Effect of education on sun-safe behaviour in kidney transplant recipients.

BACKGROUND: Organ transplant recipients (OTR) are more likely to develop skin cancer than the general population. One of the main components of the exposome that triggers the development of skin tumours is solar ultraviolet (UV) radiation. To reduce the incidence of harmful consequences of sun exposure, sun protection education is needed for patients taking long-term immunosuppressive drugs. METHODS: In a previous study, we assessed the sun-safe behaviour of 221 OTR using a questionnaire before and after transplantation and personally educated the patients about proper sun protection. After the education, there were no further reminder presentations. Presently, the sun protection and sun seeking habits of the available 176 of these patients were questioned to assess the long-term effect of the previous sun protection education. RESULTS: Two-four years after the education, more patients wore hats and protected their skin with long-sleeved clothing than before the education. In terms of sun seeking habits, both occupational and recreational sun exposure decreased significantly. Significantly fewer people went on holiday after transplantation, but those who went on holiday spent significantly less time in the sun. CONCLUSION: The long-term positive effects of education can be seen both in the patients' sun protection and in their sun seeking habits. However, the long-term goal is to maintain these results and thereby reduce the likelihood of skin tumours and consequently the associated tumour death.

KDM1A inhibition increases UVA toxicity and enhances photodynamic therapy efficacy.

BACKGROUND: Lysine-specific histone demethylase 1 (KDM1A/LSD1) regulates multiple cellular functions, including cellular proliferation, differentiation, and DNA repair. KDM1A is overexpressed in squamous cell carcinoma of the skin and inhibition of KDM1A can suppress cutaneous carcinogenesis. Despite the role of KDM1A in skin and DNA repair, the effect of KDM1A inhibition on cellular ultraviolet (UV) response has not been studied. METHODS: The ability of KDM1A inhibitor bizine to modify cell death after UVA and UVB exposure was tested in normal human keratinocytes and melanocytes, HaCaT, and FaDu cell lines. KDM1A was also downregulated using shRNA and inhibited by phenelzine in HaCaT and FaDu cells to confirm the role of KDM1A in UVA response. In addition, cellular reactive oxygen species (ROS) changes were assessed by a lipid-soluble fluorescent indicator of lipid oxidation, and ROS-related gene regulation using qPCR. During photodynamic therapy (PDT) studies HaCaT and FaDu cells were treated with aminolaevulinic acid (5-ALA) or HPPH (2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a) sodium and irradiated with 0-8 J/cm2 red LED light. RESULTS: KDM1A inhibition sensitized cells to UVA radiation-induced cell death but not to UVB. KDM1A inhibition increased ROS generation as detected by increased lipid peroxidation and the upregulation of ROS-responsive genes. The effectiveness of both ALA and HPPH PDT significantly improved in vitro in HaCaT and FaDu cells after KDM1A inhibition. CONCLUSION: KDM1A is a regulator of cellular UV response and KDM1A inhibition can improve PDT efficacy.

The measurement performance of the EQ-5D-5L versus EQ-5D-3L in patients with hidradenitis suppurativa.

PURPOSE: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that affects up to 1% of the population in Europe. The EQ-5D is the most commonly used generic instrument for measuring health-related quality of life among HS patients. This study aims to compare the measurement properties of the two adult versions of EQ-5D (EQ-5D-3L and EQ-5D-5L) in patients with HS. METHODS: We recruited 200 consecutive patients with HS (mean age 37 years, 38% severe or very severe HS) to participate in a multicentre cross-sectional survey. Patients completed the EQ-5D-3L, EQ-5D-5L, Dermatology Life Quality Index (DLQI) and Skindex-16 questionnaires. RESULTS: More than twice as many different health state profiles occurred in the EQ-5D-5L compared to the EQ-5D-3L (101 vs. 43). A significant reduction in ceiling effect was found for the mobility, self-care and usual activities dimensions. A good agreement was established between the EQ-5D-3L and EQ-5D-5L with an intraclass correlation coefficient of 0.872 (95% CI 0.830-0.903; p < 0.001) that was confirmed by a Bland-Altman plot. EQ-5D-5L improved both the absolute and relative informativity in all dimensions except for anxiety/depression. EQ-5D-3L and EQ-5D-5L demonstrated similar convergent validity with DLQI and Skindex-16. EQ-5D-5L was able to better discriminate between known groups of patients based on the number of comorbidities and disease severity (HS-Physician's Global Assessment). CONCLUSION: In patients with HS, the EQ-5D-5L outperformed the EQ-5D-3L in feasibility, ceiling effects, informativity and known-groups validity for many important clinical characteristics. We recommend using the EQ-5D-5L in HS patients across various settings, including clinical care, research and economic evaluations.

