Reducing cardiovascular risk in immune-mediated inflammatory diseases: Tumour necrosis factor inhibitors compared to conventional therapies-A systematic review and meta-analysis.

Immune-mediated inflammatory disease (IMID) patients including psoriasis, inflammatory arthritides and bowel diseases have a higher risk of developing cardiovascular (CV) diseases compared to the general population. The increased CV risk may be promoted by tumour necrosis factor (TNF)-α-mediated immunological processes, which are present both in the pathomechanism of IMIDs and atherosclerosis. Our objective was to comprehensively investigate the effect of TNF inhibitors (TNFi) on CV risk compared with conventional therapies in IMIDs. The systematic literature search was conducted in three databases (MEDLINE, EMBASE, Cochrane Library) on 14 November 2022. Randomized controlled trials, cohort and case-control studies were eligible for inclusion. Outcomes consisted of the incidence of CV events, with major adverse cardiovascular events (MACE) as a main endpoint. A random-effects meta-analysis was performed by pooling fully adjusted multivariate hazard ratios (HR) and incidence rate ratios (IRR) with a 95% confidence interval (CI) comparing TNFis with conventional systemic non-biologicals (CSNBs). Of a total of 8724 search results, 56 studies were included overall, of which 29 articles were eligible for the meta-analysis, and 27 were involved in the systematic review. Including all IMIDs, the TNFi group showed a significantly reduced risk of MACE compared with the CSNB group (HR = 0.74, 95% confidence interval (CI) 0.58-0.95, p = 0.025; IRR = 0.77, 95% CI 0.67-0.88, p < 0.001). Subgroup analysis of Pso, PsA patients by pooling IRRs also confirmed the significantly decreased risk of MACE in TNFi-treated patients compared with CSNB groups (IRR = 0.79, 95% CI 0.64-0.98). The observational nature of most included studies leading to high heterogeneity represents a limitation. Based on the results, TNFis may reduce the risk of CV events compared to CSNBs. Therefore, earlier use of TNFis compared to conventional systemic agents in the therapeutic sequence may benefit CV risk in IMID patients.

Acral lentiginous melanoma: a single-centre retrospective review of four decades in East-Central Europe.

BACKGROUND: Acral lentiginous melanoma (ALM) occurs on the palms, soles and subungual surface and has poor prognosis. It is uncommon in the Caucasian population and has remained unreported in East-Central Europe. OBJECTIVES: Our aim was to collect data from East-Central Europe by analysing the demographic and clinicopathologic features of patients with ALM and comparing data with the reports in literature. METHODS: We conducted a single-centre, retrospective review between 1976 and 2016 at one of the largest melanoma referral centres in Hungary. RESULTS: We identified 176 patients with ALM (3.83%) from 4593 patients with melanoma (mean age: 66.2 years). The tumours were mainly located on the lower extremities (88.63%). The mean Breslow tumour thickness was 3.861 mm, 37.50% of the tumours were thicker than 4.00 mm, and 71.6% exhibited microscopic ulceration. Nearly one-third of the patients underwent sentinel lymph node (SLN) biopsy, and 60.3% of the biopsies were positive for metastasis. The positive SLN status was associated with significantly thick tumours and reduced survival. Patients with ALM had 5- and 10-year overall survival rates of 60.5% and 41.6%, respectively. The mean delay in diagnosis was 18 months after the discovery of skin tumours. In multivariate analyses, age, tumour thickness and distant metastasis were independent risk factors for poor survival (P < 0.001). CONCLUSIONS: Our study, which is the first single-centre report in East-Central Europe focusing on ALM, confirms that patient and tumour characteristics and prognostic factors are similar with previous literature data involving Caucasians; however, tumour thickness and survival suggest even worse prognosis.

Long-term safety and efficacy of trifarotene 50 µg/g cream, a first-in-class RAR-γ selective topical retinoid, in patients with moderate facial and truncal acne.

