Coxsackievirus A10 impairs nail regeneration and induces onychomadesis by mimicking DKK1 to attenuate Wnt signaling.

Coxsackievirus A10 (CV-A10) infection, a prominent cause of childhood hand-foot-and-mouth disease (HFMD), frequently manifests with the intriguing phenomenon of onychomadesis, characterized by nail shedding. However, the underlying mechanism is elusive. Here, we found that CV-A10 infection in mice could suppress Wnt/ß-catenin signaling by restraining LDL receptor-related protein 6 (LRP6) phosphorylation and ß-catenin accumulation and lead to onychomadesis. Mechanistically, CV-A10 mimics Dickkopf-related protein 1 (DKK1) to interact with Kringle-containing transmembrane protein 1 (KRM1), the CV-A10 cellular receptor. We further found that Wnt agonist (GSK3ß inhibitor) CHIR99021 can restore nail stem cell differentiation and protect against nail shedding. These findings provide novel insights into the pathogenesis of CV-A10 and related viruses in onychomadesis and guide prognosis assessment and clinical treatment of the disease.

Subungual Osteochondroma of the Great Toe: A Case Report.

Bony outgrowths of the distal phalanx of the great toe have been described in the literature but rarely. These subungual bony outgrowths can be caused by subungual exostosis or subungual osteochondromas. Both of these abnormalities are bony outgrowths with differences in the cartilage cap wherein the exostoses have fibrocartilage, and osteochondromas have hyaline cartilage. The subungual exostosis and osteochondroma that are protruding present symptoms of pain, redness, and deformed nail bed, whereas the nonprotruding osteochondromas have only a lump as the presenting symptom. In both conditions, excision of the lesion and curettage of the base helps prevent a recurrence. Curettage at the end of the excision of the bony outgrowth is required to avoid recurrence. After excision, the specimen should be sent for histopathologic examination to differentiate between the exostosis and osteochondromas, which are underreported in subungual locations, and to rule out malignant transformation. We present a 13-year-old girl with an isolated subungual nonprotruding exostosis of the great toe that was treated by excisional biopsy. The histopathologic examination confirmed it as osteochondroma, which is underreported.

Retronychia: the importance of proper footwear.

Retronychia is commonly underdiagnosed and exhibits classic features of proximal nail fold elevation and nail plate layering. Herein we summarize the literature and discuss cause, diagnosis, and treatment of this condition.

Outcomes of the Transungual Approach in 56 Consecutive Digital Subungual Glomus Tumours.

Background: Glomus tumour is a painful small tumour of the glomus body commonly located under the nail bed. The aim of this study is to evaluate the correlation of clinical diagnosis with MRI findings, determine the prevalence of the tumour at different subungual locations and determine the differences in outcomes (if any) between a longitudinal and a transverse nail bed incision for excision of the tumour. Methods: This retrospective study of 56 subungual glomus tumour was conducted from May 2010 to December 2021. Data with regard to gender, age at presentation, digit involved, presenting symptoms, duration of symptoms, clinical signs, need for MRI, anatomical location, surgical approach (longitudinal versus transverse), histopathology result, period of follow-up and complications were recorded. Results: All 56 (100%) patients presented with classic triad of symptoms. The average duration of symptoms was 52.9 months (range: 3-204 months). Eleven (20%) tumours were in the sterile matrix, 38 (68%) at the junction of sterile and germinal matrix and 7 (12%) in the germinal matrix. The tumours were excised through the longitudinal incision in 31 (55.3%) patients and transverse incision in 25 (44.7%). One (1.8%) tumour was intraosseous that was diagnosed intraoperatively and excised successfully. Average follow-up was 35.4 months (range: 6-120 months). There was no difference in outcomes (pain or nail deformity) between the two incisions. One patient (1.8%) has persistent pain that was due to a missed satellite lesion in the same digit. This was excised later with resolution of symptoms. There were no recurrences and all patients were cured after excision of tumour. Conclusions: Diagnosis of glomus tumour is usually clinical, and most are located at junction of sterile and germinal matrix. Tumour can be excised either by longitudinal or transverse nail bed incisions without any change of treatment outcome. Level of Evidence: Level IV (Therapeutic).

