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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

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.

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.

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.

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.

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.

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: 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.

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.

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.

Rationale: Recent observations of abnormal immunoglobulin responses and case reports describing successful B-cell ablative therapy suggest involvement of B cells in the pathogenesis of sarcoidosis., Objectives: To investigate how abnormal B-cell maturation and function in patients with sarcoidosis contribute to disease., Methods: Patients with sarcoidosis (n = 32) were included for detailed analysis by immunohistochemistry of tissue, flow cytometry of blood B-cell subsets, and serum immunoglobulin levels. Vaccination responses in patients with sarcoidosis to influenza virus and encapsulated bacteria and molecular analysis of immunoglobulin heavy chain transcripts were studied for functional analysis of immunoglobulin responses., Measurements and Main Results: Perigranuloma localization of IgA-producing plasma cells and numerous B cells were found in affected tissues. Total blood B-cell numbers were normal, CD27(+) memory B cells were significantly reduced, and CD27(-)IgA(+) B cells were significantly increased; the results are normalized in patients treated with TNF-α blockers. Despite this, patients had normal serum immunoglobulin levels and normal antigen-specific immunoglobulin responses. IgA and IgG transcripts, however, showed high frequencies of somatic hypermutations and increased usage of downstream IgG subclasses, suggestive for prolonged or repetitive responses., Conclusions: The large B-cell infiltrates in granulomatous tissue and increased molecular signs of antibody maturation are indicative of direct involvement of B cells in local inflammatory processes in patients with sarcoidosis. Moreover, CD27(-)IgA(+) B cells could be a marker for treatment with TNF-α blockers. These findings of B cells as emerging key players provide a rationale for a systematic study on B-cell ablative therapy in patients with sarcoidosis.

In this paper we present a case history of a homosexual HIV-positive male with a painless nodule on the penis. Screening for sexually transmitted diseases did not detect any infection until the node perforated spontaneously. A diagnosis of lymphogranuloma venereum was made when chlamydia trachomatis type L2 DNA was extracted from the lesion. This case illustrates that standard screening may not be sufficient for making the diagnosis of lymphogranuloma venereum.

Diabetes mellitus can be complicated by a variety of cutaneous manifestations. Good metabolic control may prevent some of these manifestations and may support cure. Unfortunately, most glucose-lowering drugs also have cutaneous side effects. It is important to be able to recognize these signs and symptoms and to either treat them appropriately or refer the patient to a dermatologist or diabetologist.

A patient with therapy-resistant and progressive systemic sclerosis (SSc) with pulmonary involvement who was treated with imatinib mesylate is described herein. Prior to treatment, pulmonary fibroblasts obtained from the patient were cultured and incubated with imatinib mesylate. Preincubation of the fibroblasts for 16 hours with 2.5 microg/ml imatinib mesylate efficiently abrogated platelet-derived growth factor BB-induced fibroblast proliferation. Furthermore, transforming growth factor beta1-induced type I collagen gene transcription was blocked. During treatment, the patient's pulmonary involvement stabilized and her skin tightness improved. To our knowledge, this is the first report of a patient with therapy-refractory SSc responding to treatment with imatinib mesylate.

Objectives: To investigate whether serological titres of species-specific IgA and IgG antibodies in patients with rectal chlamydial infection could discriminate between infection with serovar L2 lymphogranuloma venereum (LGV) and infection with non-LGV serovars., Methods: A total of 39 male patients with chlamydial infection of the rectum were tested for titres of IgA and IgG antibodies within 14 days after detection of the infection and 6 and 12 months after adequate treatment. Data were collected regarding demographics, sexual orientation, HIV serostatus, history of chlamydial infection, concomitant sexually transmitted infection (STI) or HIV infection, hepatitis C virus antibodies and new STIs during follow-up., Results: Between May 2003 and November 2005, 24 men with confirmed L2 proctitis and 15 men with non-LGV rectal chlamydial infection were recruited. In multivariable analyses, both high titre of IgA within 14 days after detection of the infection and older age of the individual were found significantly associated with L2 proctitis (p<0.001 and p = 0.001, respectively). A total sum score of seven times IgA titre and individual's age >or=50 years resulted in an overall sensitivity of 92% and specificity of 100%. This total sum score was highly accurate for detection of LGV proctitis, with an area under the curve in a receiver operating characteristic curve of 0.989., Conclusions: An increased IgA antibody response and the age of the infected individual are of possible diagnostic value for (early) detection of LGV proctitis.

