Summary
Background
There is a need for valid and reliable biomarkers in hidradenitis suppurativa (HS) for diagnosis and disease activity monitoring. Imaging‐based biomarkers have the potential to ...fulfil this unmet need but no evaluation of analytical or clinical validity has yet been undertaken.
Objectives
To evaluate the analytical and clinical validity of sonographic epidermal thickness, Doppler ultrasound and dermal tunnel diameter in patients with HS.
Methods
Twenty‐two participants with HS were recruited and underwent a total of 65 matched ultrasound and skin biopsies of lesional, perilesional and unaffected tissue. Ultrasound measurements were performed in triplicate with mean values used. Skin biopsies underwent immunohistochemistry as per previously published methods. Analytical validity was assessed in individual ultrasound–biopsy pairs (n = 65) by comparisons of sonographic variables with histological correlates. Clinical validity was assessed in individual patients (n = 22) by comparing measures of overall disease activity with sonographic outcomes.
Results
Epidermal thickness, dermal tunnel diameter and power Doppler intensity were assessed. Sonographic epidermal thickness and dermal tunnel diameter have high analytical validity with corresponding histological measurements. Power Doppler intensity demonstrated high correlation with dermal CD3+ and CD11c+ cell counts but not neutrophil elastase‐positive cells. Power Doppler ultrasound has significant correlation with pain scores, abscess and nodule count, International HS Severity Scoring System score and number of draining tunnels.
Conclusions
Sonographic epidermal thickness and dermal tunnel diameter have acceptable levels of analytical validity in the assessment of HS lesions. Power Doppler intensity demonstrates acceptable clinical and analytical validity, suggesting it is a valid imaging‐based biomarker in HS.
What is already known about this topic?
Image‐based biomarkers have potential for monitoring of hidradenitis suppurativa disease, but no evaluation of the analytical or clinical validity of image‐based biomarkers currently exists.
What does this study add?
Power Doppler intensity has greater analytical and clinical validity than epidermal thickness and dermal tunnel thickness.
What are the clinical implications of this work?
Power Doppler intensity is a valid imaging biomarker for disease activity in hidradenitis suppurativa.
Linked Comment: Wortsman. Br J Dermatol 2021; 184:591–592.
PCR-based immunoglobulin (Ig)/T-cell receptor (TCR) clonality testing in suspected lymphoproliferations has largely been standardized and has consequently become technically feasible in a routine ...diagnostic setting. Standardization of the pre-analytical and post-analytical phases is now essential to prevent misinterpretation and incorrect conclusions derived from clonality data. As clonality testing is not a quantitative assay, but rather concerns recognition of molecular patterns, guidelines for reliable interpretation and reporting are mandatory. Here, the EuroClonality (BIOMED-2) consortium summarizes important pre- and post-analytical aspects of clonality testing, provides guidelines for interpretation of clonality testing results, and presents a uniform way to report the results of the Ig/TCR assays. Starting from an immunobiological concept, two levels to report Ig/TCR profiles are discerned: the technical description of individual (multiplex) PCR reactions and the overall molecular conclusion for B and T cells. Collectively, the EuroClonality (BIOMED-2) guidelines and consensus reporting system should help to improve the general performance level of clonality assessment and interpretation, which will directly impact on routine clinical management (standardized best-practice) in patients with suspected lymphoproliferations.
Summary
Background
Hidradenitis suppurativa (HS) is now recognized as a systemic inflammatory disease, sharing molecular similarities with psoriasis. Direct comparison of the systemic inflammation in ...HS with psoriasis is lacking.
Objectives
To evaluate the serum proteome of HS and psoriasis, and to identify biomarkers associated with disease severity.
Methods
In this cross‐sectional study, 1536 serum proteins were assessed using the Olink Explore (Proximity Extension Assay) high‐throughput panel in patients with moderate‐to‐severe HS (n = 11), patients with psoriasis (n = 10) and age‐ and body mass index‐matched healthy controls (n = 10).
Results
HS displayed an overall greater dysregulation of circulating proteins, with 434 differentially expressed proteins (absolute fold change ≥ 1·2; P ≤ 0·05) in patients with HS vs. controls, 138 in patients with psoriasis vs. controls and 503 between patients with HS and patients with psoriasis. Interleukin (IL)‐17A levels and T helper (Th)1/Th17 pathway enrichment were comparable between diseases, while HS presented greater tumour necrosis factor‐ and IL‐1β‐related signalling. The Th17‐associated markers peptidase inhibitor 3 (PI3) and lipocalin 2 (LCN2) were able to differentiate psoriasis from HS accurately. Both diseases presented increases of atherosclerosis‐related proteins. Robust correlations between clinical severity scores and immune and atherosclerosis‐related proteins were observed across both diseases.
