Association of Trimethylamine N-Oxide (TMAO) with the Clinical Severity of Hidradenitis Suppurativa (Acne Inversa).
Ontology highlight
ABSTRACT:
SUBMITTER: Barrea L
PROVIDER: S-EPMC8226830 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Comorbidities of hidradenitis suppurativa (acne inversa) were reviewed by extracting original and review publications included in MEDLINE, EMBASE and COCHRANE libraries using the terms "hidradenitis," "Verneuil" and "acne inversa." Follicular occlusion disorders, inflammatory bowel diseases, especially Crohn disease, spondylarthropathy, other hyperergic diseases, genetic keratin disorders associated with follicular occlusion and squamous cell carcinoma were the most common hidradenitis suppurativa comorbid diseases. A first classification of these major comorbidities and their possible genetic background reveals a list of chromosome loci and genes, which could be hidradenitis suppurativa candidates. Most of these diseases belong to the group of autoinflammatory disorders, where th17 cell cytokines seem to play a central role.
| S-EPMC3084959 | biostudies-literature
Project description:Since first recognized in 1839, the pathogenesis of acne inversa (AI) has undergone repeated revisions. Although there is agreement that AI involves occlusion of hair follicles with subsequent inflammation and the formation of tracts, the histologic progression of this disease still requires refinement. The objective of this study was to examine the histologic progression of AI based on the examination of a large cohort of punch biopsies and excisional samples that were examined first by hematoxylin and eosin staining. The most informative of these samples were step-sectioned and stained by immunohistochemistry for epithelial and inflammatory markers. Based on this examination, the following observations were made: 1) AI arises from the epithelium of the infundibulum of terminal and vellus hairs; 2) These form cysts and epithelial tendrils that extend into soft tissue; 3) Immunohistochemical staining demonstrates the epithelium of AI is disordered with infundibular and isthmic differentiation and de novo expression of stem cell markers; 4) The inflammatory response in AI is heterogeneous and largely due to cyst rupture. The conclusions of this investigation were that AI is an epithelial-driven disease caused by infiltrative, cyst forming tendrils and most of the inflammation is due to cyst rupture and release of cornified debris and bacteria. Cyst rupture often occurs below the depths of punch biopsy samples indicating their use for analysis may give an incomplete picture of the disease. Finally, our data suggest that unless therapies inhibit tendril development, it is unlikely they will cause prolonged treatment-induced remission in AI.
| S-EPMC8247901 | biostudies-literature
Project description:Despite the rapid development in hidradenitis suppurativa (HS) research, the immediate introduction of potent therapeutic compounds in clinical trials and the lack of definitive outcome measures have led to the discontinuation of potential therapeutic compound studies. HS is a solely human disease, and therefore, the search for preclinical human models has been given priority. The 3D-SeboSkin model, a co-culture of human skin explants with human SZ95 sebocytes as a feeder layer, has been shown to prevent the rapid degeneration of human skin in culture and has been validated for HS preclinical studies. In this work, the HS 3D-SeboSkin model has been employed to characterize cellular and molecular effects of the EMA- and FDA-approved biologic adalimumab. Adalimumab, a tumor necrosis factor-α inhibitor, was shown to target inflammatory cells present in HS lesions, inducing a prominent anti-inflammatory response and contributing to tissue regeneration through a wound healing mechanism. Adalimumab inhibited the lesional tissue expression of TNF-α, IL-3, IL-15, and MCP-3 and downregulated the secretion of IL-1α, IL-5, RANTES, MCP-2, TNF-α, TNF-β, TGF-β, and IFN-γ. In contrast, IL-6 was stimulated. The compound failed to modify abnormal epithelial cell differentiation present in the HS lesions. Patients with Hurley stage II lesions exhibited stronger expression of autophagy proteins in perilesional than in lesional skin. Adalimumab modified the levels of the pro-apoptotic proteins LC3A, LC3B, and p62 in an individual, patient-dependent manner. Finally, adalimumab did not modify the NFκB signal proteins in SZ95 sebocytes and NHK-19 keratinocytes, used to study this specific pathway. The administration of the validated HS 3D-SeboSkin model in ex vivo studies prior to clinical trials could elucidate the individual pathogenetic targets of therapeutic candidates and, therefore, increase the success rates of clinical studies, minimizing HS drug development costs.
