Body dysmorphia in common skin diseases: Results of an observational, cross-sectional multi-centre study among dermatological out-patients in 17 European countries

Background: Body dysmorphic disorder (BDD) is a common psychiatric disorder associated with high costs for healthcare systems as patients may repeatedly ask for different, often not effective interventions. BDD symptoms are more prevalent in patients with dermatological conditions than the general population, but there are no large sample studies comparing the prevalence of BDD symptoms between patients with dermatological conditions and healthy skin controls. Objectives: To compare the prevalence of BDD symptoms between patients with different dermatological conditions and healthy skin controls and to describe sociodemographic, physical and psychological factors associated with BDD symptoms to identify patients who may have a particularly high chance of having this condition. Methods: This observational cross-sectional, comparative multi-centre study included 8295 participants: 5487 consecutive patients with different skin diseases (56% female) recruited among dermatological out-patients at 22 clinics in 17 European countries and 2808 healthy skin controls (66% female). All patients were examined by a dermatologist. BDD symptoms were assessed by the Dysmorphic Concern Questionnaire (DCQ). Sociodemographic data, information on psychological factors and physical conditions were collected. Each patient was given a dermatological diagnosis according to ICD-10 by a dermatologist. Results: The participation rate of invited dermatological patients was 82.4% on average across all centres. BDD symptoms were five times more prevalent in patients with dermatological conditions than in healthy skin controls (10.5% vs. 2.1%). Patients with hyperhidrosis, alopecia and vitiligo had a more than eleven-fold increased chance (adjusted Odds Ratio (OR) > 11) of having BDD symptoms compared to healthy skin controls, and patients with atopic dermatitis, psoriasis, acne, hidradenitis suppurativa, prurigo and bullous diseases had a more than six-fold increased chance (adjusted OR > 6) of having BDD symptoms. Using a logistic regression model, BDD symptoms were significantly related to lower age, female sex, higher psychological stress and feelings of stigmatisation. Conclusions: This study reveals that clinical BDD symptoms are significantly associated with common dermatological diseases. As such symptoms are associated with higher levels of psychological distress and multiple unhelpful consultations, general practitioners and dermatologists should consider BDD and refer patients when identified to an appropriate service for BDD screening and managementpublishedVersio

Body dysmorphia in common skin diseases: results of an observational, cross-sectional multicentre study among dermatological outpatients in 17 European countries*

Background: Body dysmorphic disorder (BDD) is a common psychiatric disorder associated with high costs for healthcare systems as patients may repeatedly ask for different, often not effective, interventions. BDD symptoms are more prevalent in patients with dermatological conditions than in the general population, but there are no large sample studies comparing the prevalence of BDD symptoms between patients with dermatological conditions and healthy skin controls. Objectives: To compare the prevalence of BDD symptoms between patients with different dermatological conditions and healthy skin controls and to describe sociodemographic, physical and psychological factors associated with BDD symptoms to identify patients who may have a particularly high chance of having this condition. Methods: This observational, cross-sectional, comparative multicentre study included 8295 participants: 5487 consecutive patients with different skin diseases (56% female) recruited among dermatological outpatients at 22 clinics in 17 European countries, and 2808 healthy skin controls (66% female). BDD symptoms were assessed by the Dysmorphic Concern Questionnaire. Sociodemographic data and information on psychological factors and physical conditions were collected. Each patient was given a dermatological diagnosis according to ICD-10 by a dermatologist. The study was registered with number DRKS00012745. Results: The average participation rate of invited dermatological patients was 82.4% across all centres. BDD symptoms were five times more prevalent in patients with dermatological conditions than in healthy skin controls (10.5% vs. 2.1%). Patients with hyperhidrosis, alopecia and vitiligo had a more than 11-fold increased chance (adjusted Odds Ratio (OR) > 11) of having BDD symptoms compared with healthy skin controls, and patients with atopic dermatitis, psoriasis, acne, hidradenitis suppurativa, prurigo and bullous diseases had a more than sixfold increased chance (adjusted OR > 6) of having BDD symptoms. Using a logistic regression model, BDD symptoms were significantly related to lower age, female sex, higher psychological stress and feelings of stigmatization. Conclusions: Clinical BDD symptoms are significantly associated with common dermatological diseases. As such symptoms are associated with higher levels of psychological distress and multiple unhelpful consultations, general practitioners and dermatologists should consider BDD and refer patients when identified to an appropriate service for BDD screening and management. © 2022 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists

Feasibility and effectiveness of trifluridine/tipiracil in metastatic colorectal cancer: real-life data from The Netherlands

