Diffuse Cutaneous Mastocytosis: A Current Understanding of a Rare Disease.

Mastocytosis is a heterogeneous disease characterized by the expansion and accumulation of neoplastic mast cells in various tissues. Diffuse cutaneous mastocytosis (DCM) is a rare and most severe form of cutaneous mastocytosis, which typically occurs in childhood. There have been reports of a familial DCM with specific gene mutations, indicating both sporadic and hereditary factors involved in its pathogenesis. DCM is associated with severe MC mediator-related symptoms and an increased risk of anaphylaxis. The diagnosis is based on the appearance of skin lesions, which typically show generalized thickening, erythroderma, blistering dermographism, and a positive Darier's sign. Recognition, particularly in infants, is challenging due to DCMs resemblance to other bullous skin disorders. Therefore, in unclear cases, a skin biopsy is crucial. Treatment focuses on symptom management, mainly including antihistamines and mast cell stabilizers. In extremely severe cases, systemic steroids, tyrosine kinase inhibitors, phototherapy, or omalizumab may be considered. Patients should be equipped with an adrenaline autoinjector. Herein, we conducted a comprehensive review of literature data on DCM since 1962, which could help to better understand both the management and prognosis of DCM, which depends on the severity of skin lesions, intensity of mediator-related symptoms, presence of anaphylaxis, and treatment response.

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.

Mastocytosis and Skin Cancer: The Current State of Knowledge.

Mastocytosis is a heterogeneous group of diseases associated with excessive proliferation and accumulation of mast cells in different organs. Recent studies have demonstrated that patients suffering from mastocytosis face an increased risk of melanoma and non-melanoma skin cancer. The cause of this has not yet been clearly identified. In the literature, the potential influence of several factors has been suggested, including genetic background, the role of cytokines produced by mast cells, iatrogenic and hormonal factors. The article summarizes the current state of knowledge regarding the epidemiology, pathogenesis, diagnosis, and management of skin neoplasia in mastocytosis patients.

Assessment of the Potential Role of Selected Single Nucleotide Polymorphisms (SNPs) of Genes Related to the Functioning of Regulatory T Cells in the Pathogenesis of Psoriasis.

Recent studies have indicated a key role of the impaired suppressive capacity of regulatory T cells (Tregs) in psoriasis (PsO) pathogenesis. However, the genetic background of Treg dysfunctions remains unknown. The aim of this study was to evaluate the association of PsO development with selected single nucleotide polymorphisms (SNPs) of genes in which protein products play a significant role in the regulation of differentiation and function of Tregs. There were three study groups in our research and each consisted of different unrelated patients and controls: 192 PsO patients and 5605 healthy volunteers in the microarray genotyping group, 150 PsO patients and 173 controls in the ARMS-PCR method group, and 6 PsO patients and 6 healthy volunteers in the expression analysis group. The DNA microarrays analysis (283 SNPs of 57 genes) and ARMS-PCR method (8 SNPs in 7 genes) were used to determine the frequency of occurrence of SNPs in selected genes. The mRNA expression of selected genes was determined in skin samples. There were statistically significant differences in the allele frequencies of four SNPs in three genes (TNF, IL12RB2, and IL12B) between early-onset PsO patients and controls. The lowest p-value was observed for rs3093662 (TNF), and the G allele carriers had a 2.73 times higher risk of developing early-onset PsO. Moreover, the study revealed significant differences in the frequency of SNPs and their influence on PsO development between early- and late-onset PsO. Based on the ARMS-PCR method, the association between some polymorphisms of four genes (IL4, IL10, TGFB1, and STAT3) and the risk of developing PsO was noticed. Psoriatic lesions were characterized with a lower mRNA expression of FOXP3, CTLA4, and IL2, and a higher expression of TNF and IL1A in comparison with unaffected skin. In conclusion, the genetic background associated with properly functioning Tregs seems to play a significant role in PsO pathogenesis and could have diagnostic value.

