participants were selected using stratified, proportional sampling with a replacement design. Data were collected using a web-based online survey. All participants were asked to fill in a questionnaire with sociodemographic data and to declare if they have had one or more skin conditions or diseases during the previous 12 months. RESULTS: A total of 44 689 participants from 27 countries responded to the questionnaire, 21 887 (48.98%) men and 22 802 (51.02%) women. The proportion of participants who reported having suffered from at least one dermatological condition or disease during the previous 12 months was 43.35% (95% CI: 42.89%, 43.81%). The projection in the total population of the 27 countries included in the study resulted in 185 103 774 individuals affected by at least one dermatological condition or disease. Accordingly, we can estimate that more than 94 million Europeans complain of uncomfortable skin sensations like itch, burning, or dryness. The most frequent conditions were fungal skin infections (8.9%), acne (5.4%), and atopic dermatitis or eczema (5.5%). Alopecia, acne, eczema, and rosacea were more common in women, whereas men were more likely to suffer from psoriasis and sexually transmitted infections. CONCLUSION: Skin diseases are an important public health concern. Their high prevalence has to be taken into account in planning access to dermatological care to address patient needs.

The impact of the COVID-19 pandemic on keratinocyte carcinoma in the Netherlands: Trends in diagnoses and magnitude of diagnostic delays.

BACKGROUND: The COVID-19 pandemic impacted Dutch society and the healthcare system. Focus switched to care for COVID-19 patients, thereby altering care for non-COVID patients. Non-urgent medical visits were cancelled or postponed and patients were reluctant to visit healthcare services. OBJECTIVES: This study aimed to investigate the impact of the COVID-19 pandemic on trends in diagnoses of keratinocyte carcinoma (cutaneous squamous cell carcinoma (cSCC), basal cell carcinoma (BCC)) and to assess the magnitude of diagnostic delays. METHODS: The number of cSCC and BCC diagnoses in each month of 2020 was compared to the expected number of diagnoses for these months, using data from the Netherlands Cancer Registry. Expected diagnoses for 2020 were used as a reference to take the yearly increase in keratinocyte carcinoma incidence into account and were calculated by extrapolating the trends observed in 2017-2019. Comparisons were further stratified by age, sex and region. Estimates of diagnostic delays were calculated and corrected for the influence of excess mortality due to the pandemic on keratinocyte carcinoma incidence. RESULTS: The number of cSCC and BCC diagnoses substantially decreased when compared to the number of diagnoses expected from March to May 2020 (cSCC -29%, BCC -50%). These decreases were observed across all age groups, both sexes, and all regions. From June to September the number of cSCC and BCC diagnoses was higher than expected, after which it slightly dropped below expected in October to December. In total, 2020 keratinocyte carcinoma diagnoses continued to trail those expected, with a backlog of around 1150 cSCCs and 11 767 BCCs remaining at the end of the year. CONCLUSION: Diagnosis of keratinocyte carcinoma was suboptimal during the COVID-19 pandemic, due to diagnostic delays likely resulting from both patient and health system-related delay. Further studies will need to determine the effects of these diagnostic delays on outcomes.

Identifying the best predictive diagnostic criteria for psoriasis in children (< 18 years): a UK multicentre case-control diagnostic accuracy study (DIPSOC study).

