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Atiya Rungjang,1 Jitlada Meephansan,1 Sunchai Payungporn,2 Vorthon Sawaswong,2 Prangwalai Chanchaem,2 Purit Pureesrisak,3 Jongkonnee Wongpiyabovorn,4 Hok Bing Thio5 1Division of Dermatology, Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, Thailand; 2The Research Unit of Systems Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 3Division of Dermatology, Department of Medicine, Rajavithi Hospital, Ministry of Public Health, Bangkok, Thailand; 4Division of Immunology, Department of Microbiology, Faculty of Medicine, Center of Excellence in Immunology and Immune Mediated Diseases, Chulalongkorn University, Bangkok, 10330, Thailand; 5Department of Dermatology, Erasmus University Medical Center, Rotterdam, the NetherlandsCorrespondence: Jitlada Meephansan, Division of Dermatology, Chulabhorn International College of Medicine, Thammasat University, Rangsit Campus, Klong Luang, Pathum Thani, 12120, Thailand, Tel +66 0 2564-4444, ext.1535, Fax +66 0 2564-4440, ext.7594, Email kae_mdcu@yahoo.comPurpose: Although the pathogenesis of psoriasis involves the dermis, most previous studies collected samples using the swab technique. A recent study examining the microbiomes obtained via both skin biopsies and swabs revealed a significant difference in normal skin. We hypothesized that the microbiome profile of patients with psoriasis from tape stripping and skin biopsy might be different. This study sought to contribute to microbiome research on psoriasis by investigating the changes in the microbiome during narrowband ultraviolet B (NBUVB) therapy by comparing the results from the different sampling techniques of tape stripping and skin biopsy.Patients and Methods: Twenty-three participants, including 14 patients with chronic plaque psoriasis and nine healthy controls, were recruited, and nine patients with psoriasis completed 20-sessions of NBUVB treatment. Skin microbiota from both techniques was analyzed using the 16S rRNA gene at baseline and after treatment.Results: A clear difference was observed between the results from the two sampling techniques. Alpha diversity of the microbiota obtained from tape stripping was higher than that of the microbiota from skin biopsy, whereas beta diversity was clustered into two groups by sampling technique. The microbiome was altered during NBUVB treatment using both sampling techniques.Conclusion: Different sampling techniques resulted in different microbiome profiles in patients with psoriasis. Tape stripping and swabs are feasible procedures and are mostly used in psoriasis and other skin microbiome studies; however, skin biopsy may also expand our understanding of psoriasis and other skin diseases that pathophysiology involves deeper to the dermis or subcutaneous tissue.Keywords: skin microbiome, psoriasis, sampling techniques, NBUVB

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome and chronic nonbacterial osteomyelitis (CNO) are rare autoinflammatory/autoimmune conditions seen in adults and children. Although osteoarticular manifestations are the primary distinguishing features of SAPHO, over half of patients also have palmoplantar pustulosis (PPP). These and other associated disorders such as acne, inflammatory bowel disease, and hidradenitis suppurativa are characterized, at least in the early stages, by neutrophilic infiltration. The bone and skin manifestations exhibit both innate and adaptive immune responses and therefore share similar pathogenic molecules and overlapping treatment targets. At the Group for Research and Assessment for Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting, a 3-part presentation provided an overview of current efforts at establishing consensus on diagnosis/classification, treatment, and core outcome sets for SAPHO/CNO; an overview of PPP in SAPHO and as a standalone condition; and finally, an overview of the role of the neutrophil in these disorders., (Copyright © 2024 by The Journal of Rheumatology.)

Probiotics and synbiotics are used to treat chronic illnesses due to their roles in immune system modulation and anti-inflammatory response. They have been shown to reduce inflammation in a number of immune-related disorders, including systemic lupus erythematosus (SLE), human immunodeficiency virus (HIV), and chronic inflammatory skin conditions such as psoriasis and atopic dermatitis (AD). Akkermansia muciniphila ( A. muciniphila ) and Faecalibacterium prausnitzii ( F. prausnitzii ) are two different types of bacteria that play a significant part in this function. It has been established that Akkermansia and Faecalibacterium are abundant in normal populations and have protective benefits on digestive health while also enhancing the immune system, metabolism, and gut barrier of the host. They have the potential to be a therapeutic target in diseases connected to the microbiota, such as immunological disorders and cancer immunotherapy. There has not been a review of the anti-inflammatory effects of Akkermansia and Faecalibacterium , particularly in immunological diseases. In this review, we highlight the most recent scientific findings regarding A. muciniphila and F. prausnitzii as two significant gut microbiota for microbiome alterations and seek to provide cutting-edge insight in terms of microbiome-targeted therapies as promising preventive and therapeutic tools in immune-related diseases and cancer immunotherapy.

