Annular plaques on the back.

Annular lichen planus is a rare clinical variant of the lichen planus presenting with round-oval, red to brown macules and plaques with no central atrophy and slightly raised, nonscaly borders. Histopathological features are indistinguishable from typical lichen planus. Given that the accurate diagnosis relies on both the clinical presentation and typical histological features, it is important to be aware of the clinical spectrum of lichen planus. Click https://wileyhealthlearning.com/#/online-courses/6be3b20c-e9c3-40e9-8f36-bfcda6718a73 for the corresponding questions to this CME article.

[Paediatric vulval clinic]. / Pädiatrische Vulvasprechstunde.

In 2008 a vulval clinic was established at the University Clinic of Schleswig Holstein, Campus Luebeck, Department of Dermatology. A total of 1227 patients were referred to the clinic between 2008 and October 2020, including 91 children (age range 1-13 years) and 17 adolescents (age range 14-17 years). The most common paediatric vulval conditions encountered were lichen sclerosus (33%), vulvitis (23%) and vulval psoriasis (7%). Quality of life was measured in 81 children using the paediatric version of the Dermatology Life Quality Index (DLQI). Of a maximum 30 points, the mean score was 7.2, confirming the association between vulval diseases and impaired quality of life in children and adolescents.

Thyroxine restores severely impaired cutaneous re-epithelialisation and angiogenesis in a novel preclinical assay for studying human skin wound healing under "pathological" conditions ex vivo.

Impaired cutaneous wound healing remains a major healthcare challenge. The enormity of this challenge is compounded by the lack of preclinical human skin wound healing models that recapitulate selected key factors underlying impaired healing, namely hypoxia/poor tissue perfusion, oxidative damage, defective innervation, and hyperglycaemia. Since organ-cultured human skin already represents a denervated and impaired perfusion state, we sought to further mimic "pathological" wound healing conditions by culturing experimentally wounded, healthy full-thickness frontotemporal skin from three healthy female subjects for three days in either serum-free supplemented Williams' E medium or in unsupplemented medium under "pathological" conditions (i.e. hypoxia [5% O2], oxidative damage [10 mM H2O2], absence of insulin, excess glucose). Under these "pathological" conditions, dermal-epidermal split formation and dyskeratosis were prominent in organ-cultured human skin, and epidermal reepithelialisation was significantly impaired (p < 0.001), associated with reduced keratinocyte proliferation (p < 0.001), cytokeratin 6 expression (p < 0.001) and increased apoptosis (p < 0.001). Moreover, markers of intracutaneous angiogenesis (CD31 immunoreactivity and the number of of CD31 positive cells and CD31 positive vessel lumina) were significantly reduced. Since we had previously shown that thyroxine promotes wound healing in healthy human skin ex vivo, we tested whether this in principle also occurs under "pathological" wound healing conditions. Indeed, thyroxine administration sufficed to rescue re-epithelialisation (p < 0.001) and promoted both epidermal keratinocyte proliferation (p < 0.01) and angiogenesis in terms of CD31 immunoreactivity and CD31 positive cells under "pathological" conditions (p < 0.001) ex vivo. This demonstrates the utility of this pragmatic short-term ex vivo model, which recapitulates some key parameters of impaired human skin wound healing, for the preclinical identification of promising wound healing promoters.

[Immune checkpoint inhibition in Merkel cell carcinoma]. / Immuncheckpointinhibition beim Merkel-Zell-Karzinom.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare but aggressive form of skin cancer in which Merkel cell polyomavirus infection and chronic exposure to ultraviolet radiation are key risk factors. Immune checkpoint inhibition has revolutionized the treatment of locally advanced, inoperable and metastatic MCC. AIM: To outline the modern management of MCC based on advances in our understanding of MCC tumour biology and the development of immune checkpoint inhibitors, namely inhibitors of programmed cell death protein (PD)-1- and PD­1 ligand 1 (PD-L1). METHODS: A review of the scientific literature listed in PubMed. RESULTS: First line therapy with the PD-L1 blocking antibody avelumab is associated with a response rate of 62%. In the second line setting, for example after chemotherapy, the response rate only reaches 33%. However, in patients who responded in the second line setting, 69% remained relapse free after 2 years. Treatment responses occurred on average after 6.1 weeks of therapy. First line treatment with pembrolizumab (anti-PD­1 antibody) is associated with a 2-year survival rate of 69% and the median survival rate has not been reached. Whilst the various chemotherapy regimens are associated with similar response rates, these are typically short lived. DISCUSSION: Checkpoint inhibition offers an effective treatment option for patients with MCC. Avelumab is currently licensed as a treatment for metastatic disease. Chemotherapy remains an option to reduce tumor load, or in the context of resistance and/or contraindications to immune checkpoint therapy. Adjuvant and neoadjuvant use of checkpoint inhibition in MCC may represent a future treatment strategy pending the results of on-going clinical trials.

