An Atlas of the Human Nail.

Dermatologic literature describes nail abnormalities involving nail bed as linear erythronychia or onychomatricoma. The abnormality reflects cognitive content of the nail bed. A resourceful epidermis capable of manifesting in a variety of clinical appearances depends on initiating stimulus affecting remarkably its nail bed matrix cells. These cells are stem cells (NBMSC) migrating distally to cover remarkably the underlying nail bed dermal ridges that are homologous to finger print dermal ridges. Normally, adult nail bed epidermal cells are uniform and keratinize with the stratum corneum without a granular layer.

Onychomycosis, the Active Invasion of a Normal Nail Unit by a Dermatophytic Versus the Colonization of an Existing Abnormal Nail Unit by Environmental Fungus.

Onychomycosis was described by early investigators as the presence of an abnormal nail unit and a member of the order Mycota, producing the abnormality. This interpretation has caused more than 50 years of confusion in the dermatologic literature. Unquestionably, the clinician sees more abnormal toenails than fingernails, and investigators have described a multitude of fungi as the cause of the clinically abnormal toenail. In 2010, developmental scientists proved, what we have long recognized, that there is no bilateral symmetry in living organisms and, therefore, one sole is different from the other. This causes a gait asymmetry, coupled with the pressure the closed shoe exerts on toenails while walking. This produces a series of abnormalities, which are clinically identical to what has been described for dermatophytic onychomycosis. These are fungus free and result in toenail niches. These toenail abnormalities were recently described as the asymmetric gait nail unit syndrome (AGNUS). It is possible that environmental fungi can colonize these toenail niches and, therefore, were described by investigators as a new onychomycosis entity In the normal host, onychomycosis should be only used to describe the active invasion of the nail bed (NB) corneocytes by a dermatophyte, as seen in dermatophytic onychomycosis. Dermatophytes only affect those hosts who have inherited the dermatophytosis susceptibility gene, transmitted as an autosomal dominant trait. In studies encompassing 3,000 abnormal toenails, only 27%-30% were found as dermatophyte culture positive, 25% were negative and the rest environmental fungi were recovered.

Hereditary Yellow Nail without a Syndrome.

A 40-year-old woman presented with clinical features of yellow nail syndrome (YNS). She had no past or present associated lymphatic or respiratory abnormalities. She was accompanied by her 12-year-old daughter, who also demonstrated clinical features of YNS. Similarly, the daughter had no past or present associated lymphatic or respiratory abnormalities. At the time of evaluation, a specific treatment was not initiated for mother or daughter. (SKINmed. 2019;17:73-74).

Asymmetric gait nail unit syndrome: the most common worldwide toenail abnormality and onychomycosis.

Asymmetric gait nail unit syndrome (AGNUS) is the result of asymmetric shoe pressure on the toes and foot caused by ubiquitous uneven flat feet that affect the gait. The pressure produces clinical changes in the toenails, which are identical to all clinical types of dermatophyte and opportunistic onychomycosis, yet they are dermatophytes-free. AGNUS produces additional signs that make it easy to identify. Its coexistence with fungal disease has resulted in reports describing new clinical types of onychomycosis, identifying signs of drug resistance, assessing severity index, and defining complete clinical cure when taking a systemic or topical antifungal, as well as "retronychia." These signs are typically seen in the toenails of patients with AGNUS. AGNUS has a mechanical etiology and can coexist with dermatophytosis, which is a hereditary disease. AGNUS can coexist with any other disease affecting the toenails and results in greater clinical severity than each condition individually. AGNUS is and has been the most common worldwide toenail abnormality in shoe-wearing societies.

The asymmetric gait toenail unit sign.

The aim of this investigation was to resolve a diagnostic problem and report toenail unit changes attributable to shoe friction that resemble onychomycosis, but that are fungus-negative, and identify common skeletal causes in patients with an asymmetric walking gait. X-ray and clinical feet inspections were performed to evaluate skeletal components that change normal foot biodynamics. Forty-nine patients, all dermatophyte-negative, were reviewed. All patients were those seen in our private practice who demonstrated skeletal and toenail unit abnormalities such as onycholysis, nail bed keratosis resembling distal subungual onychomycosis, nail plate surface abnormalities, distal toe skin keratosis, a diagnostic nail plate shape, as well as several skeletal abnormalities. The clinical abnormalities of the asymmetric gait syndrome include onycholysis, nail bed keratosis, nail plate surface abnormalities, and a diagnostic nail plate shape. By the patient's history, the skeletal findings that were present worsened with age and, in many patients, they were familial. Onychomycosis does not lead to an asymmetric gait nail problem, asymmetric gait toenail does not favor dermatophyte infection, and not all nail dystrophies are the result of an asymmetric walking gait.

Pimecrolimus cream 1% in the treatment of intertriginous psoriasis: a double-blind, randomized study.

BACKGROUND: Inverse psoriasis can be difficult to treat because of the high sensitivity of intertriginous areas to cutaneous side effects, such as irritation and striae. Pimecrolimus, a well-tolerated, nonatrophogenic, skin-selective inflammatory cytokine inhibitor, has been shown to be effective in the treatment of psoriasis when applied topically under occlusion. OBJECTIVE: This study evaluated the efficacy and safety of pimecrolimus cream 1% versus vehicle twice a day in the treatment of inverse psoriasis. Methods This was a double-blind, randomized, vehicle-controlled study in 57 patients with moderate to severe inverse psoriasis. Patients were evaluated using Investigator's Global Assessment of overall severity, Target Area Score, and Patient Self-Assessment. RESULTS: A significant between-group difference was observed early on, with 54% of the pimecrolimus group versus 21% of the vehicle group having an Investigator's Global Assessment score of 0 or 1 (clear or almost clear) at week 2 ( P = .0169). By week 8, 71% of the pimecrolimus group had an Investigator's Global Assessment score of 0 or 1. Change from baseline in Target Area Score was -2.4 (pimecrolimus group) compared with -0.7 (vehicle) at day 3 ( P < .0001). By week 8, 82% of patients using pimecrolimus scored their disease as well or completely controlled versus 41% of the vehicle group ( P = .0007). Adverse events were similar between groups. CONCLUSION: Pimecrolimus cream 1% is an effective treatment for inverse psoriasis with a rapid onset of action, and is safe and well-tolerated.

