Incidence and Prevalence of 73 Different Genodermatoses: A Nationwide Study in Sweden.

This retrospective registry-based cohort study aimed to estimate the incidence and prevalence of genodermatoses in the Swedish population and to analyse associated healthcare usage. Patients diagnosed with genodermatoses were identified from the patient registry of Sahlgrenska University Hospital (Gothenburg, Sweden) between 2016 and 2020. Clinical data from medical records were used to verify diagnoses recorded in the National Patient Registry (NPR). The NPR was then searched for International Classification of Diseases, Tenth Revision (ICD-10) codes Q80-82 and Q84 from 2001 to 2020. The local cohort included 298 patients with 36 unique genodermatosis diagnoses. Verification of these diagnoses in the NPR showed positive predictive values of over 90%. The NPR search yielded 13,318 patients with 73 unique diagnoses, including ichthyoses (n = 3,341; 25%), porokeratosis (n = 2,277; 17%), palmoplantar keratodermas (n = 1,754; 13%), the epidermolysis bullosa group (n = 1011; 7%); Darier disease (n = 770; 6%), Hailey-Hailey disease (n = 477; 4%) and Gorlin syndrome (n = 402; 3%). The incidence and prevalence of each diagnosis were calculated based on the nationwide cohort and are reported. A total of 149,538 outpatient visits were registered, a mean of 4.6 visits per patient. This study provides a valuable resource for the epidemiology of genodermatoses by reporting on the incidence and prevalence of 73 different genodermatoses.

Long-term prognosis of vaccine-induced contact allergy to aluminium: Third patch-test with additional test preparations.

BACKGROUND: A high incidence of local itching subcutaneous nodules and aluminium allergy was observed in clinical trials of a new aluminium adsorbed pertussis vaccine in Gothenburg, Sweden, in the 1990s. A total of 495 children with itching nodules were patch tested with aluminium chloride hexahydrate 2% and an empty Finn Chamber®, 377 (76%) with positive reactions. When 241 of them were re-tested some years later 186 (3 out of 4) had unexpectedly lost their patch test reactivity. AIM: To investigate the long-term prognosis of vaccine-induced contact allergy to aluminium by a third patch test about 20 years after Patch test I. METHODS: Twenty individuals with positive and 11 with negative results in Patch test II were tested a third time with the same sensitisers as in in the first two tests. Three additional aluminium preparations were also tested. RESULTS: A total 15 out of 20 persons with positive results in the second test had lost their patch test reactivity. Two of 11 with negative tests had turned positive again. The addition of the preparations gave no conclusive results. CONCLUSION: Contact allergy to aluminium caused by vaccination with aluminium-adsorbed vaccines in childhood seems to fade away with time as measured by loss of patch test reactivity.

Effects of brodalumab on psoriasis and depressive symptoms in patients with insufficient response to TNF-α inhibitors.

The objective of this study was to evaluate emotions of depression and anxiety in psoriatic patients that due to insufficient response to tumor necrosis factor-alpha inhibition (TNF-α), underwent a treatment switch from TNF-α to interleukin 17 inhibition using brodalumab. The Self-rated Montgomery-Asberg Depression Rating Scale and the Hospital Anxiety and Depression Scale were used to assess depression and anxiety. A total of 20 patients with psoriasis were enrolled in the study. They were monitored for a period of 3 months following the transition to brodalumab treatment. The results showed a significant improvement in both the Psoriasis Area and Severity Index as well as symptoms of depression; anxiety symptoms showed a reduction, though not statistically significant. Perhaps of more interest, the positive effects on depression and anxiety seem to be independent of the reduction in skin related psoriatic lesions. These findings highlight the importance of addressing depressive and anxiety symptoms, together with psoriasis severity and quality of life, when managing patients with psoriasis.

The Effect of Narrow-Band Ultraviolet B Phototherapy on Free and Total Vitamin D Serum Levels in Mild to Severe Plaque Psoriasis.

