A systematic review and critical appraisal of pharmacological treatments for pediatric hidradenitis suppurativa.
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SUBMITTER: Moreno A
PROVIDER: S-EPMC11346302 | biostudies-literature | 2023 Sep
REPOSITORIES: biostudies-literature
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A systematic review and critical appraisal of pharmacological treatments for pediatric hidradenitis suppurativa.
Moreno Ariana A Williams Samuel C SC Goto Rie R Krueger James G JG Renert-Yuval Yael Y
Journal of the American Academy of Dermatology 20230509 3
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Project description: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.
| S-EPMC6392156 | biostudies-other
Project description:BackgroundThere is currently at least 1 biologic (adalimumab) approved in North America for treatment of Hidradenitis Suppurativa in the pediatric population. However, no reviews or clinical trials have specifically analyzed the effectiveness and safety data of biologic use in this population. The objective of this systematic review is to identify and summarize the outcomes of biologic therapy in pediatric patients with HS.MethodsMEDLINE and EMBASE databases were used to conduct the search on Sept 18, 2020.ResultsThe 15 included studies consisted of 26 patients, with the mean age of 15 ± 2.3 years. Females accounted for 53.8% (n = 14/26) of cases. The mean duration of HS prior to biologic initiation was 3.5 ± 2.9 years, with the majority having Hurley Stage II. The 26 patients received 34 biologics in total: 85.3% treated with TNF alpha inhibitors (adalimumab n = 17, infliximab n = 10, etanercept n = 1, unspecified n = 1), 5.9% with IL-12/23 inhibitors (ustekinumab n = 2), 5.9% with IL-1 inhibitors (i.e., anakinra n = 2) and 2.9% received IL-23 inhibitors (i.e., guselkumab n = 1) biologics. Of the 26 patients, 23.1% (n = 6/26) experienced complete resolution (CR), 73.1% (n = 19/26) experienced partial resolution (PR), and 3.8% (n = 1/26) had no resolution outcomes reported. The time to resolution of HS lesions after biologic initiation ranged from 10 days to 11.5 months (mean: 5.1 months). No adverse events were reported in the studies.ConclusionAlthough anti-TNF alpha were the most common biologics used for HS in pediatric cases, large-scale trials specific to pediatric patients with HS are needed to confirm these findings.
| S-EPMC8978460 | biostudies-literature
Project description:Background: Hidradenitis suppurativa (HS) is a chronic inflammatory disease with significant morbidity and impact on quality of life. Our understanding of the pathophysiology is incomplete, impairing efforts to develop novel therapeutic targets. Immunohistochemistry studies have produced conflicting results and no systematic evaluation of study methods and results has been undertaken to date. Methods: This systematic review aimed to collate and describe all reports of immunohistochemical staining in HS. This systematic review was registered with PROSPERO and conducted in line with the PRISMA reporting guidelines. Potential bias was assessed using the NIH Criteria and antibodies used across various studies were tabulated and compared. Results: A total of 22 articles were identified describing results from 494 HS patients and 168 controls. 87 unique immunohistochemical targets were identified. The overall quality of studies was sub-optimal with staining intensity confounded by active treatment. Conflicting data was identified and able to be reconciled through critical evaluation of the study methodology. Conclusions: Keratinocyte hyperplasia with loss of cytokeratin markers co-localizes with inflammation comprising of dendritic Cells, T-lymphocytes and macrophages, which are known to play central roles in inflammation in HS. Primary follicular occlusion as a pathogenic paradigm and the principal driver of HS is unclear based upon the findings of this review. Inflammation as a primary driver of disease with secondary hyperkeratosis and follicular occlusion is more consistent with the current published data.
| S-EPMC6593329 | biostudies-literature
Project description:The relationship between HS and obesity, while well established in adult patients, has drawn increased attention in pediatric patients given the rising prevalence of pediatric obesity worldwide. This review aims to consolidate existing evidence of the relationship between HS and obesity in the pediatric population and to hypothesize about reasons for an association between the two conditions. Our cohort comprised 2911 patients with a mean age of 11.4 years at the age of onset of HS, and based on body mass index (BMI), 42.3% of patients were classified as obese (BMI > 30), and 14% were overweight (BMI 25-29.9). Our findings indicate an association between obesity and HS in pediatric patients, which may be explained through numerous mechanisms, including shared genetic factors, hereditary relationships, and the impact of HS on adolescents' quality of life.
| S-EPMC11781012 | biostudies-literature
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.
| S-EPMC9131897 | biostudies-literature
Project description:Hidradenitis suppurativa is a chronic, suppurative condition of the pilosebaceous unit manifesting as painful nodules, abscesses, and sinus tracts mostly in, but not limited to, intertriginous skin. Great strides have been made at elucidating the pathophysiology of hidradenitis suppurativa, which appears to be the product of hyperkeratinization and inflammation brought about by environmental factors and a genetic predisposition. The identification of familial hidradenitis suppurativa has sparked research aimed at identifying underlying pathogenic variants in patients who harbor them. The objective of this review is to provide a broad overview of the role of genetics in various aspects of hidradenitis suppurativa, specifically the pathophysiology, diagnosis, and clinical application.
