Background: Hidradenitis Suppurativa (HS) is a chronic debilitating inflammatory disease, associated with metabolic syndrome, obesity and insulin resistance. Metformin, an oral hypoglycaemic agent, may play an important role in delaying or preventing the onset of diabetes and metabolic syndrome. Metformin has been reported as having efficacy in HS. It may have a role in the treatment of HS and its associated co-morbidities. Objective: To evaluate metformin use, response and tolerability in a HS population. Methods: A retrospective chart review of patients attending a specialist Dermatology HS clinic over 12-months. All patients treated with metformin were included. Results: 53 HS patients received metformin; 85% female; mean age was 37years and mean weight was 102kg. The mean duration of metformin was 11.3months and mean dose was 1.5g/day. The six and 12-month drug survival were 61% and 39% respectively. Metformin was well tolerated. Gastrointestinal side-effects were experienced by 11%. Subjective clinical response was seen in 68%(n = 36) with 19%(7/36) of these having quiescent disease with metformin monotherapy. 25% had no improvement. Insulin resistance was seen in 75%. Its presence did not predict clinical response to metformin. Conclusion: Metformin is an effective, well tolerated and inexpensive treatment, that represents a viable treatment option for HS. Key message: Metformin is an effective, well tolerated and inexpensive treatment in the management of HS

Background: Targeting immunometabolism has shown promise in treating autoimmune and inflammatory conditions. Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease involving painful lesions in apocrine gland-bearing skin. Therapeutic options for HS are limited and often ineffective; thus, there is a pressing need for improved treatments. To date, metabolic dysregulation has not been investigated in HS. As HS is highly inflammatory, we hypothesized that energy metabolism is dysregulated in these patients. Metformin, an antidiabetic drug, which is known to impact on cellular metabolic and signalling pathways, has been shown to have anti-inflammatory effects in cancer and arthritis. While metformin is not licensed for use in HS, patients with HS taking metformin show improved clinical symptoms. Objective: To assess the effect and mechanism of action of metformin in HS. Methods: To assess the effect of metformin in vivo, we compared the immune and metabolic profiles of peripheral blood mononuclear cells (PBMCs) of patients with HS taking metformin vs. those not taking metformin. To examine the effect of metformin treatment ex vivo, we employed a skin explant model on skin biopsies from patients with HS not taking metformin, which we cultured with metformin overnight. We used enzyme-linked immunosorbent assays, multiplex cytokine assays and quantitative real-time polymerase chain reaction (RT-PCR) to measure inflammatory markers, and Seahorse flux technology and quantitative RT-PCR to assess glucose metabolism. Results: We showed that metabolic pathways are dysregulated in the PBMCs of patients with HS vs. healthy individuals. In metformin-treated patients, these metabolic pathways were restored and their PBMCs had reduced inflammatory markers following long-term metformin treatment. In the skin explant model, we found that overnight culture with metformin reduced inflammatory cytokines and chemokines and glycolytic genes in lesions and tracts of patients with HS. Using in vitro assays, we found that metformin may induce these changes via the NLR family pyrin domain containing 3 (NLRP3) inflammasome and the AMP-activated protein kinase (AMPK)–mammalian target of rapamycin (mTOR) pathway, which is linked to glycolysis and protein synthesis. Conclusions: Our study provides insight into the mechanisms of action of metformin in HS. The anti-inflammatory effects of metformin support its use as a therapeutic agent in HS, while its effects on immunometabolism suggest that targeting metabolism is a promising therapeutic option in inflammatory diseases, including HS.

