The Frontal Fibrosing Alopecia Treatment Dilemma.

Frontal fibrosing alopecia (FFA) is a type of cicatricial alopecia predominantly observed in postmenopausal women, with the incidence rising since its initial description in 1994. The exact etiopathogenesis of the disease has not been completely elucidated. FFA is characterized by an inflammatory process affecting the hair follicles of the fronto-temporal hairline, leading to its gradual recession. Eyebrows, particularly the lateral parts, may also be affected. Early diagnosis and an implementation of effective therapy to limit the inflammatory process are crucial in halting disease progression. Various treatment possibilities have been reported, including anti-inflammatory and immunosuppressive agents, as well as 5-alpha-reductase inhibitors, retinoids, and antimalarial agents. The use of phototherapy and surgical procedures has also been described. However, most available data have been obtained retrospectively, frequently consisting of descriptions of case reports or small case series, and not from randomized controlled trials. In addition, the etiopathogenesis of FFA remains unclear and its course unpredictable, occasionally being linked with spontaneous stabilization. Hence, no precise guidelines exist regarding treatment modalities. Therefore, the aims of this study were to provide a comprehensive review of the efficacy of existing therapeutic modalities for FFA and to highlight novel therapeutic options.

The Efficacy and Effectiveness of the Biological Treatment of Pruritus in the Course of Atopic Dermatitis.

Atopic dermatitis is a heterogenous inflammatory disease with high variety in terms of clinical symptoms and etiopathogenesis, occurring both in pediatric and adult populations. The clinical manifestation of atopic dermatitis varies depending on the age of patients, but all age groups share certain common features, such as a chronic and recurrent course of disease, pruritus, and a co-occurrence of atopic diseases in personal or family medical history. Treating pruritus is a high priority due to its incidence rate in atopic dermatitis and substantial impact on quality of life. In recent years, treatments with biological drugs have increased the range of therapeutic possibilities in atopic dermatitis. The aim of the study is to present the safety profile, efficacy, and effectiveness of various biological treatment methods for the therapy of pruritus in the course of atopic dermatitis.

The Role of Osteopontin in Psoriasis-A Scoping Review.

Psoriasis is a chronic systemic disease with an immunological basis and a complex pathophysiology. The chronic inflammatory status of psoriasis is associated with several comorbidities, such as metabolic syndrome, obesity, and cardiovascular disease. The development of psoriasis is influenced by osteopontin, a glycoprotein that influences physiological and pathological reactions by modulating Th1 and Th17 cellular responses, stimulating keratinocyte proliferation, regulating cellular apoptosis, and promoting angiogenesis. The recent identification of immune pathways involved in psoriasis development has facilitated the development of biological treatments; however, a better understanding of the intricate relationship between underlying inflammatory processes, psoriasis development, and accompanying comorbidities is needed for improved disease management.

Assessment of NADH/NAD+ Redox Imbalance in Psoriatic Lesions Using the FMSF Technique: Therapeutic Aspects.

Mitochondrial dysfunction has been linked to psoriasis, and it may be an important underlying factor contributing to this disease. However, a precise methodology for assessing mitochondrial dysfunction has yet to be developed. One promising approach is to measure NADH autofluorescence from the affected skin areas. In this study, we show that Flow-Mediated Skin Fluorescence (FMSF) can be used for the non-invasive assessment of mitochondrial dysfunction in psoriasis. The fluorescence level at baseline and the half-time of ischemic growth (t1/2) derived from the FMSF traces can be used for the non-invasive assessment of NADH/NAD+ redox imbalance in psoriatic lesions compared to unaffected skin. These results are supported by an analysis of the key FMSF parameters: Reactive Hyperemia Response (RHR) and Hypoxia Sensitivity (HS). This method not only contributes to understanding the biochemical processes involved in the etiopathogenesis of psoriasis, but it also provides a basis for identifying new drug targets and improving the treatment process.

Dense fine speckled nuclear immunofluorescence: A mildly reassuring antinuclear antibody pattern meriting consideration.