[Cutaneous angiosarcoma : Radiochemotherapy with liposomal pegylated doxorubicin]. / Kutanes Angiosarkom : Radiochemotherapie mit liposomal verkapseltem pegyliertem Doxorubicin.

BACKGROUND: Whilst cutaneous angiosarcoma is rare tumour which primarily affects elderly patients, its management presents a significant therapeutic challenge. Indeed, complete surgical excision is often not possible due to the location and the diffuse and extensive nature of the tumour. Therefore, current treatment strategies often include chemo- and/or radiotherapy. METHODS: We report our experience of combined chemo- and radiotherapy in the clinical course of 6 patients with cutaneous angiosarcoma who were treated between 2007 and 2018. RESULTS: All patients presented non-resectable tumours and were treated with radiotherapy in combination with the administration of liposomal, pegylated doxrubicin (25 mg/m2 every 2 weeks). The mean duration of progression-free survival was 8 months (5-14 months), corresponding to an overall survival of 13 months (13-34 months). A partial response was seen in 4 patients and 1 patient developed progressive disease. One patient abandoned therapy after one administration. Two patients developed severe adverse events which led to termination of therapy after 1.5 months and 7 months, i.e. after 4 and 15 cycles respectively. DISCUSSION: Combined radio- and chemotherapy with liposomal, pegylated doxorubicin is a useful therapeutic option in the management of cutaneous angiosarcoma. Given the short-lived response rate, new treatment options are urgently required.

Combined culture and metagenomic analyses reveal significant shifts in the composition of the cutaneous microbiome in psoriasis.

BACKGROUND: The treatment of psoriasis has been revolutionized by the development of biologic therapies. However, the pathogenesis of psoriasis, in particular the role of the cutaneous microbiome, remains incompletely understood. Moreover, skin microbiome studies have relied heavily on 16S rRNA sequencing data in the absence of bacterial culture. OBJECTIVES: To characterize and compare the cutaneous microbiome in 20 healthy controls and 23 patients with psoriasis using metagenomic analyses and to determine changes in the microbiome during treatment. METHODS: Swabs from lesional and nonlesional skin from patients with psoriasis, and from controls matched for site and skin microenvironment, were analysed using both 16S rRNA sequencing and traditional culture combined with mass spectrometry (MALDI-TOF) in a prospective study. RESULTS: Psoriasis was associated with an increased abundance of Firmicutes and a corresponding reduction in Actinobacteria, most marked in lesional skin, and at least partially reversed during systemic treatment. Shifts in bacterial community composition in lesional sites were reflected in similar changes in culturable bacteria, although changes in the microbiota over repeated swabbing were detectable only with sequencing. The composition of the microbial communities varied by skin site and microenvironment. Prevotella and Staphylococcus were significantly associated with lesional skin, and Anaerococcus and Propionibacterium with nonlesional skin. There were no significant differences in the amount of bacteria cultured from the skin of healthy controls and patients with psoriasis. CONCLUSIONS: Shifts in the cutaneous microbiome in psoriasis, particularly during treatment, may shed new light on the pathogenesis of the disease and may be clinically exploited to predict treatment response. What's already known about this topic? Alterations in the composition of the cutaneous microbiome have been described in psoriasis, although methodological differences in study design prevent direct comparison of results. To date, most cutaneous microbiome studies have focused on 16S rRNA sequencing data, including both living and dead bacteria. What does this study add? This prospective observational study confirms that changes in the composition of the cutaneous microbiome, detected by 16S rRNA sequencing, are consistent with those identified by bacterial culture and mass spectrometry. The changes in the microbiome during antipsoriasis therapy should be further investigated to determine whether these represent potential novel biomarkers of treatment response. What is the translational message? Characterization of cutaneous microbiota may ultimately move into the clinic to help facilitate treatment selection, not only by optimizing currently available treatments, but also by identifying new therapeutic targets.

