Clinical guidance for podiatrists in the management of foot problems in rheumatic disorders: evaluation of an educational programme for podiatrists using a mixed methods design.

BACKGROUND: Foot and ankle problems are common in rheumatic disorders and often lead to pain and limitations in functioning, affecting quality of life. There appears to be large variability in the management of foot problems in rheumatic disorders across podiatrists. To increase uniformity and quality of podiatry care for rheumatoid arthritis (RA), osteoarthritis (OA), spondyloarthritis (SpA), and gout a clinical protocol has been developed. RESEARCH OBJECTIVES: [1] to evaluate an educational programme to train podiatrists in the use of the protocol and [2] to explore barriers and facilitators for the use of the protocol in daily practice. METHOD: This study used a mixed method design and included 32 podiatrists in the Netherlands. An educational programme was developed and provided to train the podiatrists in the use of the protocol. They thereafter received a digital questionnaire to evaluate the educational programme. Subsequently, podiatrists used the protocol for three months in their practice. Facilitators and barriers that they experienced in the use of the protocol were determined by a questionnaire. Semi-structured interviews were held to get more in-depth understanding. RESULTS: The mean satisfaction with the educational programme was 7.6 (SD 1.11), on a 11 point scale. Practical knowledge on joint palpation, programme variation and the use of practice cases were valued most. The protocol appeared to provide support in the diagnosis, treatment and evaluation of foot problems in rheumatic disorders and the treatment recommendations were clear and understandable. The main barrier for use of the protocol was time. The protocol has not yet been implemented in the electronic patient file, which makes it more time consuming. Other experienced barriers were the reimbursement for the treatment and financial compensation. CONCLUSIONS: The educational programme concerning the clinical protocol for foot problems in rheumatic disorders appears to be helpful for podiatrists. Podiatrists perceived the protocol as being supportive during patient management. Barriers for use of the protocol were identified and should be addressed prior to large scale implementation. Whether the protocol is also beneficial for patients, needs to be determined in future research.

Biopsy outperforms reflectance confocal microscopy in diagnosing and subtyping basal cell carcinoma: results and experiences from a randomized controlled multicentre trial.

BACKGROUND: Reflectance confocal microscopy (RCM) is a noninvasive method for skin assessment, allowing entire lesion evaluation up to the papillary dermis. RCM is a potentially attractive alternative to punch biopsy (PB) in basal cell carcinoma (BCC). OBJECTIVES: To determine the diagnostic accuracy of RCM vs. PB in diagnosing and subtyping BCC, and to study patient satisfaction and preferences. METHODS: Patients with a clinically suspected primary BCC were randomized between RCM and biopsy. Conventional surgical excision or follow-up were used as reference. Sensitivity and specificity for BCC diagnosis and subtyping were calculated for both methods. BCC subtype was stratified based on clinical relevance: aggressive (infiltrative/micronodular) vs. nonaggressive (superficial/nodular) histopathological subtype and superficial vs. nonsuperficial BCC. Data on patient satisfaction and preferences were collected using a questionnaire and a contingent valuation method. RESULTS: Sensitivity for BCC diagnosis was high and similar for both methods (RCM 99·0% vs. biopsy 99·0%; P = 1·0). Specificity for BCC diagnosis was lower for RCM (59·1% vs. 100·0%; P < 0·001). Sensitivity for aggressive BCC subtypes was lower for RCM (33·3% vs. 77·3%; P = 0·003). Sensitivity for nonsuperficial BCC was not significantly different (RCM 88·9% vs. biopsy 91·0%; P = 0·724). Patient satisfaction and preferences were good and highly comparable for both methods. CONCLUSIONS: Biopsy outperforms RCM in diagnosing and subtyping clinically suspected primary BCC. This outcome does not support routine clinical implementation of RCM, as a replacement for PBs in this patient group.

Neutrophil activation identifies patients with active polyarticular gout.

