Cold steel versus impedance-dependent tissue sealer tonsillectomy - a study protocol for a randomised controlled trial.

INTRODUCTION: Approximately 7,000 tonsillectomies are performed annually in Denmark on a benign basis. The cold steel surgical technique is the gold standard. The risk of post tonsillectomy bleeding (PTH) in a centre in Jutland is 7.9%. A new impedance-dependent tissue sealer (IDTS) device has been developed, with preliminary results showing a reduction in operation time, perioperative bleeding and post-operative risk of bleeding of 4.5%. METHODS: A randomised, controlled, double-blinded multicentre trial of cold steel tonsillectomy versus IDTS will be performed on 1,250 patients. The main endpoint is PTH, perioperative bleeding, operation time and post-operative pain. The secondary outcomes are days until return to work, food intake, activity and quality of life. Included in the study are patients with indication for surgery weighing ≥ 16 kg, and excluded are patients with malignancy, bleeding disorders and unwillingness to participate in the study. CONCLUSIONS: To our knowledge, the present study is the largest randomised controlled trial in ENT surgery in the Nordic countries. The study will potentially provide evidence on PTH regarding two tonsillectomy methods. FUNDING: The authors have no potential conflicts of interest to declare. The study is supplied with instruments from Medtronic needed for the surgical procedures. Furthermore, a minor part of the funding of the entire project is provided by the aforementioned company. The funding providers have no role in design or conduct of the study. CLINICALTRIALS: gov with the identification number NCT05270109.

Mild-to-moderate severity of psoriasis may be assessed remotely based on photographs and self-reported extent of skin involvement.

Background: Remote monitoring was used to assess and manage skin diseases. Objective: To investigate to what extent smartphone photographs along with a self-reported body region (BR) score can be used to evaluate psoriasis severity. Methods: Psoriasis severity was assessed in the clinic using the psoriasis area and severity index and the physician's global assessment. On the same day, the patients took a photograph of a representative lesion from 4 BR (head/neck, upper limbs, trunk, and lower limbs) and completed a questionnaire about BR score. The photographs were rated by 5 dermatologists. Intraclass correlation coefficients with 95% CIs were calculated. Results: Overall, 32 were included, of which 6% had almost clear, 69% had mild, and 25% had moderate psoriasis. Perfect agreement between the self-reported and the doctors' BR score was observed for 59%, and near-perfect agreement (deviation of maximum 1 score) was 92%. The intraclass correlation coefficient between clinical and photographic psoriasis area and severity index was 0.78 (95% CI, 0.55-0.90), and for physician's global assessment, perfect agreement was 53%. Conclusions: The agreement between psoriasis severity assessed clinically and by photographs was good in a study setting. This gives the opportunity to remotely assess psoriasis severity by combining photographs with self-reported BR scores.

A fragment of type VI collagen alpha-6 chain is elevated in serum from patients with atopic dermatitis, psoriasis, hidradenitis suppurativa, systemic lupus erythematosus and melanoma.

Extracellular matrix (ECM) remodeling of the skin is a continuous process necessary for maintaining tissue homeostasis. Type VI collagen (COL6) is characterized as a beaded filament, located in the dermal ECM, where COL6-α6-chain has been demonstrated upregulated in atopic dermatitis. The aim of this study was to develop and validate a competitive ELISA, targeting the N-terminal of COL6-α6-chain, named C6A6, and evaluate its associations with the dermatological condition's atopic dermatitis, psoriasis, hidradenitis suppurativa, systemic lupus erythematosus, systemic sclerosis, urticaria, vitiligo, and cutaneous malignant melanoma in comparison, to healthy controls. A monoclonal antibody was raised and employed in an ELISA assay. The assay was developed, technically validated, and evaluated in two independent patient cohorts. Cohort 1 showed C6A6 was significantly elevated in patients with atopic dermatitis (p < 0.0001), psoriasis (p < 0.0001), hidradenitis suppurativa (p = 0.0095), systemic lupus erythematosus (p = 0.0032) and melanoma (p < 0.0001) compared to healthy donors. Cohort 2 confirmed C6A6 being upregulated in atopic dermatitis compared to healthy controls (p < 0.0001), but also associated with disease severity (SCORAD, p = 0.046) and lowered in patients receiving calcineurin inhibitors (p = 0.014). These findings are hypothesis generating, and the utility of the C6A6 biomarker for disease severity and treatment response needs to be validated in larger cohorts and longitudinal studies.