BACKGROUND: In children, psoriasis can be challenging to diagnose. Difficulties arise from differences in the clinical presentation compared with adults. OBJECTIVES: To test the diagnostic accuracy of previously agreed consensus criteria and to develop a shortlist of the best predictive diagnostic criteria for childhood psoriasis. METHODS: A case-control diagnostic accuracy study in 12 UK dermatology departments (2017-2019) assessed 18 clinical criteria using blinded trained investigators. Children (< 18 years) with dermatologist-diagnosed psoriasis (cases, N = 170) or a different scaly inflammatory rash (controls, N = 160) were recruited. The best predictive criteria were identified using backward logistic regression, and internal validation was conducted using bootstrapping. RESULTS: The sensitivity of the consensus-agreed criteria and consensus scoring algorithm was 84·6%, the specificity was 65·1% and the area under the curve (AUC) was 0·75. The seven diagnostic criteria that performed best were: (i) scale and erythema in the scalp involving the hairline, (ii) scaly erythema inside the external auditory meatus, (iii) persistent well-demarcated erythematous rash anywhere on the body, (iv) persistent erythema in the umbilicus, (v) scaly erythematous plaques on the extensor surfaces of the elbows and/or knees, (vi) well-demarcated erythematous rash in the napkin area involving the crural fold and (vii) family history of psoriasis. The sensitivity of the best predictive model was 76·8%, with specificity 72·7% and AUC 0·84. The c-statistic optimism-adjusted shrinkage factor was 0·012. CONCLUSIONS: This study provides examination- and history-based data on the clinical features of psoriasis in children and proposes seven diagnostic criteria with good discriminatory ability in secondary-care patients. External validation is now needed.

A nationwide study of the incidence and trends of first and multiple basal cell carcinomas in the Netherlands and prediction of future incidence.

BACKGROUND: Basal cell carcinoma (BCC) is the most frequently diagnosed malignancy worldwide and an ever increasing annual incidence is observed. However, nationwide registries of BCCs are very rare, and often extrapolation of the data has been necessary to estimate the absolute number of diagnoses. As of September 2016, all histopathologically confirmed BCCs are registered in the Netherlands, due to developments in automatic notification and import in the Netherlands Cancer Registry. This offers the unique possibility to assess the nationwide population-based incidence of first and multiple BCCs. OBJECTIVES: To assess the nationwide incidence and trends of first and multiple BCCs in the Netherlands and to predict incidence rates up to 2029. METHODS: All patients with histopathologically confirmed BCC between 2001 and 2019 were selected from the population-based Netherlands Cancer Registry. Age-standardized incidence rates were calculated and trends were analysed with use of the estimated annual percentage change. Prediction of BCC incidence rates up to 2029 was based on a regression model. RESULTS: In total, 601 806 patients were diagnosed with a first BCC over the period 2001-2019. The age-standardized incidence rates for both men and women with a first BCC increased over these years, from 157 to 304 and from 124 to 274 per 100 000 person-years, respectively. For male and female patients aged 30-39 years, decreases in annual incidences of -3·6% and -3·0%, respectively, were found in recent years. For patients aged 50 years or older an ever increasing trend was found. One-quarter of the patients with a first primary BCC developed one or more subsequent BCCs within 3 years. Increases in incidence of 30·4% (male) and 25·3% (female) are expected in the next 10 years. CONCLUSIONS: BCC incidence has doubled over the past two decades. Trends have seemed to stabilize in recent years for patients aged < 50 years. This might be a first sign of a decreasing trend. The incidence continues to rise in patients aged 50 years and older. In the next decade a further increase in BCC incidence is expected.

Views on mobile health apps for skin cancer screening in the general population: an in-depth qualitative exploration of perceived barriers and facilitators.

BACKGROUND: Mobile health (mHealth) applications (apps) incorporating artificial intelligence for skin cancer screening are increasingly reimbursed by health insurers. However, an in-depth exploration of the general public's views towards these apps is lacking. OBJECTIVES: To explore the perceived barriers and facilitators towards mHealth apps for skin cancer screening among the Dutch general population. METHODS: A qualitative study consisting of four focus groups with 27 participants was conducted. A two-stage purposive sampling method was used to include information-rich participants from the Dutch general population with varying experience of mHealth. A topic guide was used to structure the sessions. All focus group meetings were transcribed verbatim and analysed in thematic content analysis by two researchers using several coding phases, resulting in an overview of themes and subthemes, categorized as (sub-)barriers and (sub)facilitators. RESULTS: Main barriers to using mHealth apps included a perceived lack of value, perception of untrustworthiness, preference for a doctor, privacy concerns, a complex user interface, and high costs. The main factors facilitating the use of mHealth among the general population were a high perceived value, a transparent and trustworthy identity of app developers, endorsement by healthcare providers and government regulating bodies, and ease and low costs of use. CONCLUSIONS: To increase successful adoption in skin cancer screening apps, developers should create a transparent identity and build trustworthy apps. Collaboration between app developers, general practitioners and dermatologists is advocated to improve mHealth integration with skin cancer care. Special attention should be given to the development of low-cost, privacy-friendly, easy-to-use apps.

