Dermoscopy, confocal microscopy and optical coherence tomography features of main inflammatory and autoimmune skin diseases: A systematic review.

BACKGROUND/OBJECTIVES: Non-invasive skin imaging features of main skin inflammatory and autoimmune diseases have been reported, although a comprehensive review of their correlation with histopathologic features is currently lacking. Therefore, the aim of this paper was to review the correlation of dermoscopic, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) criteria of main inflammatory and autoimmune skin diseases with their corresponding histopathologic criteria correlation. METHODS: Studies on human subjects affected by main inflammatory and autoimmune diseases, defining the correlation of dermoscopic, RCM or OCT with histopathologic criteria, were included in the review. Five groups of diseases were identified and described: psoriasiform, spongiotic and interface dermatitis, bullous diseases and scleroderma. RESULTS: Psoriasiform dermatitis was typified by white scales, corresponding to hyperkeratosis, and vessels, observed with RCM and OCT. Spongiosis, corresponding to dark areas within the epidermis with RCM and OCT, was the main feature of spongiotic dermatitis. Interface dermatitis was characterised by dermoepidermal junction obscuration. Blisters, typical of bullous diseases, were visualised as dark areas with RCM and OCT while scleroderma lesions were characterised by dermoscopic fibrotic beams, related to dermal thickness variations, with specific OCT and histopathologic correlations. CONCLUSIONS: Although the role of RCM and OCT has yet to be defined in clinical practice, non-invasive skin imaging shows promising results on inflammatory and autoimmune skin diseases, due to the correlation with histopathologic features.

Dabigatran-Induced Nephropathy and Gastrointestinal Bleeding and Its Successful Treatment with Idarucizumab: A Case Report.

Recently, the atrial fibrillation treatment guidelines have been updated to now recommend Non-vitamin K antagonist oral anticoagulants (NOACs) as the preferred alternative to warfarin for systemic embolism and stroke prevention in patients with non-valvular atrial fibrillation. NOACs have major pharmacologic advantages over warfarin, although the most common complications are gastrointestinal bleeding and NOAC-induced nephropathy within 6 weeks after starting therapy, as several recent case-reports stated. We are reporting for the first time a chronic delayed adverse reaction (regularly reported to Authorities) observed in an 82-year-old woman 27 months after starting dabigatran (110 mg twice a day), characterized by concomitant gastrointestinal bleeding and nephropathy. Idarucizumab administration immediately improved both bleeding and renal parameters. Moreover, we are going to highlight the importance of the compliance, the adherence to the therapeutic plan and the supervision of the Hospital Pharmacy on drug prescriptions. In fact in our case, dabigatran was firstly prescribed by the neurologist and delivered by the hospital pharmacy, but the patient continued the treatment for 27 months, prescribed by general practitioner without any laboratory control. This lack of supervision certainly contributed to the onset of the adverse reaction reported.

Dimethyl fumarate treatment for psoriasis in a real-life setting: A multicentric retrospective study.

Dimethyl fumarate (DMF) is a fumaric acid esters derivate approved for plaque psoriasis as first-line systemic therapy. It has been available in Italy since 2017 and an increasing number of patients are treated with this drug. To evaluate DMF effectiveness, side effects and drug survival in a dermatological real-life setting. We performed a retrospective multi-center study in five dermatologic clinics in Emilia-Romagna, Northern Italy, which included all consecutive patients affected by moderate-severe psoriasis treated with DMF. We assessed effectiveness (in terms of PASI50 and PASI75 in an intention to treat observation) and safety (occurrence of side effects) of DMF and their association with demographic and disease characteristics, mean daily dose taken and treatment discontinuation. We included 103 patients, 78 (75.72%) had at least one comorbidity including 19 (18.44%) with a history of cancer; the mean treatment duration was 23.61 ± 17.99 weeks (min 4, max 130) and the mean daily dose was 262.13 ± 190.94 mg. Twenty-four patients (23.30%) reached PASI75 at week 12, while a further 18 patients (17.47%) reached it at week 26. Side effects occurred in 63 patients (61.16%), the most frequent were diarrhea, epigastric discomfort, nausea, and flushing. Sixteen patients (15.53%) showed an alteration of laboratory tests. In some cases side effects were transitory, while in 53 patients (51.45%) they led to cessation of therapy. The median daily dose showed a direct association with PASI50 achievement and an indirect association with treatment discontinuation. Our study shows the peculiarities of DMF in a real-world setting: effectiveness is often reached after 12 weeks of treatment and side effects could limit the continuation of the therapy but, at the same time, DMF has no major contraindications and, due to the wide range of dosage, it can allow both to manage side effects and to personalize the prescription for each patient.