BACKGROUND: Gout is the most prevalent inflammatory arthritis in developed countries. A gout flare is mediated by phagocytosis of monosodium urate crystals by macrophages and neutrophils leading to subsequent activation of neutrophils contributing to synovitis, local joint destruction, and systemic inflammation. We hypothesize that biomarkers from activated neutrophils reflect gout disease activity. The objective of this study therefore was to investigate the clinical utility of neutrophil-derived biomarkers in gout disease activity. METHODS: Plasma samples from 75 gout patients participating in the "Reade gout cohort Amsterdam" were compared with 30 healthy controls (HC). Levels of neutrophil extracellular traps (NETs) and neutrophil activation markers (calprotectin and peroxidase activity) were analyzed by ELISA and fluorimetry, compared to healthy controls, and related to markers of inflammation and disease activity. RESULTS: Levels of NETs, as well as neutrophil activation markers, were increased in gout patients compared to HC (p < 0.01). No associations were found between markers of cell death (cell-free DNA and NETs) and disease activity. Cell-free levels of genomic DNA were elevated among gout patients compared to HC (p < 0.05) and related to the number of gout attacks in the last year (ß = 0.35, p < 0.01). Peroxidase activity correlated with disease activity (RAPID score: ß = 0.49, p < 0.01, MHAQ: ß = 0.66, p < 0.01) and inflammation markers (CRP: ß = 0.25, p = 0.04, and ESR: ß = 0.57, p < 0.001). Involvement of ankle or wrist resulted in significant higher peroxidase levels compared to mono-articular disease (ß = 0.34, p < 0.01), indicating that peroxidase activity is a marker of poly-articular gout. Calprotectin (S100A8/A9) correlated with the inflammation marker CRP (ß = 0.23, p = 0.05) and morning stiffness, especially in patients with chronic poly-articular gout (ß = 0.71, p < 0.01). CONCLUSIONS: Neutrophil activation markers are associated with characteristics of active, polyarticular gout. Furthermore, NETs are present in the peripheral blood of gout patients. However, NETs do not associate with markers of disease activity or inflammation. Future research should point out if peroxidase and calprotectin could be used in clinical practice as biomarkers for monitoring gout disease activity.

Is a single day patient friendly methyl aminolevulinate photodynamic therapy illumination scheme for superficial basal cell carcinoma feasible? A randomized multicenter pilot trial.

BACKGROUND: Topical methyl aminolevulinate photodynamic therapy (MAL-PDT) is highly effective for the treatment of superficial basal cell carcinoma (sBCC). Current European treatment protocol requires two hospital visits, which is costly and unpractical. The aim of this study was to evaluate the efficacy of fractionated MAL-PDT, using two light fractions at 3 and 4 h compared to illumination at 3 and 5 h after MAL-application. METHODS: Thirty patients were randomized into two groups. The first group received illumination at 3 and 4 h (20 + 55 J/cm2) after MAL-application (3/4 group). In the other group, two light fractions were performed at 3 and 5 h (20 + 55 J/cm2) after MAL-application (3/5 group). The lesion response was evaluated at 3 and 12 months posttreatment. RESULTS: In the 3/5 group, 70.0% showed a complete response (CR) at 3 months compared to 63.6% in the other group. At 12 months, 100% showed a CR in the 3/5 group compared to 80.0% in the other group. However, most failures/recurrences were eventually due to the presence of a more aggressive BCC subtype, mostly caused by sampling error of the primary punch biopsy. CONCLUSION: Single day protocol for MAL-PDT for sBCC is feasible and this study shows promising results.

Oncogenic activation of JAK3-STAT signaling confers clinical sensitivity to PRN371, a novel selective and potent JAK3 inhibitor, in natural killer/T-cell lymphoma.

Aberrant activation of the JAK3-STAT signaling pathway is a characteristic feature of many hematological malignancies. In particular, hyperactivity of this cascade has been observed in natural killer/T-cell lymphoma (NKTL) cases. Although the first-in-class JAK3 inhibitor tofacitinib blocks JAK3 activity in NKTL both in vitro and in vivo, its clinical utilization in cancer therapy has been limited by the pan-JAK inhibition activity. To improve the therapeutic efficacy of JAK3 inhibition in NKTL, we have developed a highly selective and durable JAK3 inhibitor PRN371 that potently inhibits JAK3 activity over the other JAK family members JAK1, JAK2, and TYK2. PRN371 effectively suppresses NKTL cell proliferation and induces apoptosis through abrogation of the JAK3-STAT signaling. Moreover, the activity of PRN371 has a more durable inhibition on JAK3 compared to tofacitinib in vitro, leading to significant tumor growth inhibition in a NKTL xenograft model harboring JAK3 activating mutation. These findings provide a novel therapeutic approach for the treatment of NKTL.

Profiling of volatile organic compounds produced by clinical Aspergillus isolates using gas chromatography-mass spectrometry.

