RESUMEN
Vitamin D plays a role in inflammatory skin conditions and can improve them. Hidradenitis suppurativa (HS) is an autoinflammatory chronic skin disease in which most patients exhibit a hypovitaminosis D. However, it is uncertain whether vitamin D supplementation could relieve the severity of HS. A systematic literature search of PubMed and Web of Science was conducted on 4 September 2023. Studies that investigated vitamin D and its potential implications for the severity of HS were included. In contrast, studies that focused on the prevalence of vitamin D deficiency were excluded, as well as studies on syndromic HS. Seven studies with a total of 575 patients were included in the qualitative synthesis, of which 3 utilized a cross-sectional design, 2 were pilot studies, 1 a controlled cohort study, and 1 a prospective case-control study. In all included studies, HS patients were vitamin D deficient. There was evidence indicating that serum vitamin D levels negatively correlated with the severity of the disease, and at least suggestive evidence that vitamin D supplementation could have a positive impact on the course of HS. To better understand these correlations, conducting a randomized controlled trial study on vitamin D and its effects on HS severity is imperative.
Asunto(s)
Hidradenitis Supurativa , Índice de Severidad de la Enfermedad , Deficiencia de Vitamina D , Vitamina D , Hidradenitis Supurativa/sangre , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/diagnóstico , Humanos , Vitamina D/sangre , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/epidemiología , Deficiencia de Vitamina D/tratamiento farmacológico , Deficiencia de Vitamina D/diagnóstico , Suplementos Dietéticos , Masculino , Biomarcadores/sangreAsunto(s)
Productos Biológicos , Hidradenitis Supurativa , Cobertura del Seguro , Medicaid , Humanos , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/economía , Estados Unidos , Productos Biológicos/uso terapéutico , Productos Biológicos/economía , Medicaid/economía , Medicaid/estadística & datos numéricos , Cobertura del Seguro/economía , Cobertura del Seguro/estadística & datos numéricosRESUMEN
BACKGROUND/AIMS: Aquaporin-3 (AQP3) is an aquaglyceroporin and peroxiporin that plays a crucial role in skin barrier homeostasis. Dysregulated AQP3 expression has been observed in different inflammatory skin conditions. Hidradenitis Suppurativa (HS) is an autoinflammatory keratinization disease that typically appears between 10 and 21 years of age, characterized by alteration of skin barrier homeostasis. METHODS: To evaluate in vitro the role of AQP3 in the development of HS, we performed real-time PCR and Western blot to analyze gene and protein levels in human keratinocyte cell lines knock-out (KO) for NCSTN and PSENEN genes, simulating genetic-associated HS. Additionally, we investigated the impact of Glyceryl Glucoside (GG) on biological processes by performing MTT, scratch, proliferation assays and proteome studies. RESULTS: We detected a significant decrease of the levels of AQP3 gene and protein in KO cell lines. GG effectively elevated the levels of mRNA and protein, significantly decreased the hyperproliferation rate, and enhanced cell migration in our in vitro model of genetic Hidradenitis Suppurativa. Pathway enrichment analysis further confirmed GG's role in the migration and proliferation pathways of keratinocytes. CONCLUSION: Our results suggest that AQP3 may act as a new novel actor in HS etio-pathogenesis, and GG could be further explored as potential treatment option for managing HS in patients.
Asunto(s)
Acuaporina 3 , Movimiento Celular , Proliferación Celular , Glucósidos , Hidradenitis Supurativa , Queratinocitos , Humanos , Acuaporina 3/metabolismo , Acuaporina 3/genética , Hidradenitis Supurativa/metabolismo , Hidradenitis Supurativa/patología , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/genética , Queratinocitos/metabolismo , Queratinocitos/efectos de los fármacos , Queratinocitos/patología , Queratinocitos/citología , Proliferación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Glucósidos/farmacología , Glucósidos/uso terapéutico , Línea CelularRESUMEN
Immune-mediated comorbidities in patients with psoriasiform eczema are common. It can be challenging to manage multiple immune-mediated diseases, especially considering that biologic treatments are prone to causing paradoxical effects. The aim of this retrospective observational case series was to describe the course of both psoriasiform eczema and immune-mediated comorbidities in five patients treated with upadacitinib for psoriasiform dermatitis. Five patients, all male, were included. All the patients suffered from psoriasiform eczema. Moreover, two of the patients suffered from alopecia areata, two from vitiligo, one from ulcerative colitis and one from hidradenitis suppurativa. In all cases, the treatment with upadacitinib was rapidly effective on the eczema. The effectiveness on alopecia areata was good in both cases, while the results on vitiligo were only partial. The only case of ulcerative colitis achieved complete remission, while the case of hidradenitis suppurativa experience partial improvement. In conclusion, upadacitinib was effective in treating not only psoriasiform eczema, but also several immune mediated comorbidities. Additional studies are necessary to determine the efficacy of upadacitinib in alopecia areata, vitiligo and hidradenitis suppurativa.
