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Notes: 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.

Notes: 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.

Notes: AbstractA 46-year-old woman presented with multiple seborrheic keratoses disseminated over her trunk and thighs. A screening for internal malignancies revealed an adenocarcinoma of the colon that was successfully treated by surgery. During a follow-up period of 18 months, the seborrheic keratoses remained unchanged. There was no evidence of recurrence of the malignancy. We conclude that this case does not fulfill the criteria of the ‘sign of Leser-Trélat’; according to present knowledge the existence of this cutaneous paraneoplastic syndrome cannot be taken as a certain indication. Patients with multiple seborrheic keratoses do not necessarily present internal malignancies.

Notes: 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.

Notes: Topically applied all-trans retinoic acid (RA) is often associated with skin irritation. A detailed quantification of RA-induced functional changes in stratum corneum is. however, still limited. U sing noti-invasive bioengineering techniques of measurements of transepidermal water loss (TEWL), stratum corneum hydration and cutaneous blood flow (CBF). we quantified the irritant effects of 0·05% and 0·1% RA in ethanol on normal skin compared with 1% sodium lauryl sulphate (SLS) in water as a model irritant in a 24-h occlusive patch-test assay. Additionally, in order to document data possibly related to the mechanism of action, skin responses to both compounds applied in tandem was also investigated over 18 daysThe extent of the irritant response to 0·05 and 0·1% RA, respectively, were similar, implying analogous irritation potency. While RA caused more intense scaling than SLS. other skin responses to RA were significantly weaker than those due to SLS. An increase in TEWL. on day 7. in RA-exposed sites indicates a secondary delayed impairment of the stratum corneum (SC) barrier. In a tandem-design assay, pretreatment with RA appeared to reduce the irritant effects of SLS on SC hydration and CBF. In contrast, pre-exposure to SLS showed a synergestic response in erythema, scaling and TEWLOur results demonstrate that RA, like SLS. is capable of impairing SC water barrier function, which may be responsible, in part, for the irritation associated with its topical use. However, the distinctive biological responses to these compounds suggest a different mode of action of RA and SLS. In addition, the precise reason for the unique results observed in the tandem-design assays is not clear.

Notes: Summary Calcipotriol. a vitamin D analogue utilized for psoriasis, has irritation as its most frequent reported adverse event. However, studies on its irritant properties in humans have produced conflicting data. This study evaluates the effect of calcipotriol on stratum corneum barrier function, hydration and cell turnover in healthy volunteers, compared with sodium lauryl sulphate (SLS) as a model irritant. Calcipotriol 0·005% ointment and 1% aqueous SLS solution were applied for 2 weeks (5 consecutive days weekly) on untreated and on dansyl-chloride-labelled skin. Irritant responses were documented by visual scoring and by measurement of the transepidermal water loss (TEWL) and stratum corneum hydration (electrical capacitance), until day 18 Stratum corneum turnover time (SCTT) was the time in days between staining (day 0) and the disappearance of dansyl fluorescence. SLS caused more erythema, scaling, and a significant TEWL increase for 18 days. In contrast, calcipotriol induced erythema, and slightly but significantly increased TEWL on day 11 only, as compared with the vehicle control (P〈0·05) SLS, but not calcipotriol, caused skin dryness from day 4 to day 18. The shortest SCTT was obtained at SLS-exposed sites (11·2 ± 0·7 days: mean± SD). Calcipotriol significantly shortened SCTT (16.3 ± 1.1 days) when compared with its vehicle. Compared with the skin irritation induced by SLS, under these test conditions, calcipotriol is a far weaker irritant on normal human skin. In addition, calcipotriol accelerates stratum corneum turnover to a significantly greater extent than its vehicle.

Notes: Recent in vivo investigations have shown that pretreatment with topical all-trans retinoic acid (RA) may diminish the skin response to sodium lauryl sulphate (SLS). This study evaluated the permeation of SLS through human skin after pretreatment with RA, and vice versa, by in vitro methods. The permeability coefficient of SLS (3.24 ± 0.21 × 103 cm/h) and the 24-h cumulative amount of SLS (3.41 ± 0.6% of dose applied) permeating RA-pretreated skin did not differ significantly from those across untreated skin (control) (P 〉 0.05). In contrast, the permeability coefficient of RA (0.23 ± 0.05 × 103 cm/h) and its 24-h cumulative amount (0.37 ± 0.05% of dose applied) penetrating SLS-pretreated skin were significantly greater than those permeating untreated skin (P〈0.05). Thus, an increase in RA penetration was induced by SLS pretreatment; however, pretreating the skin with RA did not inhibit the percutaneous permeation of SLS. Based on previous in vivo findings where RA reduced skin reactions to SLS,8 one would speculate that RA pretreatment may decrease SLS penetration. However, these penetration data do not necessarily uphold this presumption. Perhaps, other interactions between the substances and the skin, e.g. at cellular levels, may be responsible for the differing skin responses.

Notes: 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®. 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.

Notes: 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.

Notes: 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.