The skin microbiota is essential for human health; altered skin microbiome colonization and homeostasis may be associated with several inflammatory skin conditions and other inflammatory diseases. Malassezia spp. are commensal fungi commonly found on the human skin, and they also play a pathogenic role in various skin diseases. It is hypothesized that the exposure of human skin to air pollution might be associated with Malassezia spp. colonization. The aim of this study was to compare Malassezia spp. colonization on healthy human skin between people living in two major cities in Thailand with different air qualities: one city with highly polluted ambient air and the other with less polluted air. Skin microbiome samples from 66 participants were collected using swabbing and scraping techniques. The skin fungal composition was analysed using high-throughput sequencing based on internal transcribed spacer 2 (ITS2) rDNA. A significant difference was found in alpha and beta diversities and the relative abundance of fungal profiles between the groups. The relative abundance of Malassezia spp. was found to be significantly higher in the highly polluted area than in the less polluted area. This study demonstrates that high-ambient air pollution may alter Malassezia spp. colonization on healthy human skin, which could lead to dysbiosis of the cutaneous ecosystem and eventually result in some skin disorders., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Gut microbiome dysbiosis is associated with psoriasis development. A relationship between gut microbiota and psoriasis treatment response has been reported. No study has reported the effect of narrowband ultraviolet B (NBUVB) therapy, a standard treatment of psoriasis, on gut microbiota. This study aimed to evaluate gut microbiota change during NBUVB therapy. Stool samples from 22 participants, including 13 patients with chronic plaque psoriasis and nine healthy controls, were recruited. Faecal microbiota composition was analysed using 16S rRNA sequencing before and after NBUVB therapy. Serum 25-OH vitamin D of patients with psoriasis was evaluated simultaneously. The most abundant phyla of gut microbiota in patients with psoriasis were Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria in all participants. Bilophila, Paraprevotella, Alistipes, Sutterella, Romboutsia, Clostridium sensu stricto and Agathobacter are significantly more enriched in healthy controls. Lactobacillales and Ruminococus torques appeared more enriched after NBUVB treatment in responders but not non-responders. Serum vitamin D levels significantly increased after NBUVB treatment. The present study revealed that gut microbiota altered after NBUVB treatment. The change might be treatment-specific and influence the treatment response., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Approximately one fifth of the world population experiences continuous itch for 6 weeks or more during their life, that is chronic itch. It is diverse in its aetiologies, and it is notoriously hard to treat. Because itch and pain have largely overlapping pathophysiology and the demonstrated efficacy of neurostimulation in treatment of selected chronic pain conditions, we conducted a systematic review to investigate whether neurostimulation could be an effective treatment for chronic itch. We identified two randomized controlled trials and 17 open label studies or case reports investigating various neurostimulation modalities for the treatment of refractory itch of various aetiologies. Transcutaneous electrical nerve stimulation (TENS) was the most investigated modality (n = 17), and in the largest number of conditions. Other modalities were cutaneous field stimulation (n = 2), painscrambler (n = 1), transcranial direct current stimulation (n = 1) and peripheral nerve field stimulation (n = 1). Atopic dermatitis was the most studied condition (n = 5). Despite the large heterogeneity in used stimulation paradigms and outcome parameters, all studies reported a positive effect of at least one neurostimulation modality. Our review indicates that electrical neurostimulation could be considered for the treatment of refractory chronic itch of selected aetiologies, such as atopic dermatitis or burn pruritus. However, better understanding of the mechanisms of action of the neurostimulation modalities and regimens in various pruritic conditions is necessary., (© 2021 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)

Background: Leprosy is a chronic infectious disease that can lead to severe lifelong disabilities. Close contacts of patients with leprosy have a higher risk of acquiring the disease. Nevertheless, there is a lack of reliable markers to predict Mycobacterium leprae infection. We aimed to identify new potential markers for developing clinical leprosy among contacts., Methods: Serum levels of interleukin (IL) 6, IL-8, IL-10, hemoglobin, ferritin, and transferrin saturation were measured in 67 patients with multibacillary leprosy (MB), 65 household contacts (HHCs) of MB patients, and 127 endemic controls (ECs). By means of multivariate logistic regression and receiver operating characteristic (ROC) analyses, we analyzed baseline variables and laboratory parameters that showed significant differences between MB in the HHC and EC groups and obtained the respective areas under the curve (AUC). Optimal cutoff values of the associated cytokines were also determined., Results: Elevated IL-6 level was observed in MB patients compared to HHCs and ECs ( P  = .022 and .0041, respectively). Anemia and iron deficiency were also higher in the MB group compared to HHCs or ECs ( P  < .001). Likewise, we observed an increased risk of having MB leprosy in underweight HHCs (odds ratio [OR], 2.599 [95% confidence interval {CI}, .991-6.820]) and underweight ECs (OR, 2.176 [95% CI, 1.010-4.692]). Further ROC analysis showed that high serum IL-6 level, underweight, anemia, and iron deficiency can discriminate leprosy from their HHCs (AUC, 0.843 [95% CI, .771-.914]; P   =  .000; optimal cutoff value of IL-6 = 9.14 pg/mL)., Conclusions: Our results suggest that serum IL-6 and nutrition status could serve as potential prognostic markers for the development of clinical leprosy in infected individuals., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Children who live in leprosy-endemic areas are susceptible to infection due to early and frequent exposure to Mycobacterium leprae. Indonesia is on the verge of eliminating this disease (prevalence rate < 1/10,000 population), but pediatric leprosy continues to occur in low-endemic areas. This study aimed to evaluate pediatric leprosy over a decade in a tertiary hospital in Surabaya, Indonesia. A retrospective study of leprosy in children under 15 years old between 2010 and 2019 was conducted in the Morbus Hansen Division, Outpatient Clinic at Dr. Soetomo Hospital in Surabaya, Indonesia. Seventy pediatric leprosy cases were identified between 2010 and 2019, consisting of 58 multibacillary (MB)-type cases and 12 paucibacillary (PB)-type cases. Slit skin smear (SSS) was positive in 26 cases. There were two cases of grade-2 disability and 15 cases of leprosy reaction (erythema nodosum leprosum) in children at the time of diagnosis. There was an insignificant decline in the number of pediatric leprosy cases in the last 10 years. Cases and disabilities in children were found in some leprosy pocket areas even though the national elimination rate has been achieved. MB infections, disability, and treatment defaults were common problems in pediatric leprosy.

Competing Interests: Declaration of interests We declare no competing interests.

We describe an unusual case of type 2 leprosy reaction (T2R) with septic shock-like features induced by helminth infection in a 31-year-old Moluccan male patient with a history of completed treatment of WHO multidrug therapy (MDT)-multibacillary (MB) regimen 2 years before admission. During the course of illness, the patient had numerous complications, including septic shock, anemia, and disseminated intravascular coagulation (DIC). Nevertheless, antibiotic therapies failed to give significant results, and the source of infection could not be identified. Helminth infection was subsequently revealed by endoscopic examination followed by parasitological culture. Resolution of symptoms and normal level of organ function-specific markers were resolved within 3 days following anthelmintic treatment. This report demonstrated the challenge in the diagnosis and treatment of severe T2R. Given that helminth infections may trigger severe T2R that mimics septic shock, health professionals need to be aware of this clinical presentation, especially in endemic regions of both diseases., Competing Interests: The authors have declared that no competing interests exist.