The successful treatment of Trichophyton rubrum nail bed (distal subungual) onychomycosis with intermittent pulse-dosed terbinafine.

BACKGROUND: The standard treatment of Trichophyton rubrum nail bed onychomycosis (or distal subungual onychomycosis [DSO]) with daily terbinafine for 12 weeks involves treating for a fixed period shorter than the time required for complete replacement of the nail bed and overlying nail plate by normal growth. The same total amount of terbinafine pulse-dosed for approximately 12 months would treat the patient until normal replacement of the mycotic nail bed has occurred. OBJECTIVES: To determine the effectiveness of intermittent administration of oral terbinafine (250 mg/d for 7 consecutive days every 2-4 months) to cure DSO and to determine the maximum effective treatment interval. DESIGN: A prospective, nonrandomized, open study of sequential groups of office patients. SETTING: A private dermatology practice. METHODS: A sequence of 4 groups of office patients with DSO (n = 10-20 each) were treated with pulse-dosed terbinafine for 7 consecutive days at intervals of 2, 3, and 4 months, respectively. In each group, treatment was continued until the distally advancing new nail bed and nail had completely removed the mycotic defect or failure of fungistasis was detected. MAIN OUTCOME MEASUREMENT: Results were determined by monthly evaluation. Cure was noted as complete replacement of the mycotic nail bed and overlying nail plate (ascertained by monthly metric measurements of the mycosis-free nail bed and overlying nail place distal to the proximal nail fold). Treatment failure was noted when the mycosis-free proximal portion of the nail bed failed to increase in correspondence with the distally directed movement of the nail bed and overlying nail. RESULTS: Thirty-nine (93%) of the 42 patients in the first 3 groups were cured (95% binomial confidence interval, 67%-100%) with no evidence of decrease in efficacy. However, the group of patients who received the 7-day pulse treatment every 4 months experienced significantly more failures (P<.01), and cures dropped to 10 of 17 cases. CONCLUSION: Terbinafine is an effective treatment for DSO when pulse-dosed for 7 days every 3 months but not every 4 months.

Clinical and mycological status of the Trichophyton mentagrophytes (interdigitale) syndrome of chronic dermatophytosis of the skin and nails.

The syndrome of tinea pedis caused by human-adapted Trichophyton mentagrophytes (interdigitale) can be recognized by two signs not characteristically seen in tinea pedis caused by T. rubrum and Epidermophyton floccosum:1 bullous > 2 mm vesicles in the thin skin of the plantar arch and along the sides of the feet and heel adjacent to the thick plantar stratum corneum,2 and white superficial onychomycosis. The relationship of the syndrome to zoophilic T. mentagrophytes remains in question.

Single-patient drug trial methodology for allergic rhinitis.

BACKGROUND: Historically, single-patient trials (SPTs) have been specifically designed for each patient, requiring significant time and effort for execution. There has been no previous attempt to standardize an SPT for routine commercial availability. OBJECTIVE: To validate the use of an SPT method to discriminate effectiveness and adverse events while comparing drugs/doses in patients with allergic rhinitis. DESIGN: Double-blind, randomized, 4 paired-period, multiple-crossover SPT. SETTING: Academic and commercial investigative sites. PATIENTS: Thirty-six patients with allergic rhinitis were evaluated for the most appropriate treatment; 6 of these participated in 2 different SPTs. INTERVENTIONS: Treatment of symptoms of allergic rhinitis by comparing either loratadine with chlorpheniramine maleate or loratadine with placebo in a series of SPTs. MEASUREMENTS: Effectiveness endpoints were selected from a modern, Food and Drug Administration (FDA)-approved new drug application. Expected adverse events were directly solicited; unsolicited events were also recorded. Total signs and symptoms cumulatively included sneezing, runny nose, itchy nose, teary eyes, and itchy eyes. Quality of life was measured by the most bothersome symptom and the patient's global evaluation. RESULTS: Of 42 initiated SPTs, 40 (95%) provided complete data and 1 (2%) provided partial data, resulting in 41 (98%) evaluable tests. Thirty-one evaluable SPTs compared loratadine 10 mg/d with chlorpheniramine maleate 12 mg twice daily, and 10 SPTs compared loratadine 10 mg/d with placebo. Four of 31 SPTs (13%) showed significant superiority for loratadine over chlorpheniramine maleate and 5 of 31 (16%) for chlorpheniramine maleate over loratadine. Twenty-two of 31 (71%) showed parity performance between loratadine and chlorpheniramine maleate. Loratadine was significantly superior to placebo in 3 of 10 trials (30%), consistent with rates found in 3 pivotal group trials used for FDA approval (24%, 17%, and 0%). Sleepiness could be discriminated for loratadine versus placebo and for chlorpheniramine maleate versus loratadine. CONCLUSIONS: The allergic rhinitis SPT proved to be acceptable to patients, feasible to administer, and reproducible. It can statistically discriminate effectiveness and adverse events, serving as a useful, prognostic tool in community practice.