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1.
J Eur Acad Dermatol Venereol ; 38(5): 904-909, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38112226

RESUMEN

BACKGROUND: Adalimumab monotherapy for hidradenitis suppurativa (HS) is often insufficient with a maximum clinical efficacy of 60% in Hidradenitis Suppurativa Clinical Response (HiSCR) and limited effect on draining tunnels. Data suggest that adalimumab therapy could be improved by concomitant antibiotics. OBJECTIVE: To compare the clinical effectiveness of adalimumab with clindamycin and rifampicin versus adalimumab monotherapy after 12 weeks. METHODS: This retrospective study included patients who started adalimumab with additional clindamycin and rifampicin and patients treated with adalimumab monotherapy, matched on sex and refined Hurley score. The primary outcome measure was the difference in change in the International Hidradenitis Suppurativa Severity Score System (IHS4) at 12 weeks. RESULTS: In total, 62 patients were included in the combination therapy group (n = 31) and adalimumab monotherapy group (n = 31), showing comparable IHS4 scores; 32.5 versus 29, p = 0.87 at baseline respectively. The combination therapy demonstrated greater clinical effectiveness expressed in median IHS4 improvement (-20 vs. -9, p < 0.001), IHS4-55 (74% vs. 36%, p = 0.002), median draining tunnel reduction (-4 vs. -2, p < 0.001) and pain response (47% vs. 27%, p = 0.02). CONCLUSION: Adalimumab initiated with clindamycin and rifampicin shows greater clinical effectiveness than adalimumab monotherapy. An important difference in effect was observed in the decrease of draining tunnels, addressing a serious limitation of adalimumab monotherapy.


Asunto(s)
Adalimumab , Clindamicina , Quimioterapia Combinada , Hidradenitis Supurativa , Rifampin , Humanos , Hidradenitis Supurativa/tratamiento farmacológico , Adalimumab/uso terapéutico , Adalimumab/administración & dosificación , Rifampin/uso terapéutico , Rifampin/administración & dosificación , Clindamicina/uso terapéutico , Clindamicina/administración & dosificación , Estudios Retrospectivos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Resultado del Tratamiento
2.
J Eur Acad Dermatol Venereol ; 36(3): 462-471, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34724272

RESUMEN

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, inflammatory disease of the apocrine gland-rich (AGR) skin region. The initial steps of disease development are not fully understood, despite intense investigations into immune alterations in lesional HS skin. OBJECTIVES: We aimed to systematically investigate the inflammatory molecules involved in three stages of HS pathogenesis, including healthy AGR, non-lesional HS and lesional HS skin, with the parallel application of multiple mRNA and protein-based methods. METHODS: Immune cell counts (T cells, dendritic cells, macrophages), Th1/Th17-related molecules (IL-12B, TBX21, IFNG, TNFA, IL-17, IL10, IL-23A, TGFB1, RORC, CCL20), keratinocyte-related sensors (TLR2,4), mediators (S100A7, S100A8, S100A9, DEFB4B, LCN2, CAMP, CCL2) and pro-inflammatory molecules (IL1B, IL6, TNFA, IL-23A) were investigated in the three groups by RNASeq, RT-qPCR, immunohistochemistry and immunofluorescence. RESULTS: Epidermal changes were already detectable in non-lesional HS skin; the epidermal occurrence of antimicrobial peptides (AMPs), IL-1ß, TNF-α and IL-23 was highly upregulated compared with healthy AGR skin. In lesional HS epidermis, TNF-α and IL-1ß expression remained at high levels while AMPs and IL-23 increased even more compared with non-lesional skin. In the dermis of non-lesional HS skin, signs of inflammation were barely detectable (vs. AGR), while in the lesional dermis, the number of inflammatory cells and Th1/Th17-related mediators were significantly elevated. CONCLUSIONS: Our findings that non-lesional HS epidermal keratinocytes produce not only AMPs and IL-1ß but also high levels of TNF-α and IL-23 confirm the driver role of keratinocytes in HS pathogenesis and highlight the possible role of keratinocytes in the transformation of non-inflammatory Th17 cells (of healthy AGR skin) into inflammatory cells (of HS) via the production of these mediators. The fact that epidermal TNF-α and IL-23 appear also in non-lesional HS seems to prove these cytokines as excellent therapeutic targets.


