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Background: Basal cell carcinomas (BCCs) have previously been treated off-label with ingenol mebutate (IM). Ablative fractional laser (AFL) may improve efficacy of IM by increasing drug uptake in the tumour. Optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) detect BCC non-invasively. Our aim was to investigate BCC response and tolerability after combined AFL and IM treatment of low-risk BCCs., Methods: Twenty patients with histologically verified superficial (n = 7) and nodular (n = 13) BCCs were treated with combined fractional CO 2 -laser (10 600 nm) and IM 0.015% or 0.05%, the concentration depending on anatomical location. BCC response was evaluated clinically, by OCT and RCM at day 29 and 90 after first treatment, and histologically at day 90. Treatment was repeated at day 29 if BCC persisted. Local skin reactions (LSRs) were assessed using LSR scale at all visits., Results: At day 29, 18/20 patients received a second treatment due to residual BCC detected clinically, by OCT or RCM. OCT and RCM presented subclinical BCCs in five of 20 cases (25%). At day 90, overall histological cure rate was 70%, corresponding to clinical (65%) and OCT/RCM (60%) cure rates, and agreement between evaluation methods was substantial (kappa ≥ 0.796, P < 0.0001). Clearance rates were similar for sBCCs and nBCCs (P = 0.354) and for lesions treated with IM 0.015% and 0.05% (P = 0.141). LSRs were tolerable, but scarring was observed in the majority of cleared patients., Conclusion: Two treatments of combined AFL and IM show potential to treat low-risk BCCs with acceptable tolerability. OCT and RCM show promise to detect subclinical BCCs at short-term follow-up., (© 2019 European Academy of Dermatology and Venereology.)

This case report of a 36-year-old man, who had sex with men, illustrates, that early identification and diagnosis of neurosyphilis are crucial. Neurosyphilis, being a rare complication of syphilis, is associated with a high risk of severe neurological symptoms such as cranial nerve dysfunction, acute or chronic altered mental status and auditory abnormalities. Treatment with recommended antibiotic regimens can effectively cure neurosyphilis, though the risk of sequelae remains.

Background: Ablative fractional laser (AFL) increases uptake of topically applied skin agents. The coagulation zone (CZ) surrounding vertically ablated channels may influence uptake of drugs., Objectives: To investigate impact of CZ thickness on skin fluorescence intensities (FI) of a hydrophilic molecule by means of fluorescence microscopy (FM) and fluorescence confocal microscopy (FCM). Second, to compare FI of hydrophilic and lipophilic test molecules by FCM., Study Design/methods and Materials: Microchannels with CZ thicknesses of 0, 20, and 80 µm were generated by microneedles or AFL (10,600 nm). Channels were 700 µm deep and number of channels kept constant per skin area. After 4 hours of incubation, FI induced by sodium fluorescein (NAF, hydrophilic, logarithmic partition-coefficient (logP) = -1.52, MW = 376.26) were quantified in both CZ and surrounding skin by FM (0-1,500 µm) and FCM (0-90 µm). FI of NAF and carboxyfluorescein (CAF, lipophilic, logP = 2.9, MW = 376.32) were compared by FCM., Results: By FM, NAF-induced FI were higher in CZ than in surrounding skin (P ≤ 0.001). Highest NAF-FI were induced in skin pretreated with a thin CZ (CZ-20 µm), assessed by both FM and FCM and in particular, FI were higher than in skin pretreated with no CZ (CZ-0 µm) (FM P ≤ 0.041, FCM P < 0.012). Skin FI remained constant to a depth of 500 µm, which corresponded to approximate depth of microchannels (CZ-0 µm, CZ-20 µm, CZ-80 µm: 0-500 µm P ≥ 0.107). In accordance with FM data, FCM showed higher FI within CZ than in surrounding skin, but gradually decreased to zero at a depth of 90 µm. NAF-FI were higher than CAF-FI (P ≤ 0.036), and highest CAF-FI were induced by CZ-0 µm and CZ-20 µm compared to CZ-80 µm (P ≤ 0.009)., Conclusions: The influence of the CZ thickness on skin FI differs between small hydrophilic and lipophilic test molecules. Results may have clinical relevance for laser-assisted drug delivery. Lasers Surg. Med. 51:68-78, 2019. © 2018 Wiley Periodicals, Inc., (© 2018 Wiley Periodicals, Inc.)

