Quality of life measurement in rosacea. Position statement of the European Academy of Dermatology and Venereology Task Forces on Quality of Life and Patient Oriented Outcomes and Acne, Rosacea and Hidradenitis Suppurativa.

The European Academy of Dermatology and Venereology (EADV) Task Forces (TFs) on Quality of Life (QoL) and Patient-Oriented Outcomes and Acne, Rosacea and Hidradenitis Suppurativa (ARHS) do not recommend the use of any generic instrument as a single method of Health Related (HR) QoL assessment in rosacea, except when comparing quimp (quality of life impairment) in rosacea patients with that in other non-dermatologic skin diseases and/or healthy controls. The EADV TFs on QoL and Patient-Oriented Outcomes and ARHS recommend the use of the dermatology-specific HRQoL instrument the Dermatology Life Quality Index (DLQI) and the rosacea-specific HRQoL instrument RosaQoL in rosacea patients. The DLQI minimal clinically important difference may be used as a marker of clinical efficacy of the treatment and DLQI score banding of 0 or 1 corresponding to no effect on patients' HRQoL could be an important treatment goal. This information may be added to consensuses and guidelines for rosacea.

[My tongue is burning!-Glossodynia/orofacial pain disorder]. / Meine Zunge brennt! ­ Glossodynie/orofaziales Schmerzsyndrom.

Glossodynia or orofacial pain disorder is known as burning mouth syndrome. It is a therapeutic challenge. Its etiology is not well defined. Recent studies show not only a correlation with neuropathic changes, but there are also indications of comorbidities such as depression, anxiety, and carcinophobia. These can also manifest as a reaction to the disease and are not necessarily considered causative. Burning mouth syndrome poses a diagnostic challenge since its differential diagnosis is broad. With regard to dermatological aspects, lichen planus mucosae, oral leucoplakia, pemphigus vulgaris, and aphthous mouth ulcers should be considered. Diabetes, anemia, vitamin deficiency, and endocrinological influences should be considered regarding the predominance of elderly and female patients. Meta-analyses of treatment studies usually show a low level of evidence of the randomized, controlled trials. According to the literature mainly psychotherapy and antidepressants are proposed for therapy. Alpha lipoic acid as a dietary supplement shows short-term improvement and low-level laser therapy might have some benefit.

Recalcitrant erythrodermic ichthyosis with atopic dermatitis successfully treated with Dupilumab in combination with Guselkumab.

Background: Autosomal recessive congenital ichthyosis refers to a group of rare inherited disorders of keratinization and defective epidermal barrier resulting in varying clinical presentations and severities ranging from harlequin ichthyosis to congenital ichthyosiform erythroderma (CIE). Secondary atopic dermatitis (AD) can aggravate the disease state for CIE patients leading to recalcitrant CIE/AD with potentially unfavourable side effects and low tolerability. Aims: Here, we report about a 38-year-old male patient with severe CIE as well as AD over the last 30 years. Materials and Methods: The patients suffered from severe inflammation, pruritus and recurrent infections for decades without disease control and intolerable adverse events of previous therapies. Results: Dupilumab (targeting IL-4Ra, 300 mg q2w) partially controlled pruritus, but only the combination of Dupilumab with Guselkumab (anti-IL23p19) controlled both CIE and AD with markedly reduced inflammation, itch and recurrent infections. Guselkumab alone was not sufficient to treat the severe CIE/AD. Discussion: Further studies are required to assess the efficacy and safety of targeted therapies like Dupilumab/Guselkumab combination therapy in severe CIE/AD.

Potential role of INTERLEUKIN-17 in the pathogenesis of oral lichen planus: a systematic review with META-analysis.