Volatile organic compounds (VOCs) in exhaled breath may identify the presence of invasive pulmonary aspergillosis. We aimed to detect VOC profiles emitted by in vitro cultured, clinical Aspergillus isolates using gas chromatography-mass spectrometry (GC-MS). Three clinical Aspergillus isolates and a reference strain were cultured while conidiation was prevented. Headspace samples were analyzed using a standardized method. Breath samples of patients from which the cultures were obtained were checked for the presence of the VOCs found in vitro. Each Aspergillus isolate produced a distinct VOC profile. These profiles could not be confirmed in exhaled breath in vivo.

Exhaled breath profiles in the monitoring of loss of control and clinical recovery in asthma.

BACKGROUND: Asthma is a chronic inflammatory airway disease, associated with episodes of exacerbations. Therapy with inhaled corticosteroids (ICS) targets airway inflammation, which aims to maintain and restore asthma control. Clinical features are only modestly associated with airways inflammation. Therefore, we hypothesized that exhaled volatile metabolites identify longitudinal changes between clinically stable episodes and loss of asthma control. OBJECTIVES: To determine whether exhaled volatile organic compounds (VOCs) as measured by gas-chromatography/mass-spectrometry (GC/MS) and electronic nose (eNose) technology discriminate between clinically stable and unstable episodes of asthma. METHODS: Twenty-three patients with (partly) controlled mild to moderate persistent asthma using ICS were included in this prospective steroid withdrawal study. Exhaled metabolites were measured at baseline, during loss of control and after recovery. Standardized sampling of exhaled air was performed, after which samples were analysed by GC/MS and eNose. Univariate analysis of covariance (ANCOVA), followed by multivariate principal component analysis (PCA) was used to reduce data dimensionality. Next paired t tests were utilized to analyse within-subject breath profile differences at the different time-points. Finally, associations between exhaled metabolites and sputum inflammation markers were examined. RESULTS: Breath profiles by eNose showed 95% (21/22) correct classification for baseline vs loss of control and 86% (19/22) for loss of control vs recovery. Breath profiles using GC/MS showed accuracies of 68% (14/22) and 77% (17/22) for baseline vs loss of control and loss of control vs recovery, respectively. Significant associations between exhaled metabolites captured by GC/MS and sputum eosinophils were found (Pearson r≥.46, P<.01). CONCLUSIONS & CLINICAL RELEVANCE: Loss of asthma control can be discriminated from clinically stable episodes by longitudinal monitoring of exhaled metabolites measured by GC/MS and particularly eNose. Part of the uncovered biomarkers was associated with sputum eosinophils. These findings provide proof of principle for monitoring and identification of loss of asthma control by breathomics.

Improving early diagnosis of pulmonary infections in patients with febrile neutropenia using low-dose chest computed tomography.

We performed a prospective study in patients with chemotherapy induced febrile neutropenia to investigate the diagnostic value of low-dose computed tomography compared to standard chest radiography. The aim was to compare both modalities for detection of pulmonary infections and to explore performance of low-dose computed tomography for early detection of invasive fungal disease. The low-dose computed tomography remained blinded during the study. A consensus diagnosis of the fever episode made by an expert panel was used as reference standard. We included 67 consecutive patients on the first day of febrile neutropenia. According to the consensus diagnosis 11 patients (16.4%) had pulmonary infections. Sensitivity, specificity, positive predictive value and negative predictive value were 36%, 93%, 50% and 88% for radiography, and 73%, 91%, 62% and 94% for low-dose computed tomography, respectively. An uncorrected McNemar showed no statistical difference (p = 0.197). Mean radiation dose for low-dose computed tomography was 0.24 mSv. Four out of 5 included patients diagnosed with invasive fungal disease had radiographic abnormalities suspect for invasive fungal disease on the low-dose computed tomography scan made on day 1 of fever, compared to none of the chest radiographs. We conclude that chest radiography has little value in the initial assessment of febrile neutropenia on day 1 for detection of pulmonary abnormalities. Low-dose computed tomography improves detection of pulmonary infiltrates and seems capable of detecting invasive fungal disease at a very early stage with a low radiation dose.

Painful skin lesions and squamous cell carcinoma predict overall mortality risk in organ transplant recipients: a cohort study.

