Fibrotic enzymes modulate wound-induced skin tumorigenesis.

Fibroblasts are a major component of the microenvironment of most solid tumours. Recent research elucidated a large heterogeneity and plasticity of activated fibroblasts, indicating that their role in cancer initiation, growth and metastasis is complex and context-dependent. Here, we performed genome-wide expression analysis comparing fibroblasts in normal, inflammatory and tumour-associated skin. Cancer-associated fibroblasts (CAFs) exhibit a fibrotic gene signature in wound-induced tumours, demonstrating persistent extracellular matrix (ECM) remodelling within these tumours. A top upregulated gene in mouse CAFs encodes for PRSS35, a protease capable of collagen remodelling. In human skin, we observed PRSS35 expression uniquely in the stroma of high-grade squamous cell carcinomas. Ablation of PRSS35 in mouse models of wound- or chemically-induced tumorigenesis resulted in aberrant collagen composition in the ECM and increased tumour incidence. Our results indicate that fibrotic enzymes expressed by CAFs can regulate squamous tumour initiation by remodelling the ECM.

A critical re-evaluation of Mohs micrographic surgery for a facial basal cell carcinoma in older adults: Should we waive this treatment in certain patients?

BACKGROUND: Skin cancer incidences are increasing. Treatment for basal cell carcinomas (BCCs) can be questioned in certain patients. Treatment options are various, but Mohs micrographic surgery (MMS) has the highest cure rate. It is, however, time-consuming and results in high logistical burden and treatment costs for both patients and society. OBJECTIVES: This study critically re-evaluates MMS for facial BCCs in older adults. The main objective is to examine all clinical, tumour and patient characteristics in relation to safety and survival to detect a subgroup in which MMS was not the best choice. The overall aim is to identify characteristics that support clinical decision-making in daily practice. METHODS: Patients that received MMS between November 1998 and December 2012 were included. Only patients >75 years with a facial BCC were withheld for analysis. This is a retrospective cohort study, since evaluating the outcome of MMS in accordance with life expectancy is the main objective. Patient charts were evaluated towards comorbidities, complications and survival. RESULTS: This cohort comprises 207 patients. Median survival was 7.85 years. The age-adjusted Charlson comorbidity index (aCCI) was divided into low/medium scores (aCCI < 6) and high scores (aCCI ≥ 6). Median survival was 11.58 years in the low aCCI group and 3.60 years in the high aCCI group (p < 0.001). There was a very strong association between high aCCI and survival (HR, 6.25; 95% CI, 3.83-10.21). Other characteristics were not associated with survival. CONCLUSIONS: Clinicians should assess the aCCI in older patients presenting with a facial BCC before deciding if MMS is an eligible treatment option. High aCCI has shown to be an indicator for low median survival, even in MMS patients with usually high functional status. MMS should be waived as treatment in older patients with high aCCI scores in favour of other, less intensive and less expensive treatment options.

Fractional Carbon Dioxide Laser of Recent Surgical Scars in the Head and Neck Region: A Split-Scar, Evaluator-Blinded Study.

BACKGROUND: Postoperative scarring is a common cause of patient dissatisfaction. Several strategies have been developed to improve its clinical aspects. OBJECTIVE: To assess efficacy and safety of the 10,600 nm ablative fractional carbon dioxide (CO2) laser in the treatment of recent surgical scars in the head and neck region. METHODS AND MATERIALS: A prospective, randomized, single-blind intrapatient controlled study was conducted on 9 postoperative scars in the head and neck region. On half of the scar, 3 treatment sessions were performed. Physician/Patient Global Assessment (PhGA/PGA) and Patient and Observer Scar Assessment Scales (POSAS) were used to evaluate treatment efficacy. Safety was evaluated by registration of pain and adverse events. RESULTS: No statistically significant differences were noted in terms of PhGA or POSAS (observer). Patient Global Assessment (p = 0.058) and POSAS (patient) (p = 0.091) showed a trend toward better improvement of the treated half. Itch score (p = 0.046) and global end evaluation (patient) (p = 0.026) demonstrated a statistically significant difference in favor of the treated part. Adverse events were minor, and no long-term side effects were noted. CONCLUSION: The use of CO2 fractional laser is safe and is associated with high patient satisfaction. However, objective measurements could not confirm its efficacy in the treatment of recent surgical scars.