Conclusions
HS and psoriasis share significant Th1/Th17 enrichment and upregulation of atherosclerosis‐related proteins. Despite the greater body surface area involved in psoriasis, HS presents a greater serum inflammatory burden.
What is already known about this topic?
Psoriasis is an inflammatory skin disease whose molecular profile has been extensively characterized, which has allowed the development of highly efficacious and pathway‐specific treatments.
Psoriasis and hidradenitis suppurativa (HS) share overlapping immunological features, enabling the introduction of therapeutics originally developed for psoriasis into the HS therapeutic arena.
Understanding of the mechanisms underlying HS is still lacking, potentially hindering the development of HS‐targeted treatments.
What does this study add?
By utilizing the largest panel of serum biomarkers to date, this study characterizes and compares the systemic dysregulation in serum of patients with psoriasis and HS.
Despite a limited area of lesional involvement in HS, patients present with high systemic inflammation and an increase in cardiovascular/atherosclerosis‐related biomarkers.
Robust correlations between clinical severity scores and immune and atherosclerosis‐related proteins were found across both diseases.
What is the translational message?
HS exhibits an overall greater dysregulation of circulating proteins than psoriasis.
While T helper (Th)1/Th17 pathway enrichment was comparable between diseases, HS presented greater tumour necrosis factor and interleukin‐1β‐related involvement.
A model using peptidase inhibitor 3 (PI3) and lipocalin 2 (LCN2) levels was able to differentiate the diseases accurately.
These findings suggest that HS presents a great systemic burden despite limited skin involvement, with disease‐specific biomarkers that may be therapeutically targetable.
Plain language summary available online
Summary
Background
Clinical response in hidradenitis suppurativa (HS) is most commonly assessed using the Hidradenitis Suppurativa Clinical Response (HiSCR) measure. Dermal tunnels, increased body ...mass index, smoking and antibiotic use significantly decrease the odds of achieving HiSCR. However, there are few data exploring if clinical features are also associated with length of time to achieve clinical response and/or time to lose clinical response.
Aim
To explore whether variables associated with achievement of HiSCR are associated with time to achieve HiSCR and time to loss of HiSCR in patients with HS treated with adalimumab 40 mg weekly in the PIONEER open‐label extension study.
Methods
Time‐to‐event analyses were performed to estimate time to achieve HiSCR and time to loss of HiSCR. The log rank test was used to compare cumulative incidence curves for a priori patient‐ and disease‐associated factors. Cox regression analysis was performed to compare time‐to‐event outcomes in the presence of a priori variables. All statistical analyses were completed with R software (V3.5.3).
Results
Presence of dermal tunnels significantly increased the time to achieve HiSCR (median 32.6 vs. 14.3 weeks, P = 0.02) and the hazard ratio (HR) was significant after controlling for patient and disease factors (HR = 0.70, 95% CI 0.51–0.96, P = 0.03). A positive family history of HS significantly decreased the time to loss of HiSCR (median 11.4 vs. 18 weeks, P < 0.001) and remained significant in Cox regression analysis (HR = 2.01, 95% CI 1.40–2.88, P < 0.001).
Conclusion
The presence of dermal tunnels significantly influences the odds of achieving HiSCR and the time to achieve HiSCR, while family history influences time to loss of HiSCR.
Summary
Bone disease is prevalent among patients with inflammatory bowel disease (IBD), though bone density screening remains underutilized. We used CT scans performed for other indications in IBD ...patients to identify and monitor osteopenia using CT attenuation values at the lumbar spine. Significant rates of bone disease were detected which would have otherwise gone undiagnosed.
Introduction
Osteoporosis affects about 14–42% of patients with IBD. Though screening is recommended in IBD patients with risk factors, it remains underutilized. In patients with newly diagnosed IBD, we used CT scans performed for other indications to identify and monitor progression of osteopenia.
Methods
Using the Ocean State Crohn’s and Colitis Area Registry, we identified adult patients with one or more abdominal CT scans. Each patient had two age- and gender-matched controls. Radiologists measured attenuation through trabecular bone in the L1 vertebral body recorded in Hounsfield units (HU). Generalized estimating equations were used to measure how HU varied as a function of gender, type of IBD, and age.
Results
One hundred five IBD patients were included, and 72.4% were classified as “normal” bone mineral density (BMD) and 27.6% as potentially osteopenic: 8.6% with ulcerative colitis and 19.0% with Crohn’s disease. We found a decrease in bone density over time (
p
< 0.001) and that BMD decreases more in Crohn’s disease than in ulcerative colitis (
p
< 0.004).