BACKGROUND: Organ transplant recipients (OTRs) have a highly increased risk of cutaneous squamous cell carcinomas (SCCs). Sensation of pain in cutaneous tumours is a powerful patient-reported warning signal for invasive SCCs in OTRs. OBJECTIVES: To investigate the impact of painful vs. painless skin lesions and SCC vs. other skin lesions on the overall mortality risk in OTRs. METHODS: We followed 410 OTRs from 10 different centres across Europe and North America between 2008 and 2015. These patients had been enrolled in an earlier study to define clinically meaningful patient-reported warning signals predicting the presence of SCC, and had been included if they had a lesion requiring histological diagnosis. Cumulative incidences of overall mortality were calculated using Kaplan-Meier survival analysis, and risk factors were analysed with Cox proportional hazard analysis. RESULTS: There was an increased overall mortality risk in OTRs who reported painful vs. painless skin lesions, with a hazard ratio (HR) of 1·6 [95% confidence interval (CI) 0·97-2·7], adjusted for age, sex and other relevant factors. There was also an increased overall mortality risk in OTRs diagnosed with SCC compared with other skin lesions, with an adjusted HR of 1·7 (95% CI 1·0-2·8). Mortality due to internal malignancies and systemic infections appeared to prevail in OTRs with SCC. CONCLUSIONS: We suggest that OTRs have an increased overall mortality risk if they develop painful skin lesions or are diagnosed with cutaneous SCC.

Improving the applicability of guidelines on nonmelanoma skin cancer in frail older adults: a multidisciplinary expert consensus and systematic review of current guidelines.

BACKGROUND: Balancing treatment decisions in frail older adults with nonmelanoma skin cancer (NMSC) can be challenging. Clinical practice guidelines (CPGs) could provide assistance. OBJECTIVES: To collect and prioritize items related to frail older adults with NMSC for integration into CPGs and to assess the current extent of this integration. METHODS: Items were collected and prioritized by a multidisciplinary working group (29 members) using a modified Delphi procedure and a five-point Likert scale. To assess current integration of these items in CPGs, a systematic review was subsequently performed by two independent reviewers using five medical databases (PubMed, Embase, Cochrane Library, SUMsearch and Trip Database), websites of guideline developers/databases, and (inter)national dermatological societies. RESULTS: Prioritization of a final 13-item list showed that 'limited life expectancy' (4·5 ± 0·9) and 'treatment goals other than cure' (4·4 ± 0·7) were most desired to be integrated into CPGs; both were included in six (46%) of the CPGs found (n = 13). Attention to 'tumour characteristics' and 'comorbidities' were included in CPGs most often (100% and 77%, respectively). CONCLUSIONS: More attention to items related to frail older adults in NMSC CPGs is broadly desired, but CPG integration of these items is currently limited. More integration might stimulate more holistic, personalized and patient-centred care in frail older adults.

A four-phase strategy for the implementation of reflectance confocal microscopy in dermatology.

BACKGROUND: Reflectance confocal microscopy (RCM) is gradually implemented in dermatology. Strategies for further implementation and practical 'hands on' guidelines are lacking. OBJECTIVE: The primary outcome was to conduct a general strategy for further implementation of RCM. The secondary outcome was the diagnosis of psoriasis and differentiation of stable from unstable psoriatic plaques by means of the 'hands on' protocol, derived from the strategy. METHODS: We used a four-phased model; an exploring phase, a systematic literature search, a clinical approach and, finally, an integration phase to develop a clinical guideline for RCM in psoriasis. Receiver operating characteristic curve statistics was applied to define the accuracy for the diagnosis of unstable psoriasis. RESULTS: A general strategy for further implementation of RCM and practical approach was developed to examine psoriasis by RCM and to distinguish stable from unstable psoriasis. Unstable psoriasis was diagnosed by epidermal inflammatory cell counts with a sensitivity and specificity of 91.7% and 98.3%, respectively, and with an accuracy of 0.92 (area under the curve). In addition, a monitoring model was proposed. CONCLUSION: This is the first study that shows a method for implementation of RCM in dermatology. The strategy and hands on protocol for psoriasis may serve as a model for other dermatological entities and additionally may lead to specialized ready-to-use RCM protocols for clinical dermatological practice.

Daylight photodynamic therapy with methyl aminolevulinate cream is effective and nearly painless in treating actinic keratoses: a randomised, investigator-blinded, controlled, phase III study throughout Europe.