Nonablative fractional laser resurfacing for the treatment of hypertrophic scars: a randomized controlled trial.

BACKGROUND: Nonablative fractional laser (NAFL) therapy is a noninvasive procedure that has been suggested as a treatment option for hypertrophic scars. OBJECTIVES: To evaluate the efficacy and safety of 1540-nm NAFL therapy in the treatment of hypertrophic scars. MATERIALS AND METHODS: An intraindividual randomized controlled trial (RCT) with split lesion design and single-blinded outcome evaluations. Patients received four NAFL treatments at monthly intervals. Primary endpoint was a blinded on-site visual and palpable Physician Global Assessment (PhGA). Adverse event registration and pain evaluation were used to evaluate safety. Patient global assessment (PGA) was a secondary endpoint to additionally evaluate efficacy. RESULTS: The PhGA did not find a statistically significant difference between the treated and untreated control side of 18 patients, although there was significant difference on the PGA 1 (p = .006) and 3 (p = .02) months after last treatment (Wilcoxon signed rank test). Patients experienced moderate pain during treatment and mild adverse events. CONCLUSION: In this trial, blinded PhGA could not confirm the clinical efficacy of 1540-nm nonablative fractional laser in the treatment of hypertrophic scars, but the treatment is safe, and patients judged that the treated part had a better global appearance.

The therapeutic dilemma of basal cell carcinoma in older adults: A review of the current literature.

Skin cancer is known to be a significant health care threat due to the massively increasing numbers of diagnoses. In 2019, 4 million basal cell carcinoma (BCC) cases were diagnosed globally, making BCC the most frequent of all cancers worldwide in fair skinned populations. Given the increasing life-expectancy for all countries worldwide (by 2050, the world's population of people aged 60 years and older will have doubled), the incidence of BCC is expected to keep increasing in the future. Management of BCCs is challenging, especially among older adults, as mortality due to BCCs is extremely rare, whereas locally destructive growth can cause significant morbidity in certain cases. Therapeutic management in this population is further hampered because of the presence of comorbidities, frailty, and the heterogeneity of these aspects in older patients, leading to treatment dilemmas. A literature review was conducted to identify relevant patient, tumour, and treatment related factors that should be considered in the decision making for BCC treatment in older adults. This narrative review synthesizes all aspects concerning BCC treatment in older adults and aims to make some specific suggestions considering BCC treatment in older adults that can be used in daily practice. We found that nodular BCC was found to be the most common subtype in older adults, most frequently located in the head and neck region. In non-facial BCCs, current literature has shown no significant impact on the quality of life (QoL) in older patients. Besides comorbidity scores, functional status should guide clinicians in treatment decisions. Taking all aspects into account when making treatment decisions is of great importance. When treating superficial BCCs on difficult-to-reach lesions in older adults, a clinician-administered treatment should be suggested because of possible impaired mobility in these patients. Based on current literature, we recommend assessing the comorbidities, the functional status, and frailty in older patients with BCC to evaluate life expectancy. In patients with low-risk BCCs and a limited life expectancy (LLE), an active surveillance or watchful waiting strategy can be suggested.

Study protocol of the BASINEL Study: a pragmatic randomised controlled trial investigating treatment versus no treatment of low-risk basal cell carcinomas in older persons.

