The development of hair follicles and nail.

The hair follicle and nail unit develop and regenerate through epithelial-mesenchymal interactions. Here, we review some of the key signals and molecular interactions that regulate mammalian hair follicle and nail formation during embryonic development and how these interactions are reutilized to promote their regeneration during adult homeostasis and in response to skin wounding. Finally, we highlight the role of some of these signals in mediating human hair follicle and nail conditions.

Modified single pedicle reverse adipofascial flap for fingertip reconstruction.

BACKGROUND: Homodigital adipofascial flap is a well-established method for treating a distal fingertip defect; nonetheless, its use has some limitations. Reconstruction of fingertip injuries, with radial or ulnar tissue loss, may lead to some difficulties in providing an adequate bone coverage. The standard bipedicled technique did not allow the flap to cover the bone exposure without excessive tension. In our series, the reverse adipofascial flap had a single pedicle. The modified technique, because of its improved degree of rotation, granted the flap to reach either radial or ulnar tissue losses. PATIENTS AND METHODS: We treated 15 fingertip amputations distal to the lunula (9 Allen's type II and 6 type III), the mean size of defects was 2.7 cm2 (range, 1.8-3.2 cm2 ), the mean age of patients was 44 years (range, 22-63 years). Quick Disabilities of the Arm, Shoulder, and Hand score and Visual Analogue Scale were evaluated along with a 2-point discrimination test; the aesthetic satisfaction of the patients was estimated subjectively using a 5-point Likert scale. RESULTS: Mean flap size was 3.6 cm2 (range, 2.5-4.2 cm2 ), primary flap survival was observed in 14 out of 15 cases, partial flap necrosis was observed in 1 case, the nail grew in all fingers in about 6 months. Mean proximal and distal interphalangeal joint motion was 89° (range, 80°-100°) and 71° (range, 65°-80°), respectively. No complications were observed at the donor site. The median static 2-point discrimination was 4.5 mm (range, 3-8 mm), the mean quick DASH score was 2.6 (range, 0-9.1). All patients returned to work within a mean of 4.4 weeks (range, 4-5 weeks). The follow-up was 12 months. CONCLUSIONS: Single pedicle reverse adipofascial flap is an effective technique. This modified procedure allows a wider degree of flap rotation; it represents the ultimate arrow in our bow to address some particular defect geometry.

Genetics of syndromic and non-syndromic hereditary nail disorders.

The nail is a unique epithelial skin appendage made up of a fully keratinized nail plate. The nail can be affected in several systemic illnesses, dermatological diseases, and inherited nail disorders. Nail dystrophies can present as isolated disorders or as a part of syndromes. Substantial progress has been achieved in the management and diagnosis of nail diseases; however, not much is known about the underlying molecular controls of nail growth. The homeostasis and development of the nail appendage depend on the intricate interactions between the epidermis and underlying mesenchyme, and comprise different signaling pathways such as the WNT signaling pathway. Digit-tip regeneration in mice and humans has been a known fact for the past six decades; however, only recently the underlying biological mechanisms by which the nail organ achieves digit regeneration have been elucidated. Moreover, significant progress has been made in identifying nail stem cells and localizing stem cell niches in the nail unit. More fascinating, however, is the role they play in orchestrating the processes that lead to the regeneration of the digit. Further elucidating the role of nail stem cells and the signaling pathways driving epithelial-mesenchymal interactions in the nail unit might contribute to the development of novel therapeutic tools for amputees.

Combination therapy for onychomycosis using a fractional 2940-nm Er:YAG laser and 5 % amorolfine lacquer.

Onychomycosis remains difficult to cure by traditional methods. The aim of this study was to evaluate the efficacy of combination therapy with a fractional erbium yttrium aluminum garnet (Er:YAG) laser and 5 % amorolfine lacquer on onychomycosis. Nine patients with bilateral nails affected by distal and lateral subungual onychomycosis were included. The bilateral nails of each patient were divided into two groups. The 20 affected nails on one side of each patient as group 1 were treated with a fractional Er:YAG laser once a week and 5 % amorolfine lacquer twice weekly, while the 20 nails on the symmetrical side of each patient as group 2 were treated with amorolfine lacquer only. The laser treatment was conducted at weeks 1, 2, 3, 4, 8, and 12 in group 1. The clinical improvement, onychomycosis severity index (OSI), maximum linear clear nail growth (MLCNG), and mycological cure rate were evaluated. At week 24, 18 of 20 (90 %) nails in group 1 had achieved obvious clinical responses. The mean OSI score showed a significant decrease (5.24) and the average MLCNG was 3.1 mm in group 1. At week 24, 15 of 20 (75 %) nails achieved a negative mycological examination in group 1, compared with four of 20 (20 %) nails in group 2. The treatments were well-tolerated by most patients. This clinical study suggests that combination therapy of a fractional 2940-nm Er:YAG laser and 5 % amorolfine lacquer is an effective, safe, and convenient treatment method for onychomycosis.