BACKGROUND: Unmet needs exist in actinic keratosis (AK) treatment. Daylight photodynamic therapy (DL-PDT) has shown good efficacy and safety results compared to conventional PDT (c-PDT) in a recent Phase III multi-centre randomised controlled trial in Australia among 100 subjects with AKs. OBJECTIVES: Demonstrate non-inferior efficacy and superior safety of DL-PDT compared to c-PDT in treating multiple mild and/or moderate facial/scalp AKs. METHODS: Phase III, 12 week, multi-centre, randomised, investigator-blinded, controlled, intra-individual study conducted at different latitudes in Europe. AKs of adult subjects were treated once with methyl aminolevulinate (MAL) DL-PDT on one side of the face and MAL c-PDT contralaterally. Endpoints for DL-PDT concerned efficacy (non-inferiority regarding complete lesion response at week 12) and safety (superiority regarding subject's assessment of pain after treatment, on an 11-point numeric rating scale). Safety evaluation also included incidence of adverse events. Subject satisfaction was described using a questionnaire at baseline and last visit. RESULTS: At week 12, the total lesion complete response rate with DL-PDT was similar (non-inferior) to c-PDT (70% vs. 74%, respectively; 95% CI [-9.5; 2.4] in PP analysis, confirmed in ITT analysis). In addition, efficacy of DL-PDT was demonstrated regardless of weather conditions (sunny or cloudy). DL-PDT was nearly painless compared to c-PDT (0.7 vs. 4.4, respectively; P < 0.001), better tolerated and resulted in higher subject satisfaction. CONCLUSION: DL-PDT in comparison with c-PDT was as effective, better tolerated and nearly painless with high patient satisfaction, and may be considered a treatment of choice to meet needs of patients with mild or moderate facial/scalp AKs.

Combining tape stripping and non-invasive reflectance confocal microscopy : an in vivo model to study skin damage.

BACKGROUND: Evaluation of (immuno)histological and cell biological changes in damaged skin requires often an invasive skin biopsy, making in vivo models inappropriate to study skin damage. Reflectance confocal microscopy (RCM) might overcome this limitation. Therefore, we evaluated the use of a tape-stripping model in combination with RCM to provide morphological data on skin damage and recovery. METHODS: In 25 volunteers, a tape-stripping stimulus was applied. The skin was imaged with RCM during 1 week and 3 mm punch biopsies were obtained. RESULTS: Strong correlations between epidermal thickness determined by RCM and conventional histological measurements were found. RCM thickness measurements correlated well with epidermal proliferation. The 10× or 15× repeated tape-stripping resulted in skin damage similar to acute stripping. Mild repeated tape-stripping showed no skin damage. CONCLUSION: Overall, we demonstrated that non-invasive RCM in combination with tape-stripping could be used as model to obtain morphological and cell biological data on skin-material interactions.

[Marjolin ulcer; malignant degeneration in a chronic wound]. / Marjolin-ulcus; maligne ontaarding in een chronische wond.

BACKGROUND: A chronic ulcerating wound may turn malignant. The term 'Marjolin ulcer' is used to describe any skin malignancy which develops in an area of chronic ulceration, irritation or inflammation. It is generally a squamous cell carcinoma. CASE DESCRIPTION: A 66-year-old woman was admitted urgently due to pain and signs of infection in wounds on her back which she had had for six to seven years. The patient had sustained wounds to her back as a result of a hot water scalding at the age of two. These wounds had healed and scarred. Pathological examination of three punch biopsies taken from the margins of the largest ulcer indicated a squamous cell carcinoma; a Marjolin ulcer was diagnosed. CONCLUSION: If a patient has chronic skin lesions associated with non-healing ulcers, especially after sustaining burn injuries as a child, pathological examination is indicated. This can allow a potential skin malignancy to be identified and treated at as early a stage as possible.

Application of leukotriene B4 and reflectance confocal microscopy as a noninvasive in vivo model to study the dynamics of skin inflammation.

