Is mechanical stress an important pathogenic factor in hidradenitis suppurativa?

Hidradenitis suppurativa (HS) is a chronic of recurrent, inflammatory, follicular disease that usually presents after puberty with painful deep-seated, inflamed lesions in the inverse skin areas of the body. It has been hypothesized that mechanical pressure or friction is a risk factor for HS. We describe the case of a man with a lower leg amputation who presented HS-like lesions on his leg stump after wearing a leg prosthesis. Although pilonidal sinus-like disease could not be excluded, we diagnosed him with HS-like lesions, induced by prosthesis-related friction. We argue that this case supports the concept that mechanical friction and a warm humid microclimate by occlusion contribute to HS development

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 &lt; 0.05) and the clindamycin-benzoyl peroxide gel (-2; p &lt; 0.01) after 16 weeks, and the pain scores were reduced from 7 to 2.5, p &lt; 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.</p

Hidradenitis Suppurativa: A Systematic Review Integrating Inflammatory Pathways Into a Cohesive Pathogenic Model

Background: The pathogenesis of hidradenitis suppurativa (HS) is not fully understood. This systematic review examined the latest evidence for molecular inflammatory pathways involved in HS as a chronic inflammatory skin disease.Methods: A systematic literature search was performed in PubMed/Medline and EMBASE from January 2013 through September 2017, according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA). Findings on HS pathogenesis were also compared with those of other immune-mediated inflammatory diseases (IMIDs) in a non-systematic review. In addition, current therapeutic options for HS are briefly discussed on the basis of the findings for the inflammatory pathways involved in HS.Results: A total of 32 eligible publications were identified by the systematic search; these were supplemented with three additional publications. The extracted data indicated that four key themes underlie the pathogenesis of HS and related syndromic conditions. First, nicastrin (NCSTN) and PSTPIP1 mutations are directly associated with auto-inflammatory disease. Secondly, the up-regulation of several cytokines including tumor necrosis factor-α and T helper-17/interleukin-23 are connected to auto-inflammatory mechanisms in the pathogenesis of HS. Thirdly, the microbiome of lesional skin differs significantly vs. normal-appearing skin. Fourthly, HS risk is enhanced through physiological and environmental factors such as smoking, obesity, and mechanical friction. There is significant overlap between the pathogenesis of HS, its syndromic forms and other IMIDs, particularly with respect to aberrations in the innate immune response.Conclusions: The evidence presented in this review supports HS as an auto-inflammatory skin disorder associated with alterations in the innate immune system. Based on these most recent data, an integrative viewpoint is presented on the pathogenesis of HS. Current management strategies on HS consist of anti-inflammatory therapies, surgical removal of chronic lesions, and lifestyle changes such as smoking cessation and weight loss. As large gaps remain in the understanding of the pathogenesis of HS, further research is warranted to ultimately improve the management and treatment of patients with HS and related syndromic conditions

Weekly adalimumab treatment decreased disease flare in hidradenitis suppurativa over 36 weeks: integrated results from the phase 3 PIONEER trials

Background: Hidradenitis suppurativa (HS) is a chronic skin disease characterized by inflammatory lesions that flare unpredictably. The impact of weekly adalimumab (ADAew) on HS flare is not well-characterized. Objective: To evaluate the impact of disease flare on health-related quality of life (HRQOL) in moderate-to-severe HS patients and to determine the effect of ADAew on disease flare using integrated data from two phase 3 trials over 36 weeks. Methods: In period A (12 weeks), Dermatology Life Quality Index (DLQI) score change from baseline was compared in patients who flared and those who did not, regardless of treatment. The proportion of patients experiencing flare, duration of flare and time to flare was evaluated for ADAew vs. placebo (PBO). In period B (24 weeks), proportion of patients experiencing flare who received continuous ADAew treatment through 36 weeks was assessed. Results: HRQOL was markedly improved among those who did not experience flare. In period A, the proportion of patients who experienced flare was significantly lower with ADAew vs. PBO (12.3% vs. 35.3%, P < 0.001). ADAew patients also had longer time to first flare (101 days vs. 57 days; P < 0.001) and shorter flare duration (18.9 days vs. 32.0 days, respectively; P = 0.001) vs. PBO. Through 36 weeks of treatment, 20.2% of ADAew patients flared, and for those who achieved at least a partial clinical response to ADAew at 12 weeks, only 5.7% flared. Conclusions: Flare reduction is an important measure in HS that correlates with clinically meaningful improvement in HRQOL. ADAew reduces HS flare through 12 and subsequent 36 weeks of treatment