Asunto(s)
Hidradenitis Supurativa , Citocinas/metabolismo , Epidermis/patología , Hidradenitis Supurativa/genética , Humanos , Queratinocitos/patología , Piel/patología
3.
Br J Dermatol ; 185(1): 177-184, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33544917

RESUMEN

BACKGROUND: Biologics are often required for the treatment of hidradenitis suppurativa (HS). However, data on the drug survival of biologics in daily practice are currently lacking. OBJECTIVES: To assess the drug survival of antitumour necrosis factor biologics in a daily practice cohort of patients with HS and to identify predictors for drug survival. METHODS: A retrospective multicentre study was performed in two academic dermatology centres in the Netherlands. Adult patients with HS using biologics between 2008 and 2020 were included. Drug survival was analysed with Kaplan-Meier survival curves and predictors of survival with univariate Cox regression analysis. RESULTS: The overall drug survival of adalimumab (n = 104) at 12 and 24 months was 56·3% and 30·5%, respectively, which was predominantly determined by infectiveness. Older age (P = 0·02) and longer disease duration (P < 0·01) were associated with longer survival time. For infliximab (n = 44), overall drug survival was 58·3% and 48·6% at 12 and 24 months, respectively, and was predominantly determined by infectiveness and side-effects. Surgery during treatment was associated with a longer survival time (P = 0·01). CONCLUSIONS: Survival rates were comparable for adalimumab and infliximab at 12 months, and were mainly determined by ineffectiveness. Age, disease duration (adalimumab) and surgery (infliximab) are predictors for longer survival.


Asunto(s)
Hidradenitis Supurativa , Adalimumab/uso terapéutico , Adulto , Anciano , Estudios de Cohortes , Hidradenitis Supurativa/tratamiento farmacológico , Humanos , Infliximab/uso terapéutico , Países Bajos/epidemiología , Estudios Retrospectivos , Resultado del Tratamiento
4.
Br J Dermatol ; 183(6): e178-e187, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-29981245

RESUMEN

This scholarly review on the current and future treatment of hidradenitis suppurativa (HS) focuses on medical and surgical treatment options, while novel pipeline drugs are also discussed. Treatment goals are to limit the incidence and duration of flares, reducing inflammation and suppuration, achieving local cure after surgery and, most importantly, to improve the quality of life of patients with HS. The type of medication and/or surgery should be chosen based on the stage of the disease and the degree of inflammation. However, the lack of a simple scoring system and the lack of clear surgical outcome definitions hamper the interpretation of treatment efficacy and the comparison between different treatment strategies. The therapeutic pipeline for HS is gradually expanding, and will probably lead to a broader panel of more effective therapeutic options.


Asunto(s)
Hidradenitis Supurativa , Hidradenitis Supurativa/diagnóstico , Hidradenitis Supurativa/tratamiento farmacológico , Humanos , Incidencia , Inflamación , Calidad de Vida , Resultado del Tratamiento
5.
J Eur Acad Dermatol Venereol ; 34(10): 2353-2361, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32078194