| S-EPMC9967844 | biostudies-literature
Project description:Hidradenitis suppurativa (HS)/acne inversa is a debilitating chronic disease that remains poorly understood and difficult to manage. Clinical practice is variable, and there is a need for international, evidence-based and easily applicable consensus on HS management. We report here the findings of a systematic literature review, which were subsequently used as a basis for the development of international consensus recommendations for the management of patients with HS. A systematic literature review was performed for each of nine clinical questions in HS (defined by an expert steering committee), covering comorbidity assessment, therapy (medical, surgical and combinations) and response to treatment. Included articles underwent data extraction and were graded according to the Oxford Centre for Evidence-based Medicine criteria. Evidence-based recommendations were then drafted, refined and voted upon, using a modified Delphi process. Overall, 5310 articles were screened, 171 articles were analysed, and 65 were used to derive recommendations. These articles included six randomized controlled trials plus cohort studies and case series. The highest level of evidence concerned dosing recommendations for topical clindamycin in mild disease (with systemic tetracyclines for more frequent/widespread lesions) and biologic therapy (especially adalimumab) as second-line agents (following conventional therapy failure). Good-quality evidence was available for the hidradenitis suppurativa clinical response (HiSCR) as a dichotomous outcome measure in inflammatory areas under treatment. Lower-level evidence supported recommendations for topical triclosan and oral zinc in mild-to-moderate HS, systemic clindamycin and rifampicin in moderate HS and intravenous ertapenem in selected patients with more severe disease. Intralesional or systemic steroids may also be considered. Local surgical excision is suggested for mild-to-moderate HS, with wide excision for more extensive disease. Despite a paucity of good-quality data on management decisions in HS, this systematic review has enabled the development of robust and easily applicable clinical recommendations for international physicians based on graded evidence.
| S-EPMC6587546 | biostudies-literature
Project description:Hidradenitis suppurativa (HS) leads to disfigurement and painful eruptions in terminal hair follicles of the intertriginous skin, mainly of axillary, genitofemoral, and perianal sites. It is associated with an excessive impairment of quality of life, psychiatric disorders, and sexual distress. Body image impairment has been linked to depression and anxiety and has been described for some dermatologic disorders but has not yet been investigated in patients with HS.To investigate whether body image is diminished in patients with HS and whether disease severity, age at onset, disease duration, obesity, depression, and anxiety are linked to body image impairment.This 12-month (August 1, 2009, to August 31, 2010) case-control study with a prospective, observational, cross-sectional design recruited 47 consecutive patients with HS entering a tertiary care center and 45 healthy control individuals matched for age, sex, and body mass index (BMI). One patient and 4 controls failed to complete the questionnaire and were excluded from the evaluation. Data analysis was performed from December 1, 2013, to February 15, 2014.The Frankfurt Body Concept Scale (FKKS) and the Hospital Anxiety and Depression Scale (HADS) were given to patients and controls. Correlations among FKKS, HADS, and disease features were calculated.Of the 46 patients and 41 controls included in the evaluation (mean [SD] age, 35.6 [1.6] years; 40 [46%] male and 47 [54%] female), HS significantly reduced body image (mean FKKS score, 234.2 [5.4] in patients and 276.9 [5.7] in controls; P < .001), even when controlled for BMI. A correlation was found for the extent of body image disruption and BMI (r = -0.589; P < .001), HADS-depression score (r = -0.619; P < .001), and HADS-anxiety score (r = -0.340; P = .03). No association was found for the body image score and the severity of HS, age at onset of disease, and duration of disease. The body contact subscale score was the only subscale score that was not different between patients with HS and controls.Patients with HS have major body image impairment, which might lead to depression and anxiety, disorders that have been largely acknowledged in HS. This study identified another element of the psychosocial burden of patients with HS and reveals that body image could potentially be used as an outcome measure in future studies of HS.
| S-EPMC5876839 | biostudies-other
Project description:Trimethylamine N-oxide (TMAO) may play a key mediator role in the relationship between the diet, gut microbiota and cardiovascular diseases, particularly in people with kidney failure. The aim of this review is to evaluate which foods have a greater influence on blood or urinary trimethylamine N-oxide (TMAO) levels. 391 language articles were screened, and 27 were analysed and summarized for this review, using the keywords "TMAO" AND "egg" OR "meat" OR "fish" OR "dairy" OR "vegetables" OR "fruit" OR "food" in December 2020. A strong correlation between TMAO and fish consumption, mainly saltwater fish and shellfish, but not freshwater fish, has been demonstrated. Associations of the consumption of eggs, dairy and meat with TMAO are less clear and may depend on other factors such as microbiota or cooking methods. Plant-based foods do not seem to influence TMAO but have been less investigated. Consumption of saltwater fish, dark meat fish and shellfish seems to be associated with an increase in urine or plasma TMAO values. Further studies are needed to understand the relationship between increased risk of cardiovascular disease and plasma levels of TMAO due to fish consumption. Interventions coupled with long-term dietary patterns targeting the gut microbiota seem promising.
