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Background: The risk of life-threatening major cardiovascular outcomes among patients with bullous pemphigoid (BP) is inconsistent in the current literature., Objective: To evaluate the risk and prognostic outcomes of myocardial infarction (MI), cerebrovascular accident (CVA), peripheral vascular disease (PVD) and pulmonary embolism (PE) in patients with BP. We additionally aimed to explore the influence of different therapeutic approaches on the risk of these outcomes., Methods: A population-based retrospective cohort study was conducted to compare BP patients (n = 3924) with age-, gender- and ethnicity-matched control subjects (n = 19,280) with regard to incident cases of MI, CVA, PVD and PE. Adjusted hazard ratio (HR) and 95% confidence intervals (CI) were estimated by multivariate Cox regression analysis. Data were retrieved from Clalit Health Services' computerized database., Results: Relative to their matched controls, patients with BP were at an elevated risk of MI (fully-adjusted HR: 1.44; 95% CI: 1.14-1.81; p = 0.002), CVA (fully-adjusted HR: 1.24; 95% CI: 1.06-1.45; p = 0.007), PVD (fully-adjusted HR: 1.60; 95% CI: 1.27-2.03; p = 0.003) and PE (fully-adjusted HR: 1.72; 95% CI: 1.28-2.32; p < 0.008). Patients with BP experienced heightened risk of all-cause mortality in the presence of comorbid MI (fully-adjusted HR: 1.61; 95% CI: 1.44-1.81; p < 0.001), CVA (fully-adjusted HR: 1.70; 95% CI: 1.52-1.89; p < 0.001), PVD (fully-adjusted HR: 1.38; 95% CI: 1.20-1.58; p < 0.001) and PE (fully-adjusted HR: 1.44; 95% CI: 1.10-1.88; p = 0.007). The therapeutic approach utilized to manage BP did not significantly influence the risk of cardiovascular outcomes., Conclusions: BP is associated with an elevated risk of MI, CVA, PVD, PE and cardiovascular mortality. Primary, secondary and tertiary cardiovascular prevention measures should be implemented among patients with BP., (© 2024 The Author(s). Australasian Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Australasian College of Dermatologists.)

Background: There is a long-standing debate if finasteride, a medication used to treat benign prostatic hyperplasia (BPH) and androgenetic alopecia (AGA), can cause psychiatric side effects., Objective: The goal of this large-scale population-based study was to determine whether finasteride therapy for BPH and AGA is associated with the emergence of mental health conditions., Methods: This observational case-control study compared the data from patients with BPH who received finasteride 5 mg daily and patients with AGA who received finasteride 1 mg daily with age- and gender-matched controls. The incidence of psychological health outcomes such as depression, anxiety, neuroses, bipolar disorder, schizophrenia, psychoses and alcohol abuse within 2 years of the initiation of finasteride therapy has been evaluated and compared between the finasteride groups and controls., Results: The BPH group included 307 men with a mean age of 61.5 (±17.4) years and 1218 controls. Mental health outcomes recorded in 2.3% of the patients, with no significant increase in rate when compared to controls. The AGA group consisted of 23,227 men with a mean age of 31.4 (±10.3) years and 39,444 controls. Only One percent of AGA patients developed psychiatric disorders. In comparison to controls, patients with AGA had higher rates of anxiety and depression (0.6% vs. 0.4%, p = 0.04, and 0.5% vs. 0.4%, p = 0.007, respectively). In multivariate regression models, finasteride was found as one of the risk factors for anxiety (OR 1.449, p = 0.002) and depression (OR 1.439, p = 0.003) when stratified to age, sector, socioeconomic status and comorbidities., Conclusions: According to our research, finasteride users had a very low rate of adverse mental health effects, with no increase in psychological sequelae in BPH patients and a slight increase in anxiety and depression in AGA patients., (© 2024 Australasian College of Dermatologists.)

