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Importance: Bullous pemphigoid is a difficult-to-treat autoimmune blistering skin disease that predominantly affects older adults and is associated with an increased mortality rate. Objective: To examine the safety and therapeutic potential of nomacopan, an inhibitor of leukotriene B4 and complement C5, in patients with bullous pemphigoid. Design, setting, and participants: This multicenter, single-group, phase 2a nonrandomized controlled trial was conducted in the dermatology departments of universities in the Netherlands and Germany. Participants were enrolled between September 2018 and April 2020. Older adult patients (aged ≥55 years) with mild to moderate, new-onset or relapsing bullous pemphigoid were recruited into the study. Interventions: Patients received nomacopan, 90 mg, subcutaneously on day 1 and 30 mg subcutaneously daily until day 42. Main outcomes and measures: The primary end point was the proportion of patients with grade 3 to 5 (severe) adverse events associated or possibly associated with nomacopan. Secondary end points included mean absolute and percentage changes in the Bullous Pemphigoid Disease Area Index (BPDAI) activity score, the BPDAI pruritus score, and the patient-reported outcome measures Dermatology Life Quality Index (DLQI) and Treatment of Autoimmune Bullous Disease Quality of Life (TABQOL). Results: A total of 9 patients (median [range] age, 75 [55-85] years) with bullous pemphigoid were included in the trial, of whom 5 were women (55.6%). No serious adverse events associated with nomacopan were found. The mean (90% CI) BPDAI activity score decreased from 32.0 (8.7) points on day 1 to 19.6 (9.0) points on day 42. Seven of 9 patients (77.8%) responded to nomacopan with a reduction in the BPDAI activity score of at least 8 points between days 1 and 42; in 3 responders, the reduction was 80% or greater. On day 42, the mean (90% CI) BPDAI pruritus score had decreased by 6.8 (4.6) points from 17.6 (4.0) points on day 1. The mean (90% CI) DLQI score decreased from 11.3 (4.2) points at baseline to 6.4 (3.8) points by day 42, and the mean (90% CI) TABQOL score decreased from 14.6 (5.4) points at baseline to 10.3 (5.0) points on day 42. Conclusions and relevance: Results of this nonrandomized controlled trial suggest that nomacopan can be well tolerated in older patients with bullous pemphigoid and may have therapeutic benefits for suppressing acute flares of this disease. A larger, placebo-controlled randomized clinical trial is warranted to confirm this safety profile and to establish nomacopan as a new therapeutic option for bullous pemphigoid. Trial registration: ClinicalTrials.gov Identifier: NCT04035733.

The demographic trend of an ageing society is mirrored in the rising number of hospitalized geriatric patients in Germany. However, there is still a wide gap of knowledge regarding the dermatological diseases, comorbidities and performed procedures within this growingly important group of patients. The study was conducted as a retrospective monocentric data analysis of all patients 65 years or older from the Department of Dermatology, Medical Center-University of Freiburg, Germany. In total, 10,009 individual hospitalizations were included from 2009 to 2017, and there was a notable increase of geriatric patients in the study period. This study illustrates the following: leading major diagnoses included malignant neoplasm of the head and neck, ulcerated and non-ulcerated inflammatory spectrum of chronic venous insufficiency, whereas angina pectoris, type 2 diabetes and cardiac diseases were noted most frequently as secondary diagnoses. Patients with venous diseases had considerably more often cardiopulmonary minor diagnoses, whereas endocrine diagnoses peaked in the cohort of patients with psoriasis and psychiatric and muscululoskeletal disorders in patients with bullous dieseases. Moh’s surgery, dressings and multimodal dermatological treatments were the most often encoded procedures.