An Observational Study of 147 Psoriasis Patients: Overweightness and Obesity as a Significant Clinical Factors Correlated with Psoriasis.

Background and Objectives: Psoriasis is a common, chronic, and immune-mediated inflammatory skin disease recognized to lead to a wide range of comorbid disorders, mainly obesity. The study aimed to evaluate the problem of overweightness and obesity among psoriasis patients in the context of their prevalence and influence on the disease course. Materials and Methods: The study group encompassed 147 adult patients with plaque psoriasis. Results: The prevalences of overweightness (39.46%) and obesity (37.41%) demonstrated in the study showed the strong predisposition of psoriatic patients for abnormal body mass. The vast majority (77%) of subjects with psoriatic arthritis were overweight or obese. The results of the correlation analysis revealed the significant impacts of overweightness and obesity, as defined by the BMI index, on modifying the severity of psoriasis (as assessed by the PASI with a correlation coefficient of R = 0.23, p = 0.016; and BSA values with a correlation coefficient of R = 0.21, p = 0.023), particularly in contrast to patients with a normal body mass. Conclusions: Overweightness and obesity constitute a major health burden among psoriatic patients, influencing the disease course and severity. Enhanced understanding of the phenomenon may directly translate into improving disease management and overall patient care.

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.

Tattoos Dermatological Complications: Analysis of 53 Cases from Northern Poland.

BACKGROUND: The frequency of tattoos varies from 10% to 30% across the population worldwide. The growing popularity of tattooing increases the number of cutaneous reactions connected with this procedure. As we have not found any previous studies in the literature concerning tattoo complications in Poland and other Eastern European countries, we believe this to be the first study of this kind. OBJECTIVE: The primary objective of this study was to evaluate the clinical spectrum of complications associated with the procedure of permanent tattooing among patients from Northern Poland. METHODS: Medical data of 53 patients who developed tattoo-related cutaneous conditions were analyzed. All of the patients were consulted in the Dermatology, Venereology and Allergology Clinic in Gdansk in the years 2018-2021. Medical history, dermatological assessment, and photographic documentation of skin lesions were performed in each case. Dermoscopic examination was carried out in 16 cases and 20 skin biopsies of the tattoo reactions were performed. RESULTS: Twenty-one patients (40%) presented tattoo ink hypersensitivity reactions, out of which 18 were triggered by the red ink. In 11 cases (21%), contact dermatitis has developed after tattooing, while 9 of the patients (17%) presented tattoo infectious complications, including local bacterial infections, common warts, molluscum contagiosum, and demodicosis. We collected 8 cases (15%) of papulonodular reactions in black tattoos, and in 6 of them, histology showed granuloma formation. In 2 cases (4%), symptoms of anaphylaxis were observed after the tattooing procedure, and in another 2 cases (4%), Koebner phenomenon in the tattoo was diagnosed. Dermoscopy was the clue to the diagnosis in 4 cases. CONCLUSIONS: This is the first report presenting multiple cases of tattoo complications from Eastern Europe. The results of the study are consistent with other researches, showing a similar distribution of tattoo complications and that across the different pigments used, the red ink is most frequently responsible for tattoo reactions. We emphasize the usefulness of dermoscopic examination in the diagnosis of tattoo-related infections and draw the reader's attention to the rare, yet hazardous complications connected with peri-tattooing anaphylaxis.

Interleukin-17 Genes Polymorphisms are Significantly Associated with Cutaneous T-cell Lymphoma Susceptibility.

