Role of acrylates in the development of contact dermatitis in diabetic patients-A Polish dermatology tertiary centre experience.

BACKGROUND: In recent years, an increasing number of contact dermatitis cases triggered by acrylates contained in diabetes medical devices have been reported. Acrylates seem to play a major role in the development of irritant contact dermatitis and allergic contact dermatitis (ACD) in diabetic patients. OBJECTIVES: To study a group of patients with contact dermatitis caused by diabetes medical devices with a focus on acrylates as possible allergens responsible for contact dermatitis. PATIENTS AND METHODS: Fifteen patients with diabetes mellitus type 1 and contact dermatitis from diabetic devices were patch tested to 25 acrylate allergens. RESULTS: Three patients (20%) reacted to the following allergens: three patients reacted to isobornyl acrylate (IBOA) and one of them additionally to 2-hydroxyethyl acrylate (2-HEA); results were of clinical relevance. All three patients were using insulin pumps and glucose sensors (GS)-in one patient contact dermatitis was towards the insulin pump and the GS, in one patient only towards the insulin pump and in one patient only towards the GS. Twelve patients (80%) did not show any skin reaction towards the allergens tested. CONCLUSION: A majority of diabetic patients showed no reactions towards any acrylate allergen tested; yet, the presence of untested allergens must be kept in mind. IBOA proved to be a cause of ACD in diabetes patients. 2-HEA might be another culprit allergen, but its presence in the devices must first be confirmed.

Gastrointestinal Comorbidities Associated with Atopic Dermatitis-A Narrative Review.

The current understanding of atopic dermatitis (AD) seems to be extending beyond a skin-confined condition frequently associated with allergic comorbidities, as in a number of epidemiological studies, the prevalence rate of a range of illnesses has been determined to be greater in patients with AD, or inversely. In most cases, the reasons for this are vague. A subset of these conditions are gastrointestinal disorders, including food sensitization (FS) and food allergy (FA), eosinophilic esophagitis (EoE) (it is of mixed background, both IgE-dependent and independent), food protein-induced enterocolitis syndrome (FPIES) (it exemplifies an IgE-independent food allergy), Crohn's disease (CD), colitis ulcerosa (CU), celiac disease, irritable bowel syndrome (IBS), and gastroesophageal reflux disease (GERD). In this review, we performed a comprehensive search of the literature using the PubMed database. We addressed the epidemiology of the increased co-occurrence of these diseases with AD and discussed potential causes for this subject. Multiple gastroenterological comorbidities appear to be more common in patients with AD, according to our review. The mechanisms that underlie this phenomenon are largely unknown, highlighting the need for further study in this field.

Is Atopic Dermatitis Only a Skin Disease?

Atopic dermatitis (AD) is a chronic, pruritic, inflammatory dermatosis that imposes significant patient and population burdens. In addition to the cutaneous signs and symptoms, growing evidence suggests that AD is systemic in nature. Certain diseases can possibly co-occur with AD as a result of coincidental exposure to similar environmental factors. However, it is also suspected that they are linked to the pathogenesis of AD through more complex genetic and immunological mechanisms, but these correlations remain less understood. It is of great need to seek explanations for the higher frequency of the number of cardiovascular, autoimmune, neurological, psychiatric, and metabolic disorders that have been observed in epidemiologic investigations among AD patients. Moreover, analysing the immunology of chronic inflammation and its correction, activation, or suppression may prevent the development of a variety of comorbidities. As comorbid diseases in patients diagnosed with AD may potentially go undetected, physicians should be aware of them.

How to Understand Personalized Medicine in Atopic Dermatitis Nowadays?

Atopic dermatitis (AD) is a heterogeneous disease in terms of its phenotypical, barrier, and immunological presentation. Emerging therapies are undoubtedly contributing to a new chapter in the treatment of AD, bringing an excellent possibility of individualization, and thereby creating a tailored approach. The two most promising substance groups are biological drugs (dupilumab, tralokinumab, lebrikizumab, nemolizumab) and Janus kinase inhibitors (JAKis) (baricitinib, upadacitinib, and abrocitinib). The vision that certain well-defined phenotypes and endotypes, as well as personal preferences, may guide the future treatment of AD is both tempting and appealing, but not yet reality. The accessibility of new drugs such as biologics and small molecules has opened up the discussion regarding personalized medicine, referring to the complex nature of AD as well as the experiences from clinical trials and real-world evidence. We have now reached the point of creating new strategies and AD treatment goals by increasing the amount of new information concerning the efficacy and safety of new drugs. This article has reviewed the novel treatment options for AD in the light of the heterogeneity of this disease and proposes a broader vision on the strategy of personalized treatment of AD.

