Topical Treatment of Psoriasis Vulgaris: The Swiss Treatment Pathway.

Topical treatment is crucial for the successful management of plaque psoriasis. Topicals are used either as a stand-alone therapy for mild psoriasis or else in combination with UV or systemic treatment for moderate-to-severe disease. For the choice of a suitable topical treatment, the formulation matters and not just the active substances. This expert opinion paper was developed via a non-structured consensus process by Swiss dermatologists in hospitals and private practices to illustrate the current treatment options to general practitioners and dermatologists in Switzerland. Defining treatment goals together with the patient is crucial and increases treatment adherence. Patients' personal preferences and pre-existing experiences should be considered and their satisfaction with treatment and outcome regularly assessed. During the induction phase of "classical" mild-to-moderate psoriasis, the fixed combination of topical calcipotriol (Cal) 50 µg/g and betamethasone dipropionate (BD) 0.5 mg/g once daily is frequently used for 4-8 weeks. During the maintenance phase, a twice weekly (proactive) management has proved to reduce the risk of relapse. Of the fixed combinations, Cal/BD aerosol foam is the most effective formulation. However, the individual choice of formulation should be based on a patient's preference and the location of the psoriatic plaques. Tailored recommendations are given for the topical management of specific areas (scalp, facial, intertriginous/genital, or palmoplantar lesions), certain symptoms (hyperkeratotic or hyperinflammatory forms) as well as during pregnancy or a period of breastfeeding. As concomitant basic therapy, several emollients are recommended. If topical treatment alone does not appear to be sufficient, the regimen should be escalated according to the Swiss S1-guideline for the systemic treatment of psoriasis.

Diagnosis and treatment of xerosis cutis - a position paper.

BACKGROUND AND RATIONALE: Xerosis cutis (also referred to as xeroderma, dry skin, asteatosis) affects more than 10 million individuals in Germany. It is among the most common dermatological diagnoses and a cardinal symptom of many dermatological, internal and neurological diseases. Even though it has been established that basic skin care plays a significant role in the management of patients with xerosis cutis, there are as yet no evidence-based algorithms for diagnosis and treatment. OBJECTIVE: The present position paper provides physicians across all specialties with a practical, symptom-based approach to the prevention, diagnosis and treatment of xerosis cutis. METHODS: Within a structured decision-making process, a panel of experienced dermatologists first defined questions relevant to everyday clinical practice, which were then addressed by a systematic review of the literature. Based on the evidence available as well as expert consensus, diagnostic and treatment algorithms were subsequently developed and agreed upon. RESULTS: Xerosis cutis is generally diagnosed on clinical grounds. Possible trigger factors must be avoided, and comorbidities should be adequately and specifically treated. Suitable skin care products should be chosen with a view to improving skin hydration and restoring its barrier function. They should therefore contain both rehydrating and lipid-replenishing components. The "drier" the skin appears, the greater the lipid content should be (preferably using water-in-oil formulations). The choice of ingredients is based on a patient's individual symptoms, such as scaling (e.g., urea), fissures/rhagades (e.g., urea or dexpanthenol), erythema (e.g., licochalcone A) and pruritus (e.g., polidocanol). Other factors to be considered include the site affected and patient age. Ingredients or rather combinations thereof for which there is good clinical evidence should be preferentially used. The best evidence by far is available for urea, whose efficacy in the treatment of xerosis is further enhanced by combining it with other natural moisturizing components and ceramides. The "xerosimeter" is a tool developed in an effort to facilitate patient management and for training purposes. It not only includes practical tools for diagnosis and follow-up but also a classification of ingredients and a structured treatment algorithm. CONCLUSION: The structured symptom- and evidence-based approach proposed herein contains a road map for diagnosis and treatment of xerosis cutis. It aims to raise awareness in terms of prevention and early treatment of this condition and may thus improve quality of life and prevent potential sequelae.

Positionspapier: Diagnostik und Therapie der Xerosis cutis.