High magnification digital dermoscopy of basal cell carcinoma: a single-centre study on 400 cases.

The aim of this study was to assess the frequency of classic dermoscopic basal cell carcinoma (BCC) features and the sensitivity of new descriptors, such as light brown nests (homogeneous and structured) only visible employing a high magnification digital videomicroscope. A retrospective analysis of 2,024 highly magnified digital images referring to 400 BCCs was performed by 3 independent observers, who assessed 11 classic BCC descriptors and the new ones. Light brown nests were detected in 40.5% of BCCs. Homogeneous ones were observable in 17.8%, and structured nests in 32.8%. Light brown nests were visible in 14.3% of non-pigmented lesions, whereas in the pigmented groups these were observed in 42-54% of the cases. We suggest that brown nests described in this study may improve early recognition of superficial BCCs and of non-pigmented or slightly pigmented ones that may lack classic dermoscopic patterns.

High-resolution imaging of basal cell carcinoma: a comparison between multiphoton microscopy with fluorescence lifetime imaging and reflectance confocal microscopy.

AIMS: The aim of this study was to compare morphological aspects of basal cell carcinoma (BCC) as assessed by two different imaging methods: in vivo reflectance confocal microscopy (RCM) and multiphoton tomography with fluorescence lifetime imaging implementation (MPT-FLIM). METHODS: The study comprised 16 BCCs for which a complete set of RCM and MPT-FLIM images were available. The presence of seven MPT-FLIM descriptors was evaluated. The presence of seven RCM equivalent parameters was scored in accordance to their extension. Chi-squared test with Fisher's exact test and Spearman's rank correlation coefficient were determined between MPT-FLIM scores and adjusted-RCM scores. RESULTS: MPT-FLIM and RCM descriptors of BCC were coupled to match the descriptors that define the same pathological structures. The comparison included: Streaming and Aligned elongated cells, Streaming with multiple directions and Double alignment, Palisading (RCM) and Palisading (MPT-FLIM), Typical tumor islands, and Cell islands surrounded by fibers, Dark silhouettes and Phantom islands, Plump bright cells and Melanophages, Vessels (RCM), and Vessels (MPT-FLIM). The parameters that were significantly correlated were Melanophages/Plump Bright Cells, Aligned elongated cells/Streaming, Double alignment/Streaming with multiple directions, and Palisading (MPT-FLIM)/Palisading (RCM). CONCLUSION: According to our data, both methods are suitable to image BCC's features. The concordance between MPT-FLIM and RCM is high, with some limitations due to the technical differences between the two devices. The hardest difficulty when comparing the images generated by the two imaging modalities is represented by their different field of view.

Diagnosis of BCC by multiphoton laser tomography.

BACKGROUND/PURPOSE: Multiphoton Laser Tomography (MPT) is a non-linear optical technique that gives access to morphology and structure of both cells and extracellular matrix of the skin through the combination of autofluorescence imaging and second harmonic generation (SHG). The aim of this study was to identify MPT descriptors on ex vivo specimens of basal cell carcinoma (BCC) to assess the sensitivity and specificity of these criteria for the diagnosis of BCC and its differentiation from other skin tumours, inflammatory diseases and healthy skin. METHODS: In the preliminary study, MPT images referring to 24 BCCs and 24 healthy skin samples were simultaneously evaluated by three observers for the identification of features characteristic of BCC. In the main study, the presence/absence of the descriptors identified in the preliminary study was blindly evaluated on a test set, comprising 66 BCCs, 66 healthy skin samples and 66 skin lesions, including 23 nevi, 8 melanomas, 17 skin tumours and other skin lesions by 3 independent observers. RESULTS: In the preliminary study, three epidermal descriptors and six descriptors for BCC were identified. The latter included aligned elongated cells, double alignment of cells, cell nests with palisading and phantom islands. From the test set, 56 BCCs were correctly diagnosed, whereas in 10 cases the diagnosis was 'other lesions'. However, it was always possible to exclude the diagnosis of BCC in healthy skin and other lesion samples. Thus, overall sensitivity of the method was 84.85, whereas a specificity of 100% was observed with respect to both healthy skin and 'other lesions'. CONCLUSIONS: This study describes new morphological descriptors of BCC enabling its characterization and its distinction from healthy skin and other skin lesions in ex vivo samples, and demonstrates for the first time that MPT represents a sensitive and specific technique for the diagnosis of BCC.

High resolution diagnosis of common nevi by multiphoton laser tomography and fluorescence lifetime imaging.

