Human dermal fibroblast subpopulations and epithelial mesenchymal transition signals in hidradenitis suppurativa tunnels are normalized by spleen tyrosine kinase antagonism in vivo.

Hidradenitis Suppurativa is a chronic inflammatory disease of which the pathogenesis is incompletely understood. Dermal fibroblasts have been previously identified as a major source of inflammatory cytokines, however information pertaining to the characteristics of subpopulations of fibroblasts in HS remains unexplored. Using in silico-deconvolution of whole-tissue RNAseq, Nanostring gene expression panels and confirmatory immunohistochemistry we identified fibroblast subpopulations in HS tissue and their relationship to disease severity and lesion morphology. Gene signatures of SFRP2+ fibroblast subsets were increased in lesional tissue, with gene signatures of SFRP1+ fibroblast subsets decreased. SFRP2+ and CXCL12+ fibroblast numbers, measured by IHC, were increased in HS tissue, with greater numbers associated with epithelialized tunnels and Hurley Stage 3 disease. Pro-inflammatory CXCL12+ fibroblasts were also increased, with reductions in SFRP1+ fibroblasts compared to healthy controls. Evidence of Epithelial Mesenchymal Transition was seen via altered gene expression of SNAI2 and altered protein expression of ZEB1, TWIST1, Snail/Slug, E-Cadherin and N-Cadherin in HS lesional tissue. The greatest dysregulation of EMT associated proteins was seen in biopsies containing epithelialized tunnels. The use of the oral Spleen tyrosine Kinase inhibitor Fostamatinib significantly reduced expression of genes associated with chronic inflammation, fibroblast proliferation and migration suggesting a potential role for targeting fibroblast activity in HS.

Resident cutaneous memory T cells: a clinical review of their role in chronic inflammatory dermatoses and potential as therapeutic targets.

Resident memory T cells (T-RMs) remain in epithelial barrier tissues after antigen exposure and the initial effector phase. These T-RMs provide effective antimicrobial and anticancer immunity; however, pathogenic T-RMs have been shown to mediate various chronic inflammatory disorders in a variety of tissue types. In the skin, T-RMs are referred to as resident cutaneous memory T cells (cT-RMs). Understanding the mechanisms leading to the development and establishment of these cT-RMs populations may allow for targeted treatments that provide durable responses in chronic immune-mediated skin diseases, even after cessation. In this review, we summarize the evidence on cT-RMs as drivers of chronic inflammatory dermatoses, including psoriasis, vitiligo, atopic dermatitis, cutaneous lupus erythematosus and alopecia areata, among others. Data from in vitro, animal model and ex vivo human studies are presented, with a focus on the potential for cT-RMs to trigger acute disease flares, as well as recurrent disease, by establishing an immune 'memory' in the skin. Furthermore, the available data on the potential for existing and novel treatments to affect the development or survival of cT-RMs in the skin are synthesized. The data suggest a dynamic and rapidly growing area in the field of dermatology; however, we also discuss areas in need of greater research to allow for optimal treatment selection for long-term disease control.

Adalimumab therapy is associated with increased faecal short chain fatty acids in hidradenitis suppurativa.

Altered gut microbiota composition has been observed in individuals with hidradenitis suppurutiva (HS) and many other inflammatory diseases, including obesity, type 1 and type 2 diabetes. Here, we addressed whether adalimumab, a systemic anti-inflammatory therapy, may impact the microbiota biochemical profile, particularly on beneficial metabolites such as short-chain fatty acids (SCFAs). We conducted an observational single-arm pilot trial to assess gut microbiota composition by 16S rRNA gene sequence analysis and to detect metabolite signatures by gas chromatography in stool samples from participants with HS prior to and 12 weeks after commencing adalimumab therapy. HS individuals that better responded to adalimumab treatment showed a shift in the composition and function of the gut microbiota with significantly increased SCFA acetate and propionate compared to age, gender and BMI-matched healthy controls. A positive correlation was observed between propionate with Prevotella sp and Faecalibacterium prausnitsii. Increased SCFAs, changes in gut microbiota composition, function and metabolic profile following 12 weeks of adalimumab suggest that targeting SCFAs may be considered a potential biomarker to be evaluated as a complementary protective factor or as a diagnostically relevant signal in HS.

Effect of Miscanthus × giganteus ash on survival, biomass, reproduction and avoidance behaviour of the endogeic earthworm Aporrectodea caliginosa.

