Multiple Cytokine Analysis of Th1/Th2/Th9/Th17/Th22/Treg Cytokine Pathway for Individual Immune Profile Assessment in Patients with Psoriasis.

BACKGROUND Psoriasis is an autoimmune and autoinflammatory disorder that has a significant impact on patient quality of life. The aim of the study was to assess the immune profiles of patients with psoriasis with multiple cytokine analysis. MATERIAL AND METHODS Fifty-two male psoriatic patients and 24 healthy male volunteers were recruited. Granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-gamma), interleukin (IL)-1 beta, IL-2, Il-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-13, IL-17A, IL-18, IL-21, IL-22, IL-23, IL-27, and tumor necrosis factor (TNF)-alpha were measured in patients' serum with a Th1/Th2/Th9/Th17/Th22/Treg Cytokine 18-Plex Human ProcartaPlex Panel, based on Luminex xMAP technology. RESULTS The median fluorescence intensities of serum GM-CSF, IL-2, IL-5, IL-10, IL-13, IL-17A, IL-21, and IL-22 were not intensive enough to calculate the cytokine concentration. We observed elevated levels of IL-6 (P=0.001) and IL-9 (P=0.003) in patients, compared with the control group. The levels of IL-1beta (P=0.008) and IL-27 (P=0.006) were decreased. In patients with psoriatic arthritis, we noticed a decreased level of IL-9 compared with that in patients without arthritis (P=0.034). The levels of IL-12 (P<0.05) and IL-18 (P<0.05) correlated positively with the Psoriasis Area and Severity Index. We found negative correlations of IL-9 (P<0.05), IL-12 (P<0.05), and IL-23 (P<0.05) with the age of psoriatic patients; IL-12 (P<0.05) and IL-23 (P<0.05) with psoriasis duration; and IL-6 (P<0.05) and IL-9 (P<0.05) with the Nail Psoriasis Severity Index. CONCLUSIONS Multiple cytokine analysis seems to be an important form of individual immune profile assessment before treatment selection.

Assessment of Selected Matrix Metalloproteinases (MMPs) and Correlation with Cytokines in Psoriatic Patients.

Metalloproteinases (MMPs) and cytokines have a great impact on the pathogenesis of psoriasis. Cytokines, as key mediators of inflammation and autoimmune processes, play a crucial role in the regulation of MMP expression in different cell types. Parallel, MMPs have an influence on cytokine production. This interaction was not well recognized in psoriatic patients. Our study is aimed at assessing the selected serum MMP levels and their correlations with cytokine levels in the serum of psoriatic patients. We observed a significantly elevated level of pro-MMP-1 and MMP-9 in psoriatic patients' serum in comparison to the control group. We did not observe any statistically significant differences of MMP-3 and pro-MMP-10 between the psoriatic patients and the control group. We did not observe any statistically significant differences in all the studied MMP levels between the patients with and without psoriatic arthritis (PsA). MMP-3 level correlated positively with proinflammatory cytokines, i.e., IL-12p/70, IL-17A, and TNF-α as well as MMP-3 and pro MMP-1 correlated positively with IL-4 in the psoriatic patients. In the control group, a positive correlation between pro-MMP-1 and TNF-α was found. These results confirm MMPs and Th1 and Th17 cytokine interaction in the inflammatory regulation in psoriasis.

IL-17A in the Psoriatic Patients' Serum and Plaque Scales as Potential Marker of the Diseases Severity and Obesity.

The aim of the study was to evaluate concentrations of IL-17 in the serum and plaque scales of psoriatic patients. We analyzed their association with the clinical activity of the disease and with body mass index (BMI). Demographic data, medical history, serum, and scale from psoriatic plaques for assessment of IL-17 were collected from all the participants. The disease severity was assessed with PASI (Psoriasis Area and Severity Index), BSA (Body Surface Area), PGA (Physician Global Assessment), NAPSI (Nail Psoriasis Severity Index), and DLQI (Dermatology Quality of Life Index) scores. Obesity was diagnosed by calculating body mass index. Serum and scale concentration of IL-17 was determined with Human IL-17A High Sensitivity ELISA kit and Human IL-17 ELISA kit. In the psoriatic patients, BMI was statistically significantly higher than in the control group. Most of the patients presented BMI higher than normal. Our study confirms that overweight is a problem among psoriatic patients. A significant positive correlation between the IL-17 serum and scale concentrations and psoriasis severity indicates that IL-17 can be used as the marker of disease severity. More data from human studies can be crucial for understanding that relationship between IL-17, psoriasis, and obesity.

Clinical usefulness of high-frequency ultrasonography in the monitoring of basal cell carcinoma treatment effects.