BACKGROUND: Treatment for both facial and truncal acne has not sufficiently been studied. OBJECTIVES: To evaluate the long-term safety and efficacy of trifarotene in both facial and truncal acne. METHODS: In a multicentre, open-label, 52-week study, patients with moderate facial and truncal acne received trifarotene 50 µg/g cream (trifarotene). Assessments included local tolerability, safety, investigator and physician's global assessments (IGA, PGA) and quality of life (QOL). A validated QOL questionnaire was completed by the patient at Baseline, Week 12, 26 and 52/ET. RESULTS: Of 453 patients enrolled, 342 (75.5%) completed the study. Trifarotene-related treatment-emergent adverse events (TEAEs) were reported in 12.6% of patients, and none was serious. Most related TEAEs were cutaneous and occurred during the first 3 months. Signs and symptoms of local tolerability were mostly mild or moderate and severe signs, and symptoms were reported for 2.2% to 7.1% of patients for the face and 2.5% to 5.4% for the trunk. Local irritation increased during the first week of treatment on the face and up to Weeks 2 to 4 on the trunk with both decreasing thereafter. At Week 12, IGA and PGA success rates were 26.6% and 38.6%, respectively. Success rates increased to 65.1% and 66.9%, respectively at Week 52. Overall success (both IGA and PGA success in the same patient) was 57.9% at Week 52. At Week 52 visit, 92/171 (53.8%) patients who had completed their assessments had scores from 0 to 1 (i.e. no effect of acne on their QOL) vs. 47/208 (22.6%) patients at Baseline visit. CONCLUSION: In this 52-week study, trifarotene was safe, well tolerated and effective in moderate facial and truncal acne.

European S1 guidelines on the management of lichen planus: a cooperation of the European Dermatology Forum with the European Academy of Dermatology and Venereology.

Lichen planus (LP) is a chronic inflammatory and immune-mediated disease that affects the skin, hair, nails and mucous membranes. Although there is a broad clinical spectrum of lichen planus manifestations, the skin and oral cavity remain the major sites of involvement. A group of European dermatologists with a long-standing interest and expertise in lichen planus has sought to define therapeutic guidelines for the management of patients with LP. The clinical features, diagnosis and possible medications that clinicians can use, in order to control the disease, will be reviewed in this manuscript. The revised final version of the lichen planus guideline was passed on to the European Dermatology Forum (EDF) for a final consensus with the European Academy of Dermatology and Venereology (EADV).

The management and genetic background of pityriasis rubra pilaris: a single-centre experience.

BACKGROUND: Pityriasis rubra pilaris (PRP) is a rare chronic inflammatory dermatosis with multifactorial aetiology. It is known that particular caspase recruitment domain family member 14 (CARD14) gene mutations are associated with familial PRP and certain forms of psoriasis. Additionally, few data are available about the role of CARD14 gene variants in sporadic PRP. The clinical picture is variable for the different types of PRP, therefore choosing the adequate treatment is often difficult, furthermore there are no specific guidelines for therapy. OBJECTIVE: Our aim was to survey the efficacy of the applied therapies and to screen the CARD14 gene variants in our PRP patients. METHODS: In this retrospective study, patients diagnosed with PRP between 2006 and 2016 at our clinic were involved. Besides the follow-up study of the treatments, the genetic analysis of CARD14 gene was performed. RESULTS: We analysed 19 patients, among whom 17 were diagnosed with type I, one with type III, and one with type V PRP. The majority of the patients were successfully treated with acitretin in combination with systemic corticosteroids, and the remaining patients were treated with other systemic therapies with diverse effects. The genetic screening of CARD14 gene revealed two previously described mutations (rs114688446, rs117918077) and six polymorphisms (rs28674001, rs2066964, rs34367357, rs11653893, rs11652075, rs2289541). Ten of 19 patients carried different CARD14 genetic variants either alone or in combination. CONCLUSION: Based on our experience, we propose that acitretin and an initial combination of short-term systemic corticosteroid therapy could be a successful treatment option for PRP. Although we identified several CARD14 variants in almost half of our cases, we did not find a correlation between the therapeutic response and the genetic background. Our data support the previous observation that CARD14 genetic variants are not specific to PRP, although they may indicate chronic inflammation.