BACKGROUND: Multiphoton Laser Tomography (MPT) has developed as a non-invasive tool that allows real-time observation of the skin with subcellular resolution. MPT is readily combined with time resolved detectors to achieve fluorescence lifetime imaging (FLIM). The aim of our study was to identify morphologic MPT/FLIM descriptors of melanocytic nevi, referring to cellular and architectural features. METHODS: In the preliminary study, MPT/FLIM images referring to 16 ex vivo nevi were simultaneously evaluated by 3 observers for the identification of morphologic descriptors characteristic of melanocytic nevi. Proposed descriptors were discussed and the parameters referring to epidermal keratinocytes, epidermal melanocytes, dermo-epidermal junction, papillary dermis and overall architecture were selected. In the main study, the presence/absence of the specified criteria were blindly evaluated on a test set, comprising 102 ex vivo samples (51 melanocytic nevi, 51 miscellaneous skin lesions) by 2 observers. RESULTS: Twelve descriptors were identified: "short-lifetime cells in the stratum corneum", "melanin-containing keratinocytes", "dendritic cells", "small short-lifetime cells" in the upper and lower layers", "edged papillae", "non-edged papillae", "junctional nests of short-lifetime cells", "dermal cell clusters", "short-lifetime cells in the papilla", "monomorphic and regular histoarchitecture", "architectural disarray". CONCLUSION: Identified descriptors for benign melanocytic lesions proved sensitive and specific, enabling the differentiation between melanocytic nevi and non-melanocytic lesions.

Multiphoton laser tomography and fluorescence lifetime imaging of basal cell carcinoma: morphologic features for non-invasive diagnostics.

Multiphoton laser tomography (MPT) combined with fluorescence lifetime imaging (FLIM) is a non-invasive imaging technique, which gives access to the cellular and extracellular morphology of the skin. The aim of our study was to assess the sensitivity and specificity of MPT/FLIM descriptors for basal cell carcinoma (BCC), to improve BCC diagnosis and the identification of tumor margins. In the preliminary study, FLIM images referring to 35 BCCs and 35 healthy skin samples were evaluated for the identification of morphologic descriptors characteristic of BCC. In the main study, the selected parameters were blindly evaluated on a test set comprising 63 BCCs, 63 healthy skin samples and 66 skin lesions. Moreover, FLIM values inside a region of interest were calculated on 98 healthy skin and 98 BCC samples. In the preliminary study, three epidermal descriptors and 7 BCC descriptors were identified. The specificity of the diagnostic criteria versus 'other lesions' was extremely high, indicating that the presence of at least one BCC descriptor makes the diagnosis of 'other lesion' extremely unlikely. FLIM values referring to BCC cells significantly differed from those of healthy skin. In this study, we identified morphological and numerical descriptors enabling the differentiation of BCC from other skin disorders and its distinction from healthy skin in ex vivo samples. In future, MPT/FLIM may be applied to skin lesions to provide direct clinical guidance before biopsy and histological examination and for the identification of tumor margins allowing a complete surgical removal.

Efficacy of D-pigment dermocosmetic lightening product for solar lentigo lesions of the hand: A randomized controlled trial.

Solar lentigo, benign lesions which mostly appear on chronically, sun-exposed surfaces, are associated with ageing. Patients are increasingly requesting a more uniform skin texture, especially for hands. Treatment options include dermoabrasion, intense pulsed light, cryotherapy, peelings, and laser therapy. Topical compounds can be employed, in alternative or associated with dermatologic procedures. The current study was designed to evaluate solar lentigo hyperpigmentation, skin architecture and clinician and patient assessments comparing a dermocosmetic lightening product (active) with a moisturizing product (control) according to clinical, digital and subjective analyses in 72 lesions over 12-month follow up period. Statistically significant differences were observed between the lesions treated with the active compared to the control in terms of papillary brightness (p = 0.03) and contrast (p = 0.03), and in the limitation of dermal-epidermal junction destructuring (p = 0.03) according to dermal-epidermal junction destructuring score at Reflectance Confocal Microscopy. Luminance (p = 0.04) and redness (p = 0.03) were improved at color analysis, and physician and patient evaluations favored the active in efficacy and patient satisfaction investigations. The dermocosmetic lightening product utilized in the current study proved to be more effective, according to clinical, digital and subjective analyses in reducing lesion hyperpigmentation, stabilizing the lesion skin architecture and increasing patient satisfaction compared to the control in a cohort of 36 subjects, over a 12-month period. Beside demonstrating the efficacy of this topical lightening product, we propose a "destructuring score", which improves the robustness of solar lentigo's evaluation, and can be used in future studies to standardize the quantitative comparisons of different treatment options.

Long-term efficacy of high doses of intravenous immunoglobulins in generalized scleromyxoedema: Case report.

