Keratinocyte and Fibroblast Wound Healing In Vitro Is Repressed by Non-Optimal Conditions but the Reparative Potential Can Be Improved by Water-Filtered Infrared A.

It is a general goal to improve wound healing, especially of chronic wounds. As light therapy has gained increasing attention, the positive influence on healing progression of water-filtered infrared A (wIRA), a special form of thermal radiation, has been investigated and compared to the detrimental effects of UV-B irradiation on wound closure in vitro. Models of keratinocyte and fibroblast scratches help to elucidate effects on epithelial and dermal healing. This study further used the simulation of non-optimal settings such as S. aureus infection, chronic inflammation, and anti-inflammatory conditions to determine how these affect scratch wound progression and whether wIRA treatment can improve healing. Gene expression analysis for cytokines (IL1A, IL6, CXCL8), growth (TGFB1, PDGFC) and transcription factors (NFKB1, TP53), heat shock proteins (HSP90AA1, HSPA1A, HSPD1), keratinocyte desmogleins (DSG1, DSG3), and fibroblast collagen (COL1A1, COL3A1) was performed. Keratinocyte and fibroblast wound healing under non-optimal conditions was found to be distinctly reduced in vitro. wIRA treatment could counteract the inflammatory response in infected keratinocytes as well as under chronic inflammatory conditions by decreasing pro-inflammatory cytokine gene expression and improve wound healing. In contrast, in the anti-inflammatory setting, wIRA radiation could re-initiate the acute inflammatory response necessary after injury to stimulate the regenerative processes and advance scratch closure.

Treatment of pityriasis rubra pilaris type I: a systematic review.

Pityriasis rubra pilaris (PRP) is an uncommon papulosquamous inflammatory disease of the skin, which may progress to erythroderma. The diagnosis is based on both clinical and histopathological findings. There are numerous treatment options in the literature, but often reported as unsuccessful. To summarize the therapy of type I PRP in a systematic manner. We performed a systematic search following the PRISMA Guidelines based on PubMed, Web of Science, and Medline databases using the term 'pityriasis rubra pilaris treatment' (in German and English) on human subjects, published between 1997 and 2017, documenting therapy for PRP type I. A total of 449 records were identified; 148 full-text articles were assessed for eligibility and 105 articles were included in the qualitative synthesis. We identified mainly individual case reports, a few retrospective studies, and small case series. No randomized controlled trials were found. Treatment options included topical and systemic agents, and physical modalities. Based on our review, we suggest a continuous topical treatment and, when appropriate, in combination with phototherapy. As first-line therapy, we recommend a retinoid, and as second-line, a combination of retinoid and methotrexate (considering the patient's condition and side effects), azathioprine, or cyclosporine A. Biologicals can be used as third-line therapy. In case of treatment failure, biologicals can be combined with a retinoid, methotrexate, or cyclosporine A. Randomized controlled clinical trials are needed in order to provide an evidence-based high-quality standardized treatment for patients with PRP type I.

The Microbiome and Atopic Dermatitis: A Review.

The microbiome is defined as the sum of microbes, their genomes, and interactions in a given ecological niche. Atopic dermatitis is a multifactorial chronic inflammatory skin disease leading to dryness and itchiness of the skin. It is often associated with comorbidities such as allergic rhinoconjunctivitis and asthma. Today, culture-free techniques have been established to define microbes and their genomes that may be both detrimental and beneficial for their host. There are signs that microbes, both on skin and in the gut, may influence the course of atopic dermatitis. Antiseptic treatment has been used for decades, however now, with the help of traditional culture-based methods and modern metagenomics, we are beginning to understand that targeted treatment of dysbiosis may possibly become part of an integrated therapy plan in the future.

Chronic hand eczema in Germany: 5-year follow-up data from the CARPE registry.

BACKGROUND: The CARPE registry was set up in 2009 to prospectively investigate the management of patients with chronic hand eczema (CHE). OBJECTIVES: To report comprehensive follow-up data from the CARPE registry. PATIENTS AND METHODS: We investigated sociodemographic and clinical characteristics, provision of medical care, physician-assessed outcomes, and patient-reported outcomes (PROs). Data were collected between 2009 and 2016, with up to 5 years of follow-up, and are reported descriptively. RESULTS: Overall, 1281 patients were included in the registry (53.7% female). Mean age was 47.0 years. Of the patients, 793 and 231 completed the 2-year follow-up and 5-year follow-up, respectively. At baseline, 5.4% had changed or given up their job because of CHE, the average duration of CHE was 6.1 years, and, in 22.4%, the CHE was severe according to physician global assessment. Systemic treatment (alitretinoin, acitretin, and methotrexate) was prescribed at least once to 39.0% of the patients during the course of the follow-up. Disease severity, quality of life and treatment satisfaction improved over time, and the proportion of patients receiving systemic treatments decreased. CONCLUSIONS: Under continued dermatological care, substantial improvements in disease severity and PROs over time was achieved during the course of the CARPE registry, even in patients with long-standing and severe hand eczema.

