The Pathophysiology and Treatment of Pyoderma Gangrenosum-Current Options and New Perspectives.

Pyoderma gangrenosum (PG) is an uncommon inflammatory dermatological disorder characterized by painful ulcers that quickly spread peripherally. The pathophysiology of PG is not fully understood; however, it is most commonly considered a disease in the spectrum of neutrophilic dermatoses. The treatment of PG remains challenging due to the lack of generally accepted therapeutic guidelines. Existing therapeutic methods focus on limiting inflammation through the use of immunosuppressive and immunomodulatory therapies. Recently, several reports have indicated the successful use of biologic drugs and small molecules administered for coexisting diseases, resulting in ulcer healing. In this review, we summarize the discoveries regarding the pathophysiology of PG and present treatment options to raise awareness and improve the management of this rare entity.

Chitinase-3-like Protein 1 (YKL-40): A New Biomarker of Inflammation in Pyoderma Gangrenosum.

Pyoderma gangrenosum (PG) is a rare, neutrophilic dermatosis with unclear aetiopathology, considered as an autoinflammatory disease, associated with other immune-mediated disorders. Chitinase-3-like protein 1 (YKL-40) is an inflammatory biomarker secreted by a wide variety of cells, including neutrophils. To evaluate YKL-40 serum level in relation to clinicopathological data, 48 patients with PG and 40 healthy controls were enrolled in the study. Skin lesions were measured to calculate the affected area. Inflammatory parameters (C-reactive protein, white blood cell count with neutrophils) were determined from blood samples. YKL-40 and IL-6 levels were measured in serum by enzyme-linked immunosorbent assay. YKL-40 serum level was significantly higher in patients with PG than in controls (58.4 vs 36.4 ng/ml, respectively; p < 0.00001). The positive correlation between YKL-40 level and IL-6 level was observed (r=0.48, p = 0.0006) along with a trend towards significance of relationship between YKL-40 level and C-reactive protein (r=0.28, p = 0.052). YKL-40 can be considered a valuable biomarker of inflammation in PG.

Emerging biomarker in carcinogenesis. Focus on Nestin.

Nestin is a protein belonging to class VI intermediate filaments, which is involved in organogenesis, cellular metabolism and cytoskeletal organisation. Originally found to be expressed in neuroepithelial stem cells, nestin is also expressed in other tissues. It plays an important role in the carcinogenesis and angiogenesis. Its increased expression in melanoma is associated with an aggressive course of the disease and poor prognosis. Research findings for non-melanocytic skin neoplasms are inconclusive. The aim of this paper was to systematize knowledge on the role of nestin in cancerogenesis. The authors focused in particular on the expression of nestin in skin malignancies, as well as on the potential role of nestin in the pathogenesis, prognosis and treatment of cutaneous neoplasms.

Photoprotection among young children: assessment of mothers' awareness and health behaviours.

Introduction: Due to the increasing incidence of skin cancer in the last decades a wide promotion of proper sun protection is needed. Mothers and their children commonly spending time outdoors are particularly vulnerable to the harmful effects of sunlight. Aim: To assess health awareness and behaviours connected to sun protection in the group of mothers of children under 6 years of age. Material and methods: An online survey containing 23 questions (19 closed and 4 open) was carried out between July and August 2019. One hundred and seven women (mean age: 30.7 ±4.3years) participated in the study. The mean age of children was 1.9 ±1.6years (range: 0-6 years). Results: One hundred and five (98.1%) mothers declared using sunscreen. Of them, 36 women used sunscreen only in summer, while 14 women applied sunscreen all year. Mothers of younger children used sunscreen all year round significantly more often (p = 0.041) compared to mothers of older children. Mothers of children under the age of 1 used sunscreen when staying in the shade more often (p = 0.025) than mothers of older children. Only 14 (13.3%) women declared applying sunscreen on their children during cloudy weather. Conclusions: A good photoprotection awareness of mothers, especially with respect to the youngest children was observed. However, a need for further education regarding certain photoprotection aspects (proper application and damaging effect of UVA) is necessary.

Prevalence and quality of life of facial acne: a cross-sectional study in high school students in Poland.