Sebocytes contribute to skin inflammation by promoting the differentiation of T helper 17 cells.

BACKGROUND: The main function of sebocytes is considered to be the production of lipids to moisturize the skin. However, it recently became apparent that sebocytes release chemokines and cytokines and respond to proinflammatory stimuli as well as the presence of bacteria. OBJECTIVES: To analyse the functional communication between human sebocytes and T cells. METHODS: Immunofluorescence stainings for CD4 and interleukin (IL)-17 were performed on acne sections and healthy skin. Migration assays and T-cell-stimulation cultures were performed with supernatants derived from unstimulated or prestimulated SZ95 sebocytes. Dendritic cells were generated in the presence of SZ95 supernatant and subsequently used in mixed leucocyte reactions. RESULTS: We showed that CD4+ IL-17+ T cells accumulate around the pilosebaceous unit and are in close contact with sebocytes in acne lesions. By using SZ95 sebocyte supernatant, we demonstrate a chemotactic effect of sebocytes on neutrophils, monocytes and T cells in a CXCL8-dependent manner. Furthermore, sebocyte supernatant induces the differentiation of CD4+ CD45RA+ naive T cells into T helper (Th)17 cells via the secretion of IL-6, transforming growth factor-ß and, most importantly, IL-1ß. No direct effects of sebocytes on the function of CD4+ CD45RO+ memory T cells were detected. Moreover, sebocytes functionally interact with Propionibacterium acnes in the maturation of dendritic cells, leading to antigen-presenting cells that preferentially prime Th17 cells. CONCLUSIONS: Our study provides evidence that human sebocytes actively participate in inflammatory processes in the skin by recruiting and communicating with immune cells. This interaction leads to the generation of Th17 cells, which might contribute to the pathogenesis not only of acne vulgaris, but also of several inflammatory skin diseases.

Factors shaping the composition of the cutaneous microbiota.

From birth, we are constantly exposed to bacteria, fungi and viruses, some of which are capable of transiently or permanently inhabiting our different body parts as our microbiota. The majority of our microbial interactions occur during and after birth, and several different factors, including age, sex, genetic constitution, environmental conditions and lifestyle, have been suggested to shape the composition of this microbial community. Propionibacterium acnes is one of the most dominant lipophilic microbes of the postadolescent, sebum-rich human skin regions. Currently, the role of this bacterium in the pathogenesis of the most common inflammatory skin disease, acne vulgaris, is a topic of intense scientific debate. Recent results suggest that Westernization strongly increases the dominance of the Propionibacterium genus in human skin compared with natural populations living more traditional lifestyles. According to the disappearing microbiota hypothesis proposed by Martin Blaser, such alterations in the composition of our microbiota are the possible consequences of socioeconomic and lifestyle changes occurring after the industrial revolution. Evanescence of species that are important elements of the human ecosystem might lead to the overgrowth and subsequent dominance of others because of the lack of ecological competition. Such changes can disturb the fine-tuned balance of the human body and, accordingly, our microbes developed through a long co-evolutionary process. These processes might lead to the transformation of a seemingly harmless species into an opportunistic pathogen through bacterial dysbiosis. This might have happened in the case of P. acnes in acne pathogenesis.

Sebum lipids influence macrophage polarization and activation.

