Baseline characteristics, disease severity and treatment history of patients with atopic dermatitis included in the German AD Registry TREATgermany.

BACKGROUND: The Atopic Dermatitis (AD) TREATgermany registry was initiated by the German Society for Dermatology (DDG) in 2011 to evaluate the 'real-life' situation of health care for patients with AD. OBJECTIVES: Interim data analysis on baseline characteristics as well as current and prescribed systemic treatments of the TREATgermany registry patients. METHODS: Patients (≥18 years) with moderate-to-severe AD [objective (o)SCORAD > 20], or with current or previous anti-inflammatory systemic treatment for AD within 24 months, were included and are followed up over at least 24 months. To assess clinical signs, the eczema area severity index (EASI, 0-72), the oSCORAD (0-83) and the Investigator Global Assessment (IGA; 6-point scale) were used. The disease severity was globally scored by the patients [Patient Global Assessment (PGA); six-step Likert scale]. Disease symptoms were assessed by the patient-oriented eczema measure (POEM, 0-28) and numeric rating scales (NRS, 0-10). Health-related quality of life was measured using the dermatological life quality index (DLQI, 0-30). RESULTS: A total of 612 patients were recruited across 32 sites between 06/2016 and 01/2019 (mean age: 42.6 ± 14.2 years; mean oSCORAD: 40.8 ± 16.3). The mean POEM score was 16.3 ± 7.5. Pruritus was rated highest among subjective symptoms (NRS: 5.4 ± 2.7). The mean DLQI value was 11.3 ± 7.5. The frequency of arterial hypertension was lower (20.8%) compared with the general population, whilst this was higher for depression (10%). More than 60% of the patients had received systemic glucocorticosteroids, and 36.8% had received cyclosporine A prior to inclusion. Dupilumab was the leading substance documented as either 'current' (12.1%) or 'prescribed' (31.4%) at baseline. CONCLUSIONS: These 'real-life' data clearly demonstrate the substantial disease burden. Most of TREATgermany patients were already treated with or prescribed dupilumab at baseline. Moreover, current findings indicate the urgent need for further alternative agents in order to achieve a perceptible improvement of quality of life of patients with moderate-to-severe AD.

[Decreased professional performance and quality of life in patients with moderate-to-severe atopic eczema : Results from the German atopic eczema registry TREATgermany]. / Verminderte berufliche Leistungsfähigkeit und Lebensqualität bei Patienten mit moderater bis schwerer Neurodermitis : Ergebnisse aus dem Deutschen Neurodermitisregister TREATgermany.

BACKGROUND: Clinical registries may provide high-quality evidence on the use and effectiveness of therapeutic interventions under real-life conditions. Adults with moderate-to-severe atopic eczema (atopic dermatitis [AD]) are enrolled into TREATgermany and prospectively followed over at least 2 years. This paper analyses the association between dermatological quality of life and work limitations. MATERIALS AND METHODS: Treatment modalities and a broad set of physician- and patient-reported outcome measures are documented using validated instruments to assess clinical disease severity (EASI [Eczema Area and Severity Index], objective SCORAD [objective-SCORing Atopic Dermatitis]), quality of life (DLQI [Dermatology Life Quality Index]), symptoms (POEM [Patient-oriented Eczema Measure]), global disease severity, as well as patient satisfaction and work limitations including presenteeism (WLQ [Work Limitation Questionnaire]). From 06/2016 until 12/2017, 241 individuals (mean age 43 ± 15 years, 38.6% female) were enrolled at 19 recruitment centers; 69% of the patients were employed. RESULTS: Employed persons had DLQI and WLQ scores of 10.6 ± 6.9 points and 17.7 ± 18.1%, respectively. Mean presenteeism was substantial accounting for 9.2%. With coefficients of 0.39 and 0.33 WLQ and presenteeism scores significantly correlate with DLQI (p < 0.000). Bootstrapped regression models showed that the limitations in coping with work requirements increase by 1.7% as DLQI increases by one point. Lower quality of life due to AD is most strongly associated with limitations in the area of physical and performance requirements in general. Presenteeism increases by 0.5% as DLQI increases by one point. CONCLUSION: Moderate-to-severe AD has substantial adverse economic impact with mean productivity loss of patients of almost 10%. Future analyses from TREATgermany will address the impact of innovative treatment modalities on quality of life and work productivity of patients with moderate-to-severe AD.

