Evaluation of linear dermatoses by reflectance confocal microscopy in children.

Lichen striatus (LS), linear psoriasis (LPs), linear cutaneous lupus erythematosus (LCLE) and linear lichen planus (LLP) often have similar clinical manifestations, which makes clinical diagnosis with the naked eye difficult; therefore, they are easily misdiagnosed. The purpose of this study was to determine whether reflectance confocal microscopy (RCM) is helpful in differentiating between these four linear dermatoses in children. This retrospective study included 14 patients with LS, nine with LPs, eight with LCLE and 12 with LLP. All patients were analysed using RCM, and biopsies were collected from lesions previously imaged by RCM. For LS, the dermal papillary rings were partially absent, but when present, manifested with small, homogeneously round, bright cells and occasionally highly refractive plump cellular structures, aggregated in clusters. LPs exhibited dark cyst-like structures with small, bright, round cells aggregated at the epidermal level; at the dermal-epidermal junction, homogeneously distributed, enlarged, faint dermal papillary rings and numerous enlarged low-refractive canalicular structures were observed in the superficial dermis. LCLE and LLP exhibited similar manifestations, including epidermal disarray, almost total absence of dermal papillary rings, and various sized refractive structures densely distributed in the dermis. The key distinguishing features of LCLE were the different sized structures mainly clustered around hair follicles, while LLP demonstrated dense structures with a scattered distribution. RCM may be used to distinguish between the key features of LS, LPs, LCLE and LLP in children.

Diseases categorized as autoinflammatory keratinization diseases (AiKDs), and their pathologies and treatments.

Whole-exome and whole-genome sequencing have become widespread in approximately the last 15 years, and the predisposing factors and pathomechanisms of inflammatory keratinization diseases, which have been unknown for a long time, have gradually been revealed. Hence, various inflammatory keratinization diseases are recognized to cause innate immunity hyperactivation. Therefore, we have been advocating for the clinical entity, "autoinflammatory keratinization diseases (AiKDs)" since 2017. AiKDs are inflammatory keratinization diseases caused by autoinflammatory-related pathomechanisms in the skin. The aberrant activation of innate immunity and the resultant autoinflammation in the epidermis and the superficial dermis in AiKDs cause hyperkeratosis in the epidermis. Our initially proposed concept of AiKDs included generalized pustular psoriasis and related conditions, pityriasis rubra pilaris type V, and familial keratosis lichenoides chronica. Since then, the number of diseases known to be AiKDs has increased as previously unknown disease-causing factors and pathogenetic mechanisms of inflammatory keratinization diseases have been clarified one by one. To date, porokeratosis, hidradenitis suppurative, keratosis linearis with ichthyosis congenita and sclerosing keratoderma (KLICK) syndrome, and AiKDs associated with epidermal growth factor receptor (EGFR) deficiency or with hepatitis and autism have been recognized as AiKDs. The concept of AiKDs is considered extremely useful in our precise understanding of the pathogeneses behind inflammatory keratinization diseases and our appropriate treatment method selection. The number of AiKDs is expected to grow with the clarification of the pathomechanisms of further inflammatory keratinization diseases.

Infantile anogenital digitate keratoses.

Infantile anogenital digitate keratoses (IADK) represent a distinct and under-recognized pediatric condition of the perianal area of infants, significantly more frequent in males than females. The average age of onset is 3.2 months, and it is self-remitting by 2 years of age. Perianal spiny keratoses resistant to usual topical therapies are the hallmark of IADK. We present a series of three cases of IADK seen at the dermatology clinic of the CHU Sainte-Justine to raise awareness on this pediatric condition, and to prevent invasive workup.

A retrospective study on the clinical features of skin lesions in Chinese acquired digital fibrokeratoma patients.

BACKGROUND: Acquired digital fibrokeratoma (ADFK) is an uncommon benign fibro-epithelioma, which is rarely reported in China. AIMS: To analysis the clinical features of ADFK in Chinese people from current cases. METHODS: From December 2019 to October 2021, there were 21 patients diagnosed with ADFK, we made a retrospective analysis on the clinical features of skin lesions in them. To summarize the clinical morphology, location, and surgical follow-up of ADFK. RESULTS: We concluded that ADFK is more common in females than males on the hands (7:3), while the male-to-female ratio is largely the same in feet (6:5). It occurs more frequently on the third finger (60%) and first toe (45.5%). As to clinical morphology, it is typically rod-shaped (52.4%), followed by dome-shaped (42.8%) and wart-shaped (4.8%). It is typically dome-shaped on the hands (80%) and rod-shaped on the feet (81.8%). In terms of location on the fingers (toes), such skin lesions are most common at the proximal nail fold (52.4%), which can also occur at the nail matrix (14.3%), periungual area (23.8%), and subungual area (9.5%). Nevertheless, this ratio also varies on the hands and feet. All patients got surgical excision of the skin lesion, who were followed up for 6-12 months, without recurrence. CONCLUSIONS: Most ADFKs are associated with trauma, whose clinical features are related to location and gender. ADFKs on the hands are different from those on the feet regarding clinical morphology and location on fingers (toes), and surgery is effective in treating this condition.