Tumour microenvironment has an important effect on the progression of cutaneous T-cell lymphomas. Using PCR with sequence-specific primers, this study analysed single-nucleotide polymorphisms in the interleukin-17 genes of 150 patients with cutaneous T-cell lymphoma. GG homozygote rs8193036 A/G of interleukin-17A gene occurred less commonly in the cutaneous T-cell lymphoma group; however, patients with this single-nucleotide polymorphism experience significantly intense pruritus. Conversely, the rs2397084 AG heterozygote of interleukin-17F is more common in the lymphoma population. In addition, there were significant differences in the frequencies of interleukin-17 genotypes when comparing early (Ia to IIa) and advanced stages (IIb, III and IV) of this neoplasms. A similar result has been shown in comparison between Sézary syndrome and mycosis fungoides. The current data may serve as a possible explanation for the increased bacterial infection rates in the course of cutaneous T-cell lymphoma, especially caused by Staphylococcus aureus. In summary, specific single-nucleotide polymorphisms occur with different frequencies between cutaneous T-cell lymphoma and healthy patients. Moreover, genetic predisposition of several interleukin-17 single-nucleotide polymorphisms may be a factor causing impaired immune defence in cutaneous lymphomas.

Treatment of nail psoriasis with pulsed dye laser versus combined pulsed dye and Nd:YAG lasers-An intrapatient left-to-right study.

BACKGROUND AND OBJECTIVES: There are limited treatment options for nail psoriasis. It is important to find new therapies and improve existing ones. The aim of this study was to compare the effectiveness of pulsed dye laser (PDL) versus combined PDL and Nd:YAG lasers in patients with nail psoriasis. METHODS: Fourteen patients (with a total of 126 nails affected by nail psoriasis) were treated with PDL (6 J/cm2, 7 mm, 0.45 milliseconds) on both hands and additionally with Nd:YAG (10 J/cm2 , 6 mm, 15 milliseconds) on the right hand. Three treatment sessions were applied at 4-week intervals and patients were followed up for 6 months after the last session. Disease severity was assessed using the Nail Psoriasis Severity Index, both 8- and 32-point variant. Additionally, Dermatology Life Quality Index was assessed before and after treatment. RESULTS: Overall, there was a statistical difference in 8- and 32-point NAPSI score before and after treatment for both hands. However, there was no statistical difference between the score for the right and left hands based on both scale variants. Some aspects of patients' lives showed improvement due to the treatment. CONCLUSIONS: Both PDL in monotherapy and combined Nd:Yag+PDL lasers are safe and effective in treatment of nail psoriasis, although combined therapy shows no advantage over the use of a single laser.

The Pathogenesis of Giant Condyloma Acuminatum (Buschke-Lowenstein Tumor): An Overview.

Giant condyloma acuminatum, also known as Buschke-Lowenstein tumor (BLT), is a rare disease of the anogenital region. BLT is considered a locally aggressive tumor of benign histological appearance, but with the potential for destructive growth and high recurrence rates. BLT development is strongly associated with infection with low-risk human papillomaviruses (HPVs), mostly HPV-6 and -11. Immunity to HPVs plays a crucial role in the natural control of various HPV-induced lesions. Large condyloma acuminata are frequently reported in patients with primary (e.g., DOCK8 or SPINK5 deficiencies) and secondary (e.g., AIDS, solid organ transplantation) immune defects. Individuals with extensive anogenital warts, including BLT in particular, should therefore be tested for inherited or acquired immunodeficiency. Research into the genetic basis of unexplained cases is warranted. An understanding of the etiology of BLT would lead to improvements in its management. This review focuses on the role of underlying HPV infections, and human genetic and immunological determinants of BLT.

Chemokine Profile in Psoriasis Patients in Correlation with Disease Severity and Pruritus.

