Nail psoriasis and nail lichen planus: Updates on diagnosis and management.

BACKGROUND: Inflammatory diseases of the nail, including nail psoriasis and nail lichen planus, are associated with significant disease burden and have a negative impact on quality of life. Diagnosis is often delayed, especially when patients present without cutaneous findings. Therefore, recognizing clinical signs and symptoms of inflammatory nail diseases, and initiating timely and appropriate treatment, is of utmost importance. OBJECTIVE: We review recent studies on diagnostic techniques, discuss severity grading and scoring systems, and describe consensus treatment recommendations for nail psoriasis and nail lichen planus. METHODS: An updated literature review was performed using the PubMed database on studies assessing diagnostic techniques or treatment modalities for nail psoriasis and nail lichen planus. RESULTS: Recent studies on diagnostic techniques for inflammatory nail disease have focused on use of dermoscopy, capillaroscopy, and ultrasound modalities. Treatment of these conditions is dichotomized into involvement of few (≤3) or many (>3) nails. Recent psoriatic therapeutics studied for nail outcomes include brodalumab, tildrakizumab, risankizumab, deucravacitinib, and bimekizumab, while emerging treatments for nail lichen planus include JAK inhibitors and intralesional platelet rich plasma injections. CONCLUSIONS: We emphasize the need for increased awareness and expanded management strategies for inflammatory nail diseases to improve patient outcomes.

Prevalence of subungual melanoma in patients with cutaneous malignant melanoma: A systematic review and meta-analysis.

BACKGROUND: Subungual melanoma (SUM) is a rare type of cutaneous malignant melanoma (CMM) associated with poor prognosis, while data regarding its prevalence are scarce. OBJECTIVES: We sought to provide a comprehensive systematic review and meta-analysis of the prevalence rates of SUM among all types of CMM, considering certain demographic and clinical characteristics. METHODS: The MEDLINE electronic database was searched systematically to identify eligible studies providing prevalence rate estimates of SUM in patients with CMM. Included studies were further analysed to estimate the relative prevalences of SUM according to study design, study years, geographical region and sex distribution. RESULTS: Twenty-eight studies met the inclusion criteria. The overall SUM prevalence was 1.9% (95% CI [1.5%-2.3%]). The prevalence of SUM did not differ significantly between population- and hospital-based studies and remained stable over time. However, it was found to be significantly higher in Asians compared to patients of other geographical regions as well as in studies with more men than women compared to those with female preponderance (p < 0.001). CONCLUSIONS: In all, the overall SUM prevalence among all subtypes of CMM was estimated at 1.9%, without significant changes over time, and was found to exhibit significant variability between subgroups of different geographical regions.

Real-world treatment patterns, patient-reported outcomes, and effectiveness of flexibledosing etanercept in patients with plaque psoriasis in Greece.

Etanercept is approved for continuous or intermittent use and flexible dosing in plaque psoriasis (PsO). The objectives of this study were to investigate real-world treatment patterns with etanercept in Greek adults with moderate-to-severe PsO. This non-interventional multicenter study included a retrospective-to-prospective (RP) cohort, previously treated with etanercept for ≥24 months and followed for an additional 6 months, and a biologic-naïve, prospective-only (PO) cohort, followed for 6 months after treatment initiation. Parameters assessed included Psoriasis Area and Severity Index (PASI), percentage of body surface area (BSA) affected, Dermatology Life Quality Index (DLQI), and adverse events (AEs). This study enrolled 123 patients (RP, n = 56; PO, n = 67), who mostly adhered to continuous treatment (RP, 68%; PO, 95%). The two cohorts had similar mean baseline-to-endpoint decreases in PASI (-9.5 vs -10.1) and BSA (-11.9 vs -12.3). The PO-CTP population had a mean DLQI baseline-to-endpoint score decrease of -5.8, which was statistically significant and clinically meaningful. Treatment-emergent AE rates were 58.9% (RP) versus 26.9% (PO). These real-world data suggest a similar effectiveness of continuous and intermittent etanercept treatment in Greek patients with PsO.

The JAK/STAT Pathway and Its Selective Inhibition in the Treatment of Atopic Dermatitis: A Systematic Review.