A Rasch model analysis of two interpretations of 'not relevant' responses on the Dermatology Life Quality Index (DLQI).

PURPOSE: Eight of the ten items of the Dermatology Life Quality Index (DLQI) have a 'not relevant' response (NRR) option. There are two possible ways to interpret NRRs: they may be considered 'not at all' or missing responses. We aim to compare the measurement performance of the DLQI in psoriasis patients when NRRs are scored as '0' (hereafter zero-scoring) and 'missing' (hereafter missing-scoring) using Rasch model analysis. METHODS: Data of 425 patients with psoriasis from two earlier cross-sectional surveys were re-analysed. All patients completed the paper-based Hungarian version of the DLQI. A partial credit model was applied. The following model assumptions and measurement properties were tested: dimensionality, item fit, person reliability, order of response options and differential item functioning (DIF). RESULTS: Principal component analysis of the residuals of the Rasch model confirmed the unidimensional structure of the DLQI. Person separation reliability indices were similar with zero-scoring (0.910) and missing-scoring (0.914) NRRs. With zero-scoring, items 6 (sport), 7 (working/studying) and 9 (sexual difficulties) suffered from item misfit and item-level disordering. With missing-scoring, no misfit was observed and only item 7 was illogically ordered. Six and three items showed DIF for gender and age, respectively, that were reduced to four and three by missing-scoring. CONCLUSIONS: Missing-scoring NRRs resulted in an improved measurement performance of the scale. DLQI scores of patients with at least one vs. no NRRs cannot be directly compared. Our findings provide further empirical support to the DLQI-R scoring modification that treats NRRs as missing and replaces them with the average score of the relevant items.

Inhibitors of Nucleotide Excision Repair Decrease UVB-Induced Mutagenesis-An In Vitro Study.

The high incidence of skin cancers in the Caucasian population is primarily due to the accumulation of DNA damage in epidermal cells induced by chronic ultraviolet B (UVB) exposure. UVB-induced DNA photolesions, including cyclobutane-pyrimidine dimers (CPDs), promote mutations in skin cancer driver genes. In humans, CPDs are repaired by nucleotide excision repair (NER). Several commonly used and investigational medications negatively influence NER in experimental systems. Despite these molecules' ability to decrease NER activity in vitro, the role of these drugs in enhancing skin cancer risk is unclear. In this study, we investigated four molecules (veliparib, resveratrol, spironolactone, and arsenic trioxide) with well-known NER-inhibitory potential in vitro, using UVB-irradiated CHO epithelial and HaCaT immortalized keratinocyte cell lines. Relative CPD levels, hypoxanthine phosphoribosyltransferase gene mutation frequency, cell viability, cell cycle progression, and protein expression were assessed. All four molecules significantly elevated CPD levels in the genome 24 h after UVB irradiation. However, veliparib, spironolactone, and arsenic trioxide reduced the mutagenic potential of UVB, while resveratrol did not alter UVB-induced mutation formation. UVB-induced apoptosis was enhanced by spironolactone and arsenic-trioxide treatment, while veliparib caused significantly prolonged cell cycle arrest and increased autophagy. Spironolactone also enhanced the phosphorylation level of mammalian target of rapamycin (mTOR), while arsenic trioxide modified UVB-driven mitochondrial fission. Resveratrol induced only mild changes in the cellular UVB response. Our results show that chemically inhibited NER does not result in increased mutagenic effects. Furthermore, the UVB-induced mutagenic potential can be paradoxically mitigated by NER-inhibitor molecules. We identified molecular changes in the cellular UVB response after NER-inhibitor treatment, which may compensate for the mitigated DNA repair. Our findings show that metabolic cellular response pathways are essential to consider in evaluating the skin cancer risk-modifying effects of pharmacological compounds.

