Thermography as a Method for Bedside Monitoring of Infantile Hemangiomas.

Infantile hemangiomas occur in 3 to 10% of infants. To predict the clinical course and counsel on treatment, it is crucial to accurately determine the hemangiomas' extension, volume, and location. However, this can represent a challenge because hemangiomas may present irregular patterns or be covered by hair, or their depth may be difficult to estimate. Diagnosis is commonly made by clinical inspection and palpation, with physicians basing their diagnoses on visual characteristics such as area, texture, and color. Doppler ultrasonography or magnetic resonance imaging are normally used to estimate depth or to confirm difficult assessments. This paper presents an alternative diagnosis tool-thermography-as a useful, immediate means of carrying out accurate hemangioma examinations. We conducted a study analyzing infantile hemangiomas with a custom thermographic system. In the first phase of the study, 55 hemangiomas of previously diagnosed patients were analyzed with a thermal camera over several sessions. An average temperature variation before and after treatment of -0.19 °C was measured. In the second phase, we selected nine patients and assessed their evolution over nine months by analyzing their thermographic images and implementing dedicated image processing algorithms. In all cases, we found that the thermal image analysis concurred with the independent diagnoses of two dermatologists. We concluded that a higher temperature inside the tumor in the follow-up was indicative of an undesirable evolution.

Vulvar dermatoses: a cross-sectional 5-year study. Experience in a specialized vulvar unit

Abstract Background: Vulvar diseases are common in the general population and have a negative impact on the quality of life. Objectives: To describe our experience as dermatologists in the management of vulvar dermatosis consultations. Methods: A retrospective observational study was conducted with patients who attended monographic vulvar consultations over a 5-year period. Clinical information was obtained from the patient's charts. Results: 148 women were studied. Their mean age was 43.24 years (standard deviation: 15.15 years), with ages ranging from 4 months to 80 years. 53.4% of patients took between 2 and 5 years to seek medical attention for the first time. The most frequent diagnosis was lichen sclerosus (41.9%), irritative eczema of the vulva (14.9%), and lichen simplex chronicus (10.1%). 83.8% reported anogenital itching, 66.2% pain, and 45.9% dyspareunia. The most frequently prescribed treatment was ultra-potent topical corticosteroids (clobetasol propionate; 41.2%). Patients with lichen sclerosus were significantly older than those who presented with any of the other diseases. No differences were found in terms of either the time of disease evolution or in symptom presentation. Study limitations: Retrospective study. Vulvar diseases with an infectious cause are usually managed in primary care, therefore, were not included. All patients were recruited from a single private hospital which limits the comparisons with the public health system. Conclusions: Vulvar diseases frequently occur and are associated with high morbidity. It is essential to promote the development of specific vulvar consultations in hospitals. Specialties such as dermatology, gynecology, urology, or physiotherapy must be part of these units.

Inter- and intra-observer variability in the selection of therapy for infantile hemangiomas among pediatric dermatologists in Spain.

BACKGROUND: Guidelines and expert recommendations on infantile hemangiomas (IH) are aimed at increasing homogeneity in clinical decisions based on the risk of sequelae. OBJECTIVE: The objective was to analyze the inter- and intra-observer agreement among pediatric dermatologists in the choice of treatment for IH. METHODS: We performed a cross-sectional inter-rater and intra-rater agreement study within the Spanish infantile hemangioma registry. Twenty-seven pediatric dermatologists were invited to participate in a survey with 50 clinical vignettes randomly selected within the registry. Each vignette contained a picture of an infantile hemangioma with a clinical description. Raters chose therapy among observation, topical timolol, or oral propranolol. The same survey reordered was completed 1 month later to assess intra-rater agreement. Vignettes were stratified into hemangioma risk categories following the Spanish consensus on IH. The agreement was measured using kappa statistics appropriate for the type of data (Gwet's AC1 coefficient and Gwet's paired t test). RESULTS: Twenty-four dermatologists completed the survey. Vignettes represented 7.8% of the Spanish hemangioma registry. The inter-rater agreement on the treatment decision was fair (AC1  = 0.39, 95% confidence interval [CI]: 0.30-0.47). When stratified by risk category, good agreement was reached for high-risk hemangiomas (AC1  = 0.77, 95% CI: 0.51-1.00), whereas for intermediate- and low-risk categories, the agreement was only fair (AC1 0.31, 95% CI: 0.16-0.46 and AC1  = 0.38, 95% CI: 0.27-0.48, respectively). Propranolol was the main option for high-risk hemangiomas (86.4%), timolol for intermediate-risk (36.8%), and observation for low-risk ones (55.9%). The intra-rater agreement was good. The inter-rater agreement between pediatric dermatologists on the treatment of IH is only fair. Variability was most significant with intermediate- and low-risk hemangiomas.