Oral lichen planus (OLP) is a chronic inflammatory mucocutaneous disease of unknown aetiology, which may evolve into squamous cell carcinoma. Recent advances on OLP pathogenesis suggest the presence of Th17 cells and the up-regulation of interleukin-17 (IL-17) expression are crucial events. Our aim was to test the hypothesis in the literature about an important role of IL-17 in OLP by systematically investigating the overexpression of IL-17 in the lesional tissue and blood from OLP patients and healthy controls. A total of 22 studies comprising 658 OLP patients and 362 control subjects fulfilled inclusion criteria were subjected to meta-analysis. The assessment of IL-17 in the lesional tissue by quantitative real-time polymerase chain reaction (PCR) revealed a significant elevation in the OLP group (RR:1.35 95%CI: 0.20-2.50, I2 = 92%). There was a statistical overexpression of IL-17 in the serum of OLP group detected by ELISA (RR:2.47 95%CI: 1.17-3.77, I2 = 97%) and flow cytometry (RR:3.04 95%CI: 0.69-5.39, I2 = 97%). In the erosive OLP group, the tissue IL-17 assessed by PCR was higher than in reticular OLP patients (RR:0.78 95%CI: 0.21-1.36, I2 = 0%). Peripheral assessment of IL-17 by ELISA (RR:1.43 95%CI: 0.01-2.85, I2 = 94%) and flow cytometry (RR:1.55 95%CI: 0.29-2.81, I2 = 89%) revealed significant elevation in erosive OLP group. The dominating overexpression of IL-17 and Th17 cells in the local inflammatory infíltrate and serum of OLP patients confirms its role, probably in the interaction between T cells and keratinocytes. Notably, the upregulation of IL-17 is more intense in erosive than in reticular OLP suggesting a positive correlation between IL-17 levels and disease severity. Further research is warranted to investigate the potential role of anti-IL-17 drugs to manage this chronic condition.

Prevalence, pathophysiology and management of itch in epidermolysis bullosa.

Epidermolysis bullosa (EB) is a highly diverse group of inherited skin disorders, resulting from mutations in genes encoding proteins of the dermoepidermal junction. Itch (pruritus) is one of the most common symptoms across all EB subtypes. It occurs in blistered or wounded sites, or manifests as a generalized phenomenon, thereby affecting both intact skin and healing wounds. The mechanism of pruritus in EB is unclear. It is likely that skin inflammation secondary to barrier disruption, wound healing cascades and dysregulated activation of epidermal sensory nerve endings are all involved in its pathophysiology on the molecular and cellular level. Understanding these mechanisms in depth is crucial in developing optimized treatments for people with EB and improving quality of life. This review summarizes current evidence on the prevalence, mechanisms and management of itch in EB.

Evidence supporting the enhanced efficacy of pentavalent antimonials with adjuvant therapy for cutaneous leishmaniasis: a systematic review and meta-analysis.

Cutaneous leishmaniasis (CL) is one of the major neglected disease worldwide. Although many drugs have been used, the pentavalent antimonials (PA) remain as the first-line choice despite their toxicity and limited efficacy. The combination of two drugs has risen as a potential alternative to increase the cure rate while lowering the side-effects caused by pentavalent antimonials (PA). The objective of this study was to critically review and appraise the potential synergism of the adjuvant therapies of PA with other drugs/interventions previously used in the literature. We carried out a search of literature from PubMed, MEDLINE, Embase, Cochrane and clinicaltrials.gov. Articles that described a two-arm or three-arm design in which one of the arms consisted in a combination of a drug/intervention with intralesional or systemic PA were selected. The primary outcome was proportion of complete clearance of the lesions defined as complete re-epithelization and/or negative direct smear. Our literature search identified 554 references. Thirty-one records with a total sample size of 2668 participants met the eligibility criteria. The studies investigated the association of PA with the following: cryotherapy (five studies), allopurinol, imiquimod, pentoxifylline (four studies each), trichloroacetic acid 50% (three studies) and other additional interventions (eleven studies). Overall, the combined therapy of PA with a supplementary intervention was superior to PA monotherapy (RR: 1.23 95% CI: 1.11-1.35, I2  = 64%). In association with PA, the comparator-specific stratified analysis showed that cryotherapy (RR: 1.50 95% CI: 1.25-1.81, I2  = 57%) and allopurinol (RR: 1.70 95% CI: 1.37-2.12, I2  = 28%) were superior to PA in monotherapy. On the contrary, the combined therapy with imiquimod (RR: 1.08 95% CI: 0.88-1.32, I2  = 40%) and pentoxifylline (RR: 1.14 95% CI: 0.94-1.40, I2  = 41%) revealed a non-significant result. The application of TCA along with PA did not show significant differences in the clearance rate, although it was close to it (RR: 1.31 95% CI: 0.99-1.73, I2  = 84%). The present work represents an attempt to find new and reliable treatment modalities to enhance the efficacy based on the adjuvant therapy of pre-existing drugs/interventions with PA. According to our results, the combination of allopurinol-PA is the most effective adjuvant therapy. The application of cryotherapy and TCA stand as useful and encouraging supplementary interventions. The combination of imiquimod-PA and pentoxifylline adds no additional benefit. The results of this work may be helpful in devising and modifying the current guidelines for CL which face major remaining evidence gaps. Triple therapies consisting in cryotherapy-PA-TCA or allopurinol-PA-cryotherapy or allopurinol-PA-TCA can represent promising treatments yet to be confirmed in future trials.