BACKGROUND: As lipids are known to regulate macrophage functions, it is reasonable to suppose that a sebocyte-macrophage axis mediated by sebum lipids may exist. OBJECTIVES: To investigate if sebocytes could contribute to the differentiation, polarization and function of macrophages with their secreted lipids. METHODS: Oil Red O lipid staining and Raman spectroscopy were used to assess the dermal lipid content and penetration. Immunohistochemistry was used to analyse the macrophage subsets. Human peripheral blood monocytes were differentiated in the presence of either supernatant from human SZ95 sebocytes or major sebum lipid components and activated with Propionibacterium acnes. Macrophage surface markers and their capacity to uptake fluorescein isothiocyanate-conjugated P. acnes were detected by fluorescence-activated cell sorting measurements. Cytokine protein levels were evaluated by enzyme-linked immunosorbent assay and Western blot analysis. RESULTS: Sebaceous gland-rich skin had an increased dermal lipid content vs. sebaceous gland-poor skin to which all the tested sebum component lipids could contribute by penetrating the dermoepidermal barrier. Of the lipids, oleic acid and linoleic acid promoted monocyte differentiation into alternatively activated macrophages. Moreover, linoleic acid also had an anti-inflammatory effect in P. acnes-activated macrophages, inhibiting the secretion of interleukin (IL)-1ß, IL-6 and tumour necrosis factor (TNF)-α. Squalene, palmitic acid, stearic acid and oleic acid augmented the secretion of IL-1ß, even in the absence of P. acnes, whereas oleic acid had a selective effect of inducing IL-1ß but downregulating IL-6 and TNF-α secretion. CONCLUSIONS: Our results suggest a role for sebaceous glands in modulating innate immune responses via their secreted lipids that are of possible pathological and therapeutic relevance.

HuCOP1 contributes to the regulation of DNA repair in keratinocytes.

We have previously demonstrated that the E3 ligase Human Constitutive Photomorphogenic Protein (huCOP1) is expressed in human keratinocytes and negatively regulates p53. The MutS homolog 2 (MSH2) protein plays a central role in DNA MMR mechanism and is implicated in the cellular response to anticancer agents, such as cisplatin. Our aim was to clarify whether huCOP1 plays a role in DNA MMR by affecting MSH2 protein level in human keratinocytes. To define the role of huCOP1 in DNA mismatch repair, we determined whether huCOP1 affects MSH2 abundance. MSH2 protein level was detected by immunocytochemical staining using a keratinocyte cell line in which the expression level of huCOP1 was stably decreased (siCOP1). To investigate whether huCOP1 silencing influences cisplatin-induced cell death, control and siCOP1 keratinocyte cells were treated with increasing concentrations of cisplatin and cell viability was recorded after 48 and 96 h. Stable silencing of huCOP1 in human keratinocytes resulted in a reduced level of MSH2 protein. huCOP1 silencing also sensitized keratinocytes to the interstrand crosslinking inducer cisplatin. Our results indicate that decreased huCOP1 correlates with lower MSH2 levels. These protein level changes lead to increased sensitivity toward cisplatin treatment, implicating that huCOP1 plays a positive role in maintaining genome integrity in human keratinocytes.

Splicing factors differentially expressed in psoriasis alter mRNA maturation of disease-associated EDA+ fibronectin.

The EDA+ fibronectin splicing variant is overexpressed in psoriatic non-lesional epidermis and sensitizes keratinocytes to mitogenic signals. However, regulation of its abundance is only partially understood. In our recent cDNA microarray experiment, we identified three SR-rich splicing factors-splicing factor, arginine/serine-rich 18 (SFRS18), peptidyl-prolyl cis-trans isomerase G (PPIG), and luc-7 like protein 3 (LUC7L3)-which might be implicated in the preactivated states of keratinocytes in psoriatic non-involved skin and could also contribute to the regulation of fibronectin mRNA maturation. In this study, we investigated the role of LUC7L3, PPIG, and SFRS18 in psoriasis and in the mRNA maturation process of fibronectin. Regarding tissue staining experiments, we were able to demonstrate a characteristic distribution of the splicing factors in healthy, psoriatic non-involved and involved epidermis. Moreover, the expression profiles of these SR-rich proteins were found to be very similar in synchronized keratinocytes. Contribution of splicing facwwtors to the EDA+ fibronectin formation was also confirmed: their siRNA silencing leads to altered fibronectin mRNA and protein expression patterns, suggesting the participation in the EDA domain inclusion. Our results indicate that LUC7L3, PPIG, and SFRS18 are not only implicated in EDA+ fibronectin formation, but also that they could possess multiple roles in psoriasis-associated molecular abnormalities.