In recent years, the broadening understanding of the pathogenesis of atopic dermatitis (AD) has led to the development of novel therapeutic molecules, that target core inflammatory components of the disease. The Janus kinase (JAK)/signal transducer and activation of transcription (STAT) pathway constitutes the principal signaling cascade for a large number of cytokines and growth factors and is involved in intracellular signal transduction and subsequent regulation of gene transcription. Current knowledge suggests that the robust activation of the T-helper (Th)-2 [interleukin (IL)-4, IL-5, IL-13, IL-31] and Th22 (IL-22) immune responses in both skin and serum plays a pivotal role in the immunopathogenesis of AD especially at the acute stage, followed by a variable degree of Th1 (interferon-γ, tumor necrosis factor alpha) and Th17 (IL-17) activation in chronic disease. Of note, most of the aforementioned inflammatory cytokines utilize the JAK/STAT pathway for downstream signal transduction, explaining the emerging role of JAK inhibitors in the therapeutic armamentarium of AD. The present systematic review aims to discuss the involvement of JAK/STAT pathway in the pathogenesis of AD and summarize the clinical data available on the efficacy and safety of JAK inhibitors which have been used in the treatment of AD thus far.

Bibliometric Trends in Nail Psoriasis Research Publications.

Introduction: Bibliometric analysis provides an objective assessment of current research patterns and highlights the impact of selected publications in any given scientific discipline. Methods: We sought to provide information about dynamic research trends in nail psoriasis by analyzing the 50 most cited articles on this topic, which were identified utilizing the Scopus citation database. Results: The median number of citations was 79 (range, 60-337) per article. Publication dates ranged from 1969 to 2020, while the majority of articles (46%) were published between 2000 and 2009. The top 50 highly cited articles were published in 19 different journals, with a median impact factor of 5.248 (range, 1.022-16.102). The British Journal of Dermatology published the greatest number of highly cited articles (n = 9). Most publications were original articles, and most cited research topics included medical treatment and correlation of nail psoriasis with psoriatic arthritis. Most publications originated from the USA and UK, while Phoebe Rich and Dennis McGonagle were the two most contributing authors. Conclusion: This analysis provides information about emerging bibliometric trends and may guide future research in the field of nail psoriasis.

Onychomycosis: Recommendations for Diagnosis, Assessment of Treatment Efficacy, and Specialist Referral. The CONSONANCE Consensus Project.

INTRODUCTION: Onychomycosis is the most common nail disorder in adults, with high recurrence and relapse rates. Its diagnosis may be difficult by non-experts because the clinical signs may overlap with other dermatoses. The treatment may be challenging, as it should be patient-tailored. METHODS: An online survey was conducted among European Nail Society (ENS) members to provide recommendations on the diagnosis and assessment of distal lateral subungual onychomycosis (DLSO) in non-specialized clinical environments, as well as recommendations for patient referral. RESULTS: DLSO diagnosis is predominantly based on clinical aspects, and microscopy and fungal culture are commonly employed to establish the diagnosis. Assessment of clinical features is the main method for DLSO follow-up, and the main criterion to define cure is a combination of mycologic cure and clinical cure. The most commonly selected treatments for onychomycosis include oral antifungals, topical antifungals, and nail debridement. According to the nail experts, predisposing factors of DLSO to be evaluated include concurrent tinea pedis diagnosis, immunocompromised status, and diabetes. The minimum clinical aspects to be evaluated for DLSO diagnosis should include subungual hyperkeratosis, white-yellow-orange subungual scales, and absence of salmon-pink coloration. Recommendations for clinical signs that should be evaluated to confirm treatment effectiveness include normal appearance and color of the nail, reduction or absence of scales under the nail, and absence of onycholysis. Recommendations for specialist referral include lack of treatment effectiveness, need of additional therapies, concurrent presence of other diseases or comorbidities, severe DLSO, and presence of a dermatophytoma or involvement of the nail matrix. CONCLUSIONS: According to the surveyed nail experts, after evaluating clinical signs and predisposing factors for DLSO, the diagnosis should include subungual hyperkeratosis, nail color (yellow-orange), and onycholysis and thickening. In cases of severe DLSO, when there is treatment failure, concomitant diseases/comorbidities, presence of a dermatophytoma or involvement of the nail matrix, or involvement of several/all nails, referral should be considered.

Perception and Knowledge of Hidradenitis Suppurativa in Greece: A Cross-Sectional Study of 1301 Individuals.