A randomized phase 3b/4 study to evaluate concomitant use of topical ivermectin 1% cream and doxycycline 40-mg modified-release capsules, versus topical ivermectin 1% cream and placebo in the treatment of severe rosacea.

BACKGROUND: Randomized controlled studies of combination therapies in rosacea are limited. OBJECTIVE: Evaluate the efficacy and safety of combining ivermectin 1% cream (IVM) and doxycycline 40-mg modified-release capsules (ie, 30-mg immediate-release and 10-mg delayed-release beads) (DMR) versus IVM and placebo for treatment of severe rosacea. METHODS: This 12-week, multicenter, randomized, investigator-blinded, parallel-group comparative study randomized adult subjects with severe rosacea (Investigator's Global Assessment [IGA] score, 4) to receive either IVM and DMR (combination arm) or IVM and placebo (monotherapy). RESULTS: A total of 273 subjects participated. IVM and DMR displayed superior efficacy in reduction of inflammatory lesions (-80.3% vs -73.6% for monotherapy [P = .032]) and IGA score (P = .032). Combination therapy had a faster onset of action as of week 4; it significantly increased the number of subjects achieving an IGA score of 0 (11.9% vs 5.1% [P = .043]) and 100% lesion reduction (17.8% vs 7.2% [P = .006]) at week 12. Both treatments reduced the Clinician's Erythema Assessment score, stinging/burning, flushing episodes, Dermatology Life Quality Index score, and ocular signs/symptoms and were well tolerated. LIMITATIONS: The duration of the study prevented evaluation of potential recurrences or further improvements. CONCLUSION: Combining IVM and DMR can produce faster responses, improve response rates, and increase patient satisfaction in cases of severe rosacea.

Silymarin: Friend or Foe of UV Exposed Keratinocytes?

The application of natural plant extracts in UV-protection is popular and intensively studied. Silymarin (from Silibum marianum), a naturally occurring polyphenol, has recently received attention due to its antioxidant, anti-inflammatory and anti-apoptotic effects. However, its role in the UV-mediated keratinocyte cell response is still controversial. In this study, we investigated the effects of Silibum marianum extracts with different origins and formulations on UVA-exposed HaCaT keratinocytes in vitro. Our results show, that silymarin treatment caused an inverse dose-dependent photosensitivity relationship (at higher doses, a decrease in cell viability and ROS production) after UVA exposure. The attenuation of the UVA-induced ROS generation after silymarin treatment was also observed. Moreover, silymarin pre-treatment increased the cyclobutane pyrimidine dimer photolesions in keratinocytes after UVA exposure. These results indicated the dual role of silymarin in UVA-exposed keratinocytes. It scavenges ROS but still induces phototoxicity. Based on our results dermatological applications of silymarin and related compounds should be considered very carefully.

Comparison of pre- and post-transplant sun-safe behavior of kidney transplant recipients: What is needed to improve?

BACKGROUND: The role of sun exposure in the development of melanoma and nonmelanoma skin cancers is known; however, there are limited data on the contribution of pretransplantation total sun burden (TSB) to the increased skin cancer risk in organ transplant recipients (OTRs). The importance of patient education about sun-safe behaviors is understood, but educations are often unsuccessful in OTRs. METHODS: A questionnaire-based cross-sectional study was performed with kidney transplant patients at a single academic center to assess the pre- and post-transplant sun exposure, sun protection habits, and skin cancers. RESULTS: Two hundred and twenty-one patients participated in the study. 13.1% developed at least one skin cancer. High total sun burden before transplantation was reported by 58.4%, and 65.2% reported education about increased skin cancer risk at the time of transplantation. However, that education did not lead to less sun exposure or better sun protection methods after transplantation. Overall, OTR related but not sun protection-guided lifestyle changes affecting OTRs after transplantation led to reduction in sun exposure. CONCLUSION: Our findings highlight the need for more tailored, population-specific education programmes, even for patients who expect to receive a transplant in the future, and suggest the importance of pretransplantation TSB in determining the post-transplant skin cancer risk.