Atypical neurofibromatosis type 1 with unilateral limb hypertrophy mimicking overgrowth syndrome.

Neurofibromatosis type 1 (NF1; OMIM 162200), a dominantly inherited multitumor syndrome, results from mutations in the Neurofibromin 1 (NF1) gene. We present the case of a Hungarian woman with the clinical phenotype of NF1 over her whole body and the clinical features of unilateral overgrowth involving her entire left leg. This unusual phenotype suggested either the atypical form of NF1 or the coexistence of NF1 and overgrowth syndrome. Direct sequencing of the genomic DNA isolated from peripheral blood revealed a novel frameshift mutation (c.5727insT, p.V1909fsX1912) in the NF1 gene. Next-generation sequencing of 50 oncogenes and tumour suppressor genes, performed on the genomic DNAs isolated from tissue samples and peripheral blood, detected only wild-type sequences. Based on these results, we concluded that the patient is affected by an unusual phenotype of NF1, and that the observed unilateral overgrowth of the left leg might be a rare consequence of the identified c.5727insT mutation.

Neutrophil-to-lymphocyte ratio: a biomarker for predicting systemic involvement in adult IgA vasculitis patients.

BACKGROUND: IgA vasculitis (IgAV) is a small-vessel leucocytoclastic cutaneous vasculitis, often associated with kidney and gastrointestinal (GI) manifestations. Although predictive factors for systemic involvement have been extensively studied in children, there is paucity in the literature regarding adult patients. Neutrophil-to-lymphocyte ratio (NLR) is an inflammatory marker, used to assess systemic inflammation in various diseases. OBJECTIVE: We sought to evaluate whether NLR can be used for predicting renal and GI involvement in adult IgA vasculitis patients. METHODS: This was a retrospective review of adult patients who were diagnosed with IgAV at our institution between 2004 and 2016. RESULTS: A total of 40 patients met our inclusion criteria. Half of the enrolled patients had clinical symptoms suggestive of systemic involvement, of which 6 (15%) had only renal, 3 (7.5%) had only GI and 11 (27.5%) had both renal and GI involvement. Pretreatment NLR was significantly associated with renal and/or GI manifestations of the disease (P < 0.001). The optimal cut-off value of NLR, for predicting systemic involvement was 3.34, with a specificity of 95% and a sensitivity of 85%. In addition, pretreatment NLR was also found to be significantly correlated with the severity of the systemic manifestations of IgAV (P = 0.022). CONCLUSION: This study suggests that NLR is a potential indicator for prognosticating systemic involvement in adult IgAV.

Abnormal regulation of fibronectin production by fibroblasts in psoriasis.

BACKGROUND: Data indicate that in psoriasis, abnormalities are already present in nonlesional skin. Transforming growth factor-ß and keratinocyte growth factor (KGF), together with fibronectin and α5ß1 integrin, were suggested to play a crucial role in the pathogenesis of psoriasis by influencing inflammation and keratinocyte hyperproliferation. OBJECTIVES: To investigate the expression of KGF, fibroblast growth factor receptor (FGFR)2, fibronectin (FN) and extra domain A (EDA)-positive FN in healthy and nonlesional psoriatic skin, and to study the effect of KGF on the regulation of FN and EDA(+) FN production by fibroblasts. METHODS: Healthy, nonlesional psoriatic skin and lesional psoriatic skin were immunostained for α5 integrin, KGF, FGFR2, EDA(+) FN and signal transducer and activator of transcription (STAT)1. KGF-treated cell cultures were analysed for FN and EDA(+) FN mRNA and protein by real-time reverse-transcriptase polymerase chain reaction and flow cytometry, respectively. The major downstream signalling of KGF was investigated by blocking experiments using inhibitors of mitogen-activated protein kinase (MAPK) kinase (MEK1), AKT1/2, STAT1 and STAT3. RESULTS: The expression of α5 integrin, EDA(+) FN, KGF and its receptor FGFR2 is elevated in psoriatic nonlesional skin compared with healthy skin. KGF mildly induced EDA(+) FN, but not FN expression in healthy fibroblasts through MAPK signalling. Fibroblasts express the FGFR2-IIIc splice variant. STAT1 negatively regulates both FN and EDA(+) FN expression in healthy fibroblasts, and this regulation is compromised in fibroblasts derived from nonlesional psoriatic dermis. We detected active STAT1 in healthy and lesional skin, similarly to a previous report. However, in the nonlesional skin STAT1 activation was absent in tissues far away from lesions. CONCLUSIONS: The production of FN and EDA(+) FN by fibroblasts and the signalling of STAT1 are abnormally regulated in psoriatic nonlesional skin.