Vitamin D plays an important role in skin inflammation in psoriasis. The beneficial effects of ultraviolet light B (UVB) phototherapy in psoriasis are partly attributed to UVB-induced increase of vitamin D levels. In clinical practice, total 25-hydroxy vitamin D (25(OH)D) levels are measured to assess sufficiency, but it might be more accurate to measure free 25(OH)D levels. The aim of this study was to measure free serum 25(OH)D levels in psoriasis patients before and after phototherapy and to investigate if free 25(OH)D correlates stronger to disease severity than total 25(OH)D. Twenty adults (>18 years) with psoriasis were included for treatment with narrow-band UVB (NB-UVB) phototherapy for 10-12 weeks. Psoriasis Area and Severity Index (PASI) and Visual Analogue Scale (VAS) were used to assess disease severity. Serum levels of total 25(OH)D, free 25(OH)D, and 1,25(OH)2D were measured before and after NB-UVB. Total 25(OH)D, free 25(OH)D, 1,25(OH)2D and the percentage of free 25(OH)D increased after NB-UVB, and PASI and VAS improved. The increase in total and free 25(OH)D remained significant when stratifying for vitamin D confounders. No correlations between disease severity and vitamin D levels were found. Total and free 25(OH)D levels were positively correlated before and after NB-UVB. NB-UVB is an effective treatment for mild to severe plaque psoriasis and increases not only total but also free 25(OH)D levels, as well as the percentage of free 25(OH)D, suggesting an increased bioavailability of skin-produced vitamin D.

Use of methotrexate and risk of skin cancer: a nationwide case-control study.

BACKGROUND: Methotrexate (MTX) use has been suspected of increasing the risk of skin cancer. The aim of this investigation was to examine the association between the use of MTX and the risk of basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC) and cutaneous malignant melanoma (CMM). METHODS: In a nationwide Danish case-control study, we identified incident, histologically verified cases of BCC (n = 131,447), cSCC (n = 18,661) or CMM (26,068) from 2004 to 2018. We matched 10 controls to each case on sex and birth year using risk-set sampling and computed crude and adjusted odds ratios (ORs) using conditional logistic regression for the use of MTX (≥2.5 g) compared with never-use. RESULTS: Use of MTX was associated with increased risk of BCC, cSCC and CMM with adjusted ORs of (95% confidence interval) 1.29 (1.20-1.38), 1.61 (1.37-1.89) and 1.35 (1.13-1.61), respectively. For BCC and cSCC, ORs increased with higher cumulative doses. When restricting the study population to patients with psoriasis, the ORs were 1.43 (1.23-1.67), 1.18 (0.80-1.74) and 1.15 (0.77-1.72), respectively. CONCLUSIONS: We observed an increased risk of BCC and cSCC associated with the use of MTX with evidence of a dose-response pattern; however, the association was not consistent when restricting the study population to patients with psoriasis.

Basal cell carcinoma: Epidemiological impact of clinical versus histopathological diagnosis.

BACKGROUND: Low-risk basal cell carcinomas (BCCs) are to an increasing extent diagnosed by dermatologists through dermoscopic examination only and treated with non-surgical methods. Reports on increasing incidence as well as trends regarding subtypes, anatomical sites and differences related to gender are based solely on histopathologically verified tumours. How unreported clinically diagnosed BCCs affect the epidemiological data has not been sufficiently investigated. OBJECTIVES: To analyse the tumour and patient characteristics of clinically diagnosed versus histopathologically confirmed primary BCCs and to make a gross estimate on how unreported BCCs could influence the total number of new cases. METHODS: We retrospectively reviewed all primary BCCs diagnosed in 2016 at the Department of Dermatology, Sahlgrenska University Hospital in Gothenburg, Sweden. We also reviewed all histopathologically verified primary BCCs at the two largest pathology laboratories in Western Sweden during the same year to estimate the proportion of BCCs diagnosed by dermatologists. RESULTS: In total, 2365 primary BCCs were diagnosed at our centre. More than half of these tumours were clinically diagnosed (55.8%). Superficial subtype (41.7%), location on the trunk (46.3%) and destructive treatment methods (60.0%) were most common. The reports from the two pathology laboratories showed that histopathologically verified BCCs (n = 5837) were more commonly of the infiltrative or nodular subtype and located in the head and neck area. Dermatologists managed 56.0% of them. CONCLUSIONS: This study indicates that a substantial number of BCCs are not visualized in the official statistics which are solely based on reports from pathology laboratories. When taking clinically diagnosed tumours into account, truncal location and superficial subtype are more common than previously believed. Further, based on the regional calculations, the real burden of BCC in Sweden might be up to 70% higher than what is reported in official statistics.

