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CSL324, a G-CSF receptor antagonist, blocks neutrophil migration markers in hidradenitis suppurativa

Neutrophils are important in the pathophysiology of HS, but their role remains to be fully defined. Granulocyte colony-stimulating factor (G-CSF) is a major regulator of neutrophil development and survival and can be blocked by the novel, fully human anti-G-CSF receptor (G-CSFR) monoclonal antibody CSL324. In the pesent study, ex vivo experiments were performed from skin biopsies and peripheral blood in HS patients and healthy adult subjects. Cells positive for the neutrophil markers myeloperoxidase (MPO) and neutrophil elastase (NE) were more numerous in HS lesions than control skin biopsies. Neutrophil migration pathways in peripheral blood were increased in patients with HS and their neutrophils demonstrated an increased migration phenotype, with higher surface levels of CXCR1. G-CSF was a key driver of the transcriptomic changes in the peripheral blood of patients with HS and was elevated in serum from HS patients compared to controls. Incubation of purified neutrophils with G-CSF resulted in significant upregulation of the chemokine receptors CXCR1 and CXCR2 compared with media alone and this was prevented by pre-treatment with CSL324.

So, inhibition of neutrophil migration to lesions by CSL324 could be a potential treatment in HS, with a novel mode of action.

Core outcome domains for lichen sclerosus: a CORALS initiative consensus statement

The BJD continues to be a strong supporter of core outcome sets in dermatology. Lichen sclerosus (LS) has been relatively neglected in terms of clinical trials and lacks consensus on the domains (what to measure) and instruments (how to measure the domains) to define treatment success. The present study was developed in line with CHORD-COUSIN Collaboration (C3) guidance and was delivered by the Core Outcomes for Research in Lichen Sclerosus (CORALS) initiative.

The project aimed to define LS core domains and involved 123 participants in three rounds of e-Delphi consensus surveys, including 77 patients, 44 health professionals, and 2 researchers from 20 countries. A subsequent online meeting involving 42 participants from 12 countries reached consensus on three domains for all future LS clinical trials: symptoms (100% agreement), LS-specific quality of life (92% agreement), and clinical (visible) signs (97% agreement). The next step will be to define the outcome measure instruments to measure each LS core domain.

Effectiveness and persistence of acitretin, ciclosporin, fumaric acid esters and methotrexate in BADBIR psoriasis registry

The British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) includes a conventional systemic therapy arm, providing high quality real-world data for this group of patients. In total, 5430 participants were included in the analysis, 1023 receiving acitretin, 1401 on ciclosporin, 347 on fumaric acid esters (FAEs), and 2659 on methotrexate at study registration. Effectiveness was defined as achieving absolute Psoriasis Area and Severity Index (aPASI) ≤ 2 reported ≥ 4 weeks after treatment start date until date of cessation. Effectiveness was met by 21% on acitretin, 34% on ciclosporin, 30% on FAEs, and 32% on methotrexate. Factors associated with ineffectiveness included prior exposure to nonbiologic systemic therapies (acitretin) (aOR 0.64, 95% CI 0.42–0.96), male sex (methotrexate) (aOR 0.58, 95% CI 0.46–0.74), comorbidities (aOR 0.70, 95% CI 0.51–0.97) and low alcohol consumption (≤ 14 units per week) (ciclosporin) (aOR 0.70, 95% CI 0.50–0.98). Persistence associated with all reasons for discontinuation showed better survival for methotrexate compared with acitretin, ciclosporin and FAEs cohorts at 12 months [survival estimate 46.1 (95% CI 44.0–48.3), 31.9 (95% CI 29.4–34.7), 30.0 (95% CI 27.5–32.4) and 35.0 (95% CI 29.9–40.9.

Ultrasound and MRI in the management of hidradenitis suppurativa: a narrative review

Hidradenitis suppurativa (HS) remains a clinical diagnosis, however roles are developing for both ultrasound (US) and magnetic resonance imaging (MRI) in its management. Ultrasound provides an understanding of the subcutaneous elements of HS, particularly skin tunnel formation. Being able to accurately map tunnels is important prior to surgery, for example deroofing procedures. Accurate counting of tunnel branches is gaining prominence in clinical trials and in assessing patient response to treatment. For example, the International Hidradenitis Suppurativa Severity Score System (IHS4) lesion count assigns highest weighting to draining skin tunnels and so identifying tunnels and quantifying the number of tunnel branches is important. In HS affecting the perianal and pelvic regions, MRI is very helpful for pre-operative assessment, mapping disease extent and identifying any fistulae that may exist between bowel and skin, for example when there is concomitant Crohn disease. In a few specialist HS centres, imaging is in regular use, however it is not yet routinely employed due to lack of equipment, training, and staff time, which are challenges to overcome to gain the benefits of imaging in HS.

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