Novel Non-Invasive Quantification and Imaging of Eumelanin and DHICA Subunit in Skin Lesions by Raman Spectroscopy and MCR Algorithm: Improving Dysplastic Nevi Diagnosis.

Malignant melanoma (MM) is the most aggressive form of skin cancer, and around 30% of them may develop from pre-existing dysplastic nevi (DN). Diagnosis of DN is a relevant clinical challenge, as these are intermediate lesions between benign and malignant tumors, and, up to date, few studies have focused on their diagnosis. In this study, the accuracy of Raman spectroscopy (RS) is assessed, together with multivariate analysis (MA), to classify 44 biopsies of MM, DN and compound nevus (CN) tumors. For this, we implement a novel methodology to non-invasively quantify and localize the eumelanin pigment, considered as a tumoral biomarker, by means of RS imaging coupled with the Multivariate Curve Resolution-Alternative Least Squares (MCR-ALS) algorithm. This represents a step forward with respect to the currently established technique for melanin analysis, High-Performance Liquid Chromatography (HPLC), which is invasive and cannot provide information about the spatial distribution of molecules. For the first time, we show that the 5, 6-dihydroxyindole (DHI) to 5,6-dihydroxyindole-2-carboxylic acid (DHICA) ratio is higher in DN than in MM and CN lesions. These differences in chemical composition are used by the Partial Least Squares-Discriminant Analysis (PLS-DA) algorithm to identify DN lesions in an efficient, non-invasive, fast, objective and cost-effective method, with sensitivity and specificity of 100% and 94.1%, respectively.

Efficacy and Safety of Topical Timolol for the Treatment of Infantile Hemangioma in the Early Proliferative Stage: A Randomized Clinical Trial.

Importance: Treatment of infantile hemangioma (IH) with topical timolol in the first 2 months of life (early proliferative phase) may prevent further growth and the need for treatment with oral propranolol. To our knowledge, no studies have determined whether beginning early treatment with timolol for IH is better than in other proliferative stages. Objective: To evaluate the efficacy and safety of timolol maleate solution, 0.5%, for the early treatment of IH in infants younger than 60 days. Design, Setting, and Participants: This multicenter, randomized, double-blind, placebo-controlled, phase 2a pilot clinical trial included patients aged 10 to 60 days with focal or segmental hemangiomas (superficial, deep, mixed, or minimal/arrested growth). Patients were randomly assigned to treatment with topical timolol maleate solution, 0.5%, or placebo twice daily for 24 weeks. Changes in lesion size (volume, thickness) and color were evaluated from photographs taken at 2, 4, 8, 12, 24, and 36 weeks. Vital signs and adverse effects were recorded at each visit. The study was carried out from November 2015 to January 2017, and data analyses were completed in September 2019. Main Outcomes and Measures: The primary outcome of complete or nearly complete IH resolution and the secondary outcomes of changes in lesion thickness, volume, and color were evaluated by a blinded investigator. Results: Of the 69 patients recruited, the mean (SD) age was 48.4 (10.6) days; 55 (80%) were female; and 51 (74%), 11 (16%), 6 (9%), and 1 (1%) had superficial, mixed, abortive, or deep IHs, respectively. The IHs were localized, segmental, or indeterminate in 60 (87%), 7 (10%), and 2 (3%) patients, respectively. The IHs were located on the head and/or neck (n = 23 [33%]) or other body sites (n = 46 [67%]). The study was completed by 26 of 33 (79%) patients receiving timolol and 31 of 36 (86%) receiving placebo. There were no significant differences between timolol and placebo for complete or nearly complete IH resolution at 24 weeks (n = 11 [42%] vs n = 11 [36%]; P = .37). The odds ratio of complete or almost complete response vs no response at week 24 was 1.33 (95% CI, 0.45-3.89). There were no between-group differences in IH size (volume, thickness). An improvement in color was observed at week 4 in the timolol group, and timolol was well tolerated with no systemic adverse effects. Conclusions and Relevance: In this randomized clinical trial, results demonstrated that topical timolol is well tolerated for the treatment of early proliferative IH but provides limited benefit in lesion resolution when given during the early proliferative stage. Trial Registration: EudraCT Identifier: 2013-005199-17.

Unilateral clubbing-like digital thickening as a clinical manifestation of low-flow vascular malformations: a series of 13 cases.