Porokeratosis is one of the most common genodermatoses and is associated with an increased risk of keratinocyte cancer and melanoma.

BACKGROUND: Porokeratosis is a clinically heterogeneous group of keratinization disorders with a genetic background mainly affecting the mevalonate pathway, which is involved in the synthesis of cholesterol, an essential component for the formation of the extracellular lipid lamellae in the stratum corneum. Porokeratosis is reportedly associated with an increased risk of keratinocyte cancer, but to date, no large epidemiological studies have been conducted to further address this association. OBJECTIVES: The first objective was to characterize a cohort of patients diagnosed with porokeratosis at the Department of Dermatology and Venereology, Sahlgrenska University Hospital (SU), Gothenburg, Sweden. The second objective was to conduct a nationwide registry-based cohort study to investigate the association, if any, between porokeratosis and the cutaneous malignancies squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and melanoma. METHODS: For the SU cohort, the hospital registry was searched for patients with a diagnosis of porokeratosis recorded between 2016 and 2020. Clinical data were extracted from the records of the identified patients. For the nationwide cohort, national registries were searched to identify patients with a diagnosis of porokeratosis between 2001 and 2020. A tenfold control cohort was formed by Statistics Sweden. The data was cross-referenced with the Swedish Cancer Register to study the associations between porokeratosis and SCC, BCC and melanoma. RESULTS: Disseminated superficial actinic porokeratosis was the most common clinical type among the 108 patients in the SU cohort. In the nationwide search, 2277 patients with porokeratosis were identified (prevalence 1/4132). Porokeratosis was associated with an increased risk for SCC, BCC and melanoma with hazard ratios (95% CI) of 4.3 (3.4-5.4), 2.42 (1.97-2.98) and 1.83 (1.18-2.82), respectively, in the patient cohort, compared to the matched control group. CONCLUSION: Porokeratosis is a common genodermatosis, and it is associated with an enhanced risk of skin cancer.

Diagnostic Outcomes and Treatment Modalities in Patients with Mycosis Fungoides in West Sweden-A Retrospective Register-Based Study.

(1) Background: Mycosis fungoides (MF) is a variant of primary cutaneous T-cell lymphoma. The aim of this study was to describe the clinical features and epidemiological and diagnostic findings in addition to the treatment modalities and responses in patients with MF. Furthermore, comparisons between patients in the early stage and the advanced stage were evaluated. (2) Methods: A retrospective register-based study based on data collected from the primary cutaneous lymphoma register and medical records was performed at the Department of Dermatology and Venerology at Sahlgrenska University Hospital, Gothenburg, Sweden. (3) Results: Eighty-four patients with a median age of 55 years with MF were included. Most of the patients (n = 73) were diagnosed at the early stage of the disease (IA-IIA). Overall disease progression was seen in 12.5% (n = 9) of the patients. Nine (10.7%) patients were deceased, out of which four (4.8%) deaths were associated with MF-related causes. (4) Conclusions: This study contributes to the knowledge of the epidemiological and clinical features in addition to the diagnostic findings and treatment responses in patients with MF in Sweden.