Is prolactin a negative neuroendocrine regulator of human skin re-epithelisation after wounding?

Chronic wounds remain a major unmet healthcare challenge, associated with substantial morbidity and economic costs. Therefore, novel treatment strategies and therapeutic approaches need to be urgently developed. Yet, despite the increasingly recognized importance of neurohormonal signaling in skin physiology, the neuroendocrine regulation of cutaneous wound healing has received surprisingly little attention. Human skin, and its appendages, locally express the pleiotropic neurohormone prolactin (PRL), which not only regulates lactation but also hair follicle cycling, angiogenesis, keratinocyte proliferation, and epithelial stem cell functions. Therefore, we examined the effects of PRL in experimentally wounded female human skin organ culture. Overall, this revealed that PRL slightly, but significantly, inhibited epidermal regeneration (reepithelialisation), cytokeratin 6 protein expression and intraepidermal mitochondrial activity (MTCO1 expression), while it promoted keratinocyte terminal differentiation (i.e. involucrin expression) ex vivo. If the current pilot data are confirmed by further studies, PRL may serve as one of the-rarely studied-negative regulators of cutaneous wound healing that control excessive reepithelialisation. This raises the intriguing and clinically relevant question of whether PRL receptor antagonists could actually promote epidermal repair after human skin wounding.

The role of the microbiome in psoriasis: moving from disease description to treatment selection?

BACKGROUND: With several million microbes per square centimetre of skin, the task of mapping the physiological cutaneous microbiome is enormous. Indeed, the reliance on bacterial culture to identify cutaneous bacterial communities has led to a systematic underappreciation of cutaneous microbial diversity, potentially limiting our understanding of common inflammatory skin diseases, including psoriasis. However, based heavily on developments in molecular biology and bioinformatics, including next-generation sequencing, the last decade has witnessed a marked increase in our understanding of the extent and composition of the cutaneous microbiome. It is already clear that skin-specific (skin site and skin microenvironment), individual-specific (hygiene, sex, age and hormonal status), disease-specific (atopic eczema, acne) and genetic factors can all influence the cutaneous microbiome, albeit to varying and, as yet, ill-defined extents. OBJECTIVES: To investigate the role of the microbiome in psoriasis and to outline how microbiome studies can be harnessed to provide new insights into disease pathogenesis and treatment selection. METHODS: This review briefly describes the process of 16S ribosomal RNA sequencing and then charts our current understanding of the cutaneous microbiome in health and the alterations (dysbiosis) associated with chronic inflammatory diseases, with particular reference to psoriasis. RESULTS: The possibility and clinical relevance of intraindividual cross-talk between the various microbiomes is discussed and potential mechanisms underpinning the interactions between resident skin flora and the immune system are highlighted. CONCLUSIONS: Ultimately, in the age of personalized medicine, the integration of cutaneous microbiome signatures and comprehensive disease and drug response endotypes will herald a novel approach in the clinical management of chronic multisystem inflammatory diseases.

Are Sonographically Measured Vascular Haemodynamic Parameters Reproducible Using Magnetic Resonance Imaging?

