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1.
Cell Cycle ; 23(4): 385-404, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38557266

ABSTRACT

Studies indicate that mitogen-activated protein kinases (MAPKs) exhibit activation and overexpression within psoriatic lesions. This study aimed to investigate alterations in the expression patterns of genes encoding MAPKs and microRNA (miRNA) molecules that potentially regulate their expression in human adult low-calcium high-temperature (HaCaT) keratinocytes when exposed to bacterial lipopolysaccharide A (LPS) and adalimumab. HaCaT cells underwent treatment with 1 µg/mL LPS for 8 hours, followed by treatment with 8 µg/mL adalimumab for 2, 8, or 24 hours. Untreated cells served as controls. The molecular analysis involved microarray, quantitative real-time polymerase chain reaction (RTqPCR), and enzyme-linked immunosorbent assay (ELISA) analyses. Changes in the expression profile of seven mRNAs: dual specificity phosphatase 1 (DUSP1), dual specificity phosphatase 3 (DUSP3), dual specificity phosphatase 4 (DUSP4), mitogen-activated protein kinase 9 (MAPK9), mitogen-activated protein kinase kinase kinase 2 (MAP3K2), mitogen-activated protein kinase kinase 2 (MAP2K2), and MAP kinase-activated protein kinase 2 (MAPKAPK2, also known as MK2) in cell culture exposed to LPS or LPS and the drug compared to the control. It was noted that miR-34a may potentially regulate the activity of DUSP1, DUSP3, and DUSP4, while miR-1275 is implicated in regulating MAPK9 expression. Additionally, miR-382 and miR-3188 are potential regulators of DUSP4 levels, and miR-200-5p is involved in regulating MAPKAPK2 and MAP3K2 levels. Thus, the analysis showed that these mRNA molecules and the proteins and miRNAs they encode appear to be useful molecular markers for monitoring the efficacy of adalimumab therapy.


Subject(s)
Adalimumab , Lipopolysaccharides , MicroRNAs , Mitogen-Activated Protein Kinases , RNA, Messenger , Humans , Lipopolysaccharides/pharmacology , MicroRNAs/genetics , MicroRNAs/metabolism , Adalimumab/pharmacology , RNA, Messenger/metabolism , RNA, Messenger/genetics , Mitogen-Activated Protein Kinases/metabolism , HaCaT Cells , Keratinocytes/metabolism , Keratinocytes/drug effects , Gene Expression Profiling , Cell Line
3.
Br J Dermatol ; 187(6): 927-935, 2022 12.
Article in English | MEDLINE | ID: mdl-36056741

ABSTRACT

BACKGROUND: Nearly half of patients with hidradenitis suppurativa (HS) report dissatisfaction with their treatment. However, factors related to treatment satisfaction have not been explored. OBJECTIVES: To measure associations between treatment satisfaction and clinical and treatment-related characteristics among patients with HS. METHODS: Treatment satisfaction was evaluated utilizing data from a cross-sectional global survey of patients with HS recruited from 27 institutions, mainly HS referral centres, in 14 different countries from October 2017 to July 2018. The primary outcome was patients' self-reported overall satisfaction with their current treatments for HS, rated on a five-point scale from 'very dissatisfied' to 'very satisfied'. RESULTS: The final analysis cohort comprised 1418 patients with HS, most of whom were European (55%, 780 of 1418) or North American (38%, 542 of 1418), and female (85%, 1210 of 1418). Overall, 45% (640 of 1418) of participants were either dissatisfied or very dissatisfied with their current medical treatment. In adjusted analysis, patients primarily treated by a dermatologist for HS had 1·99 [95% confidence interval (CI) 1·62-2·44, P < 0·001] times the odds of being satisfied with current treatment than participants not primarily treated by a dermatologist. Treatment with biologics was associated with higher satisfaction [odds ratio (OR) 2·36, 95% CI 1·74-3·19, P < 0·001] relative to treatment with nonbiologic systemic medications. Factors associated with lower treatment satisfaction included smoking (OR 0·78, 95% CI 0·62-0·99; active vs. never), depression (OR 0·69, 95% CI 0·54-0·87), increasing number of comorbidities (OR 0·88 per comorbidity, 95% CI 0·81-0·96) and increasing flare frequency. CONCLUSIONS: There are several factors that appear to positively influence satisfaction with treatment among patients with HS, including treatment by a dermatologist and treatment with a biologic medication. Factors that appear to lower treatment satisfaction include active smoking, depression, accumulation of comorbid conditions and increasing flare frequency. Awareness of these factors may support partnered decision making with the goal of improving treatment outcomes. What is already known about this topic? Nearly half of patients with hidradenitis suppurativa report dissatisfaction with their treatments. What does this study add? Satisfaction with treatment is increased by receiving care from a dermatologist and treatment with biologics. Satisfaction with treatment is decreased by tobacco smoking, accumulation of comorbid conditions including depression, and higher flare frequency. What are the clinical implications of this work? Awareness of the identified factors associated with poor treatment satisfaction may support partnered decision making and improve treatment outcomes.