Adrenaline autoinjector is under-prescribed in typical cold urticaria patients living in tropical climate countries.

Background: The diagnosis of typical cold urticaria (ColdU) relies on whealing in response to local cold stimulation testing (CST). It can also manifest with cold-induced anaphylaxis (ColdA). Till date, it is largely unclear how often patients with ColdU receive adrenaline treatment and are provided with an adrenaline autoinjector (AAI). Methods: An international, cross-sectional study, COLD-CE (i.e., comprehensive evaluation of ColdU and other cold-induced reactions), was carried out at 32 UCAREs. Detailed histories were taken and CST with an ice cube and/or TempTest® performed. ColdA was defined as an acute cold-induced (i.e., by cold water, air, or surfaces) involvement of the skin and/or visible mucosal tissue and at least one of the symptoms (cardiovascular manifestations, difficulty breathing, or gastrointestinal symptoms). Results: Of the 551 ColdU patients, 75% (n = 412) had a positive CST. Of them, concomitant chronic spontaneous urticaria was diagnosed in 10%. Of 372 patients with stand-alone ColdU, 69% were women and 91% adults. Their median age was 36 (IQR 26 - 48) years. Patients were also categorized into residents of countries with a tropical (n = 33), temperate (n = 264), or cold (n = 75) climate (Table 1: R13C1, R17C1, R21C1). AAI was more often prescribed to residents of temperate than tropical countries (30% vs. 12%, p = .038; Table 1: R31C1), although the frequency of ColdA did not significantly differ between these countries (44% vs. 42%, p = 1.000; R29C2). Residents of tropical countries had a higher frequency of ColdA induced by cold air than residents of temperate (36% vs. 12%, p = .001; R29C4) or cold (36% vs. 12%, p = .007; R25C4) countries. Cardiovascular manifestations induced by cold air were diagnosed in 33% (n = 11) of residents of tropical countries, but only 18% (n = 2) and 36% (n = 4) of them had received adrenaline and AAI, respectively (R13 - 15C7). Furthermore, hypotension and/or loss of consciousness induced by cold air occurred in 18% (n = 6) of patients, but only 17% (n = 1) received adrenaline (R13 - 14C10). ColdA was induced by complete cold water immersion in 9% (n = 3) of patients, and none of them received adrenaline treatment nor AAI (R13 - 15C3). Conclusion: Our findings suggest that ColdA is undertreated and call for changes in ColdU management.

Risk factors for systemic reactions in typical cold urticaria: Results from the COLD-CE study.

BACKGROUND: Cold urticaria (ColdU), that is, the occurrence of wheals or angioedema in response to cold exposure, is classified into typical and atypical forms. The diagnosis of typical ColdU relies on whealing in response to local cold stimulation testing (CST). It can also manifest with cold-induced anaphylaxis (ColdA). We aimed to determine risk factors for ColdA in typical ColdU. METHODS: An international, cross-sectional study COLD-CE was carried out at 32 urticaria centers of reference and excellence (UCAREs). Detailed history was taken and CST with an ice cube and/or TempTest® performed. ColdA was defined as an acute cold-induced involvement of the skin and/or visible mucosal tissue and at least one of: cardiovascular manifestations, difficulty breathing, or gastrointestinal symptoms. RESULTS: Of 551 ColdU patients, 75% (n = 412) had a positive CST and ColdA occurred in 37% (n = 151) of the latter. Cold-induced generalized wheals, angioedema, acral swelling, oropharyngeal/laryngeal symptoms, and itch of earlobes were identified as signs/symptoms of severe disease. ColdA was most commonly provoked by complete cold water immersion and ColdA caused by cold air was more common in countries with a warmer climate. Ten percent (n = 40) of typical ColdU patients had a concomitant chronic spontaneous urticaria (CSU). They had a lower frequency of ColdA than those without CSU (4% vs. 39%, p = .003). We identified the following risk factors for cardiovascular manifestations: previous systemic reaction to a Hymenoptera sting, angioedema, oropharyngeal/laryngeal symptoms, and itchy earlobes. CONCLUSION: ColdA is common in typical ColdU. High-risk patients require education about their condition and how to use an adrenaline autoinjector.