Chronic itch, defined as an itching sensation that persists for more than 6 weeks, is a common complaint that is associated with a high burden of disease. Chronic itch can occur due to a variety of skin diseases, but can also feature as prominent symptom in various internal, neurologic, and psychiatric disorders. Importantly, chronic itch can be drug-related. Determining the underlying cause can be challenging, yet it is an essential step in the management of chronic itch. When generalized chronic itch presents with no primary skin lesions and/or secondary skin lesions, the diagnostic work-up should consist of a detailed history and physical examination with an initial limited screening of laboratory tests. Subsequent additional screening should be dictated by clinical suspicion. In 8% of patients, no underlying cause can be identified: pruritus of unknown origin. The management of chronic itch of unknown origin preferably follows a multimodal approach.

The next step in the treatment of immune diseases: jakinibs, inhibitors of the intracellular Janus kinase The intracellular Janus kinase (JAK) and the signal transduction and activator of transcription (STAT) proteins are involved in the whole spectrum of immune-mediated diseases. Currently, agents are developed that influence the JAK-STAT mechanism. JAK inhibitors (jakinibs) have only recently made their way into clinical practice. These agents exhibit both similarities and differences in terms of effectiveness and safety. In the coming years, results from basic and clinical research will improve our knowledge of these agents. For patients who suffer from immune-mediated diseases, their introduction appears to be a breakthrough that will offer new treatment options. One advantage over biologicals is that jakinibs can be taken orally. As with all new innovative medicines, with jakinibs one cannot escape a discussion over costs as well. The balance between the added value of jakinibs compared to biologicals, and the actual purchase prices for each of these treatment modalities, will influence the eventual positioning of jakinibs.

Background: Chronic spontaneous urticaria (CSU) is a skin disease with itchy hives and/or angio-oedema that last for at least 6 weeks without an obvious external trigger., Objectives: To determine the cost-effectiveness of omalizumab relative to standard of care (SoC; up to four times the daily dose of H 1 -antihistamines) in the Netherlands from a societal perspective., Methods: The Markov model used consisted of five health states based on Urticaria Activity Score over 7 days. Model settings and characteristics of the Dutch patient population were based on an online survey among clinical experts and were validated during an expert committee meeting. Transition probabilities were derived from the GLACIAL trial. Healthcare consumption, quality of life (using EuroQol-5D) and productivity losses were derived from a burden-of-illness study (ASSURE-CSU) among 93 Dutch patients. Healthcare consumption and productivity losses were evaluated using the Dutch costing manual. The comparator treatment was SoC, consisting of (updosed) antihistamines. A 10-year time horizon was used., Results: The incremental cost-effectiveness ratio (ICER) of omalizumab vs. SoC was €17 502 per quality-adjusted life-year (QALY) gained. Productivity costs played an important role in the value of the ICER; discarding productivity costs resulted in an ICER of €85 310 per QALY., Conclusions: Omalizumab is cost-effective compared with SoC. The outcomes of this study were used to establish omalizumab as third-line therapy in the Dutch treatment guidelines for CSU., (© 2018 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Recent advances have highlighted the crucial role of microbiota in the pathophysiology of chronic inflammatory diseases as well as its impact on the efficacy of therapeutic agents. Psoriasis is a chronic, multifactorial inflammatory skin disorder, which has a microbiota distinct from healthy, unaffected skin., Aim: Through an extensive review of the literature, we aim to discuss the skin and gut microbiota and redefine their role in the pathogenesis of psoriasis., Conclusions: Unfortunately, the direct link between the skin microbiota and the pathogenesis of psoriasis remains to be clearly established. Apart from improving the course of psoriasis, selective modulation of the microbiota may increase the efficacy of medical treatments as well as attenuate their side effects.

Psoriasis is a chronic, inflammatory immune-mediated skin disease that affects about 2% of the world's population. In 20% of patients with psoriasis, the characteristic skin lesions are accompanied by psoriatic arthritis (PsA). Psoriasis arises in genetically predisposed individuals who have a dysregulated immune response to various environmental factors. The human body is home to many microbial species, and both the skin and the gut microbiome influence the development and function of immune tissue development and function. Studies on the cutaneous microbiome show a trend toward an increased relative abundance of Streptococcus and a decreased level of Propionibacterium in patients with psoriasis compared to healthy controls. In the gut microbiome, the ratio of Firmicutes and Bacteroidetes was perturbed in psoriatic individuals compared to healthy controls. Actinobacteria was relatively underrepresented in patients with psoriasis compared to healthy individuals. A decrease in skin microbiome flora diversity seems to be a sign that a patient with psoriasis is at elevated risk for developing arthritis. Modulating the skin microbiota for therapeutic reasons can be achieved by antimicrobial (antibiotic) therapy, the application of prebiotics or probiotics, or the transplantation of an entire healthy microbial population.