RESUMEN

BACKGROUND: Mutations in the γ-secretase enzyme subunits have been described in multiple kindreds with familial hidradenitis suppurativa (HS). OBJECTIVE: In this study, we report a novel nicastrin (NCSTN) mutation causing HS in a Dutch family. We sought to explore the immunobiological function of NCSTN mutations using data of the Immunological Genome Project. METHODS: Blood samples of three affected and two unaffected family members were collected. Whole-genome sequencing was performed using genomic DNA isolated from peripheral blood leucocytes. Sanger sequencing was done to confirm the causative NCSTN variant and the familial segregation. The microarray data set of the Immunological Genome Project was used for thorough dissection of the expression and function of wildtype NCSTN in the immune system. RESULTS: In a family consisting of 23 members, we found an autosomal dominant inheritance pattern of HS and detected a novel splice site mutation (c.1912_1915delCAGT) in the NCSTN gene resulting in a frameshift and subsequent premature stop. All affected individuals had HS lesions on non-flexural and atypical locations. Wildtype NCSTN appears to be upregulated in myeloid cells like monocytes and macrophages, and in mesenchymal cells such as fibroblastic reticular cells and fibroblasts. In addition, within the 25 highest co-expressed genes with NCSTN we identified CAPNS1, ARNT and PPARD. CONCLUSION: This study reports the identification a novel NCSTN gene splice site mutation which causes familial HS. The associated immunobiological functions of NCSTN and its co-expressed genes ARNT and PPARD link genetics to the most common environmental and metabolic HS risk factors which are smoking and obesity.


Asunto(s)
Hidradenitis Supurativa , Secretasas de la Proteína Precursora del Amiloide/genética , Calpaína , Hidradenitis Supurativa/genética , Humanos , Glicoproteínas de Membrana , Mutación , Factores de Transcripción
6.
Br J Dermatol ; 181(2): 314-323, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-30657173

RESUMEN

BACKGROUND: Biologics targeting inflammatory mediators can achieve clinical improvements in hidradenitis suppurativa (HS). However, their clinical efficacy shows great interpatient variability in daily practice. OBJECTIVES: To investigate the anti-inflammatory potency of a selection of currently available biologics and prednisolone for the treatment of HS in an ex vivo skin culture system using lesional HS biopsies. METHODS: Lesional skin samples from 10 patients with HS and skin samples from five healthy controls were cultured ex vivo and exposed to prednisolone or biologics targeting tumour necrosis factor (TNF)-α, interleukin (IL)-17A, IL-12/23p40 or CD20 (adalimumab, infliximab, secukinumab, ustekinumab and rituximab, respectively). Real-time quantitative polymerase chain reaction and cytokine bead arrays were used to measure the inhibitory effect of the biologics on cytokines and antimicrobial peptides (AMPs). RESULTS: The relative mRNA expression of all tested cytokines and AMPs was significantly downregulated by all anti-inflammatory agents (P < 0·001). The protein production of the proinflammatory cytokines TNF-α, interferon γ, IL-1ß, IL-6 and IL-17A was significantly inhibited by adalimumab, infliximab, ustekinumab, prednisolone (all P < 0·001) and rituximab (P = 0·0071), but not by secukinumab (P = 0·0663). On both mRNA and protein levels, adalimumab, infliximab and prednisolone reduced the levels of a broader mix of individual cytokines than secukinumab, ustekinumab and rituximab. Moreover, a significant inhibitory effect on mRNA expression levels of inflammatory markers in healthy control skin was observed only for TNF-α inhibitors (P < 0·001) and prednisolone (P = 0·0015). CONCLUSIONS: This ex vivo study suggests that TNF-α inhibitors and prednisolone are the most powerful inhibitors of proinflammatory cytokines and AMPs in HS lesional skin, which concurs with our clinical experience in patients with HS.


Asunto(s)
Antiinflamatorios/farmacología , Productos Biológicos/farmacología , Hidradenitis Supurativa/tratamiento farmacológico , Prednisolona/farmacología , Piel/efectos de los fármacos , Adulto , Antiinflamatorios/uso terapéutico , Antígenos CD20/inmunología , Antígenos CD20/metabolismo , Péptidos Catiónicos Antimicrobianos/antagonistas & inhibidores , Péptidos Catiónicos Antimicrobianos/inmunología , Péptidos Catiónicos Antimicrobianos/metabolismo , Productos Biológicos/uso terapéutico , Biopsia , Femenino , Voluntarios Sanos , Hidradenitis Supurativa/inmunología , Hidradenitis Supurativa/patología , Hidradenitis Supurativa/cirugía , Humanos , Subunidad p40 de la Interleucina-12/antagonistas & inhibidores , Subunidad p40 de la Interleucina-12/inmunología , Subunidad p40 de la Interleucina-12/metabolismo , Interleucina-17/antagonistas & inhibidores , Interleucina-17/inmunología , Interleucina-17/metabolismo , Masculino , Persona de Mediana Edad , Técnicas de Cultivo de Órganos , Prednisolona/uso terapéutico , Piel/inmunología , Piel/metabolismo , Piel/patología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/inmunología , Factor de Necrosis Tumoral alfa/metabolismo
7.
Br J Dermatol ; 181(5): 967-975, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-30916379