Contact Dermatitis to Diabetes Medical Devices.

Skin adverse reactions to diabetes medical devices have been reported frequently over recent years. Adhesives attaching glucose sensors and continuous insulin infusion sets to the skin are proven to cause both allergic contact dermatitis and irritant contact dermatitis in patients with diabetes mellitus. Several allergens contained in adhesives and/or parts of medical devices are documented to cause allergic contact dermatitis, with acrylate chemicals being the most common culprit-especially isobornyl acrylate (IBOA), but also 2,2'-methylenebis(6-tert-butyl-4-methylphenol) monoacrylate or cyanoacrylates. Epoxy resin, colophonium and nickel were also identified as causative allergens. However, repetitive occlusion, maceration of the skin and resulting disruption of the skin barrier seem to have an impact on the development of skin lesions as well. The purpose of this study is to highlight the burden of contact dermatitis triggered by diabetes medical devices and to show possible mechanisms responsible for the development of contact dermatitis in a group of diabetic patients.

Altered Gene Expression of IL-35 and IL-36α in the Skin of Patients with Atopic Dermatitis.

A comprehensive understanding of atopic dermatitis (AD) pathogenesis is desired, especially in the current era of novel biologics and small molecule drugs. In recent years, new cytokines have emerged that may play a significant role in the pathogenesis of AD. Using the tape stripping (TS) method, this study analyzed the gene expression of IL-35 and IL-36α in lesional and nonlesional AD skin compared with healthy skin and their association with the clinical features of AD among the Polish population. Ten AD patients and seven healthy individuals were enrolled. The lesional skin of the AD patients showed significantly higher expression levels of IL-35 compared to healthy skin (p = 0.0001). The expression level of IL-36α was significantly higher in lesional AD skin than in nonlesional AD skin (p = 0.0039) and healthy skin (p = 0.0045). There was a significant negative correlation between AD severity and the expression level of IL-35 in both lesional (R = -0.66, p = 0.048) and nonlesional skin (R = -0.9, p = 0.0016). In summary, both IL-35 and IL-36α appear to play a role in the pathogenesis of AD. Furthermore, it might be speculated that IL-35 and IL-36α may be potential candidates for disease biomarkers. However, further studies are needed to verify these assumptions and comprehensively elucidate their importance in the pathogenesis of AD.

Dupilumab for the treatment of moderate and severe atopic dermatitis: real-life experience.

Introduction: Atopic dermatitis is a relapsing, chronic, inflammatory dermatosis. So far, treatment options for more severe forms of the disease have been limited. The prospect has changed with the advent of biological drug registrations. Dupilumab is a monoclonal antibody targeting the a subunit of the IL-4 receptor and is responsible for blocking the signalling of interleukin (IL) 4 (IL-4) and IL-13. Clinical trials conducted for over 10 years have confirmed the efficacy and safety of dupilumab's treatment for atopic dermatitis. Aim: Evaluating the efficacy of dupilumab treatment in patients with moderate and severe atopic dermatitis in real life. Material and methods: We retrospectively evaluated medical records of patients treated with dupilumab for atopic dermatitis at the Department of Dermatology, Venereology and Allergology in Gdansk. Results: Ten patients in total were studied. They received dupilumab with standard dosing. The mean percentage reduction in SCORAD score was 52.16% in 8 weeks. Dupilumab was generally well tolerated and did not cause serious side effects. The most common adverse event was conjunctivitis. Conclusions: Dupilumab is an effective disease-modifying drug for patients with moderate to severe atopic dermatitis. The effects of treatment in real life are consistent with those demonstrated in clinical trials.

Current Insight into the Role of IL-35 and Its Potential Involvement in the Pathogenesis and Therapy of Atopic Dermatitis.