Evaluation of Melanoma Thickness with Clinical Close-up and Dermoscopic Images Using a Convolutional Neural Network.

Convolutional neural networks (CNNs) have shown promise in discriminating between invasive and in situ melanomas. The aim of this study was to analyse how a CNN model, integrating both clinical close-up and dermoscopic images, performed compared with 6 independent dermatologists. The secondary aim was to address which clinical and dermoscopic features dermatologists found to be suggestive of invasive and in situ melanomas, respectively. A retrospective investigation was conducted including 1,578 cases of paired images of invasive (n = 728, 46.1%) and in situ melanomas (n = 850, 53.9%). All images were obtained from the Department of Dermatology and Venereology at Sahlgrenska University Hospital and were randomized to a training set (n = 1,078), a validation set (n = 200) and a test set (n = 300). The area under the receiver operating characteristics curve (AUC) among the dermatologists ranged from 0.75 (95% confidence interval 0.70-0.81) to 0.80 (95% confidence interval 0.75-0.85). The combined dermatologists' AUC was 0.80 (95% confidence interval 0.77-0.86), which was significantly higher than the CNN model (0.73, 95% confidence interval 0.67-0.78, p = 0.001). Three of the dermatologists significantly outperformed the CNN. Shiny white lines, atypical blue-white structures and polymorphous vessels displayed a moderate interobserver agreement, and these features also correlated with invasive melanoma. Prospective trials are needed to address the clinical usefulness of CNN models in this setting.

Ability to Predict Melanoma Within 5 Years Using Registry Data and a Convolutional Neural Network: A Proof of Concept Study.

Research relating to machine learning algorithms, including convolutional neural networks, has increased during the past 5 years. The aim of this pilot study was to investigate how accurately a convolutional neural network, trained on Swedish registry data, could perform in predicting cutaneous invasive and in situ melanoma (CMM) within 5 years. A cohort of 1,208,393 individuals was used. Registry data ranged from 4 July 2005 to 31 December 2011, predicting CMM between 1 January 2012 and 31 December 2016. A convolutional neural network with one-dimensional convolutions with respect to time was trained using healthcare databases and registers. The algorithm was trained on 23,886 individuals. Validation was performed on a holdout validation set including 6,000 individuals. After training and validation, the convolutional neural network was evaluated on a test set (1,000 individuals with an CMM occurring within 5 years and 5,000 without). The area under the receiver-operating characteristic curve was 0.59 (95% confidence interval (95% CI) 0.57-0.61). The point on the receiver-operating characteristic curve where sensitivity equalled specificity had a value of 56% (sensitivity 95% CI 53-60% and specificity 95% CI 55-58%). Albeit at an early stage, this pilot investigation demonstrates potential usefulness for machine learning algorithms in predicting melanoma risk.

Long-term clinical course and prognosis of vaccine-related persistent itching nodules (1997-2019): An observational study.

Background: Vaccines adsorbed to aluminium can induce long-lasting intensely itching subcutaneous nodules (granulomas) at the injection site as well as contact allergy to aluminium. In clinical trials of a new acellular pertussis vaccine performed in the 1990s (Gothenburg, Sweden) with 76 000 participants, itching nodules were reported in 745 children. A positive patch test to aluminium was verified in 77% of the tested children with itchy nodules. Aim: To describe the long-term clinical course and prognosis of vaccine-related itching nodules caused by aluminium-containing pediatric vaccines and to estimate the risk for new symptoms after future vaccination with aluminium-containing vaccines. Methods: 745 children with vaccine-related itching nodules were followed by regular interviews/questionnaires for more than 20 years. 723 of them received a booster dose of diphtheria/tetanus vaccine either with or without aluminium adjuvant during the follow-up time. Results: Most study participants (86%) reported a full recovery from their itching nodules after a median duration of 6.6 years. Only a few of the diphtheria/tetanus-booster-vaccinated children (3%) reported mild transient itching and swelling at the new injection site. Conclusion: Vaccine-induced itching granulomas caused by an aluminium-adsorbed acellular pertussis toxoid vaccine seem to disappear over time. Future vaccinations with aluminium-adsorbed vaccines can be performed with little risk for new itching nodules later in life.