INTRODUCTION: Antinuclear antibodies (ANAs) are regarded as a hallmark of connective tissue diseases (CTDs) and play a key role in their diagnosis, but the value of some particular antibodies in management of patients and the disease prognosis is controversial. The mechanism underlying the production of ANAs in CTDs, other chronic inflammatory conditions and even in healthy people, is not completely elucidated. Anti-DFS70 antibodies connected with the dense fine speckled autoantigen of 70 kD, known as the lens epithelium-derived growth factor p75, are a subgroup of ANAs. Their presence and coexistence with other antibodies and their clinical significance are the matter of debate. METHODS: Based on literature data, the authors focused on current knowledge explaining the role of anti-DFS70 antibodies in selected CTDs. RESULTS: However, the literature data is ambiguous and does not fully support the validity of the anti-DFS70 assay for a specific CTD diagnosis. Most researchers claim that the presence of anti-DFS70 as the only one usually exclude the diagnosis of CTD. Nevertheless, its coexistence with other ANAs is not an excluding factor but has predictive value due to more favorable course of CTD. Such situations may also suggest an enhanced risk of the development of a CTD in the future. CONCLUSIONS: Although more studies are needed in this field, it seems reasonable to ascertain the presence of anti-DFS70 in routine clinical practice.

How old is too old to work for physicians?

The healthcare systems throughout the world are facing numerous problems, including aging and shortages of medical staff. Although senior medical practitioners are important to the healthcare, their competency may decline with age. A major problem experienced nowadays by some elderly practitioners is digital exclusion caused by difficulties with adopting new technologies. Some attempts are being made to determine the optimum moment to retire, considering its possible impact on the safety and wellbeing of patients, as well as on the health system and human resource allocation. Until legal regulations are adopted, the age-related screening programs can be used to determine the optimal retirement age.

Psoriatic Arthritis: Development, Detection and Prevention: A Scoping Review.

Psoriatic arthritis is a heterogenous chronic inflammatory disease that develops over time in some patients with psoriasis. The course of the disease is variable, with a broad clinical spectrum. The management of PsA has changed tremendously over the last decade, thanks to earlier diagnosis, a multidisciplinary approach and progress in pharmacological therapies. Therefore, screening for risk factors and the early signs of arthritis is highly important and recommended. Currently, research is focused on finding soluble biomarkers and developing imaging techniques that can improve the prediction of psoriatic arthritis. Among imaging modalities, ultrasonography seems to be the most accurate in detecting subclinical inflammation. Early intervention is based on the assumption that it is possible to prevent or delay psoriatic arthritis if systemic treatment for psoriasis can be administered early enough. This review article provides an overview of the current perspectives and evidence regarding the diagnosis, management and prevention of psoriatic arthritis.

Interleukins 20 and 8 - less widely known cytokines in psoriasis.

Psoriasis is a common immune-mediated inflammatory dermatosis affecting 2-3% of the northern European population. Although its aetiology is not completely elucidated, it is widely accepted that activated immune cells and keratinocytes stimulate keratinocyte hyperproliferation by production of cytokines; indeed, elevated amounts of pro-inflammatory cytokines have been observed in skin lesions and patient serum. By identifying those playing a central role in the disease pathogenesis, it will be possible to indicate a potential therapeutic target. Drugs targeting tumour necrosis factor α (TNF-α), interleukin (IL)-12/23, IL-17, IL-22 and IL-23 and Janus kinase inhibitors have been found to successfully alleviate resistant skin lesions. However, psoriasis is a complex disease with varied cellular interactions and cytokines, and a complex receptor network. Therefore, this review paper examines the less widely known cytokines IL-20 and IL-8, their therapeutic potential and their role in skin lesion development. Although promising results have been obtained for IL-20 and IL-8 treatment, and their role in the psoriasis skin lesion development is well documented, the role of these two cytokines remains overshadowed by that of the wider systemic cytokine storm.

Zinc: an undervalued microelement in research and treatment.

Recent years have seen a growing interest in a healthy lifestyle, particularly nutrition. An important component of a balanced diet is the microelement content. Zinc is the second most abundant trace element, after iron. It has antioxidant and immunomodulatory functions, and plays important roles in the pathogenesis of various diseases, including dermatoses. Individuals with a zinc deficiency may present with nonspecific erythematous, pustular, erosive, and bullous lesions as well as alopecia, nail dystrophy, and a variety of systemic symptoms. Any individual assessment of zinc levels should consider risk factors for deficiency, clinical symptoms, type of diet, and results of laboratory analyses. Recent research has shed light on the systemic and topical effects of zinc, indicating the value of its supplementation for many conditions.

Female genital lichen sclerosus is connected with a higher depression rate, decreased sexual quality of life and diminished work productivity.