INTRODUCTION: To date, there has been no consensus either on the method, frequency or total duration of follow-up for patients that have developed a basal cell carcinoma (BCC). AIM: To evaluate usefulness of high-frequency ultrasound in monitoring patients with BCC, particularly to detect residual disease or early recurrence. MATERIAL AND METHODS: Seventy-eight patients with suspicious lesions of BCC were enrolled in this study. Only patients for whom histologic evaluation confirmed diagnosis of BCC (70) continued the study. The dermatoscopic and ultrasonographic observation started before the treatment. Three control examinations were performed 4, 12 and 24 weeks after the treatment. RESULTS: A total of 70 basal cell carcinomas were examined in this study. The presence of cancer formation was observed in the margins of removed nodular BCC in 15% (6/40), in another 25% of cases the margin of surgical removal was narrow and was < 0.2 cm (10/40). For 4 of 6 (66%) lesions, in which histopathological examination demonstrated a positive margin, hypo or heteroechogenic, irregularly shaped focal lesions were found in the ultrasonographic examination just under the entrance echo on the first follow-up visit. In 2 other cases of positive margins of the removed BCC, no signs of residual disease were observed in ultrasonographic examination. For patients with a narrow margin of healthy tissues after surgical removal, hypo or heteroechogenic foci located directly under the entrance echo were also observed in the ultrasonographic examination 4 weeks after the surgery, suggesting the presence of cancer formation. Reduction in the suspected area and scar formation were observed on the subsequent visits. It was found that the characteristic feature of residual disease presence is an enlargement of the hypoechogenic area in subsequent ultrasonographic examinations. CONCLUSIONS: The use of high-frequency ultrasonography in the monitoring of patients after surgery can accelerate and improve the diagnosis of residual disease.

Analysis of circulating soluble programmed death 1 (PD-1), neuropilin 1 (NRP-1) and human leukocyte antigen-G (HLA-G) in psoriatic patients.

INTRODUCTION: Circulating soluble programmed death 1 (PD-1), neuropilin 1 (NRP-1) and human leukocyte antigen-G (HLA-G) take part in modulating immune tolerance causing disturbances in the molecular mechanisms responsible for maintenance of balance between effector and regulatory components of the immune system. Since their cell-surface expression levels were found to be changed in lesional and/or non-lesional skin of psoriatic patients, analysis of soluble PD-1, NRP-1 and HLA-G concentrations sheds more light on their role in detecting unbalanced immune tolerance in psoriasis. AIM: To assess soluble PD-1, NRP-1 and HLA-G concentrations in psoriasis. MATERIAL AND METHODS: The study included 57 psoriatic patients and 29 controls. Duration of psoriasis was in the range 1 to 55 years; the median was 19 years. The plasma concentrations of soluble HLA-G (sHLA-G), soluble NRP-1 (sNRP-1) and soluble PD-1 (sPD-1) were examined using the ELISA method. Severity of the skin lesions was assessed by means of Psoriasis Area Severity Index (PASI), body surface area (BSA) and Physician Global Assessment (PGA). RESULTS: Psoriasis Area Severity Index in the studied group was in the range 3 to 43; the median was 12. Body surface area was in the range 2-75%; the median was 15%. The median value of PGA was 3. Soluble NRP concentration was significantly higher in the psoriatic patients (median: 1.59 pg/ml; range: 0.67-2.62 pg/ml) than in the control group (median: 1.35 pg/ml; range: 0.05-2.61 pg/ml) (p = 0.010). Soluble PD-1 and sHLA-G concentrations were not significantly different between the studied and control groups (p = 0.094 and p = 0.482, respectively). CONCLUSIONS: Increased concentrations of sNRP-1 and unchanged values of sHLA-G and sPD-1 concentrations may be indicative of impaired immune tolerance mechanisms in psoriasis.

Analysis of serum chemerin concentrations in psoriatic patients in relation to metabolic abnormalities.

