Diagnostic flow of patients in a national fast-track referral system for malignant melanoma.

INTRODUCTION. Timely diagnosis of malignant melanoma (MM) is crucial for optimal patient outcomes. Thus, the Danish Health Authority implemented a fast-track referral system (FTRS) comprising a clinical diagnostic filter function (CDFF) and a cancer package. This study aimed to characterise the flow of patients with a tentative MM diagnosis referred through the CDFF to a department of dermatology. METHODS. Retrospective data from the Danish patient and pathology file system were analysed for patients referred to the Department of Dermato-Venereology at Bispebjerg Hospital, Denmark, via the CDFF, with suspected MM in a one-year period. RESULTS. Among 860 patients with 895 skin lesions, 283 (31.6%) were discharged with a clinical benign diagnosis after their initial consultation, whereas treatment of another 77 (8.6%) patients concluded following a three-month observation period. One-year follow-up of these 360 (283 + 77) clinically benign skin lesions showed no malignancy. Among 100 MM-suspicious lesions promptly referred for excision to a department of plastic surgery, 48% were MM. CONCLUSIONS. In a Danish population with tentative MM diagnosis referred through the CDFF to a dermatological hospital department, one-third of patients were discharged with a clinically benign diagnosis. Half of the skin lesions referred for excision to the department of plastic surgery were MM. This indicates a decreased burden of overdiagnosis and a potential reduction of unnecessary surgical scars when dermatologists serve as gate keepers of the FTRS for MM. FUNDING. None TRIAL REGISTRATION. Data obtained with permission from BBH j. no. 20078406.

Fractional CO2 -laser versus microneedle radiofrequency for acne scars: A randomized, single treatment, split-face trial.

BACKGROUND: Ablative fractional CO2 laser (AFL) is an established first-line energy-based treatment for acne scars. Microneedle radiofrequency (MNRF) is an emerging treatment, also targeting the skin in fractions. No studies have so far compared AFL with MNRF for acne scars in a direct controlled, side-by-side comparison. In this study, we compared AFL and MNRF treatments for acne scars in a randomized split-face trial with blinded response evaluation, objective measures, and patient-reported outcomes. STUDY DESIGN/MATERIALS AND METHOD: Fifteen patients with moderate to severe acne scars were included. At baseline each patient had two similar test areas identified, these were randomized to receive a single treatment with either AFL or MNRF. Standardized multilayer techniques were applied with AFL and MNRF, first targeting the scar base, thereafter the entire scar area. Outcome measures included blinded evaluation of clinical improvement of scar texture (0-10 scale) at 1- and 3-months follow-up, local skin reactions (LSR), pain according to Visual Analogue Scale (VAS), skin integrity quantified by transepidermal water loss, and patient satisfaction. RESULTS: Fifteen patients completed the study with a median test area size of 24.6 cm2 (interquartile range [IQR] 14.9-40.6). A single treatment with AFL or MNRF equally resulted in a median 1-point texture improvement after 3 months follow-up (p < 0.001). Best responders achieved up to a 3-point improvement (n = 3 test areas, 10% of treatment areas). Erythema and loss of skin integrity was more intense after AFL compared with MNRF after 2-4 days (p < 0.001). Patients reported MNRF (VAS 7.0) to be significantly more painful than AFL (5.5) (p = 0.009). Patients were generally satisfied with the overall outcome on a 10-point scale at median 6 for both treatments (IQR 5-7). CONCLUSION: AFL and MNRF treatments are equally effective at improving texture in skin with acne scars. AFL resulted in more pronounced LSRs whereas MNRF was more painful. Patients were generally satisfied with the overall outcome.

Detection of cutaneous malignant melanoma by tape stripping of pigmented skin lesions - A systematic review.