Background: Poverty has long been considered a risk factor for leprosy and is related to nutritional deficiencies. In this study, we aim to investigate the association between poverty-related diet and nutrition with leprosy., Methodology/principal Findings: In rural leprosy-endemic areas in Indonesia, we conducted a household-based case-control study using two controls for each case patient (100 recently diagnosed leprosy patients and 200 controls), matched for age and gender. All participants were interviewed to collect information on their demographics, socioeconomic situation, health, and diet. Body mass index, dietary diversity score, as well as anemia and iron micronutrient profiles were also obtained. By means of univariate, block-wise multivariate, and integrated logistic regression analyses, we calculated odds ratios between the variables and the occurrence of leprosy. Unstable income (odds ratio [OR], 5.67; 95% confidence interval [CI], 2.54-12.64; p = 0.000), anemia (OR, 4.01; 95% CI, 2.10-7.64; p = 0.000), and higher household food insecurity (OR, 1.13; 95% CI, 1.06-1.21; p = 0.000) are significantly associated with an increased risk of having leprosy. Meanwhile, higher education (OR, 0.34; 95% CI, 0.15-0.77; p = 0.009) and land ownership (OR, 0.39; 95% CI, 0.18-0.86; p = 0.019) have significant protective associations against leprosy. Although lower dietary diversity, lack of food stock, food shortage, low serum iron, and high ferritin were found more commonly in those with leprosy, the occurrence of leprosy was not significantly associated with iron deficiency (OR, 1.06; 95% CI, 0.10-11.37; p = 0.963)., Conclusions/significance: Food poverty is an important risk factor for leprosy susceptibility, yet the mechanisms underlying this association other than nutrient deficiencies still need to be identified. With a stable incidence rate of leprosy despite the implementation of chemoprophylaxis and multidrug therapy, improving dietary diversity through food-based approaches should be initiated and directed toward high-prevalence villages. The possible underlying factors that link poverty to leprosy other than nutrient deficiencies also need to be identified.

Background: Psoriasis, psoriatic arthritis (PsA), and inflammatory bowel disease (IBD) are related inflammatory immune-mediated diseases, with considerable overlap. However, it is as yet unclear whether co-occurrence of these diseases affects disease course and characteristics of the individual complaints. The objective of this study was to identify the prevalence of IBD and PsA in a psoriasis cohort and to examine whether patients with concurrent psoriasis and IBD carry a distinct phenotype., Methods: Data of all patients with psoriasis visiting a general hospital in the Netherlands between 2009 and 2014 were retrospectively retrieved from electronic patient files. In addition, clinical characteristics of patients with concurrent psoriasis and IBD (n = 40) were compared with psoriasis-only (n = 1643) and IBD-only (n = 385) cohorts., Results: Among 1669 hospital-based patients with psoriasis, prevalence of PsA was 12.2% (n = 203, 95% confidence interval, 10.5-13.7) and of IBD 1.6% (n = 26, 95% confidence interval, 1.0-2.2), including 12 Crohn's disease (CD) and 14 ulcerative colitis. Psoriasis-PsA patients were more likely to have IBD than psoriasis-only patients (3.0 versus 1.4%).Psoriasis-CD patients were younger at CD diagnosis (20.0 versus 32.0 yr, P = 0.001), and psoriasis diagnosis (28.0 versus 43.5 yr, P = 0.004) than psoriasis-only patients. Psoriasis-IBD patients had a mild psoriasis phenotype similar to psoriasis-only patients, but the CD-phenotype was significantly more severe than in CD-only patients., Conclusions: The prevalence of IBD in psoriasis was approximately 4 times higher than that in the general population, with the highest risk for psoriasis-PsA patients. Psoriasis-CD patients have a mild (early-onset) psoriasis but an earlier-onset and severe CD-phenotype.

Background: Fumaric acid esters (FAEs) are a systemic treatment for psoriasis considered to have a favourable long-term safety profile without an increased risk for immunosuppression. However, progressive multifocal leukoencephalopathy (PML), a rare, opportunistic viral infection of the central nervous system, has been linked anecdotally to FAE treatment., Objective: To assess clinical features and outcomes of FAE-associated PML cases., Methods: Systematic literature search in multiple databases up to 25th February 2016 for reports of PML in psoriasis patients treated with FAEs., Results: Eight cases (four male, four female) of FAE-associated PML were identified. Median age was 64 years (range 42-74 years); median FAE treatment duration was 3 years (range 1.5-5 years). Six patients were treated with a formulation containing dimethyl fumarate (DMF) and monoethyl fumarates, and two patients with a DMF formulation. Patients exhibited neurological symptoms, such as aphasia, hemiparesis and dysarthria. PML diagnosis was based on MRI findings and presence of JC virus in cerebrospinal fluid and/or brain tissue. All cases were linked to moderate-to-severe reductions in absolute lymphocyte counts, with nadirs ranging from 200 to 792 cells per mm 3 . Median exposure to lymphocytopenia was 2 years (range 1-5 years). In all cases, FAE treatment was discontinued; PML was treated with mefloquine plus mirtazapine. Three patients improved, two had stable disease, two had residual symptoms, and one patient died to an immune reconstitution inflammatory syndrome., Conclusion: Progressive multifocal leukoencephalopathy is infrequently linked to FAE treatment, but underreporting cannot be excluded. Physicians treating patients with FAEs should be vigilant for the occurrence of PML, and both clinicians and patients should be alert for onset of new neurological symptoms. Periodic monitoring of lymphocyte counts and FAE discontinuation in case of moderate-to-severe lymphocytopenia is recommended to minimize the risk for PML., (© 2017 European Academy of Dermatology and Venereology.)

Aim: To investigate the cost-effectiveness of blue-light therapy versus a two-compound formulation (TCF) (Dovobet ® gel [calcipotriol and betamethasone]) in mild-to-moderate psoriasis., Methods: A Markov model was applied to describe the course of disease among Dutch patients with a Psoriasis Area and Severity Index (PASI) score ≤ 10 over a 52-week time horizon. Patients received either 12-week blue-light therapy or two 4-week treatments with TCF. Patients, experiencing no PASI reduction after either therapy, were assumed to receive 12-week ultraviolet B phototherapy., Results: There was no significant difference in PASI reduction between two interventions (71 vs 72%). However, blue-light therapy was associated with a cost savings of EU€248., Conclusion: Treatment of mild-to-moderate chronic plaque psoriasis using blue-light therapy may be more cost-effective than TCF.