RESUMEN

BACKGROUND: Weekly adalimumab (Humira® ) is approved for the treatment of hidradenitis suppurativa (HS) based on the 12-week placebo-controlled periods of the two phase III PIONEER trials. OBJECTIVES: Using PIONEER integrated trial results, we aimed to evaluate the optimal medium-term adalimumab maintenance dosing strategy for moderate-to-severe HS. METHODS: Each trial had two double-blind periods; 12-week Period A and 24-week Period B. Patients randomized to adalimumab 40 mg every week (ADAew) (Period A), were rerandomized in Period B to ADAew (ADAew/ew), ADA every other week (ADAew/eow), or placebo (ADAew/pbo). Placebo-randomized patients were reassigned in Period B to ADAew (PIONEER I) or placebo (PIONEER II). The primary outcome was HS Clinical Response (HiSCR). Patients who lost response during Period B were discontinued from the study and offered an option to enter the open-label extension (OLE) to receive ADAew. Results are reported across the two study periods, and data were combined from the two study periods and the OLE. RESULTS: For week-12 HiSCR achievers, the HiSCR week-36 rate was 48·1% (ADAew/ew) vs. 46·2% (ADAew/eow) and 32·1% (ADAew/pbo). Combining (post hoc) these patients with week-12 partial responders further differentiated outcomes in Period B (ADAew/ew 55·7% vs. ADAew/eow 40·0% and ADAew/pbo 30·1%). Period-B adverse-event rates were ADAew/ew 59·6% vs. ADAew/eow 57·4% and ADAew/pbo 65·0%. One patient (ADAew/ew) reported a serious infection. CONCLUSIONS: Weekly adalimumab treatment, effective throughout 36 weeks, was the optimal maintenance medium-term dosing regimen for this population. At least partial response after 12 weeks with continued weekly dosing had better outcomes than dose reduction or interruption. Patients who do not show at least a partial response to weekly adalimumab by week 12 are unlikely to benefit from continued therapy. No new safety risks were identified. What's already known about this topic? Hidradenitis suppurativa (HS) is a chronic inflammatory disease, commonly misinterpreted as an infection and treated with long-term antibiotic regimens or surgical incisions. Based on the chronicity of HS and the lack of evidence for efficacious and safe long-term HS treatments, it is important to evaluate medium- to long-term therapies for HS. Weekly adalimumab (Humira® ) is approved for the treatment of moderate-to-severe HS based on the two phase III PIONEER trials. What does this study add? This study pooled data from the two PIONEER trials, providing a more robust assessment of outcomes. After at least partial treatment success with weekly adalimumab short-term therapy (12 weeks), continuing weekly dosing during the subsequent 24 weeks had better outcomes than dose reduction or treatment interruption. Patients who do not show at least a partial response to weekly adalimumab by week 12 are unlikely to benefit from continued therapy.


Asunto(s)
Adalimumab/administración & dosificación , Hidradenitis Supurativa/tratamiento farmacológico , Quimioterapia de Mantención/métodos , Inhibidores del Factor de Necrosis Tumoral/administración & dosificación , Adalimumab/efectos adversos , Adolescente , Adulto , Anciano , Método Doble Ciego , Esquema de Medicación , Femenino , Hidradenitis Supurativa/diagnóstico , Humanos , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Placebos/administración & dosificación , Placebos/efectos adversos , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Adulto Joven
8.
Br J Dermatol ; 180(5): 1214-1220, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30512186

