Lutz Schmitz

Recent advances in clinical application of optical coherence tomography of human skin

Optical coherence tomography (OCT) is an emerging noninvasive imaging method that uses infrared light and interferometric techniques. The method has become increasingly popular in skin research as well as daily dermatology practice. In the present brief review, we focused on recent (2009–2014) OCT studies on the human skin, which included a reasonable sample size and statistics. Twenty-five papers were selected and briefly described OCT of epidermal thickness, skin appendages, wound healing, extracellular matrix and skin fibrosis, vascular malformations, and skin tumors such as basal cell carcinoma, actinic keratoses, and malignant melanoma.

Baseline laboratory parameters predicting clinical outcome in melanoma patients treated with ipilimumab: a single-centre analysis

Overall response rates (ORRs) for ipilimumab in advanced melanoma are only about 10%. Hence, it is important to explore biomarkers predicting ipilimumab responders.

The comet flap: an alternative technique for the reconstruction of facial defects

There are several techniques for the reconstruction of surgical defects of the face, with primary side-to-side closure being the simplest and most effective method [1]. However, depending on defect size, location, and adjacent free margins, primary wound closure is not always feasible. In such cases, and when there is excessive tension, skin grafts and local flaps are used [1, 2]. In the following paragraphs, we describe the comet flap (synonym: dog-ear rotation flap) as a simple solution enabling the closure of medium-sized as well as large defects. First described by Mellette in 1986, the term comet flap derives from its shape after the sutures are completed [3]. On one end, the defect is closed in a primary side-to-side fashion. On the other end, where primary closure is not possible because of high tension, a rotation flap is performed using the extra skin arising from the dog ear. Eventually, one part is closed by a single-line suture, the other by two suture lines that both merge into the single-line suture, thus resembling a shooting star or comet ś tail.

Actinic keratosis area and severity index (AKASI) is associated with the incidence of squamous cell carcinoma

Actinic keratoses (AKs) are commonly diagnosed clinically. Actinic keratosis area and severity index (AKASI) is a new easy‐to‐use tool to assess the severity of AKs on the head.

Epidermal penetration and protoporphyrin IX formation of two different 5-aminolevulinic acid formulations in ex vivo human skin

BACKGROUND Photosensitizer formation and epidermal penetration depth represent basic predictors of drug efficacy in dermatological Photodynamic Therapy (PDT). Different drug formulations and application standards are used to perform PDT in clinical practice. METHODS Thus, we developed a human ex vivo model suitable to explore drug permeation in human skin and compared in 10 patients the penetration of nanoemulsion formulation (BF-200 ALA) with that of a 20% ALA cream formulation frequently used in clinical practice. Protoporphyrin IX (PpIX) formation was assessed according to different durations of incubation with both preparations. RESULTS BF-200 ALA led to more intense PpIX fluorescence than the 20% ALA cream formulation as assessed by fluorescence microscopy: after 12h of incubation, total measured fluorescence was at 101,995 fluorescence units with BF-200 ALA and 40,960 fluorescence units with 20% ALA cream, respectively. This could be reproduced using quantitative fluorimetric measurements in tissue lysates. After the clinically relevant incubation time of 3h the PpIX concentration induced by BF-200 ALA was more than three-fold higher than that induced by the 20% ALA formulation (7.1±5.5 and 1.9±1.8nmol/l, p<0.05, Mann-Whitney U-test) and four-fold higher after 12h (30.0±4.6 and 6.7±2.0nmol/l, p<0.01, Mann-Whitney U-test). CONCLUSIONS In spite of the 50% lower ALA content BF-200 ALA triggers significantly higher PpIX concentrations than the 20% ALA formulation, indicating that clinical efficacy with BF-200 ALA may be higher. Moreover, the ex vivo eyelid skin model may represent a useful tool to investigate drug permeation in human skin.