Although compound heterozygosity, or the presence of two different mutant alleles of the same gene, is common in human recessive disease, its potential to impact disease outcome has not been well documented. This is most likely because of the inherent difficulty in distinguishing specific biallelic effects from differences in environment or genetic background. We addressed the potential of different recessive alleles to contribute to the enigmatic pleiotropy associated with XPD recessive disorders in compound heterozygous mouse models. Alterations in this essential helicase, with functions in both DNA repair and basal transcription, result in diverse pathologies ranging from elevated UV sensitivity and cancer predisposition to accelerated segmental progeria. We report a variety of biallelic effects on organismal phenotype attributable to combinations of recessive Xpd alleles, including the following: (i) the ability of homozygous lethal Xpd alleles to ameliorate a variety of disease symptoms when their essential basal transcription function is supplied by a different disease-causing allele, (ii) differential developmental and tissue-specific functions of distinct Xpd allele products, and (iii) interallelic complementation, a phenomenon rarely reported at clinically relevant loci in mammals. Our data suggest a re-evaluation of the contribution of "null" alleles to XPD disorders and highlight the potential of combinations of recessive alleles to affect both normal and pathological phenotypic plasticity in mammals., Competing Interests: Competing interests. The authors have declared that no competing interests exist.

Objective: An acute hepatitis C virus (HCV) infection in an HIV-positive man who had sex with men (MSM) was notified. In the period of his seroconversion he was also diagnosed with a rectal lymphogranuloma venereum (LGV) infection, and was part of a cluster of 15 LGV cases in 2003. Our aim was to investigate HCV transmission and to search for potential spread among sexual contacts and known LGV patients., Methods: Our case series included the index, two recent contacts, and 14 LGV cases. They were interviewed about parenteral exposure for HCV, history of sexually transmitted diseases(STDs), sexual behaviour and drug use. Laboratory investigations included anti-HCV antibodies, HCV-polymerase chain reaction, and HCV genotyping., Results: Seven out of 17 MSM recently seroconverted for HCV (41%). Three genotypes were found. Parenteral risk factors were excluded. Six out of seven had LGV proctitis coinciding with HCV seroconversion, six (86%) were HIV infected. Unprotected anal contact was practised by both HCV uninfected and infected cases. Unprotected active and passive fisting was reported by all seven HCV infected men, compared with two of nine uninfected men (P = 0.003). Non-intravenous drug use during sexual activities was common among all MSM. Numerous, often anonymous, sexual contacts in various European countries were reported., Conclusions: A cluster of acute HCV infection is reported among mostly HIV-positive MSM, with multiple partners throughout Europe. Sexual techniques potentially leading to mucosal damage (fisting), concomitant STDs such as LGV and drug use seem facilitating factors for spread. Extensive case finding and partner tracing is advocated as well as targeted prevention messages.

Background: Psoriasis is a chronic inflammatory skin disease that can be successfully treated with a mixture of fumaric acid esters (FAE) formulated as enteric-coated tablets for oral use. These tablets consist of dimethylfumarate (DMF) and salts of monoethylfumarate (MEF) and its main bioactive metabolite is monomethylfumarate (MMF). Little is known about the pharmacokinetics of these FAE. The aim of the present study was to investigate the hydrolysis of DMF to MMF and the stability of MMF, DMF and MEF at in vitro conditions representing different body compartments., Results: DMF is hydrolyzed to MMF in an alkaline environment (pH 8), but not in an acidic environment (pH 1). In these conditions MMF and MEF remained intact during the period of analysis (6 h). Interestingly, DMF was hardly hydrolyzed to MMF in a buffer of pH 7.4, but was rapidly hydrolyzed in human serum having the same pH. Moreover, in whole blood the half-life of DMF was dramatically reduced as compared to serum. The concentrations of MMF and MEF in serum and whole blood decreased with increasing time. These data indicate that the majority of the FAE in the circulation are metabolized by one or more types of blood cells. Additional experiments with purified blood cell fractions resuspended in phosphate buffered saline (pH 7.4) revealed that at concentrations present in whole blood monocytes/lymphocytes, but not granulocytes and erythrocytes, effectively hydrolyzed DMF to MMF. Furthermore, in agreement with the data obtained with the pure components of the tablet, the enteric-coated tablet remained intact at pH 1, but rapidly dissolved at pH 8., Conclusion: Together, these in vitro data indicate that hydrolysis of DMF to MMF rapidly occurs at pH 8, resembling that within the small intestines, but not at pH 1 resembling the pH in the stomach. At both pHs MMF and MEF remained intact. These data explain the observation that after oral FAE intake MMF and MEF, but not DMF, can be readily detected in the circulation of human healthy volunteers and psoriasis patients.

