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A systematic review and critical evaluation of inflammatory cytokine associations in hidradenitis suppurativa.

ABSTRACT: Background: The pathogenesis of hidradenitis suppurativa (HS) remains unclear. In order to develop effective treatment strategies, a deeper understanding of pathophysiology is needed. This is impaired by multiple small studies with inconsistent methodologies and the impact of co-occurring pro-inflammatory conditions such as smoking and obesity. Methods: This systematic review aimed to collate all published reports of cytokine studies in tissue, blood, serum and exudate. It was registered with PROSPERO (Registration number CRD42018104664) performed in line with the PRISMA checklist. Results: 19 studies were identified comprising 564 individual HS patients and 198 control patients examining 81 discrete cytokines. Methodology was highly varied and the quality of studies was generally low. There was a large degree of variance between the measured levels of cytokines. 78.2% of cytokines demonstrated heterogeneity by the chi-squared test for homogeneity and hence meta-analysis was not deemed appropriate. However, a strong and significant IL-17 signalling component was identified. Conclusions: Cytokines consistently elevated in lesional, peri-lesional and unaffected tissue are identified and discussed. Areas for further investigation include the role of dendritic cells in HS; the contribution of obesity, smoking, diabetes and the microbiome to cytokine profiles in HS; and examining the natural history of this disease through longitudinal measurements of cytokines over time.

SUBMITTER: Frew JW

PROVIDER: S-EPMC6392156 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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A systematic review and critical evaluation of inflammatory cytokine associations in hidradenitis suppurativa.

Frew John W JW Hawkes Jason E JE Krueger James G JG

F1000Research 20181213

<b>Background:</b> The pathogenesis of hidradenitis suppurativa (HS) remains unclear. In order to develop effective treatment strategies, a deeper understanding of pathophysiology is needed. This is impaired by multiple small studies with inconsistent methodologies and the impact of co-occurring pro-inflammatory conditions such as smoking and obesity. <b>Methods:</b> This systematic review aimed to collate all published reports of cytokine studies in tissue, blood, serum and exudate. It was regi ...[more]

PMID: 30828428

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Project description:ImportanceThe identification and validation of biomarkers in hidradenitis suppurativa (HS) has potential to improve the understanding and management of this chronic, burdensome disease.ObjectiveTo systematically identify all known HS biomarkers, categorize them by biomarker type, and critically evaluate their validity according to established criteria.Evidence reviewEligibility criteria for this review (PROSPERO Registration 230830) included randomized clinical trials, uncontrolled clinical trials, cohort studies, case-control studies, and other observational studies with no restrictions of patient age, sex, race or ethnicity, or language of publication up until December 31, 2020. All articles were categorized into biomarker type, defined using the US Food and Drug Administration Biomarkers, Endpoints, and other Tools (BEST) glossary. Assessment of each identified biomarker was undertaken in line with the US Food and Drug Administration and European Medicines Agency guidelines for the validation of proposed biomarkers. Assessment of the strength of overall data regarding individual biomarkers was undertaken using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach.FindingsA total of 3953 nonduplicate articles were screened, of which 1429 articles were retrieved based on the include/exclusion criteria applied. After full-text screen and data extraction, 106 articles were included in this review. The evidence of strength of 6 categories of biomarkers (susceptibility/risk, diagnostic, monitoring, predictive, prognostic, and pharmacodynamic/response biomarkers) was assessed using GRADE criteria. A total of 48 biomarkers were identified with a minimum GRADE rating of moderate. Only 1 diagnostic (serum IL-2R), 1 monitoring (dermal Doppler vascularity), and 2 predictive biomarkers (epithelialized tunnels and positive family history of HS) achieved a GRADE rating of high. None of the identified biomarkers had sufficient clinical validity to be recommended for routine use in the clinical setting.Conclusions and relevanceMajor barriers to the identification, validation, and introduction of routine biomarkers in the management of HS include lack of independent biomarker validation studies (especially assumption-free "omics"-based techniques); insufficient assessment of collinearity between identified or proposed biomarkers; and a lack of routine integration of biomarkers into the structure of clinical trials. International consensus among researchers, clinicians, and pharmaceutical stakeholders is required to standardize goals and methods and encourage biomarker integration into future HS clinical trials. This systematic review presents a number of priorities for near-term future research to overcome such barriers and limitations of biomarkers in HS.