[Assessment of health-related quality of life in psoriasis patients in Hungary]. / Psoriasisban szenvedo betegek életminoségének vizsgálata Magyarországon.

INTRODUCTION: The health status and health-related quality of life (HRQoL) of patients with psoriasis in Hungary are understudied. AIM: To assess HRQoL in psoriasis patients, to compare HRQoL of psoriasis patients to that of the general public in Hungary and to identify predictors of HRQoL. METHOD: Between 2012 and 2016, two cross-sectional surveys were carried out among psoriasis patients at two academic dermatology departments. HRQoL was assessed by EQ-5D-3L, EQ Visual Analogue Scale (EQ VAS) and Dermatology Life Quality Index (DLQI). Predictors of HRQoL were analysed by multivariate linear regression. RESULTS: 434 patients were enrolled (mean age 49 years, 65% male, 81% moderate-to-severe psoriasis, 43% treated with biologics). Mean EQ-5D-3L, EQ VAS and DLQI scores were 0.74 ± 0.28, 69.06 ± 20.98 and 6.78 ± 7.38, respectively. Overall, 54%, 43%, 40%, 32% and 15% of patients indicated at least some problems in pain/discomfort, anxiety/depression, mobility, usual activities and self-care. EQ-5D-3L index scores in patients were lower compared to the age- and gender-matched general population in Hungary. The difference was statistically significant for the age groups 25-34 and 45-64 in males, and 18-64 in females (p<0.05). Female gender (p = 0.042), psoriatic arthritis (p<0.001) and palmoplantar psoriasis (p = 0.031) were associated with lower EQ-5D-3L index scores. On the contrary, employed and highly educated patients reported higher EQ-5D-3L index scores (p<0.001). CONCLUSIONS: We were the first to assess HRQoL in psoriasis patients by using EQ-5D questionnaire in Hungary, and more broadly in Central and Eastern Europe. Our findings are useful for cost-effectiveness modelling of psoriasis treatments and decision-making in healthcare. Orv Hetil. 2018; 159(21): 837-846.

Sebocytes differentially express and secrete adipokines.

In addition to producing sebum, sebocytes link lipid metabolism with inflammation at a cellular level and hence, greatly resemble adipocytes. However, so far no analysis was performed to identify and characterize the adipocyte-associated inflammatory proteins, the members of the adipokine family in sebocytes. Therefore, we determined the expression profile of adipokines [adiponectin, interleukin (IL) 6, resistin, leptin, serpin E1, visfatin, apelin, chemerin, retinol-binding protein 4 (RBP4) and monocyte chemoattractant protein 1 (MCP1)] in sebaceous glands of healthy and various disease-affected (acne, rosacea, melanoma and psoriasis) skin samples. Sebaceous glands in all examined samples expressed adiponectin, IL6, resistin, leptin, serpin E1 and visfatin, but not apelin, chemerin, RBP4 and MCP1. Confirming the presence of the detected adipokines in the human SZ95 sebaceous gland cell line we further characterized their expression and secretion patterns under different stimuli mimicking bacterial invasion [by using Toll-like receptor (TLR)2 and 4 activators], or by 13-cis retinoic acid (13CRA; also known as isotretinoin), a key anti-acne agent. With the exception of resistin, the expression of all of the detected adipokines (adiponectin, IL6, leptin, serpin E1 and visfatin) could be further regulated at the level of gene expression, showing a close correlation with the secreted protein levels. Besides providing further evidence on similarities between adipocytes and sebocytes, our results strongly suggest that sebocytes are not simply targets of inflammation but may exhibit initiatory and modulatory roles in the inflammatory processes of the skin through the expression and secretion of adipokines.

Pigmented naevi and sun protection behaviour among primary and secondary school students in an Eastern Hungarian city.