RESUMEN

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, debilitating, heterogeneous disease requiring different treatment approaches. Recently, we refined the classic Hurley classification into a seven-stage classification in order to guide these treatment choices. This new classification subdivides Hurley stage I and II into three substages, namely mild (A), moderate (B) and severe (C) HS disease. Hurley stage III is not subcategorized and is always severe. OBJECTIVES: To investigate the correlation between the given severity grades of Hurley I and Hurley II in the refined Hurley classification, and the patient-reported quality of life and physician-assessed objective severity score. MATERIALS AND METHODS: In this cross-sectional study, patients with HS participating in the observational cohorts of two Dutch tertiary referral centres were included before June 2017. The patient-reported Dermatology Life Quality Index (DLQI) and physician-assessed International HS Severity Score System (IHS4) scores were compared between the refined Hurley stages. RESULTS: In total, 433 patients were analysed. DLQI and IHS4 scores increased within Hurley stage I and II from A through C. There was a significant positive correlation of DLQI and IHS4 with increasing refined Hurley substages [refined Hurley stage I (A, B and C) to DLQI: rs = 0·259, P < 0·001 and refined Hurley stage II (A, B and C) to DLQI: rs = 0·185, P = 0·010; refined Hurley stage I (A, B and C) to IHS4: rs = 0·603, P < 0·001 and refined Hurley stage II (A, B and C) to IHS4: rs = 0·532, P < 0·001]. CONCLUSIONS: The refined Hurley classification accurately correlates with HS severity assessed by both patients and clinicians. Therefore, the refined Hurley classification is a useful tool for the quick assessment of severity in HS.


Asunto(s)
Hidradenitis Supurativa/diagnóstico , Medición de Resultados Informados por el Paciente , Calidad de Vida , Índice de Severidad de la Enfermedad , Adulto , Estudios Transversales , Estudios de Factibilidad , Femenino , Hidradenitis Supurativa/complicaciones , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Países Bajos , Sistema de Registros/estadística & datos numéricos
10.
J Eur Acad Dermatol Venereol ; 33(1): 170-177, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30022542

RESUMEN

BACKGROUND: An aberrant interaction between commensal skin bacteria and the host skin immune system is considered important in the pathogenesis of hidradenitis suppurativa (HS). OBJECTIVE: In this study, we investigated the antibiotic susceptibility and biofilm-forming capabilities of S. epidermidis strains isolated from HS patients. METHODS: Skin biopsies were taken from active HS lesions such as inflammatory nodules and/or sinuses and non-involved skin from 26 patients and cultured under optimal microbiological conditions for 24 h. Planktonic growth, biofilm production, antibiotic susceptibility and biofilm eradication by clindamycin, doxycycline, rifampicin and tetracycline were tested including a laboratory control strain of S. epidermidis for reference. RESULTS: Staphylococcus epidermidis was cultured in 16 of 26 HS patients (62%). In total 27 different S. epidermidis isolates were identified; 16 (59%) from non-involved skin and 11 (41%) from HS lesions. All bacterial strains showed planktonic growth. Twenty-four of 27 (89%) isolates were strong biofilm producers in vitro. The biofilm-forming capability varied amongst the strains from non-involved skin and lesional skin. Twenty-four strains had an intermediate to resistant antibiotic susceptibility to clindamycin (89%). Rifampicin was the most effective antibiotic at inhibiting planktonic growth and at eradication of biofilm (P < 0.05). CONCLUSION: We observed a slight increase in S. epidermidis virulence, characterized by resistance to commonly used antibiotics, increased biofilm production and resistance to biofilm eradication. In particular, the reduced sensitivity to tetracycline and clindamycin, two standard antibiotics in the treatment of HS, is alarming. Rifampicin, also important in HS treatment, showed the greatest efficacy at eradicating the biofilm at low MIC concentrations.