Background: Poikilodermatous mycosis fungoides (pMF) is characterized by poikiloderma areas, typically involving the major flexural areas and trunk. Its presentation can be generalized or admixed with other forms of MF. Previous studies fail to correlate the clinical presentation with prognosis and laboratory findings. Some reports show pityriasis lichenoides chronica (PLC) preceding the poikiloderma. Objectives:Correlate prognostic, histopathological and molecular aspects of pMF with its clinical presentation. Methods: Retrospective analysis of 14 cases of generalized pMF (GpMF), 22 of localized pMF (LpMF) and 17 of pMF admixed with other forms of MF (mix-pMF). Results: Female predominance and lower age at diagnosis was found in all groups compared to classic MF, a high prevalence of PLC-like lesions in the GpMF group and a high rate of hypopigmented lesions in the mixpMF group. There were 2 deaths within the GpMF group. Histology was similar to previously reported findings, as was the prevalence of CD4 T-cell infiltrate, compared to CD8. The T-cell clonality positivity was lower in the GpMF group, compared to other groups (27% GpMF, 80% LpMF and 100% mixpMF). Discussion: This is the first article to categorize the different forms of pMF and correlate them with clinical and laboratory findings. The dermatological presentation differs among the groups. There was a high frequency of PLC-like lesions within the GpMF group and of hypopigmented lesions in mix-pMF. The histological and immunohistochemical findings were similar to those previously reported. Aggressive treatments are not recommended due to the good prognosis of all pMF forms. The low positivity of T-cell clonality in the GpMF group should be investigated.

In order to maintain skin in «good condition» one can use cosmetic products. Importantly, those skin care products should fulfil specific requirements for specific life phases and specific skin conditions. In this review, we focused on 2 different age groups - namely, infants and the elderly - as well as on 2 specific skin conditions occurring in both age groups - very dry skin (Xerosis) and hyperhydrated skin (diaper rash). The goal in both conditions should be to maintain skin surface in its physiological acidic state, which is in turn crucial for the permeability barrier function, stratum corneum integrity/cohesion and antimicrobial defense. Skin care products formulated with an effective buffer system at a more acidic pH, for example 4, may be the best option to improve the acid mantle and skin barrier function and thus keep the skin in «good condition».

Anti-interleukin-17 agents have recently been developed for the treatment of psoriasis. This study evaluated the tolerance and effectiveness of anti-interleukin-17 agents for psoriasis in elderly patients in daily practice. A multicentre, retrospective study was performed, involving psoriatic patients aged ≥65 years who had received an anti-interleukin-17 agent, including secukinumab, ixekizumab or brodalumab. A total of 114 patients were included: 72 received secukinumab, 35 ixekizumab, and 7 brodalumab. Treatment was stopped in 32 patients (28.9%), because of relapses in 14 patients (41.2%), primary failures in 11 patients (32.4%), or adverse events in 7 patients (20.6%). The 3 most frequently reported adverse events were injection site reactions (n = 4), oral candidiasis (n = 3), and influenza-like illness (n = 3). Regarding effectiveness, 80 patients (70%) reached a Physician Global Assessment score of 0/1, 6 months after treatment initiation. In conclusion, anti-interleukin-17 therapy appears to be an effective and safe therapeutic option for psoriasis treatment in patients aged ≥ 65 years.

Erosive pustular dermatosis of the scalp (EPDS) is an uncommon disease and primarily affects older men who have photodamaged bald scalp, as was confirmed by our case series. EPDS is probably an overlooked disease, whose diagnosis is often missed because of a higher incidence of other cutaneous diseases affecting the same area and usually secondary to chronic actinic damage, such as actinic keratosis, basal cell carcinoma, and squamous cell carcinoma. For the first time, we report a case series of misdiagnosed EPDS with the aim of understanding why a diagnosis of EPDS was initially missed and try to give some tips to avoid future diagnostic delay.

Background: Most of the data concerning the prevalence of actinic keratosis (AK) originate from the USA and Australia, and recently from Austria and Spain, but are based on populations in dermatology practices. Switzerland is the leading country with skin cancer incidence in Europe. AK prevalence among the Swiss population is therefore an important public health issue. Objective: To assess the prevalence of AK in the outpatient Swiss population in general practice. Methods: General practitioners captured AK diagnosis stage and localization in consecutive patients, who attended the physician for any reason. Results: A total of 2,844 consecutive patients (55.7% female) were enrolled in 59 general practitioners' offices. AK prevalence was 25.3% and increased steadily with age; 33% of men and 19% of women were diagnosed with AK. Every second AK patient declared leisure-related UV exposure, while only 23% were exposed to UV occupationally; 16% of the patients were UV exposed both occupationally and during leisure. AK distribution among sun-exposed body sites and extent of disease varied by sex. Conclusion: In Switzerland AK is a common diagnosis in dermatology practices. Since up to 5% of AK may progress to invasive squamous cell carcinoma (SCC), prevention of AK, as well as education of patients and general practitioners, may play a critical role for subsequent SCC development. This is the first study on AK prevalence in Switzerland identifying patients most affected by AK. These results will help to define future approaches to target general practitioners for education, screening, and specific intervention in patients with AK.