Guideline: vulvovaginal candidosis (AWMF 015/072), S2k (excluding chronic mucocutaneous candidosis).

The oestrogenised vagina is colonised by Candida species in at least 20% of women; in late pregnancy and in immunosuppressed patients, this increases to at least 30%. In most cases, Candida albicans is involved. Host factors, particularly local defence mechanisms, gene polymorphisms, allergies, serum glucose levels, antibiotics, psycho-social stress and oestrogens influence the risk of candidal vulvovaginitis. Non-albicans species, particularly Candida glabrata, and in rare cases also Saccharomyces cerevisiae, cause less than 10% of all cases of vulvovaginitis with some regional variation; these are generally associated with milder signs and symptoms than normally seen with a C. albicans-associated vaginitis. Typical symptoms include premenstrual itching, burning, redness and odourless discharge. Although itching and redness of the introitus and vagina are typical symptoms, only 35-40% of women reporting genital itching in fact suffer from vulvovaginal candidosis. Medical history, clinical examination and microscopic examination of vaginal content using 400× optical magnification, or preferably phase contrast microscopy, are essential for diagnosis. In clinically and microscopically unclear cases and in chronically recurring cases, a fungal culture for pathogen determination should be performed. In the event of non-C. albicans species, the minimum inhibitory concentration (MIC) should also be determined. Chronic mucocutaneous candidosis, a rarer disorder which can occur in both sexes, has other causes and requires different diagnostic and treatment measures. Treatment with all antimycotic agents on the market (polyenes such as nystatin; imidazoles such as clotrimazole; and many others including ciclopirox olamine) is easy to administer in acute cases and is successful in more than 80% of cases. All vaginal preparations of polyenes, imidazoles and ciclopirox olamine and oral triazoles (fluconazole, itraconazole) are equally effective (Table ); however, oral triazoles should not be administered during pregnancy according to the manufacturers. C. glabrata is not sufficiently sensitive to the usual dosages of antimycotic agents approved for gynaecological use. In other countries, vaginal suppositories of boric acid (600 mg, 1-2 times daily for 14 days) or flucytosine are recommended. Boric acid treatment is not allowed in Germany and flucytosine is not available. Eight hundred-milligram oral fluconazole per day for 2-3 weeks is therefore recommended in Germany. Due to the clinical persistence of C. glabrata despite treatment with high-dose fluconazole, oral posaconazole and, more recently, echinocandins such as micafungin are under discussion; echinocandins are very expensive, are not approved for this indication and are not supported by clinical evidence of their efficacy. In cases of vulvovaginal candidosis, resistance to C. albicans does not play a significant role in the use of polyenes or azoles. Candida krusei is resistant to the triazoles, fluconazole and itraconazole. For this reason, local imidazole, ciclopirox olamine or nystatin should be used. There are no studies to support this recommendation, however. Side effects, toxicity, embryotoxicity and allergies are not clinically significant. Vaginal treatment with clotrimazole in the first trimester of a pregnancy reduces the rate of premature births. Although it is not necessary to treat a vaginal colonisation of Candida in healthy women, vaginal administration of antimycotics is often recommended in the third trimester of pregnancy in Germany to reduce the rate of oral thrush and napkin dermatitis in healthy full-term newborns. Chronic recurrent vulvovaginal candidosis continues to be treated in intervals using suppressive therapy as long as immunological treatments are not available. The relapse rate associated with weekly or monthly oral fluconazole treatment over 6 months is approximately 50% after the conclusion of suppressive therapy according to current studies. Good results have been achieved with a fluconazole regimen using an initial 200 mg fluconazole per day on 3 days in the first week and a dosage-reduced maintenance therapy with 200 mg once a month for 1 year when the patient is free of symptoms and fungal infection (Table ). Future studies should include Candida autovaccination, antibodies to Candida virulence factors and other immunological experiments. Probiotics with appropriate lactobacillus strains should also be examined in future studies on the basis of encouraging initial results. Because of the high rate of false indications, OTC treatment (self-treatment by the patient) should be discouraged.

[Phlebology in German departments of dermatology. An analysis on behalf of the German Society of Phlebology]. / Phlebologie an deutschen Hautkliniken. Eine Bestandsaufnahme im Auftrag der Deutschen Gesellschaft für Phlebologie.

