Fibroepithelial polyps (FEPs), commonly known as acrochordons or skin tags, are benign cutaneous lesions typically found in intertriginous areas, such as the neck, axilla, and groin. Occurrence within the nail unit is exceptionally rare, presenting a diagnostic challenge as it mimics more common ungual tumors. We report a rare case of a 23-year-old woman who presented with a 4-year history of a painful, slow-growing lesion emerging from the proximal nail fold of the right fifth toe, causing nail plate deformity. Clinical differentials included acquired ungual fibrokeratoma and Koenen tumors. The lesion was completely excised, and the base was ablated. Histopathological examination revealed a FEP with keratosis, characterized by a loose collagenous core, distinguishing it from the dense vertical collagen typical of fibrokeratomas. Although FEPs are common skin lesions, their presentation in the nail unit is unusual. This case highlights the importance of considering FEP in the differential diagnosis of subungual and periungual tumors. Complete excision with ablation of the base was curative and prevented recurrence.

Pemphigus vegetans is a rare variant of pemphigus vulgaris characterized by vegetating plaques predominantly involving intertriginous areas. A 34-year-old woman presented with persistent painful oral lesions followed by progressive flexural, palmoplantar, and pan-ungual involvement. Examination revealed exuberant erosive vegetating plaques of the major folds, associated with oral erosions, palmoplantar pustules, and diffuse nail involvement. Histopathology showed papillomatosis, acanthosis, suprabasal cleavage, and acantholysis. Direct immunofluorescence demonstrated intercellular immunoglobulin G and complement C3 deposits, while indirect immunofluorescence detected circulating anti-intercellular substance antibodies, confirming Hallopeau-type pemphigus vegetans. Treatment with systemic corticosteroids and rituximab resulted in progressive healing of the cutaneous and mucosal lesions, with subsequent nail regrowth. This case highlights the importance of considering pemphigus vegetans in patients with vegetating lesions of the folds associated with mucosal involvement and extensive pan-ungual involvement, a rare but clinically distinctive feature of this disease.

Pentosidine, a pentose-derived, cross-link advanced glycation end-product (AGE), exhibits fluorescence properties which favor its analysis by liquid chromatography with fluorescence detection (LC-FL), and has been reported to be a biomarker for diabetes- and age-related disorders. Fingernails have recently garnered interest as a non-invasive matrix for the assessment of several diseases. Here, we developed and validated a LC-FL method to quantify ungual pentosidine as a companion to our tandem mass spectrometry (LC-MS/MS) method for the analysis of glycation biomarkers in nails. Method development and validation, including linearity, sensitivity, trueness, precision, and stability, proved the LC-FL method to be robust and sensitive, despite very low concentrations of pentosidine in nail keratin. Pentosidine was stable for 6 months in nails stored at 25 °C, and in nail hydrolysates stored at 4 °C. Ungual pentosidine was analyzed in fingernails from 171 type 1 and type 2 diabetic patients using this new LC-FL method, while two other AGEs and furosine were analyzed with our recently developed LC-MS/MS method. In this population with diabetes, pentosidine correlated moderately with the surrogate early-stage glycation biomarker furosine (Spearman rs = 0.461, [95% CI = 0.329-0.574]), and was respectively moderately and weakly correlated with the AGEs carboxymethyllysine (CML; rs = 0.538 [0.418-0.639]) and carboxyethyllysine (CEL; rs = 0.263 [0.117-0.402]), but showed no significant association with either HbA1c or skin autofluorescence. Ungual furosine may reflect glycemia over the previous 4-6 months in a way analogous to HbA1c, while ungual concentrations of the AGEs pentosidine, CML and CEL potentially reflect the glycation status of long-lived, extracellular matrices implicated in diabetic complications.

