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.

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.

Determinants of disease severity among patients with atopic dermatitis: association with components of the atopic march.

We aimed to explore the association of key clinical characteristics with disease severity in atopic dermatitis (AD) and its relation to components of the atopic march in a large hospital cohort. Outpatients with AD referred to the Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark, between January 2012 and December 2017, were compared based on disease severity (SCORAD); mild (< 25), moderate (25-50) and severe (> 50). A total of 470 AD patients were included: 122 small children (< 4 years of age), 103 children/adolescents (age 4-15 years) and 245 adults (> 15 years of age). A significant difference between severity groups in small children was observed for FLG mutation carrier status (16.7 vs. 30.2 vs. 60.0% mutation carriers among patients with mild, moderate and severe AD, respectively, p = 0.012) and self-rated health (3.2 vs. 2.7 vs. 2.8 with 4 being excellent health, p = 0.022). A significant difference between severity groups in adults was observed for male sex (24.4 vs. 39.8 vs. 52.9%, p = 0.003), serum total IgE (577 vs. 1269 vs. 2379 × 103 IU/L, p < 0.001), blood eosinophil count (0.28 vs. 0.39 vs. 0.61 × 109/L, p < 0.001) and asthma (42.9 vs. 38.8 vs. 72.0%, p < 0.001). Early onset of AD (< 1 year of age) and FLG mutation was associated with more severe disease and high serum total IgE levels. In conclusion, the distribution of key clinical characteristics varies significantly according to the severity of AD measured by SCORAD. Sub-typing of AD patients related to determinants of disease severity may be helpful in establishing prognosis and targeted treatment of AD.

Use of Complementary and Alternative Therapies in Outpatients with Atopic Dermatitis from a Dermatological University Department.

BACKGROUND: Treatment of atopic dermatitis (AD) may be challenging, therefore some patients seek complementary and alternative medications (CAM). We determined prevalence and predictors for CAM use in a hospital cohort of AD patients. MATERIAL AND METHODS: Between January 1, 2012, and December 31, 2017, AD patients referred to the dermatological outpatient clinic at Bispebjerg Hospital were included in the study. Information on CAM use, demographics and disease characteristics were obtained by questionnaire, and associations were determined by χ2 and t test separately for children (< 16 years) and adults (≥16 years). RESULTS: In total 441 filled in the questionnaire on AD, and 433 patients responded to the questions about CAM use: 198 children and 235 adults. A total of 137 (31.6%) had used one or more CAM. CAM use in children was significantly associated with prior use of ≥2 conventional treatments (p = 0.047) and topical calcineurin inhibitors (p = 0.021), a higher number of affected eczema sites (p < 0.001) including more frequent affection of the face and extremities, a higher SCORAD score (p = 0.045), and low mean overall self-rated health (p = 0.003). CAM use in adults was significantly associated with lower age of onset of AD (p = 0.004), comorbid allergic rhinoconjunctivitis (p = 0.039), frequent use of moisturizing cream (p = 0.024), facial and neck eczema (p = 0.005) and high educational level (p = 0.043). CONCLUSION: CAM use is frequent in both children and adult AD patients. CAM users are characterized by long disease duration, a significant disease burden and by having a longer education. The high prevalence of CAM may indicate that patients' expectations regarding treatment of AD are not redeemed in the conventional health care system.

Type 2 diabetes and psoriasis: links and risks.

Psoriasis (PsO) is one of the most common chronic inflammatory skin diseases with a world prevalence of 2%-4%. The increasing knowledge of the mechanisms driving PsO has raised focus on existing links to metabolic syndrome and type 2 diabetes (T2D). We reviewed the existing literature of the prevalence and risk of T2D in patients with PsO. The studies reviewed were mainly large retrospective cohort and case-control studies, showing an increased prevalence of T2D in PsO patients compared to controls, particularly in late onset (type 2) PsO. T2D prevalence did not correlate to patient age or severity of PsO in the reviewed studies. Conclusively, T2D was found to be more prevalent in patients with PsO compared to the background population. Several mechanisms involved in lipid transportation seem to be upregulated in PsO patients. Physicians play a key role concerning information about known comorbidity and promotion of early prophylaxis in patients with PsO.

Use of nonbiologic treatments in antihistamine-refractory chronic urticaria: a review of published evidence.

BACKGROUND: Knowledge of effectiveness and safety of the nonbiologic, nonantihistamine treatments used for chronic urticaria is important as in some cases the principal guideline-recommended drug; omalizumab, has limited effect, side effects or is too expensive or unavailable. Herein, we systematically review the evidence for the use of the nonbiologic treatments in antihistamine-refractory chronic urticaria. METHODS: We performed a systematic review of the literature using PubMed and Webofscience and identified studies that reported use of one or more of the nonbiological, nonantihistamine treatment options for chronic urticaria. The studies were evaluated based on study design, number of patients, effect of treatment and safety. RESULTS: We identified 118 studies or case series with 13 different treatments (azathioprine, chloroquine, colchicine, cyclosporine, dapsone, intravenous immunoglobulin (IVIG), methotrexate, montelukast, mycophenolate mofetil, plasmapheresis, sulfasalazine, tranexamic acid and ultraviolet light (UV) A, UVB) totaling 1682 patients. There was a paucity of controlled trials for most of the treatments reviewed albeit the strongest evidence in favor of a beneficial effect in chronic urticaria was, apart from montelukast and cyclosporine, seen for UV therapy and dapsone followed by IVIG. CONCLUSION: The treatment options reviewed should be seen as potential alternatives in treatment-resistant chronic urticaria where guideline-based selections have failed. However, larger controlled trials are warranted to advance the level of evidence, possibly supporting some treatments' future recommendation in selected patients.