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.

Pathogenesis of psoriasis in the "omic" era. Part IV. Epidemiology, genetics, immunopathogenesis, clinical manifestation and treatment of psoriatic arthritis.

Psoriatic arthritis (PsA) is a chronic, progressive, inflammatory arthropathy associated with psoriasis as well as a complex pathogenesis. Genetic and environmental factors trigger the development of the immune-mediated auto-inflammatory response in different sites: skin, bone marrow, entheses and synovial tissues. Studies of the last two decades have changed the view of PsA from a mild, non-progressive arthritis to an inflammatory systemic disease with serious health consequences, not only associated with joint dysfunction, but also with an increased risk of cardiovascular disease and socioeconomic consequences with significantly reduced quality of life. The joint damage starts early in the course of the disease, thus early recognition and treatment with modern biological treatments, which may modify the natural history and slow down progression of this debilitating disease, is essential for the patient long-term outcome.

Pathogenesis of psoriasis in the "omic" era. Part III. Metabolic disorders, metabolomics, nutrigenomics in psoriasis.

Psoriasis is a systemic disease that is strictly connected with metabolic disorders (insulin resistance, atherogenic dyslipidemia, arterial hypertension, and cardiovascular diseases). It occurs more often in patients with a more severe course of the disease. Obesity is specially an independent risk factor and it is associated with a worse treatment outcome because of the high inflammatory activity of visceral fatty tissue and the production of inflammatory mediators involved in the development of both psoriasis and metabolic disorders. However, in psoriasis the activation of the Th17/IL-17 and the abnormalities in the Th17/Treg balance axis are observed, but this pathomechanism does not fully explain the frequent occurrence of metabolic disorders. Therefore, there is a need to look for better biomarkers in the diagnosis, prognosis and monitoring of concomitant disorders and therapeutic effects in psoriasis. In addition, the education on the use of a proper diet as a prophylaxis for the development of the above disorders is an important element of holistic care for a patient with psoriasis. Diet may affect gene expression due to epigenetic modification which encompasses interactions of environment, nutrition and diseases. Patients with psoriasis should be advised to adopt proper diet and dietician support.

Pathogenesis of psoriasis in the "omic" era. Part II. Genetic, genomic and epigenetic changes in psoriasis.

Psoriasis is a multifactorial disease in which genetic, environmental and epigenetic factors regulating gene expression play a key role. In the "genomic era", genome-wide association studies together with target genotyping platforms performed in different ethnic populations have found more than 50 genetic susceptible markers associated with the risk of psoriasis which have been identified so far. Up till now, the strongest association with the risk of the disease has been proved for HLA-C*06 gene. The majority of other psoriasis risk SNPs are situated near the genes encoding molecules involved in adaptive and innate immunity, and skin barrier function. Many contemporary studies indicate that the epigenetic changes: histone modification, promoter methylations, long non-coding and micro-RNA hyperexpression are considered as factors contributing to psoriasis pathogenesis as they regulate abnormal keratinocyte differentiation and proliferation, aberrant keratinocytes - inflammatory cells communication, neoangiogenesis and chronic inflammation. The circulating miRNAs detected in the blood may become specific markers in the diagnosis, prognosis and response to the treatment of the disease. The inhibition of expression in selected miRNAs may be a new promising therapy option for patients with psoriasis.

A novel de novo mutation p.Ala428Asp in KRT5 gene as a cause of localized epidermolysis bullosa simplex.

Epidermolysis bullosa is a group of inherited blistering skin diseases resulting in most cases from missense mutations in KRT5 and KRT14 genes encoding the basal epidermal keratins 5 and 14. Here, we present a patient diagnosed with a localized subtype of epidermolysis bullosa simplex caused by a heterozygous mutation p.Ala428Asp in the KRT5 gene, that has not been previously identified. Moreover, a bioinformatic analysis of the novel mutation was performed, showing changes in the interaction network between the proteins. Identification of novel mutations and genotype-phenotype correlations allow to better understanding of underlying pathophysiologic bases and is important for genetic counselling, patients' management, and disease course prediction.

ERAP1 and HLA-C*06 are strongly associated with the risk of psoriasis in the population of northern Poland.

