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.

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.

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.

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%.

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.

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.

Artificial intelligence in medicine and dermatology.

As technology advances rapidly and vast amounts of data are collected, artificial intelligence (AI) is increasing its presence in our lives. Medicine is a major focus point of AI developers. There are examples of algorithms on par with medical professionals, the most prominent case being skin cancer recognition. However, advancement involves the necessity to adapt to technology and to patients utilizing it on a daily basis. What is more, patients present growing trust towards machine-aided health care. Dermatology is a potent field for AI use as visual data are easy to collect, hold a lot of information and are paramount for diagnosis.

Variability of the rs333 in Polish patients with lupus erythematosus.

INTRODUCTION: Lupus erythematosus (LE) is an autoimmune disease with a strong influence of genetic and environmental factors. C-C motif chemokine receptor 5 (CCR5) gene expression may affect the development and intensity of LE. AIM: To evaluate the possible association between the 32bp deletion in rs333 locus located within the CCR5 gene and the development of LE or the occurrence of various clinical symptoms in the course of the disease. MATERIAL AND METHODS: One hundred and twenty patients with LE (77 with systemic lupus erythematosus (SLE) and 43 with discoid lupus erythematosus (DLE)) and 100 healthy controls from the Polish population were genotyped for deletion in rs333. RESULTS: 32 bp deletion in the rs333 was significantly more frequent among healthy individuals than DLE patients. Moreover, heterozygotes and homozygotes with deletion in rs333 were significantly more frequent within the control group than the group of patients with discoid lupus erythematosus. In contrast, any statistically significant differences in allele or genotype frequencies between healthy persons and SLE patients were observed. Furthermore, nucleotide sequence variability of rs333 was not associated with certain clinical symptoms of LE patients. CONCLUSIONS: Deletion in the rs333 might be a protective factor for DLE, but not SLE in the Polish population. Nevertheless further studies performed on larger populations are needed to confirm these observations.

The impact of medium dose UVA1 phototherapy on pruritus, DLQI and SCORAD index in patients with atopic dermatitis.

INTRODUCTION: Atopic dermatitis (AD) is featured by pruritus, which causes diminished quality of life. Little clinical data exists concerning the use, efficacy and side effects of UVA1 phototherapy in AD patients. AIM: To determine the effectiveness of medium-dose UVA1 phototherapy in AD treatment. MATERIAL AND METHODS: Thirty-six patients with AD were irradiated with medium-dose UVA1 (45 J/cm2) as monotherapy for 4 weeks for a total of 20 sessions (daily irradiations during weekdays only). Clinical status was evaluated with the visual analogue scale for pruritus, Dermatology Life Quality Index (DLQI) for evaluating general well-being and the SCORAD index. All parameters were measured twice: before and after phototherapy. RESULTS: UVA1 phototherapy resulted in a significant (p < 0.001) decrease in pruritus, improvement in DLQI (p < 0.001) and SCORAD (p < 0.001). Before phototherapy, the intensity of pruritus and SCORAD index correlated with DLQI (r = 0.34, p < 0.05 and r = 0.61, p < 0.05, respectively). Similarly, after irradiation, pruritus correlated with DLQI, and SCORAD index correlated with DLQI (r = 0.51, p < 0.05 and r = 0.55, p < 0.05, respectively). No severe adverse effects were noted during the study. CONCLUSIONS: Phototherapy with medium-dose UVA1 irradiation exerts a significant antipruritic effect, decreases the severity of the disease and improves the quality of life of AD patients. This technique can therefore be used as a safe and effective treatment method.

The role of endocan and selected pro-inflammatory cytokines in systemic lupus erythematosus.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a multisystem inflammatory autoimmune disease with a wide spectrum of clinical manifestations. Cytokines such as interleukin-1 (IL-1) and tumour necrosis factor α (TNF-α) are involved in its pathogenesis. Endocan is a novel marker of endothelial dysfunction and is likely to be engaged in proinflammatory processes in SLE. AIM: To determine whether endocan serum concentration in SLE patients vary from healthy controls. MATERIAL AND METHODS: The study included 36 patients with SLE. SLEDAI-2K score was used to assess disease activity. The control group comprised 23 healthy volunteers. ELISA kits were used to assess serum concentrations of endocan, IL-1ß, TNF-α, vascular endothelial growth factor (VEGF) and high-sensitivity C reactive protein (hs-CRP). RESULTS: The serum concentration of endocan was significantly higher (p < 0.001) in the SLE group than in healthy individuals. A positive correlation was found between serum levels of endocan and IL-1ß (r = 0.47, p < 0.05). Active SLE patients (SLEDAI-2K score above 6 points) with an elevated total cholesterol level (above 5.17 mmol/l) were found to have VEGF concentration higher than those with a normal cholesterol level (p < 0.03). No other relevant relationships were found between the serum concentration of endocan, other laboratory parameters, anthropometric features, activity and duration of SLE. CONCLUSIONS: A higher serum level of endocan in SLE patients indicates its possible role in the pathogenesis of the disease and reflects endothelial dysfunction. Our findings indicate that endocan could serve as a potential marker of endothelial dysfunction in SLE.

