Dupilumab treatment of trichothiodystrophy in a child.

Trichothiodystrophy (TTD) is a rare congenital disorder caused by genetic mutations, leading to hair and skin abnormalities. We report successful treatment of a TTD case using dupilumab, a monoclonal antibody targeting IL-4Rα. The patient, a 7-year-old boy, exhibited significant improvement in skin and hair conditions, suggesting the potential of dupilumab as a therapeutic option for TTD. Further research is needed to elucidate its mechanism and efficacy in TTD treatment.

Ultra-High Frequency UltraSound (UHFUS) Assessment of Barrier Function in Moderate-to-Severe Atopic Dermatitis during Dupilumab Treatment.

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.

Ultra-High-Frequency Ultrasonography of Labial Glands in Pediatric Sjögren's Disease: A Preliminary Study.

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.

Dermatological findings in Rubinstein-Taybi Syndrome.

Rubinstein-Taybi Syndrome is a rare congenital multisystem syndrome inherited in an autosomal dominant pattern caused by mutations in CREBBP and EP300 genes in approximately 60% and 10% respectively. These genes encode two highly evolutionarily conserved, ubiquitously expressed, and homologous lysine-acetyltransferases, that are involved in number of basic cellular activities, such as DNA repair, cell proliferation, growth, differentiation, apoptosis of cells, and tumor suppression. It is mainly characterized by global developmental delay, moderate to severe intellectual disability, postnatal retardation, microcephaly, skeletal anomalies including broad/short, angled thumbs and/or large first toes, short stature, and dysmorphic facial features. There is an increased risk to develop tumors mainly meningiomas and pilomatrixomas, without a clear genotype-phenotype correlation. Although not considered as characteristic manifestations, numerous cutaneous anomalies have also been reported in patients with this entity. Both susceptibility to the formation of keloids and pilomatricomas are the most often associated cutaneous features. In this review, we discuss the genetics, diagnosis, and clinical features in Rubinstein-Taybi Syndrome with a review of the major dermatological manifestations.

COVID 19-associated chilblain-like acral lesions among children and adolescents: an Italian retrospective, multicenter study.

BACKGROUND: Since the COVID-19 pandemic started, great interest has been given to this disease, especially to its possible clinical presentations. Besides classical respiratory symptoms, dermatological manifestations occur quite often among infected and non-infected patients, particularly in children. A prominent IFN-I response, that is generally higher in children compared to adults, may not only cause chilblain lesions, but it could also prevent infection and viral replication, thus justifying the negative swab results, as well as the absence of relevant systemic symptoms in positive cases. Indeed, reports have emerged describing chilblain-like acral lesions in children and adolescents with either proven or suspected infection. METHODS: Patients aged from 1 to 18 years old were enrolled in this study from 23 Italian dermatological units and were observed for an overall period of 6 months. Clinical pictures were collected along with data on the location and duration of skin lesions, their association with concomitant local and systemic symptoms, presence of nail and/or mucosal involvement, as well as histological, laboratory and imaging findings. RESULTS: One hundred thirty-seven patients were included, of whom 56.9% were females. Mean age was 11.97±3.66 years. The most commonly affected sites were the feet (77 patients, 56.2%). Lesions (48.5%) featured cyanosis, chilblains, blisters, ecchymosis, bullae, erythema, edema, and papules. Concomitant skin manifestations included maculo-papular rashes (30%), unspecified rashes (25%), vesicular rashes (20%), erythema multiforme (10%), urticaria (10%) and erythema with desquamation (5%). Forty-one patients (29.9%) reported pruritus as the main symptom associated with chilblains, and 56 out of 137 patients also reported systemic symptoms such as respiratory symptoms (33.9%), fever (28%), intestinal (27%), headache (5.5%), asthenia (3.5%), and joint pain (2%). Associated comorbid conditions were observed in 9 patients presenting with skin lesions. Nasopharyngeal swabs turned out positive in 11 patients (8%), whereas the remainder were either negative (101, 73%) or unspecified (25, 18%). CONCLUSIONS: COVID-19 has been credited as the etiology of the recent increase in acro-ischemic lesions. The present study provides a description of pediatric cutaneous manifestations deemed to be potentially associated with COVID-19, revealing a possible association between acral cyanosis and nasopharyngeal swab positivity in children and teenagers. The identification and characterization of newly recognized patterns of skin involvement may aid physicians in diagnosing cases of asymptomatic or pauci-symptomatic COVID patients.

