Validation of questionnaire algorithm based on repeated open application testing with the constituents of fragrance mix II: the EDEN Fragrance Study.

BACKGROUND: In a European study on contact allergy in the general population, it has been hypothesized that the combination of contact allergy to a fragrance together with a history indicating dermatitis at exposure and thereafter subsequent avoidance of scented products implied a diagnosis of allergic contact dermatitis. OBJECTIVES: The primary aim of this study was to validate this hypothesis/algorithm. The secondary aim was to investigate whether there was any association between the outcome of the recent repeated open application test (ROAT) and the patch test reactivity. METHODS: One hundred nine subjects with and without contact allergy to fragrance mix II (FM II) were recruited. Volunteers from six European dermatology clinics participated in the study including a patch test and a ROAT. RESULTS: Twenty-four positive ROAT reactions were noted in total including 20 of those 32 with contact allergy to FM II. None of the volunteers reacted to the vehicle (P < 0.001). More individuals with a positive algorithm had positive ROATs when compared with those with a negative algorithm. However, the difference was not statistically significant (P = 0.12). The lower the patch test concentration eliciting a positive test reaction, the more likely was a positive ROAT and the more likely that the positive ROAT appeared early during the investigative period. CONCLUSIONS: The algorithm used in this study was not validated but it was indicated in this ROAT setup. The stronger the patch test reactivity the more likely was a positive ROAT and the more likely it was that the positive ROAT appeared early during the application period.

[Pre- and post-interventional skin care for laser and peel treatments]. / Prä- und postinterventionelle Hautpflege bei Laser- und Peelingbehandlungen.

Treating the signs of skin ageing or acne scars by chemical peels or ablative lasers is increasingly used worldwide. Due to their reduced invasiveness, these methods are often favored over aesthetic surgical interventions. Both procedures rely on the principle of controlled damage to the skin. The subsequent regeneration may lead to the development of new epidermal (and dermal) tissue and therefore improve the skin's aesthetic appearance. At present, there are no official guidelines in Germany concerning pre- and post-interventional skin care, which is currently based on the personal experiences and evaluations of the practitioner. It is known that an appropriate treatment regime can improve the outcome and reduces downtime pre- and post-laser as well as pre- and post-peel. The aim of this article is to present the different possibilities of pre- and post-interventional care. In most cases, priming includes intense ultraviolet (UV) protection, topical retinoids as well as skin brightening agents, and occasionally oral herpes simplex prophylaxis. In order to support post-interventional wound healing, skin care should modulate inflammation and balance skin hydration. In addition to light moisturizers, broad spectrum UV protection as well as the avoidance of sports and sweating are essential.

[Phototherapy in the "City of Light" Jena]. / Phototherapie in der "Lichtstadt" Jena.

In 1801, ultraviolet (UV) radiation was first described in Jena (Germany). Over the course of the last 200 years, the city has developed into a university and industry center for glass production, optics and spectroscopy. How this development influenced dermatotherapy in Jena is the subject of this article. In the late 19th century, the developing glass and optic industry of Jena played a leading role in the production of electric lamps for therapeutic use. Although production in Jena did not become established for dermatotherapeutic lamps, Jena glassmakers remained a supplier of UV filters. The industry's fortunes were generously spent on development of the city and university and enabled the creation of a dermatology clinic in an independent building. A department of radio- and phototherapy was established and since then has been part of the dermatology clinic's therapeutic portfolio. Although the city of Jena faced heavy economic repression, the industry and the dermatology clinic's scientific activity expanded to fluorescence and protein diagnostics in the early 1960s. Investigations by Professor Heinz Langhof led to the description of erythropoietic protoporphyria (EPP) simultaneously, but independently from English colleagues, whose publication is considered EPP's first description. The first functioning laser in the former German Democratic Republic was built at the university, although the first laser beam was created by a research group in Berlin a short time before. Use of laser technology in the dermatology department proceeded only after political changes began. Despite economic hardships, excellent research was done in Jena through intense collaborations. The dermatology clinic has thus been able to offer modern phototherapy from the very beginning.

Basal cell carcinoma risk and solar UV exposure in occupationally relevant anatomic sites: do histological subtype, tumor localization and Fitzpatrick phototype play a role? A population-based case-control study.