Background: Numerous diseases associated with COVID-19 infection and vaccination have been reported, including conditions such as the autoimmune blistering diseases (AIBD) pemphigus and pemphigoid. However, robust evidence supporting these associations is lacking., Objective: To investigate the risk of developing AIBD following COVID-19 infection and vaccination., Methods: Population-based retrospective cohort study utilizing data from over 112 million patients. The risk of AIBD within three months was compared among three cohorts: COVID-19 infection, COVID-19 vaccination, and controls, along with seven sensitivity analyses., Results: COVID-19 infection was associated with an increased risk of AIBD (HR 1.508, 95% CI 1.260-1.805), with the risk being more pronounced for pemphigus (HR 2.432, 1.618-3.657) compared to bullous pemphigoid (HR 1.376, 1.019-1.857). Conversely, COVID-19 vaccination was associated with an almost halved risk of AIBD (HR 0.514, 0.394-0.672), with the risk reduction most significant for pemphigus (HR 0.477, 0.241-0.946). Comparisons between COVID-19 infection and vaccination revealed a more than threefold increased risk of AIBD in the infection cohort (HR 3.130, 2.411-4.063), particularly for pemphigus (HR 5.508, 2.973-10.205)., Limitations: Retrospective design and potential underreporting of COVID-19 cases and vaccinations., Conclusion: COVID-19 infection significantly increases the risk of AIBD while vaccination appears to reduce this risk., (Copyright © 2024. Published by Elsevier Inc.)

The association of AA with malignancies has been a scope of controversy as the current literature is highly inconsistent in this regard. To evaluate the association between AA and hematological malignancies (HMs) and solid malignancies (SMs) using a large-scale, real-life computerized database. A cross-sectional study was conducted to compare the prevalence of HMs and SMs among patients with AA relative to age-, sex-, and ethnicity-matched control subjects. Chi-square and t-tests were used for univariate analysis, and a logistic regression model was used for multivariate analysis. The study included 51,561 patients with AA and 51,410 controls. AA was significantly associated with HMs (adjusted OR, 1.27; 95% CI, 1.07-1.51; P = 0.006). This association was more robust among patients with late-onset AA (≥ 50 years; OR, 1.33; 95% CI, 1.04-1.71; P = 0.025). On the other hand, AA was not found to be significantly associated with SM (adjusted OR, 0.97; 95% CI, 0.88-1.06; P = 0.487), excluding among patients with alopecia totalis and universalis (OR, 2.10; 95% CI, 1.03-4.27; P = 0.036). In a granular analysis including 5 HMs and 18 SMs, non-Hodgkin lymphoma was the only malignancy that proved positively associated with AA (adjusted OR, 1.32; 95% CI, 1.03-1.69; P = 0.028). AA is associated with HMs but not SMs. Further research is warranted to validate our observations in other study cohorts., (© 2024. The Author(s).)

Competing Interests: Conflicts of interest None disclosed.

Competing Interests: Conflicts of interest None disclosed.

Competing Interests: Conflicts of interest None disclosed.

Background: According to current guidelines, systemic or topical corticosteroids are both recommended as first-line treatments for bullous pemphigoid (BP). There is evidence to suggest that topical application may be associated with a lower risk of mortality. However, there is a lack of comprehensive large-scale data comparing mortality rates, as well as the risk of major adverse cardiac events (MACE), infections and relapse, between systemic and topical corticosteroid treatments., Objectives: To evaluate the risk of death, MACE, infections and relapse in patients with BP treated with systemic or topical corticosteroids., Methods: A population-based retrospective cohort study was performed using the TriNetX US Collaborative Network. As a measure against bias, propensity score matching for age, sex, 10 diseases and 6 medications was done, and 3 sensitivity analyses were conducted., Results: All-time risk of death was increased in US patients with BP exposed to any dose of systemic corticosteroids (n = 2917) vs. patients treated with topical clobetasol propionate [n = 2932; hazard ratio (HR) 1.43, 95% confidence interval (CI) 1.28-1.58 (P < 0.001)]. This was consistent in time-stratified analysis (1- and 3-year mortality rates) and in analysis contrasting prednisone (equivalent) doses of 1-10 mg (low) or 30-100 mg (medium-high) systemic corticosteroid to topical treatment. The increased risk of death in US patients with BP exposed to any dose of systemic corticosteroids vs. topical treatment was accompanied by increased risks for MACE (HR 1.33, 95% CI 1.08-1.64; P = 0.008) and infections (HR 1.33, 95% CI 1.15-1.54; P < 0.001). The risk of continued disease or relapse was decreased in patients treated with systemic vs. topical corticosteroids (HR 0.85, 95% CI 0.77-0.94; P = 0.002). Results regarding mortality and continued disease or relapse persisted in three sensitivity analyses. Potential limitations included the retrospective data collection, bias for treatment selection and miscoding., Conclusions: Pending validation in prospective studies, where feasible - and despite the heightened risk of relapse - topical corticosteroid treatment may be advantageous over systemic corticosteroid treatment owing to its significantly lower risk of death., Competing Interests: Conflict of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