Background: In recent years, various lasers have increasingly been applied during wound healing to minimize scar formation. However, no consensus regarding treatment procedures exists., Objectives: To assess scar formation clinically after three nonablative fractional laser (NAFL) exposures, targeting the inflammation, proliferation and remodelling wound healing phases in patients vs. untreated controls., Methods: A randomized controlled trial was performed using a split-wound design to assess excisional wound halves treated with 1540-nm NAFL vs. no laser treatment. Three NAFL exposures were provided: immediately before surgery, at suture removal and 6 weeks after surgery. NAFL exposures were applied using two handpieces, sequentially distributing energy deeply and more superficially in the skin (40-50 mJ per microbeam). Evaluated at 3 months of follow-up, the primary outcome was blinded, on-site evaluation using the Patient Observer Scar Assessment Scale (POSAS total; range from 6, normal skin to 60, worst imaginable scar). Secondary outcomes comprised blinded evaluation on the Vancouver Scar Scale (VSS) and standardized assessment comparing scar sides, carried out by blinded on-site, photo and patient assessments. This trial was registered with ClinicalTrials.gov (NCT03253484)., Results: Thirty of 32 patients completed the trial. At the 3-month follow-up, the NAFL-treated scar halves showed improvement compared with the untreated control halves on POSAS total: NAFL treated, median 11, interquartile range (IQR) 9-12 vs. control, median 12, IQR 10-16; P = 0·001. The POSAS subitems showed that the NAFL-treated halves were significantly less red and more pliable, and presented with smoother relief than the untreated controls. VSS total correspondingly revealed enhanced appearance in the NAFL-treated halves: median 2, IQR 1-2·5 vs. control, median 2, IQR 1·75-3, P = 0·007. The standardized assessment comparing appearance of scar halves demonstrated a low degree of correspondence between on-site, photo and patient assessments. NAFL-treated scars were rated as superior to untreated scars by 21 of 29 patients., Conclusions: NAFL-treated scars showed subtle improvement compared with untreated control scars., (© 2018 British Association of Dermatologists.)

Background: Anogenital warts (AGW) can cause physical discomfort and decreased quality of life. Recent case reports suggest that ingenol mebutate gel might be an effective treatment of AGW., Objective: To explore primarily the safety, and secondarily the efficacy of ingenol mebutate gel 0.05% in patients with AGW., Methods: This was an exploratory, open-label, 1-arm trial of ingenol mebutate gel 0.05% administered up to three times to patients with AGW. Safety was assessed by occurrence and severity of local skin reactions (LSRs) and treatment-related adverse events (AEs). Efficacy was assessed by complete clearance and reduction in AGW count 14 days after last treatment, and recurrence 12 weeks after clearance., Results: Of 41 patients enrolled, 40 received treatment and 26 completed the trial. Patients had a median AGW count of 11.0 and AGW duration of 3.0 years at baseline. All patients experienced transient LSRs following treatment with a maximum composite LSR score of 7.5 (on a scale from 0 to 18). A total of 93% of patients reported treatment-related AEs, most frequently pain (85%) and procedural complications (35%) due to smearing of the gel. 78% of patients took mild analgesics for the pain, typically for 1-2 days following treatment. The majority of AEs were of moderate-to-severe intensity. Seventeen of 39 patients (43.6%) had complete clearance 14 days after last treatment, and AGW count was reduced by 90.9%. There was a tendency towards lower clearance rate in patients with longer duration of AGW. Eight of 14 patients (57.1%) had AGW recurrence 12 weeks after clearance., Conclusion: Ingenol mebutate gel was associated with a high number of AEs and withdrawals due to painful local and adjacent skin reactions. Furthermore, it showed promising efficacy in reducing AGW despite a difficult-to-treat population. Optimization of the formulation is warranted to improve the safety profile of the treatment., (© 2017 European Academy of Dermatology and Venereology.)

