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Wound assessment is usually performed in hospitals or specialized labs. However, since patients spend most of their time at home, a remote real time wound monitoring would help providing a better care and improving the healing rate. This review describes the advances in sensors and biosensors for monitoring the concentration of C-reactive protein (CRP), temperature and pH in wounds. These three parameters can be used as qualitative biomarkers to assess the wound status and the effectiveness of therapy. CRP biosensors can be classified in: (a) field effect transistors, (b) optical immunosensors based on surface plasmon resonance, total internal reflection, fluorescence and chemiluminescence, (c) electrochemical sensors based on potentiometry, amperometry, and electrochemical impedance, and (d) piezoresistive sensors, such as quartz crystal microbalances and microcantilevers. The last section reports the most recent developments for wearable non-invasive temperature and pH sensors suitable for wound monitoring.

A subgroup of the transient receptor potential (TRP) channels, including vanilloid 1 (TRPV1), TRPV2, TRPV3, TRPV4, and TRP ankyrin 1 (TRPA1), is expressed in cutaneous peptidergic somatosensory neurons, and has been found in skin non-neuronal cells, such as keratinocytes. Different cancer cells express TRPs, where they may exert either pro- or antitumorigenic roles. Expression and function of TRPs in skin cancers have been, however, poorly investigated. Here, we have studied the distribution and expression of TRPs by immunohistochemistry and messenger RNA (mRNA) in human healthy skin and human keratinocytic tumors, including intraepidermal proliferative disorders (solar keratosis (SK) and Bowen’s disease), and non-melanoma skin cancer (NMSC; basal cell and squamous cell carcinomas). Similar TRPV1, TRPV2, and TRPV3 staining was found in keratinocytes from healthy and tumor tissues. TRPA1 staining was increased solely in SK samples. However, the marked TRPV4 staining and TRPV4 mRNA expression, observed in healthy or inflamed skin, was abrogated both in premalignant lesions and NMSC. In a human keratinocyte cell line (HaCaT), TRPV4 stimulation released IL-8, which in turn downregulated TRPV4 expression. Selective reduction in TRPV4 expression could represent an early biomarker of skin carcinogenesis. Whether the cytokine-dependent, autocrine pathway that results in TRPV4 downregulation contributes to NMSC mechanism remains to be determined.

BackgroundPropranolol (antagonist of β1-/β2-AR but minimally active against β3-AR) is currently the first-line treatment for infantile hemangiomas (IH). Its efficacy is attributed to the blockade of β2-AR. However, its success rate is ~60%. Considering the growing interest in the angiogenic role of β3-ARs, we evaluated a possible relationship between β3-AR expression and response to propranolol.MethodsFifteen samples of surgical biopsies were collected from patients with IH. Three were taken precociously from infants and then successfully treated with propranolol (responder group). Twelve were taken later, from residual lesions noncompletely responsive to propranolol (nonresponder group). A morphometrical analysis of the percentage of β1-, β2-, and β3-ARs positively stained area was compared between the two groups.ResultsWhile no difference was found in both β1- and β2-AR expression level, a statistically significant increase of β3-AR positively stained area was observed in the nonresponder group.ConclusionsAlthough the number of biopsies is insufficient to draw definitive conclusions, and the different β-AR pattern may be theoretically explained by the different timing of samplings, this study suggests a possible correlation between β3-AR expression and the reduced responsiveness to propranolol treatment. This study could pave the way for new therapeutic perspectives to manage IH.ImpactPropranolol (unselective antagonist of β1 and β2-ARs) is currently the first-line treatment for IHs, with a success rate of ~60%.Its effectiveness has been attributed to its ability to block β2-ARs.However, β3-ARs (on which propranolol is minimally active) were significantly more expressed in hemangioma biopsies taken from patients nonresponsive to propranolol.This study suggests a possible role of β3-ARs in hemangioma pathogenesis and a possible new therapeutic target.

The term ‘mosaic skin disorders’ encompasses conditions in which the skin is involved by mosaic mutations, including epidermal nevi, vascular nevi, connective tissue nevi and lipomatous nevi, among others. Mosaic skin abnormalities can present under a segmental pattern or as nonsegmental skin lesions. Nonsegmental mosaicism, which is most common, includes individual point lesions, tumours, hamartomatous lesions, or malformations, such as melanocytic nevi, Spitz tumours, and sporadic trichoepitheliomas. In some autosomal dominant genodermatoses with multiple skin lesions, a nonsegmental disseminated mosaicism emerges, often associated with neurological or multi‐organ involvement. A patchy skin involvement without midline separation is frequently observed in congenital melanocytic nevi. Segmental mosaicism is less common and presents as asymmetric cutaneous lesions in one or more separate body areas, respecting the body's midline. While the precise mechanisms remain uncertain, these segments possibly reflect clonal expansion of cells during prenatal development. In this article, we provide an overview of the types of mosaicism, discussing their patterns, clinical manifestations, and the varying degrees of severity associated with these conditions. Mosaic skin abnormalities can present under a segmental pattern or as ¡non‐segmental skin lesions. Non‐segmental mosaicism (Figure 1, a‐c), which is most common, includes individual point lesions, tumors, hamartomatous lesions, or malformations. Segmental mosaicism (Figure 2, a‐f)is less common and presents as asymmetric cutaneous lesions in one or more separate body areas, respecting the body's midline. These segments possibly reflect clonal expansion of cells during prenatal development.

