Antidrug antibody formation during tumor necrosis factor α inhibitor treatment of severe psoriatic patients in the real-life practice.

INTRODUCTION: Antidrug antibody (ADA) production may be the reason behind secondary inefficacy of anti-TNF-α therapy in psoriasis. AIM: To investigate the production of ADA, serum tumor necrosis factor α (TNF-α) and drug levels as predictors of clinical response in real-life circumstances. MATERIAL AND METHODS: Serum drug concentrations (TNFi), the presence of ADAs and serum TNF-α levels were measured in 158 patients by the ELISA method. Clinical response was evaluated by calculating PASI. Their correlation has been statistically analysed. RESULTS: In adalimumab and infliximab treated patients, ADA formation was observed in 18.4% and 33%, respectively, and the serum TNFi concentration was significantly higher in the ADA negative groups. In contrast there was no ADA formation detected among etanercept treated patients. The serum TNFi concentration was significantly lower among non-responders (n = 33). The serum TNF-α level was also measured and the correlation with the concentration of the serum TNFi level was analysed. Having evaluated the results of all patients together, the serum TNFi and TNF-α concentrations showed a significant negative correlation. However, when groups were analysed separately, in case of adalimumab, a significant negative correlation was detected between serum TNFi and TNF-α concentrations. With respect to infliximab, there was no significant correlation, and an inverse correlation was found in the etanercept group. The TNF-α levels and ADA positivity were significantly higher in non-responders. CONCLUSIONS: This study revealed the major role of ADAs against TNFi in case of secondary inefficacy in real-life circumstances. ADA levels show a stronger correlation with PASI failure than serum TNFi or TNF-α levels.

The prevalence of ADH1B and OPRM1 alleles predisposing for alcohol consumption are increased in the Hungarian psoriasis population.

Alcohol intake affects in great the symptoms and life of  psoriasis patients, although the association of SNPs related to increased alcohol consumption with psoriasis has not been elucidated. Therefore, to investigate the association of psoriasis with established alcohol consumption and dependence-related gene variants we conducted a population-based case-control study including 3743 subjects (776 psoriasis cases and 2967 controls from the general Hungarian population). Genotyping of 23 SNPs at ADH1B, ADH1C, ALDH1A1, ALDH2, SLC6A3, DDC, GABRA2, GABRG1, HTR1B, MAOA, TPH2, CHRM2, GRIN2A, POMC, OPRM1, OPRK1 and BDNF were determined and differences in genotype and allele distributions were investigated. Multiple logistic regression analyses were implemented. Analysis revealed association between C allele of the rs1229984 polymorphism (ADH1B gene) and psoriasis risk (ORadditive = 1.58, 95% CI 1.23-2.03, p < 0.001, ORrecessive = 1.58, 95% CI 1.22-2.04, p = 0.001). Furthermore, the G allele of rs1799971 polymorphism (OPRM1 gene) increased the risk of familial aggregation (ORadditive = 1.99, 95% CI 1.36-2.91, p < 0.001 ORdominant = 2.01, 95% CI 1.35-3.01, p < 0.001). In subgroups of psoriatic patients with history of early onset and familial aggregation effect allele 'C' of rs1229984 showed association in the additive and recessive models (ORadditive = 2.41, 95% CI 1.26-4.61, p < 0.01, ORrecessive = 2.42, 95% CI 1.26-4.68, p < 0.01). While effect allele 'G' of rs1799971 (OPRM1) also associated with increased risk of early onset and familial aggregation of psoriasis in the additive and dominant models (ORadditive = 1.75, 95% CI 1.27-2.43, p = 0.001, ORdominant = 1.82, 95% CI 1.26-2.63, p = 0.001). Our results suggest that genetically defined high-risk individuals for alcohol consumption are more common in the psoriasis population.

Streptococcus pyogenes-induced cutaneous lymphocyte antigen-positive T cell-dependent epidermal cell activation triggers TH17 responses in patients with guttate psoriasis.

BACKGROUND: Guttate psoriasis (GP) is characterized by acute onset of small, rounded psoriatic lesions. Although this particular phenotype of psoriasis is usually associated with streptococcal throat infections and mainly occurs in HLA-Cw6(+) patients, the specific immunologic response to this innate stimulus that causes these skin lesions is poorly understood. OBJECTIVE: This study aims to elucidate how key cellular elements of patients with GP respond to Streptococcus pyogenes and whether this initial immune response is favored by the genetic and environmental background of these patients. METHODS: Circulating memory T cells and autologous epidermal cells from samples from either patients with GP (n = 14) or healthy control subjects (n = 6) were cocultured ex vivo in the presence of an S pyogenes extract. Levels of the psoriasis-associated cytokines IL-17A, IL-17F, IFN-γ, TNF-α, IL-6, and IL-8 were determined. The expression of several genes with increased (DEFB4, S100A7, LCN2, IL36G, IL8, CXCL9, CXCL10, and CXCL11) or decreased (FLG and LOR) transcripts in psoriatic lesions was examined in keratinocytes treated with coculture supernatants. RESULTS: When skin-homing effector memory cutaneous lymphocyte antigen-positive T cells were used in cocultures, a TH17-dominant response was observed, as reflected by the higher amounts of IL-17A and IL-17F than IFN-γ. Moreover, a higher TH17 response was observed in cells isolated from patients with flares associated with a streptococcal tonsillitis and with the HLA-Cw6 allele (cohort 1). In addition, in normal keratinocytes the supernatants from these cocultures induced an increase in IL-17-associated genes, such as DEFB4, S100A7, LCN2, IL36G, and IL8 but a decrease in FLG and LOR, thereby confirming the role of activated TH17 cells. CONCLUSION: This study reveals a dominant TH17 response of cutaneous lymphocyte antigen-positive T cells activated by epidermal cells and S pyogenes in patients with GP.

