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.

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.

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.

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.

Secukinumab Use in Patients with Moderate to Severe Psoriasis, Psoriatic Arthritis and Ankylosing Spondylitis in Real-World Setting in Europe: Baseline Data from SERENA Study.

INTRODUCTION: Secukinumab, a fully human monoclonal antibody that directly inhibits interleukin-17A, has demonstrated robust efficacy in the treatment of moderate to severe psoriasis (PsO), psoriatic arthritis (PsA) and ankylosing spondylitis (AS), with a rapid onset of action, sustained long-term clinical responses and a consistently favourable safety profile across phase 3 trials. Here, we report the clinical data at enrolment from SERENA, designed to investigate the real-world use of secukinumab across all three indications. METHODS: SERENA is an ongoing, longitudinal, observational study conducted at 438 sites across Europe in patients with moderate to severe plaque PsO, active PsA or active AS. Patients should have received at least 16 weeks of secukinumab treatment before enrolment in the study. RESULTS: Overall 2800 patients were included in the safety set; patients with PsA (N = 541) were older than patients with PsO (N = 1799) and patients with AS (N = 460); patients with PsO had a higher mean body weight than patients with PsA and patients with AS; and patients with PsO and patients with AS were predominantly male. Time since diagnosis was longer in patients with PsO compared with patients with PsA and patients with AS, and about 40% of patients were either current or former smokers. The proportion of obese patients (body mass index ≥ 30 kg/m2) was similar across indications. Patients were treated with secukinumab for a mean duration of 1 year prior to enrolment (range 0.89-1.04). The percentages of patients with prior biologics exposure were 31.5% PsO, 59.7% PsA and 55% AS. The percentages of patients prescribed secukinumab monotherapy were 75% (n = 1349) in PsO, 48.2% (n = 261) in PsA and 48.9% (n = 225) in AS groups. CONCLUSION: Baseline demographics of the study population are consistent with existing literature. This large observational study across all secukinumab indications will provide valuable information on the long-term effectiveness and safety of secukinumab in the real-world setting.

Chemical Peels in Skin Cancer: A Review.

Background: Chemexfoliation is widely used to reverse signs of photodamage. Although photodamage can eventually lead to skin cancer, it remains unclear whether chemical peels also affect photocarcinogenesis. Moreover, concerns about the systemic and/or cutaneous toxicity of peeling agents have already arisen. Objective: This review sought primarily to summarize the data available on the effects of chemical peels on ultraviolet-induced skin carcinogenesis, focusing particular attention on actinic keratoses and cutaneous field cancerization. In addition, considerations about the systemic and/or cutaneous toxicity of peeling agents, particularly trichloracetic acid, are briefly discussed. Methods: The PubMed, MEDLINE, and SCOPUS databases were searched using the keywords "chemical peeling," "actinic keratosis," "cutaneous field cancerization," "skin cancer," "skin cancer prevention," and "cutaneous and systemic carcinogenicity," both alone and in combination with one another. Additional relevant references were also isolated from citations in the reviewed literature. Results: A total of 42 articles involving both in-vitro and in-vivo human and animal models were included for analysis. The data were mainly confined to laboratory animals. Conclusion: Apart from efficacy in clearing visible actinic keratoses, the findings point towards the possible clinical use of chemical peeling for the prevention of skin cancer. To date, no evidence on systemic toxicity following dermal exposure of humans to chemical peels has been identified.

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.

Serum Total 25-Hydroxyvitamin D Levels in Patients With Cutaneous Malignant Melanoma: A Case-Control Study in a Low-Risk Southern European Population.

