Akkermansia muciniphila and Faecalibacterium prausnitzii in Immune-Related Diseases.

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.

Skin Microbiota Profiles from Tape Stripping and Skin Biopsy Samples of Patients with Psoriasis Treated with Narrowband Ultraviolet B.

Purpose: 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.

Comparison of Malassezia spp. colonization between human skin exposed to high- and low-ambient air pollution.

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.

Alteration of gut microbiota during narrowband ultraviolet B therapy in psoriasis: A preliminary study.

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.

Serum Interleukin 6 Level and Nutrition Status as Potential Predictors of Clinical Leprosy Development Among Household Contacts in Endemic Areas.

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.

Pediatric Leprosy Profile in the Postelimination Era: A Study from Surabaya, Indonesia.

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.

Unusual presentations of a severe type 2 leprosy reaction mimicking sepsis induced by helminth infection.

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.

The Microbiome in Psoriasis and Psoriatic Arthritis: The Skin Perspective.

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.

Psoriasis and Microbiota: A Systematic Review.

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.

Dietary diversity and poverty as risk factors for leprosy in Indonesia: A case-control study.

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.

Prevalence and Phenotype of Concurrent Psoriasis and Inflammatory Bowel Disease.

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.

The cost-effectiveness of blue-light therapy in the treatment of mild-to-moderate psoriasis.

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.

IMO-8400, a toll-like receptor 7, 8, and 9 antagonist, demonstrates clinical activity in a phase 2a, randomized, placebo-controlled trial in patients with moderate-to-severe plaque psoriasis.

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.

Soil-transmitted helminth infections and leprosy: a cross-sectional study of the association between two major neglected tropical diseases in Indonesia.

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.

Drug-induced Fanconi syndrome associated with fumaric acid esters treatment for psoriasis: a case series.

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.

Prevalence of cutaneous adverse events associated with long-term disease-modifying therapy and their impact on health-related quality of life in patients with multiple sclerosis: a cross-sectional study.

BACKGROUND: Glatiramer acetate (GA) and interferon-beta (IFN-ß) 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.

[A neonate with a skin defect]. / Een neonaat met een huiddefect.

A male neonate was born with a defect of the skin and subcutaneous tissue on the back. The pregnancy started as a gemelli pregnancy but in the 12th week 1 fetus deceased. The diagnosis of truncal aplasia cutis was made.