BACKGROUND: The most important risk factors for malignant melanoma are skin type I or II, large number of atypical naevi and a history of sunburn in childhood and adolescence. METHODS: A cross-sectional study was performed to assess skin type, number of pigmented lesions and sun protection behaviour in 1157 12- to 19-year-old Hungarian students at 20 primary and secondary schools in Debrecen, Hungary. After receiving dermatological training, 18 school doctors examined the students' skin. A questionnaire was completed by the students with the assistance of their parents about sun protection, sunburns and the use of sunbed. Data from 612 questionnaires were evaluated. RESULTS: Based on the doctors' evaluation, most of the pupils were classified as having skin type II and majority of them had 5-20 naevi, particularly on the trunk. Based on the student's response, 5.2% purposely sunbathed daily, 10.1% did not use any form of sun protection, 32.2% wore sun-protective clothing and 65.7% applied sunscreen generally. 6.9% used sunbed, and 74.0% previously experienced serious sunburn at least once. Indoor tanning statistically correlated with the number of melanocytic naevi. CONCLUSION: A high prevalence of sunburn was reported by the students and some of them did not apply any sun protection methods but used sunbed at a critical age for developing melanoma at a later time. These data highlight the importance of educating children and parents about appropriate sun protection.

[Treatment options of non-melanoma skin tumors in organ transplant recipients in relation to a case report]. / Nonmelanoma bortumorok kezelési lehetoségei szervtranszplantált betegeknél egy esetismertetés kapcsán.

The authors present the case of a 59-year-old male patient, whose first kidney transplantation was in 1983 and the second in 2000. The first squamous cell carcinoma appeared on the skin 2 years after the first transplantation. Since 2003, at least two precancerous lesions or non-melanoma skin tumors have been removed surgically yearly. These cancers appeared predominantly on the sun-exposed skin, and were multiple. As these tumors could behave aggressively and prone to recurrence, complex treatment was applied, which included a switch in immunosuppressive drugs and the application of field therapies. The authors give an overview of these treatment options in relation to the case presentation, emphasizing that not only early detection and active treatment of the precancerous lesions and skin cancers are essential, but education of proper sun-protection methods and dermatology care are also important in order to avoid the development of these tumors.

Excessive pediatric fasciitis necrotisans due to Pseudomonas aeruginosa infection successfully treated with negative pressure wound therapy.

The case of a 10-year old female child is described with a history of myeloproliferative disorder having skin, bone and visceral involvement. Bone marrow biopsy revealed histiocytosis X. During chemotherapy necrotizing fasciitis of the lower abdominal wall was diagnosed. Multiple microbiological cultures taken from the wound base revealed Pseudomonas aeruginosa infection. Surgical necrectomy and application of negative pressure wound therapy (NPWT) was started together with intensive care treatment for sepsis. As both wound and general condition of the patient improved, autologous split thickness skin grafting was carried out in two sitting under continuing NPWT application. The applied skin grafts showed excellent take, the perilesional subcutaneous recesses resolved and complete healing was achieved after 28 days of NPWT treatment. Proper dermatological diagnosis and immediate escharectomy complemented with application of NPWT can be life-saving in the treatment of necrotizing fasciitis.

Regulatory T-cell subsets with acquired functional impairment: important indicators of disease severity in atopic dermatitis.

Our aim was to assess whether the presence of highly active effector T cells in atopic dermatitis (AD) is associated with changes in the number and/or function of regulatory T cells (Tregs). Flow cytometry was utilised to determine the percentage of CD4+ CD25bright CD127-/low FOXP3+ and skin-homing CLA+ CD4+ CD25bright FOXP3+ Tregs in healthy controls and AD patients. The correlation between disease severity and Treg percentages was estimated. Treg suppressor activity and cell proliferation were measured after T-cell stimulation. Significantly increased percentages of Tregs were found in AD patients compared to healthy individuals, and significant correlation between the frequency of Tregs and disease severity was also detected. The otherwise normal suppressor activity of Tregs decreased in the presence of Staphylococcus enterotoxin B (SEB). In conclusion, the continuous presence of SEB can trigger an acquired functional impairment of Tregs in AD patients and the correlation between the increased frequency of Tregs and disease severity supports their important role in AD pathogenesis.