Managing Assessments and Expectations: Patient Responses Following Therapy With Efinaconazole Topical Solution, 10%.

INTRODUCTION: Successful treatment of onychomycosis is both a clinical and therapeutic challenge. Effective patient education and reassurance are critical. This post hoc analysis aims to provide some guidance to physicians based on initial disease severity and influencing factors. METHODS: A post hoc analysis of two multicenter, randomized, double-blind, vehicle-controlled studies evaluating the efficacy and safety of efinaconazole topical solution, 10% in mild to moderate onychomycosis. Outcomes were assessed based on baseline severity (20%-29%, 30%-39%, 40%-49%, and ≥50% affected target toenail). RESULTS: Overall, the mean percent affected toenail following efinaconazole treatment decreased from 36.4% to 20.6% (a 43% reduction). The percent reduction in mean percent affected toenail (range, 43.6% to 59.8%) with efinaconazole was similar irrespective of baseline severity. Improvement was only seen in the very mildest patients with vehicle and not before week 36. Improvement was influenced by gender (females did better) and disease duration (long standing disease responding less well). CONCLUSIONS: Our onychomycosis patients treated with efinaconazole might expect a 50% improvement in their disease within a year, and this will be seen as significant by many, especially those who have suffered for many years. Many will do better, but they will need to be reminded of the slow growth of the toenail.

Physics of nail conditions: why do ingrown nails always happen in the big toes?

Although surgical treatment of nail conditions can be traced back centuries to the writings of Paul Aegineta (625-690 AC), little is known about the physical laws governing nail growth. Such a poor understanding together with the increasing number of nail salons in the high street should raise legitimate concerns regarding the different procedures applied to nails. An understanding of the physics of nail growth is therefore essential to engage with human medicine and to understand the aetiology of nail conditions. In this context, a theory of nail plate adhesion, including a physical description of nail growth can be used to determine the transverse and longitudinal curvatures of the nail plate that are so important in the physical diagnosis of some nail conditions. As a result physics sheds light on: (a) why/how nails/hooves adhere strongly, yet grow smoothly; (b) why hoof/claw/nail growth rates are similar across species; (c) potential nail damage incurred by poor trimming; (d) the connection between three previously unrelated nail conditions, i.e. spoon-shaped, pincer and ingrown nails and; last but not least, (e) why ingrown nails occur preferentially in the big toes.

Nail disorders in infants and children.

PURPOSE OF REVIEW: Nail diseases in infants and children are an uncommon cause of consultation and are often difficult to diagnose and to manage. This review will cover nail diseases that are most commonly seen in clinical practice, including congenital and hereditary disorders and inflammatory, infective, and neoplastic nail diseases. The purpose of the review is to help the reader to recognize nail disorders at an early age and to manage them appropriately. RECENT FINDINGS: Two recent large studies have reported the clinical findings of genetic disorders involving the nails, that is, pachyonychia congenita and epidermolysis bullosa. Only a few articles gave a comprehensive review of a disease, as occurred for onychomycosis, while the majority of the reports published in the recent literature involve single cases. SUMMARY: Nail diseases in children and neonates are not easy to diagnose by nonexperts. Basic knowledge of the anatomy and biology of the nail facilitates their diagnosis as the understanding of their pathophysiology. This review gives hints at the most common nail diseases that affect infants and children.

Chevron nails: a normal variant in the pediatric population.

A 7-month-old girl was evaluated for V-shaped ridging of the fingernails consistent with chevron nails. Chevron nails are a normal variant in the pediatric population that is frequently outgrown. This case nicely demonstrates this normal finding that has so rarely been reported in the literature.

Efinaconazole solution in the treatment of toenail onychomycosis: a phase 2, multicenter, randomized, double-blind study.