BACKGROUND: Cutaneous malignant melanoma (MM) is potentially aggressive, and numerous clinically suspicious pigmented skin lesions are excised, causing unnecessary mutilation for patients at high healthcare costs, but without histopathological evidence of MM. The high number of excisions may be lowered by using more accurate diagnostics. Tape stripping (TS) of clinically suspicious lesions is a non-invasive diagnostic test of MM that can potentially lower the number needed to biopsy/excise. MATERIALS AND METHODS: The aim is to determine the diagnostic accuracy of TS in detecting MM in clinically suspicious pigmented skin lesions. This systematic review following PRISMA guidelines searched PubMed, Web of Science, and Embase (September 2022) using melanoma combined with tape stripping, adhesive patch(es), pigmented lesion assay, or epidermal genetic information retrieval. RESULTS: Ten studies were included. Sensitivity ranged from 68.8% (95% confidence interval [CI] 51.5, 82.1) to 100% (95% CI 91.0, 100). Specificity ranged from 69.1% (95% CI 63.8, 74.0) to 100% (95% CI 78.5, 100). A pooled analysis of five studies testing the RNA markers LINC00518 and PRAME found a sensitivity of 86.9% (95% CI 81.7, 90.8) and a specificity of 82.4% (95% CI 80.8, 83.9). CONCLUSION: Overall quality of studies was low, and the reliability of sensitivity and specificity is questionable. However, TS may supplement well-established diagnostic methods as pooled analysis of five studies indicates a moderate sensitivity. Future studies are needed to obtain more reliable data as independent studies with no conflict of interest.

Excision and adjuvant treatment to prevent keloid recurrence. - a systematic review of prospective, clinical, controlled trials.

Keloids are defined as the formation of collagen-rich scar tissue extending beyond the original lesion. Not all keloids respond to conventional treatment with intralesional triamcinolone injections. Recurrence of keloids after primary excision is reported in almost 100% of cases and should therefore always be followed by adjuvant treatment. Currently, consensus on preferred adjuvant treatment in relation to keloid excision is lacking. This study seeks to systematically review evidence on the efficacy of adjuvant treatments in relation to keloid excision. A systematic literature review was conducted on PubMed. Titles, abstracts, and articles were screened and sorted according to defined inclusion- and exclusion criteria. Each study was evaluated according to the Oxford Centre for Evidence-Based Medicine, OCEBM, Levels of Evidence by two independent authors. Seven studies were eligible. Adjuvant treatment methods included intralesional triamcinolone injection, radiotherapy, silicone gel, pressure therapy, verapamil hydrochloride and 5-fluorouracil. While all the included studies reported promising results, two studies showed that minimizing dosages when treating with radiotherapy or triamcinolone should be considered to avoid adverse events. However, a high risk of bias was found in all the included studies.

Validity and reliability of the Rosacea Area and Severity Index: A novel scoring system for clinical assessment of rosacea severity.

BACKGROUND: Rosacea is a common chronic inflammatory facial skin disorder. Standardized evaluation of the severity and extent of rosacea is important for baseline assessment and treatment effect. The currently used Investigator's Global Assessment (IGA) is unspecific and fails to consider subtypes/phenotypes of rosacea and area involvement. The Rosacea Area and Severity Index (RASI) was developed to give a more nuanced evaluation of rosacea features in four facial skin areas adjusted to the relative importance of each area of the face to obtain an overall severity score. OBJECTIVES: To validate RASI against the IGA and to assess the inter- and intraobserver reliability for RASI. METHODS: Sixteen dermatologists evaluated photographs of 60 adult patients with rosacea (3 photographs per patient, one from the front and one from each side). IGA and RASI scores were performed for interobserver reliability assessment. To determine intraobserver reliability, 14 dermatologists evaluated 10 other patients twice with at least 1 week interval. RESULTS: The IGA and RASI correlated well (Spearman correlation coefficient (SCC) = 0.75, 95% confidence interval (CI) = 0.72-0.78). Interobserver reliability was moderate for RASI and poor to moderate for IGA. Reliability was strongest for rhinophyma, followed by papules/pustules and erythema, and rather weak for telangiectasia. For area scores, interobserver reliability was strongest for cheeks, followed by nose, chin and forehead. We found a moderate-to-strong intraobserver agreement both for IGA and RASI. CONCLUSIONS: We have designed a new practical tool to examine clinical severity of rosacea. RASI proved simple and reliable in scoring clinical severity of rosacea with an agreement comparable to the currently used IGA although RASI will provide a more nuanced view of the current rosacea extent and severity. We suggest that RASI is used in the daily clinical setting as well as in clinical studies assessing the efficacy of rosacea therapies.

A one-time pneumatic jet-injection of 5-fluorouracil and triamcinolone acetonide for treatment of hypertrophic scars-A blinded randomized controlled trial.

