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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.

The clinical triad of pyoderma gangrenosum, acne conglobata and hidradenitis suppurativa has been named PASH syndrome. Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism and inflammation. Hidradenitis suppurativa, like acne vulgaris, may be a feature of hyperandrogenism. Obesity may be associated with both hidradenitis suppurativa and PCOS. We describe a possible association between PASH syndrome and PCOS.

Zysten der Haut sind Tumoren oder tumorahnliche Veranderungen, die klinisch oder histologisch einen oder mehrere Hohlraume aufweisen. Echte Zysten sind von einer epithelialen Zystenwand umgeben, Pseudozysten von komprimiertem Bindegewebe oder Granulationsgewebe. Der Zysteninhalt ist von variabler Viskositat und Konsistenz, welche von kalzifiziertem Horn uber semisolides bis hin zu flussigem Material reicht. Entwicklungsbedingte Zysten sind klinisch relativ scharf umschrieben, weisen aber haufig Verbindungen zu tiefer liegenden Strukturen auf. Zystische Tumoren beinhalten ebenfalls zystische Hohlraume, entstehen jedoch primar als solide Tumoren, wie beispielsweise zystische Basalzellkarzinome oder Hidrozystome. In diesem Kapitel werden die wesentlichen Zystentypen vorgestellt.

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.

BackgroundAnhidrotic ectodermal dysplasia (AED) is an inherited syndrome, which originates mainly from genetic alteration of the ectodysplasin A (EDA) gene. It regularly affects the adnexa of the skin which results in a characteristic phenotype of the patients including hypo- or anhidrosis leading to severe disturbances in the regulation of body temperature. ObjectivesTo prevent the development of the symptoms in early childhood promising therapeutic approaches are currently under clinical investigation. In this context, timely diagnosis of this genetic syndrome is crucial. The purpose of our study was the investigation of modern non-invasive imaging methods such as optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) in the immediate diagnosis of AED. MethodsWe examined a 3-year-old boy with the suspicion for an AED syndrome and his family members with RCM and OCT to document presence and characteristic features of sweat glands in comparison to non-affected individuals. ResultsThe patient and the affected brother showed significantly reduced sweat glands in the imaging compared to the controls. The genetic analysis revealed a mutation of the EDA gene for hemizygosity previously associated with AED and the mother was revealed as the conductor of the genetic alteration. ConclusionsWith the help of non-invasive imaging, we were able to detect sweat gland dysplasia in the affected family members without performing a biopsy which led us to the diagnosis of an AED. The application of modern dermatological imaging techniques might serve as valuable supplementary tools in the immediate, non-invasive diagnosis of genetic syndromes especially in newborns when early therapeutic approaches are planned.

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.

Entzundliche Knorpelveranderungen sieht der Dermatologe relativ selten. Oft geht ihnen ein Trauma voraus, wie beim Ringerohr oder weniger offensichtlich bei Chondrodermatitis nodularis chronica helicis. Die Ohren sind auserst empfindlich gegenuber Kaltereizen. Gelegentlich kann eine kutane Vaskulitis, insbesondere arzneimittelinduziert, am Ohr ablaufen. Aufgrund der geringen Durchblutung des Knorpels sind Schadigungen schwer behandelbar und neigen zu chronischem Ablauf.

Background The group of autoinflammatory syndromes associated with Pyoderma gangrenosum, Acne, and Suppurative Hidradenitis are poorly defined and difficult to control with currently available treatment modalities. Objectives We describe a patient with PASH syndrome and report about the successful multimodal treatment with infliximab, cyclosporine, and dapsone. Methods A review of the available literature to date about this group of autoinflammatory diseases was performed. We performed genetic analysis for PSTPIP1 mutations associated with PAPA syndrome. Results A 22-year-old woman presented to our department with pyoderma gangrenosum, concomitant acne, and suppurative hidradenitis. She had previously been treated unsuccessfully with etanercept, adalimumab, fumaric acid and the IL-1 receptor antagonist (IL-1RA) anakinra without prolonged remission. Treatment with intravenous infliximab in combination with cyclosporine and dapsone lead to sudden and prolonged improvement of the clinical symptoms that we classified as PASH syndrome. We review the literature about this group of diseases and report the third case of PASH syndrome to date. Conclusion PASH syndrome and associated diseases should be considered whenever hidradenitis suppurativa is found in association with pyoderma gangrenosum. We provide a systematic overview about PASH syndrome and suggest a novel multimodal therapeutic regimen beyond isolated inhibition of TNF or IL-1.

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.