The atopic skin-like microenvironment modulates the T-cell-polarising cytokine production of myeloid dendritic cells, as determined by laser scanning cytometry.

Because it is not known exactly when or where myeloid dendritic cells (mDCs) acquire their atopic dermatitis (AD)-specific T-cell-polarising ability in patients with this condition, we used laser scanning cytometry (LSC) to determine whether isolated peripheral blood mDCs from AD patients differed from cells from controls in their cytokine expression profiles de novo and after stimulation with Staphylococcus enterotoxin B (SEB) and thymic stromal lymphopoietin (TSLP), which represents an AD-like microenvironment. Unstimulated mDCs from AD patients showed pluripotent T-cell-polarising capacity, and the surrounding skin microenvironment was essential for the distinctive, disease-specific activity of mDCs (Th2-Th22 bias). We also emphasise that LSC is an attractive technique to study the effect of new DC-targeted therapeutic modalities in AD.

[Disease burden of psoriasis associated with psoriatic arthritis in Hungary]. / Arthritis psoriaticával társuló középsúlyos és súlyos psoriasis betegségterhe Magyarországon.

INTRODUCTION: Psoriasis is a frequent, chronic, systemic immune-mediated disease mainly affecting the skin and joints. AIM: To assess health related quality of life and cost-of-illness in moderate to severe psoriasis associated with psoriatic arthritis. METHOD: A cross-sectional questionnaire survey was conducted at two academic dermatology clinics in Hungary. RESULTS: Fifty-seven patients (65% males) completed the survey with a mean age of 54.3±11.6 years and mean EQ-5D score of 0.48±0.4. Mean annual total cost was €8,977 per patient, of which 71% occurred due to biological therapy and 21% were indirect costs, respectively. Permanent work disability due to psoriasis accounted for €1,775 (95% of the indirect costs). Per patient costs of subgroups not receiving systemic therapy (21%), traditional systemic therapy (32%), and biological systemic therapy (47%) amounted to the sum of €1,729, €1,799, and €16,983, respectively. CONCLUSIONS: Patients on biological therapy showed significantly better health related quality of life. As for health economics, the efficacy of systemic treatments is appropriate to be assessed together in patients with moderate to severe psoriasis associated with psoriatic arthritis, since actual health gain might exceed that reported in psoriasis or psoriatic arthritis separately.

Catalase -262C>T polymorphisms in Hungarian vitiligo patients and in controls: further acatalasemia mutations in Hungary.

Catalase is the main regulator of hydrogen peroxide metabolism. In vitiligo patients there are conflicting data on its activity and no data on the effect of -262C>T polymorphism in the catalase gene. Blood catalase activity, -262C>T polymorphism and acatalasemia mutations were examined in 75 vitiligo patients and in 162 controls, in Hungary. We measured blood catalase activity and conducted analyses with PCR-SSCP, polyacrylamide gel electrophoresis and silver staining in combination with RFLP and nucleotide sequencing. Comparison of the wild (CC) genotype and the mutant (TT) genotype in the vitiligo patients revealed a non significant (P > 0.19) increase in blood catalase. Male controls with the CT genotype had significantly (P < 0.04) lower blood catalase activity than CC genotype controls. Female vitiligo patients with CC genotype had lower (P < 0.04) blood catalase than female controls. The frequency of wild genotype (CC) and C alleles is significantly (P < 0.04) decreased in Hungarian controls when compared to controls in Slovenia, Morocco, UK, Greece, Turkey, USA, China. The detection of a novel acatalasemia mutation (37C>T in exon 9) and the 113G>A (exon 9) mutation in Hungary are further proofs of genetic heterogeneity origin of acatalasemia mutations. In conclusion, the -262 C>T polymorphism has a reverse effect on blood catalase in vitiligo patients and in controls. In controls the mutant genotypes and alleles are more frequent in Hungary than in several other populations. The new acatalasemia mutations are further examples of heterogeneity of acatalasemia.