One mutation, two phenotypes: a single nonsense mutation of the CTSC gene causes two clinically distinct phenotypes.

BACKGROUND: Papillon-Lefévre syndrome (PLS; OMIM 245000) and Haim-Munk syndromes (HMS; OMIM 245010) are phenotypic variants of the same rare disease caused by mutations of the cathepsin C (CTSC) gene, and they exhibit autosomal recessive inheritance. AIMS: To identify diseases caused by mutations of the CTSC gene in two Hungarian patients and to perform haplotype analysis to elucidate any familial relationship between them. METHODS: Mutation screening and polymorphism analysis were performed by direct sequencing of the CTSC gene. RESULTS: Mutation screening of the CTSC gene from the two patients revealed the presence of the same homozygous nonsense mutation (c.748C/T; p.Arg250X). However, one patient exhibited the PLS phenotype and the other the HMS phenotype. Although these patients were not aware that they were related, haplotype analysis, especially the genotypes of the rs217116 and the rs217115 polymorphisms, clearly indicated that the patients carry the same haplotype, whereas the unrelated healthy controls carried several different haplotypes. CONCLUSIONS: Our results demonstrate that PLS and HMS are phenotypic variants of the same disease and, additionally, exclude the presence of a putative genetic modifier factor within the CTSC gene that is responsible for the development of the two phenotypes. We suggest that this putative genetic modifier factor is located outside the CTSC gene, or alternatively, that the development of the different phenotypes is the consequence of different environmental or lifestyle factors.

A consensus-based practical and daily guide for the treatment of acne patients.

BACKGROUND: Many current guidelines provide detailed evidence-based recommendations for acne treatment. OBJECTIVE: To create consensus-based, simple, easy-to-use algorithms for clinical acne treatment in daily office-based practice and to provide checklists to assist in determining why a patient may not have responded to treatment and what action to take. METHODS: Existing treatment guidelines and consensus papers were reviewed. The information in them was extracted and simplified according to daily clinical practice needs using a consensus-based approach and based on the authors' clinical expertise. RESULTS: As outcomes, separate simple algorithms are presented for the treatment of predominant comedonal, predominant papulopustular and nodular/conglobate acne. Patients with predominant comedonal acne should initially be treated with a topical retinoid, azelaic acid or salicylic acid. Fixed combination topicals are recommended for patients with predominant papulopustular acne with treatment tailored according to the severity of disease. Treatment recommendations for nodular/conglobate acne include oral isotretinoin or fixed combinations plus oral antibiotics in men, and these options may be supplemented with oral anti-androgenic hormonal therapy in women. Further decisions regarding treatment responses should be evaluated 8 weeks after treatment initiation in patients with predominant comedonal or papulopustular acne and 12 weeks after in those with nodular/conglobate acne. Maintenance therapy with a topical retinoid or azelaic acid should be commenced once a patient is clear or almost clear of their acne to prevent the disease from recurring. The principal explanations for lack of treatment response fall into 5 main categories: disease progression, non-drug-related reasons, drug-related reasons, poor adherence, and adverse events. CONCLUSION: This practical guide provides dermatologists with treatment algorithms adapted to different clinical features of acne which are simple and easy to use in daily clinical practice. The checklists to establish the causes for a lack of treatment response and subsequent action to take will facilitate successful acne management.