Background: The RECOURSE trial showed clinical efficacy for trifluridine/tipiracil for refractory metastatic colorectal cancer patients. We assessed the feasibility and effectiveness of trifluridine/tipiracil in daily clinical practice in The Netherlands. Methods: Medical records of patients from 17 centers treated in the trifluridine/tipiracil compassionate use program were reviewed and checked for RECOURSE eligibility criteria. Baseline characteristics, safety, and survival times were compared, and prespecified baseline characteristics were tested in multivariate analyses for prognostic significance on overall survival (OS). Results: A total of 136 patients with a median age of 62 years were analyzed. Forty-three patients (32%) did not meet the RECOURSE eligibility criteria for not having received all prior standard treatments (n = 35, 26%) and/or ECOG performance status (PS) 2 (n = 12, 9%). The most common grade ≥3 toxicities were neutropenia (n = 44, 32%), leukopenia (n = 8, 6%), anemia (n = 7, 5%), and fatigue (n = 7, 5%). Median progression-free survival (PFS) and median OS were 2.1 (95% CI, 1.8–2.3) and 5.4 months (95% CI, 4.0–6.9), respectively. Patients with ECOG PS 2 had a worse median OS (3.2 months) compared to patients with ECOG PS 0–1 (5.9 months). ECOG PS, KRAS-mutation status, white blood cell count, serum lactate dehydrogenase, and alkaline phosphatase were prognostic factors for OS. Conclusions: Our data show that treatment with trifluridine/tipiracil in daily clinical practice is feasible and safe. Differences in patient characteristics between our population and the RECOURSE study population should be taken into account in the interpretation of survival data. Our results argue against the use of trifluridine/tipiracil in patients with ECOG PS 2. Funding: Johannes J.M. Kwakman received an unrestricted research grant from Servier

High-dose alkylating chemotherapy in BRCA-altered triple-negative breast cancer:the randomized phase III NeoTN trial

Exploratory analyses of high-dose alkylating chemotherapy trials have suggested that BRCA1 or BRCA2-pathway altered (BRCA-altered) breast cancer might be particularly sensitive to this type of treatment. In this study, patients with BRCA-altered tumors who had received three initial courses of dose-dense doxorubicin and cyclophosphamide (ddAC), were randomized between a fourth ddAC course followed by high-dose carboplatin-thiotepa-cyclophosphamide or conventional chemotherapy (initially ddAC only or ddAC-capecitabine/decetaxel [CD] depending on MRI response, after amendment ddAC-carboplatin/paclitaxel [CP] for everyone). The primary endpoint was the neoadjuvant response index (NRI). Secondary endpoints included recurrence-free survival (RFS) and overall survival (OS). In total, 122 patients were randomized. No difference in NRI-score distribution (p = 0.41) was found. A statistically non-significant RFS difference was found (HR 0.54; 95% CI 0.23–1.25; p = 0.15). Exploratory RFS analyses showed benefit in stage III (n = 35; HR 0.16; 95% CI 0.03–0.75), but not stage II (n = 86; HR 1.00; 95% CI 0.30–3.30) patients. For stage III, 4-year RFS was 46% (95% CI 24–87%), 71% (95% CI 48–100%) and 88% (95% CI 74–100%), for ddAC/ddAC-CD, ddAC-CP and high-dose chemotherapy, respectively. No significant differences were found between high-dose and conventional chemotherapy in stage II-III, triple-negative, BRCA-altered breast cancer patients. Further research is needed to establish if there are patients with stage III, triple negative BRCA-altered breast cancer for whom outcomes can be improved with high-dose alkylating chemotherapy or whether the current standard neoadjuvant therapy including carboplatin and an immune checkpoint inhibitor is sufficient. Trial Registration: NCT01057069

Influence of bevacizumab, sunitinib and sorafenib as single agents or in combination on the inhibitory effects of VEGF on human dendritic cell differentiation from monocytes

Vascular endothelial growth factor (VEGF) inhibits differentiation and maturation of dendritic cells (DC), suggesting a potential immunosuppressive role for this proangiogenic factor. Bevacizumab, sorafenib and sunitinib target VEGF-mediated angiogenesis and are active against several types of cancer, but their effects on the immune system are poorly understood. In this study, VEGF and supernatants of renal carcinoma cell lines cultured under hypoxia were found to alter the differentiation of human monocytes to DC. Resulting DC showed impaired activity, as assessed by the alloreactive mixed T-lymphocyte reaction. Bevacizumab and sorafenib, but not sunitinib, reversed the inhibitory effects of VEGF, but not of those mediated by tumour supernatants. Dendritic cells matured under the influence of VEGF expressed less human leukocyte antigen-DR (HLA-DR) and CD86, and this effect was restored by bevacizumab and sorafenib. Finally, tumour-cell supernatants decreased interleukin-12 (IL-12) production by mature DC, and such inhibition was not restored by any of the tested drugs, delivered either as single agents or in combination. The deleterious effects of tumour-cell supernatants were mainly mediated by thermostable molecules distinct from VEGF. These results indicate that inhibition of the differentiation of monocytes to DC is a multifactorial effect, and that they support the development of combinations of angiogenesis inhibitors with immunological modulators

