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.

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.

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.

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.

Isolated nail lichen planus: An expert consensus on treatment of the classical form.

Lichen planus is a benign inflammatory disorder of unknown etiology that may affect the skin, mucosae, scalp, and nails. When the nails are affected, it may lead to permanent destruction with severe functional and psychosocial consequences. Therefore, prompt diagnosis and early treatment are essential, even in mild cases. There are currently no guidelines for the management of nail lichen planus and the published literature on treatment is limited. The aim of this review is to provide practical management recommendations for the classical form of nail lichen planus, especially when restricted to the nails. Topical treatment has poor short-term efficacy and may cause long-term side effects. Instead, intralesional and intramuscular triamcinolone acetonide should be considered first-line therapies. Oral retinoids are second-line choices, and immunosuppressive agents may also be considered.

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.

Another window into tumor microenvironment: a case of Β-cell rich folliculotropic mycosis fungoides responding to rituximab.

The role of tumor infiltrating immune cells in cancer development and progression is a new, promising field in oncological research. An increasing number of novel anti-cancer agents are focussing on the tumor microenvironment. Various studies have reported on B-cell infiltrates in mycosis fungoides (MF), but despite the substantial volume of interesting findings, solid evidence regarding their specific role in cancer is still vague. We present a case of tumor stage  MF responding to rituximab. We support the hypothesis that lymphoma-infltrating B-cells have a significant impact on cutaneous lymphoma course and seem to be both an important and effective therapeutic target. The reduction of B-cell population led to disease's overall remission, probably by restoring patient's immunologic tumor control.

Mitochondrial dysfunction in affected skin and increased mitochondrial DNA in serum from patients with psoriasis.

Psoriasis is characterized by keratinocyte proliferation and chronic inflammation, but the pathogenesis is still unclear. Dysregulated mitochondria (mt) could lead to reduced apoptosis and extracellular secretion of mtDNA, acting as "innate pathogen" triggering inflammation. Serum was obtained from healthy volunteers and psoriatic patients. Mitochondrial DNA was extracted from the serum and amplified with quantitative PCR (qPCR). Punch biopsies were obtained from lesional and non-lesional psoriatic skin (10 cm apart) and from healthy volunteers, were placed in RNA later and were stored at -80°C until RNA was extracted and cDNA was synthesized; gene expression of uncoupling protein 2 (UCP2), Dynamin-related protein 1 (Drp1) and calcineurin, involved in the regulation of mitochondria function, was detected with qPCR. Mitochondrial DNA was significantly increased (7s, P = 0.0496 and Cytochrome B, CytB, P = 0.0403) in the serum of psoriatic patients (n = 63) as compared to controls (n = 27). Gene expression was significantly reduced for UCP2 (P = 0.0218), Drp1 (P = 0.0001) and calcineurin (P = 0.0001) in lesional psoriatic skin, as compared to non-lesional or control skin. Increased serum extracellular mtDNA in psoriatic patients and decreased expression of mitochondrial regulatory proteins in psoriatic skin suggest increased inflammation and reduced keratinocyte apoptosis, respectively. Inhibitors of mtDNA secretion and/or UCP2 stimulants may be potential treatment options.

Real world data from the use of secukinumab in the treatment of moderate-to-severe psoriasis, including scalp and palmoplantar psoriasis: A 104-week clinical study.

Several clinical studies demonstrated the safety and efficacy of the interleukin-17 inhibitor secukinumab in the systemic treatment of moderate-to-severe psoriasis, as well as psoriatic arthritis (PsA) in adults, whereas real-world data is limited. A single-center clinical study was performed to evaluate in real-world practice the efficacy of secukinumab up to Week 104 of treatment in moderate-to-severe chronic plaque psoriasis, including scalp and palmoplantar involvement, according to Physician Global Assessment (PGA), PASI75/90/100 and scalp, and palmoplantar PGA. Drug survival, the safety profile of secukinumab, and patient's quality of life were also assessed during a 2-year observation period. Out of 83 patients included, 56.3% were biologic-naïve, and 94% had scalp, 25.3% palmoplantar, and 43.9% joint involvement. At Week 16, PASI75/PASI90/PASI100 were observed in 83.8/70.0/46.3%, respectively. Scalp and palmoplantar PGA were rapidly improved, with 98.7 and 95.5%, respectively, reaching clear/almost clear skin at Week 16. After 104 weeks, drug survival was 74.5%. A significant improvement of the quality of life was observed. Biologic-naïve patients without coexisting PsA benefited the most. Real-world data demonstrated secukinumab efficacious in chronic plaque psoriasis, including specific locations such as scalp and palmoplantar psoriasis with a safety profile similar to that in clinical trials.

Ustekinumab in severe complicated erythrodermic psoriasis: rapid clearing, safety, and sustained remission.

Erythrodermic psoriasis is a severe type of psoriasis associated with comorbidities and high mortality. Patients with erythrodermic psoriasis need hospitalization and systemic treatment. Conventional drugs and biologic agents may not manage to control refractory and complicated erythrodermic psoriasis resulting from treatment failure. Ustekinumab, a human monoclonal antibody against interleukin-12 and 23, seems to be an effective therapeutic option in erythrodermic psoriasis whenever other therapies have failed.

Evaluation of Delayed Contact Hypersensitivity in Patients with Rosacea.

Introduction: Rosacea is a common chronic inflammatory dermatosis characterized by erythema, telangiectasia, papules, and pustules on the central face. The frequency of contact sensitization complicating rosacea and its therapy is unknown, with only few studies published in the literature. In the present study, we aimed to evaluate contact sensitivity in patients with rosacea. Methods: A total of 50 rosacea patients and 50 age- and sex-matched healthy controls were enrolled. Both groups were patch tested with the European Baseline Series. Results: A positive reaction to at least one allergen of the European Baseline Series was observed in 15 (30%) of rosacea patients and 10 (20%) of the healthy controls. Although the rate of positive reaction in the rosacea group was higher than in the controls, no statistically significant difference was documented. In addition, the total number of positive reactions to allergens in the rosacea group was higher than the control group, namely, 26 versus 17. Conclusion: Contact hypersensitivity may coexist with rosacea. Its identification holds significant clinical relevance, influencing the long-term management and justifying the application of patch testing in rosacea patients.

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.

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.

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.