Aquagenic wrinkling of the palms (AWP) is a rare condition, which is characterized by appearance of whitish papules and plaques, and an excessive wrinkling and swelling of the palmar skin after exposure to water. In most cases, young women are affected, and an association of AWP with cystic fibrosis (CF) has been surmised. We report on two cases of AWP, which were not related to CF, in whom we used two innovative imaging techniques, namely high-definition optical coherence tomography and reflectance confocal microscopy, to show in vivo skin changes occurring after exposure of the skin to tap water in comparison to the findings in a healthy control person.

Background: Treatment of nail lichen planus (LP) is difficult and an optimal therapy is lacking. Objective: To report additional cases to the scant existing literature to learn more about therapeutic options for nail LP. Methods: A regimen of 30 mg alitretinoin daily in 2 cases of nail LP over a period of 9 and 8 months, respectively. Results: In either case, nail changes showed marked improvement under oral alitretinoin therapy within 2 and 4 months, respectively. In both patients, affected nails with end-stage destructive pterygium were resistant to any previously applied therapy. Conclusion: Alitretinoin is an effective treatment option for nail LP. We recommend early diagnosis of nail LP and early initiation of systemic therapy with alitretinoin to prevent the development of pterygium and permanent nail damage. However, further clinical studies are needed to establish reliable guidelines for nail LP therapy.

Background: We hypothesize that autoantibodies are induced after the blood-brain barrier is damaged by stroke and the risk of bullous pemphigoid (BP) is increased after stroke. We assess the risk of BP after first-ever stroke in a nationwide population-based cohort of first-ever stroke patients. Methods: We extracted data from the Longitudinal Health Insurance Database 2005 and identified patients with first-ever stroke as well as control patients matched for age, gender, and year of enrollment. The risk of BP in first-ever stroke patients in comparison with that in control patients was analyzed using Cox regression. Results: Of 12,607 patients with first-ever stroke, 38 (0.3%) patients developed BP in a median of 3.5 years. In the control patients, 8 persons (0.06%) had BP in a median of 3.7 years. The crude hazard ratio (HR) of BP in first-ever stroke patients was 4.83 (95% CI 2.25-10.34, p < 0.001) compared to the control group. The adjusted HR was 4.20 (95% CI 1.94-9.08, p < 0.001) after adjustments for age, gender, hypertension, diabetes, dementia, epilepsy, Parkinson disease, furosemide, and neuroleptics for stroke patients. Conclusions: The risk of BP is increased in first-ever stroke patients in a nationwide population-based cohort and this association is independent of well-known confounders of BP.

Background: Demodex mites are involved in different skin diseases and are commonly detected by skin scrape tests or superficial biopsies. A new high-definition optical coherence tomography (HD-OCT) with high lateral and axial resolution in a horizontal (en-face) and vertical (slice) imaging mode might offer the possibility of noninvasive and fast in vivo examination of demodex mites. Methods: Twenty patients with demodex-related skin diseases and 20 age- and gender-matched healthy controls were examined by HD-OCT. Mites per follicle and follicles per field of view were counted and compared to skin scrape tests. Results: HD-OCT images depicted mites in the en-face mode as bright round dots in groups of 3–5 mites per hair follicle. In the patients with demodex-related disease, a mean number of 3.4 mites per follicle were detected with a mean number of 2.9 infested follicles per area of view compared to a mean of 0.6 mites in 0.4 infested follicles in the controls. The skin scrape tests were negative in 21% of the patients. Conclusion: The innovative HD-OCT enables fast and noninvasive in vivo recognition of demodex mites and might become a useful tool in the diagnosis and treatment monitoring of demodex-related skin diseases.