Background: Psoriasis and inflammatory bowel disease (IBD) are chronic inflammatory diseases sharing similar pathogenic pathways. Intestinal microbial changes such as a decrease of bakers' yeast Saccharomyces cerevisiae have been reported in IBD, suggesting the presence of a gut-skin axis., Objective: To investigate whether the S. cerevisiae abundance was altered in psoriasis patients versus healthy controls, and whether dimethylfumarate (DMF) interacted with this yeast., Methods: Using qPCR, faecal samples were compared between psoriasis patients without DMF (n = 30), psoriasis patients with DMF (n = 28), and healthy controls (n = 32)., Results: Faecal S. cerevisiae abundance was decreased in psoriasis compared to healthy controls (p<0.001). Interestingly, DMF use raised S. cerevisiae levels (p<0.001). Gastrointestinal adverse-effects of DMF were correlated with a higher S. cerevisiae abundance (p = 0.010). In vitro, a direct effect of DMF on S. cerevisiae growth was observed. In addition, anti-Saccharomyces cerevisiae antibodies were not elevated in psoriasis., Conclusion: The abundance of baker's yeast S. cerevisiae is decreased in psoriasis patients, but appears to be restored upon DMF use. S. cerevisiae is generally classified as a yeast with beneficial immunomodulatory properties, but may also be involved in the occurrence of DMF's gastrointestinal adverse-effects. Potentially, DMF might be a new therapy for IBD.

Background: There are currently no independent data available comparing infliximab and etanercept for the treatment of psoriasis., Objectives: To compare these biologics without funding from pharmaceutical companies., Methods: Overall, 50 patients were randomized to etanercept (n = 23) 50 mg subcutaneously twice weekly or infliximab (n = 25) 5 mg kg -1 intravenously at week 0, 2, 6, 14 and 22. After 24 weeks, 19 patients stopped and 22 continued treatment and were followed up to week 48. The primary outcome was ≥ 75% improvement of Psoriasis Area and Severity Index (PASI 75) at week 24. The secondary outcomes included PASI 75 at week 6 (onset of action) and week 12, Investigator's Global Assessment (IGA), Patient Global Assessment, impact on quality of life (Skindex-17 and SF-36), Treatment Satisfaction Questionnaire of Medication, duration of remission, maintenance treatment and safety., Results: At week 24, PASI 75 was achieved in 72% (infliximab) vs. 35% (etanercept) (P = 0·01). The onset of action was achieved in 52% (infliximab) and 4% (etanercept). At week 12, 76% (infliximab) and 22% (etanercept) achieved PASI 75 (P < 0·001). At week 24, IGA 'clear or almost clear' was observed in 76% (infliximab) and 30% (etanercept) (P = 0·01). Skindex-17 symptom score was significantly better for infliximab. Maintenance treatment achieved PASI 75 for 67% (n = 6) infliximab vs. 50% (n = 5) etanercept, at week 48 (P = 0·65). Mild adverse events were reported in 76% (infliximab) vs. 66% (etanercept)., Conclusions: Infliximab showed a rapid and significant higher level of efficacy until week 24 compared with etanercept. Long-term data showed no significant differences between both groups at week 48. Safety parameters were comparable., (© 2016 British Association of Dermatologists.)

Background: Aberrant toll-like receptors (TLRs) 7, 8, and 9 activation by self-nucleic acids is implicated in immune-mediated inflammatory diseases (IMIDs) such as psoriasis. In preclinical IMID models, blocking TLR-activation reduced disease severity. IMO-8400 is a first-in-class, oligonucleotide-based antagonist of TLRs 7, 8, and 9. We evaluated the short-term safety and proof-of-concept for efficacy of IMO-8400 in a first-in-patient phase 2 trial., Methods: Forty-six psoriasis patients were randomly assigned to IMO-8400 in four dose levels or placebo for 12weeks. Post-treatment follow-up was seven weeks. Primary outcome was incidence of adverse events. Secondary, exploratory outcomes included changes in psoriasis area and severity index (PASI)., Results: IMO-8400 across all dose levels did not cause any serious or severe adverse events. The most common treatment-related adverse events were dose-dependent injection-site reactions. All IMO-8400 groups showed clinical improvement, but a clear dose-response relationship and statistically significant differences with placebo were not observed (P=0.26). Eleven (38%) of 29 subjects on IMO-8400 achieved ≥50% PASI-reduction, compared to 1 (11%) of 9 subjects on placebo. Five (17%) and 2 (7%) IMO-8400-treated subjects achieved PASI-75 and PASI-90, respectively, compared to none on placebo., Conclusions: Short-term IMO-8400-treatment was well tolerated and reduced psoriasis severity. These findings warrant further investigation of endosomal TLR-antagonism as a therapeutic approach in psoriasis and other TLR-mediated IMIDs., Trial Registration: EudraCT 2013-000164-28 and Clinicaltrials.govNCT01899729., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background and Aims: Psoriasis and hidradenitis suppurativa [HS] co-occur more often with inflammatory bowel disease [IBD] than expected, due to shared pathogenic and genetic features. It is known that IBD patients harbour an altered intestinal microbiome characterised by a depletion of Faecalibacterium prausnitzii and increase of Escherichia coli. At present, it is unclear whether a similar intestinal microbiome trend can be identified in IBD-associated skin disorders. We therefore investigated the F. prausnitzii and E. coli abundance in psoriasis and HS, with and without concomitant IBD., Methods: Using quantitative polymerase chain reaction , we compared the F. prausnitzii and E. coli abundances in faecal samples from healthy controls [n = 33] with samples from patients with psoriasis [n = 29], IBD [n = 31], and concomitant IBD and psoriasis [n = 13]. Likewise, we analysed samples from patients with HS [n = 17], and concomitant IBD and HS [n = 17]., Results: Psoriasis patients harboured a significantly lower abundance of F. prausnitzii in their stool than healthy controls [p < 0.001], which was similar to IBD patients. Together with the reduced F. prausnitzii levels, the psoriasis patients had a significantly higher abundance of E. coli [p < 0.001]. No significant difference in F. prausnitzii or E. coli abundance was found in HS. It was apparent that patients with concomitant IBD and associated skin disorder had the greatest decrease of F. prausnitzii and increase of E. coli., Conclusions: The study demonstrates, for the first time, an IBD-like decrease of F. prausnitzii together with an increase of E.coli in psoriasis, supporting the presence of a gut-microbiome-skin axis in psoriasis and IBD., (Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Fumarates or fumaric acid esters derivates (FAED) have appeared to be effective and less toxic than other systemic treatments for psoriasis. Due to its safe adverse event profile, FAED can be used as a long-term maintenance therapy. One of the greatest reasons why FAED are not preferred as a first-line treatment is that according to the recommended dosing schedule, clinically meaningful improvement is seen just after 6 to 8 weeks of therapy. In this manuscript, we suppose an alternative induction scheme with a combination therapy of fumarates and cyclosporine for a more rapid improvement and better compliance.

