Characterization of a New Variant in ARHGAP31 Probably Involved in Adams-Oliver Syndrome in a Family with a Variable Phenotypic Spectrum.

Adams-Oliver syndrome is a rare inherited condition characterized by scalp defects and limb abnormalities. It is caused by variants in different genes such as ARHGAP31. Here, we used an interdisciplinary approach to study a family with lower limb anomalies. We identified a novel variant in the ARHGAP31 gene that is predicted to result in a truncated protein with a constitutively activated catalytic site due to the loss of 688 amino acids involved in the C-terminal domain, essential for protein auto-inhibition. Pathogenic variants in ARHGAP31 exon 12, leading to a premature protein termination, are associated with Adams-Oliver syndrome. Bioinformatic analysis was useful to elucidate the impact of the identified genetic variant on protein structure. To better understand the impact of the identified variant, 3D protein models were predicted for the ARHGAP31 wild type, the newly discovered variant, and other pathogenetic alterations already reported. Our study identified a novel variant probably involved in Adams-Oliver syndrome and increased the evidence on the phenotypic variability in patients affected by this syndrome, underlining the importance of translational research, including experimental and bioinformatics analyses. This strategy represents a successful model to investigate molecular mechanisms involved in syndrome occurrence.

Cutis verticis gyrata associated with congenital heart disease.

Cutis verticis gyrata (CVG) is a very rare benign disorder characterised by convoluted folds and deep furrows of the scalp that mimic cerebral sulci and gyri. Associations with other pathologies as neuropsychiatric and/or ophthalmologic disorders, secondary cases to inflammatory or neoplastic processes, as well as cases associated to genetic disorders as Turner's syndrome have been reported, but there is no literature describing an association with a congenital structural heart defect and no other underlying condition. We report a case of primary CVG in a 3-week-old female infant associated with an echocardiographic diagnosis of cor triatriatum. Other systemic examination findings and investigations were unremarkable, and the patient has normal neurodevelopment at 1 year old. Aside from the neuropsychiatric and ophthalmologic pathologies commonly associated with primary non-essential CVG, it should be noted that isolated congenital cardiac lesions are also possible, so as to increase our index of suspicion in patients with the disorder.

Erosive pustular dermatosis of the scalp secondary to Erlotinib: A rare occurrence with trichoscopic perspective.

Epidermal growth factor receptor inhibitors are anti-tumour agents that are frequently used for the treatment of neoplastic disorders. In addition to their cutaneous adverse effects, these drugs can rarely lead to erosive pustular dermatosis of the scalp. We report a case of a 67-year-old female who developed erosive pustular dermatosis of the scalp after being started on erlotinib from a trichoscopic perspective, which has been described in literature only once till now.

Atypical pediatric presentation of alopecic and aseptic nodules of the scalp with features of dissecting cellulitis.

Alopecic and aseptic nodules of the scalp (AANS) and dissecting cellulitis of the scalp (DCS) are rare, closely related conditions of young men that exclusively affect the hair-bearing scalp. We describe a 9-year-old boy who presented with a 6-year history of chronically relapsing, sterile, partially scarring nodules of the scalp and facial skin. Histopathology revealed mixed inflammatory infiltrates consisting of neutrophils, macrophages, lymphocytes, and plasma cells in the deep dermis, consistent with the morphological pattern of suppurative, partly granulomatous dermatitis. The present atypical case is characterized by prepubertal onset and facial involvement which, to our knowledge, has not yet been described before, may be included in the spectrum of "typical" AANS and "typical" DCS.

Treatment of erosive pustular dermatosis of the scalp: our experience and review of unconventional topical drugs.

BACKGROUND: Erosive pustular dermatosis of the scalp (EPDS) is a rare inflammatory disorder of elderly individuals, characterized by relapsing pustular and eroded lesions of the scalp, which may lead to scarring alopecia. Treatment is challenging and classically based on topical and/or oral corticosteroids. CASE REPORT: From 2008 to 2022, we treated fifteen cases of EPDS. We used mainly topical and systemic steroids with good results. Nevertheless, several non-steroidal topical drugs have been described in literature for the treatment of EPDS. We have carried out a brief review of these treatments. CONCLUSIONS: Topical calcineurin inhibitors represent a valuable alternative to steroids to avoid skin atrophy. Emerging evidence about other topical treatments, such as calcipotriol, dapsone, zinc oxide, together with photodynamic therapy, are evaluated in our review.