Granulomatous diseases in childhood present a complex diagnostic landscape, particularly when histological and clinical findings overlap with those of systemic inflammatory or histiocytic disorders. A subset of these conditions may represent the clinical onset of inborn errors of immunity (IEI), such as Mendelian Susceptibility to Mycobacterial Disease (MSMD), where atypical or sterile granulomas may obscure the underlying infectious or genetic etiology. Recognition of IEI behind granulomatous diseases can radically alter patient’s prognosis and therapeutic management. This report describes the case of a 11-years-old with an initial diagnosis of Rosai-Dorfman disease based on clinical and and histological findings. Following relapse after steroid tapering the diagnosis was revised to sarcoidosis, supported by non-caseating granulomas and compatible laboratory findings. Only after cultures from biopsy specimens revealed Mycobacterium avium complex (MAC), immunological investigations were undertaken, revealing a STAT1 dominant negative deficiency, consistent with MSMD. This report underscores the need of considering IEI in pediatric patients presenting with granulomatous inflammation, especially when clinical course is atypical or refractory to standard immunosuppressive therapies. Early microbiological and immunogenetic assessment is essential to avoid diagnostic delay, prevent inappropriate treatment, and guide targeted antimicrobial therapy.

Intraoral ultrasonography has been widely employed for the preoperative assessment of tumor margins due to its capability to evaluate depth of invasion (DOI) and tumor thickness (TT). Recently, a novel ultrasonographic technique, ultra-high frequency ultrasound (UHFUS) has been increasingly applied to the study of oral lesions. This study evaluates the potential application of intraoral UHFUS to assess DOI and TT parameters of oral squamous cell carcinoma (OSCC) lesions. Patients clinically suspected of OSCC lesions were enrolled and underwent an intraoral UHFUS examination preoperatively. The parameters of TT, DOI, echogenicity, and vascularization were assessed. The parameters of TT and DOI as evaluated by means of UHFUS were compared to histology, which was set as the benchmark. Ten patients in total were enrolled. UHFUS-based DOI and TT measurements were found to positively correlate with histology (p < 0.05), although UHFUS provided a slight overestimation of DOI. No differences were found in terms of echogenicity or vascularization depending on the site of the lesion. According to these preliminary results, UHFUS could support the preoperative assessment of TT and DOI, potentially enhancing the clinical evaluation of OSCC.

Vaccination is a well-known trigger for mast cell degranulation in subjects affected by mastocytosis. Nevertheless, there is no exact standardized protocol to prevent a possible reaction after a vaccine injection, especially for patients who have already presented a previous vaccine-related adverse event, considering that these patients frequently tolerate future vaccine doses. For this reason, we aim to share our experience at Meyer Children’s University Hospital in Florence to raise awareness on the potential risk for future vaccinations and to discuss the valuable therapeutic strategies intended to prevent them, taking into account what is proposed by experts in literature. We describe the case of an 18-month-old female affected by a polymorphic variant of maculopapular cutaneous mastocytosis that presented an extensive bullous cutaneous reaction 24 hours after the second dose (booster dose) of inactivated-tetravalent influenza vaccine, treated with a single dose of oral corticosteroid therapy with betamethasone (0.1 mg/kg) and an oral antihistamine therapy with oxatomide (1 mg/kg/daily) for a week, until resolution. To the best of our knowledge, in the literature, no documented case of reaction to influenza vaccine in maculopapular cutaneous mastocytosis is described. Subsequently, the patient started a background therapy with ketotifen daily (0.05 mg/kg twice daily), a non-competitive H1-antihistamine, and a mast cell stabilizer (dual activity). A non-standardized pharmacological premedication protocol with an H1-receptor antagonist (oxatomide, 0.5 mg/kg) administered 12 hours before the immunizations, and a single dose of betamethasone (0.05 mg/kg) together with another dose of oxatomide (0.5 mg/kg) administered 2 hours before the injections was followed to make it possible for the patient to continue with the scheduled vaccinations. Indeed, no reactions were subsequently reported. Thus, in our experience, a background therapy with ketotifen associated with a premedication protocol made by two doses of oxatomide and a single dose of betamethasone was helpful to make possible the execution of the other vaccines. We suggest how in these children, it could be considered the idea of taking precaution when vaccination is planned, regardless of the kind of vaccine and if a dose of the same vaccine was previously received. However, international consensus needs to be reached to manage vaccinations in children with mastocytosis and previous adverse reactions to vaccines.