BACKGROUND: Patients with hypertrophic scars (HTS) risk reduced quality of life due to itching, pain, poor cosmesis, and restriction of movement. Despite good clinical efficacy, patients are often reluctant to undergo repeated needle injections due to pain or needle phobia. OBJECTIVES: To evaluate the applicability of needle-free pneumatic jet injection (PJI) and assess changes in hypertrophic scars following a single PJI treatment with 5-fluorouracil (5-FU) and triamcinolone acetonide (TAC). METHODS: Twenty patients completed this blinded, randomized, controlled, split-scar trial. The intervention side of the HTS received a one-time treatment with PJIs containing a mixture of TAC + 5-FU injected at 5 mm intervals (mean 7 PJI per HTS); the control side received no treatment. Assessments were made at baseline and 4 weeks posttreatment. Outcome measures included change in (1) Vancouver Scar Scale (VSS) total score and subscores, (2) scar volume and surface area assessed by three-dimensional imaging, (3) skin microarchitecture measured by optical-coherence tomography (OCT), (4) photo-assessed scar cosmesis (0-100), (5) patient-reported pain and satisfaction (0-10), and (6) depiction of drug biodistribution after PJI. RESULTS: PJI with TAC + 5-FU significantly decreased both HTS height (-1 VSS; p = 0.01) and pliability (-1 VSS; p < 0.01) with a nonstatistically significant reduction of -1 in total VSS score (0 in control; p = 0.09). On 3D imaging, a 33% decrease in scar volume (p = 0.016) and a 37% decrease in surface area (p = 0.008) was observed. OCT indicated trends towards smoother scar surface (Ra 11.1-10.3; p = 0.61), normalized dermal microarchitecture (attenuation coefficient: 1.52-1.68; p = 0.44), and a reduction in blood flow between 9% and 17% (p = 0.50-0.79). Despite advances in VSS subscores and OCT, no improved photo-assessed cosmesis was found (-3.2 treatment vs. -1.4 control; p = 0.265). Patient-reported pain was low (2/10) and 90% of the patients that had previously received needle injections preferred PJI to needle injection. Depositions of TAC + FU were imaged reaching deep into the scar at levels corresponding to the reticular dermis. CONCLUSION: A single PJI injection containing 5-FU and TAC can significantly improve the height and pliability of HTS. PJI is favored by the patients and may serve as a complement to conventional needle injections, especially for patients with needle phobia.

[The role of sex hormones in the pathogenesis of melasma].

Facial melasma is a common, acquired, skin condition, which typically presents itself as symmetric hyperpigmentation. It is multifactorial, and hormonal influence is one of the most dominant aetiologies. This review investigates the link between sex hormones and facial melasma. Ten studies were identified, and they overall conclude, that oestrogens play a role in the pathogenesis of melasma in females but not in males. Progesterone, follicle-stimulating hormone and lutropin play no significant role in males or females, while testosterone possibly plays a role in males.

[Atypical presentation of penile blue naevus].

Blue naevus is a rare lesion on genital mucosa and may cause confusion in differential diagnosis with other pigmented lesions. In this case report, a 39-year-old man presented with a sudden onset in adulthood of blue naevus on the glans penis. A biopsy confirmed the diagnosis. Due to the unusual presentation, the onset and the risk of turning invasive, a careful examination was performed in order to minimise any risk of misclassification with melanoma. Afterwards, the patient was followed in a dermatologic department every six months. To our knowledge, only few similar cases have been described in literature.

[Treatmentof rhinophyma with laser and surgery].

Rhinophyma is a disfiguring skin condition characterised by progressive hyperplasia of the nasal sebaceous glands and proliferation of blood vessels and connective tissue. It is considered the end stage of rosacea and affects primarily older males of Northern European descent. Several surgical and laser treatment options are available. None of these has been compared in randomised, controlled prospective trials. In this review, we provide an overview of the different treatment modalities and account for their respective strengths and limitations.

Clinical, microbiological, immunological and imaging characteristics of tunnels and fistulas in hidradenitis suppurativa and Crohn's disease.