Multiparametric Skin Assessment in a Monocentric Cohort of Systemic Sclerosis Patients: Is There a Role for Ultra-High Frequency Ultrasound?

Background: To assess skin involvement in a cohort of patients with systemic sclerosis (SSc) by comparing results obtained from modified Rodnan skin score (mRSS), durometry and ultra-high frequency ultrasound (UHFUS). Methods: SSc patients were enrolled along with healthy controls (HC), assessing disease-specific characteristics. Five regions of interest were investigated in the non-dominant upper limb. Each patient underwent a rheumatological evaluation of the mRSS, dermatological measurement with a durometer, and radiological UHFUS assessment with a 70 MHz probe calculating the mean grayscale value (MGV). Results: Forty-seven SSc patients (87.2% female, mean age 56.4 years) and 15 HC comparable for age and sex were enrolled. Durometry showed a positive correlation with mRSS in most regions of interest (p = 0.025, ρ = 0.34 in mean). When performing UHFUS, SSc patients had a significantly thicker epidermal layer (p < 0.001) and lower epidermal MGV (p = 0.01) than HC in almost all the different regions of interest. Lower values of dermal MGV were found at the distal and intermediate phalanx (p < 0.01). No relationships were found between UHFUS results either with mRSS or durometry. Conclusions: UHFUS is an emergent tool for skin assessment in SSc, showing significant alterations concerning skin thickness and echogenicity when compared with HC. The lack of correlations between UHFUS and both mRSS and durometry suggests that these are not equivalent techniques but may represent complementary methods for a full non-invasive skin evaluation in SSc.

Next generation sequencing panel target genes: possible diagnostic tool for ectodermal dysplasia related diseases.

BACKGROUND: Ectodermal dysplasias (EDs) are a large and complex group of disorders affecting the ectoderm-derived organs; the clinical and genetic heterogeneity of these conditions renders an accurate diagnosis more challenging. The aim of this study is to demonstrate the clinical utility of a targeted resequencing panel through enhancing the molecular and clinical diagnosis of EDs. Given the recent developments in gene and protein-based therapies for X-linked hypohidrotic ectodermal dysplasia, there is a re-emerging interest in identifying the genetic basis of EDs and the respective phenotypic presentations, in an aim to facilitate potential treatments for affected families. METHODS: We assessed seventeen individuals, from three unrelated families, who presented with diverse phenotypes suggestive of ED. An extensive multidisciplinary clinical evaluation was performed followed by a targeted exome resequencing panel (including genes that are known to cause EDs). MiSeqTM data software was used, variants with Qscore >30 were accepted. RESULTS: Three different previously reported hemizygous EDA mutations were found in the families. However, a complete genotype-phenotype correlation could not be established, neither in our patients nor in the previously reported patients. CONCLUSIONS: Targeted exome resequencing can provide a rapid and accurate diagnosis of EDs, while further contributing to the existing ED genetic data. Moreover, the identification of the disease-causing mutation in an affected family is crucial for proper genetic counseling and the establishment of a genotype-phenotype correlation which will subsequently provide the affected individuals with a more suitable treatment plan.

Fractional Epidermal Skin Grafts in Hard-to-Heal Wounds: Case Series.

Cellutome™ is a minimally invasive, automated system for harvesting fractional epidermal micrografts. This therapy is indicated for granulating, small size, poor exuding acute wounds. We enrolled 15 patients with 9 venous leg ulcers and 6 atypical ulcers. The micrografts were applied with a nonadherent dressing and covered with a polyurethane foam and multilayer bandage. We scheduled 3 weekly visits for the change of the secondary dressings and multilayer bandage and clinical assessment (Wound Bed Score [WBS], pain assessment, and healing rate). The lesions were measured with the Silhouette Star™ system, a software that allows measurement of perimeter and area from a digital image. The only symptom during the procedure was a sensation of warmth. The donor area healed in 2 weeks in all patients (n = 15). We reported an area reduction of 24.30% in typical ulcers and 38.82% in atypical ulcers after 3 weeks. The average WBS improved in all ulcers from 13.06 to 14.93. The average healing rate was 0.19 mm/day both in typical and atypical ulcers. Consequently, in our small case series fractionated epidermal graft treatment significantly promoted the healing rate in all chronic ulcers regardless of etiology. Future studies with larger case series will be needed.

Dermoscopy features of infantile perianal pyramidal protrusion.