Asunto(s)
Comorbilidad , Eccema , Compuestos Heterocíclicos con 3 Anillos , Psoriasis , Humanos , Masculino , Adulto , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Persona de Mediana Edad , Eccema/tratamiento farmacológico , Psoriasis/tratamiento farmacológico , Psoriasis/inmunología , Alopecia Areata/tratamiento farmacológico , Alopecia Areata/inmunología , Estudios Retrospectivos , Resultado del Tratamiento , Vitíligo/tratamiento farmacológico , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/inmunología , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/inmunologíaRESUMEN
Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease. Most patients with moderate-to-severe disease require long-term antibiotic treatment, or biologic treatments to control their disease. Despite these interventions, relapses are common. This study evaluated the effectiveness of piperacillin/tazobactam treatment in patients with Hurley stage II and III HS who experienced disease flares and did not respond to conventional antibiotic and biologic treatment. Methods: Patients with HS hospitalized at the Department of Dermatology, Sheba Medical Center between August 2021 and January 2023 were retrospectively analyzed. Results: A cohort of ten such patients were treated with piperacillin/tazobactam for 6-21 days. Eight (80%) and two (20%) patients respectively demonstrated 2- and 1-grade improvements, from their baseline HS-Physician Global Assessment score. During the follow-up period, nine patients were monitored. HS Clinical Response (HiSCR) was achieved in six (66.7%) and five (55.6%) patients at the 3- and 6-month follow-up visits, respectively. Conclusions: In conclusion, Piperacillin/tazobactam emerges as a promising therapeutic option for disease flare-up in patients with Hurley stage II and III HS who do not respond to conventional treatment. Thus, piperacillin/tazobactam should be considered as crisis therapy for this patient subset.
Asunto(s)
Antibacterianos , Hidradenitis Supurativa , Combinación Piperacilina y Tazobactam , Índice de Severidad de la Enfermedad , Humanos , Hidradenitis Supurativa/tratamiento farmacológico , Combinación Piperacilina y Tazobactam/uso terapéutico , Femenino , Masculino , Estudios Retrospectivos , Adulto , Antibacterianos/uso terapéutico , Persona de Mediana Edad , Resultado del Tratamiento , Brote de los Síntomas , Adulto JovenRESUMEN
Hidradenitis Suppurativa (HS) is a chronic inflammatory skin disease that may have profound effects on the patient's quality of life. A personalized HS combination therapy treatment was prescribed to a 54-year-old female suffering from multiple painful sores, as follows: naltrexone capsules titrated from 0.5 mg up to 4.5 mg; pentoxifylline 5%, rifampin 2%, clindamycin 1%, and glycolic acid topical cream. Clinical improvements were observed using two disease-specific outcome measures: Hurley Staging System and HS Score. The patient's HS improved from Stage II (moderate) to Stage I (mild), and the HS score decreased from 103 points with five anatomical regions reported, to 19 points with only three regions affected. Furthermore, the before and after treatment photographs showed a visible reduction in the number of boils/skin abscesses and an overall recovery. Improvements were also observed across all domains of the patient's self-reported quality of life (Hidradenitis Suppurativa Quality of Life Assessment). The patient did not experience any undesirable effects. Compounded medications may be customized to meet the patient's special needs and may be adjusted throughout the course of treatment to match the patient's individual progress. Although further studies are necessary, this personalized, combination therapy may be a key treatment option in HS.
Asunto(s)
Clindamicina , Quimioterapia Combinada , Hidradenitis Supurativa , Pentoxifilina , Rifampin , Humanos , Femenino , Hidradenitis Supurativa/tratamiento farmacológico , Persona de Mediana Edad , Clindamicina/administración & dosificación , Clindamicina/uso terapéutico , Pentoxifilina/administración & dosificación , Pentoxifilina/uso terapéutico , Rifampin/administración & dosificación , Administración Oral , Calidad de Vida , Administración Tópica , Antibacterianos/administración & dosificación , Resultado del Tratamiento , Combinación de MedicamentosAsunto(s)
Hidradenitis Supurativa , Psoriasis , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/complicaciones , Hidradenitis Supurativa/inducido químicamente , Humanos , Psoriasis/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab/efectos adversos , Adalimumab/uso terapéuticoRESUMEN
Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that can be challenging to treat. Biologics and targeted small molecules have become an increasingly popular area of investigation for therapeutic development for moderate-to-severe HS, though only three biologics-adalimumab, secukinumab, and bimekizumab-have received US Food and Drug Administration (FDA) or European Medicines Evaluation Agency approval for treating HS. Promising agents under investigation are targeting interleukin 17A/F, JAK/STAT pathway, interleukin 36, interleukin 1, and more.