INTRODUCTION: Basal cell carcinomas (BCCs) represent 70% of all skin cancers. These tumours do not metastasise but are locally invasive if left untreated. There is a high incidence of BCC in the elderly, and clinicians frequently face important treatment dilemmas. The approach to BCC in the elderly should be investigated thoroughly. METHODS AND ANALYSIS: Data on health-related quality of life (HrQoL), survival and complication rate will be examined in a treatment and a non-treatment arm (1:1 allocation). In the non-treatment arm, in vivo biological behaviour of low-risk BCCs in elderly patients will be examined. The main objective is to combine tumour characteristics with demographic data, in order to determine whether treatment will positively affect the patients' HrQoL within a predetermined time frame. A monocentric randomised controlled trial (RCT) was designed at the Ghent University Hospital. The study population consists of patients with the minimum age of 75 years and a new diagnosis of (a) low-risk BCC(s). Patients in the treatment arm will receive standard care. Patients in the non-treatment arm will be closely monitored: the tumour will be intensively evaluated using multispectral dermoscopy, reflectance confocal microscopy and high-definition optical coherence tomography. All patients will be asked to fill in a questionnaire concerning their HrQoL at consecutive time points. Patient-reported side effects will be evaluated via an additional questionnaire.Primary outcomes will include the difference in HrQoL and the difference in complication risks (treatment vs non-treatment) at different time points of the study. Secondary endpoints are the evolution of the BCCs in the non-treatment arm and the long-term survival in both study arms. Tertiary endpoint is the treatment effectiveness in the treatment arm. The sample size calculation was performed and resulted in a target sample size of 272 patients in this study with a 1:1 allocation. ETHICS AND DISSEMINATION: Subjects can withdraw from participating in this study at any time for any reason without any consequences. Approval for this study was received from the Ethics Committee of the Ghent University Hospital on 26 August 2021.The results of this RCT will be submitted for publication in one or more international, peer-reviewed medical journals, regardless of the nature of the study results. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT05110924).

Teledermatology in Belgium: a pilot study.

Background: Teledermatology, the application of telemedicine in the field of dermatology, can be a valuable tool to improve the efficiency of care in general practice.Objectives: In this pilot study, we implemented a teledermatology programme in Belgian context to assess the effect on referral rate and to evaluate the acceptability of teledermatology by clinicians and patients.Material and methods: A store-and-forward teledermatology service between 12 general practitioners (GPs) and 3 academic dermatologists was evaluated for a period of 3-6 months. Clinicians and patients were questioned about satisfaction, benefits and barriers.Results: In total, 54 teledermatologic consultations were performed. The referral rate was reduced. Thirty-one teleconsulations were performed instead of physical referral, of which nine patients were actually referred. In 23 cases, performed for a second opinion, two more patients were referred on the dermatologist's advice.All clinicians want to continue working with teledermatology. GPs highlighted the educational benefit, whereas dermatologists were interested in the triage effect and reduced referral rate. Patients indicated that teledermatology would encourage them to consult a GP sooner when experiencing dermatologic problems.Conclusion: Teledermatology proved to be a feasible and acceptable tool for both clinicians and patients. It also shows to be a valuable for triage and reducing unnecessary referrals. Considering the emergent pressure on health care in the next decades, teledermatology following GP selection could be useful for the Belgian health care system and deserves further elaboration in the search for effective tools to strengthen first line health care and streamline referral to secondary care.

Origin, clinical presentation, and diagnosis of hypomelanotic skin disorders.

Hypomelanotic skin disorders are cutaneous pigmentary disorders characterized by a reduced melanin content in the skin that results in a lightening of the skin. Establishing the correct diagnosis for hypomelanotic skin disorders requires a good history, a detailed physical examination, the use of special lighting techniques, such as Wood's light, and sometimes a biopsy of the abnormally pigmented skin and the normally pigmented skin. This article focuses on the origin, clinical presentation, and diagnosis of acquired hypomelanotic skin disorders. An algorithm for the diagnostic approach to these hypomelanoses is given.

Topical pimecrolimus in the treatment of vitiligo.