Cutaneous Horn Presentation in Porokeratotic Eccrine Ostial and Dermal Duct Nevus. A Brief Review and Case Report.

ABSTRACT: Porokeratotic eccrine ostial and dermal duct nevus is a rare adnexal hamartoma characterized by the presence of a cornoid lamella exclusively overlying eccrine acrosyringia. Different clinical presentations have been reported in the literature. Here, we report a case of a 6-year-old girl diagnosed with porokeratotic eccrine ostial and dermal duct nevus confirmed by histopathologic study. Atypical lesions are described as whitish, warty-looking neoformations located in the anterolateral region of the right hip (cutaneous horn).

Multiple minute digitate hyperkeratosis: 10 years from Caccetta's algorithm. A case report and narrative review.

To date, the clinical appearance and histological features of multiple minute digitate hyperkeratosis have been well characterized. However, there is no consensus on its treatment. After a comprehensive search of the databases MEDLINE, EMBASE, Web of Science, and the Cochrane Library and Database of Systematic Reviews, we have summarized the available clinical evidence regarding the therapeutic approaches already reported for this entity since its first description in 1967. Additional publications were identified within the references of retrieved papers. Sixty-five articles have been revised, resulting in a total of 73 compatible cases. The histopathological features and different classifications used through history have also been considered, updating and completing the available knowledge. Ultimately, we propose topical treatment with 5 % 5-fluorouracil formulated with 10 % salicylic acid as a potential treatment that has been used successfully in a 51-year-old woman at our facility. Further research in form of prospective or comparative studies is encouraged for a better conceptualization of the therapeutics of this disease.

External Ear Disease: Keratinaceous Lesions of the External Auditory Canal.

Keratosis obturans (KO) and external auditory canal cholesteatoma (EACC) are two distinct keratinaceous lesions of the external ear. This article reviews the signs, symptoms, pathophysiology, workup, and treatment of each. Patients with either pathology can often be managed in the clinic with debridement; however, EACC is more likely to involve osteonecrosis and require more extensive operative management if disease is not confined to the canal on account of the bony erosion characteristic of cholesteatoma. If required for extensive disease, surgical approaches to both pathologies are similar.

Pathogenic variants in the SPTLC1 gene cause hyperkeratosis lenticularis perstans.

BACKGROUND: Hyperkeratosis lenticularis perstans (HLP), also known as Flegel disease, is a rare skin disease presenting with asymptomatic small hyperkeratotic papules. The lesions often appear on the dorsal feet and lower legs, and typically develop after the fourth decade of life. A genetic basis for HLP is suspected; however, so far no gene defect linked to the development of HLP has been identified. OBJECTIVES: We aimed to identify the genetic cause of HLP. METHODS: For mutational analysis we studied a cohort of five patients with HLP using next-generation sequencing (NGS). We used DNA -extracted from fresh skin biopsies alongside ethylenediamine tetraacetic acid (EDTA) blood samples from two patients, and formalin-fixed -paraffin-embedded skin biopsy material from three patients. In addition, immunofluorescence staining of HLP lesions from four patients was investigated. RESULTS: In all samples from the five patients with HLP we identified by NGS rare variants in the SPTLC1 gene. In four patients we detected small deletions/frameshift variants and in one patient a splicing variant, predicted to disturb the splicing process. In blood samples the detected variants were heterozygous with an allele frequency of 49% and 50%, respectively. In skin biopsies the allele frequency was within the range of 46-62%. Immunofluorescence staining revealed reduced SPTLC1 protein levels in skin of patients. CONCLUSIONS: Our findings suggest that pathogenic variants in the SPTLC1 gene are the underlying genetic cause of HLP. Of note, the identified variants were either frameshift- or splicing variants probably leading to nonsense-mediated mRNA decay and thus reduced SPTLC1 protein levels. We conclude that diminished SPTLC1, the key enzyme in sphingolipid biosynthesis, leads to the development of HLP, which highlights the sphingolipid pathway as a new therapeutic target.