Background: Ablative fractional laser (AFXL) is an acknowledged technique to increase uptake of topical agents in skin. Micro thermal ablation zones (MAZs) consist of ablated vertical channels surrounded by a coagulation zone (CZ). Laser scanning confocal microscopy (LSCM) images individual MAZs at 733 nm (reflectance confocal microscopy (RCM)). Further, LSCM can image sodium fluorescein (NaF) fluorescence with 488 nm excitation (fluorescence confocal microcopy (FCM)), a small hydrophilic test molecule (370 MW, log P -1.52), which may simulate uptake, bio-distribution and kinetics of small hydrophilic drugs., Objectives: To explore LSCM for combined investigations of CZ thickness and uptake, bio-distribution and kinetics of NaF in AFXL-exposed skin., Study Designs/methods and Materials: Excised human abdominal skin samples were exposed to AFXL (15 mJ/microbeam, 2% density) and NaF gel (1000 μg/ml, 10 μl/cm2) in six repetitions, including untreated control samples. CZ thickness and spatiotemporal fluorescence intensities (FI) were quantified up to four hours after NaF application by RCM and FCM. Test sites were scanned to a depth of 200 μm, quantifying thickness of skin compartments (stratum corneum, epidermis, upper dermis), individual CZ thicknesses and FI in CZ and surrounding skin., Results: RCM images established skin morphology to a depth of 200 μm. The CZ thickness measurements were feasible to a depth of 50 μm, and remained unchanged over time at 50 μm (P > 0.5). FI were detected to a depth of 160 μm and remained constant in CZ up to four hours after NaF application (15 minutes: 79 AU (73-92 AU), 60 minutes: 72 AU (58-82 AU), four hours: 78 AU (71-90 AU), P > 0.1). In surrounding skin, FI increased significantly over time, but remained lower than FI in CZ (15 minutes: 21 AU (17-22 AU), 60 minutes: 21 AU (19-26 AU), four hours: 42 (31- 48 AU), P = 0.03). AFXL-processed skin generated higher FI compared to non-laser processed skin in epidermis and upper dermis at 60 minutes and four hours (P = 0.03)., Conclusions: By LSCM, assessment of the AFXL-induced CZ thickness was feasible to a depth of 50 μm, and assessment of FI from a small hydrophilic test molecule, NaF in CZ and surrounding skin feasible to a depth of 160 μm. Lasers Surg. Med. 50:70-77, 2018. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Background and Objective: Ablative fractional laser (AFXL) is acknowledged to increase uptake of topically applied agents in skin. AFXL channels gradually close over time, which may impair this capability. The time frame for applying a drug after AFXL exposure remains to be established. The aim of this study, was to investigate the importance of time-related topical application after AFXL exposure and to relate resultant uptake in skin with AFXL channel morphology and skin integrity., Study Design/materials and Methods: Buttock skin of healthy volunteers (n = 11) was exposed to 10,600 nm fractional CO 2 laser using 5% density, 120 μm beam diameter, 15 mJ pulse energy. Sodium fluorescein (NaF) a small, hydrophilic molecule (370 MW, log P =  -1.52) was applied under standardized conditions at specific time points after laser exposure (0, 2, 5, 10, 30, 60, 90 minute, 6, 24, and 48 hours). Fluorescence photography collected fluorescence images up to 180 minute after NaF application. Optical coherence tomography (OCT) assessed AFXL channel dimensions and transepidermal water loss (TEWL) estimated loss of skin integrity., Results: Fluorescence intensities (FI) were significantly elevated when NaF was applied up to 6 hours after laser exposure compared to non-laser-processed skin (median FI 1947 arbitrary units [interquartile range 1,246-3,560] versus 1,004 [350-1,538], P < 0.02). The highest FI occurred when NaF was applied within 30 minute after laser exposure and similar FI were reached for applications at 0, 2, 5, 10, and 30 minute after AFXL exposure (0 minute: 3,866 [3,526-4,575], 30 minute: 3,775 AU [3,070-4,484], P > 0.1). NaF application later than 30 minute after AFXL exposure resulted in gradually decreasing FI, becoming similar to intact skin when applied at 24-48 hours after AFXL exposure (P > 0.2). OCT images demonstrated that AFXL channels closed over time (100% [100-100%] open up to 30 minute, 75% [4-86%] at 6 hours and 3% [0-15%] at 24-48 hours after AFXL exposure). TEWL measurements proved loss of skin integrity up to 6 hours after AFXL exposure, while integrity was similar in laser-exposed and non-laser-exposed skin at 24-48 hours., Conclusions: The time frame to maintain enhanced drug delivery sustained for several hours after AFXL exposure, corresponding to channel morphology and loss of skin integrity. Lasers Surg. Med. 49:348-354, 2017. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Importance: Vasculopathy characterized by functional and structural abnormalities of the microcirculation plays an important role in systemic sclerosis and dermatomyositis. Although there are several advantages in using capillaroscopy, the method does not offer insight on the skin architecture, flow status, or morphology of the deeper dermal vessels. Dynamic optical coherence tomography (D-OCT) is a recently developed OCT technique that enables detection of high-speed changes in back-scattered light caused by moving cells in vessels. The high resolution of OCT enables the detection of the papillary loops., Objective: To explore the potential for OCT capillaroscopy of the nailfolds using D-OCT., Design, Setting, and Participants: In this case series study of 4 participants, the nailfolds in 2 patients with systemic sclerosis, 1 patient with dermatomyositis, and a healthy volunteer were scanned using D-OCT. The included patients were all outpatients from the department of dermatology at Bispebjerg Hospital. Data were analyzed from November 2015 to February 2016., Main Outcomes and Measures: Dynamic OCT capillaroscopy revealed a potential for imaging of the capillary morphology, the surrounding skin architecture, and flow status of the capillaries in the nailfold. Moreover, D-OCT quantified evident changes of the blood flow in normal nailfold capillaries after application of nitroglycerine and brimonidine., Results: This case series included 4 adult women. The quantitative measurements of the blood flow in the D-OCT images of the healthy participant showed significant quantitative differences in blood flow before and after application of nitroglycerine (mean difference, 0.035; 95% CI, 0.008-0.061; P = .02) and brimonidine (mean difference, -0.015; 95% CI, -0.082 to -0.039; P < .001). In the dermatomyositis patient, the en face D-OCT images showed a striking detailed Y-shaped dilated capillary correlating with the clinical finding. In the 2 patients with systemic sclerosis, D-OCT depicted megacapillaries, as well as loss of capillaries. Moreover, cross-sectional OCT images demonstrated a characteristic loss of distinct dermo-epidermal junction and more compact dermis with loss of adnexal structures., Conclusions and Relevance: Compared with conventional capillaroscopy, D-OCT offers second-to-none information on nailfold capillary morphology, overall skin architecture, as well as quantitative data on vascular abnormalities and blood flow in the nailfold in a single scan.

Background and Objective: Optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) offer high-resolution optical imaging of the skin, which may provide benefit in the context of laser-assisted drug delivery. We aimed to characterize postoperative healing of ablative fractional laser (AFXL)-induced channels and dynamics in their spatiotemporal closure using in vivo OCT and RCM techniques., Study Design/materials and Methods: The inner forearm of healthy subjects (n = 6) was exposed to 10,600 nm fractional CO2 laser using 5 and 25% densities, 120 μm beam diameter, 5, 15, and 25 mJ/microbeam. Treatment sites were scanned with OCT to evaluate closure of AFXL-channels and RCM to evaluate subsequent re-epithelialization., Results: OCT and RCM identified laser channels in epidermis and upper dermis as black, ablated tissue defects surrounded by characteristic hyper-and hyporeflective zones. OCT imaged individual laser channels of the entire laser grid, and RCM imaged epidermal cellular and structural changes around a single laser channel to the depth of the dermoepidermal junction (DEJ) and upper papillary dermis. OCT images visualized a heterogeneous material in the lower part of open laser channels, indicating tissue fluid. By OCT the median percentage of open channels was evaluated at several time points within the first 24 hours and laser channels were found to gradually close, depending on the used energy level. Thus, at 5 mJ/microbeam, 87% (range 73-100%) of channels were open one hour after laser exposure, which declined to 27% (range 20-100%) and 20% (range 7-93%) at 12 and 24 hours after laser exposure, respectively. At 25 mJ/microbeam, 100% (range 100-100%) of channels were open 1 hour after laser exposure while 53% (range 33-100%) and 40% (range 0-100%) remained open at 12 and 24 hours after exposure. Median depth and width of open channels decreased over time depending of applied energy. RCM verified initial re-epithelialization from day 2 for all energy levels used. Morphology of ablation defects by OCT and RCM corresponded to histological assessments., Conclusions: OCT and RCM enabled imaging of AFXL-channels and their spatiotemporal closure. Laser channels remained open up to 24 hours post laser, which may be important for the time perspective to deliver topical substances through AFXL channels., (© 2015 Wiley Periodicals, Inc.)