Background: Lymphogranuloma venereum (LGV) is a sexually transmitted disease (STD) and is rare in the Western world. Recently, 3 men who have sex with men presented with LGV proctitis at the Erasmus Medical Center, Rotterdam, The Netherlands. We investigated a possible outbreak in a sexual network of men who have sex with men (MSM)., Methods: After active case finding, a total of 15 men presented and were investigated. Serum antibody titers to Chlamydia trachomatis were determined. Urine and rectum specimens were analyzed by polymerase chain reaction (PCR) for the presence of C. trachomatis. C. trachomatis-positive specimens were genotyped to detect the specific C. trachomatis serovars. All subjects underwent routine STD screening. Sociodemographic, clinical, and endoscopic characteristics were evaluated., Results: Thirteen subjects had high immunoglobulin (Ig) G and IgA titers to C. trachomatis, suggesting an invasive infection. Rectal specimens of 12 subjects were PCR-positive for C. trachomatis. All urine specimens were negative. Genotyping revealed serovars L(2) (n=8) and L(1) (n=1). An ulcerative proctitis was found in all subjects obtaining sigmoidoscopy (n=9). Eleven of 13 subjects with an LGV diagnosis were seropositive for human immunodeficiency virus (HIV), 6 had another concomitant STD, and 1 had recently acquired a hepatitis C virus infection. Further sexual contacts were reported from The Netherlands, Germany, Belgium, the United Kingdom, and France., Conclusions: We revealed an outbreak of LGV proctitis among MSM in The Netherlands. The ulcerous character favors transmission of HIV, other STDs, and blood-borne diseases. From a public health perspective, it seems important to increase the awareness of possible LGV in MSM with symptomatic proctitis.

Aims: To characterize the pharmacokinetics of fumarates in healthy subjects., Methods: Ten subjects received a single fumarate tablet (containing 120 mg of dimethylfumarate and 95 mg of calcium-monoethylfumarate) in the fasted state and after a standardized breakfast in randomized order. Prior to and at fixed intervals after the dose, blood samples were drawn and the concentrations of monomethylfumarate, the biologically active metabolite, as well as dimethylfumarate and fumaric acid were measured using high-performance liquid chromatography., Results: After a lag time, a transient increase in serum monomethylfumarate concentrations in the blood was observed, whereas dimethylfumarate and fumaric acid concentrations remained below the detection limit. The tlag was 240 min [range 60-603 min; 95% confidence interval (CI) 139, 471] shorter when the tablet was taken after an overnight fast (90 min; range 60-120 min; 95% CI 66, 107) than when taken with breakfast (300 min; range 180-723 min; 95% CI 0, 1002). The tmax was 241 min (range 60-1189 min, 95% CI 53, 781) shorter when the tablet was taken after an overnight fast (182 min; range 120-240 min; 95% CI 146, 211) than when taken with breakfast (361 min; range 240-1429 min; 95% CI 0, 1062). The mean Cmax for monomethylfumarate in the blood of fasting subjects was to 0.84 mg l(-1) (range 0.37-1.29 mg l(-1); 95% CI 0.52, 1.07) and did not differ from that in fed subjects (0.48 mg l(-1); range 0-1.22 mg l(-1); 95% CI 0, 5.55)., Conclusions: The pharmacokinetics of monomethylfumarate in healthy subjects after a single tablet of fumarate are highly variable, particularly after food intake. Further experiments exploring the pharmacokinetics of oral fumarates are warranted in order to elucidate the mechanisms underlying variability in response in patients., (Copyright 2004 Blackwell Publishing Ltd)

Psoriasis is a type-1 T cell-mediated, chronic inflammatory disease. Since interleukin (IL)-12p70 promotes the development of type-1 T cells, we investigated whether psoriasis is associated with an increased production of this cyctokine by blood cells. Results revealed that the production of IL-12p70 by cells of psoriasis patients stimulated by 1 and 10 ng per mL, but not 100 ng per mL of lipopolysaccharide (LPS) was higher (p=0.03) than that by cells of healthy volunteers. The production of IL-12p40 by patients cells upon stimulation with 0.1 ng per mL LPS, but not higher concentrations, was higher (p=0.02) than that by cells of healthy volunteers. No association between IL-12p70 production by blood cells and the severity of psoriasis was observed, nor was there a difference in the LPS-stimulated production of this cytokine between cells of the early and late onset type of patients. The frequencies of the various genotypes for the promoter region of the gene encoding IL-12p40 (IL12B) did not differ between psoriasis patients and controls. No association was observed between the various IL12B promoter genotypes and the LPS-stimulated production of IL-12p70 or IL-12p40 by blood cells. Together, psoriasis is not associated with a promoter polymorphism in the IL12B gene nor with the production of IL-12p70 by LPS-stimulated blood cells.