Introduction: Acne is a frequent chronic inflammatory disease, which affects most commonly adolescents. It might have a negative effect on patients' well-being. Aim: To appraise the prevalence of facial acne among adolescents and to assess how acne of different clinical severity influences quality of life in this age group. Material and method: This cross-sectional study was conducted on a representative sample of individuals aged 15-19 years in high schools in Poland. A total of 730 students were included in the final analysis. Standardized photographs according to the Investigator's Global Assessment (IGA) were used for self-assessment of both the presence and severity of facial acne. The Dermatology Life Quality Index (DLQI) was employed to evaluate subjects' quality of life (QoL) impairment. Results: Facial acne was found in 547 (74.9%) respondents with no significant difference in acne prevalence among females (75.1%) and males (74.6%). The vast majority of acne individuals (90.9%) suffered from minimal and mild acne, moderate acne was reported by 7.3% and severe one by 1.8% of acne students. Acne had a small effect on QoL (DLQI mean score of 2.8 ±3.6 points); females had significantly more decreased QoL than males (3.17 ±3.74 and 1.76 ±2.69 points, respectively). QoL impairment positively correlated with the clinical severity of facial acne. Conclusions: Facial acne is a common health problem in adolescents. Although it is not very severe in the majority of subjects it significantly decreases their QoL. Therefore, acne should be treated as a serious skin condition requiring a holistic approach to the patients.

Sun protection among university students in Poland: a survey of awareness and attitudes.

AIM: The aim of the study was to evaluate students' awareness and attitudes related to skin protection against UVR and to check the hypothesis whether medical students differ from other faculty students in terms of health-promoting behaviour in photoprotection. MATERIAL AND METHODS: Internet-based survey containing 24 questions about students' knowledge and attitudes associated with sun exposure and photoprotection was carried out between March and May 2019. Two hundred and forty-three questionnaires were subject to statistical analysis. RESULTS: Out of 243, 149 (60.9%) respondents studied medicine and 95 (39.1%) were students of other faculties. 235 (96.7%) declared using sunscreen. 46 (18.9%) students applied it all year round and 116 (47.7%) only in the summer. Medical students chose more willingly products with SPF > 30 (p = 0.002). A hundred and fifty-nine (65.4%) students used sunscreen once when outdoors and 76 (31.3%) applied products more than once. Additional sun protective methods included wearing sunglasses (82.7%), hats or caps (62.1%) and avoiding sunlight around noon (46.5%). Students of the medical faculty avoided sun exposure statistically more frequently (p = 0.042) than students of other faculties. 28.4% had dermoscopy performed in the past. Medical students underwent dermoscopy examination statistically more frequently (p = 0.001) than students of other faculties. CONCLUSIONS: Medical students, probably due to their education, show increased pro-health attitudes associated with photoprotection. This indicates that they may be involved in creation and promotion of education activities to general public.

Comparison of serum concentrations of interleukins 10, 12, 17 and 35 between patients with alopecia areata and controls.

INTRODUCTION: Alopecia areata (AA) is one of the most common causes of non-scarring hair loss in adults and children with unknown etiopathogenesis, however immunological factors play an important role. AIM: To evaluate the concentration of interleukin (IL) 10 (IL-10), IL-12, IL-17 and IL-35 in the blood serum of patients with AA. MATERIAL AND METHODS: AA study group consisted of 118 patients. The control group consisted of 54 healthy individuals. The severity of the disease was assessed by SALT score. In the study group, the percentage of hair loss averaged 49.6% ±36.3%. The concentration of IL-10, IL-12, IL-17 and IL-35 in the serum was assessed by the enzyme-linked immunosorbent assays (ELISA). RESULTS: In patients with AA, the level of IL-12 and IL-17 was significantly higher than in the control group (p > 0.05). The level of IL-10 in patients was slightly higher, whereas the level of IL-35 was slightly lower, compared to the control group, but those differences were not statistically significant. Furthermore, in patients with more severe disease the IL-12 level was significantly higher as compared to patients with the less severe AA (p < 0.05). CONCLUSIONS: The etiopathogenesis of AA is complex, however Th1 and Th17 lymphocytes and their increased activity are undoubtedly significant contributors in this process. Disorders of immunological processes in AA require further research in order to understand the underlying pathomechanisms of the disease and to provide potential therapeutic strategies.

Epidemiology of dermatophytoses in paediatric population in Southwestern Poland, 2011-2016.