BACKGROUND: Digital clubbing is a well-known clinical sign characterized by thickening of the distal phalanges of the fingers and toes. Unilateral clubbing occurs less frequently. A previous report showed for the first time two cases of unilateral clubbing as a clinical manifestation of lower limb venous malformation. The objective of the present study is to describe a series of 13 patients with a low-flow vascular malformation where a clubbing-like unilateral digital thickening is also observed. METHODS: All patients were retrospectively included after reviewing clinical photographs from a vascular malformations database. RESULTS: A total of 13 patients with low-flow vascular malformations were included in this study. The mean age at diagnosis was 11 years (range 5-26 years) with a female predominance (nine patients). The most frequent vascular malformation collected was a blue rubber bleb nevus syndrome in four patients, followed by common venous malformations in three patients. All patients characteristically exhibited a clubbing-like digital thickening. Seven patients had foot involvement and six patients hand involvement. CONCLUSIONS: Although the number of cases is limited, our study is the first series of cases where a clubbing-like digital thickening is described in patients with a low-flow vascular malformation. The unilateral presence of clubbing or pseudoclubbing should lead to the suspicion of an underlying vascular malformation.

Sequelae following infantile haemangiomas treated with propranolol.

BACKGROUND: Oral propranolol accelerates the involution of infantile haemangiomas (IHs). However, it is not clear whether IHs treated with oral propranolol are associated with fewer sequelae than when left untreated. OBJECTIVES: To quantify and describe sequelae associated with IHs treated with oral propranolol, and to explore whether treated IHs are associated with fewer sequelae than untreated IHs. MATERIALS & METHODS: This multicentre, retrospective, cohort study included patients with IH treated with oral propranolol ≥2 mg/kg for at least six months, with photographic images available at baseline and at age 4-5 years. A historical comparison cohort comprised 185 patients with untreated IHs. Main outcomes/measures were: IH features, treatment characteristics and type/degree of sequelae. RESULTS: Oral propranolol, most commonly at 2 mg/kg/day (mean duration: nine months), was initiated in 171 patients (mean age: 6.02 months). After treatment, 125 of 171 (73.1%) IHs were associated with no/minimal sequelae. The most common sequelae were telangiectasia (78%), fibrofatty tissue (37%) and anetodermic skin (28%). Deep IHs were associated with significantly fewer sequelae than other subtypes. Ulceration appeared to increase the likelihood of severe sequelae. IHs with a stepped border was associated with more severe sequelae than those with a progressive border (44% versus 27%, p < 0.05). Treated IHs resolved without sequelae or were associated with a sequela that did not need correction in 27.7% more cases than untreated IHs (RR: 1.61; p < 0.001). CONCLUSION: Among IHs treated with oral propranolol, 73% resolved without, or were associated with minimal sequelae. Deep IHs were associated fewer sequelae than other subtypes. Oral propranolol decreased the likelihood of IH sequelae requiring correction.

Direct-to-consumer, store-and-forward teledermatology with dermoscopy using the pharmacist as patient point-of-contact.

OBJECTIVE(S): To evaluate the frequency of nonmelanoma skin cancer (NMSC), NMSC precursors, and melanoma on a store-and-forward dermatology model featuring the pharmacist as the patient's point-of-contact. The secondary objective was to define lesion changes and symptoms perceived by patients (clinical prediction rules by nonexpert observers) that can be predictive of malignity. METHODS: A cross-sectional study of teledermatology consultation was performed. All patients who underwent a teledermatology consultation between September 2018 and March 2020 were included. A patient could have more than 1 lesion per consultation. The object of the study was a defined dermatologic lesion. The differences between the variables were analyzed using a univariate model based on the chi-square test for independent qualitative variables and Fisher exact test in cases when the expected values in any of the cells of a contingency table were less than 5. Statistical significance was set at P < 0.05 (2-tailed). RESULTS: A total of 225 lesions in 218 patients were considered for this study; 53.8% (n = 121) of the lesions were classified as benign, 16.4% (n = 37) as dubious, 23.1% (n = 52) as NMSC precursors, 5.8% (n = 13) as NMSC, and 0.9% (n = 2) as melanomas. Of the reported clinical lesion changes, spontaneous pain, pruritus, surface texture changes, color changes, or form changes had no statistically significant relationship with the diagnostic group, whereas the presence of spontaneous bleeding (P = 0.015) and size changes (P = 0.026) were more frequently observed in the "dubious lesion" and "of oncological relevance lesion" groups. CONCLUSION: This "direct-to-consumer," store-and-forward teledermatology with dermoscopy model featuring the pharmacist as the patient's point-of-contact is useful for the diagnosis of melanoma, NMSC, and NMSC precursors when backed by a robust dermatology service.