Psoriasis (PsO) is a chronic, immune-mediated, inflammatory skin disease associated in most cases with pruritus. Chemokines seem to play a significant role in PsO pathogenesis. The aim of the study was to analyse serum concentrations of CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1ß, CCL5/RANTES, CCL17/TARC, CCL18/PARC, CCL22/MDC and CXCL8/IL-8, and their correlation with PsO severity and pruritus intensity. The study included 60 PsO patients and 40 healthy volunteers. Serum concentrations of six (CCL2/MCP-1, CCL3/MIP-1α, CCL5/RANTES, CCL17/TARC, CCL18/PARC and CCL22/MDC) out of eight analysed chemokines were significantly elevated in PsO patients; however, they did not correlate with disease severity. The serum level of CCL5/RANTES was significantly higher in patients with the psoriasis area and severity index (PASI) ≥ 15 (p = 0.01). The serum concentration of CCL17/TARC correlated positively with pruritus assessed using the visual analogue scale (VAS) (R = 0.47; p = 0.05). The study indicated CCL17/TARC as a potential biomarker of pruritus intensity in PsO patients. Chemokines appear to be involved in the development of PsO systemic inflammation. Further detailed studies on the interactions between chemokines, proinflammatory cytokines and immune system cells in PsO are required to search for new targeted therapies.

The Analysis of a Genome-Wide Association Study (GWAS) of Overweight and Obesity in Psoriasis.

There is evidence that the concomitance of psoriasis and obesity may originate from the interplay between multiple genetic pathways and involve gene−gene interactions. The aim of this study was to compare the genetic background related to obesity among psoriatic patients versus healthy controls by means of a Genome-Wide Association Study (GWAS). A total of 972 psoriatic patients and a total of 5878 healthy donors were enrolled in this study. DNA samples were genotyped for over 500,000 single nucleotide polymorphisms (SNPs) using Infinium CoreExome BeadChips (Illumina, San Diego, CA, USA). Statistical analysis identified eleven signals (p < 1 × 10−5) associated with BMI across the study groups and revealed a varying effect size in each sub-cohort. Seven of the alternative alleles (rs1558902 in the FTO gene, rs696574 in the CALCRL gene, as well as rs10968110, rs4551082, rs4609724, rs9320269, and rs2338833,) are associated with increased BMI among all psoriatic patients and four (rs1556519 in the ITLN2 gene, rs12972098 in the AC003006.7 gene, rs12676670 in the PAG1 gene, and rs1321529) are associated with lower BMI. The results of our study may lead to further insights into the understanding of the pathogenesis of obesity among psoriatic patients.

Hyperhidrosis: disease aetiology, classification and management in the light of modern treatment modalities.

Hyperhidrosis is a disorder of sweat glands characterized by overproduction of sweat, which is inadequate to the thermoregulatory needs of the body system. Owing to the heavy social and economic burden of the disproportionate perspiration, current treatment methods still do not seem to be sufficient enough to reach patients' expectations. Therefore, the researchers continue a robust pursuit of novel therapy modalities such as topical treatment methods, oral agents, minimally-invasive medical approach and surgical techniques. In this review article authors summarise the disease outline with the emphasis on the new era of hyperhidrosis treatment methods.

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.

Wound debridement products and techniques: clinical examples and literature review.

The term "debridement" stands for the removal of necrotic material, scabs, devitalized tissues, dried serous fluid, infected tissues, biofilm, stratified epidermis, pus, hematomas, foreign bodies, bone fragments and other impurities whose presence delays wound healing. It is an inseparable element of wound healing therapy. Properly performed debridement leads to improvement of microcirculation in the wound, reduction in inflammation and lowering of the level of metalloproteinases, stimulation of wound edges and epidermis, reduction in unpleasant odour and reduction in the risk of infection and improvement of the patient's quality of life. There are many debridement techniques approved by the European Wound Management Association. The selection of the most appropriate method depends on many factors such as tissue type, presence of biofilm, depth and location of the wound, underlying cause (venous, arterial), skills of the person performing the debridement and the preferences of the patient him/herself. In our work we present not only a systematic review of most of the debridement techniques used nowadays, but also our clinical cases showing results of those different techniques.

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.

Factors influencing epidemiology of dermatomycoses at Gdansk, Poland and Grodno, Belarus.