Dupilumab treatment in patients with atopic dermatitis: a comparative cohort study between the Netherlands and Japan shows a discrepancy in patient-reported outcome measures.

BACKGROUND: Dupilumab was equally effective among all racial subgroups in clinical trials, but a direct comparison in daily practice is lacking. OBJECTIVES: To investigate the effectiveness of dupilumab in patients with atopic dermatitis (AD) in the Netherlands and Japan over 80 weeks of treatment. METHODS: A longitudinal comparative cohort study was conducted in patients with AD who were treated with dupilumab in daily practice. We used linear mixed-effects models to determine changes over time. RESULTS: We found statistically significant differences in sex, disease onset, body mass index and therapeutic history between Dutch (n = 208) and Japanese (n = 153) patients. The baseline Eczema Area and Severity Index (EASI) score was higher in Japanese patients (23·8 vs. 14·8), while baseline Patient-Reported Outcome Measures (PROMs) were higher in Dutch patients. EASI scores decreased quickly to a level indicating 'mild disease' (EASI < 7), and remained low in both countries. However, PROMs showed different trajectories with better scores in Japan. CONCLUSIONS: Dupilumab showed significant, comparable and sustained improvement of EASI scores in Japanese and Dutch patients. However, we found striking differences in the effect on PROMs between the countries, with a better outcome in Japanese patients.

Validation of a clinicopathological and gene expression profile model for sentinel lymph node metastasis in primary cutaneous melanoma.

BACKGROUND: The Clinicopathological and Gene Expression Profile (CP-GEP) model was developed to accurately identify patients with T1-T3 primary cutaneous melanoma at low risk for nodal metastasis. OBJECTIVES: To validate the CP-GEP model in an independent Dutch cohort of patients with melanoma. METHODS: Patients (aged ≥ 18 years) with primary cutaneous melanoma who underwent sentinel lymph node biopsy (SLNB) between 2007 and 2017 at the Erasmus Medical Centre Cancer Institute were eligible. The CP-GEP model combines clinicopathological features (age and Breslow thickness) with the expression of eight target genes involved in melanoma metastasis (ITGB3, PLAT, SERPINE2, GDF15, TGFBR1, LOXL4, CXCL8 and MLANA). Using the pathology result of SLNB as the gold standard, performance measures of the CP-GEP model were calculated, resulting in CP-GEP high risk or low risk for nodal metastasis. RESULTS: In total, 210 patients were included in the study. Most patients presented with T2 (n = 94, 45%) or T3 (n = 70, 33%) melanoma. Of all patients, 27% (n = 56) had a positive SLNB, with nodal metastasis in 0%, 30%, 54% and 16% of patients with T1, T2, T3 and T4 melanoma, respectively. Overall, the CP-GEP model had a negative predictive value (NPV) of 90·5% [95% confidence interval (CI) 77·9-96.2], with an NPV of 100% (95% CI 72·2-100) in T1, 89·3% (95% CI 72·8-96·3) in T2 and 75·0% (95% CI 30·1-95·4) in T3 melanomas. The CP-GEP indicated high risk in all T4 melanomas. CONCLUSIONS: The CP-GEP model is a noninvasive and validated tool that accurately identified patients with primary cutaneous melanoma at low risk for nodal metastasis. In this validation cohort, the CP-GEP model has shown the potential to reduce SLNB procedures in patients with melanoma.

Genetics of facial telangiectasia in the Rotterdam Study: a genome-wide association study and candidate gene approach.