Recalcitrant trametinib-induced paronychia treated successfully with topical timolol in a pediatric patient.

Paronychia has been described as a side effect in patients undergoing treatment with MEK (mitogen activated protein kinase enzyme) inhibitors. It is usually a recurrent condition that can have a significant impact in the quality of life. Topical beta blocker treatment has been described as an effective therapy in antineoplastic-induced pyogenic granulomas and in antineoplastic-induced paronychia. We describe the first case treated with topical timolol for a trametinib-induced paronychia in a pediatric patient that allowed to continue the third line antineoplastic therapy for his glioma.

High SLC7A11 expression in normal skin of melanoma patients.

BACKGROUND: Melanoma is one of the highest metastatic cancers and its incidence is rapidly increasing. A great effort has been devoted to determine gene mutations and expression profiles in melanoma cells, but less attention has been given to the possible influence of melanin synthesis in melanocytes on melanomagenesis. SLC7A11 encodes the cystine/glutamate antiporter xCT and its expression increases the antioxidant capacity of cells by providing cysteine that may be used for glutathione (GSH) synthesis. Melanocytes, however, can also use cysteine for pheomelanin synthesis and pigmentation. Therefore, pheomelanin synthesis may lead to chronic oxidative stress. Possible consequences of this for melanomagenesis have never been explored. METHODS: We quantified the expression of SLC7A11 and other genes that are involved in the synthesis of pheomelanin but do not regulate the transport of cysteine from the extracellular medium to the cytosol (CTNS, MC1R, ASIP and SLC45A2) in non-tumorous skin of 45 patients of cutaneous melanoma and 50 healthy individuals. We controlled for the effects of Fitzpatrick skin type, age, gender, body mass, frequency of sun exposure and sunburns and number of melanocytic nevi, as well as for the intrinsic antioxidant capacity as given by the expression of the gene NFE2L2. RESULTS: The expression of SLC7A11, but not of the other genes, was significantly higher in melanoma patients than in healthy individuals. This was independent of phenotypic factors and antioxidant capacity, thus supporting an effect of pheomelanin-induced oxidative stress on melanomagenesis. CONCLUSION: Our findings indicate that SLC7A11 downregulation in normal epidermal melanocytes may represent a preventive treatment against melanoma.

Expression patterns of aquaporin 1 in vascular tumours.

BACKGROUND: Aquaporins (AQPs) are a family of water channels expressed in various body tissues. Beyond osmotic balance, AQPs have recently been confirmed to be involved in processes related to cancer (tumour proliferation, angiogenesis, etc.). OBJECTIVES: To analyse the presence of these proteins in the endothelium of several vascular tumours, both benign and malignant, in order to establish whether AQPs may be used as a marker or future therapeutic target. MATERIALS AND METHODS: We studied AQP1 expression in 39 patients with vascular tumours, classified into six groups according to ISSVA classification: haemangiomas, benign vascular tumours different from infantile haemangiomas, angiosarcomas, classic Kaposi's sarcoma (KS), and epidemic KS. RESULTS: AQP1 expression was present in 28 of 39 patients, representing 92.9% benign lesions, whereas no expression was found in 72% of malignant lesions. AQP1 expression was associated with benign lesions with an OR of 34.5 (95% CI: 5-250); p<0.0005, and was most frequently identified with a focal endothelial pattern (38%). A kappa index of 0.823 (95% CI: 0.678-0.971) was determined regarding the patterns of expression overall. CONCLUSION: The expression of AQP1 was greater in benign lesions than malignant lesions and this difference was statistically significant, thus AQP1 expression could serve as a marker for benignity of vascular tumours. In addition, the expression pattern of AQP1 was different according to the type of vascular tumour.

Expression Pattern of Aquaporin 1 and Aquaporin 3 in Melanocytic and Nonmelanocytic Skin Tumors.

