B-cell and complement signature in severe hidradenitis suppurativa that does not respond to adalimumab.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder with significant morbidity. The pathogenesis remains incompletely understood although immune dysregulation plays an important role. It is challenging to treat and approximately 50% of patients respond clinically to adalimumab, the only licensed treatment. OBJECTIVES: To examine differences between lesional and nonlesional HS skin at baseline using bulk RNA sequencing, and to compare the transcriptome in the skin before and after 12 weeks of treatment with adalimumab. To examine transcriptomic differences between adalimumab responders and nonresponders using Hidradenitis Suppurativa Clinical Response and the International Hidradenitis Suppurativa Severity Score System (IHS4); and to compare transcriptomic differences based on disease severity (Hurley stage and IHS4). METHODS: We completed bulk RNA sequencing on lesional and nonlesional skin samples of patients before and after 12 weeks of treatment with adalimumab. RESULTS: Baseline differentially expressed genes and pathways between lesional and nonlesional skin highlighted chemokines and antimicrobial peptides produced by keratinocytes; B-cell function; T-cell-receptor, interleukin-17 and nuclear factor-κB signalling; and T-helper-cell differentiation. Transcriptomic differences were identified in lesional skin at baseline, between subsequent responders and nonresponders. Patients with severe HS who did not respond to adalimumab had enriched complement and B-cell activation pathways at baseline. In addition, logistic regression identified CCL28 in baseline lesional HS skin as a potential biomarker of treatment response. CONCLUSIONS: This highlights the potential for targeting B-cell and complement pathways in HS treatment and the potential of stratifying patients at baseline to the most suitable treatment based on the skin transcriptome. CCL28 has not previously been identified in HS skin and has potential clinical relevance due to its antimicrobial function and homing of B and T cells at epithelial surfaces. Our results provide data to inform future translational and clinical studies on therapeutics in HS.

The benefit of introducing a virtual trauma assessment clinic during a global pandemic.

Sars-CoV2/COVID-19 pandemic created a national emergency in Ireland. Our institution implemented a virtual trauma assessment clinic to reduce attendance to our district hospital which was stimulated by the development of 'safe-distanced' care. The audit aimed to evaluate the impact of our trauma assessment clinic on care provision and presentation to hospital. All patients were managed according to the newly implemented virtual trauma assessment clinic protocol. Data was prospectively collected over a 6.5 week period from 23rd March 2020 to 7th May 2020. These referrals were reviewed twice weekly by a Consultant-led multidisciplinary team. 142 patients were referred to the virtual trauma assessment clinic. Mean age of referrals was 33.04 years. 43% (n=61) were male patients. Overall 32.4% (n=46) of new referrals were discharged directly to their family doctor. 30.3% (n=43) were discharged for physiotherapy follow up. 36.6% (n=52) required presentation to the hospital for further clinical review and 0.7% (n=1) was admitted for surgical intervention. Overall, this represents a reduction of 63% of patients attending the hospital. A simple virtual trauma assessment clinic model resulted in significant reduction in unnecessary attendance at face-to-face fracture clinics enhancing patient and staff safety during a global pandemic. This virtual trauma assessment clinic model has allowed the mobilisation of staff to assist with other essential duties in other areas of our hospital without compromising care.