Cutaneous squamous cell carcinoma in an autosomal-recessive Adams-Oliver syndrome patient with a novel frameshift pathogenic variant in the EOGT gene.

Aplasia cutis congenita (ACC) of the scalp and terminal transverse limb defects (TTLD) are the characteristic findings of Adams-Oliver syndrome (AOS). The variable clinical spectrum further includes cardiac, neurologic, renal, and ophthalmological findings. Associated genes in AOS are in the Notch and the CDC42/Rac1 signaling pathways. Both autosomal-dominant and autosomal-recessive inheritances have been reported, the latter with pathogenic variants in DOCK6 or EOGT. The EOGT-associated recessive type of AOS has been postulated to present a more favorable prognosis. We here report a 12-year-old girl from a refugee family of Iraq with consanguineous parents. She was born with a severe phenotype of AOS presenting a large ACC of the scalp with an underlying skull defect, which was often infected and inflamed. Afterward, additional ulceration developed. Furthermore, the girl showed microcephaly, TTLD on both hands and feet, and neurological findings: spastic paresis, epilepsy and suspicion of intellectual deficit. Molecular genetic analysis (next-generation sequencing) revealed a novel frameshift mutation in the EOGT gene in Exon 13 in homozygous constellation: c.1013dupA p.(Asn338Lysfs*24). A biopsy within an ulceration at the scalp ACC showed a cutaneous squamous cell carcinoma (cSCC) with local invasive growth into the dura, the meninges, and the cortex. Treatment including surgical resection and focal irradiation was not curative and the girl deceased 6 months after initial diagnosis. This report on a patient with AOS and an autosomal-recessive EOGT gene variant dying of a local aggressive cSCC at an ACC lesion shows that close monitoring of ACC is essential.

Nonmelanoma skin cancer in the setting of erosive pustular dermatosis of the scalp: A case series and comment on management implications.

BACKGROUND: Erosive pustular dermatosis of the scalp (EPDS) is an inflammatory cutaneous disorder typically affecting sun-damaged skin of mature individuals. Clinical features of EPDS include sterile pustules and chronic crusted erosions that can be hyperkeratotic and lead to scarring alopecia, atrophy, and telangiectasia. While the condition occurs on sun-damaged skin, a relationship with non-melanoma skin cancer (NMSC) has not been investigated. OBJECTIVES: Here we attempted to identify cases of NMSC developing in the setting of EPDS. METHODS: Retrospective review of EPDS cases in a dermatology practice. RESULTS: Six patients with mean (range) age 82 (65-92) years that developed NMSC in the setting of EPDS are reported. Five patients had skin phototype I or II associated with substantial solar elastosis. Four patients had history of NMSC. Four patients developed squamous cell carcinoma and two patients basal cell carcinoma on the scalp in the setting of EPDS. A morphologic change in an EPDS lesion, such as a crusted plaque becoming nodular and/or growing significantly within a relatively short period of time, prompted a biopsy that revealed NMSC. CONCLUSIONS: NMSC may develop in the setting of EPDS. Possible mechanisms underlying this association include the chronic inflammation associated with EPDS and ultraviolet light exposure. It is crucial to promptly obtain a biopsy in EPDS cases showing signs suspicious for NMSC. Further studies are required to confirm whether NMSC shows a higher prevalence in the setting of EPDS.

Lichen planopilaris and frontal fibrosing alopecia: review and update of diagnostic and therapeutic features.

Lichen planopilaris and frontal fibrosing alopecia are primary scarring alopecias where diagnosis can be suggested by clinical and trichoscopy features, especially in the early stages, but scalp biopsy is the standard exam for definitive diagnosis. Frontal fibrosing alopecia is considered a variant of lichen planopilaris, as the histopathological findings are similar, with a perifollicular lymphohistiocytic infiltrate, sometimes with a lichenoid pattern. A thorough clinical examination, trichoscopy and photographic documentation are essential to assess the evolution and therapeutic response. To date, there are no validated treatments or guidelines for these diseases, but there are recommendations that vary with the individual characteristics of each patient. This article presents a comprehensive review of the literature, including an update on topics related to the diagnosis, follow-up, histopathological aspects and available treatments for lichen planopilaris and frontal fibrosing alopecia, highlighting their similarities, differences and peculiarities.

Regression of lipoedematous scalp following cryolipolysis using an icepack, with a novel dermoscopic feature of yellow background.