BACKGROUND: The severity of facial telangiectasia or red veins is associated with many lifestyle factors. However, the genetic predisposition remains unclear. OBJECTIVES: We performed a genome-wide association study (GWAS) on facial telangiectasia in the Rotterdam Study (RS) and tested for replication in two independent cohorts. Additionally, a candidate gene approach with known pigmentation genes was performed. METHODS: Facial telangiectasia were extracted from standardized facial photographs (collected from 2010-2013) of 2842 northwestern European participants (median age 66.9, 56.8% female) from the RS. Our GWAS top hits (P-value <10-6 ) were tested for replication in 460 elderly women of the SALIA cohort and in 576 additional men and women of the RS. Associations of top single nucleotide polymorphisms (SNPs) with expression quantitative trait loci (eQTL) in various tissues were reviewed (GTEx database) alongside phenotype associations in the UK biobank database. SNP-based associations between known pigmentation genes and facial telangiectasia were tested. Conditional analysis on skin colour was additionally performed. RESULTS: Our most significant GWAS signal was rs4417318 (P-value 5.38*10-7 ), an intergenic SNP on chromosome 12 mapping to the SLC16A7 gene. Other suggestive SNPs tagged genes ZNF211, ZSCAN4, ICOS and KCNN3; SNP eQTLs and phenotype associations tagged links to the vascular system. However, the top signals did not pass significance in the two replication cohorts. The pigmentation genes KIAA0930, SLCA45A2 and MC1R, were significantly associated with telangiectasia in a candidate gene approach but not independently of skin colour. CONCLUSION: In this GWAS on telangiectasia in a northwestern European population, no genome-wide significant SNPs were found, although suggestive signals indicate genes involved in the vascular system might be involved in telangiectasia. Significantly associated pigmentation genes underline the link between skin colour and telangiectasia.

Principal component analysis of seven skin-ageing features identifies three main types of skin ageing.

BACKGROUND: The underlying phenotypic correlations between wrinkles, pigmented spots (PS), telangiectasia and other related facial-ageing subphenotypes are not well understood. OBJECTIVES: To analyse the underlying phenotypic correlation structure between seven features for facial ageing: global wrinkling, perceived age (PA), Griffiths photodamage grading, PS, telangiectasia, actinic keratosis (AK) and keratinocyte cancer (KC). METHODS: This was a cross-sectional study. Facial photographs and a full-body skin examination were used. We used principal component analysis (PCA) to derive principal components (PCs) of common variation between the features. We performed multivariable linear regressions between age, sex, body mass index, smoking and ultraviolet radiation exposure and the PC scores derived from PCA. We also tested the association between the main PC scores and 140 single-nucleotide polymorphisms (SNPs) previously associated with skin-ageing phenotypes. RESULTS: We analysed data from 1790 individuals with complete data on seven features of skin ageing. Three main PCs explained 73% of the total variance of the ageing phenotypes: a hypertrophic/wrinkling component (PC1: global wrinkling, PA and Griffiths grading), an atrophic/skin colour component (PC2: PS and telangiectasia) and a cancerous component (PC3: AK and KC). The associations between lifestyle and host factors differed per PC. The strength of SNP associations also differed per component with the most SNP associations found with the atrophic component [e.g. the IRF4 SNP (rs12203592); P-value = 1·84 × 10-22 ]. CONCLUSIONS: Using a hypothesis-free approach, we identified three major underlying phenotypes associated with extrinsic ageing. Associations between determinants for skin ageing differed in magnitude and direction per component. What's already known about this topic? Facial ageing is a complex phenotype consisting of different features including wrinkles, pigmented changes, telangiectasia and cancerous-related growths; it is not clear how these phenotypes are related to each other and to other phenotypes. A few studies have described two main clinical phenotypes for photoageing, namely hypertrophic ageing and atrophic ageing, which have been based solely on the clinical assessment of photoageing characteristics. What does this study add? We are the first to use epidemiology data to identify three main components associated with photoageing, namely a hypertrophic component (global wrinkling; perceived age; Griffiths grading) and atrophic component (pigmented spots; telangiectasia) and a cancer component (actinic keratosis; keratinocyte cancer). Association analysis showed different effects and direction of environmental determinants and genetic associations with the three components, with the most significant gene variants associations found for the atrophic component.