[Genitourethral infections caused by D-K serotypes of Chlamydia trachomatis]. / Chlamydia trachomatis D-K szerovariáns által okozott genitourethralis fertozések.

Sexually transmitted infections of the urogenital tract are most commonly caused by the intracellular bacteria Chlamydia trachomatis worldwide, resulting the clinical picture of acute urethritis in men as well as urethritis and endocervicitis in women. As women often present with few symptoms only or a completely symptom-free disease course, one of the most important long-term complications is chronic pelvic inflammatory disease often followed by the development of infertility caused by chronic scar formation. Well-organized screening programs are considered to have a leading role in the prevention of disease spreading and long lasting unwanted complications. Antibiotic treatment options are often influenced by special circumstances, such as pregnancy and several complicated clinical forms. The aims of the authors are to give a concise review on the current knowledge regarding Chlamydia trachomatis infections and summarize typical clinical signs, modern diagnostic techniques as well as accepted treatment protocols and basic aspects of screening.

[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.

Cost-of-illness in patients with moderate to severe psoriasis: a cross-sectional survey in Hungarian dermatological centres.

BACKGROUND: Despite the widespread availability of biological drugs in psoriasis, there is a shortage of disease burden studies. OBJECTIVES: To assess the cost-of-illness and quality of life of patients with moderate to severe psoriasis in Hungary. METHODS: Consecutive patients with Psoriasis Area and Severity Index (PASI) > 10 and Dermatology Life Quality Index (DLQI) > 10, or treated with traditional systemic (TST) or biological systemic treatment (BST) were included. Demographic data, clinical characteristics, psoriasis related medication, health care utilizations and employment status in the previous 12 months were recorded. Costing was performed from the societal perspective applying the human capital approach. Quality of life was assessed using DLQI and EQ-5D measures. RESULTS: Two-hundred patients were involved (females 32%) with a mean age of 51 (SD 13) years, 103 (52%) patients were on BST. Mean PASI, DLQI and EQ-5D scores were 8 (SD 10), 6 (SD 7) and 0.69 (SD 0.3), respectively. The mean total cost was €9,254/patient/year (SD 8,502) with direct costs accounting for 86%. The main cost driver was BST (mean €7,339/patient/year). Total costs differed significantly across treatment subgroups, mean (SD): no systemic therapy €2,186 (4,165), TST €2,388 (4,106) and BST €15,790 (6,016) (p < 0,001). Patients with BST had better PASI and DLQI scores (p < 0.01) than the other two subgroups. CONCLUSIONS: Patients with biological treatment have a significantly better quality of life and higher total costs than patients with or without traditional systemic treatment. Our study is the largest in Europe and the first in the CEE region that provides cost-of-illness data in psoriasis involving patients with BST.

Exploring the relationship between EQ-5D, DLQI and PASI, and mapping EQ-5D utilities: a cross-sectional study in psoriasis from Hungary.

BACKGROUND: There is a growing interest in policy making for using utility measures and identifying algorithms to convert disease-specific measures into utilities. OBJECTIVES: To analyse the relationship between EQ-5D, Dermatology Life Quality Index (DLQI) and Psoriasis Area and Severity Index (PASI) in psoriasis. To transform DLQI scores, and key clinical, demographic and health service utilisation variables into utilities. METHODS: A cross-sectional questionnaire survey of 200 consecutive adult patients with moderate to severe psoriasis was carried out in two Hungarian university clinics. The relationship between the outcome measures were analysed with correlations and with the known-groups method. Bivariate and multivariate regression algorithms on EQ-5D scores were formulated. RESULTS: The mean age of respondents was 51 years (SD = 12.9), 68.5% were male, and 51.5% received biological therapy. Median EQ-5D, DLQI, and PASI scores were 0.73, 3.0, and 3.45, respectively. EQ-5D showed a moderate correlation with the DLQI and with the PASI (r s = -0.48 and -0.43, p < 0.05). Strong correlation was found between DLQI and PASI (r s = 0.81, p < 0.05). DLQI and PASI discriminated better among groups categorised by the localisation of the lesions than EQ-5D. Presence of psoriasis on the neck and/or décolletage was associated with the greatest health related quality of life (HRQOL) impairment. Ten variables were incorporated in a multivariate algorithm that accounted for 48.8% of EQ-5D variance (ANOVA p < 0.001). CONCLUSIONS: This study provided the first evidence that patients with visible psoriatic lesions have significantly worse HRQOL compared to those with non-visible lesions, measured not only with DLQI but also with EQ-5D. In addition to demographic and clinical variables, our model included health service utilisation variables related to psoriasis, and explained higher proportion of EQ-5D variance than any previous findings in the literature.