Hidradenitis suppurativa (HS) tunnels and Crohn's disease (CD) fistulas are a challenge to treat. Although pathogenic similarities have been described between HS and CD, recent studies indicate that clinical, microbiological, immunological and imaging characteristics differ between these diseases. This review highlights the differences between HS tunnels and CD fistulas. Next-generation sequencing studies demonstrate a microbiome in HS tunnels dominated by Porphyromonas spp., Prevotella spp. whereas no specific bacteria have been associated with cutaneous CD. Immunologically, TNF has been found upregulated in HS tunnels along with various interleukins (IL-8, IL-16, IL-1α and IL-1ß). In CD fistulas, Th1, Th17, IL-17, IFN-ɤ, TNF and IL-23 are increased. US imaging is an important tool in HS. US of HS tunnels depict hypoechoic band-like structure across skin layers in the dermis and/or hypodermis connected to the base of a widened hair follicle. In CD, MR imaging of simple perianal fistulas illustrates a linear, non-branching inflammatory tract relating to an internal opening in the anus or low rectum and an external opening to the skin surface. An increased awareness of the immediate potential differences between HS tunnels and CD fistulas may optimize treatment regimens of these intractable skin manifestations.

Topical brimonidine reduces IPL-induced erythema without affecting efficacy: A randomized controlled trial in patients with facial telangiectasias.

BACKGROUND: Laser and intense pulsed light (IPL) are standard symptomatic treatments for superficial telangiectasias, but postoperative erythema, oedema, and pain may prolong downtime. OBJECTIVES: To investigate whether topical brimonidine reduces IPL-induced inflammation in patients with moderate to severe facial telangiectasias. METHODS: A randomized, two-centre, single-blinded, split-face trial on adjuvant brimonidine and air-cooling versus air-cooling alone (control) in 19 patients treated in Denmark (n = 10 patients) and Belgium (n = 9). Brimonidine was applied to the allocated side after each of three facial IPL-treatments, given at 3-week intervals. Patients were assessed up to 1 month after the final treatment. Outcome measures included blinded clinical on-site evaluation of erythema and oedema (5-point-scales), objective erythema-scores (red-filter analysis), patient-evaluated pain (Visual Analogue Scale), IPL-efficacy (blinded photo-evaluation of telangiectasia clearance), and patient preference. RESULTS: In total, 19 patients were enrolled and completed the study. IPL induced moderate to severe erythema after each treatment. Application of brimonidine, reduced erythema to baseline values compared to air-cooling alone and sustained efficacy 24 hours after treatment (median difference reduction: score 1 at each assessment, P ≤ 0.022). Objective erythema-scores supported clinical findings, demonstrating a median erythema reduction of 50-95% after application of brimonidine and air-cooling compared to 9-28% reduction after air-cooling alone (P ≥ 0.002). No difference in reduction of IPL-induced oedema was observed between facial sides (P ≥ 0.227). Brimonidine and air-cooling slightly and consistently reduced postoperative pain compared to air-cooling alone (VAS 1.0 after brimonidine versus VAS 1.5-2.0 after air-cooling alone at treatment 1-3, P ≤ 0.032). At 1-month follow-up, patients experienced excellent clearance of telangiectasias (75-100% clearance) on both facial sides (P = 1.000). Patient preference supported clinical data and 79% of patients preferred brimonidine to control (P = 0.019). CONCLUSION: Compared to air-cooling alone, adjuvant brimonidine reduces IPL-induced erythema and associated pain while maintaining a high IPL-efficacy. Lasers Surg. Med. 50:1002-1009, 2018. © 2018 Wiley Periodicals, Inc.

Early intervention with non-ablative fractional laser to improve cutaneous scarring-A randomized controlled trial on the impact of intervention time and fluence levels.