Immunoinflammatory Biomarkers in Serum Are Associated with Disease Severity in Atopic Dermatitis.

BACKGROUND: A growing body of evidence links various biomarkers to atopic dermatitis (AD). Still, little is known about the association of specific biomarkers to disease characteristics and severity in AD. OBJECTIVE: To explore the relationship between various immunological markers in the serum and disease severity in a hospital cohort of AD patients. METHODS: Outpatients with AD referred to the Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark, were divided into groups based on disease severity (SCORAD). Serum levels of a preselected panel of immunoinflammatory biomarkers were tested for association with disease characteristics. Two machine learning models were developed to predict SCORAD from the measured biomarkers. RESULTS: A total of 160 patients with AD were included; 53 (33.1%) with mild, 73 (45.6%) with moderate, and 34 (21.3%) with severe disease. Mean age was 29.2 years (range 6-70 years) and 84 (52.5%) were females. Numerous biomarkers showed a statistically significant correlation with SCORAD, with the strongest correlations seen for CCL17/thymus and activation-regulated chemokine (chemokine ligand-17/TARC) and CCL27/cutaneous T cell-attracting-chemokine (CTACK; Spearman R of 0.50 and 0.43, respectively, p < 0.001). Extrinsic AD patients were more likely to have higher mean SCORAD (p < 0.001), CCL17 (p < 0.001), CCL26/eotaxin-3 (p < 0.001), and eosinophil count (p < 0.001) than intrinsic AD patients. Predictive models for SCORAD identified CCL17, CCL27, serum total IgE, IL-33, and IL-5 as the most important predictors for SCORAD, but with weaker associations than single cytokines. CONCLUSIONS: Specific immunoinflammatory biomarkers in the serum, mainly of the Th2 pathway, are correlated with disease severity in patients with AD. Predictive models identified biomarkers associated with disease severity but this finding warrants further investigation.

Guselkumab for hidradenitis suppurativa in a patient with concomitant Crohn's disease: Report and systematic literature review of effectiveness and safety.

Guselkumab appears to be safe and effective in the treatment of patients with HS, who do not respond to adalimumab and other systemic therapies. Guselkumab can be used in patients with comorbid Crohn's disease.

Omalizumab for cholinergic urticaria: 6 months prospective study and systematic review of the literature.

To examine the effectiveness of omalizumab on disease activity and quality of life in patients with cholinergic urticaria (CholU). Further, a systematic review of the literature was performed to identify all studies of use of omalizumab in CholU. A total of 23 patients (63.9%) were refractory to updosed non-sedating antihistamines and initiated omalizumab in the observation period. Among these, an improvement of 10.8 UAS7 points (4.6-17.0), P = .002, was seen at 6 months follow up. DLQI and disease bother score VAS also improved significantly from before initiating treatment with omalizumab to follow-up; 7.0 points (3.6-10.3), P < .001 and 3.1 points (1.5-4.8), P = .001, respectively. The overall mean drug survival time for omalizumab (discontinued due to any cause) was 30.6 months (22.2-39.0). A total of five patients (21.7%) reported suspected side effects (headache, muscle pain, fatigue and injection site reactions) during treatment with omalizumab until 6 months follow-up. The systematic literature review identified 58 additional antihistamine refractory patients with CholU treated with omalizumab. The available studies reported that omalizumab is effective in patients with CholU and improves their disease-related quality of life. Omalizumab is safe, reduces disease activity and improves disease-related quality of life in patients with CholU.

