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.

Etiopathogenesis and Emerging Methods for Treatment of Vitiligo.

Vitiligo is an acquired chronic depigmenting disorder of skin. It is mostly asymptomatic and characterized by amelanotic macules and patches that affects 0.5% to 2% of the world's population. The etiology of vitiligo has not been clearly elucidated and multiple theories have been proposed regarding the causes of the disorder. Among the most prevalent theories, the genetic predisposition, oxidative stress theory, promotion of cellular stress and pathologic influence of lymphocytes T have been highlighted. As a result of increases in in-depth knowledge concerning the pathogenetic processes in vitiligo, we review the most recent information concerning its etiopathogenesis and treatment methods including topical and oral Janus kinase inhibitors, prostaglandins and their analogues, namely afamelanotide, Wnt/ß-catenin-signaling agonists and cell-based therapies. Topical ruxolitinib has been registered for vitiligo treatment, whereas other agents as oral ritlecitinib, afamelanotide and latanoprost have been studied in ongoing clinical trials. New highly effective therapeutic strategies may be developed thanks to molecular and genetic studies.

Dermatoscopy of nodular/plaque-type primary cutaneous T- and B-cell lymphomas: A retrospective comparative study with pseudolymphomas and tumoral/inflammatory mimickers by the International Dermoscopy Society.

BACKGROUND: Limited data on dermatoscopy of nodular/plaque-type T-/B-cell primary cutaneous lymphomas (PCLs) is available. OBJECTIVE: To describe dermatoscopic features of nodular/plaque-type PCLs, comparing them with those of clinical mimickers (pseudolymphomas, tumors, and inflammatory lesions) and investigating possible differences according to histologic subtypes. METHODS: Participants were invited to join this retrospective, multicenter case-control study by submitting histologically/immunohistochemically confirmed instances of nodular/plaque-type PCLs and controls. Standardized assessments of the dermatoscopic images and comparative analyses were performed. RESULTS: A total of 261 lesions were included (121 PCLs and 140 controls). Orange structureless areas were the strongest PCL dermatoscopic predictor on multivariate analysis compared with tumors and noninfiltrative inflammatory dermatoses. On the other hand, a positive association was found between PCLs and either unfocused linear vessels with branches or focal white structureless areas compared with infiltrative inflammatory dermatoses, whereas white lines were predictive of PCLs over pseudolymphomas. Differences in the vascular pattern were also seen between B- and T-cell PCLs and among B-cell PCL subtypes. LIMITATIONS: Retrospective design and the lack of a dermatoscopic-pathologic correlation analysis. CONCLUSION: Nodular/plaque-type PCLs display dermatoscopic clues, which may partially vary according to histologic subtype and whose diagnostic relevance depends on the considered clinical differential diagnoses.

Interleukin-31 is overexpressed in skin and serum in cutaneous T-cell lymphomas but does not correlate to pruritus.

Introduction: Cutaneous T-cell lymphomas (CTCL) are malignant lymphoproliferative disorders accompanied by persistent pruritus. Pruritogenic role of interleukin-31 (IL-31) has been studied extensively and was proven in atopic dermatitis (AD), while its role in CTCL is still rather vague. Aim: To investigate IL-31 serum level along with IL-31, IL-31 receptor α (IL-31RA) and oncostatin M receptor ß (OSMR) skin expression in CTCL and compare it to controls: AD and healthy volunteers. Material and methods: The level of IL-31 in serum was measured using ELISA, while IL-31 and receptors' expression in the skin were measured using immunohistochemistry and correlated with the stage of disease and pruritus severity. Results: Expression of IL-31 and IL-31 receptor in serum and skin were significantly higher in CTCL and AD in comparison to healthy controls. No significant correlation between the IL-31 serum level and pruritus severity in CTCL patients was found. There was also no correlation between IL-31/IL-31RA/OSMR expression in the skin and CTCL pruritus, while IL-31 and IL-31RA in CTCL skin negatively correlated with the stage of disease. Conclusions: Our data indicate that IL-31 does not play a crucial role in pruritus in CTCL but it is rather involved in the pathogenesis of the disease. It seems that IL-31 plays an essential role in the pruritus pathomechanism that is unique to AD.

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.

Safety and danger of biologic treatments in psoriasis in context of cutaneous T-cell lymphoma (CTCL).

Microenvironment has a significant impact on the pathogenesis of cutaneous T-cell lymphoma (CTCL), especially in the context of new emerging biologic therapies. Our aim was to review the literature on interleukins 12, 17, 23 and tumour necrosis factor-α in mycosis fungoides in order to clarify the safety of using biologics in the treatment of psoriasis. Our analysis suggests that these drugs may have an impact on the progression of CTCL. Concluding, in case of uncertain psoriatic lesions, a biopsy followed by pathologic examination should exclude the possibility of co-existence of a primary cutaneous lymphoma before administration of therapies affecting cytokine profiles.