Resource utilization, work productivity and costs in patients with hidradenitis suppurativa: a cost-of-illness study.

BACKGROUND: Hidradenitis suppurativa (HS) is a, chronic skin disease affecting up to 1% of the population in Europe. This study aims to assess the cost-of-illness of HS from a societal perspective in Hungary and to analyze the predictors of costs. METHODS: A multicentre, cross-sectional cost-of-illness study was performed among 200 adult HS patients. We evaluated direct medical (physician consultations, inpatient admissions, medical, and surgeries), direct non-medical (transportation and caregiving), and indirect costs (productivity loss). RESULTS: The mean annual cost-of-illness of HS was €6,791 per patient. The main cost components were productivity loss (53.3%), biological treatment (21.5%), and informal care (9.2%). Patients missed, on average, 26 and 63 days from work annually due to absenteeism and presenteeism, respectively. Male sex, more severe disease, gluteal involvement, and coexisting inflammatory bowel disease were associated with higher direct medical costs, while lower education level and worse quality-of-life outcomes predicted higher indirect costs. CONCLUSION: This is the first study to assess both direct and indirect costs in HS patients. HS imposes a substantial burden on patients and society, predominantly arising from productivity loss and biological therapy. Resource utilization data and cost-of-illness estimates provide valuable inputs into cost-effectiveness analyses of health interventions in HS.

Altered peripheral invariant natural killer T cells in atopic dermatitis.

BACKGROUND: Conflicting data exist on the number of invariant NKT (iNKT) cells in atopic dermatitis (AD); furthermore, no data have been published on their functional capacity. METHODS: The frequency and number of circulating CD3+6B11+ iNKT cells and their CD4+ and CD4- subpopulations were evaluated in peripheral blood obtained from 41 patients with AD by four-color flow cytometry. Likewise, functional properties of iNKT cells were measured by five-color intracellular cytokine staining. RESULTS: The number and percentage of total iNKT cells and their CD4/CD8 subpopulations were significantly lower than the controls. Of further importance, the CD4-CD8- (double negative, DN) iNKT subgroup showed the strongest positive correlation with total iNKT cells. In addition, the DN subgroup exhibited the most pronounced functional alteration with significantly decreased levels of intracellular IFNγ and significantly increased levels of intracellular IL-4 in AD patients compared with the controls. CONCLUSION: The significantly altered number and cytokine production of iNKT cells from AD patients suggests that these cells may play an important role in the pathogenesis of AD.

Association between serum IL-16 levels and the degree of sensitization in patients with atopic dermatitis.

BACKGROUND: Interleukin (IL)-16 has been characterized as an immunomodulatory cytokine. Besides its chemotactic properties, IL-16 amplifies inflammatory processes and possesses immunoregulatory functions. Our aim was to investigate the association between serum IL-16 levels and the degree of allergic sensitization in patients with atopic dermatitis (AD). METHODS: The serum level of IL-16 was measured by immunoenzymatic assays. Eosinophil cell count, serum total and specific IgE levels were assessed; prick tests were also carried out. Based on specific IgE levels and prick tests, AD patients were divided into sensitized and nonsensitized subgroups, and correlations among serum IL-16, total IgE levels and eosinophil cell counts were measured in the total patient group and in subgroups. RESULTS: In the total patient group, significantly higher levels of IL-16 were found in the sera of patients with AD, compared to healthy individuals and patients with psoriasis. A significant correlation was detected between serum levels of IL-16 and total IgE, total IgE and eosinophil counts, but not between IL-16 and eosinophils. When sensitized and nonsensitized subgroups were compared, IL-16 levels showed a significant difference in subgroups that were divided based on specific IgE measurements, but not in those subgroups which were divided based on prick tests. On the other hand, serum total IgE levels showed a significant difference between sensitized and nonsensitized subgroups, assessed by the specific IgE method and also by prick test. CONCLUSION: Serum IL-16 levels of AD patients correlate to some extent with sensitization. This correlation is not as strong as the correlation between total IgE levels and allergic sensitization.