Vitamin D-Binding Protein and the Free Hormone Hypothesis for Vitamin D in Bio-Naïve Patients with Psoriasis.

High levels of vitamin D-binding protein (DBP) have been reported in patients with psoriasis and the possibility of DBP as a marker of inflammation has been discussed. Furthermore, high DBP levels might negatively affect free 25(OH)D concentrations. According to the free hormone hypothesis, only the free fraction of a steroid hormone is capable of exerting biological action. Thus, free 25(OH)D level could be a better biomarker of vitamin D status than total 25(OH)D level. The objectives of this study were to identify the strongest determinants for DBP levels and to test the free hormone hypothesis for vitamin D in psoriasis. Additionally, we also aimed to investigate correlations between directly measured free 25(OH)D levels in serum and psoriasis disease severity compared to total 25(OH)D levels. This was a retrospective cross-sectional study including 40 bio-naïve patients with mild to severe plaque psoriasis. Psoriasis disease severity was evaluated using high sensitivity C-reactive protein (hsCRP), Psoriasis Area Severity Index (PASI) and visual analogue scale (VAS). Vitamin D metabolites including directly measured free 25(OH)D and serum DBP levels were measured. DBP levels were higher in patients with self-reported arthropathy than those without irrespective of confounding factors like sex, age and body weight. Total and free 25(OH)D levels correlated well (ρ = 0.77, p < 0.0001) and both were inversely correlated to intact parathyroid hormone (iPTH) (ρ = -0.33, p = 0.038 for total 25(OH)D and ρ = -0.40, p = 0.010 for free 25(OH)D). Only total 25(OH)D correlated to serum calcium levels (ρ = 0.32, p = 0.047). No correlations between any of the vitamin D metabolites and psoriasis disease severity were observed. In conclusion, DBP might be a new inflammatory biomarker in psoriasis, especially in psoriatic arthritis. Total 25(OH)D was a reliable measure for vitamin D status in this psoriasis cohort. However, evaluation of free 25(OH)D in patients with psoriatic disease and multiple co-morbidities and/or ongoing biologic treatment should be considered.

Sun protection behaviour in organ transplant recipients and non-transplant patients attending a dermatology outpatient clinic in Sweden: A questionnaire survey.

BACKGROUND/PURPOSE: Organ transplant recipients (OTRs) are at high risk of developing skin cancer and are therefore advised to protect their skin against ultraviolet radiation from the sun. Specialized OTR clinics with dermatological follow-up may improve sun habits among OTRs. In this study, we compared self-reported sun exposure and sun protection behaviour between OTRs and non-transplant patients (non-TPs) and between OTRs with and without special dermatological follow-up. METHODS: Patients from Sahlgrenska University Hospital, Gothenburg, Sweden, completed a sun exposure questionnaire. Between 2011 and 2015, 282 OTRs transplanted in the period 1976-2014 and 414 non-TPs were recruited among dermatological outpatients. Participants were stratified into five groups by their status as OTRs or non-TPs and by attendance to dermatological follow-up. RESULTS: More non-TPs than OTRs reported one or more sunburns in the past year, 46% vs. 20%, P < .0001). More OTRs with than OTRs without dermatological follow-up reported frequent use of sunscreens (63% vs 44%, P = .006). More OTRs with follow-up used one or more sun protection measure such as covering clothes, than other OTRs (54% vs 34%, P = .016). CONCLUSION: In this study, OTRs reported less sun exposure than non-TPs. Specialized dermatological follow-up seems to improve sun protection behaviour among OTRs. We suggest that specialized OTR clinics should be more broadly implemented.