BACKGROUND AND OBJECTIVES: Laser treatment in the early phases of wound healing may reduce scar formation. However, little is known on when in the early wound healing phases laser exposure most optimally should be provided and at which fluence levels. This study investigates the clinical effect of non-ablative-fractional-laser (NAFL) performed at three early time points at a range of fluence levels versus untreated control scars. MATERIALS AND METHODS: A randomized, controlled, intra-individual trial with erbium-glass 1,540 nm NAFL versus no laser treatment on sixteen subjects receiving 10 standardized full-thickness punch-biopsy wounds. A single NAFL-exposure was applied to test-wounds 1 day before, immediately after, or 2 weeks after wounding. Three fluence levels provided deep and superficial energy depositions (range 30-70 mJ/microbeam). Primary outcome comprised the total-score of the observer part of Patient-Observer-Scar-Assessment-Scale (POSAS), performed by blinded on-site assessment at 3 months follow-up. Secondary outcomes were clinical evaluation on visual-analogue-scale (VAS), reflectance measurements, and histology. RESULTS: NAFL-treatment applied 1 day before, immediately after or 2 weeks after wounding had the potential to offer subtle but detectable improvement in clinical scar appearance compared to untreated controls. Thus, NAFL-exposure 1 day before wounding (POSAS-total: median of 15 vs. control-median of 16, P = 0.03, VAS: median 4.1 vs. control-median 5.5, P = 0.03, medium-fluence), as well as immediately-, and 2 weeks after wounding (POSAS-total: P ≤ 0.05, low-fluence) induced improvement compared to untreated controls. No significant differences in dyschromia were detected between NAFL-treated and control scars. Histology showed subtle changes towards more mature interwoven bundles of collagen in NAFL-treated scars as compared to controls. CONCLUSIONS: This study indicates that a single NAFL-treatment at low to medium fluence performed 1 day prior, or in the early phases of wound healing, may have the potential to optimize scar formation in full thickness wounds. Lasers Surg. Med. 50:28-36, 2018. © 2017 Wiley Periodicals, Inc.

Fractional CO2 laser treatment of caesarean section scars-A randomized controlled split-scar trial with long term follow-up assessment.

BACKGROUND AND OBJECTIVES: Caesarean section (c-section) scars can be pose functional and cosmetic challenges and ablative fractional laser (AFXL) treatment may offer benefit to patients. We evaluated textural and color changes over time in AFXL-treated versus untreated control scars. MATERIALS AND METHODS: A randomized, controlled, intra-individual split-scar trial with three sessions of AFXL-treatments for mature c-section scars. Settings of AFXL were adjusted to each individual scar. End-points were blinded on-site clinical evaluations at 1, 3, and 6 months follow-up (Patient and Observer Scar Assessment Scale [POSAS] and Vancouver Scar Scale [VSS]), blinded photo-evaluations, reflectance measurements, tissue histology, and patients satisfaction. RESULTS: Eleven of 12 patients completed the study. At 1 month follow-up, AFXL-treated scars were significantly improved in pliability (POSAS P = 0.01 VSS P = 0.02) and smoother in surface relief (POSAS P = 0.03) compared to control scars. At 1-3 months, overall scar appearance was dominated by transient erythema and hyperpigmentation, confirmed by reflectance measurements (erythema% and pigmentation% peaked at 1 and 3 month follow-up, respectively). At 6 months follow-up, AFXL-treated scars improved on POSAS-total score though not significantly (P = 0.06). Correspondingly, blinded photo-evaluation found AFXL-treated scars significantly improved compared to controls (VAS P = 0.02). Histology indicated new dermal collagen and elastic fibers on AFXL-treated scars. At 6 months follow-up, a majority of patients (64%) favored subsequent AFXL-treatment of their untreated control scar tissue. CONCLUSIONS: Scar remodeling is initiated 1 month after AFXL treatment, but overall scar improvement is concealed until laser-induced color changes resolve. At 6 months follow-up, the benefit of AFXL treatment on c-section scars emerges. Lasers Surg. Med. 49:189-197, 2017. © 2016 Wiley Periodicals, Inc.

[Dermatological laser- and light treatments of scars].

Many patients struggle with tender, rigid and erythematous scars. Various modalities are used to treat cutaneous scars and in recent years, laser treatments are emerging as promising procedures. This article describes laser systems used for scar treatment according to scar type, evaluates the highest available level of evidence from randomized controlled trials (RCTs) and introduces a guideline for laser treatment of scars. Twelve RCTs documented effect on acne, burn and surgical scars. It is recommended that laser- and light-based treatments are considered according to the scar type.

Topical corticosteroid has no influence on inflammation or efficacy after ingenol mebutate treatment of grade I to III actinic keratoses (AK): A randomized clinical trial.

