Frontal Fibrosing Alopecia: Role of Dermoscopy in Differential Diagnosis

Frontal fibrosing alopecia (FFA) is more common in postmenopausal women, but it can occur in younger women. Some authors consider FFA to be a distinct frontal variant of lichen planopilaris. From a clinical point of view, this relatively uncommon condition is characterized by progressive frontotemporal recession due to inflammatory destruction of hair follicles. Dermoscopy can be very useful, as the differential diagnosis between traction alopecia, alopecia areata, FFA and cicatricial marginal alopecia may be difficult. It is not clear whether or not treatment alters the natural history of the disease - the disease stabilized with time in most of the patients with or without continuing treatment. Here we report a case of a 50-year-old woman with FFA and discuss the relevance of dermoscopy in the differential diagnosis of this disease

Line-field confocal optical coherence tomography: a new tool for non-invasive differential diagnosis of pustular skin disorders

Background The spectrum of pustular skin disorders (PSD) is large and particularly challenging, including inflammatory, infectious and amicrobial diseases. Moreover, although pustules represent the unifying clinical feature, they can be absent or not fully developed in the early stage of the disease. The line-field confocal optical coherence tomography (LC-OCT) is a recently developed imaging technique able to perform a non-invasive, in vivo, examination of the epidermis and upper dermis, reaching very high image resolution and virtual histology. Objectives We aimed to investigate the potentialities of LC-OCT in the non-invasive differential diagnosis of a series of 11 PSD with different aetiology, microscopic features, body location and incidence rates. Materials and Methods Complete LC-OCT imaging (i.e. 2D/3D frames, videos) was performed on a total of 19 patients (10 females and 9 males) aged between 35 and 79 years. Images were blindly evaluated and compared with corresponding histopathologic findings. Results The LC-OCT imaging was able to detect with high accuracy the pustule structure including shape, margins, morphology and cellular content, along with peculiar epidermal and adnexal alterations in each condition, including: Acute Generalized Exanthematous Pustulosis, Generalized pustular psoriasis, Generalized pustular figurate erythema, Subcorneal Pustular Dermatosis, Intraepidermal IgA pustulosis, Palmoplantar pustulosis, Palmoplantar pustular psoriasis. Herpetic whitlow, Acrodermatitis continua of Hallopeau, Vesicopustular Sweet syndrome and Vesicopustular Eosinophilic cellulitis, with pustular appearance, were also compared. Conclusions The new LC-OCT can represent a rapid, non-invasive and painless tool which can help differentiating among PSD of different aetiology and microscopic morphology in clinical mimickers in daily practice

Phenotypic definition and genotype-phenotype correlates in pmpca-related disease

Background: Peptidase mitochondrial processing alpha (PMPCA) biallelic mutations cause a spectrum of disorders ranging from severe progressive multisystemic mitochondrial encephalopathy to a milder non-progressive cerebellar ataxia with or without intellectual disability. Recently, we and others described an intermediate phenotype in two unrelated patients. Methods: We report a second Italian patient carrying novel PMPCA variants (p.Trp278Leu; p.Arg362Gly). Molecular modeling, dynamics simulation, RT-qPCR, and Western blotting were performed to predict the pathogenic impact of variants in the two Italian patients and attempt genotype-phenotype correlates. Results: In line with the two patients with intermediate phenotypes, our case presented global psychomotor delay with regression, intellectual disability, spastic-ataxic gait, and hyperkinetic movements, with cerebellar atrophy and bilateral striatal hyperintensities. However, blood lactate, muscle biopsy, and MRI spectroscopy were normal. PMPCA protein levels were significantly higher than controls despite normal cDNA levels. Dynamics simulation of several PMPCA missense variants showed a variable impact on the flexibility of the glycine rich loop and, for some cases, on the overall protein stability, without clear genotype-phenotype correlates. Conclusion: We confirm the expansion of PMPCA phenotypic spectrum including an intermediate phenotype of progressive encephalopathy without systemic involvement. The association of cerebellar atrophy with “Leigh-like” striatal hyperintensities may represent a “red flag” for this condition

Myoimaging in the NGS era: The discovery of a novel mutation in MYH7 in a family with distal myopathy and core-like features -a case report