Asunto(s)
Hidradenitis Supurativa , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/inmunología , Humanos , Terapia Molecular Dirigida/métodos , Productos Biológicos/uso terapéutico , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Acne vulgaris, rosacea, and hidradenitis suppurativa are enduring inflammatory skin conditions that frequently manifest with akin clinical attributes, posing a considerable challenge for their distinctive diagnosis. While these conditions do exhibit certain resemblances, they also demonstrate distinct underlying pathophysiological mechanisms and treatment modalities. Delving into both the molecular parallels and disparities among these three disorders can yield invaluable insights for refined diagnostics, effective management, and targeted therapeutic interventions. In this report, we present a comparative analysis of transcriptomic data across these three diseases, elucidating differentially expressed genes and enriched pathways specific to each ailment, as well as those shared among them. Specifically, we identified multiple zinc-binding proteins (SERPINA1, S100A7, S100A8, S100A9 and KRT16) as consistently highly upregulated genes across all three diseases. Our hypothesis suggests that these proteins could bind and sequester zinc, potentially leading to localized zinc deficiency and heightened inflammation. We identified high-dose dietary zinc as a promising therapeutic approach and confirmed its effectiveness through validation in an acne mouse model.
Asunto(s)
Acné Vulgar , Perfilación de la Expresión Génica , Hidradenitis Supurativa , Rosácea , Zinc , Acné Vulgar/tratamiento farmacológico , Acné Vulgar/genética , Zinc/uso terapéutico , Zinc/metabolismo , Rosácea/tratamiento farmacológico , Rosácea/genética , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/genética , Animales , Ratones , Humanos , Proteína A7 de Unión a Calcio de la Familia S100/metabolismo , Proteína A7 de Unión a Calcio de la Familia S100/genética , Calgranulina A/genética , Calgranulina A/metabolismo , Calgranulina B/genética , Calgranulina B/metabolismo , Transcriptoma , Proteínas S100/genética , Proteínas S100/metabolismo , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Modelos Animales de Enfermedad , Regulación hacia ArribaRESUMEN
Real-world data on the long-term effectiveness of the anti-IL17 agent secukinumab in treating moderate-to-severe Hidradenitis suppurativa (HS) are lacking. In this study, 24 patients with moderate-severe HS received five weekly subcutaneous injections followed by maintenance doses every 4 weeks. Primary outcomes included HiSCR, IHS4 reduction, and DLQI measures assessed at 12-week intervals. The median secukinumab drug survival was 16.0 months (range 3-51), with a 56.5% maximal response rate at 6 months and dropout exceeding 40% at 1 year. Baseline disease burden emerged as a key predictor of treatment response, overshadowing factors like sex or BMI. Prior systemic steroid use negatively impacts drug survival. The study underscores the critical 6-month window for assessing treatment efficacy, emphasizing the importance of initial induction dosing. Additionally, the newly developed scoring system, IHS4-55, showed analogies to the older HiSCR score in capturing treatment response. In this real-life scenario, challenges persist in HS management, necessitating innovative therapeutic approaches and predictive markers.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Hidradenitis Supurativa , Interleucina-17 , Humanos , Hidradenitis Supurativa/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Masculino , Femenino , Adulto , Interleucina-17/antagonistas & inhibidores , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Inyecciones Subcutáneas , Resultado del Tratamiento , Adulto JovenAsunto(s)
Adalimumab , Hidradenitis Supurativa , Cicatrización de Heridas , Humanos , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/cirugía , Adalimumab/uso terapéutico , Cicatrización de Heridas/efectos de los fármacos , Antiinflamatorios/uso terapéutico , Adulto , Femenino , MasculinoAsunto(s)
Antibacterianos , Hidradenitis Supurativa , Moxifloxacino , Humanos , Hidradenitis Supurativa/tratamiento farmacológico , Estudios Retrospectivos , Moxifloxacino/uso terapéutico , Moxifloxacino/administración & dosificación , Masculino , Femenino , Adulto , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Resultado del Tratamiento , Persona de Mediana Edad , Adulto JovenRESUMEN
Hidradenitis suppurativa (HS) is a chronic, debilitating skin condition that requires multimodal treatment. Adherence remains a significant challenge for many patients due to complex nature of treatment, thus presenting a barrier to management success. This review summarizes the current literature on the factors associated with adherence to medications, and lifestyle behaviors in patients with HS and proposes strategies to improve adherence. In February 2023, a systematic literature search was conducted by two independent authors on PubMed and EMBASE for articles from 2000 to 2023 on hidradenitis suppurativa adherence. A total of 21 articles met inclusion/exclusion criteria for this review. Of the studies, 11 addressed systemic medication adherence, 3 addressed topical medication adherence, 2 addressed both systemic and topical medication adherence, and 5 addressed lifestyle/behavioral modification adherence. The generalizability of results was limited by differences in study design, outcome measures, and sample size. English-only articles with full texts were used. The most reported reasons for non-adherence included presence of side effects, cost of medications, low efficacy, and unclear instructions. Proposed strategies to improve adherence in HS patients include management of side effects, use of reminder systems, improved patient education, patient support groups, aid of family and caregivers, personalization of the medication regimen, and regular follow-ups with patients. PROSPERO Registration Number: CRD42023488549.