To achieve the EU's targets for reducing energy production from fossil fuels, the use of energy crops, such as Miscanthus × giganteus, is increasing resulting in a corresponding increase in waste ash from incineration. The chemical properties of Miscanthus ash (e.g. phosphorus and potassium content) may allow this waste material (currently landfilled) to be used as a fertiliser, but no information exists on the effect of the ash on the biological properties of soil. The main aim of this study was to determine the potential impact of Miscanthus ash on earthworms by assessing the effect on survival, change in biomass, reproduction and avoidance behaviour of the geophagous, soil dwelling earthworm, Aporrectodea caliginosa. Tests utilised a range of Miscanthus ash doses from 0 to 50 t ha-1 (0, 1, 2.5, 5, 10, 25, 50). Results showed that Miscanthus ash had no significant impact on A. caliginosa survival, biomass and reproduction, but negative trends were observed for biomass from 2.5 t ha-1 and for reproduction from 10 t ha-1. In contrast, a significant avoidance response was observed in the 25 and 50 t ha-1 treatment and according to ISO guideline 17512 there is a negative impact of the Miscanthus ash on soil habitat function at 25 t ha-1 and above as more than 80% of earthworms were in the control soil. It is suggested that this negative effect on soil habitat function could be attributed to a range of factors including the presence of heavy metals in the ash and a change in substrate pH, texture and/or osmotic stress. Further laboratory-based studies conducted over extended time periods with a more refined range of ash doses and associated field-based studies are required to validate the results and determine a more precise assessment of the threshold ash value inducing a loss of soil habitat function.

Zosteriform cutaneous metastases: an unusual presentation of metastatic lung carcinoma.

Zosteriform cutaneous metastases are an unusual and rare morphological variant. We discuss the case of a 78-year-old gentleman with a background of end-stage renal disease with metastatic adenocarcinoma of the lung which was diagnosed due to the development of zosteriform cutaneous metastases around his vascular catheter (vascath) site. The vascath may have acted as a traumatic nidus for lymphatic spread.

Prevalence of inflammatory bowel disease (IBD) in hidradenitis suppurativa (HS): systematic review and adjusted meta-analysis.

BACKGROUND: Several case reports and case series have recently explored the association between hidradenitis suppurativa (HS) and inflammatory bowel disease (IBD). OBJECTIVE: We performed a systematic review and meta-analysis of case-control studies to determine  (i) the pooled prevalence of IBD in HS cohorts, and (ii) whether HS is more strongly associated with Crohn's disease or ulcerative colitis. METHODS: Electronic searches were performed using five databases, from their inception to August 2018. Case-control studies reporting the proportion of IBD cases in HS cohorts were included and meta-analysis performed. RESULTS: From six included studies, a significant association between HS and IBD after pooling of adjusted effect sizes was identified (OR 2.12; 95% CI 1.62-2.77; P = 0.03). Subgroup analysis demonstrated a significant association between HS and Crohn's disease (OR 2.25; 95% CI 1.52-3.32; P < 0.0001, I2  = 92%) and with ulcerative colitis (OR 1.56; 95% CI 1.26-1.94; P < 0.0001; I2  = 36%). LIMITATIONS: Studies reviewed were observational by design which are susceptible to bias and lack of randomization. CONCLUSIONS: Our results indicate a statistically significant association between HS and IBD. Our results highlight that all patients with HS should be clinically screened for symptoms of IBD and symptomatic patients referred for further investigations.

Prevalence of asthma, aspirin sensitivity and allergy in chronic rhinosinusitis: data from the UK National Chronic Rhinosinusitis Epidemiology Study.

BACKGROUND: Chronic rhinosinusitis (CRS) is a common disorder associated with other respiratory tract diseases such as asthma and inhalant allergy. However, the prevalence of these co-morbidities varies considerably in the existing medical literature and by phenotype of CRS studied. The study objective was to identify the prevalence of asthma, inhalant allergy and aspirin sensitivity in CRS patients referred to secondary care and establish any differences between CRS phenotypes. METHODS: All participants were diagnosed in secondary care according to international guidelines and invited to complete a questionnaire including details of co-morbidities and allergies. Data were analysed for differences between controls and CRS participants and between phenotypes using chi-squared tests. RESULTS: The final analysis included 1470 study participants: 221 controls, 553 CRS without nasal polyps (CRSsNPs), 651 CRS with nasal polyps (CRSwNPs) and 45 allergic fungal rhinosinusitis (AFRS). The prevalence of asthma was 9.95, 21.16, 46.9 and 73.3% respectively. The prevalence of self-reported confirmed inhalant allergy was 13.1, 20.3, 31.0 and 33.3% respectively; house dust mite allergy was significantly higher in CRSwNPs (16%) compared to CRSsNPs (9%, p < 0.001). The prevalence of self- reported aspirin sensitivity was 2.26, 3.25, 9.61 and 40% respectively. The odds ratio for aspirin sensitivity amongst those with AFRS was 28.8 (CIs 9.9, 83.8) p < 0.001. CONCLUSIONS: The prevalence of asthma and allergy in CRS varies by phenoytype, with CRSwNPs and AFRS having a stronger association with both. Aspirin sensitivity has a highly significant association with AFRS. All of these comorbidities are significantly more prevalent than in non-CRS controls and strengthen the need for a more individualised approach to the combined airway.