Interobserver Agreement on Dermoscopic Features and their Associations with In Situ and Invasive Cutaneous Melanomas.

Several melanoma-specific dermoscopic features have been described, some of which have been reported as indicative of in situ or invasive melanomas. To assess the usefulness of these features to differentiate between these 2 categories, a retrospective, single-centre investigation was conducted. Dermoscopic images of melanomas were reviewed by 7 independent dermatologists. Fleiss' kappa (κ) was used to analyse interobserver agreement of predefined features. Logistic regression and odds ratios were used to assess whether specific features correlated with melanoma in situ or invasive melanoma. Overall, 182 melanomas (101 melanoma in situ and 81 invasive melanomas) were included. The interobserver agreement for melanoma-specific features ranged from slight to substantial. Atypical blue-white structures (κ=0.62, 95% confidence interval 0.59-0.65) and shiny white lines (κ=0.61, 95% confidence interval 0.58-0.64) had a substantial interobserver agreement. These 2 features were also indicative of invasive melanomas >1.0 mm in Breslow thickness. Furthermore, regression/peppering correlated with thin invasive melanomas. The overall agreement for classification of the lesions as invasive or melanoma in situ was moderate (κ=0.52, 95% confidence interval 0.49-0.56).

Impact of Etanercept on Vitamin D Status and Vitamin D-binding Protein in Bio-naïve Patients with Psoriasis.

High levels of serum vitamin D-binding protein have been shown previously in patients with psoriasis compared with healthy controls; a possible role in inflammation is implied. The primary objective of this study was to investigate the impact of 24-week etanercept treatment on vitamin D status and vitamin D-binding protein in patients with psoriasis. The secondary aim was to explore whether pre-treatment vitamin D levels could predict the treatment effect. A prospective observational study was performed, including 20 patients with psoriasis and 15 controls. Serum samples were analyzed for, among others, vitamin D metabolites, vitamin D-binding protein and highly sensitive C-reactive protein. Baseline levels of vitamin D-binding protein were higher in patients with self-reported arthropathy than in those without. After 24 weeks' treatment, an improvement in psoriasis was noted, as was a decrease in highly sensitive C-reactive protein. Vitamin D-binding protein decreased in those with self-reported arthropathy. Higher baseline levels of vitamin D were associated with faster and greater improvement in psoriasis. Vitamin D-binding protein may have an inflammatory biomarker role.

Discrimination Between Invasive and In Situ Melanomas Using Clinical Close-Up Images and a De Novo Convolutional Neural Network.

Background: Melanomas are often easy to recognize clinically but determining whether a melanoma is in situ (MIS) or invasive is often more challenging even with the aid of dermoscopy. Recently, convolutional neural networks (CNNs) have made significant and rapid advances within dermatology image analysis. The aims of this investigation were to create a de novo CNN for differentiating between MIS and invasive melanomas based on clinical close-up images and to compare its performance on a test set to seven dermatologists. Methods: A retrospective study including clinical images of MIS and invasive melanomas obtained from our department during a five-year time period (2016-2020) was conducted. Overall, 1,551 images [819 MIS (52.8%) and 732 invasive melanomas (47.2%)] were available. The images were randomized into three groups: training set (n = 1,051), validation set (n = 200), and test set (n = 300). A de novo CNN model with seven convolutional layers and a single dense layer was developed. Results: The area under the curve was 0.72 for the CNN (95% CI 0.66-0.78) and 0.81 for dermatologists (95% CI 0.76-0.86) (P < 0.001). The CNN correctly classified 208 out of 300 lesions (69.3%) whereas the corresponding number for dermatologists was 216 (72.0%). When comparing the CNN performance to each individual reader, three dermatologists significantly outperformed the CNN. Conclusions: For this classification problem, the CNN was outperformed by the dermatologist. However, since the algorithm was only trained and validated on 1,251 images, future refinement and development could make it useful for dermatologists in a real-world setting.