| S-EPMC8145508 | biostudies-literature
Project description:Acne Vulgaris (AV) and Hidradenitis suppurativa (HS) are common chronic inflammatory skin conditions that affect the follicular units that often coexist or are involved in differential diagnoses. Inflammation in both these diseases may result from shared pathways, which may partially explain their frequent coexistence. MicroRNAs (miRNAs) are a class of endogenous, short, non-protein coding, gene-silencing or promoting RNAs that may promote various inflammatory diseases. This narrative review investigates the current knowledge regarding miRNAs and their link to AV and HS. The aim is to examine the role of these molecules in the pathogenesis of AV and HS and to identify possible common miRNAs that could explain the similar characteristics of these two diseases. Five miRNA (miR-155 miR-223-, miR-21, and miRNA-146a) levels were found to be altered in both HS and AV. These miRNAs are related to pathogenetic aspects common to both pathologies, such as the regulation of the innate immune response, regulation of the Th1/Th17 axis, and fibrosis processes that induce scar formation. This review provides a starting point for further studies aimed at investigating the role of miRNAs in AV and HS for their possible use as diagnostic-therapeutic targets.
| S-EPMC8955726 | biostudies-literature
Project description:ImportanceThe variation in both clinical appearance and responses to diverse treatment options emphasize the importance of an accurate, clinically relevant, yet easy-to-use scoring system in hidradenitis suppurativa.ObjectiveTo propose and provide validation data for the newly designed Severity Assessment of Hidradenitis Suppurativa score.Design, setting, and participantsWe prospectively assessed disease severity using Hurley staging and the modified Hidradenitis Suppurativa Score in 355 patients referred to Ruhr-University Bochum Department of Dermatology between March 2016 and June 2017. We also assessed disease severity via the Severity Assessment of Hidradenitis Suppurativa score.Main outcomes and measuresEvaluation and assessment of convergent validity and responsiveness to treatment of the Severity Assessment of Hidradenitis Suppurativa score.ResultsEighty-eight of the 355 patients (134 [37.7%] men and 221 [62.3%] women with a median [IQR] age of 40 [30-49] years) were classified as Hurley stage I, 221 were Hurley stage II, and 46 were Hurley stage III, with an overall median modified Hidradenitis Suppurativa Score of 31 (interquartile range [IQR], 19.3-53). The median total Severity Assessment of Hidradenitis Suppurativa score was 6 (IQR, 4-9), significantly different among the 3 Hurley groups. The median SAHS score for patients in Hurley stage I was 5 (IQR, 3-6), 6 (IQR, 5-9) for patients in Hurley stage II, and 9 (IQR, 7-12) for patients in Hurley stage III (P < .001, Kruskal-Wallis test). Correlation analysis showed a significant correlation between the modified Hidradenitis Suppurativa Score and the Severity Assessment of Hidradenitis Suppurativa score (r = 0.79, P < .001). Disease severity assessment before and after 3 months of conservative systemic treatment showed a significant correlation between the Severity Assessment of Hidradenitis Suppurativa score and modified Hidradenitis Suppurativa Score. Both the mHSS (P = .001) and the SAHS score (P < .001) significantly differed between the baseline visit (median mHSS, 33 [IQR, 24-52]; median SAHS score, 6 [IQR, 5-9]) and the 3-month visit (median mHSS, 28 [IQR, 15-43.5]; median SAHS score, 5 [IQR, 4-6.3]). The 2 patient-reported items demonstrated excellent test-retest reliability with intraclass correlation coefficient values greater than 0.8.Conclusions and relevanceOur validation data demonstrated that the Severity Assessment of Hidradenitis Suppurativa score is a disease severity instrument that significantly correlates with Hurley staging and the modified Hidradenitis Suppurativa Score, and is responsive enough to measure treatment outcome.