INTRODUCTION: Recent data depict psoriasis as a systemic disease with many comorbidities, especially metabolic syndrome and cardiovascular diseases. Chemerin, an adipokine secreted by adipose tissue cells, may prove to be an important link between psoriasis and its comorbidities. AIM: Assessment of serum concentrations of chemerin in patients with psoriasis and the healthy control group as well as evaluation of a possible correlation between adipokine concentrations and selected psoriasis severity indices and metabolic syndrome components. MATERIAL AND METHODS: One hundred and two patients with diagnosed psoriasis and 40 healthy volunteers were enrolled in the study. In all subjects, serum chemerin concentrations and selected metabolic syndrome components including lipid and glucose levels were determined. Psoriasis severity was assessed using the PASI and BSA indices. RESULTS: A higher concentration of chemerin was demonstrated in the group of psoriasis patients compared to the control group (p < 0.05). A positive correlation between chemerin concentration and C-reactive protein concentration (p = 0.001), body mass index (p = 0.031) and triglyceride concentration (p = 0.043) was found. An inverse correlation with high-density lipoprotein cholesterol concentrations (p = 0.015) was also noted. Significantly higher concentrations of chemerin were observed in psoriatic patients with elevated low-density lipoptotein (LDL) cholesterol levels in comparison with patients with normal LDL values (p = 0.032). Chemerin concentrations were also significantly higher in patients with both psoriasis and elevated glucose levels compared to patients with normal blood glucose values (p = 0.043). CONCLUSIONS: The results obtained suggest a possible role of chemerin as an adipokine linking psoriasis with metabolic syndrome.

Decreased blood CD4+PD-1+ and CD8+PD-1+ T cells in psoriatic patients with and without arthritis.

INTRODUCTION: Psoriasis with and without arthritis have common immunological mechanisms which among others involve the interactions between cytokines produced by T cells, including Th1, Th17 and Th22. Although quite a lot is known about psoriasis pathogenesis, the cause of chronic immune activation and response in the disease remains unclear. One of the negative regulators of the immune system is programmed death 1 (PD-1). AIM: To assess the expression level of PD-1 in the peripheral T cells of psoriatic patients with and without arthritis. MATERIAL AND METHODS: The study included 23 psoriatic patients with arthritis, 52 psoriatic patients without arthritis and 52 healthy controls. The percentages of CD3+, CD4+, CD8+, CD4+PD-1+ and CD8+PD-1+ T cells were analyzed using flow cytometry. RESULTS: The percentages of CD4+PD-1+ as well as CD8+PD-1+ T cells in the psoriatic patients both with and without arthritis were significantly lower than in the control group. The percentages of CD4+PD-1+ as well as CD8+PD-1+T cells were not significantly different between the psoriatic patients with and without arthritis. A significant positive correlation between PD-1 expression on the CD4+ and CD8+ T cells was found in the psoriatic patients without arthritis. CONCLUSIONS: Impairment of the negative co-stimulation from PD-1 may be another common characteristic of psoriasis both with and without arthritis.

Suppressed Programmed Death 1 Expression on CD4+ and CD8+ T Cells in Psoriatic Patients.

Psoriasis is a chronic inflammatory disease mediated by T cell immunity. Programmed death 1 (PD-1), a coinhibitory receptor, plays an important role in immune regulation and maintaining peripheral tolerance. The aim of the study was to compare the expression of PD-1 on the peripheral T cells between psoriatic patients and healthy controls. The study included 75 psoriatic patients and 52 healthy volunteers. The percentages and absolute numbers of CD3+, CD4+, CD8+, CD4+PD-1+, and CD8+PD-1+ T cells were analyzed using flow cytometry. The absolute numbers and percentages of CD4+PD-1+ and CD8+PD-1+ T cells were significantly decreased in the psoriatic patients in comparison with the control group. No significant correlations were found between the absolute numbers and percentages of CD4+PD-1+ or CD8+PD-1+ T cells and clinical characteristics of psoriasis. Decreased PD-1 expression on the T cells may be responsible for impaired negative regulation of immune response in psoriasis pathogenesis.

The Role of Vitamin D in Non-Scarring Alopecia.

Non-scarring hair loss is a common problem that affects both male and female patients. Since any disturbances in the hair follicle cycle may lead to hair shedding, or alopecia, it is not surprising that the possible role of vitamin D in alopecia was investigated in many studies. Vitamin D has been shown to have many important functions. A growing body of evidence shows that vitamin D and its receptor are responsible for maintaining not only calcium homeostasis but also skin homeostasis. Moreover, vitamin D could also regulate cutaneous innate and adaptive immunity. This paper presents a review of current literature considering the role of vitamin D in alopecia areata, telogen effluvium, and female pattern hair loss. The majority of studies revealed decreased serum 25-hydroxyvitamin D levels in patients with different types of non-scarring alopecia, which could suggest its potential role in the pathogenesis of hair loss. According to the authors, vitamin D supplementation could be a therapeutic option for patients with alopecia areata, female pattern hair loss, or telogen effluvium. However, further studies on a larger group of patients are required.

The Assessment of Selected Bone and Cartilage Biomarkers in Psoriatic Patients from Poland.