BACKGROUND: Onychomycosis is a common nail infection that is difficult to treat successfully. The prevalence increases with age and is associated with diabetes. Oral treatments are limited by drug interactions and potential hepatotoxicity; topical treatments, by modest efficacy. OBJECTIVE: We investigated the efficacy and safety of a solution using a novel topical triazole antifungal, efinaconazole, in distal lateral subungual onychomycosis (DLSO). METHODS: Multicenter, randomized, double-blind, vehicle-controlled phase 2 study in mild to moderate toenail DLSO (n=135). Subjects randomized (2:2:2:1 ratio) to receive efinaconazole 10% solution (with or without semiocclusion), efinaconazole 5% solution, or vehicle, once daily for 36 weeks, with one 4-week posttreatment follow-up (week 40). Efficacy assessments included complete cure, mycologic cure, clinical efficacy, and other assessments of overall treatment effectiveness. No efficacy variables were designated as primary. RESULTS: At follow-up, complete cure was numerically higher in all active groups (16%-26%) compared with vehicle (9%). Mycologic cure rates with efinaconazole 10% semiocclusion, efinaconazole 10%, and efinaconazole 5% were 83%, 87%, and 87%, respectively. Efinaconazole 10% (with or without semiocclusion) demonstrated significantly greater clinical efficacy and treatment effectiveness when compared with vehicle (P=.0088 and .0064; .0056 and .0085, respectively, for both efinaconazole 10% groups). Adverse events were generally similar and mild. Local-site reactions were restricted to few subjects and did not differ meaningfully from those produced by vehicle. CONCLUSIONS: This study provided evidence that once-daily efinaconazole 10% solution (with or without semiocclusion) applied topically for 36 weeks was more effective than vehicle in treating DLSO and was well tolerated. Based on these results, efinaconazole 10% solution was chosen for the phase 3 development program.

Update: nail unit dermatopathology.

Nail unit dermatopathology is a growing field filled with many challenges. Many advances in this field have been made in the last 5 years. This review article provides an update on new information and studies published in that period of time. We divided these works into different sections, including clinical and pathologic challenges in diagnosis and treatment of nail disorders, nail unit biopsy and processing techniques, normal nail unit histology, nail plate structural and growth pathology, metabolic disease, inflammatory conditions, onychomycosis, benign growths, malignant growths, and dyschromias. Specific highlights include advances in the marking and orientation of nail unit biopsies for improved histologic interpretation, improved nail plate softening techniques, new methods for histologic evaluation of onychomycosis, descriptions of newly described benign growths unique to the nail unit, and the morphologic and immunohistochemical distinction between benign and malignant pigmented lesions of the nail unit.

Influence of mechanical forces as a part of nail configuration.

BACKGROUND: Clinicians encounter pincer nails at a high incidence among bedridden cases who are free from weight bearing. The mechanical force transmitted by walking and loading may affect the nail configuration. This study was aimed at evaluating the influence of mechanical forces on the nail configuration. METHODS: Study 1 was conducted on a sample size of 318 great toenails, with the subjects classified into the following 3 groups: healthy volunteers, participants who were bedridden for less than 3 months, and participants who were bedridden for more than 3 months. Study 2 was conducted in 12 subjects with unilateral loading. ASSESSMENTS: The configuration of the great toenails, in terms of the curve index (defined as the nail height/nail width), was compared. RESULTS: In study 1, the curve index increased significantly as the duration of the bedridden state became longer (17.5 ± 4.75, 28.9 ± 11.0, 36.4 ± 9.58, respectively). In study 2, the curve index on the nonloaded side was significantly higher than that on the loaded side (40.0 ± 8.63 vs. 27.0 ± 8.39). CONCLUSION: Our results suggest that mechanical forces may affect the nail configuration and be involved in the pathophysiology of nail deformities.

The nail plate biopsy may pick up gout crystals and other crystals.

The rewarding use of nail clippings processed histologically for the diagnosis of some nail diseases is well established. A new application of the nail plate biopsies (NPBs) is the detection of crystals in the subungual horn. Besides other subungual crystals, urate crystals are heretofore undescribed. This presentation adds to the advantages of an NPB: the detection of some cases of gout on which urate crystals are extruded subclinically. While searching for fungi, 2 cases of gout were diagnosed histologically, aided by unstained thick sections. A history of gout was then confirmed. No tophi were noted in or near the nail field. Chasing for crystals opens the study of fluids that may exude or transude into nail structures, a kind of "nail window" into hematic or metabolic abnormalities. In sum, the abundance of cytologic and histologic findings in an NPB can expand the armamentarium of physicians to evaluate nail diseases and even systemic diseases in a noninvasive manner.