Treatment of acquired reactive perforating dermatosis - a systematic review.

Reactive perforating dermatosis is a rare chronic skin disease defined by the transepidermal elimination of collagen and/or elastin. In the acquired form in adults, it is frequently associated with diseases such as diabetes and chronic renal failure. No systematic reviews of treatment options are available for this disease. The aim of this systematic review is to summarize all reported treatment options for acquired reactive perforating dermatosis (ARPD). This is a systematic review based on a MEDLINE search of articles in English and German from 1990 to 2016. Most medical literature on the treatment of ARPD is limited to individual case reports and small series of patients. Various therapies that have been tried include antihistamines, topical keratolytics, corticosteroids, tretinoin, oral drugs such as allopurinol or antibiotics, and phototherapy or photochemotherapy. While there are no specific criteria for the evidence-based selection of treatment options for ARPD, the first priority in management of these conditions should be treatment of an underlying disease if present. None of the described modalities has been approved for first-line therapy. It is recommended to choose a combination of drugs that reduce itching and assist in the resolution of the skin lesions at the same time.

Treatment of Scleroedema Adultorum Buschke: A Systematic Review.

Scleroedema adultorum Buschke is a rare skin disease, which can be divided into 3 subtypes: classic type, occurring after respiratory infections; a type lacking association with infections; and a type associated with diabetes. Scleroedema adultorum Buschke is characterized by thickening and tightening of the skin, which typically starts at the neck. In half of patients, spontaneous remission may occur. The aim of this systematic review is to summarize all reported treatments for scleroedema adultorum Buschke, based on articles from PubMed database, using the query "scleroedema adultorum Buschke treatment", English and German, published between 1970 and 2016 and documenting adequate treatments. The results are based mainly on individual case reports, small case series, and retrospective studies often reporting unsuccessful results. Treatment options include topical as well as systemic treatments, and physical modalities. There is a need for randomized controlled trials and studies on long-term outcomes after treatment.

Light and Laser Modalities in the Treatment of Cutaneous Sarcoidosis: A Systematic Review.

Sarcoidosis is a systemic non-caseating granulomatous disease of unknown aetiology. Cutaneous manifestations are present in approximately 10-30% of the patients with the systemic form. Therapy is indicated in case of disabling symptoms, organ dysfunction or cosmetically distressing manifestation. Despite different therapeutic possibilities, cutaneous sarcoidosis remains exceptionally difficult to treat. Light and laser therapy may be a promising alternative. In this systematic review, we summarised the available treatments according to the literature concerning light and laser therapy for cutaneous sarcoidosis. Publications written in English and German, published between January 1990 and July 2016 in the database PubMed, MEDLINE, Embase, and Scopus were analysed. Light therapy with intense pulsed light, photodynamic therapy, and ultraviolet A light therapy, as well as laser therapy with pulsed dye laser, YAG laser, and Q-switched ruby laser were described. The results are based on individual case reports and small case series. Randomised controlled studies are lacking.

Primary Localized Cutaneous Amyloidosis: A Systematic Treatment Review.

BACKGROUND: Primary localized cutaneous amyloidosis (PLCA) is characterized by extracellular deposition of heterogenic amyloid proteins in the skin without systemic involvement. Lichen amyloidosis, macular amyloidosis, and (primary localized cutaneous) nodular amyloidosis are different subtypes of PLCA. OBJECTIVE: The aim of this study was to review the current reported treatment options for PLCA. METHODS: This systematic review was based on a search in the PubMed database for English and German articles from 1985 to 2016. RESULTS: Reports on the treatment of PLCA were limited predominantly to case reports or small case series. There were a few clinical trials but these lacked control groups. A variety of treatment options for PLCA were reported including retinoids, corticosteroids, cyclophosphamide, cyclosporine, amitriptyline, colchicine, cepharanthin, tacrolimus, dimethyl sulfoxide, vitamin D3 analogs, capsaicin, menthol, hydrocolloid dressings, surgical modalities, laser treatment, and phototherapy. CONCLUSION: No definitive recommendation of preferable treatment procedures can be made based on the analyzed literature. Randomized controlled trials are needed to offer patients an evidence-based therapy with high-quality standardized treatment regimens for PLCA.

