Comprehensive Molecular Analysis of Disease-Related Genes as First-Tier Test for Early Diagnosis, Classification, and Management of Patients Affected by Nonsyndromic Ichthyosis.

Inherited ichthyoses are a group of clinically and genetically heterogeneous rare disorders of skin keratinization with overlapping phenotypes. The clinical picture and family history are crucial to formulating the diagnostic hypothesis, but only the identification of the genetic defect allows the correct classification. In the attempt to molecularly classify 17 unrelated Italian patients referred with congenital nonsyndromic ichthyosis, we performed massively parallel sequencing of over 50 ichthyosis-related genes. Genetic data of 300 Italian unaffected subjects were also analyzed to evaluate frequencies of putative disease-causing alleles in our population. For all patients, we identified the molecular cause of the disease. Eight patients were affected by autosomal recessive congenital ichthyosis associated with ALOX12B, NIPAL4, and TGM1 mutations. Three patients had biallelic loss-of-function variants in FLG, whereas 6/11 males were affected by X-linked ichthyosis. Among the 24 different disease-causing alleles we identified, 8 carried novel variants, including a synonymous TGM1 variant that resulted in a splicing defect. Moreover, we generated a priority list of the ichthyosis-related genes that showed a significant number of rare and novel variants in our population. In conclusion, our comprehensive molecular analysis resulted in an effective first-tier test for the early classification of ichthyosis patients. It also expands the genetic, mutational, and phenotypic spectra of inherited ichthyosis and provides new insight into the current understanding of etiologies and epidemiology of this group of rare disorders.

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.

Bilateral Chilblain-like Lesions of the Toes Characterized by Microvascular Remodeling in Adolescents During the COVID-19 Pandemic.

Importance: Chilblain-like lesions have been one of the most frequently described cutaneous manifestations during the COVID-19 pandemic. Their etiopathogenesis, including the role of SARS-CoV-2, remains elusive. Objective: To examine the association of chilblain-like lesions with SARS-CoV-2 infection. Design, Setting, and Participants: This prospective case series enrolled 17 adolescents who presented with chilblain-like lesions from April 1 to June 30, 2020, at a tertiary referral academic hospital in Italy. Main Outcomes and Measures: Macroscopic (clinical and dermoscopic) and microscopic (histopathologic) analysis contributed to a thorough understanding of the lesions. Nasopharyngeal swab, serologic testing, and in situ hybridization of the skin biopsy specimens were performed to test for SARS-CoV-2 infection. Laboratory tests explored signs of systemic inflammation or thrombophilia. Structural changes in peripheral microcirculation were investigated by capillaroscopy. Results: Of the 17 adolescents (9 [52.9%] male; median [interquartile range] age, 13.2 [12.5-14.3] years) enrolled during the first wave of the COVID-19 pandemic, 16 (94.1%) had bilaterally localized distal erythematous or cyanotic lesions. A triad of red dots (16 [100%]), white rosettes (11 [68.8%]), and white streaks (10 [62.5%]) characterized the dermoscopic picture. Histologic analysis revealed a remodeling of the dermal blood vessels with a lobular arrangement, wall thickening, and a mild perivascular lymphocytic infiltrate. SARS-CoV-2 infection was excluded by molecular and serologic testing. In situ hybridization did not highlight the viral genome in the lesions. Conclusions and Relevance: This study delineated the clinical, histologic, and laboratory features of chilblain-like lesions that emerged during the COVID-19 pandemic, and its findings do not support their association with SARS-CoV-2 infection. The lesions occurred in otherwise healthy adolescents, had a long but benign course to self-resolution, and were characterized by a microvascular remodeling with perivascular lymphocytic infiltrate but no other signs of vasculitis. These results suggest that chilblain-like lesions do not imply a concomitant SARS-CoV-2 infection. Ongoing studies will help clarify the etiopathogenic mechanisms.

Efficacy and safety of oral minoxidil in female androgenetic alopecia.

Oral minoxidil (OM) has been reported to be effective for androgenetic alopecia (AGA). In this retrospective study, we share our experience of using OM for >24 weeks in 12 patients with female AGA (Ludwig scale I-3-III). Twelve women (aged 18-66 years; mean age 36.66 ± 18.79 years) with AGA (Ludwig scale I-3-III) were recruited. The starting dose of minoxidil was 0.50 mg daily; at 3 months, the dose was increased to 1.50 to 2 mg daily. Efficacy outcome measures were evaluated at baseline and after 24 weeks and included global clinical photography, quantitative digital videotrichoscopic assessment and quality-of-life evaluation. An overall improvement of 38% and 23% in hair density in the frontal and vertex area, respectively, was observed after 24 weeks. The quantitative digital videotrichoscopic evaluation highlighted a statistically significant improvement in the frontal area of the total average hair density and of the total number of hairs per unit area at 24 weeks (131.47 ± 36.11 vs 181.40 ± 57.38; P = .025 and 118.72 ± 32.61 vs 163.81 ± 51.82; P = .025, respectively). In conclusion, OM was effective and had an acceptable safety profile in treating female AGA. The low number of patients and retrospective design of this study are limitations.

An Undetected Case of Tinea Capitis in an Elderly Woman Affected by Dermatomyositis: How Trichoscopy Can Guide to the Right Diagnosis.

Dermatomyositis (DM) is an autoimmune disease that primarily affects the skin and muscles, but may also have a systemic involvement. The frequency of scalp involvement in DM varies from 28 to 82% and is often encountered as part of a DM flare. However, it frequently presents as a treatment-resistant disease, and patients reporting no improvement with conventional therapies require further investigation. We report a case of tinea capitis (TC) in a 79-year-old woman affected by DM with scalp involvement which did not respond to conventional therapies. Thanks to trichoscopy we could detect "comma hairs," "zigzag hairs," and "pigtail hairs" at scalp examination, made the right diagnosis of TC, and instituted the best treatment without delay.

Atypical Manifestations in Classic Kaposi Sarcoma: Case Series of Two Patients HIV - Negative.

BACKGROUND: Kaposi's sarcoma (KS) is a tumour of endothelial, blood and lymphatic cells, caused by an infection with human herpesvirus-8 (HHV-8). The skin lesions of KS, especially of the classical or Mediterranean variant (CKS), are represented by red-purple macules, plaques and nodules, localised mainly on the extremities. CASE REPORT: This case series intend to describe multifocal atypical kaposian manifestations in two HIV negative subjects, affected by CKS, treated with successful chemotherapy. CONCLUSIONS: Although atypical manifestations are extremely rare events, we suggest an accurate, objective examination because a prompt diagnosis can lead to a vital intervention in the patient's health and sometimes to the identification of the disease itself.