Punctate palmoplantar keratoderma (PPKP1; Buschke-Fischer-Brauer) is a rare autosomal dominant inherited skin disease characterized by multiple hyperkeratotic papules involving the palms and soles. Mutations have been found at 2 loci, on chromosomes 15q22-15q24 and 8q24.13-8q24.21. We recently identified mutations in 3 families, in the AAGAB gene on 15q, which encodes the alpha- and gamma-adaptin-binding protein p34. The current study examined 14 additional families, comprising a total of 26 affected individuals and identified 8 novel mutations in 9 families. In one family a mutation representing a known SNP that was present only in the affected individuals was found, and in 4 other families, previously reported mutations were found (1, 2). These results confirm the role of AAGAB in PPKP1. Our findings suggest that there is no correlation with age, but with mechanical factors. No additional obvious genotype phenotype correlation was observed, even when comparing different types of mutations. Rather, identical genotypes presented a very broad interfamilial and intrafamilial variability of phenotypes.

Summary Background Optical coherence tomography (OCT) allows real-time, in vivo examination of nonmelanoma skin cancer. An innovative high-definition (HD)-OCT with a horizontal (en-face) and vertical (slice) imaging mode offers additional information in the diagnosis of actinic keratosis (AK) and may potentially replace invasive diagnostic biopsies. Objectives To define the characteristic morphological features of AK by using HD-OCT in the two imaging modes compared with histopathology as gold standard. Methods In total, 20 AKs were examined by HD-OCT in the en-face and slice imaging modes and characteristic features were described and evaluated in comparison with the histopathological findings. Furthermore, the HD-OCT images of a subgroup of AKs were compared with those of the clinically normal adjacent skin. Results The preoperative in vivo diagnostics showed the following features in the en-face imaging mode of HD-OCT: disruption of stratum corneum, architectural disarray, cellular/nuclear polymorphism in the stratum granulosum/stratum spinosum, and bright irregular bundles in the superficial dermis. In the vertical slice imaging mode the following characteristics were found: irregular entrance signal, destruction of layering, white streaks and dots, and grey areas. In contrast, the clinically healthy adjacent skin showed mainly a regular epidermal ‘honeycomb’ pattern in the en-face mode and distinct layering of the skin in the slice mode. Conclusions HD-OCT with both the en-face and slice imaging modes offers additional information in the diagnosis of AK compared with conventional OCT and might enhance the possibility of the noninvasive diagnosis of AK prior to treatment procedures and possibly in the monitoring of noninvasive treatment strategies.

Background Optical coherence tomography (OCT) allows real-time, in vivo examination of basal cell carcinoma (BCC). A new high definition OCT with high lateral and axial resolution in a horizontal (en-face) and vertical (slice) imaging mode offers additional information in the diagnosis of BCC and may potentially replace invasive diagnostic biopsies. Objectives To define the characteristic morphologic features of BCC by using high definition optical coherence tomography (HD-OCT) compared to conventional histology. Methods A total of 22 BCCs were examined preoperatively by HD-OCT in the en-face and slice imaging mode and characteristic features were evaluated in comparison to the histopathological findings. Results The following features were found in the en-face mode of HD-OCT: lobulated nodules (20 ⁄ 22), peripheral rimming (17 ⁄ 22), epidermal disarray (21 ⁄ 22), dilated vessels (11 ⁄ 22) and variably refractile stroma (19 ⁄ 22). In the slice imaging mode the following characteristics were found: grey ⁄ dark oval structures (18 ⁄ 22), peripheral rimming (13 ⁄ 22), destruction of layering (22 ⁄ 22), dilated vessels (7 ⁄ 22) and peritumoural bright stroma (11 ⁄ 22). In the en-face mode the lobulated structure of the BCC was more distinct than in the slice mode compared to histology. Conclusion HD-OCT with a horizontal and vertical imaging mode offers additional information in the diagnosis of BCC compared to conventional OCT imaging and enhances the feasibility of non-invasive diagnostics of BCC.