Histopathological analysis of chronic paronychia.

BACKGROUND: Chronic paronychia is an inflammatory process of the nail folds lasting more than 6 weeks. Clinically, there is hypertrophy and retraction of the folds and absence of the cuticle. Treatment involves clinical measures and, when there is no response or the hypertrophy of the folds is very pronounced, surgical treatment is indicated. Post-surgical histopathology is little studied in the literature. In this sense, we believe that the histopathological study is important not only for the individualized understanding of the patient's chronic disease, avoiding relapses, but also for the understanding of its pathophysiology and treatment possibilities. OBJECTIVE: To describe the histopathological changes found in biopsies of the proximal nail fold of patients with chronic paronychia undergoing surgical treatment. MATERIALS AND METHODS: A histopathological study of 16 nail folds from 6 patients after surgery was performed at 2 study centers. RESULTS: The most prevalent epidermal findings were orthokeratosis, hypergranulosis, acanthosis and spongiosis and the dermal findings were fibrosis and mononuclear inflammatory infiltrate. CONCLUSION: The histopathological study allowed us to conclude that chronic paronychia is primarily an inflammatory process, but it is not possible to conclude whether microorganisms such as Candida and bacterial cocci are part of the etiology or just secondary and opportunistic agents.

[Verrucous exophytic tumor of the glans penis]. / Verruköser exophytischer Tumor der Glans penis.

A 59-year-old man presented with a growing tumor on the glans penis, which we excised. Histologically, there was an acanthotic epidermis under which the papillary dermis was filled with foamy macrophages, best seen in a CD 68 stain. Verruciform xanthoma was diagnosed. Knowledge of this benign diagnosis may prevent an overly hasty, aggressive approach, since the differential diagnosis of penile carcinoma requires much more radical therapy, and mutilating penile surgery is associated with considerable psychosexual distress for patients.

A possible role for second-hit postzygotic GJB2 mutation in porokeratotic eccrine ostial and dermal duct nevus.

Porokeratotic eccrine ostial and dermal duct nevus (PEODDN) is a rare type of epidermal nevus involving the eccrine acrosyringia. It typically presents as asymptomatic linear keratotic papules and plaques along the lines of Blaschko and predominantly affects the extremities. This disease has recently been linked to somatic mutations within the GJB2 locus. Only four GJB2 mutations have been previously documented for PEODDN, and the underlying genetic basis remains inconclusive. Herein, we report an 18-year-old female with a hyperkeratotic plaque on the dorsa of the proximal interphalangeal joint of her right ring finger, as well as multiple small hyperkeratotic papules linearly distributed on the lateral sides of her fingers occurring since birth. Histopathological results revealed prominent parakeratotic cornoid lamella-like tiers at the opening of the eccrine secretory ducts. Whole-exome sequencing of the affected skin tissue revealed a heterozygous germline mutation and a postzygotic somatic mutation in GJB2. In summary, this study presents a case of PEODDN with compound heterozygous mutations in GJB2, which broadens the genetic spectrum of this disease entity and implies a possible role for second-hit mutations in the pathogenesis of PEODDN.

[Therapeutic escalation in a case of nevoid hyperkeratosis of the areola and the nipple]. / Escalade thérapeutique devant un cas d'hyperkératose nævoïde de l'aréole et du mamelon.

Nevoid hyperkeratosis of the nipple areola complex (NAC) is a rare dermatological pathology of unknown etiology, first described in 1923. It is a benign condition characterized by verrucous thickening and brownish discoloration of the NAC. We described the case of a 26-year-old woman with bilateral nevoid hyperkeratosis of the NAC. Several lines of treatment have been used with varying efficacy: conservative (calcipotriol and local retinoids), semi-conservative (CO2 laser) and surgical (excision and total skin graft). The final result is very satisfactory and without recurrence at 1 year follow-up.

Bowen Disease Within a Circumscribed Palmar Hypokeratosis.

ABSTRACT: Circumscribed palmar or plantar hypokeratosis is a focal disorder of keratinization that consists of a reduction in the thickness of the corneal layer of the epidermis of palms or soles. Although it is considered a benign entity, the thinning of the stratum corneum facilitates ultraviolet damage in the affected skin, which may result in an increased risk of developing focal epidermal dysplasia. Other factors, such as immunosuppression in transplanted patients, may play a role as well. We present a case of circumscribed palmar or plantar hypokeratosis with features of Bowen disease limited to the hypokeratotic epidermis.