Hintergrund: Die Entstehung freier Radikale in der menschlichen Haut infolge von ultravioletter Sonneneinstrahlung gilt als wichtigster extrinsischer Faktor der Hautalterung. Die Antioxidanzien im menschlichen Gewebe stellen ein effizientes Schutzsystem gegenuber der destruktiven Kraft der reaktionsfreudigen freien Radikale dar. In der vorliegenden Studie untersuchten wir verschiedene Parameter der Haut - die Dicke der Epidermis, den Feuchtigkeitsgehalt der Hornschicht, die Elastizitat und das Faltenvolumen - vor und nach der Behandlung mit antioxidanzienhaltigen Tabletten und Cremes bzw. Placebo. Methoden: In die Studie wurden 5 Gruppen zu je 15 Probanden aufgenommen, die 2 Monate lang mit antioxidanzienhaltigen Tabletten oder Cremes bzw. Placebo oder einer Kombination aus antioxidanzienhaltigen Tabletten und Cremes behandelt wurden. Die Hautparameter wurden zum Zeitpunkt 0 und in Woche 8 gemessen; hierbei wurde die Epidermisdicke mittels Ultraschall ermittelt, der Feuchtigkeitsgehalt der Hornschicht mit einem Corneometer, das Faltenvolumen mittels Hautprofilometrie und die Elastizitat mit einem Cutometer. Ergebnisse: Die Verum-Creme zeigte eine positive Wirkung auf Epidermisdicke, Elastizitat und Hautfeuchtigkeit, die Verum-Tabletten hingegen verbesserten lediglich die Epidermisdicke. Die Kombinationsbehandlung mit Verum-Tabletten und -Cremes fuhrte zur signifikanten Verbesserung aller untersuchten Hautparameter, wahrend die Placebo-Tabletten und -Cremes keinen der Parameter beeinflussten. Schlussfolgerung: Die topische und orale Supplementierung von Antioxidanzien kann ein Mittel zur Verbesserung verschiedener Hautparameter darstellen und insbesondere dem Prozess der extrinsischen Hautalterung potenziell entgegenwirken bzw. diesen verzogern.

Hintergrund: Bei aktinischen Keratosen (AK) wird oft von Herd zu Herd separat behandelt. In den letzten Jahren sind jedoch AK vermehrt als Flächenerkrankungen beschrieben worden, die nicht auf die einzelnen klinisch erkennbaren Läsionen begrenzt sind. Entsprechend sollte auch feldweise behandelt werden, um so möglicherweise das Risiko weiterer AK-Läsionen, Sekundärtumoren und lokaler Rezidivierung zu verringern. Ziel: Das Primärziel der Studie war die Ermittlung der Anzahl neuer Läsionen 9 Monate nach der Photodynamischen Therapie mit Methylaminolävulinat (MAL-PDT). Als Sekundärziele ermittelten wir die Anzahl neuer Läsionen 3 und 6 Monate nach der Therapie sowie die prozentuale Reduktion der AK gegenüber Studienbeginn 3, 6 und 9 Monate nach der MAL-PDT. Methoden: Es handelte sich um eine monozentrische, prospektive, randomisierte, für den Prüfer verblindete Pilotstudie im Seitenvergleich mit einer Studiendauer von einem Jahr. Die Studienpopulation bestand aus Patienten mit AK des Gesichts oder der Kopfschwarte, mit maximal 10 AK-Läsionen pro Seite. Eine Seite wurde mit einer Sitzung einzelläsionsorientierter MAL-PDT behandelt (LT-Seite) und die andere Seite mit einer Sitzung MAL-PDT-Feldtherapie (FT-Seite). Ergebnisse: Nach 9 Monaten waren unter FT signifikant weniger neue Läsionen zu verzeichnen. Zu allen Zeitpunkten der Nachbeobachtung lag eine signifikante Reduktion der Anzahl AK-Läsionen sowohl auf der LT- als auch auf der FT-Seite vor. Nach 3 und 6 Monaten stellten wir keine signifikanten Unterschiede zwischen den Seiten fest. Nach 9 Monaten waren jedoch unter LT signifikant weniger verbleibende AK-Läsionen zu verzeichnen, unter FT hingegen signifikant weniger neue Läsionen. Schlussfolgerungen: Die FT führt im Vergleich zur LT zu einer signifikanten Reduktion der Anzahl neu auftretender AK- Läsionen.

The development of safe and efficient gene transfer vectors is crucial for the success of gene therapy trials. A viral vector system promising to meet these requirements is based on the apathogenic adeno-associated virus (AAV-2), a member of the parvovirus family. The advantages of this vector system is the stability of the viral capsid, the low immunogenicity, the ability to transduce both dividing and non-dividing cells, the potential to integrate site specifically and to achieve long-term gene expression even in vivo, and its broad tropism allowing the efficient transduction of diverse organs including the skin. All this makes AAV-2 attractive and efficient for in vitro gene transfer and local injection in vivo. This review covers the progress made in AAV vector technology including the development of AAV vectors based on other serotypes, summarizes the results obtained by AAV targeting vectors and outlines potential applications in the field of cutaneous gene therapy.