Association of Trimethylamine N-Oxide (TMAO) with the Clinical Severity of Hidradenitis Suppurativa (Acne Inversa).
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SUBMITTER: Barrea L
PROVIDER: S-EPMC8226830 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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:BackgroundHidradenitis suppurativa (HS), also known as acne inversa, is a recurring, painful, chronic, and sometimes disfiguring inflammatory skin disease.ObjectivesOur objective was to report the baseline clinical characteristics, natural history, and associated outcomes of patients with HS from the ongoing, prospective, non-interventional UNITE registry that is collecting data regarding the natural history and associated outcomes of HS.MethodsPatients with inflammatory HS lesions were enrolled, including adolescents (aged 12 to < 18 years) and adults (aged ≥ 18 years). None had participated in previous or current originator-adalimumab studies/registries. Patients received treatment consistent with site-specific, routine clinical practice. HS disease status was assessed by HS lesions and disease flare; treatment and outcomes data were collected at enrolment and every 6 months for ≤ 4 years.ResultsEnrolment (N = 594; 89.1% adults; 10.9% adolescents) occurred from 29 October 2013 to 29 December 2015 at 73 sites in 12 countries. At baseline, the majority were female (69.7%) and White (81.2%), had moderate-to-severe disease (Hurley stage II or III; 93.3%), and had undergone prior procedures/surgery for HS (68.7%). In total, 61.6% of adults and 49.2% of adolescents were obese; 40.2% of patients reported current tobacco use. Scarring due to lesions occurred in 91.2% of patients. The prevalence of comorbidities of interest was as follows: depression (13.3%), other psychiatric disorders (9.6%), inflammatory bowel disease (2.7%), diabetes (9.1%), and polycystic ovary syndrome (5.2%).ConclusionsIn this population from the UNITE HS registry, obesity and smoking were common, and disease burden was high, manifesting as multiple lesions, scarring, surgical history, and considerable comorbidities.
| S-EPMC7371670 | 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:IntroductionHidradenitis suppurativa (HS) is considered to be the most burdensome dermatosis, with a well-documented negative influence on quality of life (QoL). The patient's perception of the disorder, assessed as the self-reported severity, has been used in other dermatoses but not in HS. The aim of this study was to evaluate the usefulness of self-reported HS severity in clinical practice.MethodsThe study was performed on a group of 130 Spanish HS patients. HS severity was assessed for all the subjects. Hurley staging and patient self-reported severity were used. Moreover, QoL impairment was evaluated using the Dermatology Life Quality Index (DLQI) and the Hidradenitis Suppurativa Quality of Life 24 (HSQoL-24) questionnaire.ResultsThe severity of HS according to the Hurley staging was most commonly assessed as Hurley II (47.7%), indicating moderate disease, followed by severe disease (Hurley III, 26.9%) and mild disease (Hurley I, 25.4%). According to the patient self-reported HS severity, most of the patients reported having mild disease (76 patients, 58.5%), followed by moderate disease (31 patients, 23.8%). Only 23 patients (17.7%) assessed their disease as severe. Moreover, men reported mild disease significantly more frequently than women (70.9% and 49.3%, respectively; p = 0.014). The self-reported HS severity correlated positively with the effect of the disease on patient QoL assessed with DLQI (r = 0.288, p < 0.001). Likewise, a strong positive correlation was found between self-reported HS severity and QoL impairment assessed with HSQoL-24 (r = 0.404, p = 0.001). No statistically significant correlation between Hurley severity stage and DLQI or HSQoL-24 was found. Moreover, there were significant differences in both DLQI and HSQoL-24 total score between different self-reported HS severities. This was not seen for any of the QoL instruments or for Hurley severity staging.ConclusionThe results show that self-assessment severity may reflect patients' subjective feelings more adequately than popular objective instruments, and there should be a place for its use in daily clinical practice.
| S-EPMC9021336 | 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:Pyoderma gangrenosum, acne, and hidradenitis suppurativa syndrome is a rare inflammatory disease characterized by pyoderma gangrenosum (PG), mild to severe facial acne, and hidradenitis suppurativa (HS). It only affects the skin and represents cutaneous characteristics of a spectrum of autoinflammation. Lack of pyogenic sterile arthritis (PA) distinguishes the pyoderma gangrenosum, acne, and hidradenitis suppurativa (PASH) syndrome from pyogenic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PA-PASH), pyoderma gangrenosum, acne, hidradenitis suppurtiva, and ankylosing spondylitis (PASS), and pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndromes. The exact etiology and pathogenesis of PASH syndrome remain unknown. Both PG and HS are contained in the spectrum of neutrophilic dermatitis, which is considered as an autoinflammatory syndrome. From a pathophysiological point of view, they show similar mechanisms, including neutrophil-rich cutaneous infiltration and overexpression of the interleukin-1 (IL-1) family. These findings provide guidance for these intractable diseases. In this review, we described a case of PASH syndrome in a patient who initially failed to respond to immunosuppressive treatment but responded to a combination of colchicine and thalidomide. We reviewed the relevant literature that focuses on PASH syndrome management.
| S-EPMC8987973 | biostudies-literature