Background: Myosin heavy chain 7 related myopathies are rare disorders characterized by a wide phenotypic spectrum and heterogeneous pathological features. In the present study, we performed clinical, morphological, genetic and imaging investigations in three relatives affected by autosomal dominant distal myopathy. Whilst earlier traditional Sanger investigations had pointed to the wrong gene as disease causative, next-generation sequencing allowed us to obtain the definitive molecular genetic diagnosis in the family.Case presentation: The proposita, being found to harbor a novel heterozygous mutation in the RYR1 gene (p. Glu294Lys), was initially diagnosed with core myopathy. Subsequently, consideration of muscle magnetic resonance imaging (MRI) features and extension of family study led this diagnosis to be questioned. Use of next-generation sequencing analysis identified a novel mutation in the MYH7gene (p.Ser1435Pro) that segregated in the affected family members.Conclusions: This study identified a novel mutation in MYH7 in a family where the conclusive molecular diagnosis was reached through a complicated path. This case report might raise awareness, among clinicians, of the need to interpret NGS data in combination with muscle MRI patterns so as to facilitate the pinpointing of the main molecular etiology in inherited muscle disorders

Skin Lesion Segmentation Ensemble with Diverse Training Strategies

This paper presents a novel strategy to perform skin lesion segmentation from dermoscopic images. We design an effective segmentation pipeline, and explore several pre-training methods to initialize the features extractor, highlighting how different procedures lead the Convolutional Neural Network (CNN) to focus on different features. An encoder-decoder segmentation CNN is employed to take advantage of each pre-trained features extractor. Experimental results reveal how multiple initialization strategies can be exploited, by means of an ensemble method, to obtain state-of-the-art skin lesion segmentation accuracy

Unfolding dermatologic spectrum of Behçet’s disease in Italy: real-life data from the International AIDA Network Behçet’s disease Registry

Behçet’s disease (BD) is a heterogeneous multifactorial autoinflammatory disease characterized by a plethora of clinical manifestations. Cutaneous lesions are considered hallmarks of the disease. However, their evolution over time and a thorough description are scarcely reported in non-endemic regions. The aim of this study was to detail BD skin manifestations and their evolution over time in Italy, as well as the dermatological prognostic impact of specific cutaneous features in long-standing disease. Data were collected in a double fashion, both retrospectively and prospectively, from the AutoInflammatory Disease Alliance (AIDA) international registry dedicated to BD, between January 2022 and December 2022. A total of 458 Italian patients were included. When assessing skin manifestations course, the constant or sporadic presence or absence of cutaneous involvement between onset and follow-up was considered. Oral ulcers (OU) (88.4%) and genital ulcers (GU) (52.6%), followed by skin involvement (53.7%) represented the most common presenting mucocutaneous manifestations at disease onset. Up to the time of enrolment into the AIDA registry, 411 (93.8%) patients had suffered from OU and 252 (57.9%) from GU; pseudofolliculitis (PF) accounted for the most common skin manifestation (170 patients, 37.1%), followed by erythema nodosum (EN) (102 patients, 22.3%), skin ulcers (9 patients, 2%) and pyoderma gangrenosum (4 patients, 0.9%). A prospective follow-up visit was reported in 261/458 patients; 24/148 (16.2%) subjects with skin involvement as early as BD onset maintained cutaneous lesions for the entire period of observation, while 120 (44.1%) patients suffered from sporadic skin involvement. Conversely, 94/113 (83.2%) with no skin involvement at disease onset did not develop skin lesions thereafter. At follow-up visits, cutaneous involvement was observed in 52 (20%) patients, with a statistically significant association between PF and constant skin involvement (p = 0.031). BD in Italy is characterized by a wide spectrum of clinical presentations and skin manifestations in line with what is described in endemic countries. Patients with skin disease at the onset are likely to present persistent cutaneous involvement thereafter; mucocutaneous lesions observed at the onset, especially PF, could represent a warning sign for future persistent skin involvement requiring closer dermatological care

Amelanotic/hypomelanotic lentigo maligna: Dermoscopic and confocal features predicting diagnosis