Update: Treatment of necrobiosis lipoidica.

Necrobiosis lipoidica (NL) is a rare granulomatous disease of hitherto unclear etiology frequently seen in patients with diabetes. Characterized by its potential for ulcerations, it often presents a serious burden for those affected. There are currently neither German nor European guidelines for the treatment of NL. At the same time, standard treatment with topical or intralesional corticosteroids does not always show satisfactory results. We therefore set out to evaluate whether the various treatment regimens published since 2000 have actually expanded the therapeutic armamentarium in a relevant manner. Included were all publications that described more than one patient being treated with any given therapeutic modality. Overall, we analyzed data for 16 different treatment regimens reported in 49 publications. The largest amount of data exists for topical PUVA therapy, photodynamic therapy (PDT), and systemic treatment with fumaric acid esters. Remarkably, our analysis showed that with an increase in the number of documented patients treated with a given therapeutic modality, the proportion of those achieving a complete or partial response actually decreased. This was interpreted as publication bias. Thus, no clear recommendation can be given for second-line therapy in case topical or intralesional corticosteroids fail.

S1 guideline on occupational skin products: protective creams, skin cleansers, skin care products (ICD 10: L23, L24)--short version.

Job-related hand dermatitis heads up the list of reported occupational diseases. So-called skin products - understood to mean protective creams, skin cleansers and skin care products - are used for the primary and secondary prevention of job- related hand dermatitis. In the interests of evidence-based medicine, the only preventive measures and/or occupational skin products that should be used are those whose potential uses and efficacy are underpinned by scientific research. To this end, the Arbeitsgemeinschaft für Berufs- und Umweltdermatologie e.V. (Working Group for Occupational and Environmental Dermatology, ABD) of the DDG (German Dermatological Society) and the Deutsche Gesellschaft für Arbeits- und Umweltmedizin (German Society for Occupational and Environmental Medicine, DGAUM) have summed up the latest scientific findings and recommendations in the updated guideline. The benefit of the combined application of protective creams and skin care products in the primary and secondary prevention of work-related contact dermatitis has been widely confirmed by recent clinical-epidemiological studies. The guideline clearly explains the necessity of demonstrating the efficacy of protective creams and cleansing products by means of in vivo methods in the sense of repetitive applications. Transferable standardised testing systems designed to examine the irritation potential and thus the compatibility of occupational skin cleansers and the reduction of irritation by protective skin creams have now been developed and validated by multicentre studies for skin protection creams and cleansers. The status of the current assessment of the safety of occupational skin products is also summarised.

Hand dermatitis: a review of clinical features, prevention and treatment.

Hand dermatitis is a socially significant health problem. This review provides a discussion on the clinical features and patterns as well as the differential diagnosis of hand dermatitis, because these are essential for proper diagnosis in clinical practice. The morphology, however, is poorly related to the etiology in chronic cases. In all cases of chronic hand dermatitis, a full diagnostic examination should be undertaken and the etiology should be clarified and addressed in the treatment concept, instead of just moving directly from a morphological diagnosis to therapy. Preventive measures should be included in the treatment concept according to etiology. A stepwise approach for escalating therapy is advised, including basic topical therapy, topical corticosteroids, calcineurin inhibitors, as well as phototherapy and systemic therapy with corticosteroids, alitretinoin, cyclosporine, methotrexate, azathioprine, and others.

Characteristics and provision of care in patients with chronic hand eczema: updated data from the CARPE registry.

The aim of the CARPE registry is to investigate characteristics and medical care in patients affected by chronic hand eczema. Patients are assessed by dermatological examination and patient questionnaire. Socio-economic and clinical data are collected, and quality of life is measured using the Dermatology Life Quality Index (DLQI). A total of 1,163 patients with chronic hand eczema were eligible for analysis (mean age 47.0 years; 54.6% female; mean disease duration 7.6 years). At inclusion, chronic hand eczema was very severe in 23.4%, severe in 47.0%, moderate in 20.1%, and clear or almost clear in 9.6% of patients. Median DLQI was 8.0. In all, 93.8% of patients reported use of topical corticosteroids, 25.6% systemic antihistamines, 28.3% topical calcineurin-inhibitors, 38.0% ultraviolet phototherapy, and 35.3% systemic treatment (19.7% alitretinoin) prior to inclusion in the registry. A significant proportion of patients may not receive adequate treatment according to the guideline on management of hand eczema.

Management of chronic hand eczema.