A balanced immune system is essential to maintain adequate host defense and effective self-tolerance. While an immune system that fails to generate appropriate response will permit infections to develop, uncontrolled activation may lead to autoinflammatory or autoimmune diseases. To identify drug candidates capable of modulating immune cell functions, we screened 1200 small molecules from the Prestwick Chemical Library for their property to inhibit innate or adaptive immune responses. Our studies focused specifically on drug interactions with T cells, B cells, and polymorphonuclear leukocytes (PMNs). Candidate drugs that were validated in vitro were examined in preclinical models to determine their immunomodulatory impact in chronic inflammatory diseases, here investigated in chronic inflammatory skin diseases. Using this approach, we identified several candidate drugs that were highly effective in preclinical models of chronic inflammatory disease. For example, we found that administration of pyrvinium pamoate, an FDA-approved over-the-counter anthelmintic drug, suppressed B cell activation in vitro and halted the progression of B cell-dependent experimental pemphigoid by reducing numbers of autoantigen-specific B cell responses. In addition, in studies performed in gene-deleted mouse strains provided additional insight into the mechanisms underlying these effects, for example, the receptor-dependent actions of tamoxifen that inhibit immune-complex-mediated activation of PMNs. Collectively, our methods and findings provide a vast resource that can be used to identify drugs that may be repurposed and used to promote or inhibit cellular immune responses., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Psoriasis (PsO) is currently regarded as a systemic inflammatory disease with a growing burden of post-diagnosis associated comorbidities. To determine the initial burden of comorbiditis we evaluated the comorbidome at PsO onset., Methods: In a matched case-control study, we extracted data on 57,228 patients and 125 morbidities from the Clalit Health Services Israeli insurance database. PsO cases were matched with control individuals by sex and age at enrolment. As pre-existing comorbidities, we considered all conditions already present in controls at the same age as the matched PsO case at the time of their diagnosis. To test for differences in the odds of comorbidities between the case and control groups, logistic regression analyses were run to calculate the odds ratio (OR) for each comorbidity, after which the comorbidome was graphically represented., Results: In this study we enrolled 28,614 PsO patients and 28,614 controls with an average age of 45.3 ± 19.6 years. At the time of diagnosis, PsO patients were more likely to be diagnosed with 2-4 comorbidities (28.8% vs 23.8%) and > 5 (19.6% vs 12.9%,). PsO patients' specific comorbidomes evidenced several pathological cores: autoimmune and inflammatory systemic diseases [i.e., hidradenitis suppurativa (OR 3.55, 95% CI 1.88-7.28) or polymyalgia rheumatica (OR 3.01 95% CI 1.96-4.77)], inflammatory bowel diseases [i.e., Crohn's disease (OR 2.99 95% CI 2.20-4.13)], pulmonary inflammatory diseases [i.e., chronic obstructive pulmonary disease (OR 1.81 95% CI 1.61-2.04)], hepatological diseases [i.e., cirrhosis (OR 2.00 95% CI 1.36-3.00)], endocrine diseases [dysthyroidisms (OR 1.82 95% CI 1.30-2.59)], mental disorders [i.e., depression (OR 1.72 95% CI 1.57-1.87)], and cardiovascular diseases (i.e., hypertension (OR 1.47 95% CI 1.41-1.53)]., Conclusion: The PsO-onset comorbidome may help health professionals plan more comprehensive patient management. By screening for these common PsO-linked conditions, early diagnosis and treatment may become more frequent, thus greatly benefiting patients on their medical journey., (© 2023. The Author(s).)