Interleukin 35 (IL-35), a new member of the IL-12 family of heterodimeric cytokines, could induce two different types of regulatory cells including regulatory T and B cells such as IL-35-induced regulatory T cells and IL-10-producing regulatory B cells (IL-10+Bregs), and IL-35-producing regulatory B cells (IL-35+Bregs). These cells appear to play an important role in modulating the immune system in numerous diseases. Several findings suggested that the expression of IL-35 is dysregulated in many autoimmune, inflammatory, and allergic diseases. Due to the functions of IL-35, it seems that this cytokine may act as an efficient therapeutic strategy for numerous conditions including atopic dermatitis (AD). We aimed to provide a comprehensive overview of the role of IL-35 in modulating the immune system. Additionally, we highlight IL-35 as a specific immunological target, discuss its possible involvement in the pathogenesis of AD, and hypothesize that IL-35 may become a novel target for the treatment of AD. However, further studies are required to evaluate this hypothesis.

Combination of FLG mutations and SNPs of IL-17A and IL-19 influence on atopic dermatitis occurrence.

Introduction: Atopic dermatitis (AD) is a heterogeneous inflammatory skin disease. A fresh look on the AD pathophysiology has focused on the skin barrier defect and immune dysfunctions. IL-17A and IL-19 seem to play role in AD pathogenesis. Aim: The aim was to investigate associations of SNPs of IL-17A (rs2275913) and IL-19 (rs22431188) with AD features, course and occurrence. Searching for prognostic panels composed of FLG (2282del4, R501X) mutations with IL-17A and IL-19 polymorphisms. Material and methods: Blood samples were collected from 239 patients with AD and 170 controls. Two SNPs, IL-17A and IL-19 and FLG null mutations were analyzed. PCR and RFLP restriction fragment length polymorphism analysis were used. SCORAD score to establish AD severity, VAS to estimate pruritus. Results: None polymorphisms of studied cytokines caused more frequent AD occurrence compared to controls. We found no associations between IL-17A and IL-19 gene polymorphisms and AD severity (respectively p = 0.954; p = 0.498), IgE level (p = 0.707; p = 0.584), VAS (p = 0.953; p = 0.478), concomitant asthma (p = 0.488, p = 0.764). The G/G genotype in IL-17A (rs2275913) occurrence with coexisting 2282del4 FLG gene mutation increased the AD frequency 9 times (p = 0.0266). Conclusions: The SNPs of IL-17A rs2275913 and IL-19 rs22431188 SNP seem not to have influence on AD course and occurrence while studied alone. The coexistence of GG genotype of IL-17A and 2282del4 FLG mutation may play a role as prognostic AD factor.

Combination of FLG mutations and SNP of TSLP (rs1898671) influence on atopic dermatitis occurrence.

Introduction: Atopic dermatitis (AD) is a common, chronic, relapsing and heterogeneous inflammatory skin disease. Its main causes are genetic predispositions, the epidermal barrier defect, and immune system dysfunction. Thymic stromal lymphopoietin (TSLP) is highly expressed in the epidermis of AD patients and its production is triggered by exposure to environmental factors, allergens, microorganisms and irritants. Aim: To search for the associations between rs1898671 polymorphism in the promotor region of the TSLP gene (SNP) and AD occurrence and course. Material and methods: The frequency of polymorphism occurrence was examined, connection with IgE level, the severity of AD, itching, and concomitant asthma occurrence and combination with FLG gene mutations (2282del4, R501X) in the population of northern Poland. Blood samples were collected from 239 patients with AD and 170 controls. SNP of TSLP and FLG null mutations were analysed. PCR and RFLP restriction fragment length polymorphism analysis was used. Results: No polymorphisms of studied cytokines caused more frequent occurrence of AD compared to controls. We found no associations between TSLP gene polymorphism and AD severity (p = 0.395), IgE level (p = 0.895), VAS (p = 0.918) or concomitant asthma (p = 0.742). Conclusions: The SNP of TSLP rs1898671 does not influence the AD course and occurrence. 2282del4 FLG mutation is a key influencer in AD. However, the coexistence of FLG mutations and SNP of TSLP may play a protective role.

Serum levels and single nucleotide polymorphisms of the interleukin-33 gene in atopic dermatitis.