Ceratopsid dinosaurs, such as Triceratops, are well-known for the striking horns and frills that are ubiquitous among members of the clade. But their postcranium has received little attention by comparison. Many questions persist regarding surprisingly fundamental aspects of the anatomy of the distal part of the hindlimb, such as the proper configuration of the metatarsals and the number and position of the distal tarsals. Here we use a taxonomically indeterminate but nearly complete lower hindlimb of a ceratopsid from the Upper Cretaceous Dinosaur Park Formation of southern Alberta, Canada, originally collected more than a century ago but never previously described, to address some of these uncertainties. The bones were CT scanned and segmented to create digital models that were then positioned based on morphological fit and comparisons with articulated specimens to establish the most plausible arrangement of the lower hindlimb elements. Proximally, the fibula articulated with the posterior surface of the laterally directed cnemial crest of the tibia and the lateral surface of the lateral condyle. The only distal tarsals present, distal tarsals III and IV, articulated with the proximal ends of the corresponding metatarsals, and their proximal surfaces were likely convex and concave, respectively. The metatarsals were closely appressed to one another throughout their lengths. The phalanges are asymmetric in varying ways and to varying degrees. Unguals of some ceratopsids have a visible shelf between the shaft and blade on the posterior side, while others, including the specimen described here, do not. The anatomical and arthrological insights obtained in this investigation of the distal part of the ceratopsid hindlimb will inform future biomechanical studies and contribute to comparisons of crural and pedal osteology among various ceratopsid taxa.

From the Jurassic to the Cretaceous, most medium- to large-bodied non-avian theropods evolved towards predominantly head-driven predatory strategies. Megaraptorid dinosaurs represent a striking exception, retaining well-developed forelimbs and hypertrophied manual unguals hypothesized as a key adaptation within the clade. However, the macroevolutionary processes underlying the mode and tempo of megaraptorid claw evolution remain poorly understood. Here, we investigate the macroevolutionary trends of the megaraptorid manual claw by quantifying the shape and size of 22 manual phalanx I-2 (= manual ungual I) across different lineages of medium- to large-bodied non-avian theropods, using 2D geometric morphometric and phylogenetic comparative methods. Our results indicate that manual claw shape and size were evolutionarily coupled in Megaraptoridae, supporting a major reconfiguration of allometric trajectories during the evolution of the clade. This evolutionary coupling triggered directional shape modifications towards a distinct adaptive optimum associated with enlarged manual claws. This adaptation emerged following an early phase of rapid morphological divergence near the middle Early Cretaceous boundary and was subsequently maintained, likely under stabilizing selection throughout the Late Cretaceous, resulting in a canalized claw morphology. We further show that medium- to large-bodied non-avian theropods with well-developed forelimbs exhibit strong phylogenetic integration between distal and proximal forelimb elements. Despite this integration, the phalanx-I-2 and ulna-radius complex evolved at substantially higher evolutionary rates than the humerus. These results highlight Megaraptoridae as the only large-bodied carnivorous theropod lineage retaining a specialized forelimb-based predatory strategy until the end of the Cretaceous, with no evidence of overall claw shape convergence.

Systemic amyloid light-chain (AL) amyloidosis is a multisystem disorder caused by extracellular deposition of monoclonal immunoglobulin light chains. Cutaneous manifestations are diverse, but nail involvement is uncommon and may lead to diagnostic delay. We report the case of a 53-year-old man presenting with progressive dystrophy affecting all 20 nails for 18 months. Clinical examination revealed marked nail plate atrophy and onychorrhexis. Dermoscopy demonstrated nail plate atrophy, subungual hyperkeratosis, and splinter hemorrhages. A longitudinal lateral nail-bed biopsy revealed abundant amorphous eosinophilic deposits in the papillary dermis on hematoxylin and eosin staining. Congo red staining confirmed amyloid deposition. Subsequent systemic evaluation revealed markedly elevated free lambda light chains and bone marrow plasmacytosis, establishing the diagnosis of systemic AL amyloidosis associated with multiple myeloma. This case highlights that unexplained progressive pan-ungual dystrophy may represent an early manifestation of systemic amyloidosis. Early recognition and nail-unit biopsy can facilitate prompt diagnosis of this potentially fatal systemic disease.