Dupilumab for prurigo nodularis: Case series and review of the literature.

Dupilumab is a recombinant complete human monoclonal antibody modulating the signaling of interleukin-4 and interleukin-13 pathways and has been approved for the treatment of moderate/severe atopic dermatitis. Here, we present three cases of prurigo nodularis treated off-label with dupilumab, and a review of the existing literature. All patients in this study had longstanding severe disease and had tried multiple treatment modalities. They were treated with dupilumab at an initial dose of 600 mg subcutaneously, followed by 300 mg every 2 weeks. Systematic literature searches were performed to identify literature describing the evaluation of the effect of treatment with dupilumab in prurigo nodularis. The physician's assessment of the patients revealed a good or excellent response to the treatment with dupilumab. Patients were evaluated after treatment for 4 and 7 months. Treatment was generally well-tolerated; one in three patients reported dry eyes. Four studies with a total of 11 patients (range: 1-4) were identified by the literature search. Complete response was noted in all 11 patients. Treatment with dupilumab appears to be safe and well-tolerated with clinical benefit in recalcitrant prurigo nodularis. Larger randomized and controlled trials using validated outcome measures are needed before dupilumab could be applied in clinical settings.

Factors affecting quality of life in patients with hidradenitis suppurativa.

Hidradenitis suppurativa (HS) has a substantial impact on patients' lives. We identified factors associated with decreased quality of life (QoL) in patients with HS. Consecutive newly referred patients with HS attending a tertiary referral centre for HS were evaluated with the dermatology life quality index (DLQI). Clinical evaluation was performed according to the Hurley stage. Furthermore, disease duration, number of boils in the past month, boil-associated pain score, overall disease-related distress score, smoking status, employment status and comorbidities were recorded. A total of 339 patients with a mean age of 39.4 years were included; 218 (64.3%) females and 121 (35.7%) males. Of these, 96 (28.3%) had Hurley stage I, whereas 195 (57.5%) and 48 (14.2%) had Hurley II and III, respectively. The mean BMI was 29.0 (SD 7.1) kg/m2 and 75.2% of patients were current or former smokers. The mean overall DLQI score was 11.9 (SD 7.6). After mutual adjustment for clinical characteristics a significant difference in mean overall DLQI score was observed between severity groups (8.6 vs. 12.6 vs. 16.1, adjusted p < 0.001, for Hurley I, II and III, respectively), age group (12.1 vs. 12.1 vs. 12.5 vs. 7.1, adjusted p = 0.002, for ≤ 20, 21-40, 41-60 and > 60 years, respectively), employment status (11.0 vs. 14.6, adjusted p = 0.003, for employed and unemployed, respectively), presence of boils in the preceding month (8.3 vs. 13.6, adjusted p = 0.001, for no boils and presence of boils, respectively), higher overall disease-related distress score (6.3 vs. 13.9, adjusted p < 0.001, for low and high score, respectively), involvement of the groins (8.7 vs. 13.0, adjusted p = 0.035 for no and involvement, respectively), high number of anatomical regions involved (9.8 vs. 12.4 vs. 14.5, adjusted p = 0.007 for 0-1, 2 and ≥ 3 anatomical regions involved, respectively) and diabetes (11.5 vs. 15.2, adjusted p = 0.043, for no and diabetes, respectively). All ten individual DLQI question scores increased significantly with increasing Hurley stage. Patients with HS referred for specialized hospital care report substantial impact on the quality of life. Disease severity (Hurley stage), younger age, diabetes, recent and increasing disease activity and specific anogenital localization are major aggravating factors.