BACKGROUND: Phlebologic diseases have become extremely common and have major socio-economic impact. However, the percentage of dermatologists working in phlebology appears to be decreasing according to the data of the German Society of Phlebology (DGP). METHODS: To investigate the reasons for this development, we--on behalf of the DGP--sent a questionnaire to 120 German Departments of Dermatology in autumn 2012. RESULTS: In 76 returned questionnaires, the number of physicians with additional fellowship training in phlebology averaged 1.5; the average number of those who fulfill the criteria for training fellows in phlebology was 0.9. In 71.1 % of the departments there was a phlebologist. A special phlebologic outpatient clinic existed in 73.7 % of the departments. Sonography with Doppler (89.5 %) and duplex (86.8 %) was used as the most frequent diagnostic tool. For therapy, compression (94.7 %), sclerotherapy (liquid 78.9 %, foam 63.2 %, catheter 18.4 %), endoluminal thermic procedures (radio wave 28.9 %, laser 17.1 %) and surgery (especially crossectomy and stripping 67.1 %, phlebectomy of tributaries 75 %) were used. The average number of treatments was very heterogenous in the different departments. CONCLUSIONS: Phlebology definitely plays an important role in dermatology. Most departments fulfill the formal criteria for the license to conduct advanced training in phlebology. A wide spectrum of phlebological diagnostic and therapeutic procedures is available.

Onychomycosis.

The guideline on onychomycosis, as passed by the responsible German medical societies, is presented in the present study.

Tinea capitis: ringworm of the scalp.

The guideline tinea capitis, as passed by three German medical societies, is presented in the present study.

Epidemiology and clinical classification of onychomycosis.

OBJECTIVES: To review recent data - what is new in the epidemiology of onychomycoses? To identify the most relevant diagnostic criteria for effective therapy. METHODS: The preliminary results of the European Onychomycosis Observatory (EUROO) study were analysed. In this international study, physicians completed questionnaires concerning patient profile and the disease. RESULTS: One of the most interesting novel findings was that sampling requests were often not made [only 3.4% of general physicians (GPs) and 39.6% of dermatologists]. This means that no information about causative agent(s) was available, hindering appropriate treatment choice. Furthermore, contrary to previous findings, 70.7% of participants did not practice sports. Lastly, these preliminary findings showed that treatment strategy depends largely on the type of treating physician, with GPs preferring monotherapy and dermatologists preferring combination therapy. CONCLUSIONS: A consensus was reached that treatment strategy should depend on the severity of nail involvement and the causative fungus. It is thus important to promote the importance of sampling. To simplify the choice of an appropriate treatment, onychomycosis may be divided into just two clinical groups: onychomycosis with and without nail matrix area involvement. However, the distinct clinical findings (number and type of affected nails, multimorbidity, drug interaction, etc.) in each individual case must be taken into account to ensure an appropriate treatment decision.

Treatment options--development of consensus guidelines.

BACKGROUND: There are currently three main treatment strategies for onychomycosis: topical, oral and combination. Amorolfine nail lacquer appears to be the most effective form of topical monotherapy. However, the best mycological and clinical cure rates are obtained with combination therapy. Combination therapy increases antifungal spectrum, fungicidal activity and safety. New antifungals (triazoles and echinocandins) were recently developed, enabling new protocols. OBJECTIVES: To review available therapies. To design an algorithm for the management of onychomycoses in daily practice. RESULTS: Therapeutic choice should be based on numerous factors including patient's age and health, aetiology, extent of involvement and clinical form. The consensus was that topical monotherapy is recommended when < 50% of the nail is affected without matrix area involvement. Oral monotherapy or combination therapy is indicated when > 50% of the nail, including the matrix area, is involved. Topical treatments should not be used alone when topical drug transport is suboptimal (i.e. when dermatophytoma, onycholysis or spikes are present). Chemical or mechanical removal should also be considered whenever applicable (interruption of drug transport). CONCLUSION: In conclusion, treatment decision-making tools (e.g. an illustrated booklet or CD-ROM presenting each type of onychomycosis and criteria to be considered before selecting treatment regimen) would be valuable supports for the successful treatment of onychomycoses.

Artificial disruption of skin barrier prior to irritant patch testing does not improve test design.