[Cutaneous adverse events to systemic anticancer therapies : Hand-foot syndrome and nail changes]. / Kutane Nebenwirkungen onkologischer Systemtherapien : Hand-Fuß-Syndrom und Nagelveränderungen.

BACKGROUND: Hand-foot syndrome (HFS) and nail changes are frequent adverse events of anticancer therapies. OBJECTIVES: To provide a review of current evidence in HFS and nail disorders associated with medical tumor treatment. MATERIALS AND METHODS: Basis is the current German S3 guideline "Supportive therapy in oncologic patients" and literature on this topic published since the guideline was finalized. RESULTS: Two variants of HFS are distinguished: a chemotherapy-associated and a kinase-inhibitor-associated variant. In the first form, painful erythema, blisters and ulceration can occur, also in other areas with a high number of sweat glands such as axillary and inguinal regions. Thus, the secretion of toxic substances through sweat glands is a proposed pathogenetic mechanism. For the second form, which results in callus-like painful thickening of the horny layer on areas of mechanic pressure, a vascular mechanism is proposed. For prophylaxis of HFS, avoidance of mechanical stress, regular cleaning of predisposed areas, and also urea- and diclofenac-containing ointments are recommended; in case of infusions (taxanes, doxorubicine), cooling of hands and feet during infusion is recommended. In case of manifest HFS, dose reduction or prolongation of intervals of the associated treatment are recommended. Nail changes often develop under therapy with chemotherapeutic agents but also under treatment with agents such as checkpoint inhibitors or under targeted therapy. Different components of the nail unit may be involved such as the nail matrix, nail bed, nail plate, hyponychium, lunula and proximal and lateral nail folds. CONCLUSION: This work gives insight into the pathophysiology of HFS and nail disorders that develop under systemic oncologic treatments and gives recommendations for prophylaxis and treatment.

Single-cell RNA sequencing unveils tumor heterogeneity and immune microenvironment between subungual and plantar melanoma.

Acral melanoma (AM) is a subtype of melanoma with high prevalence in East Asians. AM is characterized by greater aggressiveness and lower survival rates. However, there are still fewer studies on immune mechanisms of AM especially subungual melanoma (SM) versus non-subungual melanoma (NSM). In order to explore tumor heterogeneity and immune microenvironment in different subtypes of AM, we applied single-cell RNA sequencing to 24,789 single cells isolated from the SM and plantar melanoma (PM) patients. Aspects of tumor heterogeneity, melanocytes from PM and SM had significant differences in gene expression, CNV and pathways in which tumor-associated such as NF-kb and Wnt were involved. Regarding the immune microenvironment, PM contained more fibroblasts and T/NK cells. The EPHA3-EFNA1 axis was expressed only in cancer-associated fibroblast (CAF) and melanocytes of PM, and the TIGIT-NECTIN2 axis was expressed in both AM subtypes of T/NK cells and melanocytes. Altogether, our study helps to elucidate the tumor heterogeneity in AM subpopulations and provides potential therapeutic targets for clinical research.

Long-term outcomes after amputation and sentinel node biopsy for subungual melanoma: A single-institution series.