Background: Hidradenitis suppurutiva (HS) is a chronic auto-inflammatory disease with recurrent painful deep-seated nodules. Aims: The aim of this study was to qualitatively assess patients' perception for HS. Methods: A descriptive two-step questionnaire survey was conducted from January 2017 to December 2018. The survey was performed through self-assessed, online, standardized questionnaires. Clinico-epidemiological characteristics, medical history, comorbidities, personal perceptions and the impact of the disease on participants' professional and everyday life were recorded. Results: A total number of 1301 Greek people completed the questionnaire. Of them, 676 (52%) reported symptoms resembling HS, whereas 206 (16%) reported that have been officially diagnosed with HS. The mean age of the study group was 39.2 ± 11.3 years. More than half of the diagnosed patients (n = 110, 53.3%) reported that they developed their first symptoms between 12 and 25 years of age. Of the diagnosed patients (n = 206), the majority (n = 140, 68.0%) were females and active smokers (n = 124, 60.1%). Seventy-nine (n = 79, 38.3%) patients reported a positive family history for HS. Ninety-nine (n = 99, 48.1%) patients reported that HS has a negative effect on their social life, 95 (46.1%) on personal life, 115 (55.8%) on sexual life, 163 (79.1%) on their mental health and 128 (62.1%) on their overall quality of life. Conclusion: Our study showed that HS seems to be an underteated, time-consuming and cost-intensive disease.

Colchicine Improves Clinical Outcomes and Quality of Life in Hidradenitis Suppurativa Patients: A Retrospective Study.

Introduction: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder of the follicular epithelium. The aim of the study was to investigate the effectiveness of colchicine on the clinical outcomes of HS patients, and to evaluate wither colchicine as monotherapy or in combination with doxycycline would provide better outcomes. Methods: A retrospective study was conducted including 44 patients with established HS, divided into three groups. The first group (n = 15 patients) received colchicine as monotherapy, the second group (n = 14 patients) received colchicine and doxycycline 100 mg/d, while the third group (n = 15 patients) received colchicine and doxycycline 40 mg/d. Disease severity during treatment was assessed at baseline and follow-up, using the Hurley Scoring System and the International Hidradenitis Suppurativa Severity Score System (IHS4). All patients were also asked to complete a Dermatology Life Quality Index (DLQI) questionnaire. These scores were compared among the study groups. Results: The DLQI and IHS4 scores significantly improved after treatment with colchicine (p < 0.001) in all groups. All colchicine regimes, including the single colchicine regime, colchicine plus doxycycline 100 mg regime, and colchicine plus doxycycline 40 mg regime, resulted in significant improvements in the DLQI and IHS4 scores (p < 0.001). Clinical improvement based on DLQI and IHS4 scores was similar in all groups. None of the patients had to discontinue the treatment due to adverse events. Discussion: In conclusion, our findings suggest that colchicine may improve clinical severity and quality of life in HS patients, either as monotherapy or in combination with doxycycline, both at antimicrobial (100 mg) and sub-antimicrobial (40 mg) doses.

Saliva Proteomics as Fluid Signature of Inflammatory and Immune-Mediated Skin Diseases.

Saliva is easy to access, non-invasive and a useful source of information useful for the diagnosis of serval inflammatory and immune-mediated diseases. Following the advent of genomic technologies and -omic research, studies based on saliva testing have rapidly increased and human salivary proteome has been partially characterized. As a proteomic protocol to analyze the whole saliva proteome is not currently available, the most common aim of the proteomic analysis is to discriminate between physiological and pathological conditions. The salivary proteome has been initially investigated in several diseases: oral squamous cell carcinoma and oral leukoplakia, chronic graft-versus-host disease, and Sjögren's syndrome. Otherwise, salivary proteomics studies in the dermatological field are still in the initial phase, thus the aim of this review is to collect the best research evidence on the role of saliva proteomics analysis in immune-mediated skin diseases to understand the direction of research in this field. The results of PRISMA analysis reported herein suggest that human saliva analysis could provide significant data for the diagnosis and prognosis of several immune-mediated and inflammatory skin diseases in the next future.

Duration of anti-treponemal immunoglobulin M seroreversion after successful syphilis treatment in HIV-positive and -negative patients.

Treponemal immunoglobulin M (IgM) antibody detection is currently among serologic tests used for syphilis diagnosis. However, the exact role of these antibodies is unclear. In this retrospective study of 326 (198 HIV positive and 128 negative) patients with early syphilis and positive IgM serology, data were analysed to investigate the time of IgM seroreversion after treatment and correlation with covariate factors. Median time of IgM seroreversion in the study population was 9 months (range 3-84, interquartile range 5-12). No statistically significant difference was observed between HIV-positive and -negative patients. At 12 months, 80.1% of the patients had a negative IgM test. At 6 months, 100% of HIV-positive patients had a fourfold decrease or greater in Venereal Disease Research Laboratory titres, but only 35.4% had a negative treponemal IgM. Secondary and early latent stage patients had a slower seroreversion of IgM (Hazard Ratio (HR) = 0.73, p = 0.064 and HR = 0.60, p = 0.023, respectively) than those with primary syphilis. A very strong association was observed of time to seroreversion of treponemal IgM with baseline VDRL titre (p < 0.001). Treponemal IgM antibody detection often cannot distinguish between active and successfully treated syphilis. Treponemal IgM may only be useful in the cases recommended in the guidelines, and in cases of untreated syphilis, it could support but not confirm the diagnosis.