Translation, cross-cultural adaptation and validation of the vitiligo-specific health-related quality of life instrument (VitiQoL) into Polish.

INTRODUCTION: Vitiligo is an acquired chronic depigmenting disorder of the skin, predominantly asymptomatic. Although vitiligo does not cause direct physical impairment, it is commonly believed that it can produce an important psychosocial burden. AIM: To translate, cross-culturally adapt and validate the vitiligo-specific health-related quality of life instrument (VitiQoL) into Polish. MATERIAL AND METHODS: The study was conducted online on 97 patients with vitiligo from our private outpatient departments in Gdynia and Gdansk, Poland from May 2018 to December 2019. RESULTS: There was a significant correlation between VitiQoL and DLQI (r = 0.90, p < 0.001) and also between VitiQoL-PL and subjects' assessment of the severity of their disease (r = 0.94, p < 0.001). We also found a good correlation between the total DLQI and subjects' assessment of the severity of their disease (r = 0.87, p < 0.001). CONCLUSIONS: The physicians treating this disease still do not have a specific instrument for assessing patients' QoL in Poland. They have to administer other non-vitiligo specific questionnaires to do so. A Polish version of a specific index for estimating quality of life of patients with vitiligo was validated and implemented through an online survey.

The incidences of other primary cancers in patients with mycosis fungoides and Sézary syndrome.

INTRODUCTION: Cutaneous T-cell lymphomas (CTCLs) are a diverse group of non-Hodgkin's lymphomas with malignant T lymphocytes infiltrating the skin. Mycosis fungoides (MF) and Sézary syndrome (SS) belong to the group of CTCLs, among others. In previous studies it was suggested that primary cancers more often occur in patients with cutaneous lymphoma. AIM: To analyse the incidence of other malignancies in CTCL patients. MATERIAL AND METHODS: The evaluation of the coexistence of primary malignant neoplasms in CTCL patients was conducted by analysis of the patients' database, with diagnosis of mycosis fungoides and Sézary syndrome, treated in the Dermatological Department of the Medical University of Gdansk between 2010 and 2018. RESULTS: Among CTCL patients, 177 were diagnosed with MF/SS (stage MFIA 37.61%, MFIB 30.77%, MFIIA 0.85%, MFIIB 11.11%, MFIII 8.55% MFIV 4.27%; SS 6.84%). The group was characterized by a male-to-female ratio of 1.21 : 1. 16.94% of MF/SS patients had one co-existing cancer, while 1.13% of patients had 2 co-existing cancers; the most common were basal cell carcinoma, lymphomatoid papulosis, lung cancer, and B-cell lymphoma. The obtained data highlight that MF/SS is associated with increased risk of cancer. CONCLUSIONS: Our study suggests that special attention should be paid to careful examination of CTCL patients - what force to perform solid clinical examination, the X-ray chest examination, abdomen USG, mammography, and others, even in early stages of MF/SS. Clinicians should be aware of the coexistence of other neoplasms such as lung, skin, and breast cancer.

Significance of interleukin-31 (IL-31) gene polymorphisms and IL-31 serum level in psoriasis in correlation with pruritus.

INTRODUCTION: Interleukin-31 (IL-31) impact on the development and clinical presentation of psoriasis as well as pruritus has not been widely investigated so far. AIM: To analyse IL-31 -1066G/A and -2057G/A promoter gene polymorphisms as well as serum IL-31 level and their correlation with severity of psoriasis and pruritus in the population of northern Poland. MATERIAL AND METHODS: The study included 300 psoriasis patients and 186 healthy volunteers. The polymorphisms were analysed using amplified refractory mutation system - polymerase chain reaction (ARMS-PCR) method. Serum levels of IL-31 were measured using the enzyme-linked immunosorbent assay (ELISA) test. RESULTS: The -1066 AA genotype of the IL-31 gene was statistically more frequent in patients and it increased the risk of psoriasis (OR = 1.80; p = 0.04). The GG genotype as well as G allele of the IL-31 -2057 gene polymorphism were rarely observed in psoriasis and were associated with a decreased risk of the disease (OR = 0.6, p = 0.007 and OR = 0.7, p = 0.01, respectively). Serum levels of IL-31 were significantly elevated in psoriasis patients (p < 0.000001), however, they did not correlate with the studied polymorphic variants of the IL-31 gene, severity of psoriasis, disease onset, presence of psoriatic arthritis and pruritus intensity. CONCLUSIONS: Distinct IL-31 promoter gene polymorphisms may be involved in psoriasis development. It seems that serum concentration of IL-31 may not be a reliable marker of psoriatic pruritus.