Sjögren’s disease (SD) is a chronic autoimmune disease primarily affecting lacrimal and salivary glands. The diagnosis of pediatric SD mostly relies on clinical suspect, resulting in a significant diagnostic delay. Recently, ultrahigh-frequency ultrasound (UHFUS) of labial glands has been proposed as a diagnostic method in adults with suspected SD. Until now, there have been no studies about UHFUS in pediatric diagnostic work-up. The aim of the study was to evaluate the potential role of UHFUS of minor salivary glands in pediatric SD. Consecutive pediatric patients with a diagnosis of pediatric SD seen at AOU Meyer IRCSS were evaluated. Intraoral UHFUS scan of the lip mucosa was performed with Vevo MD equipment, using a 70 MHz probe with a standardized protocol and the images were independently reviewed by two operators. Lip salivary glands were assessed by using a four-grade semiquantitative scoring system for parenchymal alteration and vascularization. Twelve patients were included. When applying UHFUS to this cohort of patients, all patients showed a UHFUS grade of ≥1 with 8/12 showing a mild glandular alteration (i.e., grade 1), 2/12 a moderate glandular alteration (i.e., grade 2) and finally 2/12 a severe glandular alteration (i.e., grade 3). Moderate intraglandular vascularization was seen in 9/12, with only 3/12 showing mild intraglandular vascularization. Due to limited size of the sample, the relationship between histological findings, autoantibodies status and UHFUS grade could not be performed. This preliminary study seems to report UHFUS as feasibility technique to identify salivary gland alterations in children with a clinical suspect of SD.

Atopic dermatitis (AD) is a chronic multifactorial inflammatory disease characterized by intense itching and inflammatory eczematous lesions. Biological disease-modifying drugs, such as dupilumab are recommended for patients with moderate-to-severe AD, refractory to systemic immunosuppressive therapies. Disease monitoring is performed by clinical scores. Since 1970, however, the use of ultrasound and particularly high-frequency ultrasound (HFUS), has identified alterations in dermal echogenicity, called the subepidermal low-echogenic band (SLEB), that correlates with disease severity and response to treatment. We enrolled 18 patients with moderate-to-severe AD, divided into two groups: twelve patients in the dupilumab treatment (Group A) and six patients in standard treatment, from February 2019 to November 2019. We performed ultra-high frequency ultrasound (UHFUS) evaluation of lesional and non-lesional skin, focusing on SLEB average thicknesses measurement, epidermal thickness, and vascular signal in correlation with objective disease scores (EASI, IGA), patient’s reported scores (Sleep Quality NRS and Itch NRS), and TEWL and corneometry at baseline (T0), after 1 month (T1) and 2 months (T2). The SLEB average thickness measurement, vascular signal, and epidermal thickness showed a statistically significant reduction in lesional skin of the biological treatment group and no significant reduction in non-lesional skin in both groups. In the lesional skin of the standard treatment group, only epidermal thickness showed a statistically significant reduction. Our study demonstrates that SLEB measurement, vascular signals, and epidermal thickness could be used as objective parameters in monitoring the AD treatment response, while the presence of SLEB in non-lesional skin could be used as a marker of subclinical inflammation and could predict development of clinical lesions, suggesting a pro-active therapy. Further follow-up and research are needed to clarify the association of SLEB decrease/disappearance with a reduction of flares/prolongment of the disease remission time.

Introduction Psoriasis affects children with a considerable burden in early life. Treating pediatric psoriasis is challenging also because of the lack of updated specific guidelines. With the recent approval of several biologics for pediatric psoriasis and the ongoing COVID-19 pandemic, the management of young psoriatic patients is facing major changes. A revision of treatment recommendations is therefore needed. Methods In September 2021, a board of six Italian dermatologists convened to update treatment recommendations. The board issued evidence- and consensus-based statements covering relevant areas of pediatric psoriasis, namely: assessment of psoriasis severity, management of children with psoriasis, and treatment of pediatric psoriasis. To reach consensus, the statements were submitted to a panel of 24 experts in a Delphi process performed entirely via videoconference. A treatment algorithm was produced. Results There was full consensus that psoriasis severity is determined by the extension/severity of skin lesions, site of lesions, and impact on patient quality of life. Agreement was reached on the need for a multidisciplinary approach to pediatric psoriasis and the importance of patient/parents education. The relevance of vaccinations, including COVID-19 vaccination, for psoriatic children was acknowledged by all participants. Management issues that initially failed to reach consensus included the screening for psoriasis comorbidities and early treatment with biologics to prevent them and the use of telemedicine to facilitate patient follow-up. There was full consensus that topical corticosteroids are the first choice for the treatment of mild pediatric psoriasis, while phototherapy and systemic therapy are used in children with moderate-severe psoriasis. According to the proposed treatment algorithm, biologics are the first line of systemic therapy. Conclusions Targeted systemic therapies are changing the treatment of moderate-severe pediatric psoriasis, while topical corticosteroids continue to be the first choice for mild disease. Children-centered research is needed to further improve the treatment of pediatric psoriasis.