Urticaria from the Neurodermatological Perspective: A Temporal Analysis of Urticaria and Cognition.

Chronic spontaneous urticaria (CSU, or CU) is a disease that significantly affects the quality of life of patients. The connection between the cognitive state of an individual and dermatological diseases has been previously reported, and it is known, although not thoroughly investigated, that there is a cognitive and quality of life relation to dermal pathologies. Urticaria is a chronic disease that requires a specialized approach to diagnosis and treatment but also a holistic approach with respect to the consideration of both the pathophysiology of the disease and the cognition status of the patient. The present study aims at analyzing CU score and cognitive indexes with respect to time, as a time series and their subsequent interactions. We have attempted to model the investigated time series in order to unravel possible causative relationships between cognitive/quality of life factors and urticaria. One hundred and eleven patients (29 males/82 females) admitted to our department were diagnosed with CU. CU was estimated on UAS7 score basis, which was used in order to define disease severity. Indexes used for assessing the cognitive and quality of life of patients' status included the Urticaria Control Test (UCT) and Dermatology Life Quality Index (DLQI). Significant correlations were found between UAS7 score and the UCT and DLQI scores, respectively. Interestingly, each score time series was modelled by different sets of equations, indicating the unique effect each one has on the disease, as well as that each score probably is manifested by a different pathophysiological mechanism.

Thyroid Disease and Active Smoking May Be Associated with More Severe Hidradenitis Suppurativa: Data from a Prospective Cross Sectional Single-Center Study.

INTRODUCTION: Hidradenitis suppurativa (HS) is an obscure disease presenting with painful, deep-seated nodules and abscess formation in body areas rich in apocrine glands. Several factors, including thyroid disease and active smoking, have been reported to be associated with HS, but it remains unclear if such associations are related to clinical HS severity. The aim of this prospective cross-sectional study is to investigate the association between active smoking and thyroid disease and HS, as well as to determine if these associations are related to HS severity. METHODS: Eligible were all patients seen in our HS outpatient clinic between September 2018 and February 2020. Data regarding demographic characteristics, clinical disease severity, comorbidities, and treatment modalities were registered. Descriptive statistics of demographic and disease characteristics was conducted. In order to evaluate the association between the disease stage and certain variables of interest, ordered logistic regression was performed. RESULTS: A total of 290 patients were included in the study. Of these, 48.9% were males, and 51.1% females. The patients had a mean age of 37.3 years. A total of 42.4% of the patients were at Hurley stage I, 43.1% at stage II, and 14.5% at stage III. According to the IHS4 score system, 30.7% of the patients had mild, 50.3% moderate, and 19.0% severe disease. The median duration of disease was 10 years. Among the patients, 56.5% were active smokers, and 55.5% patients reported that stress triggers the disease's flares. Univariable analyses demonstrated that among the various covariates, active smoking and thyroid disease were associated with a higher stage of disease. CONCLUSION: We conclude that thyroid disease and active smoking may be associated with more severe HS.

Impact of vitamin D receptor gene polymorphisms on vitiligo susceptibility and clinical features in a Southeastern European Caucasian population.

