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.

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.

D-dimer concentrations in acute urticaria in children.

INTRODUCTION: Urticaria is a clinical entity presenting as wheals, angioedema, or both simultaneously. Elevated D-dimer levels were reported in the course of chronic spontaneous urticaria. Data regarding D-dimer levels in acute urticaria in children are limited. OBJECTIVES: To assess potential associations between duration of glucocorticosteroid (GCS) therapy and D-dimer concentrations in children with acute urticaria. PATIENTS, MATERIALS, AND METHODS: Hospital records of 106 children (59 females), aged 5.57 ± 4.91 years, hospitalized in 2014-2018 were analyzed retrospectively. The study group consisted of pediatric patients admitted to the hospital due to severe acute urticaria resistant to antihistaminic treatment that was ordered in the ambulatory care (out-patient clinic). Patients were divided into subgroups: no GCS treatment, short-duration treatment (up to 5 days) and long-duration treatment (6 and more days) GCS treatment. Simultaneously, patients received antihistaminic drugs. D-dimer level and other inflammatory factors such as white blood cell (WBC) count, platelet (PLT) count, and C-reactive protein (CRP) in each group were analyzed. RESULTS: The D-dimer level was elevated in 51% of cases. In the subgroup with longer GCS treatment, D-dimer concentration was significantly higher in comparison to patients with a shorter GCS course. There were no differences in the distribution of CRP, PLT, and WBC concentrations between these subgroups. CONCLUSIONS: In the studied group of children, there was a tendency for higher D-dimer levels in patients, who required a longer GCS treatment. This finding is hypothesis-generating and requires further investigation to confirm if D-dimers can be used as a prognostic factor in acute urticaria in children.

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.

Rare COVID-19 vaccine side effects got lost in the shuffle. Primary cutaneous lymphomas following COVID-19 vaccination: a systematic review.

Introduction: COVID-19 vaccines are generally safe and effective; however, they are associated with various vaccine-induced cutaneous side effects. Several reported cases of primary cutaneous lymphomas (CLs) following the COVID-19 vaccination have raised concerns about a possible association. This systematic review aims to investigate and elucidate the potential link between CLs and SARS-CoV-2 vaccines. Methods: We performed a systematic literature search on PubMed, EBSCO and Scopus from January 01, 2019, to March 01, 2023, and analyzed studies based on determined eligibility criteria. The systematic review was performed based on the PRISMA protocol. Results: A total of 12 articles (encompassing 24 patients) were included in this analysis. The majority of CLs were indolent cutaneous T-cell lymphomas (CTCLs) (66,7%; 16/24), with Lymphomatoid papulosis (LyP) being the most common type (33,3%; 8/24). Most patients (79,2%; 19/24) developed lesions after receiving the COVID-19 mRNA-based vaccines, and predominantly after the first immunization dose (54,2%; 13/24). The presented CLs cases exhibited a tendency to exacerbate following subsequent COVID-19 vaccinations. Nevertheless, CLs were characterized by a favorable course, leading to remission in most cases. Conclusion: The available literature suggests an association between the occurrence and exacerbation of CLs with immune stimulation following COVID-19 vaccination. We hypothesize that post-vaccine CLs result from an interplay between cytokines and disrupted signaling pathways triggered by vaccine components, concurrently playing a pivotal role in the pathomechanism of CLs. However, establishing a definitive causal relationship between these events is currently challenging, primarily due to the relatively low rate of reported post-vaccine CLs. Nonetheless, these cases should not be disregarded, and patients with a history of lymphoproliferative disorders require post-COVID-19 vaccination monitoring to control the disease's course.Systematic review registrationwww.researchregistry.com, identifier [1723].

Erythrodermic Presentation of Atopic Dermatitis in a Patient with Secondary Adrenal Insufficiency Caused by Oral Glucocorticosteroid Abuse.