BACKGROUND: Subungual melanoma (SUM) is a rare tumor with historically poor outcomes. Thus, the benefit of proximal versus distal amputation in SUM remains unclear. METHODS: We performed a retrospective review of our prospectively-maintained institutional melanoma database, including SUM and non-subungual acral melanoma (AM) patients who underwent sentinel lymph node biopsy (SLNB) between 1999 and 2022. All SUMs had distal joint or proximal amputations. Primary endpoints were overall survival (OS) and recurrence free survival (RFS). Kaplan-Meier estimates, and Cox univariate and multivariate analyses were performed. Tests were repeated on propensity score matched (PSM) populations in a 2:1 ratio. RESULTS: 123 patients underwent resection with SLNB for SUM (n â€‹= â€‹27) and AM (n â€‹= â€‹96). Median follow-up was 9.2 years. Unadjusted median OS was 149.1 months for AM and 198.1 months for SUM. In the PSM comparison, median OS and RFS remained comparable between SUM and AM (149.5 months versus 198.1 months; p â€‹= â€‹0.612). Sentinel node positivity was associated with significantly worse overall survival outcome (Hazard Ratio 5.49; CI (1.59-18.97), p â€‹= â€‹0.007). In the PSM population, male sex was also associated with a significant hazard of death (HR 3.00, CI (1.03-8.71), p â€‹= â€‹0.043). Proximal amputations were associated with significantly worse OS (p â€‹< â€‹0.002) and RFS (p â€‹< â€‹0.01) compared to distal amputations in SUM. CONCLUSION: SUM was well-treated with distal amputations, and had better OS and RFS compared to SUM treated with proximal amputations. Sentinel lymph node status is an important prognostic factor for SUMs and AMs. SUMs can be treated similarly to AMs with comparably good long-term outcomes.

Onychocytic Matricoma: A Clinical, Dermoscopic, and Pathological Analysis of 14 Cases.

ABSTRACT: Onychocytic matricoma (OCM) is a benign neoplasm of the nail matrix. Only 18 cases of this tumor have been reported in the literature to date. We retrospectively analyzed the clinical features of 14 patients with OCM. The most common clinical feature was longitudinal xanthopachyonychia (n = 9), followed by longitudinal leukopachyonychia (=3) and longitudinal pachymelanonychia (n = 2). The most common clinical findings identified following dermoscopy and analysis at high magnification of classical photographs were free-edge thickening of the nail plate without pitting (n = 14), longitudinal ridging (n = 7), round white clods (n = 7), white dots (n = 7), and filiform hemorrhages (n = 7), followed by oval and linear white clods (n = 5), fuzzy lateral border (n = 5), and red-purple blood clods (n = 3). Nail clipping histopathology showed a thickened nail plate with multiple, small, round-to-oval spaces. The tumor expressed immunopositivity for LEF-1. Dermoscopy of the nail plate and nail clipping histology provides useful information with regards to the differential diagnosis with subungual squamous cell carcinoma and nail melanoma. Ex vivo-in vivo correlation facilitates a better dermoscopic assessment of this unique underrecognized disease. However, the differential diagnosis between OCM and onychocytic carcinoma requires biopsy of the tumor. LEF-1 as an onychogenic marker can be used to resolve the differential diagnosis between OCM and subungual longitudinal acanthoma/seborrheic keratosis.

Measuring Psoriasis Severity at Home.

Psoriasis plaque severity metrics, such as induration (thickness), erythema (redness), and desquamation (scaliness), are associated with the subsequent development of psoriatic arthritis (PsA) among cutaneous-only psoriasis patients (patients with skin or nail psoriasis but no psoriatic arthritis). These metrics can be used for PsA screening. However, a key challenge in PsA screening is to optimize accessibility and minimize costs for patients, while also reducing the burden on healthcare systems. Therefore, an ideal screening tool consists of questions that patients can answer without a physician's assistance. Although reference images can be used to help a patient self-assess erythema and desquamation severity, a patient would need a tactile induration reference card to self-assess induration severity. This protocol describes how to create an induration reference card, the Psoriasis Thickness Reference Card, as well as how to use it to assess lesion induration severity. Administration of reference images for erythema and desquamation and a Psoriasis Thickness Reference Card for induration to 27 psoriasis patients showed that patients were moderately successful at self-assessing the severity of these three metrics. These findings support the feasibility of a future PsA screening test that patients can complete without the need for physician assistance.