Effect of etanercept therapy on psoriasis symptoms in patients from Latin America, Central Europe, and Asia: a subset analysis of the PRISTINE trial.

BACKGROUND: Psoriasis prevalence and characteristics in Asia, Central Europe, and Latin America have not been thoroughly investigated and there are no large trials for biologic treatments for patients from these regions. The goal of this analysis was to report clinical response to anti-tumor necrosis factor-alpha treatment in these patients. METHODS: Patients from Argentina, Czech Republic, Hungary, Mexico, Taiwan, and Thailand (N=171) were included in this subset analysis of the PRISTINE trial. Patients with stable moderate-to-severe plaque psoriasis were blinded and randomized to receive etanercept 50 mg once weekly (QW) or biweekly (BIW) for 12 weeks, followed by 12 weeks of open-label QW treatment with etanercept 50 mg through week 24 (QW/QW vs. BIW/QW). Concomitant methotrexate (≤20 mg/week) and mild topical corticosteroids or other agents were permitted at the physician's discretion, in accordance with therapeutic practice. RESULTS: As early as week 8, 26.7 % in the etanercept QW group and 44.0 % in the BIW group achieved Psoriasis Area and Severity Index (PASI) 75. At weeks 12 and 24, respectively, PASI 75 increased to 39.5 % and 62.8 % in the QW/QW group and 66.7 % and 83.3 % in the BIW/QW group. PASI 75 was significantly different between treatment groups from week 8 through the end of study (p<0.05). The Kaplan-Meier estimate of the proportions achieving PASI 75 in QW/QW and BIW/QW groups, respectively, was 27.4 % and 45.8 % through week 8; 41.9 % and 68.7 % through week 12; and 72.5 % and 95.2 % through week 24. CONCLUSIONS: Treatment with etanercept 50 mg provided rapid relief of psoriasis symptoms in patients from Asia, Central Europe, and Latin America. A more rapid response was observed in patients who received BIW treatment for the first 12 weeks which was sustained after reducing to QW dosing for the subsequent 12 weeks. Response rates were similar to those observed in the overall PRISTINE population. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00663052 .

Current practice of methotrexate use for psoriasis: results of a worldwide survey among dermatologists.

BACKGROUND: Methotrexate is one the most commonly used systemic therapies for psoriasis. Despite its widespread use in psoriasis therapy, dermatologists' practice regarding the use of methotrexate has not been investigated on global scale. OBJECTIVE: To evaluate the real life use of methotrexate for psoriasis treatment in the dermatological community worldwide. METHODS: A questionnaire consisting of 41 questions was designed by the Psoriasis International Network (PIN). Questions focused on safety, dosing, administration, folic acid supplementation and combination therapy aspects of methotrexate use. The anonymous web-based survey was distributed to dermatologists by the national coordinators of PIN. RESULTS: Between 2 April and 7 August 2012, 481 dermatologists from 63 countries completed the questionnaire. Most respondents were from European and South American countries, whereas the response rate from Central America and the Near East was lowest. The majority of responders were experienced dermatologists (86% had more than 5 years of experience in psoriasis treatment). Starting and maintenance doses of 10 mg of methotrexate or lower were reported by 67% and 42% of respondents respectively. Thirty-eight per cent of respondents stop treatment at a cumulative dose of 2 g, whereas 36% did not consider cumulative dose important in this respect. The primary mode of administration was oral, and the majority of respondents administer folic acid supplementation. Almost all respondents monitored full blood count, liver and renal function tests, whereas procollagen 3 amino terminal peptide measurement and transient elastography is used by only a minority of dermatologists. There were significant differences concerning the doses, routes of administration and safety monitoring among the clinical practices in different geographical locations. CONCLUSION: Current clinical practice of methotrexate use in psoriasis is not uniform, depends on geographical location, and is not in full agreement with clinical guidelines.