Photodynamic therapy leads to significant improvement of actinic keratosis area and severity index (AKASI)

BACKGROUND Actinic keratosis area and severity index (AKASI) is a new quantitative tool for assessing AK severity on the head and can be used to monitor outcomes of different therapies. The aim of this study was to determine treatment outcomes of AK applying AKASI three months after conventional photodynamic therapy (PDT). METHODS We performed a retrospective analysis of patients who have undergone PDT on the head and had a documented AKASI evaluation prior to PDT and at follow-up visits. RESULTS Of the 33 patients included, 32 (97.0%) patients showed an AKASI reduction and 1 (3.0%) patient an increase of AKASI at follow-up visits compared to baseline. The median (range) follow-up period was 96days (70-161). The median difference of AKASI values between both visits was 73.7% (-34.8 to 100.0%). The Wilcoxon test showed highly significant differences (P<0.0001) between visits. 14 (42.4%) patients showed an AKASI 100 (complete clearance), 16 (48.5%) an AKASI 75 and 24 (72.7%) an AKASI 50, respectively. The Mann-Whitney U test showed in a subgroup analysis of patients with a positive history of at least more than one intervention and treatment naïve patients significant differences in these two groups (P=0.0302). CONCLUSIONS AKASI represents a feasible and comparable tool for objectively assessing field-directed treatment modalities such as PDT in daily routine. The establishment of AKASI 50, 75, 100 serves as an objective measure to compare treatment outcomes to baseline severity of AK.

Altered epigenetic pathways and cell cycle dysregulation in healthy appearing skin of patients with koebnerized squamous cell carcinomas following skin surgery

Koebnerized non‐melanoma skin cancer following skin trauma represents a rare and obscure event.

Actinic keratoses show variable histological basal growth patterns - a proposed classification adjustment

Common histological classification schemes of actinic keratoses (AK) do not evaluate growth patterns at basal epidermal aspects of AK. Until now, the importance of basal epidermal growth patterns of AK has not been studied.

A Novel Severity Assessment Scoring System for Hidradenitis Suppurativa

Importance The variation in both clinical appearance and responses to diverse treatment options emphasize the importance of an accurate, clinically relevant, yet easy-to-use scoring system in hidradenitis suppurativa. Objective To propose and provide validation data for the newly designed Severity Assessment of Hidradenitis Suppurativa score. Design, Setting, and Participants We prospectively assessed disease severity using Hurley staging and the modified Hidradenitis Suppurativa Score in 355 patients referred to Ruhr-University Bochum Department of Dermatology between March 2016 and June 2017. We also assessed disease severity via the Severity Assessment of Hidradenitis Suppurativa score. Main Outcomes and Measures Evaluation and assessment of convergent validity and responsiveness to treatment of the Severity Assessment of Hidradenitis Suppurativa score. Results Eighty-eight of the 355 patients (134 [37.7%] men and 221 [62.3%] women with a median [IQR] age of 40 [30-49] years) were classified as Hurley stage I, 221 were Hurley stage II, and 46 were Hurley stage III, with an overall median modified Hidradenitis Suppurativa Score of 31 (interquartile range [IQR], 19.3-53). The median total Severity Assessment of Hidradenitis Suppurativa score was 6 (IQR, 4-9), significantly different among the 3 Hurley groups. The median SAHS score for patients in Hurley stage I was 5 (IQR, 3-6), 6 (IQR, 5-9) for patients in Hurley stage II, and 9 (IQR, 7-12) for patients in Hurley stage III (P < .001, Kruskal-Wallis test). Correlation analysis showed a significant correlation between the modified Hidradenitis Suppurativa Score and the Severity Assessment of Hidradenitis Suppurativa score (r = 0.79, P < .001). Disease severity assessment before and after 3 months of conservative systemic treatment showed a significant correlation between the Severity Assessment of Hidradenitis Suppurativa score and modified Hidradenitis Suppurativa Score. Both the mHSS (P = .001) and the SAHS score (P < .001) significantly differed between the baseline visit (median mHSS, 33 [IQR, 24-52]; median SAHS score, 6 [IQR, 5-9]) and the 3-month visit (median mHSS, 28 [IQR, 15-43.5]; median SAHS score, 5 [IQR, 4-6.3]). The 2 patient-reported items demonstrated excellent test-retest reliability with intraclass correlation coefficient values greater than 0.8. Conclusions and Relevance Our validation data demonstrated that the Severity Assessment of Hidradenitis Suppurativa score is a disease severity instrument that significantly correlates with Hurley staging and the modified Hidradenitis Suppurativa Score, and is responsive enough to measure treatment outcome.

Cutaneous squamous cell carcinomas are associated with basal proliferating actinic keratoses

In addition to the extent of atypical keratinocytes throughout the epidermis, actinic keratoses (AKs) are histologically characterized by downward‐directed basal‐layer expansion. It is not known whether this growth pattern correlates with the risk of developing invasive squamous cell carcinoma (iSCC).