BACKGROUND: A two-fold risk increase to develop basal cell carcinoma was seen in outdoor workers exposed to high solar UV radiation compared to controls. However, there is an ongoing discussion whether histopathological subtype, tumor localization and Fitzpatrick phototype may influence the risk estimates. OBJECTIVES: To evaluate the influence of histological subtype, tumor localization and Fitzpatrick phototype on the risk to develop basal cell carcinoma in highly UV-exposed cases and controls compared to those with moderate or low solar UV exposure. METHODS: Six hundred forty-three participants suffering from incident basal cell carcinoma in commonly sun-exposed anatomic sites (capillitium, face, lip, neck, dorsum of the hands, forearms outside, décolleté) of a population-based, case-control, multicenter study performed from 2013 to 2015 in Germany were matched to controls without skin cancer. Multivariate logistic regression analysis was conducted stratified for histological subtype, phototype 1/2 and 3/4. Dose-response curves adjusted for age, age2, sex, phototype and non-occupational UV exposure were calculated. RESULTS: Participants with high versus no (OR 2.08; 95% CI 1.24-3.50; p = 0.006) or versus moderate (OR 2.05; 95% CI 1.15-3.65; p = 0.015) occupational UV exposure showed a more than two-fold significantly increased risk to develop BCC in commonly UV-exposed body sites. Multivariate regression analysis did not show an influence of phototype or histological subtype on risk estimates. The restriction of the analysis to BCC cases in commonly sun-exposed body sites did not influence the risk estimates. The occupational UV dosage leading to a 2-fold increased basal cell carcinoma risk was 6126 standard erythema doses. CONCLUSION: The risk to develop basal cell carcinoma in highly occupationally UV-exposed skin was doubled consistently, independent of histological subtype, tumor localization and Fitzpatrick phototype.

Validation of a questionnaire algorithm based on repeated open application testing with the constituents of fragrance mix I.

BACKGROUND: In a European study on contact allergy in the general population, it was hypothesized that the combination of contact allergy to a fragrance together with a history indicating dermatitis at exposure, and thereafter subsequent avoidance of scented products, implied a diagnosis of allergic contact dermatitis. OBJECTIVES: The primary aim of this study was to validate this hypothesis and algorithm. The secondary aim was to investigate whether there was any association between the outcome of the repeated open application test (ROAT) and the patch test reactivity. METHODS: In total, 109 patients with and without contact allergy to fragrance mix (FM) I were recruited. Volunteers from six European dermatology clinics participated in the study including a patch test and a ROAT. RESULTS: Positive ROAT reactions were noted in 26 of the 44 volunteers with contact allergy to FM I. None of the volunteers reacted to the vehicle (P < 0·001). More individuals with a positive algorithm had positive ROATs than those with a negative algorithm. However, the difference was not statistically significant. The lower the patch test concentration eliciting a positive test reaction, the more likely a positive ROAT and the more likely that the positive ROAT appeared early during the investigative period. CONCLUSIONS: The algorithm used in this study was not substantiated in this ROAT set-up. The stronger the patch test reactivity the more likely was a positive ROAT and the more likely it was that the positive ROAT appeared early during the application period. What's already known about this topic? To the best of our knowledge, a scientifically designed and conducted repeated open application test (ROAT) has never been performed before to validate a diagnosis of allergic contact dermatitis partly based on a questionnaire. What does this study add? This is the largest controlled, randomized and blinded ROAT performed to date. Higher patch test reactivity to fragrance mix I indicated a greater likelihood of a positive ROAT. What are the clinical implications of this work? Further refinement of the questions is required in order to diagnose allergic contact dermatitis from fragrances based on a questionnaire.

Efficacy and safety of topical delgocitinib in patients with chronic hand eczema: data from a randomized, double-blind, vehicle-controlled phase IIa study.