| S-EPMC5885841 | biostudies-literature
Project description:Large size, protein binding and intracellular sequestration are well known to limit dialytic removal of compounds. In studying the normal renal and dialytic handling of trimethylamine oxide (TMAO), a molecule associated with cardiovascular disease in the general population, we discovered two largely unrecognized additional limitations to sustained reduction of a solute by chronic hemodialysis. We measured solute levels and handling in subjects on chronic hemodialysis (ESRD, n = 7) and compared these with levels and clearance in normal controls (NLS, n = 6). The ESRD patients had much higher peak predialysis plasma levels of TMAO than NLS (77 ± 26 vs 2±1 ?M, mean ± SD, p<0.05). For comparison, predialysis BUN levels in ESRD subjects were 45±11 mg/dl and 15±3 mg/dl in NLS. Thus TMAO levels in ESRD average about 40 fold those in NLS while BUN is 3 fold NLS. However, the fractional reduction of TMAO concentration during dialysis, was in fact greater than that of urea (86±3 vs 74±6%, TMAO vs urea, p < 0.05) and its dialytic clearance while somewhat lower than that of urea was comparable to creatinine's. Also production rates were similar (533±272 vs 606 ± 220 ? moles/day, ESRD vs NLS, p>0.05). However, TMAO has a volume of distribution about one half that of urea. Also in NLS the urinary clearance of TMAO was high (219±78 ml/min) compared to the urinary urea and creatinine clearances (55±14 and 119±21 ml/min, respectively). Thus, TMAO levels achieve multiples of normal much greater than those of urea due mainly to 1) TMAO's high clearance by the normal kidney relative to urea and 2) its smaller volume of distribution. Modelling suggests that only much more frequent dialysis would be required to lower levels Thus, additional strategies such as reducing production should be explored. Furthermore, using urea as the sole marker of dialysis adequacy may be misleading since a molecule, TMAO, that is dialyzed readily accumulates to much higher multiples of normal with urea based dialysis prescriptions.
| S-EPMC4674074 | biostudies-literature
Project description:BackgroundHidradenitis suppurativa (HS) is a chronic, inflammatory skin disease with a large impact on patients' health-related quality of life. However, reliable and consistent outcome measures to assess body surface area (BSA) of HS have not been established.ObjectivesTo develop and assess the reliability and validity of a novel outcome instrument for assessment of HS BSA in a clinical trial setting.MethodsQualitative interviews and focus groups were conducted from July to August 2015 and October 2017 to January 2018. Evaluation of the measurement was assessed during a single-day grading session with patients in April 2018. Participants, who included clinicians or patients, were recruited from academic medical centres in the U.S. mid-Atlantic region.ResultsConcept elicitation included input from 10 providers, of which 60% (n = 6) were female, 80% (n = 8) dermatology specialists and 20% (n = 2) gynaecology specialists. Cognitive debriefing was conducted with 11 providers, of which 82% (n = 9) were dermatologists and 18% (n = 2) gynaecologists. The evaluation stage included 10 clinicians and 23 patients. The intraclass correlation coefficient (ICC) for inter-rater reliability was 0·60 [95% confidence interval (CI) 0·44-0·74]. The ICC for intrarater reliability was 0·98 (95% CI 0·94-1·00). Transformation of the BSA score resulted in an increase in inter-rater reliability to 0·75 (95% CI 0·62-0·85) or 0·76 (95% CI 0·62-0·85). Scores all demonstrated concurrent validity, with statistically significant correlations with extant scoring methods.ConclusionsThis novel scale is a reliable and valid HS outcome instrument and may capture a wide range of patients by assessing BSA. Future research is necessary to demonstrate its responsiveness. What's already known about this topic? The major HS disease activity scales rely on lesions counts and have moderate-to-good reliability. Body surface area (BSA) is one of the physical signs included in the Core Outcome Set for HS, but is not a part of existing HS disease activity scales. What does this study add? A novel disease severity scale, the Severity and Area Score for Hidradenitis (SASH), was developed and the psychometric properties assessed. There was high inter-rater reliability of 0·75 and 0·76 when BSA was scored on an ordinal scale, and an excellent intrarater reliability of 0·98. The SASH score also demonstrated convergent validity with extant instruments. What are the clinical implications of this work? The ability of clinicians to accurately assess disease status will be improved. Implementation of the SASH score will help guide and assess the effectiveness of appropriate treatment choice.
| S-EPMC6928447 | biostudies-literature