Introduction: Interleukin 33 (IL-33) is considered significant in the pathogenesis of atopic dermatitis (AD). Aim: To determine the correlation between the serum levels of IL-33 and single nucleotide polymorphisms of its gene in the -9894 T/C (rs1929992) and -11877 C/T (rs10975519) loci and the course of AD. Material and methods: The study group consisted of 191 patients with AD and 168 controls. Results: The TT genotype appeared to be most frequent in patients with severe pruritus (OR = 6.69, 95% CI: 1.24-35.99, p = 0.01). Conclusions: The results of our study are particularly important in the light of personalized medicine and might significantly contribute to further studies in this field.

Molecular Mechanisms of Atopic Dermatitis Pathogenesis.

Atopic dermatitis is a chronic, non-infectious inflammatory dermatosis. Acharacteristic feature is persistent itching of the skin. The chronic, relapsing course of the disease, economic burden, and the whole family's involvement in the treatment process immensely reduce the quality of life of patients and their families. The disease emerges as a social problem by increasing indirect costs, such as visiting a doctor, absenteeism from work and school, and avoiding social interactions. Thepathophysiology of atopic dermatitis is complex and multifactorial. It includes genetic disorders, a defect in the epidermal barrier, an altered immune response, anddisruption of the skin's microbial balance. The numerous complex changes at thegenetic level and innate and adaptive immunity provide the basis for characterizing the various phenotypes and endotypes of atopic dermatitis. Emerging therapies rely on the action of specific molecules involved in the disease's pathogenesis. It may be the starting point for the individualization of atopic dermatitis treatment. This paper will try to present some molecular mechanisms of atopic dermatitis and their clinical implications.

Safety and Danger Considerations of Novel Treatments for Atopic Dermatitis in Context of Primary Cutaneous Lymphomas.

The impact of new and emerging therapies on the microenvironment of primary cutaneous lymphomas (PCLs) has been recently raised in the literature. Concomitantly, novel treatments are already used or registered (dupilumab, upadacitinib) and others seem to be added to the armamentarium against atopic dermatitis. Our aim was to review the literature on interleukins 4, 13, 22, and 31, and JAK/STAT pathways in PCLs to elucidate the safety of using biologics (dupilumab, tralokinumab, fezakinumab, nemolizumab) and small molecule inhibitors (upadacitinib, baricitinib, abrocitinib, ruxolitinib, tofacitinib) in the treatment of atopic dermatitis. We summarized the current state of knowledge on this topic based on the search of the PubMed database and related references published before 21 October 2021. Our analysis suggests that some of the mentioned agents (dupilumab, ruxolitinib) and others may have a direct impact on the progression of cutaneous lymphomas. This issue requires further study and meticulous monitoring of patients receiving these drugs to ensure their safety, especially in light of the FDA warning on tofacitinib. In conclusion, in the case of the rapid progression of atopic dermatitis/eczema, especially in patients older than 40 years old, there is a necessity to perform a biopsy followed by a very careful pathological examination.

Genetic and Epigenetic Aspects of Atopic Dermatitis.

Atopic dermatitis is a heterogeneous disease, in which the pathogenesis is associated with mutations in genes encoding epidermal structural proteins, barrier enzymes, and their inhibitors; the role of genes regulating innate and adaptive immune responses and environmental factors inducing the disease is also noted. Recent studies point to the key role of epigenetic changes in the development of the disease. Epigenetic modifications are mainly mediated by DNA methylation, histone acetylation, and the action of specific non-coding RNAs. It has been documented that the profile of epigenetic changes in patients with atopic dermatitis (AD) differs from that observed in healthy people. This applies to the genes affecting the regulation of immune response and inflammatory processes, e.g., both affecting Th1 bias and promoting Th2 responses and the genes of innate immunity, as well as those encoding the structural proteins of the epidermis. Understanding of the epigenetic alterations is therefore pivotal to both create new molecular classifications of atopic dermatitis and to enable the development of personalized treatment strategies.

Angioedema. Interdisciplinary diagnostic and therapeutic recommendations of the Polish Dermatological Society (PTD) and Polish Society of Allergology (PTA).

Angioedema is a non-inflammatory oedema of the subcutaneous tissue and/or mucosal membranes. It most commonly coexists with urticaria wheals and is considered to be a deep form of urticaria. Less commonly, it occurs in isolation and can take two basic forms: acquired angioedema and hereditary angioedema. Currently, there are 4 defined types of acquired angioedema and 7 types of hereditary angioedema. Treatment of angioedema depends on its form and etiological factors. Especially the genetic form, i.e. hereditary angioedema, is a considerable challenge for medical specialists, particularly dermatologists and allergists.