Iontophoretic delivery of terbinafine in onychomycosis: a preliminary study.

Background Onychomycosis is a common disease; topical treatment is usually poorly effective, while systemic treatment is more effective but may be associated with side-effects. Iontophoretic drug delivery may improve drug penetration through the nail and lead to better therapeutic results. Objectives To evaluate the efficacy, safety and tolerability of topical treatments with terbinafine HCl delivered with or without an iontophoretic patch in patients with onychomycosis of the toenails. Methods Patients enrolled into the study were divided randomly into two groups. Group A was treated with terbinafine and an iontophoretic patch (at a constant current density of 100 microA cm(-2)). Group B was treated with terbinafine without iontophoresis. Treatment was overnight wear, every day, 5 days per week, for 4 weeks. Follow-up period was 8 weeks from the end of treatment. Results A significant clinical response was recorded in patients of group A (active group). The percentage of patients having healthy toenail growth of more than 1.5 mm at the end of treatment was 40% compared with 11% in patients treated with terbinafine without current (passive group). The percentage of patients having fungal elements (KOH) in nail specimens decreased significantly at 8 weeks following the completion of treatment: 16% in the active group vs. 53% in the passive group. Patients in the active group reported a tingling sensation that is expected when using an iontophoretic drug delivery treatment. Conclusions The delivery of terbinafine under an electrical current of 100 microA cm(-2) appears to be efficacious and safe and is well tolerated for the treatment of nail onychomycosis.

Growth rate of human fingernails and toenails in healthy American young adults.

BACKGROUND: Human nail clippings are increasingly used in epidemiological studies as biomarkers for assessing diet and environmental exposure to trace elements or other chemical compounds. However, little is known about the growth rate of human nails. OBJECTIVE: To estimate the average growth rate of fingernails and toenails and examine factors that may influence nail growth rate. METHODS: Twenty-two healthy American young adults marked their nails close to the proximal nail fold with a provided nail file following a standardized protocol, and recorded the date and the distance from the proximal nail fold to the mark. One to three months later, participants recorded the date and distance from the proximal nail fold to the mark again. Nail growth rate was calculated based on recorded distance and time between the two measurements. RESULTS: Average fingernail growth rate was faster than that of toenails (3.47 vs. 1.62 mm/month, P < 0.01). There was no significant difference between right and left fingernail/toenail growth rates. The little fingernail grew slower than other fingernails (P < 0.01); the great toenail grew faster than other toenails (P < 0.01). Younger age, male gender, and onychophagia were associated with faster nail growth rate; however, the differences were not statistically significant. CONCLUSION: Nail growth rates have increased compared with previous estimates conducted decades ago. Toenail clippings may reflect a long exposure time frame given the relatively slow growth rate.

Do we need to repair the nerves when replanting distal finger amputations?

Distal replantation is an excellent model to study the results of nerve repair. We aim to demonstrate differences in aesthetic, sensory, and functional outcomes in fingertip replantation, with and without nerve repair. We recruited 28 fingers in 28 patients, who had successful distal replantation in 5 years. Half of the fingers had nerves repaired. Mean follow-up was 39 months. Symptoms of pain, numbness, cold intolerance, scar hypersensitivity, pulp atrophy, and weakness were reported. Nail width, pulp length, 2-point discrimination, Semmes-Weinstein test, and power were evaluated. We used chi-square tests of independence to examine association between nerve repair and symptoms, and independent T tests and Mann-Whitney U tests to analyze difference between replantation with and without nerve repair according to objective results. Chi-square tests reviewed no significant association between nerve repair and symptoms. Mann-Whitney U tests showed no significant difference between the groups, with and without nerve repair. All fingers showed mean 2-point discrimination of 5.6 mm, and Semmes-Weinstein test results of green in 3 fingers and blue in 17. There was no significant difference in overall outcomes in repairing nerve or not in distal finger replantation. Both groups had satisfactory outcomes. Possibly, spontaneous neurotization is present, and nerve repair is not necessary, which may help to shorten the operation time and decrease extensiveness of surgeries.

Lower extremity changes experienced during pregnancy.