Background: Safety of dupilumab in atopic dermatitis (AD) was investigated in randomized controlled trials (RCT). However, head-to-head trials comparing with conventional systemic drugs are lacking and large real-world data on the long-term safety profile as compared are scarce., Objective: To compare long-term safety profile of dupilumab with conventional systemic drugs used in the management of moderate to severe AD., Methods: Data from electronic health records of AD patients treated with either dupilumab, azathioprine, Cyclosporine A, mycophenolate mofetil, methotrexate, or oral glucocorticoids were retrieved from the TriNetX US Collaborative Network . Risks of adverse events and new onset of type-2-inflammatory diseases within 5 years after treatment initiation was investigated., Results: 5 propensity-matched cohorts, up to 18,708 individuals per cohort, were created. Dupilumab treatment displayed reduced risk for diseases of the circulatory, the upper respiratory, and the musculoskeletal system, infections, and type 2 diseases as compared to all other treatment options. In contrast risk for conjunctivitis was increased in dupilumab treated patients as compared to mycophenolate mofetil and methotrexate., Conclusion: Here presented data indicates that treatment with dupilumab for AD has reduced risk for adverse effects of conventional systemic drugs and thus might be safer. Obtained data should be verified in prospective studies.

The extracellular matrix of most bacterial biofilms contains polysaccharides, proteins, and nucleic acids. These biopolymers have been shown to mediate fundamental biofilm-related phenotypes including surface attachment, intercellular adhesion, and biocide resistance. Enzymes that degrade polymeric biofilm matrix components, including glycoside hydrolases, proteases, and nucleases, are useful tools for studying the structure and function of biofilm matrix components and are also being investigated as potential antibiofilm agents for clinical use. Dispersin B is a well-studied, broad-spectrum antibiofilm glycoside hydrolase produced by Aggregatibacter actinomycetemcomitans . Dispersin B degrades poly- N -acetylglucosamine, a biofilm matrix polysaccharide that mediates biofilm formation, stress tolerance, and biocide resistance in numerous Gram-negative and Gram-positive pathogens. Dispersin B has been shown to inhibit biofilm and pellicle formation; detach preformed biofilms; disaggregate bacterial flocs; sensitize preformed biofilms to detachment by enzymes, detergents, and metal chelators; and sensitize preformed biofilms to killing by antiseptics, antibiotics, bacteriophages, macrophages, and predatory bacteria. This review summarizes the results of nearly 100 in vitro and in vivo studies that have been carried out on dispersin B since its discovery 20 years ago. These include investigations into the biological function of the enzyme, its structure and mechanism of action, and its in vitro and in vivo antibiofilm activities against numerous bacterial species. Also discussed are potential clinical applications of dispersin B.

Background: Hematologic malignancies (HMs) are well-known underlying comorbidities of pyoderma gangrenosum (PG). However, studies quantifying the likelihood of PG after HMs are yet to be performed., Objective: To investigate the bidirectional association between PG and several HMs, namely acute leukemia, chronic leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma, and multiple myeloma., Methods: A population-based retrospective cohort study was conducted to study the risk of HMs in patients with PG ( n = 302) as compared to age-, sex-and ethnicity-matched control subjects ( n = 1,799). A case-control design was used to estimate the likelihood of PG in individuals with a preexisting history of HMs. Adjusted hazard ratios (HRs) and adjusted odds ratios (ORs) were estimated by Cox regression and logistic regression, respectively., Results: The prevalence of preexisting HM was higher in patients with PG than in controls (6.7% vs. 0.9%, respectively). The likelihood of having PG was significantly greater among patients with a history of HM (adjusted OR, 7.88; 95% CI, 3.85-16.15; p < 0.001), particularly during the first year following the diagnosis. This association was significant for acute leukemia, chronic leukemia, non-Hodgkin lymphoma, and multiple myeloma but not for Hodgkin lymphoma. The incidence rate of HM was 3.3 (95% CI, 1.2-7.4) and 1.6 (95% CI, 0.9-2.6)/1,000 person-years among patients with PG and controls, respectively. Relative to controls, patients with PG were not more likely to develop subsequent HM (adjusted HR, 2.22; 95%CI, 0.77-6.45; p = 0.142). Compared to other patients with PG, those with HM-associated PG experienced an increased all-cause mortality rate (adjusted HR, 2.19; 95%CI, 1.09-4.40; p = 0.028)., Conclusion: HM, particularly acute leukemia and multiple myeloma, are associated with an elevated likelihood of provoking PG., Competing Interests: AC served as an advisor, investigator, or speaker for Abbvie, BI, Dexcel Pharma, Janssen, Novartis, Perrigo, Pfizer, and Rafa. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kridin, Ankary-Khaner, Kridin, Cohen and Badarny.)

