Rifampin-moxifloxacin-metronidazole combination therapy for severe Hurley stage 1 hidradenitis suppurativa: prospective short-term trial and 1-year follow-up in 28 consecutive patients.

BACKGROUND: Severe Hurley stage 1 hidradenitis suppurativa (HS1) is a difficult-to-treat form of the disease. OBJECTIVE: To assess the efficacy and tolerance of the oral combination of rifampin (10 mg/kg once daily)/moxifloxacin (400 mg once daily)/metronidazole (250-500 mg 3 times daily) (RMoM) treatment strategy in patients with severe HS1. METHODS: Prospective, open-label, noncomparative cohort study in 28 consecutive patients. Nineteen patients were treated for 6 weeks by RMoM, followed by 4 weeks of rifampin/moxifloxacin alone, then by cotrimoxazole after remission. Moxifloxacin was replaced by pristinamycin (1 g 3 times daily) in 9 patients because of contraindications or intolerance. The primary endpoint was a Sartorius score of 0 (clinical remission) at week 12. RESULTS: The median Sartorius score dropped from 14 to 0 (P = 6 × 10-6) at week 12, with 75% of patients reaching clinical remission. A low initial Sartorius score was a prognosis factor for clinical remission (P = .049). The main adverse effects were mild gastrointestinal discomfort, mucosal candidiasis, and asthenia. At 1 year of follow-up, the median number of flares dropped from 21/year to 1 (P = 1 × 10-5). LIMITATIONS: Small, monocentric, noncontrolled study. CONCLUSIONS: Complete and prolonged remission can be obtained in severe HS1 by using targeted antimicrobial treatments.

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.

Dysregulation of tryptophan catabolism at the host-skin microbiota interface in hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic skin disorder of unknown etiology that manifests as recurrent, painful lesions. Cutaneous dysbiosis and unresolved inflammation are hallmarks of active HS, but their origin and interplay remain unclear. Our metabolomic profiling of HS skin revealed an abnormal induction of the kynurenine pathway of tryptophan catabolism in dermal fibroblasts, correlating with the release of kynurenine pathway-inducing cytokines by inflammatory cell infiltrates. Notably, overactivation of the kynurenine pathway in lesional skin was associated with local and systemic depletion in tryptophan. Yet the skin microbiota normally degrades host tryptophan into indoles regulating tissue inflammation via engagement of the aryl hydrocarbon receptor (AHR). In HS skin lesions, we detected contextual defects in AHR activation coinciding with impaired production of bacteria-derived AHR agonists and decreased incidence of AHR ligand-producing bacteria in the resident flora. Dysregulation of tryptophan catabolism at the skin-microbiota interface thus provides a mechanism linking the immunological and microbiological features of HS lesions. In addition to revealing metabolic alterations in patients with HS, our study suggests that correcting AHR signaling would help restore immune homeostasis in HS skin.

The Surface Microbiome of Clinically Unaffected Skinfolds in Hidradenitis Suppurativa: A Cross-Sectional Culture-Based and 16S rRNA Gene Amplicon Sequencing Study in 60 Patients.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the skin associated with specific lesional dysbiotic features. We studied the microbiome of clinically unaffected typical HS sites (armpits, inguinal folds, and gluteal clefts) in 60 patients with HS and 17 healthy controls. A total of 192 samples obtained by swabbing were analyzed by bacterial cultures. Of these, 116 randomly selected samples were studied by 16S rRNA gene amplicon sequencing. Patients and controls showed similar characteristics, except for smoking (87% vs. 6%, respectively). HS skinfolds were characterized by an increased abundance of anaerobes, predominantly Prevotella, but also Actinomyces, Campylobacter ureolyticus, and Mobiluncus, contrasting with a lower abundance of skin commensals such as Staphylococcus epidermidis, a major component of the skin microbiome; Kocuria; and Micrococcus luteus. The following three independent factors were associated with an abundance of high anaerobes by multivariate analysis: samples originating from patients with HS patients (P = 2.1 × 10-4); body mass index (P = 5 × 10-5); and the sampling site, the gluteal cleft being the most anaerobic area, followed by inguinal folds and axilla (P = 3 × 10-6). The microbiome of clinically unaffected HS skinfolds is reminiscent, albeit to a minor extent, of the microbiome of chronic suppurative HS lesions and may fuel inflammation at a preclinical stage of the disease.

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.

The Microbiological Landscape of Anaerobic Infections in Hidradenitis Suppurativa: A Prospective Metagenomic Study.