Although the treatment of vitiligo has improved during the last decade, therapy is still not satisfactory for many patients. Recently topical calcineurin inhibitors were introduced in the treatment of atopic dermatitis. Considering the autoimmune hypothesis of vitiligo pathogenesis, the use of these topical calcineurin inhibitors seems reasonable. Most clinical vitiligo trials have been performed with tacrolimus and show beneficial effects. Concerning the value of pimecrolimus in the treatment of vitiligo only few data are available. Therefore we performed an open pilot study in 26 patients to evaluate the efficacy and safety of 1% pimecrolimus in the treatment of vitiliginous lesions in the head and neck region. In 13 of 26 (50%) evaluated target lesions, repigmentation was noted after a 6 month treatment period with a median percentage of repigmentation of 72.9% (interquartile range: 30.5-98.3%). Duration of vitiligo and total affected body surface area tended to be inversely correlated with the success rate of treatment. Side effects were mainly limited to a burning sensation at the application site. Despite the promising results of topical immunomodulators in the treatment of vitiligo, prudence is in order, as long-term follow up studies are still lacking.

Total-Body Examination vs Lesion-Directed Skin Cancer Screening.

IMPORTANCE: Skin cancer is the most frequent cancer type. It remains unknown if and how screening programs can be organized in a cost-effective manner. OBJECTIVE: To compare the 2 screening strategies of systematic total-body examination (TBE) and lesion-directed screening (LDS), with a focus on the participation rate, detection rate, anxiety, and cost. DESIGN, SETTING, AND PARTICIPANTS: Population-based cross-sectional screenings by a team of 6 dermatologists were organized in 2 sociodemographically similar regions. The TBE was organized in a community of 9325 inhabitants 18 years and older (Wichelen, East Flanders, Belgium) during a 5-day screening (March 14-18, 2014). The LDS was organized in a sociodemographically comparable community (Nevele, East Flanders, Belgium) of 9484 adult inhabitants during a 4-day screening (April 22 and 25-27, 2014). The first population received a personal invitation for a standard TBE. In the second population, individuals were invited for an LDS if they had a lesion meeting 1 or more of the following criteria: ABCD rule (A, asymmetry; B, borders; C, colors; and D, differential structures), ugly duckling sign, new lesion lasting longer than 4 weeks, or red nonhealing lesions. MAIN OUTCOMES AND MEASURES: In total, 1982 individuals were screened, and 47 skin cancers (2.4%) were histologically confirmed, including 9 melanomas (0.5%), 37 basal cell carcinomas (1.9%), and 1 squamous cell carcinoma or Bowen disease (0.1%). RESULTS: The positive predictive value for all suspicious lesions was 56.6% (47 of 83). The participation rate was 17.9% (1668 of 9325) in the TBE group vs 3.3% (314 of 9484) in the LDS group (P < .01). The skin cancer detection rate per 100 participants did not differ significantly between the 2 groups, with rates of 2.3% (39 of 1668) in the TBE group vs 3.2% (8 of 248) in the LDS group (P = .40). The operational effectiveness per 100 invitees was 0.4% (39 of 9325) in the TBE group vs 0.1% (8 of 9484) in the LDS group (P < .01). In addition, LDS was 5.6 times less time consuming than TBE. Participants in the LDS group had significantly higher baseline anxiety levels compared with participants in the TBE group (3.7 vs 3.3 points on a visual analog scale, P < .01). In screenees without a suspicious lesion, anxiety levels significantly dropped after screening. CONCLUSIONS AND RELEVANCE: Total-body examination yielded a higher absolute number of skin cancers. Lesion-directed screening had a similar detection rate of 3.2% (8 of 248) but was 5.6 times less time consuming. When performed by dermatologists, LDS is an acceptable alternative screening method in health care systems with limited budgets or long waiting lists.

Double-blind placebo-controlled study of autologous transplanted epidermal cell suspensions for repigmenting vitiligo.