Asunto(s)
Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Hidradenitis Supurativa/microbiología , Staphylococcus epidermidis/efectos de los fármacos , Staphylococcus epidermidis/crecimiento & desarrollo , Biopelículas/crecimiento & desarrollo , Clindamicina/farmacología , Doxiciclina/farmacología , Farmacorresistencia Bacteriana , Humanos , Pruebas de Sensibilidad Microbiana , Rifampin/farmacología , Staphylococcus epidermidis/aislamiento & purificación , Tetraciclina/farmacología
12.
J Eur Acad Dermatol Venereol ; 33(4): 761-765, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30451329

RESUMEN

BACKGROUND: Treatment with apremilast has recently demonstrated clinically meaningful improvement in moderate hidradenitis suppurativa (HS). OBJECTIVE: To evaluate the change in expression of inflammatory markers in lesional skin of HS patients receiving apremilast 30 mg twice daily (n = 15) for 16 weeks compared with placebo (n = 5). METHODS: At baseline, 5-mm punch biopsies were obtained from an index lesion (HSL) and non-lesional (HSN) skin in the same anatomical area. Subsequent HSL samples were taken as close as possible to the previously biopsied site at week 4 and week 16. After sampling, biopsies were split; one half was processed for in vivo mRNA analysis using real-time quantitative PCR; the other half was cultured for ex vivo protein analysis using a proximity extension assay (Olink). Linear mixed effects models were calculated to compare the levels of inflammatory markers in HSL skin between apremilast and placebo over time. RESULTS: At baseline, 17 proteins with a fold change >2 in HSL vs. HSN skin were identified in 20 patients. The top five were IL-17A (5), S100A12, CST5, IL-12/23p40, CD6 (1) with fold changes ranging from 6.6 to 1638, respectively (FDR <0.044). Linear mixed effects models for 75 assays were calculated. Protein levels of S100A12 decreased during treatment in the apremilast group compared with the placebo group (p = 0.014, FDR = 0.186). None of the 14 genes exhibited significant changes in expression over time. However, an evident downward trend in relative mRNA expression of IL-17A and IL-17F was demonstrated in patients receiving apremilast. CONCLUSION: We did not detect statistically significant changes in inflammatory markers in HSL skin of HS patients receiving apremilast compared with placebo, despite clinical improvement in the apremilast group. Nonetheless, S100A12 and IL-17A were significantly elevated in HSL skin and showed a decrease in response to apremilast. The translational model in clinical trials involving HS clearly needs further improvement.


Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/metabolismo , ARN Mensajero/metabolismo , Talidomida/análogos & derivados , Adulto , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos de Diferenciación de Linfocitos T/genética , Antígenos de Diferenciación de Linfocitos T/metabolismo , Biomarcadores/metabolismo , Cistatinas/genética , Cistatinas/metabolismo , Femenino , Hidradenitis Supurativa/genética , Humanos , Interleucina-12/genética , Interleucina-12/metabolismo , Interleucina-17/genética , Interleucina-17/metabolismo , Masculino , Persona de Mediana Edad , Proteína S100A12/genética , Proteína S100A12/metabolismo , Talidomida/uso terapéutico , Adulto Joven
14.
J Eur Acad Dermatol Venereol ; 33(1): 19-31, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30176066

RESUMEN

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.


Asunto(s)
Antibacterianos/uso terapéutico , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/epidemiología , Fumar/epidemiología , Adalimumab/uso terapéutico , Antiinflamatorios/uso terapéutico , Productos Biológicos/uso terapéutico , Comorbilidad , Consenso , Técnica Delphi , Hidradenitis Supurativa/cirugía , Humanos , Guías de Práctica Clínica como Asunto
15.
Br J Dermatol ; 178(3): 715-721, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29080368