INTRODUCTION: Dermatophytoses are the most common superficial fungal infections in paediatric population. Its pathogen pattern has changed over years. AIM: To analyse the spectrum of dermatophytoses in children living in Southwestern Poland, in the years 2011-2016. MATERIAL AND METHODS: A total of 1705 patients were diagnosed with fungal skin infection in the Mycological Laboratory, Dermatology Department of the Wroclaw Medical University. Of them, 163 were under 18 years of age. RESULTS: In 105 cases, dermatophytoses were detected. The collected specimens were examined using direct microscopy examination, staining, culture on specific media and PCR technique. The most common dermatophytes were Trichophyton rubrum and Trichophyton tonsurans (31.4% each), followed in the descending order by Trichophyton mentagrophytes (21.9%), Microsporum canis (13.3%) and Epidermophyton floccosum (1.9%). The most commonly affected body sites were glabrous skin of the trunk and extremities (41.7%), followed by face (22.2%), scalp (15.7%) and toe nails (14.8%). CONCLUSIONS: This study revealed the most common types of dermatophytoses and their pathogens in children in Southwestern Poland. In comparison to earlier data obtained from this region, new epidemiological trends have been revealed. We observed the shift towards anthropophilic dermatophyte infections and an increasing number of onychomycosis in children. Because of climatic variations, migration, and changing lifestyle practices, further studies on dermatophytoses are necessary to improve our knowledge on the epidemiology of fungal infections.

Impact of Childhood Psoriasis on Caregivers' Quality of Life, Measured with Family Dermatology Life Quality Index.

Psoriasis is a chronic skin disease, that often develops below the age of 18. In an integrated approach to childhood psoriasis, the impact of psoriasis on family members merits consideration. In this study, the impact of childhood psoriasis on caregivers (61 mothers and 4 fathers) of 65 children (age range 5-17.5 years) was measured using Family Dermatology Life Quality Index (FDLQI). Childhood psoriasis exerted a substantial impact on the QoL of caregivers (mean FDLQI 13.62±6.15 points). Caregivers rated routine household expenditure, time spent caring for the skin of the child, and emotional distress as the areas most impacted by psoriasis. The areas least affected were parent-child relationships, and caregivers' social lives. The impact of other people's reactions to the child's disease was rated as more severe by caregivers of girls compared with those of boys (p=0.004).

Clinical characteristics and epidemiology of chronic urticaria: a nationwide, multicentre study on 1091 patients.

INTRODUCTION: Urticaria is one of the most common skin diseases. Depending on the length of symptoms, acute (lasting less than 6 weeks) and chronic urticaria (CU) (> 6 weeks) are distinguished. According to the current European guidelines, CU is divided into inducible urticaria (IU) and chronic spontaneous urticaria (CSU). AIM: To assess the epidemiology and clinical characteristics of CU in Poland. MATERIAL AND METHODS: This was a nationwide, multicentre, cross-sectional, questionnaire-based study performed under the auspices of the Polish Dermatological Society. A total of 102 physicians (dermatologists and allergists) recruited 1091 patients suffering from CU. RESULTS: Among 1091 adults with CU, IU was found in 35.1% (n = 383) of patients and CSU was responsible for 61.1% (n = 667) of CU cases. The remaining patients (n = 41, 3.8%) suffered from both, IU and CSU. Persons with CSU were twice more likely to report family history of urticaria than those with IU (12.1% vs. 6.0%, p = 0.001). Generalized eruptions of wheals predominated in CSU (generalized wheals: 57.9%, localized wheals: 42.1%), whereas wheals localized in particular body areas were found more commonly in IU (generalized wheals: 45.2%, localized wheals: 54.8%, p < 0.001). The CU was the cause of absenteeism in almost every fifth patient suffering from this disease. CONCLUSIONS: The CSU is about twice as frequent cause of CU as compared to IU. The treatment of CU is a major challenge for physicians of various specialties and the treatment choice is closely associated with the specialist knowledge of current treatment guidelines.

Epidemiology of dermatomycoses in southwest Poland, years 2011-2016.