Subject(s)
Biological Products , Hidradenitis Suppurativa , Humans , Female , Hidradenitis Suppurativa/drug therapy , Hidradenitis Suppurativa/complications , Cross-Sectional Studies , Personal Satisfaction , Patient Satisfaction , Biological Products/therapeutic use
5.
J Clin Med ; 10(18)2021 Sep 16.
Article in English | MEDLINE | ID: mdl-34575300

ABSTRACT

Hidradenitis suppurativa (HS) is a chronic, debilitating skin condition that negatively affects patients' quality of life. Indirect self-destructiveness refers to activities extended over time, such as addictions, risky behaviors, neglects, resignation, helplessness. These can be an additional factor impeding the achievement of positive clinical effects in the treatment of HS patients, therefore the objective of the study was to assess the indirect self-destructive behaviors in patients suffering from HS. The study group involved 100 adult HS patients with 59 males and 41 females. Indirect self-destructiveness was investigated with the Polish version of the Kelley's Indirect Self-Destructiveness Scale (CS-DS). The study revealed that the average total score of indirect self-destructiveness in HS population was 130.16 ± 21.3 (median 128 points). The CS-DS scores were significantly higher in smoking patents (p = 0.006). The most expressed class of indirect self-destructiveness was A5 (Helplessness and Passivity). The indicated results pointed out a strong domination of passive forms of indirect self-destructiveness over its active forms. Due to related low self-esteem, social isolation and exclusion, HS patients are more prone to behave in a self-destructive manner, which may lead to poor health maintenance in a form of leaving appointments and non-adherence.

7.
Arch Dermatol Res ; 312(10): 715-724, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32166376

ABSTRACT

Hidradenitis suppurativa (HS) rarely affects pediatric patients. The literature on pediatric HS patients is scarce. This is a cross-sectional study based on case note review or interviews and clinical examination of 140 pediatric patients undergoing secondary or tertiary level care. Patients were predominantly female (75.5%, n = 105) with a median age of 16. 39% reported 1st-degree relative with HS. Median BMI percentile was 88, and 11% were smokers (n = 15). Median modified Sartorius score was 8.5. Notable comorbidities found were acne (32.8%, n = 45), hirsutism (19.3%, n = 27), and pilonidal cysts (16.4%, n = 23). Resorcinol (n = 27) and clindamycin (n = 25) were the most frequently used topical treatments. Patients were treated with tetracycline (n = 32), or oral clindamycin and rifampicin in combination (n = 29). Surgical excision was performed in 18 patients, deroofing in five and incision in seven patients. Obesity seemed to be prominent in the pediatric population and correlated to parent BMI, suggesting a potential for preventive measures for the family. Disease management appeared to be similar to that of adult HS, bearing in mind that the younger the patient, the milder the disease in majority of cases.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Dermatologic Surgical Procedures , Hidradenitis Suppurativa/therapy , Obesity/epidemiology , Smoking/epidemiology , Acne Vulgaris/epidemiology , Administration, Cutaneous , Administration, Oral , Adolescent , Body Mass Index , Child , Clindamycin/administration & dosage , Comorbidity , Cross-Sectional Studies , Drug Therapy, Combination/methods , Female , Hidradenitis Suppurativa/epidemiology , Hirsutism/epidemiology , Humans , Male , Pilonidal Sinus/epidemiology , Resorcinols/administration & dosage , Rifampin/administration & dosage , Risk Factors , Severity of Illness Index , Tetracycline/administration & dosage , Treatment Outcome , Young Adult
8.
J Am Acad Dermatol ; 82(2): 366-376, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31279015

ABSTRACT

BACKGROUND: A needs assessment for patients with hidradenitis suppurativa (HS) will support advancements in multidisciplinary care, treatment, research, advocacy, and philanthropy. OBJECTIVE: To evaluate unmet needs from the perspective of HS patients. METHODS: Prospective multinational survey of patients between October 2017 and July 2018. RESULTS: Before receiving a formal HS diagnosis, 63.7% (n = 827) of patients visited a physician ≥5 times. Mean delay in diagnosis was 10.2 ± 8.9 years. Patients experienced flare daily, weekly, or monthly in 23.0%, 29.8%, and 31.1%, respectively. Most (61.4% [n = 798]) rated recent HS-related pain as moderate or higher, and 4.5% described recent pain to be the worst possible. Access to dermatology was rated as difficult by 37.0% (n = 481). Patients reported visiting the emergency department and hospital ≥5 times for symptoms in 18.3% and 12.5%, respectively. An extreme impact on life was reported by 43.3% (n = 563), and 14.5% were disabled due to disease. Patients reported a high frequency of comorbidities, most commonly mood disorders. Patients were dissatisfied with medical or procedural treatments in 45.9% and 34.6%, respectively. LIMITATIONS: Data were self-reported. Patients with more severe disease may have been selected. CONCLUSION: HS patients have identified several critical unmet needs that will require stakeholder collaboration to meaningfully address.


Subject(s)
Hidradenitis Suppurativa/therapy , Needs Assessment , Adolescent , Adult , Female , Health Care Surveys , Humans , Male , Middle Aged , Prospective Studies , Young Adult
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