Methotrexate use and NAD+/NADH metabolism in psoriatic keratinocytes.

Methotrexate inhibits tetrahydrofolic acid production and influences mitochondrial oxygen uptake and activity of several enzymes in the respiratory chain reactions, which utilize nicotinamide adenine dinucleotide-linked (NAD-linked) substrates. Hyperproliferation of keratinocytes in psoriasis requires oxidative phosphorylation, in which the reduced form of nicotinamide adenine dinucleotide (NADH) is an electron donor. One hypothesis links increased cellular metabolism to the increased NADH/NAD+ ratio; as expected, the topical application of NAD+ (oxidized form of nicotinamide-adenine dinucleotide) resulted in a clinical improvement of psoriatic lesions in one study. Nevertheless, another report revealed reduced fluorescence of NADH in psoriatic plaques. The biological activity of NADH is not limited only to serving as the electron donor. It was also found to regulate gene transcription.

The preliminary association study of osteopontin 707 C/T polymorphism with systemic lupus erythematosus in a Polish population.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease caused by genetic, environmental, and still unknown factors which lead to deregulation of the immune system. Osteopontin (OPN) is a multifunctional glycoprotein, expressed in various cell types, and found to play key roles in immunity. OPN and variants of the OPN gene are involved in inflammatory conditions, however, their role in SLE are controversial. AIM: To investigate the frequency of single nucleotide polymorphism (SNP) rs1126616 (707 C/T) variants in the OPN gene and its associations with SLE manifestations in Polish patients. MATERIAL AND METHODS: The study population consisted of 83 SLE patients and 100 gender-, age- and ethnically matched healthy controls. DNA was extracted from whole blood samples using the standard procedure. Genotyping was performed by real-time polymerase chain reaction (RT-PCR). The association between clinical features of SLE and 707 C/T genotypes was determined. RESULTS: The mutant (CT, TT) genotypes were observed more frequently than the wild-type (CC) genotype in SLE patients compared to controls (p = 0.037). However, no association between 707 C/T variants and SLE clinical manifestations or laboratory parameters was found. CONCLUSIONS: The present data suggest that CT and TT genotypes of OPN 707 C/T SNP are associated with a higher SLE risk, but do not affect the clinical course of the disease in the Polish population.

Interleukin 22 and 6 serum concentrations decrease under long-term biologic therapy in psoriasis.

INTRODUCTION: Psoriasis, affecting approximately 2% of the worldwide population, is a chronic, inflammatory skin disease in which overexpression of proinflammatory cytokines is observed. Most of the available data on the influence of antipsoriatic therapy on the cytokine serum concentration are inconsistent and based on short-term observations. AIM: To evaluate the influence of long-term biologic therapy with tumor necrosis factor α (TNF-α) blockers (adalimumab, etanercept, infliximab) and IL-12/23 inhibitor (ustekinumab) on the level of IL-6, IL-22 in the sera of patients with psoriasis. MATERIAL AND METHODS: Blood samples were collected from 42 psoriatic patients in order to determine IL-6 and IL-22 serum concentrations prior to and at the 3rd, 12th, 24th and 36th month of biologic therapy. Psoriasis Activity and Severity Index (PASI) was assessed at the same time points. The control group consisted of 30 sex- and age-matched healthy volunteers. RESULTS: Mean PASI index at baseline was 14.49 ±3.69 and decreased significantly until the end of the observation. Mean IL-6 serum concentration decreased significantly in all study groups (p < 0.05). A statistically significant decrease in IL-22 concentrations was demonstrated during the treatment with adalimumab and infliximab but not etanercept or ustekinumab. CONCLUSIONS: According to obtained results, IL-6 and IL-22 serum concentration may be an accurate marker of response to antipsoriatic therapy, even though not correlated with PASI index. Biologic therapy in psoriasis allows for long-term clinical improvement expressed not only by the remission of skin lesions, but also by lowering serum concentrations of pro-inflammatory interleukins.

Immunometabolic disorders in the pathogenesis of systemic lupus erythematosus.