Sixty patients had two CT scans, and mean loss of 9.3 HU was noted. There was a non-significant decrease in BMD over time in patients exposed to > 31 days of steroids and BMD was stable with < 30 days of steroid exposure (
p
< 0.09).
Conclusion
Using CT scans obtained for other indications, we found low rates of osteopenia and osteoporosis that may otherwise have gone undiagnosed. Refinement of opportunistic screening may have advantages in terms of cost-savings and earlier detection of bone loss.
Summary
Background
The association of adalimumab therapy with malignancy and infection is established in other inflammatory diseases; however, rates of hidradenitis suppurativa (HS) are based on case ...reports or retrospective healthcare data and the effect of adalimumab therapy on these rates is unknown. Previously reported rates in the PIONEER OLE Phase 3 study reported on rates only in a subpopulation of 88 participants rather than the entire cohort.
Aim
To quantify rates of malignancy and serious infection in all patients with HS treated with adalimumab 40 mg weekly.
Methods
Reanalysis was undertaken of individual patient data from the PIONEER 1, PIONEER 2 and PIONEER open‐label extension Phase 3 trial data encompassing 591 unique patients with HS administered adalimumab 40 mg weekly without concurrent antibiotic exposure. Incidence rates of serious infection and malignancy were calculated.
Results
Incidence rates of serious infection and malignancy were 2.14 and 0.46 per 100 patient‐years, respectively. Rates of infection and malignancy were comparable to those in other inflammatory conditions examined.
Conclusion
Incidence of serious infection in patients with HS on adalimumab is comparable to those with psoriasis and inflammatory arthropathies, but the incidence of malignancy is increased. This may reflect disease‐specific malignancy risk rather than an effect of adalimumab.
Surveillance and control of Mycoplasma spp. responsible for contagious agalactia (CA) in caprine herds are important challenges in countries with a large small-ruminant dairy industry. In the absence ...of any clinical signs, being able to determine the potential circulation of mycoplasmas within a herd could help to prevent biosecurity issues during animal exchanges between farms and improve health management practices. The objective of this study was to determine whether regular sampling of bulk tank milk was suitable for such surveillance. Twenty farms were sampled once a month for 2 yr and CA-responsible mycoplasmas were detected by real-time PCR on DNA extracted from milk, using 3 different DNA extraction methods. The pattern of mycoplasma excretion in bulk tank milk was assessed over time and several herd characteristics were recorded together with any event occurring within the herds. In general, the results obtained with the different detection methods were comparable and mainly agreed with the culture results. Several patterns of excretion were observed but were not related to herd characteristics (size, breed, and so on). Recurrence of the same (sub)species and same pulsed-field gel electrophoresis subtype during the 2-yr period is indicative of the considerable persistence of mycoplasmas. This persistence was associated with intermittent excretion. In conclusion, bulk tank milk sampling could be valuable for controlling CA in caprine herds provided it is repeated several times, yet to be defined, per year and analyzed using an appropriate methodology and the right cut-off for interpretation.
Aim To evaluate the sensitivity and specificity of eight previously reported computed tomography (CT) signs in diagnosing internal mesenteric hernia following Roux-en-Y gastric bypass surgery. ...Materials and methods Preoperative CT images of nine patients with surgically proven internal mesenteric hernia as a complication of gastric bypass surgery and 10 matched control patients were reviewed in a blinded fashion by three radiologists. The presence of eight previously reported signs of internal mesenteric hernia was assessed: mesenteric swirl sign, hurricane eye sign, mushroom sign, small bowel obstruction, clustered small bowel loops, small bowel other than duodenum located behind the superior mesenteric artery (SMA), presence of the jejunal anastomosis to the right of the midline, and engorged mesenteric lymph nodes. The sensitivity and specificity were calculated for each sign, as well as inter-observer reliability in recognizing these signs. Results Mesenteric swirl was the most predictive sign of internal hernia (sensitivity 78–100%, specificity 80–90%). Other CT signs showed good specificity (70–100%), but sensitivities were low (0–44%). The presence of a small-bowel obstruction and engorged mesenteric nodes was found to be 100% specific in predicting the presence of an underlying hernia. There was substantial inter-observer agreement in detecting mesenteric swirl sign (κ = 0.48–0.79), but agreement was relatively poor for all other signs. Conclusion Mesenteric swirl is an easily recognized CT sign, and is the best indicator of internal hernia following Roux-en-Y gastric bypass surgery. Other reported CT signs are diagnostically insensitive. The presence of small-bowel obstruction with engorged mesenteric nodes is highly specific in diagnosing internal mesenteric hernia.
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