BACKGROUND: Psoriasis is an inflammatory disease in which joints involvement may be insidious and difficult to detect. Bone and cartilage biomarkers may be helpful in screening patients with psoriasis for psoriatic arthritis (PsA). OBJECTIVES: To assess bone and cartilage serum biomarkers in psoriasis. Methods. The study was conducted in 2014 and included 61 psoriatic patients and 30 healthy individuals. In both groups, the serum concentrations of soluble receptor activator of nuclear factor-κB ligand (sRANKL), cartilage oligomeric matrix protein (COMP), osteoprotegerin (OPG), and interleukin-20 (IL-20) were examined. Severity of skin lesions was assessed by Psoriasis Area and Severity Index (PASI), body surface area (BSA), and Physician Global Assessment (PGA) scores. RESULTS: The duration of psoriasis was from 1 year to 45 years. 22 patients suffered from concomitant PsA. The mean value of PASI was 23.1 ± 12.0 and BSA was 27.6 ± 20.6%. COMP, OPG, and IL-20 concentrations in psoriatic patients were significantly higher than in the control group. OPG/sRANKL ratio was significantly lower in PsA patients than in psoriatic patients without arthritis. CONCLUSIONS: Results of the conducted study suggest that COMP, OPG, IL-20, and OPG/sRANKL ratio may appear useful biomarkers of bone and cartilage involvement in psoriasis.

[Stigmatization in psoriasis patients]. / Stygmatyzacja osób chorych na luszczyce.

Psoriasis is a chronic disease that affects the skin, nail plates and/or joints in which correlation between the onset of skin changes or more severe symptoms and the psychical condition of a patient is observed. At present it is assumed that stigmatization are events and situations in a person's life that are recognized by the society as those that stigmatize a given person and lead to their rejection and finally downgrade and ruin their social status. Opinions and behaviour patterns of the members of the society create the sigma feeling in a patient and affect his/her psyche. The aim of the present paper is the analysis of the latest data presented in the literature on the sigma feeling in psoriasis patients. In the study, the analysis of the types of stigmatization experienced by patients has been carried out. Life events influence the severity of psoriatic changes, but also psoriasis as a somatic disease affects the everyday life of a patient. Some reactions and behaviours of other people may create the feeling of rejection in social situations and the subjective feeling of being stigmatized. Then, as a result of the sigma feeling, the general health condition, functioning in the society and quality of life are affected.

Bullous pyoderma gangrenosum associated with pancytopenia of unknown origin.

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis of unknown origin. Clinically it starts with a pustule, nodule or bulla that rapidly progresses and turns into a painful ulcer with raised, undermined borders. The etiopathogenesis of PG remains unknown. However it is frequently associated with systemic diseases such as inflammatory bowel disease (IBD), haematological disorders or arthritis. The latest multicentric retrospective analysis published by Ghazal et al. shows that anaemia has been observed very often in German patients suffering from PG (in 45.6% of 259) so this disorder is supposed to be a possible cofactor in the pathogenesis of PG. According to its progressive course, patients require intensive diagnostic procedures and rapid initiation of the treatment. In this article, we report a case of bullous pyoderma gangrenosum in association with pancytopenia of unknown origin, according to its diagnostic and therapeutic difficulties.

Diffuse cutaneous bullous mastocytosis in a newborn.

Diffuse cutaneous mastocytosis is the rarest subtype of mastocytosis among those that affect children. A 7-month-old girl presented at birth dry and thickened skin. On the second day of life, tense blisters appeared on erythrodermic areas and during the next days spread over the face, trunk, and limbs. The skin was bright red, had a "peau d'orange" appearance, and was considerably thickened with numerous translucent and hemorrhagic blisters. A skin biopsy revealed massive infiltration of the dermis with mast cells, leading to the diagnosis of diffuse erythrodermic mastocytosis. Systemic corticosteroids were given along with antihistamines with good results. Despite the progresses in the understanding of pathogenesis, genetics, and diagnostic criteria of mastocytosis, clear and reliable prognostic markers are still lacking, especially in order to predict systemic involvement. not only in diffuse but also in the commoner forms of the disease.

Future diagnosis, today's treatment - cardiomyopathy in the course of psoriasis: a case report.

Psoriasis is a relatively common, chronic skin disease of inflammatory origin. In recent years, public attention has been drawn to a more and more frequently observed relationship between psoriasis and cardiovascular disease. Nowadays, psoriasis is independently held responsible for increased cardiovascular mortality. It seems that the actual significance of the problem, together with a heart-related death risk for these patients is often underestimated. This study presents clinical evidence collected during a long-term observation and treatment of an 80-year-old psoriatic patient with concomitant diabetes, hypertension, and ischemic heart disease, whose overall clinical picture also suggested a congestive, inflammation-related cardiomyopathy with conduction disorders and severe heart failure. Despite the patient's advanced age and associated serious, long-established psoriasis-related problems, he was successfully treated with the use of interventional cardiology methods, as well as cardiac resynchronization therapy.