Female genital lichen sclerosus is an underdiagnosed, distressing, chronic dermatosis affecting the well-being of women. The aim of this retrospective case-control study was to assess whether the disease is connected with work productivity and activity impairment, depression and decreased sexual quality of life. Fifty-one female patients with genital lichen sclerosus and forty-five healthy women were enrolled to the study and filled out an online survey including: Work Productivity and Activity Impairment: General Health (WPAI:GH), Patient Health Questionnaire-9 (PHQ-9) and The Sexual Quality of Life-Female (SQOL-F) questionnaires. The results showed that women with genital lichen sclerosus are at risk of having a diminished work productivity, are more often screened for depression and have a decreased sexual quality of life. The study highlights the importance of a multidisciplinary approach to treating female genital lichen sclerosus.

Can Methotrexate Be Employed as Monotherapy for Bullous Pemphigoid? Analysis of Efficiency and Tolerance of Methotrexate Treatment in Patients with Bullous Pemphigoid.

The European Academy of Dermatology and Venerology (EADV) consensus states that the treatment of choice for bullous pemphigoid is systemic glucocorticosteroid therapy. Bearing in mind that long-term steroid therapy is associated with numerous side effects, an effective and safer treatment regimen for these patients is still being sought. A retrospective analysis was performed of the medical reports of patients with diagnosed bullous pemphigoid. The study included 40 patients with moderate or severe disease, and who had continued ambulatory treatment for at least six months. The patients were divided into two groups: one treated with methotrexate in monotherapy, or with combined methotrexate and systemic steroid therapy. A slightly better survival rate was noted in the methotrexate group. No significant differences were observed between the groups in time to achieve clinical remission. The combination therapy group demonstrated more frequent disease recurrence and exacerbations during treatment, and a higher mortality rate. None of the patients in either group presented with severe side effects related to methotrexate treatment. The treatment of bullous pemphigoid with methotrexate in monotherapy is an effective and safe therapeutic method for elderly patients.

Risankizumab Therapy for Moderate-to-Severe Psoriasis-A Multi-Center, Long-Term, Real-Life Study from Poland.

The present multi-center, long-term, real-life study made an attempt to assess the efficacy of risankizumab in the treatment of moderate-to-severe plaque psoriasis. The study comprised 185 patients from 10 Polish dermatologic departments undergoing risankizumab treatment. The disease severity was measured using the Psoriasis Area and Severity Index (PASI) before the start of the risankizumab treatment and next at the defined timepoints, i.e., 4, 16, 28, 40, 52 and 96 weeks of treatment. The percentage of patients achieving PASI90 and PASI100 responses as well as the PASI percentage decrease at the defined timepoints were calculated, and correlations with clinical characteristics and therapeutic effect were analyzed. The number of patients evaluated at the defined timepoints was: 136, 145, 100, 93, 62, and 22 at 4, 16, 28, 40, 52 and 96 weeks of treatment, respectively. At 4, 16, 28, 40, 52 and 96 weeks, the PASI90 response was achieved in 13.2%, 81.4%, 87.0%, 86.0%, 88.7% and 81.8% of patients, whereas the PASI100 response was achieved in 2.9%, 53.1%, 67.0%, 68.8%, 71.0% and 68.2% of patients, respectively. Our study revealed a significant negative correlation between a decrease in the PASI and the presence of psoriatic arthritis as well as the patient's age and duration of psoriasis at several timepoints throughout the observation period.

A study of attitudes among Polish dermatologists and dermatology trainees regarding modern technologies in medicine.

Introduction: Dermatology offers great potential for the use of modern technologies such as remote online consultations, initial diagnostics via smartphone and computer applications, and artificial intelligence (AI)-based support for doctors. Aim: To investigate the attitude of dermatologists to such technologies. Material and methods: The participants completed a paper questionnaire comprising 16 questions regarding data such as age, gender and advancement in specialization, as well as views on the safety, benefits and future role of technologies such as AI and telemedicine in the future of medicine. The participants were chosen by snowball sampling. In total, 140 questionnaires were obtained; this was reduced to 90 by removing 50 respondents who were not familiar with term "telemedicine". The obtained data were subjected to statistical analysis. Results: The prevailing opinion was that while AI will not be able to replace doctors in the future, it could be used to improve the skills of medical personnel. Among the possible applications of these technologies in medicine, most of the responses indicated disease prevention (32%) and education (26%). None of the participants indicated that telemedicine could completely replace the traditional visit to the doctor's office. Conclusions: While the connection between medicine and modern technology is becoming stronger, most respondents believe that it is not possible for technologies such as AI or telemedicine to replace the work of human doctors.

Risk Factors and Clinicopathological Features for Developing a Subsequent Primary Cutaneous Squamous and Basal Cell Carcinomas.