RESUMEN

BACKGROUND: A core outcomes set (COS) is an agreed minimum set of outcomes that should be measured and reported in all clinical trials for a specific condition. Hidradenitis suppurativa (HS) has no agreed-upon COS. A central aspect in the COS development process is to identify a set of candidate outcome domains from a long list of items. Our long list had been developed from patient interviews, a systematic review of the literature and a healthcare professional survey, and initial votes had been cast in two e-Delphi surveys. In this manuscript, we describe two in-person consensus meetings of Delphi participants designed to ensure an inclusive approach to generation of domains from related items. OBJECTIVES: To consider which items from a long list of candidate items to exclude and which to cluster into outcome domains. METHODS: The study used an international and multistakeholder approach, involving patients, dermatologists, surgeons, the pharmaceutical industry and medical regulators. The study format was a combination of formal presentations, small group work based on nominal group theory and a subsequent online confirmation survey. RESULTS: Forty-one individuals from 13 countries and four continents participated. Nine items were excluded and there was consensus to propose seven domains: disease course, physical signs, HS-specific quality of life, satisfaction, symptoms, pain and global assessments. CONCLUSIONS: The HISTORIC consensus meetings I and II will be followed by further e-Delphi rounds to finalize the core domain set, building on the work of the in-person consensus meetings.


Asunto(s)
Hidradenitis Supurativa/terapia , Ensayos Clínicos como Asunto , Consenso , Conferencias de Consenso como Asunto , Técnica Delphi , Salud Global , Humanos , Resultado del Tratamiento
16.
J Eur Acad Dermatol Venereol ; 32(3): 459-462, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29265421

RESUMEN

BACKGROUND: Surgery is an important treatment modality for hidradenitis suppurativa (HS). Various methods of HS surgery have been described. Even though wide excision is a common surgical procedure for HS, data on the recurrence rate and patient satisfaction are scarce. OBJECTIVE: To determine the recurrence rate and patient satisfaction of HS lesional wide excision (complete excision) with secondary intention healing. METHODS: A single centre retrospective study. Hundred and twenty eligible patients were identified from our medical files, and an individualized questionnaire was sent. RESULTS: Eighty-six patents responded to our questionnaire (71.7%). Of whom, 84 patients underwent in total 253 procedures. The mean follow-up time per procedure was 36.2 months. In 37.6% of the procedures, recurrence occurred within a mean follow-up period of 3 years (after a median of 6.0 months). Total remission of an anatomical area was achieved in 49% of the procedures, whereas natural disease progression occurred in 13%. The genital region was the most prone to recurrence. The majority of the patients were glad that they had undergone the procedure and would recommend the surgical procedure to other HS patients. CONCLUSION: Lesional wide excision (complete excision) with secondary intention healing yields a meaningful local cure rate for HS and is well tolerated.


Asunto(s)
Hidradenitis Supurativa/cirugía , Satisfacción del Paciente , Cicatrización de Heridas , Adolescente , Adulto , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Hidradenitis Supurativa/complicaciones , Humanos , Masculino , Recurrencia , Inducción de Remisión , Adulto Joven
18.
Br J Dermatol ; 176(1): 81-86, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27377616

RESUMEN

BACKGROUND: Pain is a common adverse effect of dermatological laser procedures. Currently, no standard topical anaesthetic cream exists for deeper dermal laser procedures. OBJECTIVES: To compare the efficacy of lidocaine/tetracaine cream and lidocaine/prilocaine cream in reducing self-reported pain during deeper dermal laser treatment of acne keloidalis nuchae (AKN) and tattoos. METHODS: We conducted two randomized, double-blind, controlled clinical trials with intrapatient, split-lesion designs: study A included patients with AKN (n = 15); study B included patients with black tattoos (n = 15). The primary end point was the patients' self-reported pain on a 10-cm visual analogue scale (VAS). Secondary objectives were the percentage of patients with adequate pain relief, willingness to pay €25 for the cream that provided the best pain relief and safety of the creams. RESULTS: In both studies, VAS scores were lower for lidocaine/prilocaine cream, with a mean VAS difference in study A of 1·9 [95% confidence interval (CI) 1·0-2·8] and in study B of 0·6 (95% CI -0·7 to 1·9). In study A, adequate pain relief was achieved in 13% (n = 2) with lidocaine/tetracaine cream vs. 73% (n = 11) with lidocaine/prilocaine cream (P = 0·004), and in study B in 53% (n = 8) vs. 80% (n = 12), respectively (P = 0·289). In study A, 47% (n = 7) were willing to pay an additional €25 vs. 73% (n = 11) in study B. No serious adverse events occurred. CONCLUSIONS: Lidocaine/prilocaine cream under plastic occlusion is the preferred topical anaesthetic during painful laser procedures targeting dermal chromophores.


