Complement activation in Hidradenitis suppurativa: Covert low-grade inflammation or innocent bystander?

Hidradenitis suppurativa (HS) is a chronic auto-inflammatory skin disease with a complex and multifactorial pathogenesis involving both the innate and adaptive immune system. Despite limited evidence for local complement activation, conflicting results have been published on the role of systemic complement activation in HS. It was hypothesized that complement was consumed in highly inflamed HS skin, trapping complement from the circulation. Therefore, the aim of this study was to evaluate this local complement deposition in HS skin lesions using routine and commonly used complement antibodies.Direct immunofluorescence for C1q, C3c, C4d, C5b-9, and properdin was performed on frozen tissue sections of 19 HS patients and 6 controls. C5a receptor 1 (C5aR1) was visualized using immunohistochemistry. Overall, we found no significant local complement deposition in HS patients versus controls regarding C1q, C3c, C4d, C5b-9, or properdin on either vessels or immune cells. C5aR1 expression was exclusively found on immune cells, predominantly neutrophilic granulocytes, but not significantly different relatively to the total infiltrate in HS lesions compared with controls. In conclusion, despite not being able to confirm local complement depositions of C1q, C3c, C4d, or properdin using highly sensitive and widely accepted techniques, the increased presence of C5aR1 positive immune cells in HS suggests the importance of complement in the pathogenesis of HS and supports emerging therapies targeting this pathway.

Randomized clinical trial of 940- versus 1470-nm endovenous laser ablation for great saphenous vein incompetence.

BACKGROUND: The independent effect of wavelength used for endovenous laser ablation (EVLA) on patient-reported outcomes, health-related quality of life (HRQoL), treatment success and complications has not yet been established in a randomized clinical trial. The aim was to compare two different wavelengths, with identical energy level and laser fibres, in patients undergoing EVLA. METHODS: Patients with great saphenous vein incompetence were randomized to receive 940- or 1470-nm EVLA. The primary outcome was pain at 1 week. Secondary outcomes were: patient satisfaction, duration of analgesia use and time without normal activities assessed at 1 week; HRQoL after 12 weeks; treatment success after 12 and 52 weeks; change in Venous Clinical Severity Score (VCSS) after 12 weeks; and adverse events at 1 and 12 weeks. RESULTS: A total of 142 legs were randomized (940-nm EVLA, 70; 1470-nm EVLA, 72). Patients in the 1470-nm laser group reported significantly less pain on a visual analogue scale than those in the 940-nm laser group: median (i.q.r.) score 3 (2-7) versus 6 (3-8) (P = 0.004). Duration of analgesia use was significantly shorter after 1470-nm EVLA: median (i.q.r.) 1 (0-3) versus 2 (0-5) days (P = 0.037). HRQoL and VCSS improved equally in both groups. There was no difference in treatment success rates. Complications were comparable in both groups, except for more superficial vein thrombosis 1 week after 1470-nm EVLA. CONCLUSION: EVLA using a 1470-nm wavelength fibre was associated with improved postoperative pain and a reduction in analgesia use in the first week after surgery compared with use of a 940-nm fibre. Treatment success and adverse event rates were similar. REGISTRATION NUMBER: NCT01637181 (http://www.clinicaltrials.gov).