HINTERGRUND UND RATIONALE: Die Xerosis cutis (Synonym: Xerodermie, trockene Haut, hydrolipidarme Haut) ist mit > 10 Millionen Betroffenen nicht nur eine der häufigsten dermatologischen Diagnosen in Deutschland, sondern auch Leitsymptom vieler dermatologischer, internistischer und neurologischer Erkrankungen. Trotz der medizinischen Relevanz der topischen Basistherapie für die Xerosis cutis gibt es in Deutschland für ihr Management bisher keinen wissenschaftlich belegten Diagnostik- und Therapiealgorithmus. ZIEL: Dieses Positionspapier vermittelt Ärzten fachübergreifend einen an individuellen Symptomen orientierten, praxisnahen Leitfaden für die Prävention, Diagnostik und Therapie der Xerosis cutis. METHODIK: Im Rahmen eines strukturierten Entscheidungsprozesses wurden von erfahrenen dermatologischen Experten zunächst praxisrelevante Fragestellungen definiert und systematisch aufgearbeitet. Auf der Basis von Evidenz und Expertenkonsens wurden daraus diagnostische und therapeutische Algorithmen mit Empfehlungen für die Praxis entwickelt und konsentiert. ERGEBNIS: Die Xerosis cutis kann grundsätzlich klinisch diagnostiziert werden. Auslöser und/oder Grunderkrankungen müssen abgeklärt und vermieden bzw. spezifisch behandelt werden. Bei der Wahl der geeigneten Basistherapie ist es wichtig, dass nicht nur die Hauthydratation verbessert, sondern auch die Barrierefunktion der Haut wiederhergestellt wird. Sie sollte daher aus einer Kombination von rückfeuchtenden und rückfettenden Inhaltsstoffen bestehen. Je trockener die Haut, desto lipidhaltiger sollte die Hautpflege sein (bevorzugt Wasser-in-Öl-Formulierungen). Die individuelle Auswahl der Inhaltsstoffe orientiert sich nach kausaler Prüfung an den Symptomen Schuppung (v.a. Urea), Fissuren/Rhagaden (v.a. Urea oder Dexpanthenol), Rötung (v.a. Licochalcone A) und Pruritus (v.a. Polidocanol), sowie an der Lokalisation und dem Alter der Patienten. Inhaltsstoffe bzw. Inhaltsstoffkombinationen mit guter Studienevidenz sind zu bevorzugen. Die mit Abstand beste Evidenz bei der Xerosis cutis weist Urea auf, dessen Wirksamkeit in Kombination mit anderen natürlichen Feuchthalte-Komponenten und Ceramiden noch gesteigert werden kann. Zur Arbeitserleichterung am Patienten und zum besseren Erlernen wurde das Xerosimeter entwickelt, das die praktische Umsetzung der Diagnostik und Verlaufskontrolle, eine Klassifikation der Inhaltsstoffe und einen strukturierten Therapiealgorithmus enthält. SCHLUSSFOLGERUNG: Das hier vorgeschlagene strukturierte symptom- und evidenzorientierte Vorgehen mit Diagnostik- und Behandlungspfad soll für die Prävention und frühzeitige Behandlung der Xerosis cutis sensibilisieren. Damit können die Lebensqualität verbessert und Folgeerkrankungen verhindert werden.

Gene Therapy in Lipoprotein Lipase Deficiency: Case Report on the First Patient Treated with Alipogene Tiparvovec Under Daily Practice Conditions.

One-year results are reported of the first lipoprotein lipase deficiency (LPLD) patient treated with alipogene tiparvovec, which is indicated for the treatment of patients with genetically confirmed LPLD suffering from acute and recurrent pancreatitis attacks (PAs) despite dietary restrictions and expressing >5% of lipoprotein lipase (LPL) mass compared to a healthy control. During clinical development, alipogene tiparvovec has shown improvement of chylomicron metabolism and reduction of pancreatitis incidence up to 5.8 years post treatment. A 43-year-old female presented with severe hypertriglyceridemia (median triglyceride [TG] value of 3,465 mg/dL) and a history of 37 PAs within the last 25 years, despite treatment with fibrates, omega 3 fatty acids, and-since 2012-twice-weekly lipid apheresis. LPLD was confirmed by identification of two different pathogenic variants in the LPL gene located on separate alleles and therefore constituting a compound heterozygous state. With a detectable LPL mass level of 55.1 ng/mL, the patient was eligible for alipogene tiparvovec treatment, and in September 2015, she receved 40 injections (1 × 1012 genome copies/kg) in the muscles of her upper legs under epidural anesthesia and immunosuppressive therapy. Alipogene tiparvovec was well tolerated: no injection site or systemic reactions were observed. Median TG values decreased by 52%, dropping to 997 mg/dL at month 3 and increasing thereafter. Within the first 18 months post treatment, the patient discontinued plasmapheresis and had no abdominal pain or PAs. In March 2017, the patient suffered from a PA due to diet violation. Within the first 12 months post treatment, overall quality of life improved, and no change in humoral or cellular immune response against LPL or AAV-1 was observed. In conclusion, alipogene tiparvovec was well tolerated, with a satisfactory response to treatment. Long-term effects on the recurrence of pancreatitis continue to be monitored.

The role of registries in rare genetic lipid disorders: Review and introduction of the first global registry in lipoprotein lipase deficiency.

A good understanding of the natural history of rare genetic lipid disorders is a pre-requisite for successful patient management. Disease registries have been helpful in this regard. Lipoprotein Lipase Deficiency (LPLD) is a rare, autosomal-recessive lipid disorder characterized by severe hypertriglyceridemia and a very high risk for recurrent acute pancreatitis, however, only limited data are available on its natural course. Alipogene tiparvovec (Glybera®) is the first gene therapy to receive Marketing Authorization in the European Union; GENIALL (GENetherapy In the MAnagement of Lipoprotein Lipase Deficiency), a 15-year registry focusing on LPLD was launched in 2014 as part of its Risk Management Plan. The aim of this publication is to introduce the GENIALL Registry within a structured literature review of registries in rare genetic lipid disorders. A total of 11 relevant initiatives/registries were identified (homozygous Familial Hypercholesterolemia (hoFH) [n = 5]; LPLD [n = 1]; Lysosomal Acid Lipase Deficiency [LALD, n = 1], detection of mutations in genetic lipid disorders [n = 4]). Besides one product registry in hoFH and the LALD registry, all other initiatives are local or country-specific. GENIALL is the first global prospective registry in LPLD that will collect physician and patient generated data on the natural course of LPLD, as well as long-term outcomes of gene therapy. CONCLUSION: There is a limited number of international initiatives focusing on the natural course of specific rare genetic lipid disorders. The GENIALL LPLD Registry could be the first step towards a future broader global initiative that collects data related to familial chylomicronemia syndrome and their underlying genetic causes.