BACKGROUND: Irritant patch testing is often performed as a 24- or 48-h occlusive patch test with low concentrations of sodium lauryl sulphate (SLS). OBJECTIVES: The aim of this study was to investigate potential ways to shorten this test procedure and obtain precise test results. PATIENTS AND METHODS: Thirty-six healthy volunteers underwent irritant patch testing with different pretreatments (PT) of the test fields. Occlusive test chambers were applied on the upper back with SLS 0.5%, 1%, 2% and 5% in large Finn Chambers(R). The patches were removed after 4 and 24 h, respectively, depending on the concentration used. Test fields were pretreated as follows: PT 0, field without any PT (control); PT 1, prick with lancet; PT 2, prick with test stamp; PT 3, scratch with lancet; PT 4, incision with standardized incision instrument (0.1-0.2 mm depth). Skin reactions were evaluated by transepidermal water loss (TEWL), skin erythema and skin hydration and as well by a visual score (VS) at 4, 24 and 72 h. RESULTS: Our data show an obvious distinction between PT 0-2 and PT 3-4 at all measurement methods. The average TEWL values with PT 3-4 were higher than those with PT 0-2, especially on the 4-h course. This distinction may derive from the shape and size of the skin impairment achieved by PT 3-4, leading to a mechanical barrier disruption. However, SLS may infiltrate directly into deeper skin layers supported by capillarity. Consequently, no or little penetration through the epidermis and interaction with its structures occurs, which is responsible for irritant skin reactions. The SLS dose in the upper skin layers is therefore lower at these PTs. The lower remaining dose of SLS also explains this distinction, especially for the VS. Additionally, there are presumed reactions in deeper layers of the epidermis and dermis at PT 3-4. CONCLUSIONS: In summary, all data suggest a different reaction pattern from the classical irritant response. Therefore, application without any PT seems to be best suited for irritancy skin testing, especially for visual assessment. PTs prior to irritant patch testing have been shown to be unjustifiable.

[Nail changes during childhood]. / Nagelveränderungen im Kindesalter.

Nail changes occur frequently in adults, but are relatively rare in children. There are, however, certain nail changes that emerge particularly during childhood. Ingrown nails, onychoschizia, congenital slanted alignment of the large toenail, and psoriasiform nail dystrophies can be frequently observed in toddlers and in schoolchildren the syndrome of an ingrown nail, nail artifacts, periungual warts or fibromas, trachyonychia, and nail mycoses. Connatal nail changes can appear as isolated events or together with other symptoms whereas acquired nail changes are caused by infections, traumatic injuries, or tumors, in conjunction with skin diseases or general illnesses, or even develop spontaneously.

Effects of skin occlusion in patch testing with sodium lauryl sulphate.

BACKGROUND: When evaluating transepidermal water loss (TEWL) in patch testing, the occlusive effect of the patch must be considered as an important artificial impairment of the measurement. OBJECTIVES: To investigate the time course of effects of occlusion. METHODS: Epicutaneous patches with sodium lauryl sulphate (SLS) 0.25%, SLS 0.5%, water and an empty test chamber (control) were applied on the volar forearm for different time intervals (12, 24, 48 h). Test reactions were evaluated by measurement of TEWL immediately, every 15 min during the first hour, every 30 min during the following 3 h and 24 h after patch removal. RESULTS: After patch removal, TEWL values showed a steep increase. When compared with basal values, TEWL values after SLS patch testing remained increased for 24 h, whereas TEWL values on water patch sites were only significantly increased for up to 180 min, and on empty patch sites for only up to 120 min after patch removal. The prolonged increase in TEWL values in SLS patch testing seemed to be induced by barrier function damage caused by SLS itself, as shown in various earlier studies. After the initial increase, TEWL values showed a significant decrease for all patches from 0 to 120 min after patch removal. Patch testing with water gave a significant decrease in TEWL values up to 180 min, and for empty chambers (control) up to 150 min after removal of patches. These data suggest that the occlusive effect on TEWL in patch testing ends 3 h after the removal of test chambers. CONCLUSIONS: We recommend TEWL measurement in SLS patch testing after a period of at least 3 h after patch removal. For practical purposes a 24-h period after patch removal may be useful.

Changes in skin physiology during bath PUVA therapy.