OBJECTIVES: Study of aquaporin 1 (AQP1) and aquaporin 3 (AQP3) expression to understand its potential role in the pathophysiology of skin cancer. METHODS: Analysis of AQP1 and AQP3 expression by immunohistochemistry of 72 skin biopsy specimens from melanocytic skin tumors, nonmelanocytic tumors, or healthy samples. RESULTS: AQP1 showed strong labeling in 100% of benign common melanocytic nevi. Small blood vessels, stroma, and melanophages surrounding different types of melanomas tumors also were positive. Tumoral melanocytes in atypical nevi and melanomas were negative for AQP1. AQP3 showed strong labeling in 100% of melanocytic nevi, 100% of atypical melanocytic nevi, and 100% of melanomas. In all basal cell carcinomas and squamous cell carcinomas, staining for AQP3 was positive. CONCLUSIONS: To our knowledge, this work represents the first demonstration of AQP1/AQP3 expression in human melanocytic skin tumors. More studies are needed to understand the underlying molecular mechanisms of expression of both AQPs in melanocytic tumors and their potential as molecular therapeutic targets.

Congenital tufted angioma: A multicenter retrospective study of 30 cases.

BACKGROUND: Recent reports indicate that tufted angioma is a rare vascular neoplasm that manifests more frequently at birth than previously thought. Few studies specifically address congenital presentation. OBJECTIVES: We analyzed the clinicopathological characteristics, clinical course, and treatment of congenital tufted angioma (cTA) and evaluated variables that were indicative of problematic lesions. METHODS: We performed an observational retrospective study of 30 patients with cTA in 9 Spanish hospitals over a 14-year period. Histopathology and immunohistochemistry studies were performed. RESULTS: Congenital tufted angioma mainly affected the limbs (56.67%), followed by the face and/or neck (23.33%). Almost three-quarters of facial cTA were located over the mandibular area. Immunohistochemically, proliferating cells expressed markers of endothelial cells, with some clusters of cells, especially at the periphery of the aggregates, showing positivity for podoplanin. As no associated complications were observed in 66.67% of cases, no treatment was started. LIMITATIONS: Data were collected retrospectively. CONCLUSIONS: Our findings emphasize the clinical features and course of cTA. The possibility of cTA should be considered when a poorly defined congenital infiltrative vascular tumor with(out) overlying hirsutism appears over the mandibular area. Location on the face and/or neck requires a more comprehensive workup, since potentially severe complications often appear early.

Iatrogenic Calcinosis Cutis Successfully Treated with Topical Sodium Thiosulfate.

Calcinosis cutis is a term used to describe a group of disorders in which calcium salt deposits form in the skin and subcutaneous tissue. We report a 6-year-old boy with hypoparathyroidism after thyroidectomy who was admitted to the hospital for severe hypocalcemia being treated with calcium gluconate intravenous infusion through peripheral veins. Within a few days we made a diagnosis of iatrogenic calcinosis cutis and treatment with 10% topical sodium thiosulfate was prescribed; complete resolution of lesions was achieved after 6 months, with no local or systemic adverse effects. Because of the lack of noninvasive alternatives and the good tolerance of the treatment, especially in childhood, we suggest the topical use of this drug as an option for this condition.

"Sky Full of Stars" Pattern: Dermoscopic Findings in a Desmoplastic Giant Congenital Melanocytic Nevus.

Desmoplastic giant congenital melanocytic nevus (DGCN) is an uncommon variant of congenital nevus, presenting as a progressive induration and hypopigmentation of the lesion that occasionally causes hair loss and even total or partial disappearance of the nevus. A 6-month-old girl with a giant congenital melanocytic nevus that involved the entire posterior side of the right thigh was seen in our department. Nine months later, the peripheral area of the nevus presented as a marked induration with hypopigmentation. Dermoscopy demonstrated a reticular pattern exclusively located in the perifollicular areas, with a radial distribution from the follicular ostium that mimicked a "sky full of stars." We report a case of DGCN, including a dermoscopic description of the findings noted in the indurated and hypopigmented areas that appear as a "sky full of stars" image.

Immunolocalization of substance P and NK-1 receptor in vascular anomalies.

The peptide substance P (SP) shows a widespread distribution in both the central and peripheral nervous systems, but it is also ubiquitous in the human body. After binding to the neurokinin-1 (NK-1) receptor, SP regulates tumoral angiogenesis and proliferation. Thus, knowledge of this system is the key for a better understanding and, hence, a better management of many human diseases, including vascular anomalies (VA). This study aims to examine the expression and localization of both SP and the NK-1 receptor in different vascular anomalies using an immunohistochemical technique. Our results demonstrated predominantly nuclear localization of SP in venous malformations and in one haemangioma sample, in contrast with cytoplasmic expression in capillary malformations and rapidly involuting congenital hemangioma (RICH). NK-1 receptor showed a cytoplasmic localization in all VA. In summary, all these findings demonstrate that SP and NK-1 receptor are expressed in VA, with different expression patterns depending on the nature of the anomaly, suggesting that they could play an important role in the pathogenesis of VA.