Introduction: An increase in numbers of cutaneous fungal infections is being observed around the world. Dermatomycoses occur in every age group and can significantly decrease quality of life. Examining the prevalence and epidemiological trends of cutaneous fungal infections is necessary for developing new effective preventive, diagnostic and therapeutic methods. Many factors can influence the growth and patterns of global spread of the different species of fungi. Aim: To investigate the differences between the prevalence of dermatophytes and cutaneous fungal infections observed at two mycological laboratories and their plausible causes. Material and methods: Mycological examination was performed in 7324 patients in Gdansk, Poland and in 4729 patients in Grodno, Belarus who exhibited clinical signs and symptoms of cutaneous fungal infections. Direct preparations was made in 20% KOH with 40% DMSO. Additionally cultures were prepared on modified Sabouraud dextrose agar. Results: Dermatophytes were cultured in 642 (53.58%) cases in Gdansk. The most common species of dermatophytes were Trichophyton rubrum (306 cases), Trichophyton mentagrophytes var. granulosum (193 cases) and Microsporum canis (127 cases). Yeasts were isolated in 531 (44.40%) cases out of which Candida albicans was the most frequently identified in 323 cases. Similarly, dermatophytes were the most common in 1158 (68.72%) cases in Grodno. Candida were isolated in 527 (31.28%) cases. Analysing the localization of dermatomycoses onychomycosis was observed in majority of the infected patients in Gdansk. In Grodno the most common location of superficial cutaneous infection was tinea corporis In the Gdansk region dermatomycoses were observed in 688 female patients and in 508 male patients. In Grodno the prevalence is inverted with the majority of cases observed in 921 males and 764 females. Conclusions: The prevalence of superficial fungal infections is higher in Grodno, Belarus when compared to Gdansk, Poland. Similarly, dermatophytes were most commonly observed in both Laboratories.

Clinical and histopathological characteristics of primary and recurrent basal cell carcinoma: a retrospective study of the patients from a tertiary clinical centre in the northern Poland.

Introduction: Basal cell carcinoma (BCC) is the most common malignant neoplasm of the skin. Management of patients with recurrent BCC remains a current clinical issue. Data concerning BCC recurrence rates as well as characteristics of this group of patients in the Polish population are scarce. Aim: Identification and analysis of clinical, epidemiological and histopathological factors influencing BCC recurrence. Material and methods: Histopathological diagnoses of BCC patients treated by surgical methods at the Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, between 2013 and 2018, were retrospectively analysed. The analysis included 1097 tumours diagnosed in 802 patients, of which 1061 were primary BCC (pBCC) and 36 - recurring BCC (rBCC). Results: In the analysed cohort, rBCCs constituted 3.3% of cases. 49.8% of pBCCs occurred in women; while in the rBCC group - 47.2%. The most common histopathological type was infiltrative BCC, however, it was significantly more prevalent in rBCCs (36.9% and 52.8%, respectively). The average maximum size of pBCC was 12.3 ±8.8 mm, while of rBCC 18.4 ±15.1 mm (p = 0.036). The most common location of both pBCC and rBCC was the nose (tumours in this localization constituted 23.2% and 25.0%, respectively). Conclusions: In the analysed cohort a relatively low percentage of rBCC was found. Among analysed risk factors, the most important ones were the infiltrative histopathological type of BCC and the non-radical treatment of the primary tumour.

Agminated blue nevi: a case series and updated dermoscopic review.

Blue nevi, usually presenting as solitary, bluish, asymptomatic macules or nodules, are formed by collections of dermal melanocytes that failed to complete their migration from the neural crest to the dermo-epidermal junction. The term "agminated blue nevi" refers to multiple lesions grouped, linear, or arranged in a blashkoid distribution. It is a relatively rare phenomenon with less than 35 cases reported in the literature, but only 14 cases with dermoscopic features. We report another 4 cases along with an updated dermoscopic review.