BACKGROUND: Application of leukotriene B4 (LTB4) is an established in vivo model that locally induces skin inflammation. Currently in this model, a biopsy is inevitable. In vivo reflectance confocal microscopy (RCM), a noninvasive imaging technique, could overcome this limitation. To find out to what extent RCM may be an in vivo investigative and diagnostic tool in neutrophilic conditions, we studied the dynamics of polymorphonuclear leukocytes (PMN) migration from dermis to stratum corneum using an established LTB4 model. METHODS: Leukotriene B4 was topically applied on the skin of the lower back of seven volunteers. The skin sites were evaluated by RCM for three consecutive days with a 24 h time interval. For histological correlation, 3-mm punch biopsies were obtained. The tissue sections were hematoxylin-eosin and immunohistochemical stained. Minimal and average epidermal thickness was measured. RESULTS: Reflectance confocal microscopy imaging showed highly reflective ill-defined particles with a granular content throughout the epidermis 24 h after application of LTB4. Over time, the appearance of these cells changed throughout the epidermis. Epidermal thickness increased over time, and the measurements based on the RCM images corresponded very well with the histological images. CONCLUSIONS: Reflectance confocal microscopy was able to visualize PMN migration, accumulation, and degeneration over time in the used LTB4 model. The noninvasive character and the possibility to obtain multiple in vivo images from the same location over time make that RCM in combination with this model a useful tool to study the dynamics and function of PMN in inflammatory processes in the skin.

Reflectance confocal microscopy: non-invasive distinction between actinic keratosis and squamous cell carcinoma.

BACKGROUND: Early recognition of squamous cell carcinoma (SCC) is difficult. Non-invasive reflectance confocal microscopic (RCM) imaging of the skin is a promising diagnostic technique. Although several RCM features for SCC and AK have been described, it is not determined whether RCM has the ability to distinguish between SCC and actinic keratosis (AK). OBJECTIVE: To determine in vivo reflectance confocal microscopic features that are specific for making a distinction between AK and SCC. METHODS: In 24 patients, 30 lesions clinically suspicious for AK or SCC were selected for RCM imaging. Following the imaging procedure, a 3 mm skin biopsy was obtained for confirmation of the histopathological diagnosis. Two observers evaluated the RCM images according to a literature based list of RCM features. The obtained data were evaluated by an univariate and forward multivariate logistic regression analysis, kappa analysis and independent T-test. RESULTS: The univariate logistic regression showed statistically significant odds ratios for several RCM features, including architectural disarray in the stratum granulosum, architectural disarray in the spinous layer and nest-like structures in the dermis. The forward multivariate logistic regression analysis showed that the combination of these features increased the ability to make the correct diagnosis AK and SCC non-invasively. The interobserver agreement between a starting and an experienced RCM observer ranged from poor to no agreement. CONCLUSION: This study revealed specific RCM features that can distinguish between AK and SCC, stimulating further prospective, large cohort research in this field. This will result in correct, efficient and adequate diagnosis and treatment of clinically difficult to distinguish AK and SCC lesions.

Prospective differentiation of clinically difficult to distinguish nodular basal cell carcinomas and intradermal nevi by non-invasive Reflectance Confocal Microscopy: a case series study.

BACKGROUND: Clinical differentiation between a nodular basal cell carcinoma (nBCC) and a benign intradermal nevus can be difficult. Even with additional dermoscopic evaluation, a correct diagnosis may be difficult. Currently, histopathological examination of a biopsy is the gold standard to differentiate between these lesions. However, this is an invasive technique and sampling errors can occur. In vivo Reflectance Confocal Microscopy (RCM) is a non-invasive technique to evaluate a skin lesion at a microscopic level. RCM features of nBCCs and intradermal nevi have been described in research setting. However, the use of RCM for prospective differentiation between difficult to diagnose nodules into nBCCs and intradermal nevi in clinical practice has not been demonstrated yet. OBJECTIVE: In this study, we aim to address a common clinical scenario; to differentiate clinically and dermoscopically difficult to distinguish nodules, into nBCCs and intradermal nevi by RCM. MATERIAL AND METHODS: Six patients with clinically and dermoscopically difficult to distinguish nodular skin lesions were evaluated by RCM to differentiate prospectively between nBCCs and intradermal nevi. In five out of six cases, a 3 mm punch biopsy was obtained to confirm the RCM diagnosis. RESULTS: Observed RCM features that allowed differentiation between nBCCs and intradermal nevi were the dermal-epidermal junction patterns, the appearance of the nests and the degree of vascularization. CONCLUSIONS: This case series study demonstrates the value of non-invasive in vivo RCM imaging in routine patient care, with respect to the prospective diagnosis of clinically difficult to distinguish nBCCs and intradermal nevi. Subsequently, biopsies of benign lesions in cosmetic areas could be avoided.