BACKGROUND: Frequent bathing leads to a skin barrier damage with various changes in physiological skin parameters. Conversely, ultraviolet (UV) irradiation may improve the impaired skin barrier by reducing inflammatory reactions. OBJECTIVES: The aim of this study was to investigate the changes of physiological skin parameters during a therapy with 8-methoxypsoralen (8-MOP) bathing and subsequent UVA irradiation. METHODS: Thirty patients with a skin disease without barrier disruption were treated with daily bathing in a 8-MOP solution (0.0005%) and subsequent UVA irradiation. Multiple physiological skin parameters (transepidermal water loss, skin blood flow, skin colour, sebum content, skin hydration) were measured repeatedly on clinically non-affected skin on the back, forearm and forehead. In addition, patch testing with sodium lauryl sulphate (SLS) (0.5%) was performed on the forearm and on the back. RESULTS: We found a moderate but significant disturbance of skin barrier and hydration on the forearm and the back (bathing + irradiation) after increasing dosages of therapy. In addition, SLS testing leads to stronger reactions. CONCLUSIONS: We conclude that on clinically healthy skin the impairment of skin barrier by frequent bathing cannot be completely compensated by subsequent UVA irradiation. When conducting a treatment with 8-MOP bathing and UVA irradiation a concomitant therapy supporting the recovery of skin barrier, e.g. with moisturizer, should be performed.

[In vitro growth of human pathogenic fungi on different stocking fabrics]. / Wachstumsverhalten humanpathogener Pilze in vitro auf verschiedenen Strumpfgeweben.

Athlete's foot and onychomycosis can be aggravated due to inappropriate footwear. In this study we examined whether stockings of synthetic and mixed fabrics may influence the growth behaviour of the commonly isolated fungi Trichophyton rubrum, Trichophyton mentagrophytes and Candida albicans. A standardized suspension of each fungus was given to each sample of twelve stockings of different materials. The size of the growing colonies and the velocity of their growth were measured and compared to each other. Based on our data stockings depending on their fabric mixture seem to support or inhibit respectively the growth of fungi. Stockings composed of polyamide and a high percentage of polyurethane (Elasthan) and silk stockings as well may likely promote the fungal growth.

Differences of skin irritation between Japanese and European women.

BACKGROUND: After using cosmetics, Japanese women frequently complain about sensitive, stinging skin. We wondered whether Japanese women's skin is more sensitive than that of Caucasians. OBJECTIVES: To examine possible racial differences of skin irritation and subjective sensations. METHODS: We performed patch testing on the forearm with sodium lauryl sulphate (SLS) at different concentrations (0.25%, 0.5%) and 24-h exposure time. Skin reaction was evaluated by measurement of transepidermal water loss (TEWL), stratum corneum hydration, sebum secretion, laser Doppler flowmetry (LD), content of melanin and erythema. During a stinging test with 10% lactic acid (applied to one side of the cheeks) the subjects were asked to describe the present intensity of any sensation. We used a Chromameter to measure skin colour before and after application of lactic acid. This study was performed in Marburg, Germany, with healthy Japanese and German women living in Marburg. RESULTS: After SLS testing, we found no significant differences of the barrier function in the stratum corneum, but we found significant subjective sensory differences between Japanese and German women. CONCLUSIONS: Japanese women may complain about stronger sensations reflecting a different cultural behaviour rather than measurable differences in skin physiology; however, a faster penetration of SLS in Japanese cannot be excluded.

Irritant patch testing with sodium lauryl sulphate: interrelation between concentration and exposure time.

BACKGROUND: It is well known that the degree of skin reaction to an irritant depends on its concentration and exposure time. OBJECTIVES: To determine the interrelationship between the concentration of sodium lauryl sulphate (SLS) and exposure time in both weak (subclinical) and severe reactions. METHODS: Patch testing with SLS was performed at different concentrations (0.125%, 0.25%, 0.5%, 1.0% and 2.0%) and with different exposure times (3, 6, 12, 24 and 48 h). Evaluation was conducted by measurement of transepidermal water loss and by laser-Doppler flowmetry both 30 min and 24 h after patch removal. RESULTS: We found more reliable and constant skin reactions 24 h after patch removal, and a higher correlation between SLS concentration and skin reaction. CONCLUSIONS: We conclude that the concentration of SLS influences the test outcome to a larger degree than the exposure time. We present formulae by which the outcome of SLS patch testing at various SLS concentrations ranging from 0.125% to 2% and any exposure time between 3 and 24 h can be estimated.