Dear Editor, A 41-year-old man presented to the Department of Dermatology for the first time due to an exacerbation of atopic dermatitis (AD) in the form of erythroderma. The patient had a history of atopic diseases, with being AD active from infancy. On clinical examination, generalized erythematous skin lesions causing acute pruritus and accompanied by severe skin exfoliation and dryness were present. On closer examination, the patient had a collection of signs and symptoms characterizing Cushing syndrome that included a round and full face (''moon face''), supraclavicular fat pads, and proximal muscle atrophy. The patient stated that AD had exacerbated six years earlier. He had received systemic treatment consisting of methotrexate followed by cyclosporine in another medical facility. However, both medications had proven ineffective and caused malaise. Only oral glucocorticosteroids had proven successful. The patient had been satisfied with the quick and observable effects, and, as he stated, he refrained from regular dermatological visits for six years. During that time, he consistently took 4 mg of methylprednisolone twice daily. Laboratory tests showed undetectably low levels of cortisol, triacylglycerols (TAG) at 288 mg/dL, and total cholesterol levels (CHC) of 81 mg/dL. Based on laboratory findings, clinical presentation, and histopathological evaluation of the skin biopsy, the diagnoses were secondary adrenal insufficiency caused by oral glucocorticosteroid abuse and AD in the form of erythroderma. The endocrinologist suggested a progressive reduction of the dose of methylprednisolone, starting at 2 mg twice daily. Total and sudden drug withdrawal was unacceptable, as it could cause an adrenal crisis. Methylprednisolone was eventually discontinued after being administered for 5 months while the blood levels of ACTH, cortisol, ionized sodium, and ionized potassium were monitored every 4 weeks. 25 mg of hydroxycortisol in divided doses was the actual treatment for adrenal insufficiency, with plans to also gradually reduce the dose. Since the commencement of endocrinological treatment, the dose was reduced to 15 mg after 5 months and to 10 mg after 7 months. Following an 8-month period, the patient began taking 10 mg as needed, usually a few times each month. Calcium carbonate in a dose of 1000 mg taken once daily before a meal for 5 months and vitamin D3 protected the patient from osteoporosis, another manifestation of Cushing syndrome. An initial dose of 4000 IU was prescribed. It is vital to emphasize that all dose adjustments in the endocrinological treatment of Cushing syndrome were a direct consequence of laboratory testing that was performed. In terms of erythrodermic AD management, the patient was treated with cyclosporin, which was once again ineffective. The patient was then prepared for the introduction of dupilumab. A 300 mg dose of the medication was subcutaneously administered every 2 weeks for over a year with positive outcomes, with an initial dose of 600 mg. The patient developed gynecomastia at the beginning of the treatment, initially categorized as another manifestation of Cushing syndrome. However, due to its unilateral nature, it was later identified a benign adverse event of dupilumab, as described in the literature (1). Due to a decline in effectiveness, the treatment was recently switched from dupilumab to baricitinib, with positive outcomes. Erythroderma, which the patient presented in our case, is an acute condition characterized by erythema and scaling that involves more than 90% of the skin's surface area (2,3). It can be potentially fatal due to electrolyte imbalance, fluid loss from capillary dilation, and significant heat dissipation (3). According to estimates, erythroderma is relatively rare, affecting approximately 1-2 patients for every 100,000 people per year, with AD comprising 8.7% of all cases of erythroderma (2,4). Despite growing therapeutic possibilities for AD, corticosteroids remain the drug of choice in severe exacerbations, including erythroderma, when we cannot afford to wait for the effects of therapy. Oral glucocorticosteroids can be an effective treatment for acute flares of AD (5). However, there is a lack of evidence for the long-term efficacy and safety of oral glucocorticosteroids in the treatment of AD (5). Reported side-effects include endocrine disturbances, gastric ulcers, cardiovascular disorders (arterial hypertension, atherosclerotic disease), osteoporosis, glaucoma, cataracts, and an increased risk of infections. Corticosteroids also have an undesired action on the skin that can result in steroid acne, skin atrophy, striae, telangiectasias, hypertrichosis, and impaired wound healing. The psychological adverse effects of steroid treatment can be quite severe and include depression and psychosis (6), The therapy should only be applied in the short-term, not exceeding one week, due to the occurrence of the abovementioned side-effects, which presented in as Cushing syndrome our patient (5). However, glucocorticoids are one of the most commonly used drugs in clinical dermatology practice, raising concerns about the risk of their misuse, which can lead to secondary adrenal insufficiency, among other complications (7). When no other treatment options are available, it should be noted that many of the side-effects of oral glucocorticosteroids can be mitigated through close monitoring and the implementation of appropriate preventive measures (7).

The incidence and clinical analysis of non-melanoma skin cancer.

Non-melanoma skin cancers (NMSCs) are the most common malignancies diagnosed in Caucasian populations. Basal cell carcinoma (BCC) is the most frequent skin cancer, followed by squamous cell carcinoma (SCC). Unfortunately, most European cancer registries do not record individual types of NMSC. To evaluate the incidence of primary BCCs and SCCs regarding age, sex, tumour site and tumour subtype to determine trends in epidemiology of both cancers. Retrospective analysis of BCCs and SCCs diagnosed and treated across seven sites in Poland from 1999 to 2019. We recorded 13,913 NMSCs occurring in 10,083 patients. BCC represented 85.2% of all cases. SCC patients were older than BCC patients (77.1 ± 11.3 years vs. 70.1 ± 12.3 years, p < 0.01). The nodular subtype was the most common subtype of BCC, followed by the superficial and infiltrative subtypes. The superficial BCC subtype was more common on photoprotected areas (p < 0.01), whereas the nodular BCC subtype occurred on the face (p < 0.01). The high-risk SCC subtypes were more common on face compared to low-risk SCC subtypes (p < 0.01). BCC and SCC are common malignancies developing at various ages and anatomical sites. These data underline the need for better registration policies regarding NMSC in order to improve prevention and treatment strategies for these tumours.

Clinical and epidemiological analysis of basosquamous carcinoma: results of the multicenter study.

Basosquamous carcinoma (BSC) is a rare non-melanoma skin cancer that shares the characteristic features of both basal and squamous cell carcinomas (BCC, SCC). Our research enables better characterization of BSC in comparison to high-risk subtypes of BCC and SCC. Paper includes a retrospective analysis of BSC cases regarding sex, age, number of tumors and anatomical distribution in comparison to BCC and SCC evaluating the differences and defining the implications. Histologically confirmed carcinomas recorded between 1999 and 2019 were studied. 181 diagnosed BSC cases were identified, making this study the largest cohorts of BSC patients reported worldwide. Most cases were reported on head and neck. Analysis of facial anatomic distribution shows that most commonly affected sites were the nose (43%) and the cheek (25%). The age at excision of metatypical BCC was higher than those of low-risk BCC (P < 0.05), however similar to high-risk BCC (P = 0.20). We revisited that the concept of BSC is the most similar to high-risk subtypes of BCC. Patients with diagnosed BSC have higher risk of second nonmelanoma skin cancer. Therefore, the frequency of follow-up examination should be adjusted to the individual risk of another skin cancer.