SAPHO syndrome associated with hidradenitis suppurativa and pyoderma gangrenosum successfully treated with adalimumab and methotrexate: a case report and review of the literature.

SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome is a rare inflammatory condition describing the combination of skin, bone, and joint manifestations that has a heterogeneous presentation. We report a case of severe SAPHO syndrome in association with hidradenitis suppurativa and pyoderma gangrenosum in a 27-year-old male. The patient had an initial migratory arthritis affecting the knees, ankles, metacarpophalangeal joints, proximal interphalangeal joints, wrists, shoulder, and lower back, which progressed to a persistent arthritis and swelling at the sternum, shoulders, wrists, hands, feet, and lower back. Radiographic changes were consistent with the diagnosis of SAPHO syndrome. Serum proinflammatory cytokine levels were significantly elevated and improved substantially after 3 months of therapy. Rationale for therapy in this patient was the observation that tumor necrosis alpha antagonists have been successfully used in SAPHO syndrome, and since arthropathy was so prominent in our patient, we elected to use adalimumab combined with methotrexate.

Hidradenitis suppurativa: A neglected disease in Indigenous Australians.

We report the first case series of hidradenitis suppurativa in patients of Indigenous Australian heritage. The incidence and ethnicity of populations affected by this condition are not known. The high comorbid disease burden and socioeconomic disadvantage that is well recognised in the Indigenous Australian population poses significant challenges to therapeutic outcomes.

Inter-observer reliability of the PASI in a clinical setting.

BACKGROUND: With the evolving emphasis on evidence-based practice, the use of reliable clinical scales forms an important foundation for clinical assessment. The psoriasis area and severity index (PASI) is the most widely used tool for the measurement of psoriasis severity; however, there has been some debate over the potential reproducibility of PASI scoring. OBJECTIVES: To determine the inter-observer reliability of the PASI at a large tertiary hospital with a psoriasis treatment centre. METHODS: In total, 34 patients who were due for their 3-monthly follow up at a psoriasis treatment centre were independently evaluated by five clinical staff (observers) from the Department of Dermatology. Each observer independently determined the PASI score of each patient and the inter-observer reliability coefficient was determined by employing intra-class correlation coefficients (ICC). RESULTS: There was a significant degree of concordance among the PASI scoring of observers (ICC = 0.804; CI 95%: 0.706-0.883). CONCLUSIONS: Our cross-sectional study suggests that the PASI provides a reproducible method of assessing psoriasis severity among patients seen in a busy dermatology clinic at a large tertiary hospital.

On-chip integrated labelling, transport and detection of tumour cells.

Microflow cytometry represents a promising tool for the investigation of diagnostic and prognostic cellular cancer markers, particularly if integrated within a device that allows primary cells to be freshly isolated from the solid tumour biopsies that more accurately reflect patient-specific in vivo tissue microenvironments at the time of staining. However, current tissue processing techniques involve several sequential stages with concomitant cell losses, and as such are inappropriate for use with small biopsies. Accordingly, we present a simple method for combined antibody-labelling and dissociation of heterogeneous cells from a tumour mass, which reduces the number of processing steps. Perfusion of ex vivo tissue at 4°C with antibodies and enzymes slows cellular activity while allowing sufficient time for the diffusion of minimally active enzymes. In situ antibody-labelled cells are then dissociated at 37°C from the tumour mass, whereupon hydrogel-filled channels allow the release of relatively low cell numbers (<1000) into a biomimetic microenvironment. This novel approach to sample processing is then further integrated with hydrogel-based electrokinetic transport of the freshly liberated fluorescent cells for downstream detection. It is anticipated that this integrated microfluidic methodology will have wide-ranging biomedical and clinical applications.

Isolated symptomatic cutaneous disease in hypereosinophilic syndrome.

A 41-year-old Phillipino man presented with a 3-year history of a relapsing and remitting generalized chronic pruritic erythematous papular and plaque-like eruption. Investigations showed a persistently elevated eosinophil count. His disease was limited to cutaneous involvement with an absence of demonstrable internal organ involvement, despite extensive investigations and multidisciplinary review. Other causes of eosinophilia were excluded. A diagnosis of idiopathic hypereosinophilic syndrome was made. Our patient's presentation raises a number of issues related to hypereosinophilic syndrome. In particular, relating to managing hypereosinophilic syndrome and the challenge of minimizing therapy side-effects. Our case highlights the considerable morbidity of untreated isolated cutaneous disease, for which he was hospitalized with suicidal ideations. In a minority of reports, skin involvement is the only manifestation of hypereosinophilic syndrome.