Accuracy of a smartphone application for triage of skin lesions based on machine learning algorithms.

BACKGROUND: Machine learning algorithms achieve expert-level accuracy in skin lesion classification based on clinical images. However, it is not yet shown whether these algorithms could have high accuracy when embedded in a smartphone app, where image quality is lower and there is high variability in image taking scenarios by users. In the past, these applications were criticized due to lack of accuracy. OBJECTIVE: In this study, we evaluate the accuracy of the newest version of a smartphone application (SA) for risk assessment of skin lesions. METHODS: This SA uses a machine learning algorithm to compute a risk rating. The algorithm is trained on 131 873 images taken by 31 449 users in multiple countries between January 2016 and August 2018 and rated for risk by dermatologists. To evaluate the sensitivity of the algorithm, we use 285 histopathologically validated skin cancer cases (including 138 malignant melanomas), from two previously published clinical studies (195 cases) and from the SA user database (90 cases). We calculate the specificity on a separate set from the SA user database containing 6000 clinically validated benign cases. RESULTS: The algorithm scored a 95.1% (95% CI, 91.9-97.3%) sensitivity in detecting (pre)malignant conditions (93% for malignant melanoma and 97% for keratinocyte carcinomas and precursors). This level of sensitivity was achieved with a 78.3% (95% CI, 77.2-79.3%) specificity. CONCLUSIONS: This SA provides a high sensitivity to detect skin cancer; however, there is still room for improvement in terms of specificity. Future studies are needed to assess the impact of this SA on the health systems and its users.

Effectiveness of dupilumab treatment in 95 patients with atopic dermatitis: daily practice data.

BACKGROUND: Dupilumab is the first biologic registered for the treatment of moderate-to-severe atopic dermatitis (AD), and efficacy was shown in phase III clinical trials (primary outcome at week 16 was reached in 38% of patients). Currently, there are limited daily practice data available for dupilumab, especially when it is combined with systemic immunosuppressants. OBJECTIVES: To evaluate dupilumab treatment in daily practice in patients with AD. METHODS: In this observational cohort study, we prospectively included all adult patients with AD who had been treated with dupilumab in two university hospitals in the Netherlands. Concomitant systemic immunosuppressive treatment was monitored. Physician-reported outcome measures and patient-reported outcome measures (PROMs) after ≥ 12 weeks of follow-up were analysed. We used a linear mixed-effects model to determine changes in scores during follow-up. RESULTS: Ninety-five patients were included. Of these, 62 patients were using systemic immunosuppressants at baseline; the use of systemic immunosuppressants was continued during dupilumab treatment in 43 patients. From baseline to 16 weeks of treatment, the estimated mean Eczema Area and Severity Index score (0-72) decreased from 18·6 [95% confidence interval (CI) 16·0-21·4)] to 7·3 (95% CI 5·4-10·0), and the estimated mean PROMs showed a decrease of 41-66%. Investigator's Global Assessment 0 or 1 (clear/almost clear) was reached in 38% of the patients. Five patients discontinued dupilumab treatment due to side-effects or ineffectiveness. Eye symptoms and orofacial (nonocular) herpes simplex virus (HSV) reactivation were reported in 62% and 8% of the patients, respectively. CONCLUSIONS: Dupilumab treatment in daily practice shows a clinically relevant improvement of physician-reported outcome measures and PROMs, which is in line with efficacy data from clinical trials. Besides frequently reported eye symptoms and orofacial (nonocular) HSV reactivation, there were no apparent safety concerns. What's already known about this topic? Dupilumab has been shown to be an efficacious treatment for atopic dermatitis in several clinical trials. However, it is known that there may be considerable differences in patient characteristics and treatment responses between clinical trials and daily practice. What does this study add? This study presents the first experience with dupilumab treatment in 95 patients with atopic dermatitis in daily practice in two Dutch university hospitals. Less stringent inclusion and exclusion criteria and follow-up schedules, in contrast to those used in clinical trials, might better represent daily practice. Dupilumab treatment shows a clinically relevant improvement of physician- and patient-reported outcome measures; besides patient-reported eye symptoms (in 59 of 95 patients; 62%) and an apparent increase in orofacial (nonocular) herpes simplex virus reactivation (eight of 95 patients; 8%), there were no other safety concerns during follow-up up to 16 weeks of dupilumab treatment.