Recommendations for rosacea diagnosis, classification and management: update from the global ROSacea COnsensus 2019 panel.

BACKGROUND: A transition from a subtyping to a phenotyping approach in rosacea is underway, allowing individual patient management according to presenting features instead of categorization by predefined subtypes. The ROSacea COnsensus (ROSCO) 2017 recommendations further support this transition and align with guidance from other working groups. OBJECTIVES: To update and extend previous global ROSCO recommendations in line with the latest research and continue supporting uptake of the phenotype approach in rosacea through clinical tool development. METHODS: Nineteen dermatologists and two ophthalmologists used a modified Delphi approach to reach consensus on statements pertaining to critical aspects of rosacea diagnosis, classification and management. Voting was electronic and blinded. RESULTS: Delphi statements on which the panel achieved consensus of ≥ 75% voting 'Agree' or 'Strongly agree' are presented. The panel recommends discussing disease burden with patients during consultations, using four questions to assist conversations. The primary treatment objective should be achievement of complete clearance, owing to previously established clinical benefits for patients. Cutaneous and ocular features are defined. Treatments have been reassessed in line with recent evidence and the prior treatment algorithm updated. Combination therapy is recommended to benefit patients with multiple features. Ongoing monitoring and dialogue should take place between physician and patients, covering defined factors to maximize outcomes. A prototype clinical tool (Rosacea Tracker) and patient case studies have been developed from consensus statements. CONCLUSIONS: The current survey updates previous recommendations as a basis for local guideline development and provides clinical tools to facilitate a phenotype approach in practice and improve rosacea patient management. What's already known about this topic? A transition to a phenotype approach in rosacea is underway and is being recommended by multiple working groups. New research has become available since the previous ROSCO consensus, necessitating an update and extension of recommendations. What does this study add? We offer updated global recommendations for clinical practice that account for recent research, to continue supporting the transition to a phenotype approach in rosacea. We present prototype clinical tools to facilitate use of the phenotype approach in practice and improve management of patients with rosacea.

Lichen planus: a comprehensive evidence-based analysis of medical treatment.

Lichen planus (LP) is a chronic-relapsing inflammatory skin disease. Although many drugs have been used for the management of LP, some of them lack the backup by strong therapeutic evidence, while others are not suitable for some patients due to safety profile issues. The aim of this study was to review the recent status of available medical therapies for LP to help physicians make better decisions upon best medical practice while facing patients with this condition. A review of published articles on management of LP was conducted with the MEDLINE and PubMed databases. The quality of the evidence was graded as high, moderate, low or very low. A total of 1366 articles were retrieved, and 219 (16%) were included in the final analysis. Twenty-one different treatment modalities were analysed. The quality of evidence was high for topical steroid and calcineurin inhibitor, while it was moderate for oral steroids. All the other modalities reached low or very low quality of evidence. Topical steroids and calcineurin inhibitors are the current first-line therapies, while for other therapies the strength of recommendation is not so evident. Unfortunately, larger randomized, controlled trials to support the efficacy, safety and tolerability of other therapies in LP are lacking, and many of them are recommended based on studies with small sample sizes, lack of standardized outcome measures or lack of controlled duration or even in anecdotal evidence. Thus, large-scale randomized clinical trials are still warranted to establish the exact benefits of other topical treatments, phototherapy, immunosuppressant and new immunomodulators for an optimized treatment of LP.

Updating the diagnosis, classification and assessment of rosacea: recommendations from the global ROSacea COnsensus (ROSCO) panel.