Background: Staphylococcal scalded skin syndrome (SSSS) and toxic epidermal necrolysis (TEN) both present with acute onset, high morbidity and significant mortality. Rapid diagnosis is therefore of importance. The aim of this study was to investigate and compare the presentation of these diseases using optical coherence tomography (OCT)., Methods: Two male patients with bullous diseases, SSSS and TEN, respectively, were photographed digitally, examined using dermoscopy, OCT scanned and subsequently biopsied in the said order., Results: The bullous skin was visualized by OCT showing two distinct images: the SSSS-patient displayed superficial hyporefletive flaccid structures with a split high in the thickened (0.51 mm vs. 0.12 mm) epidermis while the TEN-patient demonstrated a larger hyporeflective ovoid structure with a split right below the thickened epidermis (0.18 mm vs. 0.06 mm)., Conclusion: These findings suggest that there is a potential for the application of OCT scanning in the acute phase of SSSS and TEN in order to distinguish them for a faster diagnosis and better management and treatment., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: To explore the application of optical coherence tomography (OCT) imaging of basal cell carcinomas (BCC) and actinic keratosis (AK) before, during and after imiquimod treatment and the ability of OCT to predict treatment outcome., Methods: The study subjects were 20 patients with biopsy-verified BCC (9) or AK (11). Patients were OCT-scanned before, after 1 and 4 weeks of imiquimod treatment and after 3 months. Lesions were identified clinically and with OCT. Thickness and morphology of the lesions were recorded at each visit. Any remaining lesions were biopsied at follow-up., Results: Complete data sets were available for 16 patients (8 women and 8 men aged 52-82 years), four in-compliant patients were excluded. OCT identified all lesions. Previously suggested OCT-criteria identified 5/8 BCCs. Crusting, ulceration and active treatment significantly reduced image quality. All BCCs cleared, but at follow-up residual structures were seen clinically in 4 cases. OCT and histology both ruled out residual BCC. For AKs significant thinning occurred after 1 week of treatment (P = 0.04). Imiquimod cleared 2/8 AKs, and significantly decreased the thickness of all lesions (P = 0.02)., Conclusions: OCT could identify superficial BCC and AK before treatment. Monitoring during imiquimod treatment revealed impaired image quality most likely caused by inflammation, crusting and ulceration. On follow-up, OCT showed thinning of AKs indicating effect of treatment. All treated BCCs cleared, but where residual tissue was suspected clinically this could be ruled out by OCT., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Photodynamic therapy with methyl aminolaevulinate (MAL-PDT) is a widely used non-invasive treatment modality for non-melanoma skin cancer (NMSC). The outcome of MAL-PDT is usually primarily evaluated clinically. Optical coherence tomography (OCT) is a non-invasive imaging technology based on interferiometry. OCT has been proven to provide high accuracy in identifying NMSC lesions and performing thickness measurements of thin tumours., Objectives: To describe the OCT morphology in in-vivo NMSC lesions during MAL-PDT treatment and to investigate the use of OCT in evaluating the response of MAL-PDT treated NMSC lesions., Methods: A total of 18 biopsy-proven basal cell carcinomas and actinic keratoses were monitored by OCT during 2 sessions of MAL-PDT treatment. At 3-months follow-up the patients were assessed both by OCT and clinically. If the clinical and OCT evaluation came to different conclusions on recurrence of the lesion, patients were followed more closely at clinical appointments for up to one year after the PDT treatment., Results: All lesions displayed at least one OCT characteristic before MAL-PDT treatment. At 3 months follow-up, recurrence was suspected clinically in 5/18 cases, with OCT in 7/18 cases. OCT correctly identified all of the partial responses also found by the clinical examinations. In both cases where recurrence was only found in OCT, this was subsequently confirmed by histology., Conclusions: Our study suggests that OCT identified 29% more recurrences than clinical examination alone. OCT can detect subclinical residual NMSC lesions after MAL-PDT treatment and may therefore be an accurate tool for early detection of residual lesional tissue., (Copyright © 2013 Elsevier B.V. All rights reserved.)