Asunto(s)
Hidradenitis Supurativa , Cumplimiento de la Medicación , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/terapia , Humanos , Cumplimiento de la Medicación/estadística & datos numéricos , Educación del Paciente como Asunto , Estilo de Vida , Sistemas RecordatoriosRESUMEN
The S2k guideline on hidradenitis suppurativa/acne inversa (HS/AI) aims to provide an accepted decision aid for the selection/implementation of appropriate/sufficient therapy. HS/AI is a chronic recurrent, inflammatory, potentially mutilating skin disease of the terminal hair follicle-glandular apparatus, with painful, inflammatory lesions in the apocrine gland-rich regions of the body. Its point prevalence in Germany is 0.3%, it is diagnosed with a delay of 10.0 ± 9.6 years. Abnormal differentiation of the keratinocytes of the hair follicle-gland apparatus and accompanying inflammation form the central pathogenetic basis. Primary HS/AI lesions are inflammatory nodules, abscesses and draining tunnels. Recurrences in the last 6 months with at least 2 lesions at the predilection sites point to HS/AI with a 97% accuracy. HS/AI patients suffer from a significant reduction in quality of life. For correct treatment decisions, classification and activity assessment should be done with a validated tool, such as the International Hidradenitis Suppurativa Severity Scoring System (IHS4). HS/AI is classified into two forms according to the degree of detectable inflammation: active, inflammatory (mild, moderate, and severe according to IHS4) and predominantly inactive, non-inflammatory (Hurley grade I, II and III) HS/AI. Oral tetracyclines or 5-day intravenous therapy with clindamycin are equal to the effectiveness of clindamycin/rifampicin. Subcutaneously administered adalimumab, secukinumab and bimekizumab are approved for the therapy of HS/AI. Various surgical procedures are available for the predominantly non-inflammatory disease form. Drug/surgical combinations are considered a holistic therapy method.
Asunto(s)
Hidradenitis Supurativa , Hidradenitis Supurativa/terapia , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/diagnóstico , Humanos , Alemania , Antibacterianos/uso terapéutico , Guías de Práctica Clínica como Asunto , Calidad de Vida , Índice de Severidad de la Enfermedad , Fármacos Dermatológicos/uso terapéuticoRESUMEN
This scoping review aims to characterize the use of biologics and Janus Kinase inhibitors (JAKi) in the treatment of Hidradenitis Suppurativa (HS), which is a chronic inflammatory condition. A comprehensive literature search was conducted in PubMed/NCBI, Embase, Web of Science databases, and the Clinicaltrials.gov register. The search included interventional trials assessing the use of biologics or JAKi in HS, with no geographic or time restrictions. Secukinumab and adalimumab were identified as the only two drugs approved by the FDA for treating moderate to severe HS in adults. Several other drug classes showed promising results based on clinical studies reviewed. IL-12/23 inhibitor ustekinumab demonstrated improvements in disease severity scores and HiSCR rates in small trials. IL-17 inhibitors such as brodalumab, bimekizumab, and CJM112 showed preliminary positive responses in early-phase clinical studies and case reports. While evidence was mixed, some TNF-α inhibitors such as infliximab provided benefits according to a randomized controlled trial, though etanercept trials yielded non-significant or inconsistent findings. Larger, well-designed studies are required to further establish their efficacy and safety, but biologics and JAKis show potential as alternative treatment options for moderate to severe HS. The findings of this review contribute to the growing interest among patients and to enhancing the understanding of physician's regarding potential alternative therapeutic options for HS and provide a basis for further research in this field.