BACKGROUND: Ingenol mebutate (IngMeb) is approved for treatment of actinic keratoses (AK) and may cause unpredictable local skin responses (LSR). OBJECTIVES: We sought to investigate whether IngMeb-induced LSR, pain, and pruritus could be alleviated with a topical glucocorticoid and, further, to assess efficacy, cosmetic outcome, and patient satisfaction in patients with severe photodamage. METHODS: In this blinded, randomized controlled clinical trial, patients with multiple AK and field cancerization of the face or scalp were treated in 2 areas with IngMeb (0.015%) daily for 3 days. After finalized IngMeb treatment, 1 area was randomized to receive topical clobetasol propionate (0.05%) twice daily for 4 days. Assessments included LSR (0-24; days 1, 4, 8, 15, 57), pain (0-10) and pruritus (0-3; days 1-15), AK clearance (days 15, 57), and cosmetic outcome (0-3; day 57). RESULTS: Clobetasol propionate application had no influence on LSR (P = .939), pain (P = .500), pruritus (P = .312), or AK cure rate (P = .991). Overall, IngMeb cleared 86% of all AK lesions, exerting a therapeutic effect on all AK severity grades; cure rates were 88%, 70%, and 60% for grade I, II, and III AK, respectively. Skin texture improved significantly in remedied areas (2.0 vs 1.0; P < .001); no hypopigmentation, hyperpigmentation, or scarring were observed. LIMITATIONS: These results do not provide safety and efficacy beyond 2 months of follow-up. CONCLUSION: Application of clobetasol propionate does not alleviate IngMeb-induced LSR after 3 days of IngMeb treatment.

Physical activity for primary prevention of disease. Systematic reviews of randomised clinical trials.

BACKGROUND: Drugs are heavily promoted for primary prevention of disease whereas possible benefits of physical activity have received less attention. We have studied whether there is reliable evidence that exercise is effective. METHODS: We searched MEDLINE and The Cochrane Library for systematic reviews of randomised clinical trials published 1998-2004. RESULTS: We identified 31 eligible reviews and excluded 20 that contained trials covered in larger reviews or were older than other reviews on the same subject. The 11 included reviews comprised altogether 252 trials and 16,179 participants. Generally, the included trials were of poor quality. The most reliable result was that exercise in the elderly can reduce falls resulting in injury, relative risk 0.7 (95% confidence interval 0.5 to 0.9), although this effect could be due to modification of risk factors. Other results were a reduction in systolic blood pressure by 3.8 mmHg (2.7 to 5.0) and diastolic blood pressure by 2.6 mmHg (1.8 to 3.4), beneficial changes in blood lipids, a positive effect on bone mineral density in the spine of 1.8% (0.6% to 3.0%), and a lack of effect on smoking cessation. The reporting of harms of exercise was virtually non-existent. CONCLUSION: Exercise can have important benefits. There is a need for large trials that live up to accepted standards and include measurement of harms, in particular for trials that compare exercise with drugs.

Physical activity for secondary prevention of disease. Systematic reviews of randomised clinical trials.

BACKGROUND: Physical activity is recommended for secondary prevention of several diseases but it is not always clear how reliable the evidence is. METHODS: We searched MEDLINE and The Cochrane Library for systematic reviews of randomised clinical trials published 1998-2004. RESULTS: We identified 30 eligible systematic reviews and excluded 13 that contained trials covered in larger reviews or were older than other reviews on the same subject. Physical activity decreased all-cause mortality in patients with coronary heart disease, odds ratio 0.73 (95% confidence interval 0.54 to 0.98), increased maximum walking time in patients with intermittent claudication by 6.5 min (4.4 to 8.7), and decreased pain in patients with osteoarthritis of the knee, standardised mean difference 0.34 (0.24 to 0.44). There were positive effects also in heart failure, chronic obstructive lung disease, type 2 diabetes and fibromyalgia, but they need confirmation in high-quality trials. Exercise improved quality of life in several conditions and generally led to improved physical performance. An effect was not shown in stroke, asthma, rheumatoid arthritis, acute or chronic low back pain, chronic fatigue syndrome, depression, cystic fibrosis or HIV/AIDS. The occurrence of harms was generally not reported. CONCLUSION: Physical activity can have important, and even life-saving, effects as secondary prevention of disease, but more and better trials are needed to fully assess its benefits and harms, in particular trials that compare exercise with drugs.