Efficacy, quality of life, and safety of methotrexate versus interferon in head-to-head treatment in advanced stages of mycosis fungoides and Sezary syndrome. Prospective trial (NCT02323659).

Introduction: ESMO guidelines recommend interferon (IFN) and methotrexate (MTX) as first-line systemic therapies in mycosis fungoides (MF) and Sezary syndrome (SS). Aim: A prospective, head-to-head trial comparing the efficacy and safety of INF-α and MTX as first-line treatment in MF/SS patients. Material and methods: Forty-three patients were enrolled in the trial. The response to treatment and side effects were assessed. Study variables included mSWAT, DLQI, and VAS scores. Results: The response rate in stage IV including SS was significantly higher in the IFN-α group than in the MTX group (100% vs. 40%; p = 0.03, respectively). No significant differences were found in response rate in stage IIB and III between treatment groups. Patients treated with IFN-α had significantly shorter time to achieve response (TTR). Significantly fewer in the IFN-α group experienced adverse events (AE) in comparison to patients treated with MTX (81% vs. 45%; p = 0.02). There was no statistically significant difference between both groups in terms of time to progression (TTP), progression-free survival (PFS), time on treatment (ToT), and time to next treatment (TTNT). The improvement in quality of life and reduction of pruritus was comparable in both treatment groups. Conclusions: The obtained data suggest that the efficacy of IFN-α as first-line treatment in advanced stage (IV) MF and SS is significantly better than MTX. IFN-α presented significantly better safety and tolerability and shorter TTR than MTX. However, the results should be interpreted with caution due to scarce study groups.

The ambiguous pruritogenic role of interleukin-31 in cutaneous T-cell lymphomas in comparison to atopic dermatitis: a review.

Cutaneous T-cell lymphomas (CTCLs) comprise a group of chronic heterogeneous diseases of unknown pathogenesis, characterized by non-specific skin lesions such as patches, plaques and tumours. CTCL is accompanied by persistent pruritus poorly responding to antihistamines and therefore significantly reducing quality of life in patients with lymphomas. According to research data, interleukin-31 (IL-31) contributes to initiation and maintenance of the inflammatory process of the skin and pruritus in inflammatory dermatoses such as atopic dermatitis (AD), which is well established. The studies of a similar role of IL-31 in CTCLs are less homogenous. Due to contradictory reports concerning IL-31 and CTCL we have analysed available literature to summarize its role, focusing on CTCL and AD.

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.

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.

Efficacy of suction blister epidermal grafting with concomitant phototherapy in vitiligo treatment.

INTRODUCTION: There are many surgical methods for vitiligo treatment that have been used for over 30 years. Suction blister epidermal grafting (SBEG) is considered one of the simplest and most effective of them. AIM: To determine how effective suction blister grafts with concomitant phototherapy are in vitiligo treatment. MATERIAL AND METHODS: The study was conducted on 10 patients with vitiligo that was resistant to previous treatment including phototherapy in monotherapy. Involvement of affected sites was different for every patient. We used cryotherapy for blistering at the recipient site and an automatic suction device for blistering at the donor site. The blister was separated from the donor site and fixed with dressing to the recipient site. After removing the final dressing (about 7 days after SBEG) patients started phototherapy (6 patients had UVB 311 nm and 4 had PUVA). All patients treated with UVB 311 nm were qualified for treatment in our clinic and the method was chosen according to expert recommendations from the European Dermatology Forum (EDF) Guidelines for Vitiligo where narrowband (NB) UVB is the phototherapy of choice. Three patients who had PUVA therapy were treated with this method in other clinical centers and sent to us only to undergo SBEG. One patient had previously received UVB 311 nm for 3 months, which showed no effects. Repigmentation of lesions was evaluated at 3 and 6 months after the surgical procedure. RESULTS: Ten patients (9 females with a mean age of 36.88 years and 1 man aged 39 years) were enrolled in the study. Nine patients showed progressive repigmentation at 3 and 6 months follow-up with a rate varying from 13 to 76% (mean: 44.5%) and 35 to 100% (mean: 67.5%). One patient showed 5% depigmentation at a visit after 6 months in comparison to the follow-up visit 3 months after SBEG. CONCLUSIONS: With this technique, patients who did not respond to the usual treatments showed very good repigmentation over a 6-month follow-up. There were no side effects such as scarring.

Presence of Chlamydophila pneumoniae DNA in blood cells is a frequent event in patients with the late stage of primary cutaneous lymphomas and with atopic dermatitis.