Predicting keratinocyte carcinoma in patients with actinic keratosis: development and internal validation of a multivariable risk-prediction model.

BACKGROUND: Patients with actinic keratosis (AK) are at increased risk for developing keratinocyte carcinoma (KC) but predictive factors and their risk rates are unknown. OBJECTIVES: To develop and internally validate a prediction model to calculate the absolute risk of a first KC in patients with AK. METHODS: The risk-prediction model was based on the prospective population-based Rotterdam Study cohort. We hereto analysed the data of participants with at least one AK lesion at cohort baseline using a multivariable Cox proportional hazards model and included 13 a priori defined candidate predictor variables considering phenotypic, genetic and lifestyle risk factors. KCs were identified by linkage of the data with the Dutch Pathology Registry. RESULTS: Of the 1169 AK participants at baseline, 176 (15·1%) developed a KC after a median follow-up of 1·8 years. The final model with significant predictors was obtained after backward stepwise selection and comprised the presence of four to nine AKs [hazard ratio (HR) 1·68, 95% confidence interval (CI) 1·17-2·42], 10 or more AKs (HR 2·44, 95% CI 1·65-3·61), AK localization on the upper extremities (HR 0·75, 95% CI 0·52-1·08) or elsewhere except the head (HR 1·40, 95% CI 0·98-2·01) and coffee consumption (HR 0·92, 95% CI 0·84-1·01). Evaluation of the discriminative ability of the model showed a bootstrap validated concordance index (c-index) of 0·60. CONCLUSIONS: We showed that the risk of KC in patients with AK can be calculated with the use of four easily assessable predictor variables. Given the c-index, extension of the model with additional, currently unknown predictor variables is desirable. Linked Comment: Kim et al. Br J Dermatol 2020; 183:415-416.

Clinical and histopathological characterization of paradoxical head and neck erythema in patients with atopic dermatitis treated with dupilumab: a case series.

Dupilumab is the first biologic registered for the treatment of atopic dermatitis (AD). We report on seven patients with AD presenting with a paradoxical head and neck erythema that appeared 10-39 weeks after the start of dupilumab treatment. The patients presented with a relatively sharply demarcated, patchy erythema in the head and neck area that showed no or less scaling compared with their usual eczema. Only one patient experienced symptoms of itch and burning, although this was notably different from his pre-existent facial AD. Except for a notable 'red face', eczema on other body parts had greatly improved in six of the seven patients, with a mean numerical rating scale for treatment satisfaction of 9 out of 10 at the time of biopsy. Treatment of the erythema with topical and systemic drugs was unsuccessful. Despite the presence of this erythema, none of our patients discontinued dupilumab treatment. Lesional skin biopsies showed an increased number of ectatic capillaries, and a perivascular lymphohistiocytic infiltration in all patients. In addition, epidermal hyperplasia with elongation of the rete ridges was observed in four patients, resembling a psoriasiform dermatitis. Additional immunohistochemical stainings revealed increased numbers of plasma cells, histiocytes and T lymphocytes. Interestingly, spongiosis was largely absent in all biopsies. We report on patients with AD treated with dupilumab developing a paradoxical erythema in a head and neck distribution. Both clinically and histopathologically we found a heterogeneous response, which was most suggestive of a drug-induced skin reaction.