Infantile perianal pyramidal protrusion (IPPP) is a benign condition generally noted in childhood but may persist for several years. Dermoscopy may help to distinguish it from other conditions, particularly genital warts. We report six cases of IPPP and describe the dermoscopic features that will distinguish these lesions from verrucae.

Non-invasive imaging techniques in presurgical margin assessment of basal cell carcinoma: Current evidence.

BACKGROUND: The diagnosis of basal cell carcinoma (BCC) is based on clinical and dermoscopical features. In uncertain cases, innovative imaging techniques, such as reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), have been used. The main limitation of these techniques is the inability to study deep margins. HFUS (high-frequency ultrasound) and the most recent UHFUS (ultra-high-frequency ultrasound) have been used in various applications in dermatology, but they are not yet routinely used in the diagnosis of BCC. A key point in clinical practice is to find an imaging technique that can help to reduce post-surgical recurrences with a careful presurgical assessment of the lesional margins. This technique should show high sensitivity, specificity, reproducibility and simplicity of execution. This concept is very important for the optimal management of patients who are often elderly and have many comorbidities. The aim of the paper is to analyse the characteristics of current imaging techniques and the studies in the literature on this topic. MATERIALS AND METHODS: The authors independently searched the MEDLINE, PubMed, Embase, Scopus, ScienceDirect and Cochrane Library databases for studies looking for non-invasive imaging techniques for the presurgical margin assessment of BCC. RESULTS: Preoperative study of the BCC subtype can help to obtain a complete excision with free margins. Different non-invasive imaging techniques have been studied for in vivo evaluation of tumour margins, comparing the histologic evaluation with a radical surgery. The possibility to study the lateral and deep margins would allow a reduction of recurrences and sparing of healthy tissue. CONCLUSION: HFUS and UHFUS represent the most promising, non-invasive techniques for the pre-operative study of BCC facilitating the characterization of vascularization, deep lateral margins and high-risk subtypes, although they are limited by insufficient literature unlike RCM and OCT.

The Association Between pH and Fluorescence as Noninvasive Diagnostic Tools in Chronic Wounds.

MolecuLight i:X is a noninvasive, portable device that captures images, measures wound areas, and allows the evaluation of the bacterial environment in real time. The aim of the study was to correlate the different fluorescence (light green, red, cyan) and dark red-purple-black color areas with average pH values in these areas and with average wound bed score (WBS). During a 4-week period, we enrolled 43 adult patients (23 females and 20 males) with clinically infected and uninfected chronic ulcers. In our study, the mean age was 68 years old. The etiologies were 21 venous ulcers, 3 arterial ulcers, 4 vasculitis, 7 pyoderma gangrenosum, 7 traumatic ulcers, and 1 neoplastic ulcer. The average area was 16.92 cm2 and the average WBS was 9.17. A total of 16 ulcers (37%) were positive for clinical signs and symptoms of infection and 27 ulcers were negative (63%). Thirty-six ulcers emitted a single fluorescence: cyan (n = 13), red (n = 1), light green (n = 14), and dark red-purple-black (n = 8). Six wounds showed a double fluorescence area: red and cyan (n = 1) and cyan and light green (n = 5). One ulcer emitted a triple fluorescence area: red, cyan, and light green. Overall in 43 ulcers, we found 43 fluorescence and 8 dark red-purple-black color. We found significant data between pH and fluorescence. pH values on wound bed confirm in a noninvasive way the correlation between fluorescence and bacterial burden. Moreover, MolecuLight i:X is able to detect objectively the bacterial proliferation, in contrast with pH which cannot distinguish different types of bacteria.

Ultra-High Frequency Ultrasound in Melanoma Management: A New Combined Ultrasonographic-Histopathological Approach.

OBJECTIVES: The main aim of this study is to evaluate the correspondence between the ultrasonographic thickness and the Breslow thickness in melanoma using ultra-high frequency ultrasound and the intra- and inter-operator repeatability in the ultrasonographic measurements of melanoma depth. Moreover, we propose a new protocol based on a combined ultrasonographic-histopathological approach. METHODS: We analyzed 27 melanomas in a population consisted of 27 patients (mean age 57.6 years, 51.8% males), who came at the Department of Dermatology (University of Pisa, Pisa, Italy) from April 2016 to March 2018 and had an ultrasonographic examination of a suspected lesion before the surgical removal using ultra-high frequency ultrasound (Vevo®MD, Fujifilm, Visualsonics, Toronto, Canada; 70 MHz probe). B-mode images were analyzed by two skilled and blinded operators, and the maximum depth of the lesions was measured using a dedicated graphical user interface developed in Matlab R2016b (MathWorks Inc., Natick, MA), to obtain repetitive measurements. RESULTS: All melanomas appeared as band-like or oval/fusiform shaped hypoechoic inhomogeneous lesions. We observed an excellent agreement between the Breslow thickness of melanomas and the ultrasonographic thickness, as well as a reduced intra- and inter-operator variability in the ultrasonographic measurements of melanoma depth. CONCLUSIONS: We propose a ultrasonographic-histopathological protocol which may help clinicians to reduce the diagnostic delay, improve prognosis and survival rates, perform a surgical excision with negative margins, and reduce the variability in the assessment of Breslow thickness.