OBJECTIVES: To investigate the efficacy of epidermal noncultured cellular grafting in patients with vitiligo and the role of postinflammatory, spontaneous, or UV-induced pigmentation in obtaining repigmentation. DESIGN: A prospective, randomized, double-blind, placebo-controlled study. SETTING: Ambulatory patients in an institutional practice. Patients were followed up for 3 to 12 months. PATIENTS: A total of 33 paired, symmetrically distributed leukodermic lesions, all resistant to therapy, were observed in 28 patients. Nineteen patients appeared to have a stable vitiligo (group 1), whereas there was doubt about the stability of the disease in 9 patients (group 2). INTERVENTION: After laser ablation, a hyaluronic acid-enriched cellular graft was applied to 1 lesion while the paired lesion received placebo. Three weeks later all lesions were exposed to UV irradiation twice per week for approximately 2 months. MAIN OUTCOME MEASURES: Primarily, the percentage of repigmentation was assessed after 3, 6, and 12 months using a digital image analysis system. The repigmentation pattern was also evaluated after 1 and 3 months. RESULTS: A strongly significant difference between cellular grafts and placebo was observed after 3, 6, and 12 months (P<.001, P = .002, and P = .002, respectively). In group 1, repigmentation of at least 70% of the treated area was achieved in 55%, 57%, and 77% of the actively treated lesions 3, 6, and 12 months after treatment, whereas in group 2 repigmentation of at least 70% of the treated area was not observed at any time point. The repigmentation pattern was diffuse in 94% of the responding patients. CONCLUSIONS: After a strict preoperative selection for disease stability, transplantation resulted in repigmentation of at least 70% of the treated area in most actively treated vitiligo lesions. Repigmentation was primarily caused by the transplanted melanocytes.

A new digital image analysis system useful for surface assessment of vitiligo lesions in transplantation studies.

So far there is no uniformity in the evaluation methods used in the assessment of treatment outcome in vitiligo studies. The ability to objectively measure surfaces of vitiligo lesions is important for both clinical practice and research. Our objective was to assess the reproducibility, accuracy, user-friendliness and time effectiveness of a new digital image analysis system for surface measurement of vitiligo lesions. Three different observers performed both a visual estimation and a digital image analysis on 30 images of 10 vitiligo lesions. Inter- and intra-observer variation were evaluated and results were compared with the 2D gold standard measurements and a 3D measurement. A high inter- and intra-observer variability was observed for the visual estimation of surfaces. With the digital image analysis system a significant improvement of the reproducibility was achieved (p = 0.01). Moreover, results were accurate and the measurement procedure was user-friendly. Importantly, a systematic underestimation was demonstrated when comparing the 2D with the 3D measurements. We introduced an objective measurement method that might be useful in the future for consistently measuring surfaces of selected vitiligo lesions both before and after different therapeutic modalities.

Management of vitiligo patients and attitude of dermatologists towards vitiligo.

As vitiligo does not cause any physical impairment, it is often considered unimportant by physicians. Vitiligo patients repeatedly experience disinterest from the medical world regarding their skin problem. A questionnaire survey was used to assess the management of vitiligo patients and the attitude of dermatologists towards vitiligo in Belgium. Vitiligo patients (n = 244) visiting an academic affiliated dermatology department were included and 454 out of 558 Belgian dermatologists returned a mailed questionnaire. Vitiligo patients do not often visit a doctor concerning their disease and do not often treat their disease. Disease severity as reported by the patient is correlated with the number of doctor visits (p = 0.001) but not to treatment of the disease. Information about the treatment and physician's encouragement to treat seem important in motivating patients to treat their vitiligo, but 50% of the patients were not adequately informed about their disease and its treatment during their first doctor visit. Today, nearly all the dermatologists report widely informing their patients, but only 36% of them encourage their patients to treat their disease, being pessimistic concerning expected treatment results. Interestingly, two thirds of the patients who ever treated their disease find it worthwhile.

Cross-cultural inequivalence of dermatology-specific health-related quality of life instruments in psoriasis patients.