| S-EPMC8986338 | biostudies-literature
Project description:BackgroundAcne inversa/hidradenitis suppurativa (HS) is a chronic, recurrent inflammatory disease of the skin that can significantly affect patients' quality of life. The etiology and pathogenesis of HS are unclear and gene mutations might play a role.SummaryThe primary focus of the review is on aggregating the gene mutations reported, summarizing the structure of γ-secretase and analyzing and speculating about the mechanism and the underlying relations between gene mutation and functional changes of protein. The systematic literature review was done by searching the PubMed, Embase, and Web of Science databases. γ-Secretase is an intramembrane protease complex responsible for the intramembranous cleavage of more than 30 type-1 transmembrane proteins including amyloid precursor protein and Notch receptors. The protein complex consists of four hydrophobic proteins: presenilin, presenilin enhancer-2 (PSENEN), nicastrin, and anterior pharynx defective 1 (APH1). To date, 57 mutations of γ-secretase genes have been reported in 70 patients or families worldwide, including 39 in NCSTN, 14 in PSENEN, and 4 in PSEN1, of which 17 are frameshifts, 15 result in nonsense mutations, 13 in missense mutations, and 12 are splice site mutations. Given the structure of γ-secretase and analysis of related mutation loci of NCSTN, PSENEN, and PSEN1, mutations in γ-secretase genes could affect activation of presenilin, prevent substrate binding, and hinder intramembrane cleavage of select proteins.
| S-EPMC8491499 | biostudies-literature
Project description:Hidradenitis suppurativa (HS) is a chronic inflammatory disease manifesting in inverse body regions. In a systematic review, the role of hormones in HS will be presented to better understand the pathomechanisms of HS. The review is based on the PRISMA criteria. Systematic research was carried out using keywords. Subsequently, the data were analyzed based on the clinical response and other relevant information. The main focus of our systematic review was on HS manifestation, exacerbation, sex hormones, antiandrogen therapy, thyroid function, polycystic ovary syndrome, insulin resistance, and adipokines. In HS, there appears to be a dysregulated adipokine release that is shifted towards pro-inflammatory adipokines. Insulin resistance is significantly more common in HS than in healthy patients regardless of BMI, age, and gender. Insulin resistance in HS patients leads to further cardiovascular disease. The mechanism of insulin resistance and role of adipokines should be investigated in future studies to better provide the pathomechanisms of HS. The role of androgens seems to be important in a certain subgroup of female patients. Anti-androgenic therapy can be useful and helpful in some patients. However, further studies are needed to better understand the hormonal relationship in HS.
| S-EPMC9736970 | biostudies-literature
Project description:ObjectiveTo perform a systematic review of available literature regarding the use of 5-aminolevulinic acid (ALA) and ALA derivative photodynamic therapy (PDT) in the treatment of hidradenitis suppurativa (HS) and provide recommendations on its use.MethodsA systematic review was performed of all published studies up to September 1, 2019 from nine databases, including PubMed, that evaluated PDT in the treatment of HS. For each study, quality of evidence and risk of bias was evaluated. Recommendations from the body of evidence were created based on Strength of Recommendation and Taxonomy (SORT) criteria.ResultsEighteen studies met inclusion criteria. The majority of studies had a high risk of bias. Blue light PDT with 20% ALA and red light PDT with 16% methyl aminolevulinate (MAL) demonstrated some benefit based on a small number of poor-quality studies with a high risk of bias (Grade C, level III evidence). The most promising results were for 1%-5% ALA with intralesional diode, with good to complete response in 78%-94% of anatomic sites treated (Grade B, level II evidence).LimitationsThe majority of studies contained high levels of bias, with significant heterogeneity between studies. Conclusions are limited by small samples sizes, lack of randomized controlled trials, and differing protocols.ConclusionFurther studies are needed to determine the clinical efficacy of 20% ALA with blue light and MAL with red light. Intralesional diode PDT shows the most promise and warrants further investigation in larger, randomized controlled trials.
| S-EPMC10087637 | biostudies-literature
Project description:ImportanceHidradenitis suppurativa/acne inversa (HS) is a chronic inflammatory skin disease characterized by occlusion of hair follicles as a primary pathogenic factor. There are scarce data regarding the prevalence of HS.ObjectiveTo estimate overall HS prevalence.Data sourcesThis review and meta-regression analysis was conducted using the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline. The academic search included PubMed, Cochrane registry, ClinicalTrials.gov, and evidence by NHS UK and Trip databases from inception through May 2020. To analyze HS prevalence, only cross-sectional studies or baseline assessments of longitudinal cohorts using census-based surveys or probabilistic and nonprobabilistic epidemiologic methods were considered. The search terms were (prevalence OR incidence OR epidemiology) AND (hidradenitis suppurativa OR acne inversa OR Verneuil's disease). No language restriction was applied.Study selectionOriginal investigations that reported HS prevalence were included. After exclusion criteria were applied, 17 studies qualified for qualitative analysis, but only 16 studies were quantitatively assessed.Data extraction and measuresTwo reviewers extracted data by age, diagnostic criteria, presence of any comorbidity, sample sizes, continent/location, sex, and other characteristics. Assessment of bias risk used the Joanna Briggs Institute Critical Appraisal Instrument for Studies Reporting Prevalence Data using random-effects models to synthesize available evidence.Main outcomes and measuresHidradenitis suppurativa prevalence (with 95% CI) among the overall population and among subgroups. Between-study heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic).ResultsIn 16 quantitatively assessed studies included, prevalence estimates were reported only from Western European and Scandinavian countries, the US, and Australia. Meta-analysis with random effects, after adjusting for publication bias in the prevalence estimates, revealed a 0.40% prevalence (95% CI, 0.26%-0.63%) for HS. Studies based on clinical samples revealed a higher pooled prevalence of HS (1.7%) than population-based studies (0.3%).Conclusions and relevanceThe findings of this systematic review and meta-regression analysis may help facilitate policy formulation, channeling funding and guiding principles for better disease diagnosis using universal valid tools and management.
| S-EPMC8156162 | biostudies-literature