Project description:Background: The pathogenesis of hidradenitis suppurativa (HS) is not fully understood. This systematic review examined the latest evidence for molecular inflammatory pathways involved in HS as a chronic inflammatory skin disease. Methods: A systematic literature search was performed in PubMed/Medline and EMBASE from January 2013 through September 2017, according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA). Findings on HS pathogenesis were also compared with those of other immune-mediated inflammatory diseases (IMIDs) in a non-systematic review. In addition, current therapeutic options for HS are briefly discussed on the basis of the findings for the inflammatory pathways involved in HS. Results: A total of 32 eligible publications were identified by the systematic search; these were supplemented with three additional publications. The extracted data indicated that four key themes underlie the pathogenesis of HS and related syndromic conditions. First, nicastrin (NCSTN) and PSTPIP1 mutations are directly associated with auto-inflammatory disease. Secondly, the up-regulation of several cytokines including tumor necrosis factor-α and T helper-17/interleukin-23 are connected to auto-inflammatory mechanisms in the pathogenesis of HS. Thirdly, the microbiome of lesional skin differs significantly vs. normal-appearing skin. Fourthly, HS risk is enhanced through physiological and environmental factors such as smoking, obesity, and mechanical friction. There is significant overlap between the pathogenesis of HS, its syndromic forms and other IMIDs, particularly with respect to aberrations in the innate immune response. Conclusions: The evidence presented in this review supports HS as an auto-inflammatory skin disorder associated with alterations in the innate immune system. Based on these most recent data, an integrative viewpoint is presented on the pathogenesis of HS. Current management strategies on HS consist of anti-inflammatory therapies, surgical removal of chronic lesions, and lifestyle changes such as smoking cessation and weight loss. As large gaps remain in the understanding of the pathogenesis of HS, further research is warranted to ultimately improve the management and treatment of patients with HS and related syndromic conditions.

Project description:ImportanceHidradenitis suppurativa (HS) and inflammatory bowel disease (IBD) are inflammatory diseases that share common genetic susceptibility and immunologic features. However, the link between HS and IBD has been largely unclear.ObjectiveTo conduct a meta-analysis to investigate the association between HS and IBD.Data sourcesA search of the MEDLINE, Cochrane Central Register of Controlled Trials, and Embase databases yielded 397 relevant studies from inception to June 10, 2018. Two additional studies were supplied by one of the investigators.Study selectionCase-control, cross-sectional, or cohort studies that examined the odds or risk of IBD in patients with HS were included. No geographic or language limitations were imposed.Data extraction and synthesisThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The Newcastle-Ottawa Scale was used to assess the risk of bias of included studies. Crohn disease and ulcerative colitis were analyzed separately, and a random-effects model meta-analysis was conducted.Main outcomes and measuresThe odds ratios (ORs) and hazard ratios (HRs) of IBD, Crohn disease, and ulcerative colitis in association with HS.ResultsFive case-control studies, 2 cross-sectional studies, and 1 cohort study with a total of 93 601 unique participants were included. The meta-analysis of case-control and cross-sectional studies showed significant associations of HS with Crohn disease (pooled OR, 2.12; 95% CI, 1.46-3.08) and ulcerative colitis (pooled OR, 1.51; 95% CI, 1.25-1.82). Two case-control studies found significant association of HS with IBD (ORs, 2.16 [95% CI, 1.40-3.34] and 10.00 [95% CI, 1.94-51.50]). One cohort study found an increased risk of IBD in patients with HS (HR, 5.6; 95% CI not reported; P < .002).Conclusions and relevanceThe evidence to date supports an association of HS with IBD. These results suggest that consultation with gastroenterologists should be sought when patients with HS present with recurrent abdominal pain, chronic diarrhea, bloody stool, and body weight loss.

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A systematic review and critical evaluation of inflammatory cytokine associations in hidradenitis suppurativa.

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A systematic review and critical evaluation of inflammatory cytokine associations in hidradenitis suppurativa.

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