Asunto(s)
Acné Queloide/terapia , Dolor Agudo/prevención & control , Anestésicos Combinados/administración & dosificación , Anestésicos Locales/administración & dosificación , Terapia por Láser/efectos adversos , Tatuaje , Adulto , Técnicas Cosméticas , Método Doble Ciego , Femenino , Humanos , Terapia por Láser/métodos , Lidocaína/administración & dosificación , Masculino , Prilocaína/administración & dosificación , Tetracaína/administración & dosificación
19.
Br J Dermatol ; 176(4): 1042-1047, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27534591

RESUMEN

BACKGROUND: Hidradenitis suppurativa (HS) has a major impact on patients' quality of life (QoL). Although it has commonly been assumed that HS impairs sexual health, only a single case-control study has been performed on sexual functioning in a small group of patients with HS. OBJECTIVES: To investigate the QoL with a particular focus on sexual health in a substantial population of patients with HS. METHODS: In total 916 patients with HS received an invitation to participate in this multicentre cross-sectional survey. RESULTS: Three hundred patients completed the questionnaires. This study showed a diminished QoL and sexual health in patients with HS (Female Sexual Function Index: 21·6 ± 9·6, International Index of Erectile Function: 49·7 ± 20·7, Arizona Sexual Experience Scale: 16·7 ± 5·3, Dermatology Life Quality Index: 12·5 ± 7·5). Sexual health was associated with QoL in women but not in men. Female sex and late onset of HS were associated with poor sexual function. Impairment of QoL was associated with anogenital involvement, early onset of HS, disease severity and disease activity. CONCLUSIONS: HS is associated with impaired sexual health and QoL. Physicians should not hesitate to ask patients with HS about their sexual function and, when needed, offer them psychological support.


Asunto(s)
Hidradenitis Supurativa/psicología , Calidad de Vida , Disfunciones Sexuales Fisiológicas/etiología , Edad de Inicio , Anciano , Estudios Transversales , Femenino , Humanos , Enfermedades de Inicio Tardío , Masculino , Persona de Mediana Edad , Salud Reproductiva/estadística & datos numéricos , Encuestas y Cuestionarios
20.
Br J Dermatol ; 177(6): 1495-1502, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-28646580

RESUMEN

The introduction of biological drugs for the treatment of patients with psoriasis has revolutionized treatment paradigms and enabled numerous patients to achieve disease control with an acceptable safety profile. However, the high cost of biologics limits access to these medications for the majority of patients worldwide. In recent years, the introduction of biosimilars for inflammatory diseases has become a fast evolving field. The future use of biosimilars offers the potential for decreased cost and increased access to biologics for patients with psoriasis. For approval of biosimilars, different regulatory agencies use highly variable methods for definition, production, approval, marketing and postmarketing surveillance. Due to potential interchangeability between biologics and biosimilars, traceability and pharmacovigilance are required to collect accurate data about adverse events in patients with psoriasis; spontaneous reporting, registries and use of 'big data' should facilitate this process on a global basis. The current article describes biosimilar regulatory guidelines and examples of biosimilar uptake in clinical practice in several countries around the world. As it is apparent that biological therapy treatment decisions may become more physician independent, the International Psoriasis Council recommends that dermatologists should take an active role in the development of biosimilar prescribing policies with their respective healthcare settings and government agencies.


Asunto(s)
Biosimilares Farmacéuticos/uso terapéutico , Fármacos Dermatológicos/uso terapéutico , Psoriasis/tratamiento farmacológico , Biosimilares Farmacéuticos/efectos adversos , Fármacos Dermatológicos/efectos adversos , Dermatólogos/psicología , Aprobación de Drogas , Salud Global , Humanos , Legislación de Medicamentos , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina , Vigilancia de Productos Comercializados
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