INTRODUCTION: Superficial mycosis is one of the most common diseases worldwide, however its epidemiology is changing over time. AIM: To present epidemiological data of the skin fungal infections diagnosed in the years 2011-2016 in Lower Silesia. MATERIAL AND METHODS: A total of 11 004 patients with a clinically suspected superficial mycosis were investigated. Skin scrapings, nail clippings and plucked hair were examined with a direct microscopy, Wood's lamp and culture. Particular species were identified via polymerase chain reaction (PCR) examination. The lesions suspected for pityriasis versicolor were screened for Malassezia with Wood's lamp and direct microscopy. RESULTS: Dermatomycosis was diagnosed in 1653 (15.00%) patients with 1795 fungi identified. 1858 specimens were indicative of fungal infection including dermatophytes, yeasts and moulds. Out of 924 cases of dermatophytic infections (51.48%), Trichophyton rubrum accounted for the majority (71.75%) and was followed by Trichophyton tonsurans (16.77%). Among the yeasts (716; 39.89%), Candida spp. was the most common agent identified (521; 67.66%). The sites affected most often were toenails (956; 51.45%) and fingernails (319; 17.17%). In paediatric population the most common diagnosis was tinea corporis (60, 41.10%). CONCLUSIONS: Our study revealed that toenail onychomycosis remains the most common superficial mycosis and T. rubrum is the most common pathogen. However, in a longer period of observation, a decrease in the number of tinea capitis cases and an increase in infections caused by T. tonsurans were noticed. Observed changes indicate the need for continuing studies to detect the upcoming epidemiological trends.

Efficacy of diphenylcyclopropenone in alopecia areata: a comparison of two treatment regimens.

INTRODUCTION: Alopecia areata (AA) is a skin disease of unclear etiology. In AA, topical immunotherapy with diphenylcyclopropenone (DPCP) is considered the most effective treatment; however, the most common therapies give unsatisfactory results. AIM: To assess the efficacy of a topical application of a solution of DPCP based on the intensity, duration and number of exacerbations of AA and to compare the efficacy of two treatment regimens. MATERIAL AND METHODS: In this prospective study, 39 patients with AA were enrolled. Group A was treated at weekly intervals and group B at 3-week intervals. Hair loss was assessed by independent dermatologists and documented by photography and dermoscopy. RESULTS: After 6 months' therapy, hair regrowth greater than 50% was observed in 21 patients, while worsening, no regrowth, or regrowth of less than 50% was seen in 18 patients. Regrowth exceeding 50% of initial loss was observed in 12 of 17 patients with baseline hair loss < 50%, in 9 of 22 patients with severe alopecia, and in 4 of 9 patients with alopecia totalis. Both groups showed significant improvement with higher efficacy in group B (54%) than group A (46%). CONCLUSIONS: Treatment at longer intervals may be safer and more comfortable for patients; however, further research is required.

Podoplanin Expression Correlates with Disease Progression in Mycosis Fungoides.

The aim of this study was to investigate the role of lymphangiogenesis in the clinical progression and outcome of mycosis fungoides. Immunohistochemistry and Western blot techniques were used to assess the expression of podoplanin and vascular endothelial growth factor C in mycosis fungoides. Expression of vascular endothelial growth factor C measured by immunohistochemistry was significantly higher in mycosis fungoides samples in comparison with control cases (chronic benign dermatoses) (p = 0.0012). Increased expression of podoplanin was found in advanced vs. early mycosis fungoides (p < 0.0001), and was positively correlated with cutaneous and nodal involvement (p < 0.001, p < 0.0001; respectively). Higher podoplanin expression was also significantly associated with shorter survival (p < 0.001). Strong positive correlation was observed between expression of podoplanin analysed by immunohistochemistry and Western blot (r = 0.75, p < 0.0001). A similar association was shown regarding expression of vascular endothelial growth factor C (r = 0.68, p = 0.0007). In conclusion, these results suggest that increased expression of podoplanin is associated with poor clinical course, as well as shorter survival, of patients with mycosis fungoides.

Expression of SOX18 in Mycosis Fungoides.

SOX18 is a transcription factor involved in the development of hair follicle, blood and lymphatic vessels, as well as regenerative processes. In addition, accumulated data indicate the role of SOX18 in tumourigenesis. So far, no studies on the role of SOX18 expression in mycosis fungoides (MF), the most common primary cutaneous T-cell lymphoma, have been performed. Therefore, we evaluated SOX18 expression in MF at the mRNA and protein level. SOX18 expression was observed predominantly on the blood and lymphatic vessels, in the intratumoural and peritumoural microenvironment of MF. The intra-tumoural, but not peritumoural, expression of SOX18 correlated positively with the advancement of the disease, cutaneous involvement and extracutaneous meta-stases at the protein level (p < 0.001, p < 0.001, p = 0.004; respectively). Significantly lower SOX18 mRNA expression was correlated with lymph node involvement (p = 0.01). In conclusion, we hypothesize that SOX18, as a marker of neovascularization, may be involved in the progression of MF.