Somatic and non-somatic problems connected with psoriasis in pregnancy.

Hormonal, metabolic and immunological changes occurring during pregnancy have significant effects on the function of the skin. Psoriasis is one of the most common dermatological diseases and it is known as a nonspecific dermatosis in pregnancy. The aim of this article is to present the importance of support in the course of psoriasis in pregnant women. Psoriasis may cause recurrent miscarriages, chronic hypertension, diabetes or obesity leading to perinatal complications and premature birth. The coexistence of psoriasis and pregnancy requires emotional prophylaxis, as well as support and psychotherapeutic care. Medical staff requires knowledge of skin diseases and skills to assess a patient's mental state.

Cutaneous larva migrans syndrome: a case report.

Cutaneous larva migrans (CML) is a frequent parasitic infestation caused by migration of animal hookworm larvae into the human epidermis. This skin disease is common in warmer climates among people, who have contact with contaminated soil. Clinical manifestation of CML is an itchy, erythematous, linear tract, which appears days to even months after exposure to infested sand or soil. Diagnosis is established on the clinical presentation. We describe a case of CML acquired during a holiday in Brazil.

Metabolic syndrome in vitiligo.

Vitiligo is an acquired, depigmenting skin disease with still unclear, multifactorial etiopathogenesis. However, there is growing evidence that vitiligo affects not only the skin but it may also be connected with metabolic abnormalities, including glucose intolerance and lipid abnormalities, all of which confirms the systemic nature of the disease. Recently, it has been shown that melanocytes, especially those found in the adipose tissue, due to their ability to decrease inflammation and oxidative damage, are capable of preventing the metabolic syndrome. The article presents updated knowledge on potential metabolic disturbances in vitiligo.

Angiopoietins-1 and -2 are differentially expressed in the sera of patients with systemic sclerosis: high angiopoietin-2 levels are associated with greater severity and higher activity of the disease.

OBJECTIVES: The aim of the study was to investigate serum concentration of angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) in SSc patients and to correlate Ang-1 and -2 levels with clinical manifestations. METHODS: Serum levels of Ang-1 and -2 were determined by ELISA in 47 SSc patients and 27 healthy controls matched for age and sex. RESULTS: In SSc patients, Ang-1 was significantly lower [mean (s.d.): 21,666.09 (11,516.06) pg/ml], while Ang-2 was significantly increased [2739.60 (1009.25) pg/ml] when compared with the control group [Ang-1: 28607.13 (10,506.93) pg/ml; Ang-2: 1706.28 (556.28) pg/ml, P < 0.01, for both comparisons]. No correlation was observed between Ang-1 and -2 levels. Serum concentrations of Ang-2 correlated with the modified Rodnan skin score (P < 0.01, r =0.422), the European Scleroderma Study Group (EScSG) disease activity index score (P < 0.001, r =0.403), ESR (P < 0.05, r = 0.366) and CRP concentration (P < 0.05, r =0.292), and showed inverse correlation with diffusing capacity for carbon monoxide (DL(CO)) (P < 0.01, r = -0.281). Ang-2 was significantly increased in SSc patients with more advanced capillary damage, as indicated by the presence of late capillaroscopic pattern, than in those with less severe microangiopathy (active pattern), and in SSc patients with intermediate/late stage of disease than in SSc subjects with early disease. In multivariate regression analysis, Ang-2 was independently associated with the EScSG activity index [ß-coefficient (ß = 0.305, P= 0.038], ESR (ß= 0.390, P =0.006) and, inversely, with the presence of digital ulcers (ß =-0.426, P = 0.003). CONCLUSIONS: Differential expression of Ang-1/Ang-2 might contribute to the pathogenesis of SSc. Ang-2 might be a new biomarker of disease activity in SSc.

Candida parapsilosis infection following the electrosurgery procedure.

Subcutaneous mycoses are fungal infections that predominantly affect the dermis and subcutaneous tissue. The most common pathogen responsible for these infections is Candida albicans; however, another yeast from this group, Candida parapsilosis, becomes the cause of increasing numbers of mycotic infections. Recent reports suggested that this microorganism may be particularly resistant to disinfectants, which can facilitate its spread through the medical staff, instruments, and biomaterial. We report a case of a patient in whom a C. parapsilosis infection occurred as a complication following a minor electrocoagulation procedure. Because all obtained laboratory findings were nonspecific, the infection could be properly diagnosed only through cultures from the skin lesion.