Molekulargenetische Methoden ermoglichten in den letzten Jahrzehnten eine immense Zunahme unseres Wissens uber biologische Vorgange in gesunden Individuen und verbesserten unser Verstandnis uber pathophysiologische Prozesse bei zahlreichen dermatologischen Krankheiten. Diese Methoden wurden initial im Rahmen der molekularbiologischen bzw. genetischen Grundlagenforschung entwickelt und erfahren zunehmend eine translative Anwendung als anspruchsvolles zusatzliches Diagnostikum. Hierzu zahlen Immunhistochemie, Polymerasekettenreaktion (PCR), Fluoreszenz-in-situ-Hybridisierung (FISH), Chromogen-in-situ-Hybridisierung (CISH), komparative genomische Hybridisierung (CGH) und Mikroarray-Technologie. Die Immunhistochemie und PCR-Analyse sind bereits zu einem Grad standardisierbar, dass sie fur die Routinediagnostik zahlreicher dermatologischer Krankheiten eingesetzt werden konnen. Andere wie FISH und CISH erfahren derzeit eine Etablierung fur spezielle Indikationen bei einigen Groslaboratorien, wohingegen CGH und Mikroarrays noch einzelnen wenigen Labors vorbehalten sind, die sich mit sehr speziellen Fragestellungen auseinandersetzen. Diese modernen Methoden haben das Potenzial, als Erganzung zur traditionellen Diagnostik gerade in solchen Fallen wichtige Informationen zu liefern, in denen die konventionelle histomorphologische Beurteilung an ihre Grenzen stost. Daruber hinaus bieten sie die Moglichkeit, Aussagen uber Prognose, Verlauf und Therapieoptionen zu machen.

Background The clinical diagnosis of amelanotic melanoma is often challenging, because the classical clinical and dermoscopic features of pigmented melanoma are usually missing. The reflectance confocal microscopy (RCM) offers an additional possibility of an in vivo diagnosis of both pigmented and amelanotic melanoma lesions. Objectives To test the value of RCM in vivo in the preoperative prediction of melanoma lesions lacking significant pigment and to compare the results with the evaluation by dermoscopy and histopathology. Methods We examined seven patients with the clinically uncertain differential diagnosis of partially or completely amelanotic melanoma by RCM and dermoscopy prior to surgical excision of the lesions according to the previously suggested dermoscopy algorithm and RCM score for melanoma. The following RCM features were evaluated: major criteria scored +2 (non-edged papillae, cytological atypia at the dermo-epidermal junction) and minor criteria +1 (roundish pagetoid cells, widespread pagetoid infiltration, nucleated cells within dermal papillae, cerebriform cell clusters). The dermoscopic evaluation included the following criteria: polymorphous vessels, dotted and linear irregular vessels, hairpin vessels, pink-erythematous colour, milky red areas, irregularly shaped depigmentation, blue-grey dots and subtle pigmentation. Results The preoperative in vivo RCM analysis revealed common features of melanoma also found in pigmented melanoma lesions. All lesions showed a score above three in the applied RCM algorithm which was proposed earlier as the threshold for malignancy. In dermoscopy, five of seven lesions showed characteristic vascular changes. Conclusion In vivo RCM is a valuable tool in the preoperative diagnosis of partially and completely amelanotic tumours suspicious for melanoma in addition to dermoscopic evaluation.

Punctate palmoplantar keratodermas (PPKPs) are rare autosomal-dominant inherited skin diseases that are characterized by multiple hyperkeratotic plaques distributed on the palms and soles. To date, two different loci in chromosomal regions 15q22-15q24 and 8q24.13-8q24.21 have been reported. Pathogenic mutations, however, have yet to be identified. In order to elucidate the genetic cause of PPKP type Buschke-Fischer-Brauer (PPKP1), we performed exome sequencing in five affected individuals from three families, and we identified in chromosomal region 15q22.33-q23 two heterozygous nonsense mutations-c.370C>T (p.Arg124(star)) and c.481C>T (p.Arg161(star))-in AAGAB in all affected individuals. Using immunoblot analysis, we showed that both mutations result in premature termination of translation and truncated protein products. Analyses of mRNA of affected individuals revealed that the disease allele is either not detectable or only detectable at low levels. To assess the consequences of the mutations in skin, we performed immunofluorescence analyses. Notably, the amount of granular staining in the keratinocytes of affected individuals was lower in the cytoplasm but higher around the nucleus than it was in the keratinocytes of control individuals. AAGAB encodes the alpha-and gamma-adaptin-binding protein p34 and might play a role in membrane traffic as a chaperone. The identification of mutations, along with the results from additional studies, defines the genetic basis of PPKP1 and provides evidence that AAGAB plays an important role in skin integrity.

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.

Galli-Galli disease, a rare genodermatosis belonging to the spectrum of reticulate pigment dermatoses, is classified as an acantholytic variant of Dowling-Degos disease on the basis of its characteristic clinical and histological findings. In the context of this case series, Galli-Galli disease is characterized in detail based on the clinical and histopathological evaluation of 18 patients. The disease pattern is discussed in view of the current literature. In addition, a classification into two clinical subtypes is made and a genotype/phenotype correlation with mutations in the keratin 5 (KRT5) gene is established.