OBJECTIVE/BACKGROUND: Hemodynamic measurements of blood flow in the common femoral vein and artery can be performed readily using duplex sonography. The ratio of venous to arterial volume flow in these vessels, the venous arterial flow index (VAFI), is increased in patients with varicose veins and/or chronic venous disease. The objective was to determine the reproducibility of sonographically measured hemodynamic flow parameters using phase contrast magnetic resonance imaging (MRI). METHODS: Based on hemodynamic volume flow measurements from the common femoral vein and artery the VAFI was calculated in seven patients with varicose veins (C2, Ep, As, Pr) and 32 healthy controls using standard duplex sonography and MRI. RESULTS: Based on duplex sonography, the average VAFI (VAFI_d) was 1.05 ± 0.17. The same ratio, using MRI (VAFI_mri) was 1.05 ± 0.19. There was a significant correlation between the VAFI_d and the VAFI_MRI (p = .0021). In patients with venous disease, the average VAFI_d and VAFI_mri were 1.36 ± 0.21 and 1.36 ± 0.20, respectively. In contrast, in the healthy cohort the VAFI_d was 1.00 ± 0.12 and the VAFI_mri measured 1.01 ± 0.15. As expected, there was a significant difference between the VAFI measured in those with venous disease when compared with that of healthy controls (p < .0001). CONCLUSION: There is a significant correlation between the VAFI measured using sonography and MRI. The study confirmed the elevation of VAFI in patients with chronic venous disease.

Dopamine is a novel, direct inducer of catagen in human scalp hair follicles in vitro.

BACKGROUND: Although there are clinical reports of hair loss associated with levodopa and dopamine agonists, it is unclear whether dopamine exerts any direct effects on the human hair follicle (HF). OBJECTIVES: Given the widespread use of dopamine agonists and antagonists in clinical medicine, we sought to determine whether dopamine exerts direct effects on human HF growth and/or pigmentation in vitro, and whether human HFs express dopamine receptors (DRs). METHODS: Microdissected human scalp HFs from women were treated in serum-free organ culture for 7 days with dopamine (10-1000 nmol L ), and the effects on hair shaft production, HF cycling (i.e. anagen-catagen transition), hair matrix keratinocyte proliferation and apoptosis, and HF pigmentation were measured by quantitative (immuno-) histomorphometry. RESULTS: Dopamine had no consistent effect on hair shaft production, but did promote HF regression (catagen). It was also associated with significantly reduced proliferation of HF matrix keratinocytes (P < 0·01) and reduced intrafollicular melanin production. Dopamine receptor transcripts were identified in HFs and skin. CONCLUSIONS: These data provide evidence that dopamine is an inhibitor of human hair growth, via the promotion of catagen induction, at least in vitro. This may offer a rational explanation for the induction of telogen effluvium in some women treated with dopamine agonists such as bromocriptine. Moreover, dopaminergic agonists deserve further exploration as novel inhibitors of unwanted human hair growth (hirsutism, hypertrichosis).

Immunohistological pointers to a possible role for excessive cathelicidin (LL-37) expression by apocrine sweat glands in the pathogenesis of hidradenitis suppurativa/acne inversa.

BACKGROUND: The cause of follicular occlusion, a key early event in the pathogenesis of hidradenitis suppurativa (HS), also known as acne inversa, remains unknown. OBJECTIVES: To identify changes, if any, in the antimicrobial peptide (AMP) and cytokine expression profile of HS affected human skin. METHODS: Quantitative immunohistomorphometry was used to compare the in situ protein expression of selected AMPs and cytokines in lesional HS skin from 18 patients with that in healthy skin (n = 12). The lesional skin from patients with HS was histologically subclassified based on the predominance of inflammation vs. scarring. RESULTS: Compared with healthy controls, significantly increased immunoreactivity for cathelicidin (LL-37) was noted in the apocrine sweat gland and distal outer root sheath (ORS) of the hair follicle (HF) epithelium in lesional HS skin. Immunoreactivity for LL-37, psoriasin, human ß-defensin 3 (hBD3), α-melanocyte stimulating hormone (α-MSH), macrophage migration inhibitory factor (MIF), tumour necrosis factor (TNF)-α and interleukin (IL)-8 was significantly increased in HS epidermis. LL-37 and TNF-α immunoreactivity was also increased in the dermis of lesional HS skin. In contrast, lysozyme expression was decreased in the epidermis of lesional HS skin, while that of TNF-α and IL-8 was decreased in the proximal ORS of HFs in HS lesions. These differences were most pronounced in HS with predominant inflammation. CONCLUSIONS: Our observations raise the question as to whether excessive secretion of AMPs by the skin, in particular by the apocrine sweat glands, distal HF epithelium, and epidermis, may attract inflammation and thus facilitate or promote HS development.