Visión frontal distal de la uña / Frontal Examination of the Distal Nail Unit

Los signos clínicos que acompañan a muchas alteraciones ungueales habitualmente no son patognomónicos de ninguna enfermedad concreta. Por tanto, la exploración del aparato ungueal desde diferentes ángulos de visión es fundamental para realizar un diagnóstico acertado. En el presente artículo se revisan los signos clínicos que pueden obtenerse mediante la exploración frontal del borde distal de la lámina ungueal y el hiponiquio, y se correlacionan con los signos de la exploración aérea. Dicho abordaje permite facilitar el diagnóstico clínico de la enfermedad ungueal en la práctica diaria (AU)

Clinical findings in many nail disorders are not usually pathognomonic. An accurate diagnosis therefore relies on inspection of the nail unit from different angles. We review clinical features of different nail disorders that can be observed during frontal examination of the distal edge of the nail plate and the hyponychium and correlate these with features observed when the nail is viewed from above. Frontal examination of the distal nail unit can help establish a clinical diagnosis in routine practice (AU)

[Translated article] Frontal Examination of the Distal Nail Unit / Visión frontal distal de la uña

Clinical findings in many nail disorders are not usually pathognomonic. An accurate diagnosis therefore relies on inspection of the nail unit from different angles. We review clinical features of different nail disorders that can be observed during frontal examination of the distal edge of the nail plate and the hyponychium and correlate these with features observed when the nail is viewed from above. Frontal examination of the distal nail unit can help establish a clinical diagnosis in routine practice (AU)

Los signos clínicos que acompañan a muchas alteraciones ungueales habitualmente no son patognomónicos de ninguna enfermedad concreta. Por tanto, la exploración del aparato ungueal desde diferentes ángulos de visión es fundamental para realizar un diagnóstico acertado. En el presente artículo se revisan los signos clínicos que pueden obtenerse mediante la exploración frontal del borde distal de la lámina ungueal y el hiponiquio, y se correlacionan con los signos de la exploración aérea. Dicho abordaje permite facilitar el diagnóstico clínico de la enfermedad ungueal en la práctica diaria (AU)

Outcomes Following Excision of Toe Glomus Tumors.

BACKGROUND: Glomus tumors are uncommon tumors and their occurrence in the foot is even less common. Glomus tumors of the toes are often missed, causing delays in diagnosis and treatment. We report an ambispective observational study of glomus tumors of the toes that were treated at our institution. METHODS: We reviewed the records of all the patients who underwent excision of toe glomus tumors in our department from January 2010 to September 2022. The follow-up data were collected from the outpatient records and by telephonic interview. Single Assessment Numeric Evaluation (SANE) score, Foot and Ankle Outcome Score (FAOS), and the Foot Function Index (FFI) were collected. RESULTS: Out of all the patients treated for glomus tumors, we found that 7 patients had glomus tumors of the toes. Of the 7 patients, 6 were women and 1 was a male. The mean follow-up of our patients was 66.4 months (range, 7-109 months). Of the 7 patients, 1 presented with recurrent glomus tumor 30 months following the primary operation, for which she underwent excision again, after which she was symptom free. Another patient who developed recurrent symptoms on telephonic interview refused any further treatment. Among the 6 patients who were symptom-free at follow-up (including the patient who underwent excision for the recurrent tumor), the median SANE score, and FFI were 99.5 (IQR, 96-100) and 0.5 (IQR, 0-2) respectively. The mean FAOS was 96 (SD, 3.3). CONCLUSION: Surgical excision of the subungual toe glomus tumors can be curative. Recurrence of toe glomus tumors was noted in 2 patients (29%), one of whom refused further surgery. Re-excision in the other patient resulted in complete resolution of symptoms. LEVEL OF EVIDENCE: Level III, ambispective observational study.

Successful treatment of onychomatricoma with minimally invasive surgical procedures based on its pathogenesis: A case report.

Onychomatricoma is a rare, fibroepithelial tumor of the nail. Although it is benign, unnecessary and excessive treatment, such as extensive or total removal of the nail matrix, has been reported in the past. Recently, it was speculated that onychomatricoma is derived from onychomatricodermis, the dermal stroma of the nail matrix. Excision of the stromal rather than the epithelial component of the tumor is important. However, since the boundary between the normal and diseased stroma is usually unclear, minimal excision at the base of the tumor projection should be sufficient. We report a case of onychomatricoma and suggest a method of surgical treatment that would minimize postoperative deformity of the nail plate.