BACKGROUND: Recent data have shown an inverse association between serum 25-hydroxyvitamin D concentration and incidence of several cancers, including cutaneous malignant melanoma (CMM). In addition, lower serum 25-hydroxyvitamin D levels have been associated with thicker or higher stage melanomas and worse survival in observational studies. MATERIALS AND METHODS: Ninety-nine patients diagnosed with primary CMM and 97 matched healthy controls entered the study. Demographic characteristics, risk factors for CMM, and clinical and histological characteristics were recorded for patients with primary CMM. Total serum 25-hydroxyvitamin D levels of melanoma patients measured by fully automated chemiluminescent vitamin D total immunoassay (Elecsys vitamin D total, Roche) at the time of diagnosis were compared with those of healthy controls. In addition, we tested the association of serum total 25-hydroxyvitamin D levels at melanoma diagnosis with known risk and prognostic factors for CMM. RESULTS: Of the melanoma patients, 49 (49.49%) had deficient serum total 25-hydroxyvitamin D levels (<20 ng/mL), 23 (23.23%) had insufficient levels (21-29 ng/mL), and 27 (27.27%) had adequate levels (>30 ng/mL). The median serum total 25-hydroxyvitamin D levels were significantly lower in melanoma patients (20.62 ng/mL) compared with healthy controls (24.71 ng/mL), but statistical significance was not reached (chi-square test, P = 0.051) No statistically significant association was found between serum total 25-hydroxyvitamin D levels and demographic characteristics; risk factors for CMM; prognostic factors, such as Breslow thickness and ulceration; as well as clinical characteristics, such as melanoma stage, clinical type, and location. CONCLUSIONS: Lower serum 25-hydroxyvitamin D levels were found in our Greek cohort of melanoma patients compared with healthy controls, without reaching, however, statistical significance; these levels were not statistically associated with established risk and prognostic factors for CMM.

Lymphoprolipherative skin reactions induced by anti-TNFα: an open question.

Although anti-TNFα agents have revolutionized the treatment of many inflammatory diseases, various concerns have been reported regarding the risks of cancer development, as well as acceleration of the progression of subclinical, preexisting malignancies. In this case series, we investigated the provocative effect of anti-TNFα drugs in the development of cutaneous mycosis fungoides (MF)-like lymphoproliferative reactions. We describe five patients aged between 25-63 diagnosed with autoimmune disorders (psoriatic arthritis - one patient, Crohn's disease - one patient and ankylosing spondylitis - three patients) who received anti-TNFα agents before the development of a cutaneous lymphoproliferative reaction. Histological and immunophenotypical analysis was typical for mycosis fungoides in all of them. Anti-TNFα agents were stopped with regression of the skin rash. A direct effect of anti-TNFα agents in the development of lymphoproliferative reactions (including MF) is suggested and further analyzed. Treatment cessation can be therapeutic.

The different faces of mycosis fungoides: results of a single-center study.

BACKGROUND: Mycosis fungoides (MF) accounts for the majority of cutaneous lymphomas. Apart from the predominant Alibert-Bazin type, several clinicopathological variants of diverse prevalence and biological behavior have been described. Data on clinical and epidemiological aspects of MF clinical subtypes are still weak. AIM: To outline the clinical and epidemiological profile of the different MF types in a large volume of Greek patients. METHODS: Retrospective analysis of 688 MF cases treated in our lymphoma clinic. Epidemiological, clinical, pathological, and immunohistochemical data were retrieved. RESULTS: Six-hundred and thirty-six patients (416 males, 220 females) were included. The mean age at diagnosis was 60.2 years; the mean duration of disease prior to diagnosis was 63.2 months. Early-stage MF (I-IIA) involved 475 cases (74.7%). The prevalent type was classical MF (68.5%), followed by folliculotropic (17%), poikilodermic (5.5%), and psoriasiform (4.7%) MF. Atypical MF lesions as the sole manifestation of folliculotropic mycosis fungoides (FMF) - alopecia areata-like lesions (n = 10), keratosis pilaris-like lesions (n = 9) or acneiform rash (n = 4) - were also observed. Both poikilodermic and folliculotropic subtypes mainly involved younger patients. A significant diagnostic latency concerning poikilodermic and psoriasiform MF cases was recorded. Only 23 (3.3%) cases were of juvenile onset, with classical and poikilodermic MF equally affecting this age group, closely followed by FMF. CONCLUSIONS: Our study presents the whole clinical-epidemiological spectrum of MF in a large Greek cohort. The high prevalence of atypical MF manifestations characterized by early onset and indolent clinical course stood out among our FMF sample.

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.

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.

Poikilodermatous changes on the forearms of a woman practicing aroma-therapy: extracervical poikiloderma of Civatte?

We report the case of a 48-year-old, Caucasian female who presented with slowly progressing asymptomatic poikilodermatous changes of the extensor aspects of the forearms. She also had typical Poikiloderma of Civatte on the V of the neck and erythemato-telangiectatic rosacea of the central face. The patient had been practicing aroma-therapy for many years. Histologic examination revealed findings consistent with PC. Patch-testing revealed positive reactions to Fragrance mix and Nickel sulphate. Based on clinical and histological findings, a diagnosis of extracervical PC was suggested. PC with extra-cervical or extra-facial involvement is rare. In addition, this case supports the theory that contact sensitization to fragrances may contribute to the development of PC.