BACKGROUND: Management of chronic hand eczema (CHE) remains a challenge; effective topical treatment is limited to corticosteroids. OBJECTIVES: To assess the efficacy and safety of a novel, pan-Janus kinase inhibitor (delgocitinib) in patients with CHE. METHODS: In this randomized, double-blind, phase IIa study, patients with CHE received delgocitinib ointment 30 mg g-1 or vehicle ointment for 8 weeks. The primary end point was the proportion of patients achieving treatment success ['clear'/'almost clear' skin with ≥ 2-point improvement in the Physician's Global Assessment of disease severity (PGA)] at week 8. Secondary end points included Hand Eczema Severity Index (HECSI) score changes and the proportion of patients achieving treatment success on the Patient's Global Assessment of disease severity (PaGA). RESULTS: Ninety-one patients were randomized. More patients receiving delgocitinib (46%) than vehicle (15%) [odds ratio 4·89, 95% confidence interval (CI) 1·49-16·09; P = 0·009] achieved treatment success (PGA). Adjusted mean HECSI score at week 8 was lower with delgocitinib (13·0) than with vehicle (25·8) (adjusted mean difference -12·88, 95% CI -21·47 to -4·30; P = 0·003). More patients receiving delgocitinib than vehicle achieved treatment success by PaGA, but this did not reach statistical significance. The incidence of adverse events was similar with delgocitinib and vehicle; none led to discontinuation of delgocitinib. CONCLUSIONS: Delgocitinib ointment was efficacious and well tolerated. As a plateau of efficacy was not observed, a longer treatment period may lead to increased efficacy. Further clinical studies are warranted to confirm these findings in patients with CHE. What's already known about this topic? Chronic hand eczema (CHE) has a significant burden. Few randomized controlled studies have evaluated current treatments for CHE; only limited data are available to inform and guide clinical practice decisions. There is currently an unmet need for efficacious and well-tolerated topical treatment options for patients with CHE. What does this study add? Delgocitinib is a novel, pan-Janus kinase (JAK) inhibitor specific for JAK1, JAK2, JAK3 and tyrosine kinase 2. Topical use of delgocitinib ointment resulted in clearance of CHE after 8 weeks of treatment in a significantly greater number of patients than vehicle; delgocitinib was also well tolerated. Results from this proof-of-concept clinical study suggest that topical delgocitinib may provide therapeutic benefit to patients with CHE with inadequate responses to topical corticosteroids.

Hand eczema: epidemiology, prognosis and prevention.

Hand eczema (HE) is a heterogeneous and often chronic disease located to the hands and wrist, and frequently associated with eczema on the feet. The aetiology is diverse, and the eczema may present with a variety of clinical symptoms. Acute and chronic stages appear; severity varies from mild to moderate and severe, and flares may be frequently recurrent or rare. The divergent aetiology and varied morphology of HE is sometimes tricky and may be challenging to the dermatologist. This review has focus on epidemiology, prognosis and prevention of HE, and intends to point towards some practical advice on how to diagnose, inform and guide HE patients.

Hand eczema: treatment.

Hand eczema is a highly prevalent, multietiological disease with a wide spectrum of severity and chronicity. The treatment of hand eczema, especially in severe and chronic cases, is a challenge to the dermatologist requiring not only diagnostic and therapeutic, but also excellent patient communication skills. This review discusses the spectrum of therapeutic options for hand eczema, the evidence for their efficacy and safety, and proposes a stepwise approach of intensity of treatment depending on disease severity and chronicity. In the near future, hand eczema patients may benefit from new therapeutic principles such as biologics for the treatment of atopic eczema and topical Janus Kinase inhibitors.

[Dermatophytosis caused by rare anthropophilic and zoophilic agents]. / Dermatophytosen, verursacht durch seltene anthropophile und zoophile Erreger.

The basis for effective treatment of any dermatomycosis is the correct and timely identification of the pathogen, which allows the targeted choice of the most suitable antimycotic and is important for the prevention of repeated infections. In recent years, infections with dermatophytes seem to have increased. In fact, from 2007 to 2018, there was an increase in the number of samples processed in the Mycology Laboratory of the Department of Dermatology at the University Hospital Jena. The most common isolated dermatophytes between 2007 and 2018 were Trichophyton (T.) rubrum, T. interdigitale, Microsporum (M.) canis and T. benhamiae. However, dermatophytoses may also be caused by rare anthropophilic agents such as Epidermophyton floccosum, zoophiles such as T. verrucosum, T. quinckeanum or Nannizzia (N.) persicolor as well as by geophiles such as N. gypsea. Therefore, these dermatophytes should at least be known, so that in case of unusual observations investigations can be performed accordingly. Changes in the pathogen spectrum of dermatophytoses have taken place over time and it is expected that the occurrence of dermatophytes will be subject of continuous fluctuations, which may mean that the incidence of some of these "rare" dermatophytes, as described here in five clinical examples, may be changing.