[Angiogenesis and lymphangiogenesis in primary cutaneous T-cell lymphomas]. / Angiogeneza i limfangiogeneza w pierwotnie skórnych chloniakach T-komórkowych.

Primary cutaneous T-cell lymphomas are a group of rare hematologic malignancies, derived from mature T lymphocytes and initially developing only in the skin. The most common lymphomas representing this group are mycosis fungoides and Sezary syndrome. Mycosis fungoides is an indolent disease with a chronic course and characteristic evolution of the skin lesions from erythematous patches, through plaques to tumors. Sezary syndrome is characterized by an aggressive course and a triad of symptoms (erythroderma, generalized lymphadenopathy, and the presence of atypical cells in the skin, lymph nodes and peripheral blood). The etiopathogenesis of cutaneous lymphomas is not fully understood, but a few studies on angiogenesis and lymphangiogenesis in these malignancies indicate a significant role in their development and progression. Angiogenesis is a process of formation of new blood vessels from existing ones. Lymphangiogenesis is a similar process concerning lymphatic vasculature. Development of new vessels is a complex process composed of several successive stages: migration, proliferation, and differentiation of endothelial cells, extracellular matrix degradation and formation and stabilization of new vessels, regulated by growth factors, cytokines and other proteins. Both phenomena are essential in the development and progression of solid tumors and hematological malignancies. Therapeutic strategies involving the inhibition of tumor angiogenesis and lymphangiogenesis are a promising new direction of studies in antitumor therapy, requiring further experiments.

Expression of CXCR4 and CXCL12 and their correlations to the cell proliferation and angiogenesis in mycosis fungoides.

INTRODUCTION: Chemokines play an important role in tumor growth, invasion and metastasis. The CXCR4/CXCL12 axis has been implicated in development of both solid tumors and hematological malignancies and is also relevant in the pathogenesis of the most common primary cutaneous T-cell lymphoma, mycosis fungoides (MF). AIM: To evaluate the expression of CXCR4 and CXCL12 in MF and to examine their associations with cell proliferation and angiogenesis. MATERIAL AND METHODS: The material for the study consisted of skin samples obtained from 56 patients with MF and 20 healthy volunteers. The expression of CXCR4 and CXCL12 was assessed by immunohistochemistry on the paraffin blocks and compared to the expression of angiogenesis marker (CD34) and proliferation indicators (Ki-67, AgNORs). RESULTS: The expression of chemokine CXCL12 and its receptor CXCR4 was significantly higher in MF than in the healthy skin (p < 0.001). There was no significant difference between early and advanced stages of MF. Similarly, there was no statistically important correlation between the expression of CXCR4/CXCL12 and angiogenesis and proliferation markers, however a significant correlation between CD34 and AgNORs expression was found (p < 0.001). CONCLUSIONS: The CXCR4/CXCL12 axis seems to play an important role in MF development in the early as well as in the advanced stages of the disease. Therefore, the CXCR4/CXCL12 axis seems to be an interesting potential target for the future strategies of new drug development, giving hope for more efficacious therapies for mycosis fungoides.

Erythroderma: A Retrospective Study of 212 Patients Hospitalized in a Tertiary Center in Lower Silesia, Poland.

Erythroderma is a condition characterized by erythema affecting at least 90% of the skin surface area. It can be caused by various underlying conditions. Due to nonspecific clinical and laboratory findings, determining the cause may pose a challenge. In the retrospective study, we identified 212 patients hospitalized for erythroderma in the Department of Dermatology, Venereology, and Allergology at Wroclaw Medical University between January 2012 and March 2022. Clinical, laboratory, and histopathological features, as well as the management of patients, were studied. The median age of adults was 61 years (IQR = 47-68). The most common causes of erythroderma were psoriasis (n = 49, 24.01%), followed by atopic dermatitis (AD) (n = 27, 13.23%), and cutaneous T-cell lymphomas (CTCL) (n = 27, 13.23%). Despite laboratory tests and histopathological examination, the etiology of erythroderma remained undetermined in 39 cases (19.12%). In 70.59% of patients, it was the first episode of erythroderma, while 29.41% experienced a recurrent episode. Regardless of the etiology of erythroderma, patients were most frequently treated with systemic antihistamines (146 cases, 71.57%) and systemic steroids (132 cases, 64.71%). Patients with idiopathic erythroderma constitute the greatest diagnostic and therapeutic challenge, requiring particularly thorough evaluation.