The dermatology life questionnaire index (DLQI) and the Skindex are the most commonly used dermatology-specific health-related quality of life (HRQOL) instruments. Although these tools are used in international surveys and clinical trials, the cross-cultural equivalence of their items has not been documented. We used differential item functioning (DIF), which is part of the Rasch model, to assess the impact of cultural background on the items of the DLQI and Skindex-29 and-17. The data of the 450 psoriasis patients, who attended in- and outpatient dermatology centers, was collected retrospectively from five European and one US center. The DLQI and Skindex-29 scales did not fit the Rasch model (P<0.0008) and 10/10 of the DLQI and 19/29 of the Skindex-29 items displayed significant DIF. Although the psychosocial scale of the Skindex-17 fitted the Rasch model, half or more of the items of the psychosocial (6/12) and the symptom scale (4/5) showed significant DIF across countries. These findings suggest that psoriasis patients from different countries respond differently to a substantial proportion of DLQI and Skindex items despite having the same level of underlying HRQOL impairment. Therefore, these instruments should not be used in their current form in international studies.

Subjective and objective evaluation of noncultured epidermal cellular grafting for repigmenting vitiligo.

BACKGROUND: Noncultured epidermal cell transplantation in vitiligo permits the coverage of relatively large areas without culturing cells. OBJECTIVE: To investigate the effectiveness of noncultured epidermal cell transplantation in treating stabilized vitiligo using objective and subjective evaluation methods. METHODS: Noncultured autologous melanocytes and keratinocytes were grafted in a hyaluronic-acid-enriched suspension on superficially laser-abraded vitiligo lesions in 40 patients with refractory stable vitiligo (30 with generalized and 10 with localized vitiligo). The repigmentation was evaluated 3-12 months after grafting using a digital image analysis system. Furthermore the treatment was evaluated from the patients' point of view with the DLQI (Dermatology Life Quality Index) and a 'global assessment'. RESULTS: The mean percentage of repigmentation, evaluated at the last follow-up visit, was 72% (median 84%), and a repigmentation of >or=70% was observed in 62% of patients. The best results were achieved in the neck and the presternal region. A subjective evaluation was performed in half of the subjects. The mean DLQI score at inclusion (6.95, SD = 6.68, n = 20) was significantly decreased after treatment (p = 0.013, mean 3.85, SD = 4.13, n = 20). The patients were satisfied with the achieved result, found it worthwhile to undergo the treatment and would choose it again. CONCLUSION: According to both subjective and objective evaluation methods, noncultured epidermal cell transplantation is promising in patients with stable vitiligo.

Evidence for an autoimmune pathogenesis of vitiligo.

Vitiligo is a depigmenting disorder characterized by the development of white patches in various distributions, which are due to the loss of melanocytes from the epidermis. A variety of arguments from clinical observations to research findings in human and animal models support the hypothesis of autoimmunity and are reviewed in this article. The association with autoimmune diseases and organ-specific autoantibodies is well known. Various effective treatment options have an immunosuppressive effect. Today the autoimmune pathogenesis of the disease has become a rapidly evolving field of research. Detection of circulating melanocyte antibodies in human and animal models implicates a possible role of humoral immunity. Histological and immunohistochemical studies in perilesional skin suggest the involvement of cellular immunity in vitiligo. Recently, T-cell analyses in peripheral blood further support this hypothesis. Interestingly, new insights in the association of vitiligo and melanoma may help to clarify the role of autoimmunity in the development of vitiligo.

Bowen's disease of the nail.

We present a case of Bowen's disease of the nail bed in a 60-year-old male. This case should remind us to biopsy any chronic lesion of the nail in order to reduce the delay in diagnosis. Indeed Bowen's disease of the nail unit often presents as a clinically misleading 'benign' lesion. Early diagnosis is important as this precancerous lesion appears to have a more aggressive behavior when it affects the nail unit. Bowen's disease of the nail is therefore considered as a squamous cell carcinoma, and both entities are grouped under the term 'epidermoid carcinoma'. Surgical excision is the first treatment option for those tumors without bone involvement. Our patient was treated with Mohs' micrographic surgery which is considered the ideal surgical treatment as it ensures a complete eradication of the tumor in over 90% of the cases but also maximally preserves normal tissue and function. This case illustrates the challenge of Mohs' surgery on the nail unit due to its particular anatomy and histology.