BACKGROUND: Patients with diagnosed keratinocyte carcinomas (KCs) have an increased risk of subsequent skin cancers development. Current studies indicate that patients with subsequent tumors should be followed up regularly. However, none of the studies indicate the connection between the specific subtypes and an increased risk for further KCs development. The study assesses the differences in the risk of developing a subsequent skin cancer after a previous diagnosis of KC, especially considering individual types of skin malignances, and identifies potential factors associated with an increased risk of new cutaneous tumor describing non-invasive diagnosis and monitoring. METHODS: Pathology and medical records were examined to identify the characteristics of patients with multiple KCs diagnosed between 1999 and 2019. RESULTS: The study group comprised 13,913 KCs occurring in 10,083 patients. Multiple KCs were observed in 2300 patients (22.8%). The analysis showed aggressive subtypes, multiple tumors, and male sex as significant prognostic factors. CONCLUSIONS: The most crucial risk factors for developing subsequent KC are being of a male gender, an aggressive tumor subtype, and previous history of multiple skin cancers. Basal cell carcinoma subtypes, such as infiltrative basosquamous, with aggressive growth patterns predispose not only to increased risk for the recurrence but are also expected to be at higher risk of subsequent KCs.

Antimalarials - old drugs are new again.

The aim of this study was to discuss the therapeutic mechanism of action of antimalarials, in particular hydroxychloroquine (HCQ), in patients with lupus erythematosus. It examines the results of recent studies indicating the need to revise the indications, dosage and duration of safe therapy, thus limiting the possibility of adverse effects. Historically, HCQ was recommended for patients with arthritis as a predominant symptom, whereas today, it is recommended for all lupus patients, even those with lupus nephritis and pregnant women; it has a favourable therapeutic profile, particularly regarding its effect on the activity of the disease, and the possibility of prolonging survival time and preventing organ damage and dysfunction. Antimalarials are basic, disease-modifying antirheumatic drugs, which not only relieve the symptoms of inflammation, but also affect the underlying processes; therefore, they should be administered chronically, and the expected effects may sometimes take a long time to become apparent. In the past, the recommended dose was 6.5 mg/kg ideal body weight, whereas today it is up to 5.0 mg/kg real body weight. A very important aspect of long-term therapy is the strict adherence to the medical prescription; hence, the introduction of a new formulation containing 400 mg of hydroxychloroquine sulphate per tablet is an interesting proposal.

Neonatal lupus erythematosus - prevention is better than cure.

Neonatal lupus erythematosus (NLE) is a congenital autoimmune condition in which the transplacental passage of immunoglobulin G (IgG) directed against auto-antigens causes clinical symptoms in the foetus or neonate. Anti-Ro/SS-A, anti-La/SS-B, and to a lesser extent, anti-U1RNP autoantibodies (aAbs) have the strongest association with NLE. However, ~ 50% of affected mothers are asymptomatic despite carrying those aAbs. The clinical picture of the disease is very diverse. Cardiac manifestations are the most severe, including congenital heart block (CHB), with a mortality rate of ~18%. Preventative therapy with hydroxychloroquine (HCQ) reduces the recurrence rate of CHB in subsequent pregnancies by ~50%.

An Analysis of IL-10, IL-17A, IL-17RA, IL-23A and IL-23R Expression and Their Correlation with Clinical Course in Patients with Psoriasis.

Being one of the most common dermatological inflammatory disorders, psoriasis is a frequent subject of research. It is considered to be a T cell-dependent immune disease whose pathogenesis is influenced by cytokines, such as IL-10, IL-17A, IL-17RA, IL-23A and IL-23R. The present study examines whether the expression of selected genes is correlated with the clinical course of psoriasis, assessed by the PASI, BSA and DLQI scales. Skin biopsies and blood from 60 patients with psoriasis and 24 healthy controls were obtained for RNA isolation. These were subjected to RT-PCR for IL-10, IL-17A, IL-17RA, IL-23A and IL-23R genes. The results were presented as an RQ value. IL-17A and IL-23R expression levels were higher in psoriatic skin compared to controls, while IL-10 expression was lower. A positive correlation was also found between RQ for IL-23A and PASI index. Psoriatic skin is characterised by elevated expression of IL-17A and IL-23R and decreased expression of IL-10. This indicates that the selected cytokines may be one of the factors involved in the pathogenesis and pathomechanism of psoriasis, but more studies need to be made before we can elucidate the exact reason for the unbalance in cytokine expression levels.

Evaluation of a smartphone application for diagnosis of skin diseases.