Scleromyxoedema is a rare disease with a progressive and disabling course involving dermal deposition of mucin and fibroblast proliferation; it is characterized clinically by a diffuse papular eruption, skin thickening, oedema and decreased skin flexibility, especially of the face and hands. Current therapy options are based on evidence from a limited number of case reports. The clinical manifestations and treatment of a 64-year-old man affected by scleromyxoedema with severe skin involvement of the face, arms and hands, decreased mouth opening and hypomotility of the fingers are reported. Dysphagia, asthenia and immunoglobulin G lambda monoclonal gammopathy were also present. Previous treatment with topical and systemic corticosteroids, psoralen plus ultraviolet A radiation therapy, plasmapheresis, extracorporeal photochemotherapy, hydroxychloroquine and cyclophosphamide had been unsuccessful. Treatment with intravenous immunoglobulins at a dosage of 2 g/kg monthly was started. Considerable improvements were observed after seven cycles of therapy, with recovery of skin elasticity, an increase in facial mimic movement, restoration of joint function and improvement in the modified Rodnan score. There were no observed side-effects. The patient remains in remission on monthly maintenance intravenous immunoglobulins, 2 years after initial treatment.

Crescentic flap for the reconstruction of the nose after skin cancer resection.

PURPOSE: Non-melanoma skin cancers are the most frequent skin tumours; in 25.5% of cases, they are reported to affect the nasal area. For an excellent surgical outcome, first of all the radical excision of the lesion is important, with appropriate margins of healthy skin in order to avoid recurrences. Moreover is important to achieve a good aesthetical result, avoiding distortion of the aesthetic units and preserving their functions. MATERIAL AND METHODS: We have applied the modified crescentic flap, described by Smadja in 2007, to 24 nasal skin defects left by oncologic surgery. It consists of the crescent-shaped resection of Burow's triangle all around the alar groove that allows the advancement of the flap to the tip of the nose, hiding the scar in the alar groove. RESULTS: The outcome and the long-term follow-up were completely satisfactory both for patients and for surgeons. CONCLUSION: For skin defects localized in the midline or paramedian line of the dorsum of the nose, the crescentic flap seems to be a good solution to obtain the better aesthetic result with respect to both anatomy and function of the nasal area, sparing the patient a second intervention or an overly invasive procedure.

Multiphoton laser tomography and fluorescence lifetime imaging of melanoma: morphologic features and quantitative data for sensitive and specific non-invasive diagnostics.

Multiphoton laser tomography (MPT) combined with fluorescence lifetime imaging (FLIM) is a non-invasive imaging technique, based on the study of fluorescence decay times of naturally occurring fluorescent molecules, enabling a non-invasive investigation of the skin with subcellular resolution. The aim of this retrospective observational ex vivo study, was to characterize melanoma both from a morphologic and a quantitative point of view, attaining an improvement in the diagnostic accuracy with respect to dermoscopy. In the training phase, thirty parameters, comprising both cytological descriptors and architectural aspects, were identified. The training set included 6 melanomas with a mean Breslow thickness±S.D. of 0.89±0.48 mm. In the test phase, these parameters were blindly evaluated on a test data set consisting of 25 melanomas, 50 nevi and 50 basal cell carcinomas. Melanomas in the test phase comprised 8 in situ lesions and had a mean thickness±S.D. of 0.77±1.2 mm. Moreover, quantitative FLIM data were calculated for special areas of interest. Melanoma was characterized by the presence of atypical short lifetime cells and architectural disorder, in contrast to nevi presenting typical cells and a regular histoarchitecture. Sensitivity and specificity values for melanoma diagnosis were 100% and 98%, respectively, whereas dermoscopy achieved the same sensitivity, but a lower specificity (82%). Mean fluorescence lifetime values of melanocytic cells did not vary between melanomas and nevi, but significantly differed from those referring to basal cell carcinoma enabling a differential diagnosis based on quantitative data. Data from prospective preoperative trials are needed to confirm if MPT/FLIM could increase diagnostic specificity and thus reduce unnecessary surgical excisions.

Multiphoton laser microscopy and fluorescence lifetime imaging for the evaluation of the skin.

Multiphoton laser microscopy is a new, non-invasive technique providing access to the skin at a cellular and subcellular level, which is based both on autofluorescence and fluorescence lifetime imaging. Whereas the former considers fluorescence intensity emitted by epidermal and dermal fluorophores and by the extra-cellular matrix, fluorescence lifetime imaging (FLIM), is generated by the fluorescence decay rate. This innovative technique can be applied to the study of living skin, cell cultures and ex vivo samples. Although still limited to the clinical research field, the development of multiphoton laser microscopy is thought to become suitable for a practical application in the next few years: in this paper, we performed an accurate review of the studies published so far, considering the possible fields of application of this imaging method and providing high quality images acquired in the Department of Dermatology of the University of Modena.