Innate immune response of human epidermal keratinocytes and dermal fibroblasts to in vitro incubation of Trichophyton benhamiae DSM 6916.

BACKGROUND: Superficial cutaneous infection caused by the zoophilic dermatophyte Trichophyton benhamiae is often associated with a highly inflammatory immune response. As non-professional immune cells, epidermal keratinocytes and dermal fibroblasts contribute to the first line of defence by producing pro-inflammatory cytokines and antimicrobial peptides (AMP). OBJECTIVE: Purpose of this study was to gain a deeper understanding of the pathogenesis and the fungal-host interaction as not much is known about the innate immune response of these cutaneous cells against T. benhamiae. METHODS: Using a dermatophytosis model of fibroblasts and keratinocytes incubated with T. benhamiae DSM 6916, analyses included determination of cell viability and cytotoxicity, effects on the innate immune response including expression and secretion of pro-inflammatory cytokines/chemokines and expression of AMP, as well as alterations of genes involved in cell adhesion. RESULTS: Trichophyton benhamiae DSM 6916 infection led to severe cell damage and direct induction of a broad spectrum of pro-inflammatory cytokines and chemokines in both cutaneous cells. Only keratinocytes differentially up-regulated AMP genes expression after T. benhamiae DSM 6916 infection. Expression of AMPs in fibroblasts was not inducible by fungal infection, whereas their absences potentially contributed to a continuous increase in the fungal biomass on fibroblasts, which in turn was reduced in keratinocytes possibly due to the antimicrobial actions of induced AMPs. On mRNA level, T. benhamiae DSM 6916 infection altered cell-cell contact proteins in keratinocytes, indicating that targeting specific cell-cell adhesion proteins might be part of dermatophytes' virulence strategy. CONCLUSION: This study showed that in addition to immune cells, keratinocytes and fibroblasts could participate in antimicrobial defence against an exemplary infection with T. benhamiae DSM 6916.

Mating analyses of Trichophyton benhamiae offspring reveals linkage of genetic markers used in taxonomy.

Mating experiments were conducted with four clinical Trichophyton benhamiae isolates, genetically similar to the Trichophyton benhamiae CBS 112371, featuring the plus mating type and with two minus type strains. One minus type strain belonged to the white subgroup, and the other minus type strain, DSM 6916, showed genetic kinship to the yellow subgroup. Only two plus type strains were able to form mature, pigmented gymnothecia with DSM 6916. These two plus type strains demonstrated dark pigmentation and powdery mycelium on Takashio agar, whereas the other three strains exhibited a low degree of pigmentation on the same medium. All five plus strains were able to mate with the minus type strain of their own white subgroup. Cultures from single ascospore isolates showed highly variable morphology and pigmentation. Three genetic markers (ITS, mating type, EF1 alpha) were analyzed in polymerase chain reaction (PCR) experiments with optimized primers and PCR conditions to discriminate between subgroups. Furthermore, RAPD-PCR was used to generate a DSM 6916-specific DNA-fragment which served as an additional genetic marker. Assessing the isolates with recombinant genotypes, it was found that three genetic markers behave like linked genes. The recombination of plus mating type went together with ITS, EF1 alpha and RAPD marker of the DSM 6916 parental strain and was most frequently isolated, whereas plus types recombinants in this case were completely missing. This shows a high imbalance in mating type distribution of recombinants.

[When sunscreens do not help: allergic contact dermatitis to UV filters]. / Wenn Sonnenschutzprodukte nicht mehr helfen: Allergisches Kontaktekzem auf UV-Filter.

Ultraviolet (UV) filters may cause allergic and more frequently photoallergic contact dermatitis. Therefore, a photopach test should always be performed in case of a suspected contact sensitivity to UV filters. We report a case of a 65-year-old woman with a recurrent erythema of the face and décolleté after sun exposure despite application of a sunscreen. The (photo)patch test revealed a contact sensitivity to the UV filter butyl-methoxybenzoylmethane. Treatment with a topical glucocorticoid and avoidance of the particular UV filter led to a rapid improvement.