Acrokeratosis of Bazex as a sign of thyroid cancer: first description and review of thyroid-associated paraneoplastic dermatoses.

OBJECTIVE: Bazex syndrome is a rare paraneoplastic skin disorder of unknown pathogenesis. Cutaneous findings are usually noticed before the diagnosis of the underlying malignancy, more frequently squamous cell carcinomas of the upper aerodigestive tract or metastasis to cervical lymph nodes. Association with other malignancies has been reported. CASE REPORT: Herein, we describe a case in course of metastatic papillary thyroid carcinoma and review the relevant literature. RESULTS: A bibliographic search was conducted and a total of 8 studies concerning the association were reviewed. CONCLUSIONS: Physicians be aware of unexpected cutaneous conditions as a possible sign of underlying tumors.

Pseudoepitheliomatous keratotic and micaceous balanitis: a series of eight cases.

BACKGROUND: Pseudoepitheliomatous keratotic and micaceous balanitis (PEKMB) is a clinicopathological entity characterized clinically by micaceous scale on the glans, and histologically by acanthosis, hyperkeratosis and pseudoepitheliomatous hyperplasia. We present a series of eight cases of this rare condition, the first series of more than two cases to be reported. OBJECTIVES: To determine the clinical and histological characteristics of cases of PEKMB, and evaluate treatments used and clinical course. METHODS: This monocentric case series was conducted at the University College London Hospitals tertiary male genital dermatology clinic between April 2018 and August 2020. Eight patients with PEKMB were evaluated. Data were collected on demographics, clinical presentation, histological features, presence of human papilloma virus (HPV), history of lichen sclerosus, treatment of PEKMB and subsequent response, and presence or development of squamous cell carcinoma (SCC) or penile intraepithelial neoplasia (PeIN) during follow-up. RESULTS: Eight Caucasian males presented with clinical and histological evidence of PEKMB. Seven had a background of lichen sclerosus; two had failed treatment with superpotent topical steroids and four had symptoms for three or more years prior to circumcision. There was no clinical or histological relationship with HPV infection, and p16 staining was negative. HPV PCR, performed in two cases, was negative. Basal atypia, insufficient to amount to PeIN, was present in six patients. One patient progressed to PeIN during follow-up, and no patient progressed to invasive malignancy. Five patients were treated successfully with glans resurfacing and split skin graft reconstruction. CONCLUSIONS: Our observations demonstrate that PEKMB represents a form of chronic, undiagnosed or misdiagnosed, inadequately treated or treatment refractory, unstable lichen sclerosus. The significant potential for squamous carcinogenesis (differentiated PeIN and verrucous carcinoma) can be mitigated by timely diagnosis and treatment. Glans resurfacing and split skin graft reconstruction appears to be a successful treatment modality in patients with refractory disease.

Relationship between histomorphological findings and platelet activation in psoriasis.

BACKGROUND: Elevated platelet count (PC), mean platelet volume (MPV), and Platelet Mass Index (PMI) are reported in patients with psoriasis, while platelet activation is associated with psoriasis severity. Available studies examining the relationship between platelet activation markers and psoriasis have mostly focused on psoriasis area severity index. To the best of our knowledge, there is no study examining the relationship between histopathological features of a single psoriatic plaque and platelet activation. The present study examined the relationship between histomorphological findings obtained by morphometric analysis and psoriasis patients' PC, MPV, and PMI values. MATERIALS AND METHODS: Morphometric analysis was performed on hematoxylin and eosin-stained preparations of skin biopsies to measure minimum suprapapillary epidermis thickness (SPETmin ) and maximum epidermal thickness (ETmax ), maximum suprapapillary keratosis thickness (SPKTmax ), and maximum keratosis thickness (KTmax ). The relationship between PC, MPV, PMI, and morphometric skin biopsy outcomes was evaluated. RESULTS: While an inverse correlation was found between SPETmin and PC and PMI in cases with psoriasis (p values = 0.015 and 0.005, r values = -0.238 and -0.271, respectively), no significant correlation was found between SPETmin and MPV (p value = 0.600, r value = -. 052). On the contrary, no significant correlation was found between SPKTmax, ETmax, and KTmax values and platelet parameters. CONCLUSION: We assume that an increased risk of platelet activation-related diseases is expected in psoriasis patients displaying histopathological findings of suprapapillary thinning due to increased platelet activation; therefore, it may be beneficial to monitor these patients in terms of such risks.