The novel use of cryolipolysis via icepacks, a readily available and inexpensive device, is described for lipoedematous scalp with subjective and objective relief. This is a simple solution to a troublesome, intractable condition and may readily be utilized for patient benefit. Juxtaposing pre and post clinical images.

Percutaneous ethanol sclerotherapy is a promising treatment for recalcitrant angiolymphoid hyperplasia with eosinophilia.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare benign vascular proliferation, which manifests as characteristic red nodules and papules, mostly located on the scalp and periauricular regions. Patients seek treatment for both aesthetic and functional reasons, as lesions may ulcerate, bleed and itch. Many therapeutic approaches have been reported, with variable success, and relapse remains a troublesome issue. The aim of this study was to report our experience treating ALHE using percutaneous ethanol sclerotherapy (PES). We present a retrospective case series of three patients treated with PES (1-2 treatment sessions each). All patients had tried and failed other treatments prior to this intervention, but following PES treatment, all patients demonstrated significant improvement, which was sustained at follow-up (range 8-17 months after first treatment). Adverse effects were tolerable and transient. This case series demonstrates PES as a promising treatment for recalcitrant ALHE.

A Practical Approach to the Diagnosis and Management of Classic Lichen Planopilaris.

Lichen planopilaris is a primary lymphocytic cicatricial alopecia that commonly presents with hair loss at the vertex or parietal scalp. Patients may also have associated scalp itching, burning or tenderness. Due to scarring, hair loss is typically permanent. The main goals of treatment are reducing symptoms and preventing disease progression and further hair loss. Currently, the literature has limited evidence on treatments for this difficult condition, and most available evidence is from case reports and case series. Furthermore, the evidence shows a varied response to therapy, with frequent reports of poor response. This article reviews the diagnosis of this rare disease, summarize the currently available treatments, and provide insights and practices from alopecia experts.

Primary nonessential cutis verticis gyrata with acne keloidalis nuchae.

Cutis verticis gyrata is a rare disorder characterized by redundant skin forming deep furrows and convolutions. It has been associated with several systemic and cutaneous disorders. We report a case of primary non-essential cutis verticis gyrata in association with acne keloidalis nuchae in a schizophrenic patient.

Demographic, clinical and dermoscopic features of melanocytic nevi on the scalp.

BACKGROUND: The scalp is a special anatomical area and dermoscopic findings of this region may significantly differ from other body parts. OBJECTIVE: To investigate and compare the clinical and dermoscopic patterns of scalp melanocytic nevi in patients ≤15 years of age and above, and to analyse their relevance to demographic features, atypical mole syndrome (AMS) and total body nevus count (TBNC). METHODS: In this retrospective cohort study, the clinical data and dermoscopic images of patients with scalp melanocytic nevi were retrieved, reviewed and analysed. Demographic, clinical and dermoscopic features were compared in patients ≤15 years of age and above. RESULTS: A total of 196 scalp melanocytic nevi in 126 patients (female/male:64/62; ≤15/>15 years of age: 49/77) with a median age of 18.5 years (range 0-72) were evaluated. Statistically, the globular pattern was significantly higher in all age groups, and the papillomatous pattern was significantly lower in patients ≤15 years of age (P = 0.008 and P = 0.005, respectively). The eclipse pattern was significantly higher, and the homogenous pattern was significantly lower in patients ≤15 years of age with AMS (P = 0.003 and P = 0.014, respectively). Finally, patients ≤15 years of age with 50 to 100 TBNC had a higher eclipse pattern than those with 0 to 25 TBNC. CONCLUSION: The findings of this retrospective study might implicate that children with eclipse pattern of scalp melanocytic nevi might be 'moley' in the future with an impending risk of AMS. This hypothesis requires confirmation in future prospective studies on a larger cohort of patients.

The chameleon rash: a review of the polyphenotypic dermatoses of dermatomyositis.

Dermatomyositis (DM) is an autoimmune connective tissue disease that is included in the idiopathic inflammatory myopathies. Cutaneous manifestations are a prominent part of the condition: some skin signs in DM are common to most patients, while other signs are encountered infrequently. A number of features are pathognomic for DM. The demonstration of myositis-specific antibodies (MSAs) in DM has extended the ability to define phenotypic subgroups. It appears that the presence of certain MSAs confers susceptibility to specific clinical features, an association which reveals a serotype-phenotype relationship. In this review article we have provided a detailed summary of common and under-recognized cutaneous manifestations of DM.