BACKGROUND: Rosacea is currently diagnosed by consensus-defined primary and secondary features and managed by subtype. However, individual features (phenotypes) can span multiple subtypes, which has implications for clinical practice and research. Adopting a phenotype-led approach may facilitate patient-centred management. OBJECTIVES: To advance clinical practice by obtaining international consensus to establish a phenotype-led rosacea diagnosis and classification scheme with global representation. METHODS: Seventeen dermatologists and three ophthalmologists used a modified Delphi approach to reach consensus on statements pertaining to critical aspects of rosacea diagnosis, classification and severity evaluation. All voting was electronic and blinded. RESULTS: Consensus was achieved for transitioning to a phenotype-based approach to rosacea diagnosis and classification. The following two features were independently considered diagnostic for rosacea: (i) persistent, centrofacial erythema associated with periodic intensification; and (ii) phymatous changes. Flushing, telangiectasia, inflammatory lesions and ocular manifestations were not considered to be individually diagnostic. The panel reached agreement on dimensions for phenotype severity measures and established the importance of assessing the patient burden of rosacea. CONCLUSIONS: The panel recommended an approach for diagnosis and classification of rosacea based on disease phenotype.

Rosacea treatment update: recommendations from the global ROSacea COnsensus (ROSCO) panel.

BACKGROUND: Rosacea is currently treated according to subtypes. As this does not adequately address the spectrum of clinical presentation (phenotypes), it has implications for patient management. The ROSacea COnsensus panel was established to address this issue. OBJECTIVES: To incorporate current best treatment evidence with clinical experience from an international expert panel and establish consensus to improve outcomes for patients with rosacea. METHODS: Seventeen dermatologists and three ophthalmologists reached consensus on critical aspects of rosacea treatment and management using a modified Delphi approach. The panel voted on statements using the responses 'strongly disagree', 'disagree', 'agree' or 'strongly agree'. Consensus was defined as ≥ 75% 'agree' or 'strongly agree'. All voting was electronic and blinded. RESULTS: The panel agreed on phenotype-based treatments for signs and symptoms presenting in individuals with rosacea. First-line treatments were identified for individual major features of transient and persistent erythema, inflammatory papules/pustules, telangiectasia and phyma, underpinned by general skincare measures. Multiple features in an individual patient can be simultaneously treated with multiple agents. If treatment is inadequate given appropriate duration, another first-line option or the addition of another first-line agent should be considered. Maintenance treatment depends on treatment modality and patient preferences. Ophthalmological referral for all but the mildest ocular features should be considered. Lid hygiene and artificial tears in addition to medications are used to treat ocular rosacea. CONCLUSIONS: Rosacea diagnosis and treatment should be based on clinical presentation. Consensus was achieved to support this approach for rosacea treatment strategies.

Molecular mechanisms of pruritus.

Pruritus is an unpleasant sensation that evokes the urgent desire to scratch. It is a symptom derived from many nervous system disorders that affects a large population of humans and is treated by a variety of pharmacological agents with variable access. Chronic itch is a huge unmet health problem which affect upward 20% of people worldwide. The mechanisms underlying the chronic pruritus are complex. Studies of the neurobiology, neurophysiology and cellular biology of itch have gradually been clarifying the mechanism of chronic itch both peripherally and centrally. The discussion has been focused on pruriceptive nerves and their receptors as well as the cytokines/chemokines that play major roles in itch induction. Though it is historically hypothesized that pain convey signal generated with the stimuli under high intensity, and itch transduces signal from the same nerves of pain but under low intensity, recently, with the identification of distinct itch specific sensory afferent fibers the theory has twisted the "intensity" to a existence of a complete separation of pain and itch pathways. This review helps to understand the unique properties of itch signaling pathways and their clinical importance of the itch perception and pruritic diseases.

Pathogenesis and clinical presentation of rosacea as a key for a symptom-oriented therapy.

Rosacea is a common chronic inflammatory skin disorder that typically occurs in adults and affects the face. Synonyms of rosacea include "acne rosacea", "couperose" and "facial erythrosis", in German also "Kupferfinne" and "Rotfinne". The disorder is characterised by a chronic and flaring course and is caused by a genetically predisposed, multifactorial process. A higher incidence is seen in people with fair skin and a positive family history. The characteristic rosacea symptoms manifest primarily, but not exclusively centrofacially, with forehead, nose, chin and cheeks significantly affected. Based on the various main symptoms a classification of the individual clinical pictures can be performed. However, a classification often does not reflect the clinical reality, since the various symptoms commonly coexist. The present review provides an introduction on pathogenesis and clinical manifestations of rosacea and prefers a symptom-oriented therapy approach.