Biological drugs in the treatment of atopic dermatitis - current recommendations of the Polish Dermatological Society, the Polish Society of Allergology, the Polish Pediatric Society and the Polish Society of Family Medicine.

Atopic dermatitis (AD) is secondary to genetic, immunological and microbiological disorders as well as epidermal barrier defects, which are the main targets of therapy. The disease proceeds with periodic exacerbations. Its development and course are influenced by numerous environmental and individual factors. In recent decades, in industrialized countries, there has been a threefold increase in the incidence of AD. There is also an increasing number of cases resistant to topical treatment. Effective treatment of AD should provide control of clinical symptoms, prevent exacerbations and improve the quality of life of patients. The multifactorial etiopathogenesis and various endotypes and phenotypes of AD justify the tendency to optimize and personalize the therapy. Currently, we recommend the use of dupilumab for the treatment of patients from 12 years of age with moderate and severe atopic dermatitis, who do not respond to topical treatment.

Atopic dermatitis. Interdisciplinary diagnostic and therapeutic recommendations of the Polish Dermatological Society, Polish Society of Allergology, Polish Pediatric Society and Polish Society of Family Medicine. Part I. Prophylaxis, topical treatment and phototherapy.

Atopic dermatitis is a chronic and recurrent inflammatory dermatosis with concomitant intensive pruritus, and is diagnosed both in children and adults. Atopic dermatitis-patients are predisposed to have bacterial, viral and fungal skin infections; they also suffer from an increased risk of developing food allergies (especially, at an infantile age), allergic rhinitis, or bronchial asthma (a so-called atopic march). Currently, an increasing atopic dermatitis incidence constitutes a serious medical problem that regards not only dermatology and allergology, but also paediatrics, and family medicine. The basis for atopic dermatitis treatment and prophylaxis is restoration of epidermal barrier functions by means of tailored emollients. Atopic dermatitis therapies should effectively eliminate clinical symptoms of the disease, prevent exacerbations as well as complications, and improve patients' quality of life.

Atopic dermatitis. Interdisciplinary diagnostic and therapeutic recommendations of the Polish Dermatological Society, Polish Society of Allergology, Polish Pediatric Society and Polish Society of Family Medicine. Part II. Systemic treatment and new therapeutic methods.

The treatment goal in atopic dermatitis is eliminating clinical symptoms of the disease, preventing exacerbations and complications, as well as improving patients' quality of life. In cases of severe atopic dermatitis and lack of response it is recommended to introduce systemic therapy. Patients ofter require multi-specialist consultations, and occasionally hospitalization. It is not recommended to use acupuncture, acupressure, bioresonance, homeopathy, or Chinese herbs in the treatment of atopic dermatitis.

Rural-urban differences in children's musculosceletal injuries in north-eastern Poland

OBJECTIVE: To investigate rural-urban differences in severity of injuries, by means of age, sex and duration of hospitalization of injured children in northeastern Poland. METHODS: The study included children admitted to the Department of Pediatric Orthopaedics and Traumatology in between 2002-2005 (1322 patients) and 2012-2013 (1725 patients) due to injury. We applied the rural-urban division on the base of number of inhabitants (rural ­ below, urban ­ over 25000). We divided injuries into four categories based on severity. Statistical analysis was performed to compare the risk of hospitalization due to different types of injuries among children in different age and sex groups, living in rural and urban areas RESULTS: Children from urban areas have a higher risk of hospitalization compared to their peers living in rural areas due to two least severe categories of injuries. Children from rural areas had much higher risk of hospitalization due to most severe injuries. Results were consistent for both time intervals.. The average duration of hospitalization was significantly longer among rural populations. However, in both rural and urban areas the mean length of stay has been shortened in comparison with the years 2002-2005. The average age of urban patients has been reduced over the years and remained stable among rural population. In both groups boys comprised the majority of patients with all kinds of injuries. CONCLUSIONS: Analysis of the risk of hospitalization among children from rural and urban areas brings constructive conclusions only after applying the division based on severity of injuries. Children living in rural areas and small towns are at a higher risk of suffering severe injuries that pose a risk of permanent disability, and of longer hospitalization because of them, compared to children living in larger cities.