Psoriasis is a chronic autoimmune disease mediated by dysregulated immune responses in dendritic cells (DC) and T cells. The stress-response enzyme heme oxygenase-1 (HO-1) has been described as protective in animal models of psoriasis, however, implementation of HO-1-based therapies is hindered by the lack of clinically-suitable HO-1 inducers. The plant-derived polyphenols, carnosol and curcumin, have been identified as candidate HO-1 inducers however there has been little investigation into their effects on human immune cells. We demonstrate that treatment of human DC with these polyphenols limits DC maturation, reduces pro-inflammatory cytokine production, and prevents induction of allospecific T cell responses, in a manner partially dependent on carbon monoxide (CO). We also characterised their effects in ex-vivo psoriasis PBMC and report that curcumin, but not carnosol, strongly reduces T cell proliferation and cytokine poly-functionality, with reduced expression of psoriatic cytokines IFNγ, IL-17, GM-CSF and IL-22. This study therefore supports reports highlighting the therapeutic potential of curcumin in psoriasis by providing insight into its immunological effects on healthy human DC and psoriasis PBMC. We also demonstrate, for the first time, the anti-inflammatory effects of carnosol in human immune cells.

Methadone maintenance treatment in primary care is cost-effective and improves outcomes for opiate-dependent patients. A more developed understanding of the evolving needs of this important cohort will facilitate further improvements in their integrated care within the community. The aim of this study was to compare the burden of chronic disease, multi-morbidity and intensity of health-service use between methadone-maintained patients (MMPs) and matched controls in primary care. This is a retrospective matched case-control design. Data on chronic disease and health service use was collected in 13 computerized GP surgeries on 414 patients (207 MMPs and 207 controls). Twelve months of records were examined. MMPs were compared with controls matched by gender, age, socio-economic status (SES) and GP surgery. MMPs suffered more chronic disease (OR = 9.1, 95% CI: 5.4-15.1, P < 0.001) and multi-morbidity (OR = 6.6, 95% CI: 4.3-10.2, P < 0.001). They had higher rates of respiratory, psychiatric and infectious disease. MMPs of lower SES had more chronic disease than their peers (OR = 7.2, 95% CI: 2.4-22.0, P < 0.001). MMPs attended the doctor more often with medical problems (OR = 15.4, 95% CI: 8.2-28.7, P < 0.001), with a frequent requirement to have medical issues addressed during methadone-management visits. Their care generated more telephone calls (OR = 4.4, 95% CI: 2.8-6.8, P < 0.001), investigations (OR = 1.8, 95% CI: 1.2-2.7, P = 0.003), referrals (2.6, 95% CI: 1.7-4.0, P < 0.001), emergency department visits (2.1, 95% CI: 1.3-3.6, P = 0.004), outpatient attendances (2.3, 95% CI: 1.51-1.43, P < 0.001) and hospital admissions (3.6, 95% CI: 1.6-8.1, P = 0.001). Correcting for routine methadone care and drug-related illnesses, MMPs had a higher burden of chronic disease and used both primary and secondary health services more intensively than matched controls.

Hidradenitis suppurativa (HS) is a common cutaneous and systemic inflammatory disease with a significant impact on mental health and quality of life. It is associated with obesity, insulin resistance, metabolic syndrome, cardiovascular (CV) disease, and increased all-cause mortality. Metformin is used frequently in HS treatment and is effective for some patients. The mechanism of action of metformin in HS is unknown. A case-control study of 40 patients with HS (20 on metformin and 20 controls) was conducted to assess differences in metabolic markers, inflammation (C-reactive protein [CRP], serum adipokines, and CV risk biomarkers), and serum immune mediators. Body mass index (BMI), insulin resistance (77%), and metabolic syndrome (44%) were high overall, but not significantly different between the groups. This highlights the need for co-morbidity screening and management. A significant reduction in fasting insulin and a trend towards a reduction in insulin resistance were identified in the metformin group compared with pre-treatment levels. CV risk biomarkers were significantly favourable in the metformin group (lymphocytes, monocyte–lymphocyte ratio, neutrophil–lymphocyte ratio, and platelet–lymphocyte ratio). CRP was lower in the metformin group but was not statistically significant. Adipokines were dysregulated overall but were not different between the two groups. Serum IFN-γ, IL-8, TNF-α, and CXCL1 trended lower in the metformin group but did not reach significance. These results suggest that metformin improves CV risk biomarkers and insulin resistance in patients with HS. When the results of this study are considered alongside other studies in HS and related conditions, it is likely that metformin also has beneficial effects on metabolic markers and systemic inflammation in HS (CRP, serum adipokines, and immune mediators), warranting further research.