Clindamycin-Benzoyl Peroxide Gel Compared with Clindamycin Lotion for Hidradenitis Suppurativa: A Randomized Controlled Assessor-Blinded Intra-Patient Pilot Study.

BACKGROUND: Antibiotic resistance is a major concern, especially in hidradenitis suppurativa (HS). However, antibiotics form a cornerstone in its treatment. Topical clindamycin is known to cause bacterial resistance but is still advised as monotherapy for the treatment of mild to moderate HS. METHODS: This is a randomized, controlled, assessor-blinded, intra-patient pilot trial to compare the clinical efficacy of clindamycin-benzoyl peroxide gel with clindamycin lotion in patients with mild to moderate HS. Two contralateral body sites were randomized for treatment in each patient. The primary outcome was the difference in the International Hidradenitis Suppurativa Severity Score (IHS4) between the two groups after 12 weeks. Secondary objectives were feasibility of the intra-patient design, efficacy within treatment groups, effect on HS pain, HS itch, patient satisfaction, antibiotic resistance, and the prolonged efficacy after 16 weeks. RESULTS: Ten patients were included, resulting in two groups of 10 treated body sites. No significant differences were found between the two groups for all measurements after 12 or 16 weeks, while both therapies led to an improvement in the IHS4, pain, and itch scores. A significant decrease was observed in the IHS4 for both the clindamycin lotion (-1.5; p < 0.05) and the clindamycin-benzoyl peroxide gel (-2; p < 0.01) after 16 weeks, and the pain scores were reduced from 7 to 2.5, p < 0.01 and 6.5 to 3, p = 0.03, respectively. Using the IHS4-55, we identified 50% of patients as responders in both groups after 12 weeks. The intra-patient design, however, unexpectedly appeared to hinder the inclusion of patients. CONCLUSION: Clindamycin-benzoyl peroxide gel showed favorable clinical efficacy results, similar to clindamycin lotion, suggesting that it could replace clindamycin lotion in the treatment of mild to moderate HS and to prevent antibiotic resistance. A larger controlled trial is needed to validate these results.

Factors associated with treatment satisfaction in patients with hidradenitis suppurativa: results from the Global VOICE project.

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.

Evaluating patients' unmet needs in hidradenitis suppurativa: Results from the Global Survey Of Impact and Healthcare Needs (VOICE) Project.

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.

High prevalence of hidradenitis suppurativa in patients with perianal fistula.

BACKGROUND: Perianal fistula is an abnormal communication between the anal canal and perianal skin. Hidradenitis suppurativa (HS) is a chronic, auto-inflammatory skin disease in the intertriginous body areas, presenting with recurring abscesses, inflammatory nodules, and sinus tracts. The aim of this study was to determine the prevalence of HS in patients with a perianal fistula. METHODS: All patients with perianal fistula visiting a specialized proctology clinic between July and September 2017 were included and asked a validated diagnostic question for HS. Subsequently, physical examination was performed to objectively assess the diagnosis and relevant patient characteristics. RESULTS: In 6.6% (8/122) of patients, HS was diagnosed outside the perianal region. Four of these patients were newly diagnosed. The fistulas in HS patients were classified as a superficial fistula (three), a blind ending fistula (two), and a transsphincteric fistula (two). One patient had more than one type of fistula. CONCLUSION: The prevalence of HS in patients with a perianal fistula is at least 6.6%. This is higher than the prevalence reported in the general European population (1%) suggesting an association between perianal fistulas and HS. We stress the importance to screen for HS in patients with perianal fistulas in order to start appropriate anti-inflammatory treatment to reduce symptoms and disease progression.

Neurotensin, substance P, and insulin enhance cell migration.

Neurotensin, substance P, and insulin have been demonstrated to improve wound healing in vivo. However, the mechanism behind their effect is still not fully understood. This study investigates the effects leading to enhanced scratch closure by these peptides in vitro. The skin keratinocyte cell line, HaCaT, was used to test scratch closure effects of the peptides and alterations of cytokine levels. HUVEC cells were used to test the angiogenic effect of the peptides. Furthermore, clinical isolates of Staphylococcus lugdunensis were used to examine the potential antimicrobial activity of each peptide. Our results demonstrate that neurotensin, substance P, and insulin had significant migratory effects in scratch assays were neurotensin had the lowest effect. Furthermore, we investigated use of the peptides in combination. When substance P was used in combination with neurotensin, the cell migratory capacity was decreased, and the peptides showed a negative correlation (r = -0.298, P < .001). Neurotensin and insulin significantly increased levels of monocyte chemoattractant protein-1 (P < .001) secreted from white blood cells, whereas substance P showed a tendency. Interestingly, neurotensin increased the level of monocyte chemoattractant protein-1 significantly compared to substance P (P < .01). Additionally, the peptides decreased TNFα mRNA levels (P < .001) in HaCaT cells, whereas only neurotensin and insulin decreased IL-8 mRNA (P < .001) but had no significant effect on IL-6 mRNA levels. Surprisingly, substance P increased IL-6 mRNA 9-fold (P < .001). Furthermore, we demonstrate that the peptides increased angiogenesis in the HUVEC cells (P < .001). Finally, S. lugdunensis isolates were not susceptible to the peptides. We demonstrate that the peptides worked differently on HaCaT cells, but substance P acted differently than neurotensin on cytokine levels expression as well as on migration of HaCaT cells. On the contrary, neurotensin and insulin worked similarly. All of these aspects are crucial for proper wound healing, and the results suggest multiple mechanisms for wound-healing properties of these peptides.

Clinical Implementation of Biologics and Small Molecules in the Treatment of Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic, recurrent, auto-inflammatory skin disease originating from the hair follicles. The typical inflammatory nodules, abscesses, and draining sinus tracts (tunnels) are characterized by a massive influx of neutrophils, macrophages, B-cells, plasma cells, T helper (Th)1, Th17 cells and upregulation of pro-inflammatory cytokines such as IL-1, IL-17, IL-12/23, and TNF-α. Over the last decades, several clinical trials evaluated the clinical efficacy of different biologics targeting these pro-inflammatory cytokines, in particular TNF-α and IL-1. However, adalimumab is still the only registered drug for HS. This review discusses biologics and small molecules with high level of evidence for their clinical application, provides guidance on when and how to use these biologics and small molecules in clinical practice, and elaborates on the combination with medical and surgical treatment options beyond the current guidelines. Furthermore this review provides an overview of potential biologics and small molecules currently under investigation for novel targets in HS such as IL-36, C5a, Janus kinase family members, CD-40, LTA4 and CXCR1/2.