Rosazea-Management: Update über allgemeine Maßnahmen und topische Therapieoptionen.

Obwohl bislang für die Rosazea keine kurative Therapie besteht, können verschiedene Optionen zur Behandlung der Symptome und zur Vorbeugung von Exazerbationen empfohlen werden. Neben Selbsthilfemaßnahme wie der Vermeidung von Triggerfaktoren und einer geeigneten Hautpflege sollte das Rosazea-Management bei Patienten mit erythematöser und leichter bis schwerer papulopustulöser Rosazea die Anwendung topischer Präparate als First-Line-Therapie umfassen. Da Überlappungen der charakteristischen Rosazea-Symptome im klinischen Alltag die Regel sind, sollte die medikamentöse Therapie auf die individuellen Symptome zugeschnitten werden; auch eine Kombinationstherapie kann erforderlich sein. Zu den für die Behandlung der Hauptsymptome der Rosazea zugelassenen Wirkstoffen gehören Brimonidin gegen das Erythem sowie Ivermectin, Metronidazol oder Azelainsäure gegen entzündliche Läsionen. Ihre Wirksamkeit wurde in zahlreichen validen, gut kontrollierten Studien belegt. Darüber hinaus existieren verschiedene nicht zugelassene topische Behandlungsmöglichkeiten, deren Wirksamkeit und Sicherheit noch in größeren, kontrollierten Studien zu untersuchen ist.

State of the art: systemic rosacea management.

Based on numerous trials, oral tetracyclines and most commonly their second-generation derivative doxycycline have become the main pillar in systemic rosacea treatment. However, the only preparation that has been approved so far in this setting is 40 mg doxycycline in an anti-inflammatory dosage and with a modified release formulation. With the introduction of this once-daily, non-antibiotic dosing of doxycycline, oral therapy is more commonly prescribed as first-line treatment in moderate to severe papulopustular rosacea. In addition, topical and oral strategies are often used in combination due to the more substantial improvements compared to monotherapy. Although several other non-approved oral agents like macrolides, isotretinoin, and carvedilol have been evaluated for systemic treatment and showed promising results, yet the experience with these drugs in rosacea is limited, and thus they should be reserved for special situations.

Aktueller Stand der systemischen Rosazea-Therapie.

Basierend auf den Daten zahlreicher Studien sind orale Tetracycline - und hier insbesondere Doxycyclin als Tetracyclin der zweiten Generation - die Grundpfeiler der systemischen Rosazea-Therapie. Bisher ist dafür jedoch nur Doxycyclin 40 mg in antientzündlicher Dosierung mit veränderter Wirkstofffreisetzung zugelassen. Seit Einführung der Therapie mit Doxycyclin einmal täglich in nicht antibiotischer Dosierung wird die orale Therapie häufiger als Erstbehandlung bei mittelschwerer bis schwerer papulopustulöser Rosazea verschrieben. Oft wird diese Behandlung aufgrund der besseren Wirksamkeit im Vergleich zur Monotherapie auch mit einer topischen Behandlung kombiniert. Obwohl in der Systemtherapie weitere, nicht zugelassene Wirkstoffe wie Makrolide, Isotretinoin und Carvedilol mit viel versprechenden Ergebnissen untersucht wurden, ist die vorliegende Erfahrung bisher begrenzt, so dass diese Substanzen speziellen Situationen vorbehalten bleiben sollten.

Pathogenese und Klinik der Rosazea als Schlüssel für eine symptomorientierte Therapie.