The anatomic and physiologic changes occurring with pregnancy result in a variety of symptoms affecting the lower extremity. The purpose of this investigation is to provide a comprehensive look at the lower extremity changes experienced during pregnancy and correlate symptoms with underlying etiology in a literature review. In this retrospective study, 100 postpartum women were interviewed regarding the lower extremity changes experienced in pregnancy. The interview included dermatologic, vascular, neurologic, and musculoskeletal portions. Results demonstrate more than 50% of women reported faster toenail growth, roughened toenail texture, increased dryness of the skin, swelling of the foot, ankle, and leg, unsteady gait, increased foot width, and hip pain. Though a majority of patients did not experience the remaining symptoms represented in the interview, all results are pertinent and deserve understanding to provide better insight and care for the pregnant woman. Therefore, a thorough literature review is presented to correlate the outcomes of the present study with previously published research.

Risk factors for infection following ingrowing toenail surgery: a retrospective cohort study.

BACKGROUND: Ingrowing toenails are a common and painful condition often requiring surgical management. Practitioners who perform surgery on ingrowing toenails include orthopaedic surgeons, general practitioners, podiatrists and podiatric surgeons. There has been limited investigation into the specific surgical approaches used by Australian podiatric surgeons for ingrowing toenails, or the associated infection rates for these procedures. The aim of this study was to assess the frequency and type of ingrowing toenail surgery performed by podiatric surgeons, and identify risk factors for post-operative infection. METHODS: Data was entered into the Australian College Podiatric Surgeons (ACPS) National Audit Tool for all patients who underwent foot and ankle surgery performed by podiatric surgeons in Australia between January 2014 and December 2017. Infection within the first 30 days following surgery was recorded according to the ACPS national audit descriptors. Infection rates, risk ratios (RR) and 95% Confidence Intervals (CI) were calculated to determine postoperative infection risk. RESULTS: Of 7682 records, 1831 reported 2712 diagnoses of ingrowing nails. Patients with a diagnosis of ingrowing toenails were younger, less likely to have systemic disease, and a lower proportion were female compared to those without ingrowing toenails. Furthermore, they were more likely to be diagnosed with a post-operative infection than those without ingrowing toenails (RR = 2.72; CI = 2.00-3.69; P < 0.01). Univariate risk factors for post-operative infection following ingrowing toenail surgery include age greater than 60 years (RR = 3.16; CI = 1.53-6.51; P < 0.01), surgery performed in an office setting (RR = 1.77; CI = 1.05-2.98; P = 0.04), and radical excision of toenail bed procedure (RR = 2.35; CI = 1.08-5.01; P = 0.04). Patients that underwent radical excision or office based procedures were on average older, and more likely to have systemic disease. Further, radical excision procedures were more likely to be performed in office base settings. CONCLUSIONS: Ingrowing toenail surgery carries a greater risk of postoperative infection than other procedures performed by podiatric surgeons. Radical excision of toenail bed was associated with higher postoperative infection rates compared to other ingrowing toenail procedures. Procedures performed in an office setting carry a higher risk of infection. Further research into these associations is recommended.

The effect of oral hydrolyzed eggshell membrane on the appearance of hair, skin, and nails in healthy middle-aged adults: A randomized double-blind placebo-controlled clinical trial.

BACKGROUND: Many over the counter and consumer packaged goods are promoted to enhance the appearance of hair, skin, and nails for the consumer. Nutrition is a major factor in affecting the health and appearance of hair, skin, and nails. In addition to how one eats, dietary supplementation may play a role in overall health and in the physical appearance. AIMS: It was the aim of this study to objectively and subjectively evaluate the impacts of a nutritional intervention as compared to placebo on the appearances of hair, skin, and nails in healthy middle-aged adults. METHODS: Randomized, double-blind placebo-controlled study with 88 subjects randomized evenly to Study Product (BiovaBio™ 450 mg/d, n = 44) or Placebo (n = 44) for 12-weeks. Outcome tests included TrichoScan HD (hair), Canfield Visia® -CR (skin), modified FACE-Q (skin), and anchored Likert Scales (nails). RESULTS: Oral hydrolyzed eggshell membrane ingestion was associated with a significant improvement in facial skin appearance in crow's feet in 4 weeks and skin tone in 8 weeks, with significant impact on hair thickness, reduction in hair breakage and improvement in hair growth at 4, 8, and 12 weeks. There were no observed subjective improvements for nails (appearance, strength or growth). CONCLUSIONS: Oral supplementation of 450 mg/d hydrolyzed eggshell membrane for 12 weeks is associated with improvement in the appearance of facial skin and hair.