Hand eczema (HE) is one of the most frequent skin diseases and has often a chronically relapsing course with a poor prognosis resulting in a high social and economic impact for the individual and the society. In this article, we highlight the results of an expert workshop on the 'management of severe chronic hand eczema' with the focus on the epidemiology, the burden of severe HE, its classification and diagnostic procedures, and the current status of treatment options according to an evidence-based approach (randomized controlled clinical trials, RCTs). We conclude that despite the abundance of topical and systemic treatment options, disease management in patients with severe chronic HE is frequently inadequate. There is a strong need for RCTs of existing and new treatment options based on clearly diagnosed subtypes of HE and its severity.

Prevention of experimentally induced irritant contact dermatitis by extracts of Isatis tinctoria compared to pure tryptanthrin and its impact on UVB-induced erythema.

Lipophilic extracts of Isatis tinctoria L. exhibit significant activity against several clinically relevant targets of inflammation. The alkaloid tryptanthrin was identified as one of the active principles in woad and characterised as a potent dual inhibitor of COX-2 and 5-LOX. Here, the anti-inflammatory efficacy of topical application of three different Isatis extracts and tryptanthrin was investigated in human volunteers. Two different models were used, namely the sodium lauryl sulphate (SLS)-induced irritant contact dermatitis (ICD) and UVB-induced erythema. Twenty healthy volunteers without any skin disease participated in the study. Cumulative irritant contact dermatitis was induced on test fields on the volunteers' backs by twice daily application of 0.5 % sodium lauryl sulphate over a period of four days. Half of the test fields were treated with the test substances during the eliciting phase, while the remaining test fields were treated over a period of 4 days after induction of dermatitis. In the second model, a UVB erythema on the volunteers' lower backs was induced using the double minimal erythema dose (MED). Twenty-four hours after irradiation the test fields were treated with the test substances over a period of 3 days. All reactions were assessed visually and by non-invasive bioengineering methods (evaporimetry and chromametry). Treatment with extracts during the ICD eliciting phase led to a significantly smaller increase of visual scores and transepidermal water loss compared to the untreated test field. For tryptanthrin this benefit was also observed, but the improvement was not statistically significant. When treatment was performed after completing the eliciting phase, accelerated resolution of the irritant reaction could not be observed. In the UVB erythema model anti-inflammatory effects of the test substances were not observed.

Effects of electrostimulation on glycogenolysis in cultured rat myotubes.

A model for electrostimulation causing contractions of primary cultures of rat myotubes was established. The kinetics of glycogen degradation was investigated for a 2-h period to elucidate the coupling between contraction and glycogenolytic flux. Electrostimulation caused contraction and increased glycogenolytic flux, but had no effect on glycogen phosphorylase-a activity. Forskolin increased glycogenolytic flux more than electrostimulation, and caused a fast activation of glycogen phosphorylase, while it did not elicit contraction. The effects of electrostimulation and forskolin on glycogenolytic flux were partly additive. The metabolism of glucose and glycogen was almost equally anaerobic and aerobic. The ATP content remained constant during glycogenolysis, but phosphocreatine decreased with the largest decrease in electrostimulated cells. The calculated ATP turnover rate increased about 3 times by electrostimulation. For all conditions, pHi decreased from about 7.0 to about 6.6 at 2 h. It is concluded that in the present in vitro system glycogenolytic flux may be enhanced without eliciting contraction, a condition normally not observed in vivo. The system also shows much less dynamic range of energy metabolism than in vivo, primarily because of a high resting ATP turnover.

A comparative study on the skin penetration of pure tryptanthrin and tryptanthrin in Isatis tinctoria extract by dermal microdialysis coupled with isotope dilution ESI-LC-MS.

The indolo[2,1- b]quinazoline alkaloid tryptanthrin has recently been identified as a pharmacologically active compound in Isatis tinctoria, with potent dual inhibitory activity on prostaglandin and leukotriene synthesis. To investigate the skin penetration of tryptanthrin from solutions of pure compound and Isatis extracts, we developed and validated a cutaneous microdialysis model using ex vivo pig foreleg. Microdialysis was performed by placing linear probes in the dermis of the skin in situ, and tryptanthrin concentrations in the dialysates were determined by isotope dilution electrospray ionization LC-MS in the selected ion mode. Measurable concentrations of tryptanthrin were detected 30 min after application. A dose-dependent increase in tryptanthrin concentrations in the dialysate was observed for the Isatis extracts, but not for pure tryptanthrin. Microscopic analysis showed that the pure compound crystallized from the solution but remained in an amorphous state in the extracts.