Fumaric acid esters (FAEs) are increasingly used as a systemic treatment for psoriasis, but there are still uncertainties regarding their suitability. The objective of this systematic review was to assess the evidence for the efficacy and safety of FAEs in psoriasis treatment. A systematic literature search was performed in seven databases up to 17 August 2015. Inclusion criteria were studies that reported clinical effects of FAEs in patients with psoriasis without restrictions in study design, language or publication date. Methodological quality of randomized controlled trials (RCTs) and overall level of quality were assessed using the Cochrane risk of bias tool and the Grading of Recommendation, Assessment, Development and Evaluation approach, respectively. A total of 68 articles were included. There were seven RCTs (total 449 patients) that had an unclear risk of bias and were too clinically heterogeneous to allow a meta-analysis. Overall, mean Psoriasis Area and Severity Index decreased by 42-65% following 12-16 weeks of treatment. There were 37 observational studies (a total of 3457 patients) that supported the RCT findings, but most were uncontrolled with a high risk of bias. Commonly reported adverse events included gastrointestinal complaints and flushing, leading to treatment withdrawal in 6-40% of patients. Several case-reports described rare adverse events, such as renal Fanconi syndrome and progressive multifocal leukoencephalopathy. There was a lack of studies focusing on long-term use and comparisons with other treatments. This review concluded that there is low-quality evidence to recommend the use of oral FAEs to treat plaque psoriasis in adult patients. Studies focusing on long-term safety and comparison with systemic psoriasis treatments could lead to a better understanding of the role of FAEs as a treatment for psoriasis., (© 2016 British Association of Dermatologists.)

Background: The clinical spectrum of leprosy is dependent on the host immune response against Mycobacterium leprae or the newly discovered Mycobacterium lepromatosis antigen. Helminth infections have been shown to affect the development of several diseases through immune regulation and thus may play a role in the clinical manifestations of leprosy and leprosy reactions. The purpose of this study is to determine the proportion of helminth infections in leprosy and its association with the type of leprosy and type 2 leprosy reaction (T2R)., Methods: History or episode of T2R was obtained and direct smear, formalin-ether sedimentation technique, and Kato-Katz smear were performed on 20 paucibacillary (PB) and 61 multibacillary (MB) leprosy participants., Results: There are more helminth-positive participants in MB leprosy compared to PB (11/61 versus 0/20, p = 0.034) and in T2R participants compared to non-T2R (8/31 versus 3/50, p = 0.018)., Conclusions: Our results suggest that soil-transmitted helminth infections may have a role in the progression to a more severe type of leprosy, as well as the occurrence of T2R. These findings could serve as a fundamental base for clinicians to perform parasitological feces examination in patients who have MB leprosy and severe recurrent reactions to rule out the possibility of helminth infection. Further secondary confirmation of findings are needed to support these conclusions.

Background: Fumaric acid esters (FAEs), an oral immunomodulating treatment for psoriasis and multiple sclerosis, have been anecdotally associated with proximal renal tubular dysfunction due to a drug-induced Fanconi syndrome. Few data are available on clinical outcomes of FAE-induced Fanconi syndrome., Methods: Descriptive case series with two cases of Fanconi syndrome associated with FAE treatment diagnosed at two Dutch university nephrology departments, three cases reported at the Dutch and German national pharmacovigilance databases and six previously reported cases., Results: All 11 cases involved female patients with psoriasis. The median age at the time of onset was 38 years [interquartile range (IQR) 37-46]. Patients received long-term FAEs treatment with a median treatment duration of 60 months (IQR 28-111). Laboratory tests were typically significant for low serum levels of phosphate and uric acid, while urinalysis showed glycosuria and proteinuria. Eight (73%) patients had developed a hypophosphataemic osteomalacia and three (27%) had pathological bone fractures. All patients discontinued FAEs, while four (36%) patients were treated with supplementation of phosphate and/or vitamin D. Five (45%) patients had persisting symptoms despite FAEs discontinuation., Conclusions: FAEs treatment can cause drug-induced Fanconi syndrome, but the association has been reported infrequently. Female patients with psoriasis treated long term with FAEs seem to be particularly at risk. Physicians treating patients with FAEs should be vigilant and monitor for the potential occurrence of Fanconi syndrome. Measurement of the urinary albumin:total protein ratio is a suggested screening tool for tubular proteinuria in Fanconi syndrome.