Cutaneous metastases of internal malignancies still seem to occur infrequently, although medical publications report an incidence rate of up to 10.4%. Common sense, however, fosters suspicion that we might underdiagnose the problem distracted by harder striking facets of an advanced disease. With contemporary knowledge, morphology and behavior of cutaneous metastases resemble each other regardless of the site of origin. This article itemizes clinical presentations according to organ systems, specific features, and differential diagnoses. In general, the survival turned out to be less than 12 months. But incremental awareness of cutaneous metastases proclaims this paradigm insufficient. Although excision is the local treatment of choice, investigations attempt to propose tumor-specific chemotherapeutic/immunological approaches. This paper endeavors to critically review the state of the art concerning the clinic, prognosis, and therapeutic concepts.

Pigmentation in human skin differs individually and is regulated by more than 100 genes. The discovery of an increasing number of these genes has shed light on the molecular basis and pathogenesis of genetic pigmentary disorders. They are very rare and can be caused by changes in melanocyte number or melanin synthesis as well as development, transport and transfer of melanosomes. Pigmentary disorders can be divided into hyper- and hypopigmentation, of which the distribution can be diffuse or localized. Localized hypopigmentation can be found in piebaldism, Waardenburg syndrome and Tietz syndrome, whereas diffuse forms are typical for oculocutaneous albinism, Hermansky-Pudlak syndrome, Chediak-Higashi syndrome and Griscelli syndrome. Hyperpigmentation can be divided into diffuse, reticular or localized forms. They must be distinguished from endocrinopathies which may show hyperpigmentation, and from poikilodermatous syndromes displaying internal involvement.

Summary Background Galli–Galli disease (GGD) is a rare genodermatosis. Its clinical presentation is identical to that of Dowling–Degos disease (DDD), but the presence of the histopathological feature of acantholysis in GGD is thought to distinguish the two disorders. Mutations in the keratin 5 gene (KRT5) have been identified in the majority of patients with DDD and in a small number of patients with GGD. Objectives To provide further support for the hypothesis that GGD is merely a variant of DDD, and to examine whether acantholysis is genuinely rare in DDD or rather a common but under-reported histological feature of DDD. Methods We conducted the first systematic mutational investigation of patients with GGD and re-examined the histopathology of patients previously assigned a diagnosis of DDD. For the mutational investigation, KRT5 was sequenced in seven unrelated patients with clinically and histopathologically confirmed GGD. In addition, the histopathological findings of six patients with DDD were re-evaluated. Results The mutation c.418dupA was found in five patients with GGD. The typical histopathological features of GGD were identified in six patients who had previously been assigned a diagnosis of DDD. Conclusions We found further evidence to suggest that GGD is indeed a variant of DDD and not a distinct disease entity. Two facts in particular support this conclusion: the same KRT5 mutation was found in patients with GGD and in patients with DDD, and acantholysis seems to be present in a large number of patients who had previously been assigned a diagnosis of DDD.

Hereditary palmoplantar keratodermas (PPK) comprise a clinically and genetically heterogeneous group of genodermatoses, which share impaired epidermal differentiation resulting in prominent palmoplantar hyperkeratosis. Classically, keratodermas have been separated according to their clinical appearance into diffuse, focal, and as a feature of ectodermal dysplasias and many other syndromes. Since molecular genetic analyses have helped characterize the underlying genetic defects in an increasing number of hereditary PPK over the last two decades, a pathophysiological separation seems more reasonable. Today PPK can be classified based on defects in keratins, loricrin, desmosomes, connexins, and cathepsins. Although these proteins have different structures and functions, all of them influence epidermal differentiation and cornified envelope assembly. Depending on tissue distribution and location of mutation with a certain gene, the clinical spectrum of PPK range from a pure palmoplantar restricted skin abnormality to a complex combination of symptoms with dental anomalies, deafness, progressive cardiomyopathy and even cancer. Solely for those reasons, a correct diagnosis based on molecular genetic analyses is mandatory, although a causal therapy is still not available. Instead, several therapeutic modalities including topical ointments, surgical interventions and systemic retinoids help to reduce the patients' symptoms.