Evaluation of nail diffusion of active pharmaceutical ingredients (API) is a challenge but a necessity during pre-clinical studies of antifungals for the treatment of onychomycosis. Nevertheless, available model are expensive or poorly accessible. Thus, a model based on a 3D printable cell and bovine hoof slices was designed. This model was assessed with two Amphotericine B (AmB) based preparations, a gel and a cream. After 7 days diffusion in the 3D printed cell, AmB was extracted from the hooves slices and quantitated by high-performance liquid chromatography (HPLC). Obtained AmB mean concentrations in hooves were 125.9 ± 7.4 µg/cm[3] for AmB gel and 95.6 ± 15.9 µg/cm[3]for AmB cream, with "cm[3]" referring to hoof thickness multiplied by diffusion surface. To complete the hoof diffusion test in the 3D printed cell, agar diffusion was also performed to access the ability of the API to diffuse through a water based matrix and to keep its antifungal properties. An ungual penetration model, using a 3D printed diffusion cell, that is simple to implement and easily accessible has been developed. Although it cannot produce results directly extendable to humans, it allows the comparison of several semi-solid formulation solutions with each other.

Onychomycoses are fungal infections of the nail unit, mainly caused by dermatophytes, and have a high prevalence worldwide. Current treatments for onychomycosis face challenges with the penetration of topically applied antifungal drugs through the nail barrier. Caryophyllene oxide is a sesquiterpenoid found in several essential oils that has antifungal properties. Clioquinol (CLI) is a broad-spectrum antifungal agent with potential for topical use. Combining a sesquiterpenoid compound with a synthetic antifungal drug offers a promising therapeutic and technological approach for treating onychomycoses, once both can be easily combined in a nanoemulsion formulation. This strategy requires the development of a quick and reliable method to evaluate their in vitro permeation and retention in the nail matrix, serving as a measure of formulation performance. In this study, using the Analytical Quality by Design (AQbD) approach, we developed and validated a rapid, sensitive bioanalytical method capable of simultaneously identifying and quantifying CLI and CAROX via high-performance liquid chromatography with a UV detector (HPLC-UV) at 215 nm, with retention times below 15 min. Additionally, an ungual permeation protocol was established, and the in vitro permeation and retention of CLI and CAROX in porcine hooves were assessed. Results showed that CLI retention within the nanoemulsion was four times higher than in solution (28.11 ± 4.85 vs 7.54 ± 3.03 μg/cm[2] after 72 h). For both CLI and CAROX, loading into nanostructured systems demonstrated a sustained release profile.

Onychocytic matricoma (OCM) is a benign tumor of the onychocyte. It clinically presents as localized longitudinal pachyonychia and melanonychia. It has many clinical and histopathological differential diagnoses. A 54-year-old male presented with a 2-year history of melanonychia on the left thumb. Local examination revealed a 2 mm skin colored papule over the proximal nail fold. The proximal nail plate showed longitudinal melanonychia with subungual hyperkeratosis. Histopathological examination of the nail bed revealed proliferation of basaloid epithelial cells. There were many organized spheres composed of prekeratogenous and keratogenous layers. No nuclear atypia was noted. The nail plate biopsy showed septate, thin-walled fungal hyphae, which were highlighted by periodic acid Schiff (PAS) stain. We report an additional case of the acanthotic subtype of onychocytic matricoma in skin of color. Additionally, this case also showed onychomycosis. We also discuss the literature review and diagnostic approach. Knowledge about this rare tumor will help to arrive at the correct diagnosis.

Terbinafine is considered the first-line treatment for dermatophyte-induced onychomycosis. This study aimed to develop a fast, selective, and sensitive UHPLC-MS/MS method for the quantification of terbinafine in porcine hooves, a cost-effective surrogate for human nails. The objectives were to (i) optimise specific chromatographic and detection settings, (ii) evaluate terbinafine extraction recovery, (iii) validate the method with regard to standardised operating procedure guidelines using terbinafine-d3 as an internal standard and (iv) investigate the method's performance through a preliminary study involving deposition of an in-house high-loading topical formulation into fractional laser-ablated porcine hooves. An extraction with MeOH:H2O (9:1) achieved ~90% recovery. Extracts were centrifuged, filtered and analysed under gradient conditions, with analyte and internal standard detected by selected reaction monitoring. The validated method demonstrated appropriate sensitivity to quantify concentration ranges between 1 and 200 ng/mL with a 7.2-min runtime and a limit of quantification of 1 ng/mL. Preliminary studies detected terbinafine from the formulation within intact and laser-ablated porcine hooves, corresponding to deposited amounts of 89.04 ± 4.02 and 217.49 ± 8.98 μg/cm2, respectively. In conclusion, the sensitivity and specificity of the method make it suitable for use in further investigations into ungual delivery enhancement strategies involving terbinafine formulations.