Background: Fumaric acid esters (FAEs) are considered an effective and safe long-term treatment for psoriasis. However, 30-40% of patients need to discontinue FAE treatment due to intolerable adverse events., Objectives: To assess whether the addition of cetirizine, an oral histamine-1 receptor antagonist, to FAEs would reduce the incidence of adverse events., Methods: In a randomized, double-blind, placebo-controlled trial, patients with psoriasis with a Psoriasis Area and Severity Index ≥ 10 starting an FAE up to a dose of dimethylfumarate 720 mg per day were randomized 1 : 1 to receive either additional cetirizine 10 mg once daily (n = 25) or placebo (n = 25) for 12 weeks. Randomization and treatment allocation were done at our hospital trial pharmacy. Primary outcomes were the incidence of adverse events and the proportion of patients discontinuing treatment., Results: Fifty patients (33 male, 17 female; median age 44 years) were enrolled. Addition of cetirizine did not reduce the incidence of adverse events compared with placebo (84% vs. 84%, P = 1·00). The types of adverse events were not different between the cetirizine and placebo groups, the most common being gastrointestinal complaints (68% vs. 64%) and flushes (60% vs. 48%). The proportion of patients discontinuing treatment was not statistically different between the cetirizine and placebo groups (24% vs. 32%, P = 0·53)., Conclusions: Addition of oral cetirizine 10 mg once daily to FAE treatment did not reduce adverse events in patients with psoriasis during the first 12 weeks of treatment. The mechanisms underlying FAE-induced gastrointestinal and flushing symptoms likely involve mediators other than histamine., (© 2014 British Association of Dermatologists.)

Fibrosis is one of the leading causes of morbidity and mortality in the Western world. This disorder is characterised by an abnormal and increased rate of fibroblast proliferation and by an excessive deposition of connective tissue. The key player in fibrosis is the myofibroblast. Fibrosis leads to loss of organ structure and, eventually, to decrease in organ function. To date, there are hardly any effective therapies for the treatment of patients with fibrosis. Pirfenidone targets the myofibroblast and is effective in the treatment of idiopathic pulmonary fibrosis. Tyrosine kinase inhibitors are effective for the treatment of patients with some forms of systemic sclerosis. Here we describe various novel therapeutic targets, such as transforming growth factor beta (TGF-β), platelet-derived growth factor (PDGF), interleukin-13 (IL-13), lysyloxidase-2 and macrophage-fibroblast interactions. These new therapies are currently under investigation in pre-clinical and clinical studies.

Background: Fumaric acid esters (FAEs) are widely used in Europe for the treatment of psoriasis because of their clinical efficacy and favourable safety profile. However, the mechanisms of action by which FAEs improve psoriasis remain largely unknown., Objectives: To identify pathways and mechanisms affected by FAE treatment and to compare these with pathways affected by treatment with the antitumour necrosis factor (anti-TNF)-α biologic etanercept., Methods: In a prospective cohort study, 50 patients with plaque psoriasis were treated with FAEs for 20 weeks. Nine patients were randomly selected for gene expression profiling of plaque biopsies from week 0 and week 12. The groups consisted of FAE responders [> Psoriasis Area and Severity Index (PASI)-75 improvement] and nonresponders (< PASI-50 improvement). Changes in gene expression profiles were analysed using Ingenuity Pathway Analysis (IPA) and the outcome was compared with gene expression affected by etanercept., Results: Response to FAE treatment was associated with a ≥ 2-fold change (P < 0.05) in the expression of 458 genes. In FAE responders the role of interleukin-17A in the psoriasis pathway was most significantly activated. Glutathione and Nrf2 pathway molecules were specifically induced by FAE treatment and not by etanercept treatment, representing an FAE-specific effect in psoriatic skin. In addition, FAE treatment specifically induced the transcription factors PTTG1, NR3C1, GATA3 and NFκBIZ in responding patients., Conclusions: FAE treatment induces glutathione and Nrf2 pathway genes in lesional skin of patients with psoriasis. In responders, FAEs specifically regulate the transcription factors PTTG1, NR3C1, GATA3 and NFκBIZ, which are important in normal cutaneous development, and the T-helper (Th)2 and Th17 pathways, respectively., (© 2014 British Association of Dermatologists.)

Background: The prevalence of IgE-mediated diseases has been increasing worldwide, yet IgE-expressing B cells are poorly characterized, mainly because of their scarcity and low membrane IgE levels., Objective: We sought to study the immunobiology of human IgE-expressing B cells in healthy subjects and patients with allergic disease., Methods: We used a stepwise approach for flow cytometric detection and purification of human IgE-expressing B cells in control subjects, CD40 ligand-deficient patients, and patients with atopic dermatitis. Molecular analysis of replication histories, somatic hypermutation (SHM), and immunoglobulin class-switching was performed., Results: Using multicolor flow cytometry, we reliably detected IgE-expressing plasma cells and 2 IgE-expressing memory B-cell subsets. These IgE-expressing cells showed molecular and phenotypic signs of antigen responses. The replication history and SHM levels of IgE(+) plasma cells and CD27(+)IgE(+) memory B cells fitted with a germinal center (GC)-dependent pathway, often through an IgG intermediate, as evidenced from Sγ remnants in Sμ-Sε switch regions. CD27(-)IgE(+) cells showed limited proliferation and SHM and were present in CD40 ligand-deficient patients, indicating a GC-independent origin. Patients with atopic dermatitis had normal numbers of blood IgE(+) plasma cells and CD27(+)IgE(+) memory B cells but increased numbers of CD27(-)IgE(+) memory B cells with high SHM loads compared with those seen in healthy control subjects and patients with psoriasis., Conclusions: We delineated GC-dependent and GC-independent IgE(+) B-cell responses in healthy subjects and indicated involvement of the GC-independent pathway in a human IgE-mediated disease. These findings provide new insights into the pathogenesis of IgE-mediated diseases and might contribute to accurate monitoring of IgE(+) B cells in patients with severe disease undergoing anti-IgE treatment., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Psoriasis vulgaris is a T-cell mediated disease that affects 2-3% of the worldwide white-skinned population. Fumaric acid esters are mentioned as an effective therapy for moderate-to-severe psoriasis vulgaris in adult patients in the new guidelines for psoriasis treatment., Objectives: To obtain an insight into the use of fumaric acid esters by Dutch dermatologists in the Netherlands., Methods: This was a cross-sectional postal survey. An anonymous survey was posted to all Dutch dermatologists. In this survey, data were collected on the extent of fumaric acid esters use, the reasons for use, the reasons for non- or limited use of fumaric acid esters, the perception of fumaric acid esters as a mono-therapy with regards to the effectiveness, the safety, the adverse events and the overall satisfaction of fumaric acid esters as a mono-therapy., Results: Sixty-three per cent of the 300 responders indicated to prescribe fumaric acid esters for the treatment of psoriasis. About 37% of the dermatologists indicated (almost) never to prescribe it. Biologicals were considered as the most effective therapy. Fumaric acid esters were regarded as the safest therapy. They were generally well-tolerated by the patients similar to that for methotrexate according to the respondents., Conclusion: A large proportion of the dermatologists in our survey indicated to prescribe fumaric acid esters. It is considered to be effective, safe and without adverse events profile that is favourable in the practice, also as compared with other systemic therapies such as methotrexate and biologicals., (© 2013 European Academy of Dermatology and Venereology.)