Limited Transplantation of Antigen-Expressing Hematopoietic Stem Cells Induces Long-Lasting Cytotoxic T Cell Responses

Harnessing the ability of cytotoxic T lymphocytes (CTLs) to recognize and eradicate tumor or pathogen-infected cells is a critical goal of modern immune-based therapies. Although multiple immunization strategies efficiently induce high levels of antigen-specific CTLs, the initial increase is typically followed by a rapid contraction phase resulting in a sharp decline in the frequency of functional CTLs. We describe a novel approach to immunotherapy based on a transplantation of low numbers of antigen-expressing hematopoietic stem cells (HSCs) following nonmyeloablative or partially myeloablative conditioning. Continuous antigen presentation by a limited number of differentiated transgenic hematopoietic cells results in an induction and prolonged maintenance of fully functional effector T cell responses in a mouse model. Recipient animals display high levels of antigen-specific CTLs four months following transplantation in contrast to dendritic cell-immunized animals in which the response typically declines at 4–6 weeks post-immunization. Majority of HSC-induced antigen-specific CD8+ T cells display central memory phenotype, efficiently kill target cells in vivo, and protect recipients against tumor growth in a preventive setting. Furthermore, we confirm previously published observation that high level engraftment of antigen-expressing HSCs following myeloablative conditioning results in tolerance and an absence of specific cytotoxic activity in vivo. In conclusion, the data presented here supports potential application of immunization by limited transplantation of antigen-expressing HSCs for the prevention and treatment of cancer and therapeutic immunization of chronic infectious diseases such as HIV-1/AIDS

Standards of care for obsessive–compulsive disorder centres

In recent years, many assessment and care units for obsessive–compulsive disorder (OCD) have been set up in order to detect, diagnose and to properly manage this complex disorder, but there is no consensus regarding the key functions that these units should perform. The International College of Obsessive- Compulsive Spectrum Disorders (ICOCS) together with the Obsessive Compulsive and Related Disorders Network (OCRN) of the European College of Neuropsychopharmacology (ECNP) and the Anxiety and Obsessive Compulsive Disorders Section of the World Psychiaric Association (WPA) has developed a stand- ards of care programme for OCD centres. The goals of this collaborative initiative are promoting basic standards, improving the quality of clinical care and enhance the validity and reliability of research results provided by different facilities and countries

Dermatological patients with itch report more stress, stigmatization experience, anxiety and depression compared to patients without itch: Results from a European multi‐centre study

Background: Itch as the most common symptom in dermatology has been shown to be related to psychological factors such as stress, anxiety and depression. Moreover, associations were found between perceived stigmatization and itch. However, studies investigating the differences between patients with dermatoses with and without itch regarding perceived stress, stigmatization, anxiety and depression are missing. Therefore, one of the aims of the second study of the European Society for Dermatology and Psychiatry (ESDaP study II) was to investigate these relationships in a large cohort of patients with different itchy dermatoses. Results: 3399 patients with 14 different itchy dermatoses were recruited at 22 centres in 17 European countries. They filled in questionnaires to assess perceived stigmatization, stress, signs of clinically relevant anxiety or depression, itch‐related quality of life, the overall health status, itch duration, frequency and intensity. The most significant association between the severity of itching and the perception of stress was observed among individuals with rosacea (correlation coefficient r = 0.314). Similarly, the strongest links between itch intensity and experiences of stigmatization, anxiety, and depression were found in patients with seborrheic dermatitis (correlation coefficients r = 0.317, r = 0.356, and r = 0.400, respectively). Utilizing a stepwise linear regression analysis, it was determined that within the entire patient cohort, 9.3% of the variation in itch intensity could be accounted for by factors including gender, levels of anxiety, depression, and perceived stigmatization. Females and individuals with elevated anxiety, depression, and perceived stigmatization scores reported more pronounced itch intensities compared to those with contrary attributes. Conclusion: This study underscores the connection between experiencing itch and its intensity and the psychological strain it places on individuals. Consequently, psychological interventions should encompass both addressing the itch itself and the interconnected psychological factors. In specific cases, it becomes imperative for dermatologists to direct individuals towards suitable healthcare resources to undergo further psychological assessment