Background Acute meningoencephalitis (ME) from varicella zoster virus (VZV) reactivation is a rare and serious complication of herpes zoster (HZ). Objectives and methods As early diagnostic detection is mandatory to prevent long-term sequelae, any clinical indication is helpful to identify patients that are at higher risk of the development of VZV-ME. In order to find such risk factors, the clinical data of 38 patients consecutively hospitalized for the treatment of HZ over a 1-year period were analyzed. Results Four of the 38 patients with HZ developed ME. Of these, three had involvement of the trigeminal nerve branch, one including an ophthalmic affection, and one presented with disseminated HZ. All were women with an average age of 83.5 years, in comparison with patients with HZ but without ME who had an average age of 69.3 years and a female preponderance of 60%. The first clinical signs of ME were rapidly progressing somnolence and meningism. Patients with HZ-ME were treated with intravenous acyclovir, oral glucocorticosteroids, and antiseizure therapy, and recovered almost completely without major residual symptoms. Conclusion Progression of HZ to ME seems to occur more often than normally believed. Female patients above 80 years of age with either ophthalmic involvement or disseminated HZ are at a potentially high risk of the development of ME. The general recommendation of starting oral glucocorticosteroids from day 1 of antiviral treatment in older patients must be questioned, as it may stimulate VZV replication and dissemination.

Summary Background: Granular parakeratosis describes chronic skin lesions within the intertriginous areas that demonstrate microscopically parakeratosis together with retention of keratohyalin granules within a thickened stratum corneum. Granular parakeratosis is rarely diagnosed, since it is still relatively unknown within the differential diagnoses of intertriginous eruptions, and a skin biopsy is required for diagnosis. In order to gain insight into the clinical-histopathologic correlation, we present 10 cases of granular parakeratosis. Methods: The files of the DermatoHistologisches Labor Dr. H. Laaff, Freiburg, were searched for the diagnosis of granular parakeratosis. Identified cases were evaluated for clinical information and histopathologic characteristics. Result: From 2004 to 2007 10 cases (7 women, 3 men) of granular parakeratosis were found corresponding to a frequency of 0.004%. The average age was 62 (33–82). In women lesions occurred in submammary region (4), axillae (2) and popliteal fossa; in men, groin (2) and genital region. Clinically two different patterns are recognized – lichen planus-like red-brown slightly hyperkeratotic or scaly papules, and larger plaques which are either bright red shiny or grey-brown with lichenification. Histologically the typical granular parakeratosis was seen in a prominently thickened stratum corneum. It remains unclear whether granular parakeratosis is a disease entity or whether it reflects a reaction pattern to unknown stimuli.

A high prevalence of all types of chromosomal abnormalities has been found in male (4.29%) and female (5.88%) partners of infertile couples undergoing intracytoplasmic sperm injection (ICSI) (Morel et al, 2004). Aside from sex chromosome abnormalities (male, 1.82%; female, 4.44%), balanced reciprocal translocations are the most frequently found chromosomal abnormalities (male, 0.98%; female, 0.66%). In ICSI men, the probability of finding a balanced reciprocal translocation has been calculated to be 11.5-times higher than among newborns based on data on 7895 males referred for ICSI and 36 855 newborn males (Morel et al, 2004). Reciprocal translocation is defined as the exchange of chromosomal material between the arms of two heterologous chromosomes, thus changing the order, but usually not the amount of genetic material. Although all chromosomes can be involved in reciprocal translocations, chromosomes 12, 22, and Y are involved more often than expected on the basis of their relative lengths. A balanced reciprocal Y;autosome translocation has been demonstrated between almost every autosome, except chromosome 20 (Hsu, 1994), and even the participation of chromosome 1 seems to be relatively rare in infertile men. To our knowledge, only 10 cases of Y;1 translocation have been published previously (AlAwadi et al, 1985; Moreau et al, 1987; Narahara et al, 1987; Gregori-Romero et al, 1990; Teyssier et al, 1993; Maraschio et al, 1994; Morel et al, 2002, Pabst et al, 2002; Pinho et al, 2005). We present a new variant of a balanced reciprocal (Y;1) translocation associated with azoospermia and we review the literature on this subject.

Viral vectors based on recombinant adeno-associated virus (rAAV) have gained increasing interest over the last 20 years as a promising and safe gene-delivery vehicle for gene therapy. rAAV vectors posess many favorable characteristics, including an excellent safety profile, no pathogenicity, a wide host range comprising proliferating and nondividing cell types, the ability to deliver genes in vivo and in vitro, the competence to establish long-term transgene expression even in the absence of integration, and the relatively low immunogenicity. Although not used widely in dermatology, this review focuses on recent applications of rAAV vectors within the field of cutaneous gene therapy covering aspects of ex vivo gene transfer into keratinocytes, direct in vivo application to the skin, potential indications, such as wound healing and genodermatoses, as well as the basics of rAAV vectorology.