Asunto(s)
Productos Biológicos , Hidradenitis Supurativa , Inhibidores de las Cinasas Janus , Índice de Severidad de la Enfermedad , Hidradenitis Supurativa/tratamiento farmacológico , Humanos , Inhibidores de las Cinasas Janus/uso terapéutico , Productos Biológicos/uso terapéutico , Resultado del Tratamiento , Adalimumab/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéuticoRESUMEN
This post hoc analysis of PIONEER I and II randomized clinical trials assesses whether receiving adalimumab is associated with decreased hematologic abnormalities and increased clinical improvement in patients with hidradenitis suppurativa.
Asunto(s)
Adalimumab , Hidradenitis Supurativa , Humanos , Hidradenitis Supurativa/tratamiento farmacológico , Adalimumab/efectos adversos , Adalimumab/uso terapéutico , Adalimumab/administración & dosificación , Femenino , Masculino , Adulto , Persona de Mediana Edad , Enfermedades Hematológicas , Antiinflamatorios/uso terapéutico , Antiinflamatorios/administración & dosificación , Antiinflamatorios/efectos adversosRESUMEN
BACKGROUND: Patients with hidradenitis suppurativa have substantial unmet clinical needs and scarce therapeutic options. We aimed to assess the efficacy and safety of bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F and IL-17A, in patients with moderate-to-severe hidradenitis suppurativa. METHODS: BE HEARD I and II were two identically designed, 48-week randomised, double-blind, placebo-controlled, multicentre phase 3 trials. Patients aged 18 years or older with moderate-to-severe hidradenitis suppurativa were randomly assigned 2:2:2:1 using interactive response technology (stratified by worst Hurley Stage at baseline and baseline systemic antibiotic use) to receive subcutaneous bimekizumab 320 mg every 2 weeks; bimekizumab 320 mg every 2 weeks to week 16, then every 4 weeks to week 48; bimekizumab 320 mg every 4 weeks to week 48; or placebo to week 16, then bimekizumab 320 mg every 2 weeks. The primary outcome was an hidradenitis suppurativa clinical response of at least 50%, defined as a reduction in total abscess and inflammatory nodule count of at least 50% from baseline with no increase from baseline in abscess or draining tunnel count (HiSCR50) at week 16. Efficacy analyses included all randomly assigned study patients (intention-to-treat population). Safety analyses included all patients who received at least one full or partial dose of study treatment in the safety set, and of bimekizumab in the active-medication set. These trials are registered at ClinicalTrials.gov, NCT04242446 and NCT04242498, and both are completed. FINDINGS: Patients for BE HEARD I were recruited from Feb 19, 2020, to Oct 27, 2021, and 505 patients were enrolled and randomly assigned. Patients for BE HEARD II were recruited from March 2, 2020, to July 28, 2021, and 509 patients were enrolled and randomly assigned. The primary outcome at week 16 was met in the group who received bimekizumab every 2 weeks using modified non-responder imputation; higher responder rates were observed with bimekizumab versus placebo in both trials: 138 (48%) of 289 patients versus 21 (29%) of 72 patients in BE HEARD I (odds ratio [OR] 2·23 [97·5% CI 1·16-4·31]; p=0·0060) and 151 (52%) of 291 patients versus 24 (32%) of 74 patients in BE HEARD II (2·29 [1·22-4·29]; p=0·0032). In BE HEARD II, HiSCR50 was also met in the group who were administered bimekizumab every 4 weeks (77 [54%] of 144 vs 24 [32%] of 74 with placebo; 2·42 [1·22-4·80]; p=0·0038). Responses were maintained or increased to week 48. Serious treatment-emergent adverse events were reported in 40 (8%) patients in BE HEARD I and in 24 (5%) patients in BE HEARD II treated with bimekizumab over 48 weeks. The most frequently reported treatment-emergent adverse events to week 48 were hidradenitis in both trials, in addition to coronavirus infection and diarrhoea in BE HEARD I, and oral candidiasis and headache in BE HEARD II. One death was reported across the two trials, and was due to congestive heart failure in a patient with substantial cardiovascular history treated with bimekizumab every 2 weeks in BE HEARD I (considered unrelated to bimekizumab treatment by the investigator). No new safety signals were observed. INTERPRETATION: Bimekizumab was well tolerated by patients with hidradenitis suppurativa and produced rapid and deep clinically meaningful responses that were maintained up to 48 weeks. Data from these two trials support the use of bimekizumab for the treatment of patients with moderate-to-severe hidradenitis suppurativa. FUNDING: UCB Pharma.