Ultra-high frequency ultrasound detection of the dermo-epidermal junction: Its potential role in dermatology.

Traditional high-frequency ultrasound (HFUS; 20 MHz) is a non-invasive method used to study skin in vivo but is not able to measure skin thickness accurately and to identify the dermal-epidermal junction (DEJ). Ultra-high frequency ultrasound (UHFUS; 70-100 MHz) has sub-millimetre resolution comparable to histology. The aim of this study was to identify, by UHFUS, the DEJ and to describe skin differences in healthy individuals by providing a measure of skin thickness, based on age and gender. We also described the bullous pemphigoid lesion. We enrolled 42 patients divided into 2 groups: A and B. Group A included 32 healthy volunteers aged 22-74 years. Group B consisted of 10 patients with bullous pemphigoid. For each patient in group A, 8 ultrasound (US) clips by 70 MHz probe were performed at forehead, cheek, nose, forearm, abdomen, chest, back and leg. For each patient in group B, 5 US images were acquired at blisters roofs and edges. In each US image, we measured thickness of stratum corneum (α-ß), epidermis (α-γ) and epidermis plus dermis (α-δ). In both groups, we found the presence of 4 lines delimiting: the stratum corneum (the layer between α-line and ß-line), the epidermis (distance between α- and γ-line), and the boundary between dermis and subcutis (δ-line). The γ-line corresponds to the point of detachment of the bullae. The abdominal α-ß layer was thicker in males (p = 0.019) and α-δ thickness at cheeks (p < 0.001), chest (p = 0.007), back (p = 0.025) and forearm (p < 0.001). In females, α-γ thickness of the back was greater (p = 0.005). In old people compared to young, we noticed an increase of α-ß layer at forehead and chest (p = 0.014), an increase of α-γ layer at forearm (p = 0.001), back (p = 0.024) and leg (p = 0.010) and an increase of α-δ layer at forehead (p = 0.001) and nose (p = 0.049). UHFUS is an advanced imaging technique that can detect both the DEJ and the boundary between dermis and subcutaneous tissue so that epidermal and dermal thickness can be measured with good accuracy. Regarding gender and age, skin differences obtained with UHFUS were comparable to other non-invasive methods.

Update on the Management of Pediatric Psoriasis: An Italian Consensus.

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.

Cutis marmorata telangiectatica congenita being caused by postzygotic GNA11 mutations.

Cutis marmorata telangiectatica congenita (CMTC) is characterized by coarse-meshed capillary malformations arranged in asymmetrically distributed patches. The disorder may be associated with hyper- or hypoplastic limbs, syndactyly, cleft palate, and glaucoma. Because the disease usually occurs sporadically, the concept of a lethal mutation surviving by mosaicism was proposed about 30 years ago. Here we describe three children with CMTC due to a postzygotic GNA11 mutation c547C > T (p.Arg183Cys), documented in saliva (patient 1) or lesional cutaneous tissue (patients 2 and 3). All three individuals had widespread and asymmetric CMTC which was present from birth and became fainter during the first years of life. Variably associated anomalies included glaucoma, choroidal capillary malformation, and body asymmetry. In previous case reports, postzygotic GNA11 mutations were documented in two cases of phacomatosis cesiomarmorata, being characterized by CMTC coexisting with segmental dermal melanocytosis. Moreover, postzygotic GNA11 mutations were noted in two CMTC patients described under the incorrect diagnosis of "nevus vascularis mixtus". Hence, the present cases convincingly support the concept that CMTC can be caused by mosaic GNA11 mutations and thus belongs to the GNA11-Related Capillary Nevus (GNARCAN) spectrum. In two other bona fide cases of CMTC, however, we were unable to find a mutation in GNA11, which may be explained either by our inability to detect a very low percentage of mutant cells or by genetic heterogeneity of the phenotype.