This document provides a summary of the Dutch S3-guidelines on the treatment of psoriasis. These guidelines were finalized in December 2011 and contain unique chapters on the treatment of psoriasis of the face and flexures, childhood psoriasis as well as the patient's perspective on treatment. They also cover the topical treatment of psoriasis, photo(chemo)therapy, conventional systemic therapy and biological therapy.

Psoriatic arthritis is a chronic inflammatory joint disease, seen in combination with the chronic inflammatory skin disease psoriasis and belonging to the family of spondylarthritides (SpA). A link is recognized between psoriatic arthritis and inflammatory bowel disease (IBD). Environmental factors seem to induce inflammatory disease in individuals with underlying genetic susceptibility. The microbiome is a subject of increasing interest in the etiology of these inflammatory immune-mediated diseases. The intestinal microbiome is able to affect extra-intestinal distant sites, including the joints, through immunomodulation. At this point, evidence regarding a relationship between the microbiome and psoriatic arthritis is scarce. However, we hypothesize that common immune-mediated inflammatory pathways seen in the "skin-joint-gut axis" in psoriatic arthritis are induced or at least mediated by the microbiome. Th17 has a crucial function in this mechanism. Further establishment of this connection may lead to novel therapeutic approaches for psoriatic arthritis.

Background: Glatiramer acetate (GA) and interferon-beta (IFN-β) are disease-modifying therapies (DMTs) for multiple sclerosis that are administered through subcutaneous (SC) or intramuscular (IM) injections. Skin reactions associated with DMTs are common and may influence patient's health-related quality of life (QoL). We aimed to determine the prevalence of cutaneous adverse events associated with long-term DMT use, and to assess the impact of cutaneous adverse events on QoL., Methods: A cross-sectional study among patients with multiple sclerosis who had been treated with their first DMT for at least 2 years. Cutaneous events were assessed from photographs of injection-sites by dermatologists blinded for DMT. Generic and dermatology-specific health-related QoL were assessed using validated patient-reported questionnaires., Results: A total of 229 patients were enrolled, of whom 156 (68%) had at least one skin reaction. The prevalence of cutaneous adverse events was higher for SC DMTs (75-82%) compared to IM DMT (41%) (P < 0.001). Erythema and lipoatrophy were the most common skin reactions, observed in 156 (68%) and 45 (20%) patients, respectively. Dermatology-specific, but not generic, QoL was significantly lower among patients with skin reactions compared to those without., Conclusions: The prevalence of cutaneous adverse events was high in long-term DMT-treatment. Patients with cutaneous adverse events had a lower perceived dermatology-specific QoL.

The objective of this paper is to answer the clinical question whether the location of the lesion in an individual patient with actinic keratosis (AK) influences the absolute risk of the development of skin cancer. Between 0.025% and 16% of AK lesions advance towards squamous cell carcinoma per year. It is not well known whether this risk differs between locations on the body. A systematic search of available literature resulted in seven articles of which the two highest scoring on relevance and validity were selected. These two studies indicate that the absolute risk on the development of skin cancer in patients with AK differs between locations of the lesion and that time to progression from AK to squamous cell carcinoma is not different among the locations of the lesions. However, both studies have very limited sample sizes., (© 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.)

Background: Fumaric acid esters (FAE) are used as an effective and safe oral treatment for plaque psoriasis in adult patients, but little is known about their efficacy and safety in children with psoriasis., Objectives: To assess the effectiveness and safety of FAE in the treatment of paediatric psoriasis., Methods: This is a retrospective analysis of 14 paediatric patients with psoriasis (age <18 years) treated with FAE between 2004 and 2012 at several Dutch university and regional clinics. Patients were identified through databases or registries., Results: The median age at the start of FAE treatment was 15 years (range 8-17 years). The median duration of FAE treatment was 10 months (range 1-80 months), and the median maintenance dosage per day was 360 mg dimethylfumarate (range 240-600 mg). Five patients (36%) achieved a complete clearance of their psoriasis, one patient (7%) had a good improvement, three patients (21%) had a partial response and five patients (36%) were nonresponders. FAE treatment was well tolerated, but two patients (14%) discontinued FAE, one with severe diarrhoea and one with flushes. Five patients (36%) had transient, slightly abnormal laboratory values of liver-function tests or leucocytes that did not necessitate FAE dosage reduction or treatment discontinuation. No serious adverse events occurred., Conclusions: In this retrospective case series FAE seemed to be an effective and safe treatment for children with psoriasis. FAE may be an attractive therapeutic alternative to the currently used systemic immunosuppressive agents for paediatric patients with psoriasis. Further studies are needed to evaluate the suitability of FAE in paediatric psoriasis., (© 2013 The Authors. BJD © 2013 British Association of Dermatologists.)