Rosazea ist eine häufige chronisch-entzündliche Hauterkrankung, die typischerweise bei Erwachsenen vorkommt und das Gesicht betrifft. Synonyme der Rosazea sind Acne rosacea, Kupferfinne, Rotfinne, Couperose und Rosacea. Die Erkrankung ist durch einen chronischen und schubartigen Verlauf gekennzeichnet und wird durch ein genetisch prädisponiertes, multifaktorielles Geschehen bedingt. Ein vermehrtes Auftreten wird bei hellem Hauttyp und positiver Familienanamnese verzeichnet. Die charakteristischen Rosazea-Symptome manifestieren sich vorwiegend, aber nicht ausschließlich zentrofazial, wobei Stirn, Nase, Kinn und die Wangen maßgeblich betroffen sind. Dabei werden unterschiedliche Hauptsymptome voneinander unterschieden, anhand derer eine Klassifikation der verschiedenen klinischen Bilder vorgenommen werden kann. Eine Klassifizierung wird oftmals jedoch nicht der klinischen Realität gerecht, da die verschiedenen Symptome häufig gemeinsam auftreten. Diese Übersichtarbeit führt in die Pathogenese und Klinik der Rosazea ein und plädiert für einen symptomorientierten Therapieansatz.

Rosacea Management: Update on general measures and topical treatment options.

Although there is presently no cure for rosacea, there are several recommended treatment options available to control many of the symptoms and to prevent them from getting worse. In addition to self-help measures like avoidance of trigger factors and proper skin care, rosacea management should include topical medications as one of the first-line choices for patients with erythematous and mild to severe papulopustular rosacea. Since mixed forms of characteristic rosacea symptoms are more common, medical treatment must be symptom-tailored for each individual case and will often involve a combination therapy. Approved topical agents for the major symptoms of rosacea encompass brimonidine for erythema and ivermectin, metronidazole or azelaic acid for inflammatory lesions, all of which have shown their efficacy in numerous valid, well-controlled trials. In addition, there are several other, not approved topical treatments which are possible options that require further validation in larger well-controlled studies.

Racial disparities in cord blood vitamin D levels and its association with small-for-gestational-age infants.

OBJECTIVE: To examine the relationship of race and maternal characteristics and their association with cord blood vitamin D levels and small-for-gestational-age (SGA) status. STUDY DESIGN: Cord blood vitamin D levels were measured in 438 infants (276 black and 162 white). Multivariable logistic regression models were used to evaluate associations between maternal characteristics, vitamin D status and SGA. RESULTS: Black race, Medicaid status, mean body mass index at delivery and lack of prenatal vitamin use were associated with vitamin D deficiency. Black infants had 3.6 greater adjusted odds (95% confidence interval (CI): 2.4, 5.6) of vitamin D deficiency when compared with white infants. Black infants with vitamin D deficiency had 2.4 greater adjusted odds (95% CI: 1.0, 5.8) of SGA. Vitamin D deficiency was not significantly associated with SGA in white infants. CONCLUSION: Identification of risk factors (black race, Medicaid status, obesity and lack of prenatal vitamin use) can lead to opportunities for targeted prenatal vitamin supplementation to reduce the risk of neonatal vitamin D deficiency and SGA status.

Transient receptor potential vanilloid 4 inhibits mouse colonic motility by activating NO-dependent enteric neurotransmission.

UNLABELLED: Recent studies implicate TRPV4 receptors in visceral pain signaling and intestinal inflammation. Our aim was to evaluate the role of TRPV4 in the control of gastrointestinal (GI) motility and to establish the underlying mechanisms. We used immunohistochemistry and PCR to study TRPV4 expression in the GI tract. The effect of TRPV4 activation on GI motility was characterized using in vitro and in vivo motility assays. Calcium and nitric oxide (NO) imaging were performed to study the intracellular signaling pathways. Finally, TRPV4 expression was examined in the colon of healthy human subjects. We demonstrated that TRPV4 can be found on myenteric neurons of the colon and is co-localized with NO synthase (NOS-1). In vitro, the TRPV4 agonist GSK1016790A reduced colonic contractility and increased inhibitory neurotransmission. In vivo, TRPV4 activation slowed GI motility and reduced stool production in mouse models mimicking pathophysiological conditions. We also showed that TRPV4 activation inhibited GI motility by reducing NO-dependent Ca(2+) release from enteric neurons. In conclusion, TRPV4 is involved in the regulation of GI motility in health and disease. KEY MESSAGES: • Recent studies implicate TRPV4 in pain signaling and intestinal inflammation. • Our aim was to characterize the role of TRPV4 in the control of GI motility. • We found that TRPV4 activation reduced colonic contractility. • Our studies also showed altered TRPV4 mRNA expression in IBS-C patients. • TRPV4 may be a novel pharmacological target in functional GI diseases.