Background: Amelanotic/hypomelanotic lentigo maligna and lentigo maligna melanoma (AHLM/LMM) may be very difficult to diagnose at an early stage. Objectives: To quantify the predictive value of dermoscopic and reflectance confocal microscopy (RCM) features for AHLM/LMM. Methods: Dermoscopic and RCM images of histopathologically diagnosed AHLM/LMM, amelanotic/hypomelanotic benign lesions (AHBL), and amelanotic/hypomelanotic basal and squamous cell carcinomas (AHBCC/AHSCC) of the head and neck from consecutive patients were retrospectively collected and blindly evaluated by three observers to assess presence or absence of dermoscopic and RCM criteria. Results: Overall, 224 lesions in 216 patients including LM/LMM (n = 55, 24.6%), AHBL (n = 107, 47.8%) and AHBCC/AHSCC (n = 62, 27.7%) were analysed. Multivariable analysis showed that milky-red areas (OR = 5.46; 95% CI: 1.51–19.75), peripheral light brown structureless areas (OR = 19.10; 4.45–81.96), linear irregular vessels (OR = 5.44; 1.45–20.40), and asymmetric pigmented follicles (OR = 14.45; 2.77–75.44) at dermoscopy, and ≥3 atypical cells in five fields (OR = 10.12; 3.00–34.12) and focal follicular localization of atypical cells at dermo-epidermal junction (DEJ) (OR = 10.48; 1.10–99.81) at RCM were significantly independent diagnostic factors for AHLM/LMM vs. AHBL. In comparison with AHBCC/AHSCC, peripheral light brown structureless area (OR = 7.11; 1.53–32.96), pseudonetwork around hair follicles (OR = 16.69; 2.73–102.07), and annular granular structures (OR = 42.36; 3.51–511.16) at dermoscopy and large dendritic (OR = 6.86; 3.15–38.28) and round pagetoid cells (OR = 26.78; 3.15–227.98) at RCM led to a significantly increased risk of diagnosing AHLM/LMM. Conclusions: Amelanotic/hypomelanotic lentigo maligna and lentigo maligna melanoma may have the same dermoscopic features of AHM on other body sites, such as milky red areas, peripheral light brown structureless areas and linear irregular vessels. These features, asymmetric pigmented follicles and at RCM ≥ 3 atypical cells in five fields and focal follicular extension of atypical cells at DEJ may help in recognizing AHLM/LMM even when LM conventional features (e.g., obliteration of hair follicles under dermoscopy and large pagetoid cells under RCM) are absent or present only in very small areas of the lesion

Next-generation sequencing approach to hyperCKemia: A 2-year cohort study

ObjectiveNext-generation sequencing (NGS) was applied in molecularly undiagnosed asymptomatic or paucisymptomatic hyperCKemia to investigate whether this technique might allow detection of the genetic basis of the condition.MethodsSixty-six patients with undiagnosed asymptomatic or paucisymptomatic hyperCKemia, referred to tertiary neuromuscular centers over an approximately 2-year period, were analyzed using a customized, targeted sequencing panel able to investigate the coding exons and flanking intronic regions of 78 genes associated with limb-girdle muscular dystrophies, rhabdomyolysis, and metabolic and distal myopathies.ResultsA molecular diagnosis was reached in 33 cases, corresponding to a positive diagnostic yield of 50%. Variants of unknown significance were found in 17 patients (26%), whereas 16 cases (24%) remained molecularly undefined. The major features of the diagnosed cases were mild proximal muscle weakness (found in 27%) and myalgia (in 24%). Fourteen patients with a molecular diagnosis and mild myopathic features on muscle biopsy remained asymptomatic at a 24-month follow-up.ConclusionsThis study of patients with undiagnosed hyperCKemia, highlighting the advantages of NGS used as a first-tier diagnostic approach in genetically heterogeneous conditions, illustrates the ongoing evolution of molecular diagnosis in the field of clinical neurology. Isolated hyperCKemia can be the sole feature alerting to a progressive muscular disorder requiring careful surveillance

Pigmented nodular melanoma: the predictive value of dermoscopic features using multivariate analysis

BACKGROUND: Nodular melanoma (NM), representing 10-30% of all melanomas, plays a major role in global mortality related to melanoma. Nonetheless, the literature on dermoscopy of NM is scanty. OBJECTIVES: To assess odds ratios (ORs) to quantify dermoscopic features of pigmented NM vs. pigmented superficial spreading melanoma (SSM), and pigmented nodular nonmelanocytic and benign melanocytic lesions. METHODS: To assess the presence or absence of global patterns and dermoscopic criteria, digitized images of 457 pigmented skin lesions from patients with a histopathological diagnosis of NM (n = 75), SSM (n = 93), and nodular nonmelanocytic and benign melanocytic lesions (n = 289; namely, 39 basal cell carcinomas, 85 seborrhoeic keratoses, 81 blue naevi, and 84 compound/dermal naevi) were retrospectively collected and blindly evaluated by three observers. RESULTS: Multivariate analysis showed that ulceration (OR 4.07), homogeneous disorganized pattern (OR 10.76), and homogeneous blue pigmented structureless areas (OR 2.37) were significantly independent prognostic factors for NM vs. SSM. Multivariate analysis of dermoscopic features of NM vs. nonmelanocytic and benign melanocytic lesions showed that the positive correlating features leading to a significantly increased risk of NM were asymmetric pigmentation (OR 6.70), blue-black pigmented areas (OR 7.15), homogeneous disorganized pattern (OR 9.62), a combination of polymorphous vessels and milky-red globules/areas (OR 23.65), and polymorphous vessels combined with homogeneous red areas (OR 33.88). CONCLUSIONS: Dermoscopy may be helpful in improving the recognition of pigmented NM by revealing asymmetric pigmentation, blue-black pigmented areas, homogeneous disorganized pattern and abnormal vascular structures, including polymorphous vessels, milky-red globules/areas and homogeneous red areas