Systemic lupus erythematosus is a chronic autoimmune disease connected with complex and unclear disorders of the immune system, which causes inflammation of body tissues and internal organs. It leads to the formation of anti-nuclear antibodies (ANA) and immune complexes. Numerous immune system disorders and dysfunctions in the biochemical processes can occur in the course of the disease, and a wide range of abnormalities associated with cellular respiratory processes and mitochondrial function have been documented. The following paper presents the current understanding of the contribution of these disorders to the pathogenesis of lupus.

Ingenol mebutate treatment in actinic keratosis - clinical effectiveness and potential side effects.

INTRODUCTION: Actinic keratosis is a common skin disease that occurs in response to prolonged exposure to ultraviolet radiation. This problem affects up to 60% of the population over 40 years of age. Actinic keratosis is considered to be a precancerous lesion leading to squamous cell carcinoma (SCC). The new therapeutic option for the treatment of actinic keratosis is ingenol mebutate gel (0.015%, 0.05%). AIM: Retrospective evaluation of response and potential side effects of ingenol mebutate treatment in clinical practice. MATERIAL AND METHODS: Eight patients with actinic keratosis lesions on the face or scalp self-applied a 0.015% gel for 3 consecutive days on the 25 cm2 marked area. They were assessed at baseline and on day 4, 7, 14 and 57. RESULTS: All patients on day 57 presented a complete absence of AK lesions in the area of ingenol mebutate application. No adverse events were observed. CONCLUSIONS: Our study shows that ingenol mebutate is highly efficacious field treatment for actinic keratosis.

Cellulite: a cosmetic or systemic issue? Contemporary views on the etiopathogenesis of cellulite.

Cellulite (also known as gynoid lipodystrophy or orange peel syndrome) is one of the most common lipodystrophy syndromes, which affects millions of post-adolescent women. Cellulite is manifested by topographic disorders of subcutaneous tissue such as nodules, edema, and abnormal fibrosis. It is located mainly on the pelvic area, especially on the buttocks. Its pathogenesis is complexed and unclear. There are several theories about its pathophysiology. Hormonal disorders, endothelial dysfunction and genetic predispositions are taken under consideration.

Trends in basal cell carcinoma incidence rates: a 16-year retrospective study of a population in central Poland.

INTRODUCTION: Basal cell carcinoma (BCC) is the most commonly occurring cancer worldwide, and the overall incidence is still rising. Unfortunately, the cancer registry in Poland does not record BCC individually. Thus, the incidence of BCC in a defined population is unknown. AIM: Analysis of incidence rates of primary BCC in central Poland during 16 years considering sex, site distribution and age to determine trends. MATERIAL AND METHODS: We retrospectively included all cases of BCC which were diagnosed and treated in the Department of Dermatology and Venereology, Medical University of Lodz, during the 16-year period from 1999 to 2015. RESULTS: We recorded 945 BCCs occurring in 890 patients (504 females - 57%, 386 males - 43%). Patient's age was between 21 and 94. A distinct increase in BCC was observed after 1999, while after 2010 during the next 2-year period a slight decrease was noted. A statistically significant correlation was observed between histopathological types of BCC and the location of the lesions. The superficial type predominates on photoprotected areas, especially on the trunk, while the nodular type occurs mainly in facial areas. No statistically significant correlation was observed between histopathological types of BCC and sex. We found a significant increase in incidence for superficial BCC among middle-age patients, while the nodular type was observed more frequently among elderly subjects. CONCLUSIONS: Basal cell carcinoma is quite common in Poland and predominantly develops in the facial area. In middle-age patients the most common is superficial BCC, while in elderly people the nodular type is most common. Based on our results we assume that there is a strong need to educate general physicians to enable them to diagnose BCC in the early stages.

Omalizumab for urticaria treatment in clinical practice: a case series.

INTRODUCTION: Omalizumab (Xolair) originally intended to reduce symptoms of moderate to severe asthma uncontrollable with steroids is the first monoclonal antibody approved for treatment of chronic spontaneous urticaria in 2014. AIM: To evaluate response and potential side effects to omalizumab treatment in clinical practice. MATERIAL AND METHODS: Eleven patients (6 males and 5 females) were recruited into the study. All participants signed written informed consent before enrollment to the study. At the beginning they were receiving 300 mg of omalizumab in a subcutaneous injection every 4 weeks in an outpatient clinic. Five the clinical response was sufficient, the dose of omalizumab was decreased to 150 mg. We evaluated response to the treatment using the Urticaria Activity Score in the last 7 days and the Urticaria Control Test at certain time points. RESULTS: Nine out of 11 patients achieved complete syndrome resolution. Five patients achieved clinical remission after the first dose of omalizumab. Mean time to remission was 9.3 weeks. During the study, no side effects were observed. CONCLUSIONS: Omalizumab appears to be a safe drug, which in a quick and effective way inducts remission in patients who have not responded to previous treatment.