INTRODUCTION: Microbial infection and associated super antigens have been implicated in the pathogenesis of cutaneous T-cell lymphoma (CTCL), and many patients die from complicating bacterial infections. It has been postulated that Chlamydophila pneumoniae (C. pneumoniae) infection may be involved in the pathogenesis of Mycosis fungoides (MF) but published data are limited and controversial. AIM: To analyze the frequency of (C. pneumoniae) DNA presence in blood samples of lymphoma cases. MATERIAL AND METHODS: Using Q-PCR method we analyzed the presence of DNA in the blood samples obtained from 57 patients with CTCL (55 - mycosis fungoides (MF)/Sézary syndrome (SS), one primary cutaneous anaplastic large cell lymphoma (CD30+) and one NKT cell lymphoma) and 3 patients with cutaneous B-cell lymphomas, and 120 individuals from control groups (40 patients with psoriasis, 40 patients with atopic dermatitis and 40 healthy controls). RESULTS: Chlamydophila pneumoniae DNA was identified in 13 of 55 cases in the MF/SS group (23.6%), in 1 patient with CD30+ large cell lymphoma and in 1 of 3 patients with B-cell lymphoma. The presence of C. pneumoniae was confirmed in 1 of 40 psoriatic patients (2.5%), in 5 of 40 patients with atopic dermatitis (12.5%) and in none of 40 healthy individuals. Presence of C. pneumoniae DNA in MF patients was strongly associated with disease progression; rs = 0.756; p = 0.0123 for groups IA → IVB, and was noted more frequently in advanced (III + IV) stages than in early (I-II) stages (p = 0.0139). There are no differences in the mean age of MF/SS patients with and without infection. CONCLUSIONS: The presence of C. pneumoniae DNA in the blood cells is a frequent event in late stages of MF/SS and may be explained by Th2 shift and suppression of the immune system during the course of the disease.

Clinicopathologic retrospective analysis of blastic plasmacytoid dendritic cell neoplasms.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is one of the aggressive rare hematopoietic malignancies with predilection to the skin, primarily found in adults. The precise incidence of BPDCN is difficult to estimate due to constantly changing nomenclature and lack of precise defining criteria prior to the 2008 WHO classification system. There are not many cases described in the literature, what makes the diagnostic process challenging. Skin lesions such as erythematous infiltrates and nodules are usually the first manifestation of the disease. Therefore, in doubtful diagnostic cases, dermatologists should perform histopathological and immunohistochemistry examinations along with hematological and oncological cooperation, as early diagnosis and appropriate treatment is essential for improvement of the disease course. This analysis, despite the small number of patients may provide useful information on the clinical and histopathological features of this rare malignancy.

Interleukin-31 Polymorphisms and Serum IL-31 Level in Patients with Mastocytosis: Correlation with Clinical Presen-tation and Pruritus.

Data on interleukin-31 (IL-31) involvement in the patho-genesis of mastocytosis, and its impact on pruritus development in the disease, are limited. The aim of this study was to analyse distinct IL-31 gene polymorphisms in 127 patients (age 0.5-76 years) with mastocytosis and their correlation with clinical presentation, pruritus and serum IL-31 levels. In patients with mastocytosis, the frequency of IL-31 IVS2+12AA genotype and IVS2+12A allele was higher than in control subjects and they were linked to an increased risk of development of mastocytosis. In adult patients, but not in children, -2057AA genotype was also associated with an increased risk of occurrence of mastocytosis. Pruritus affected 83.3% of 78 adult patients with mastocytosis, and a positive correlation between serum IL-31 levels and pruritus was found in these patients. In conclusion, distinct polymorphic variants of the IL-31 gene may be involved in the patho-genesis of mastocytosis, and IL-31 may be involved in the induction of pruritus in patients with mastocytosis.

The role of regulatory T cells and genes involved in their differentiation in pathogenesis of selected inflammatory and neoplastic skin diseases. Part I: Treg properties and functions.

Regulatory T cells (Treg) can be divided into two types: the natural cells (tTreg), which arise in the thymus, and the induced cells (iTreg), which are produced in peripheral tissues during immune response. The most recently published studies indicate that the supervisory functions of these cells are weakened in the pathogenesis of autoimmune and neoplastic diseases of the skin. This may be a result of the domination of other immune cells in the skin, such as Th1/Th17/Th22 and Tc1 type in psoriasis and Th2 in atopic dermatitis. The excessive activity of Treg cells can lead to immunosuppression and decrease in the number of Th1 cells, which promote the development and progression of skin cancers. In the case of cutaneous T-cell lymphomas, there are suggestions that tumor progression is associated with the acquisition of the suppressor phenotype of malignant cells. There is genetic background of Treg dysfunction in skin disorders. This article describes the types and functions of Treg cells.