INTRODUCTION: Artificial intelligence (AI) could offer equal, or even more accurate, diagnoses of melanoma than most dermatologists. However, the value of popular smartphone applications for diagnosing unpigmented skin lesions remains unclear. AIM: To compare the diagnostic accuracy of a popular, free-to-use web application for automatic dermatosis diagnosis against expert diagnosis of selected skin diseases. MATERIAL AND METHODS: Skin lesion images of patients with verified diagnosis were collected using a smartphone and were diagnosed by the application. The AI provided five diagnoses of varying probability. For each patient, accuracy of the diagnosis was evaluated by three criteria, i.e. whether the expert diagnosis was matched by the most probable automated diagnosis, one of the top three diagnoses or one of the top five diagnoses. Reliability was analysed using intraclass correlation coefficients. RESULTS: The chance of a correct diagnosis increased when more outcomes were considered and more samples of a skin condition were included. However, the probability of a diagnosis repeating for the same patient was below 25%. Reliability, sensitivity and specificity were insufficient for clinical purposes. CONCLUSIONS: Although AI diagnostics are encouraging, there is also a large margin for improvement, and AI is not yet an adequate replacement for medical professionals.

Osteopontin Gene Polymorphisms rs1126616 C>T and rs1126772 A>G are Associated with Atopic Dermatitis in Polish Population.

PURPOSE: Atopic dermatitis (AD) is a chronic, relapsing inflammatory disease, caused by environmental and genetic factors, which lead to immunological abnormalities. Osteopontin (OPN), also named secreted phosphoprotein 1 (SPP1), is a protein involved in the pathogenesis of numerous autoimmune and inflammatory conditions. However, its role in AD has not been fully elucidated. Therefore, we aim to gain an insight into the role of OPN in AD pathogenesis through investigating its gene single nucleotide polymorphisms (SNPs) and their possible associations with disease clinical features. PATIENTS AND METHODS: A total of 182 Caucasian participants (45 AD patients and 137 gender- and age-matched controls) were studied. Genomic DNA was isolated from peripheral blood samples. Genotyping for the rs1126616 C>T, rs1126772 A>G, rs9138 A>C, and rs3841116 T>G SNPs was performed by real time polymerase chain reaction (RT-PCR). RESULTS: The frequency of the minor TT genotype and the T allele of rs1126616 C>T was higher in AD patients compared to controls (P = 0.019, OD = 4.86, 95% CI = 1.46-16.20, and P = 0.047, OR = 1.77, 95% CI = 1.04-3.00, respectively) and was associated with the higher prevalence of asthma (P = 0.017, OR = 3.73, 95% CI = 0.71-19.67, and P = 0.004, OR = 3.96, 95% CI = 1.53-10.25, respectively). Likewise, the minor GG genotype and the G allele of rs1126772 A>G were more frequent in AD patients (P = 0.026, OR = 3.27, 95% CI = 1.29-8.33, and P = 0.013, OR = 1.94, 95% CI = 1.18-3.21, respectively) and were associated with the increased incidence of asthma (P = 0.016, OR = 5.06, 95% CI = 1.14-22.49, and P = 0.002, OR = 4.40, 95% CI = 1.71-11.35, respectively). Furthermore, haplotype frequency estimation determined the four-loci haplotype TGCT, as a significant risk factor for AD compared to controls (P = 0.031, OR = 9.48, 95% CI = 1.23-71.91). CONCLUSION: Our results suggest that the variation in the OPN gene might be associated with AD and increased incidence of asthma in Caucasians. Further studies should be conducted to look into the possible role of OPN as a biomarker for AD.

The Pancreatitis, Panniculitis, and Polyarthritis (PPP) Syndrome: Subcutaneous Nodular Fat Necrosis, a Cutaneous Marker of Pancreatic Neoplasia.

The pancreatitis, panniculitis, polyarthritis (PPP) syndrome is a rare skin, joint, and pancreatic disorder, also known as subcutaneous nodular fat necrosis. It results from obstruction of pancreatic ducts with direct secretion of pancreatic enzymes into the bloodstream, causing extra pancreatic fat necrosis with subcutaneous tissue and joint inflammation. It is usually a cutaneous sign of pancreatic cancer or pancreatitis. To our knowledge, this is the first case associated with a pancreatic pseudotumor. We describe a 59-year-old man initially presenting with numerous painful erythematous subcutaneous nodules due to a fibrous pancreatic pseudotumor and its extreme dermatologic disease, resulting in necrosis of the shin and foot so severe that an amputation of the lower leg above the knee was required, a complication not previously described, to our knowledge. We emphasize that PPP syndrome is a cutaneous marker of internal malignancy, most often of pancreatic cancer or pancreatitis, but in this case of a rare pancreatic pseudotumor.