BACKGROUND: Hidradenitis suppurativa (HS) is a frequent and severe disease of the skin, characterized by recurrent or chronic skinfold suppurative lesions with a high impact on quality of life. Although considered inflammatory, antimicrobial treatments can improve or lead to clinical remission of HS, suggesting triggering microbial factors. Indeed, mixed anaerobic microbiota are associated with a majority of HS lesions. Our aim in this study was to characterize the landscape of anaerobic infections in HS using high-throughput sequencing. METHODS: We sampled and cultured 149 lesions and 175 unaffected control skinfold areas from 65 adult HS patients. The microbiome of 80 anaerobic lesions was compared to that of 88 control samples by 454 high-throughput sequencing after construction of 16S ribosomal RNA gene libraries. RESULTS: Bacterial cultures detected anaerobes in 83% of lesions vs 53% of control samples, combined with milleri group streptococci and actinomycetes in 33% and 26% of cases, respectively. High-throughput sequencing identified 43 taxa associated with HS lesions. Two gram-negative anaerobic rod taxa, Prevotella and Porphyromonas, predominated, contrasting with a reduced abundance of aerobic commensals. These rare taxa of normal skinfold microbiota were associated with lesions independently of gender, duration and familial history of HS, body mass index, and location. Two main additional taxa, Fusobacterium and Parvimonas, correlated with the clinical severity of HS. CONCLUSIONS: In this study we reveal the high prevalence and particular landscape of mixed anaerobic infection in HS, paving the way for rationale targeted antimicrobial treatments.

Efficacy of ertapenem in severe hidradenitis suppurativa: a pilot study in a cohort of 30 consecutive patients.

OBJECTIVES: Hidradenitis suppurativa (HS) is an inflammatory skin disease typically localized in the axillae and inguinal and perineal areas. In the absence of standardized medical treatment, severe HS patients present chronic suppurative lesions with polymicrobial anaerobic abscesses. Wide surgery is the cornerstone treatment of severe HS, but surgical indications are limited by the extent of lesions. Intravenous broad-spectrum antibiotics may help control HS, but their efficacy is not documented. This study was designed to assess the efficacy of a 6 week course of ertapenem (1 g daily) and of antibiotic consolidation treatments for 6 months (M6) in severe HS. PATIENTS AND METHODS: Thirty consecutive patients with severe HS were retrospectively included in this study. The clinical severity of HS was assessed using the Sartorius score, which takes into account the number and severity of lesions. RESULTS: The median (IQR) Sartorius score dropped from 49.5 (28-62) at baseline to 19.0 (12-28) after ertapenem (P < 10(-4)). Five patients were lost to follow-up thereafter. At M6 the Sartorius score further decreased for the 16 patients who received continuous consolidation treatments, since 59% of HS areas reached clinical remission at M6 (i.e. absence of any inflammatory symptoms, P < 10(-4)). Nine patients interrupted or received intermittent consolidation treatments due to poor observance or irregular follow-up. Their Sartorius score stopped improving or returned to baseline. No major adverse event occurred. CONCLUSIONS: Ertapenem can dramatically improve severe HS. Consolidation treatments are needed to further improve HS and are mandatory to prevent relapses. Combined with surgery, optimized antibiotic treatments may be promising in severe HS.

Remission of refractory pyoderma gangrenosum, severe acne, and hidradenitis suppurativa (PASH) syndrome using targeted antibiotic therapy in 4 patients.

Pyoderma gangrenosum, severe acne, and suppurative hidradenitis (PASH) syndrome can prove refractory to treatment and is characterized by relapses and recurrences. The combination of antibiotic therapy and surgery can produce success in the management of the syndrome. Acute treatment is required, but maintenance therapy is also necessary to prevent disease relapse. The response to antibiotic therapy is hypothesis generating, raising the issue of a modified host response. To date, anecdotal reports support the use of surgery and medical therapy, but controlled investigations with extended follow-up are necessary to substantiate preliminary data observed with individual cases.

Efficacy of infliximab for hidradenitis suppurativa: assessment of clinical and biological inflammatory markers.

Treatment of hidradenitis suppurativa (HS) is often unsatisfactory. The efficacy of infliximab for treatment of the disease has been suggested. The main objective of this study was to evaluate the efficacy and side-effects of infliximab in the treatment of moderate to severe HS, resistant to local and systemic treatments. The secondary objective was to determine whether inflammation blood test results were changed. A retrospective monocentric study of all the patients seen consecutively for HS and treated with infliximab was performed. A median of six intravenous infusions (range 3-19) were performed. The end-points were self-improvement of HS (globally and in terms of pain, seeping and quality of life). The condition of six of seven patients improved (by nearly 50%) and none was aggravated. Adverse effects occurred in two patients; eczematous eruption in one case and cervical abscess in another case. We found no significant changes in inflammatory blood marker values. In conclusion, infliximab therapy was shown to be efficient and well tolerated in six of seven patients with HS resistant to previous therapy in our series. This was in agreement with pre-existing literature showing that 52 of 60 patients (87%) were improved after infliximab therapy.