An association of vitamin D receptor (VDR) polymorphisms and vitiligo has been suggested. However, previous studies have reported contradictory results while including limited data among Caucasians. The aim of this single­center study was to evaluate the effect of three common VDR gene polymorphisms (FokI, TaqI and BsmI) on susceptibility and clinical aspects of vitiligo in a Southeastern European Caucasian population. A total of 110 unrelated vitiligo cases and 509 general population controls were enrolled from October 2018 to November 2019. Genomic DNA was extracted from whole blood after de­identification and anonymization of the samples and genotyped for the selected VDR polymorphisms by the qPCR (melting curve analysis). Subgroup analysis by clinical features among subsets of patients indicated that, compared to subjects with the FokI TT genotype or T allele, carriers of the FokI CC genotype or C allele exhibited significantly decreased risk of developing vitiligo before the age of 30 [TT vs. CC: odds ratio (OR)=0.286, 95% confidence interval (CI): 0.083­0.984, P=0.041; T vs. C: OR=0.545, 95% CI: 0.313­0.948, P=0.031]. Intra­patient analysis also revealed that, compared to T allele, the presence of TaqI C allele was adversely associated with the incidence of concurrent leukotrichia (T vs. C: OR=1.874, 95% CI: 1.018­3.451, P=0.042). Comparisons between the case and control groups showed no evidence to support an association between susceptibility to vitiligo and the VDR BsmI, TaqI, and FokI polymorphisms in this cohort. Thus, the studied VDR polymorphisms might indirectly impact the clinical course and treatment decision­making despite their lack of association with vitiligo per se. Further research with larger sample sizes, especially across Caucasian individuals, should be performed to confirm these findings.

Ciclopirox Hydroxypropyl Chitosan (HPCH) Nail Lacquer: A Review of Its Use in Onychomycosis.

Ciclopirox 8% hydroxypropyl chitosan (HPCH) [Marketed in different countries as the following registered (®) brands: Ciclopoli, Fulcare, Kitonail, Myconail, Niogermos, Niogermox, Onytec, Ony-Tec, Polinail, Privex, Rejuvenail] is the first topical nail lacquer developed using innovative drug formulation technology. It is indicated for the treatment of mild-to-moderate fungal infections of the nails that are caused by dermatophytes and/or other ciclopirox-sensitive fungi, without nail matrix involvement. HPCH is a patented drug formulation technology for the delivery of active principles into the nails based on a hydrosoluble semisynthetic amino-polysaccharide biopolymer derivative of chitosan. The lacquer acts as a protective barrier against microbiological attack, physical damage and/or aggressive chemicals. Results from in vitro studies suggest that the application of ciclopirox 8% HPCH nail lacquer improves drug permeation into and/or drug penetration through the nail, relative to the water-insoluble ciclopirox 8%, amorolfine 5% and efinaconazole 10% reference lacquers. In addition, in vitro and clinical studies in healthy subjects found that the concentration of ciclopirox reached in subungual fluids after application of ciclopirox 8% HPCH was sufficient for inhibiting fungal growth. In clinical studies in patients with mild-to-moderate onychomycosis, ciclopirox 8% HPCH was found to be more effective than the commercial water-insoluble ciclopirox 8% and amorolfine 5% lacquers, as indicated by higher complete cure, response and mycological cure rates at 48 weeks after treatment initiation. Ciclopirox 8% HPCH has been found to be generally well tolerated, with no treatment-related adverse events reported in patients using this nail lacquer. Thus, current evidence indicates that ciclopirox 8% HPCH represents a valuable treatment option for the treatment of patients with onychomycosis.

Clinical significance of Candida isolation from dystrophic fingernails.

BACKGROUND: Candida onychomycosis mostly involves fingernails. Yet, in contrast to dermatophytes, Candida isolation from dystrophic fingernails does not prove casualty, as sample contamination and non-pathogenic Candida growth occur. Characterising treatment outcome of Candida-positive dystrophic nails is crucial to avoid unnecessary treatment. OBJECTIVE: To investigate predicators associated with treatment outcome among Candida-positive dystrophic fingernails. PATIENTS AND METHODS: A retrospective cohort study was carried out among 108 adults with Candida-positive dystrophic fingernails not cured with adequate systemic anti-fungal course. Diagnosis was based on a single mycological culture. Patients with treatment failure (n = 85; 78.7% of the cases) were compared to patients with partial response (mild to almost cure; n = 23; 21.3% of the cases) at 9 to 12 months following treatment initiation. RESULTS: Treatment failure was significantly associated with primary onycholysis (odds ratio [OR] 2.8; 95% confidence interval [CI] 1.1-7.4) and prolonged dystrophy (12.8 vs. 3.7 years in average), compared to partial treatment response. Non-responders had lower odds to present with distal lateral subungual onychomycosis, compared to partial responders (OR 0.3; 95% CI 0.1-0.7). Demographic and mycological characteristics, as well as number of nails affected, co-presence of paronychia, and treatment regime were not found to be associated with treatment response. CONCLUSION: Candida-positive primary onycholysis was shown to be non-responsive to systemic anti-fungal treatment, suggesting that anti-fungal treatment is not indicated. For other clinical scenarios, high proportions of treatment non-response suggest that determining causality of Candida should not be based on a single positive mycological culture.