Skin biopsy in the context of dermatological diagnosis: a retrospective cohort study.

Background. Skin biopsy is an established method for allying the dermatologist in overcoming the diagnostic dilemmas which occur during consultations. However neither do all skin biopsies produce a conclusive diagnosis nor the dermatologists routinely perform this procedure to every patient they consult. The aim of this study was to investigate the favourable clinical diagnoses set by dermatologists when performing skin biopsy, the diagnoses reached by the dermatopathologists after microscopic examination, and the relationship between them and finally to comment on the instances that skin biopsy fails to fulfill the diagnostic task. Methods. Six thousand eight hundred and sixteen biopsy specimens were reviewed and descriptive statistics were performed. Results. The mean age of the patients was 54.58 ± 0.26 years, the most common site of biopsy was the head and neck (38.3%), the most frequently proposed clinical diagnoses included malignancies (19.28%), and the most prevalent pathological diagnosis was epitheliomas (21.9%). After microscopic examination, a specific histological diagnosis was proposed in 83.29% of the cases and a consensus between clinical and histological diagnoses was observed in 68% of them. Conclusions. Although there are cases that skin biopsy exhibits diagnostic inefficiency, it remains a valuable aid for the dermatology clinical practice.

Study of platelet-rich plasma injections in the treatment of androgenetic alopecia through an one-year period.

BACKGROUND: Platelet-rich plasma (PRP) is defined as an autologous concentration of plasma with a greater count of platelets than that of whole blood. Its action depends on the released growth factors from platelets. It has been investigated and used in numerous fields of medicine. Recently, PRP has received growing attention as a potential therapeutic tool for hair loss. AIMS: To evaluate the efficacy and safety of PRP injections in the scalp of patients with androgenetic alopecia. SETTINGS AND DESIGN: Prospective cohort study. MATERIALS AND METHODS: 20 patients, 18 males and 2 females, with androgenetic alopecia were enrolled in the study. PRP was prepared using a single spin method (Regenlab SA). Upon activation, it was injected in the androgen-related areas of scalp. Three treatment sessions were performed with an interval of 21 days and a booster session at 6 months following the onset of therapy. STATISTICAL ANALYSIS: Statistical analysis of the data was performed using the Statistical Package for the Social Sciences (SPSS), version 19.0 (IBM, NY, USA). RESULTS: Hair loss reduced and at 3 months it reached normal levels. Hair density reached a peak at 3 months (170.70 ± 37.81, P < 0.001). At 6 months and at 1 year, it was significantly increased, 156.25 ± 37.75 (P < 0.001) and 153.70 ± 39.92 (P < 0.001) respectively, comparing to baseline. Patients were satisfied with a mean result rating of 7.1 on a scale of 1-10. No remarkable adverse effects were noted. CONCLUSIONS: Our data suggest that PRP injections may have a positive therapeutic effect on male and female pattern hair loss without remarkable major side effects. Further studies are needed to confirm its efficacy.

Cutaneous metastasis of colon adenocarcinoma: case report and review of the literature.

Skin metastases from colorectal carcinoma are rare and signal advanced disease. We present a case of an 80-year-old male with a large skin metastatic focus in the lower abdomen, a year after resection of a colonic adenocarcinoma. The patient had already finished receiving his first cycle of chemotherapy shortly before the discovery of the abdominal nodules and at the same period a chest X-ray, revealed shadows at the base of the right lung.

Cutaneous metastasis of colon adenocarcinoma: case report and review of the literature / Metastasis cutanea de adenocarcinoma colorretal: relato de caso e revisao da literatura

Skin metastases from colorectal carcinoma are rare and signal advanced disease. We present a case of an 80-year-old male with a large skin metastatic focus in the lower abdomen, a year after resection of a colonic adenocarcinoma. The patient had already finished receiving his first cycle of chemotherapy shortly before the discovery of the abdominal nodules and at the same period a chest X-ray, revealed shadows at the base of the right lung.

Metástases cutáneas provocadas por carcinoma colorretal são raras e sinalizam doença avançada. Apresentamos o caso de um homem de 80 anos com um grande foco metastático na pele do baixo abdômen, um ano após a ressecção de um adenocarcinoma do cólon. O paciente já havia acabado de receber o seu primeiro ciclo de quimioterapia pouco antes da descoberta dos nódulos abdominais e, no mesmo período, um raio-X do tórax revelou sombras na base do pulmão direito.