INTRODUCTION: HLA-C*06 is a major psoriasis genetic risk marker. Recent reports have been focused on the role of different polymorphisms within genes involved in the functioning of the epidermal barrier and antigen processing in the pathogenesis of psoriasis. Data on the association between genetic variants of LCE3B_LCE3C, CSTA, ERAP1, ZAP70 and this dermatosis in the population from Eastern Europe are lacking. AIM: To compare the association between known genetic risk markers and psoriasis in a cohort of northern Polish patients with psoriasis and healthy controls. MATERIAL AND METHODS: Based on previous studies' results, five susceptibility loci: HLA-C, LCE3C_LCE3B, ERAP1, ZAP70 and CSTA were selected for genotyping in 148 patients with chronic plaque psoriasis and 146 healthy controls. Each patient with this disease was clinically assessed with the Psoriasis Area and Severity Index. RESULTS: The study population showed a significant association of psoriasis and a single nucleotide polymorphism in the ERAP1 - rs26653 (p = 3.11 × 10-5) and HLA-C*06 allele (p = 1.02 × 10-11) when compared with the control group. The presence of HLA-C*06 or rs26653 G allele significantly increased the risk of psoriasis by 2.4 times or twice, respectively. Carrying rs26653 C allele considerably decreased the risk of psoriasis by 1.5 times. CONCLUSIONS: In the context of pathogenesis of psoriasis, our findings might give the evidence on disturbances in the proteolytic processing of N-terminal fragments of antigens presented via major histocompatibility complex class I to T cells.

[Cutaneous sarcoidosis - a great imitator]. / Sarkoidoza skóry ­ wielki nasladowca.

Skin manifestation occurs in approximately 25% of patients with sarcoidosis and is often the first symptom of the disease. The availability of skin biopsy material is helpful in establishing the early diagnosis. Cutaneous sarcoidosis is characterized by clinical polymorphism and therefore its diagnosis may cause dilemma. The systemic sarcoidosis should be excluded in every patient with cutaneous sarcoidosis, because systemic involvement has a significant impact on course, treatment and prognosis of the disease.

Evaluation of Psoriasis Genetic Risk Based on Five Susceptibility Markers in a Population from Northern Poland.

Psoriasis genetic background depends on polygenic and multifactorial mode of inheritance. As in other complex disorders, the estimation of the disease risk based on individual genetic variants is impossible. For this reason, recent investigations have been focused on combinations of known psoriasis susceptibility markers in order to improve the disease risk evaluation. Our aim was to compare psoriasis genetic risk score (GRS) for five susceptibility loci involved in the immunological response (HLA-C, ERAP1, ZAP70) and in the skin barrier function (LCE3, CSTA) between patients with chronic plaque psoriasis (n = 148) and the control group (n = 146). A significantly higher number of predisposing alleles was observed in patients with psoriasis in comparison to healthy individuals (6.1 vs. 5.2, respectively; P = 8.8×10-7). The statistical significance was even more profound when GRS weighted by logarithm odds ratios was evaluated (P = 9.9×10-14). Our results demonstrate the developed panel of five susceptibility loci to be more efficient in predicting psoriasis risk in the Polish population and to possess higher sensitivity and specificity for the disease than any of the markers analyzed separately, including the most informative HLA-C*06 allele.

Genetic background of skin barrier dysfunction in the pathogenesis of psoriasis vulgaris.

Psoriasis is a common inflammatory skin disease. It is known to be a complex condition with multifactorial mode of inheritance, however the associations between particular pathogenic pathways remain unclear. A novel report on the pathogenesis of psoriasis has recently included the genetic determination of the skin barrier dysfunction. In this paper, we focus on specific genetic variants associated with formation of the epidermal barrier and their role in the complex pathogenesis of the disease.

Malignant acanthosis nigricans, florid cutaneous papillomatosis and tripe palms syndrome associated with gastric adenocarcinoma.

Malignant acanthosis nigricans is a rare paraneoplastic skin syndrome mostly associated with gastric adenocarcinoma. Florid cutaneous papillomatosis and tripe palms syndrome are considered to be abortive clinical variants of acanthosis nigricans. Clinical manifestations include pruritic, hyperkeratotic and hyperpigmented plaques with a subsequent formation of velvety papillomas in the involved areas. This case report describes an unusual case of the patient diagnosed with a combination of malignant acanthosis nigricans, florid cutaneous papillomatosis and tripe palms syndrome associated with gastric adenocarcinoma.