Objectives: This study investigated psoriatic arthritis (PsA) risk across varied psoriasis manifestations, considering sex and ethnicity., Methods: Using TriNetX, a federated database encompassing over 120 million electronic health records (EHRs), we performed global retrospective cohort studies. Psoriasis vulgaris (Pso), pustulosis palmoplantaris (PPP), and generalized pustular psoriasis (GPP) cohorts were retrieved using ICD-10 codes. Propensity score matching, incorporating age, sex, and ethnicity, was employed. An alternative propensity matching model additionally included established PsA risk factors., Results: We retrieved data from 486 (Black or African American-stratified, GPP) to 35,281 (Pso) EHRs from the US Collaborative Network. Significant PsA risk variations emerged: Pso carried the highest risk [hazard ratio (HR) 87.7, confidence interval (CI) 63.4-121.1, p  < 0.001], followed by GPP (HR 26.8, CI 6.5-110.1, p  < 0.0001), and PPP (HR 15.3, CI 7.9-29.5, p  < 0.0001). Moreover, we identified significant sex- and ethnicity-specific disparities in PsA development. For instance, compared to male Pso patients, female Pso patients had an elevated PsA risk (HR 1.1, CI 1.1-1.2, p  = 0.002). Furthermore, White Pso patients had a higher likelihood of developing PsA compared to their Black or African American counterparts (HR 1.3, CI 1.04-1.7, p  = 0.0244). We validated key findings using alternative propensity matching strategies and independent databases., Conclusion: This study delineates nuanced PsA risk profiles across psoriasis forms, highlighting the pivotal roles of sex and ethnicity. Integrating these factors into PsA risk assessments enables tailored monitoring and interventions, potentially impacting psoriasis patient care quality., Competing Interests: DT has received honoraria or fees for serving on advisory boards, as a speaker, as a consultant from AbbVie, Amgen, Almirall, Beiersdorf, Bristol-Meiers-Squibb, Boehringer Ingelheim, Galapagos, Leo Pharma, Merck Sharp & Dohme, Morphosys, Lilly, Novartis, Janssen-Cilag, Pfizer, Regeneron, Sanofi, Hexal, Sun Pharmaceuticals, and UCB and grants from Leo Pharma and Novartis. RL has received honoraria for speaking or consulting or has obtained research grants from Monasterium Laboratories, Novartis, Lilly, Bayer, Dompe, Synthon, Argen-X, and Incyte during the last 3 years. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Gershater, Bieber, Vorobyev, Ludwig, Zirpel, De Luca, Thaci, Kridin and Ludwig.)

A knowledge gap exists regarding the association between vitiligo and rheumatoid arthritis (RA) due to the absence of large-scale cohort studies designed to investigate this association. To investigate the bidirectional epidemiological association between vitiligo and RA. A population-based study was conducted using Clalit Health Services (CHS) database (2002-2019) using both a cohort study and a case-control study design. Adjusted hazard ratio (HR) and odds ratio (OR) were calculated by multivariate Cox and logistic regressions, respectively. Overall, 20,851 vitiligo patients and 102,475 controls were included. The incidence of new-onset RA was 4.1 (95% CI 3.0-5.4) and 2.9 (95% CI 2.4-3.3) cases per 10,000 person-years among patients with vitiligo and controls, respectively. Patients with vitiligo had a significantly increased risk of developing new-onset RA (adjusted HR, 1.44; 95% confidence interval [CI], 1.02-2.02, P = 0.036). The likelihood of having vitiligo was significantly elevated after a preexisting diagnosis of RA (adjusted OR, 1.67; 95% CI, 1.38-2.03; P < 0.001). Relative to the remaining patients with vitiligo, those with vitiligo and comorbid RA demonstrated an elevated risk of all-cause mortality (adjusted HR, 1.61; 95% CI, 1.03-2.51; P = 0.037). Our study confirms the bidirectional association between vitiligo and RA. Physicians treating patients with vitiligo should be aware of the association in clinical practice., (© 2024. The Author(s).)

Khalaf Kridin Department of Dermatology, Rambam Health Care Campus, Haifa, Israel Abstract: Pemphigus vulgaris (PV) is a life-threatening disease belonging to the pemphigus group of autoimmune intra-epidermal bullous diseases of the skin and mucosae. The therapeutic management of PV remains challenging and, in some cases, conventional therapy is not adequate to induce clinical remission. The cornerstone of PV treatment remains systemic corticosteroids. Although very effective, long-term corticosteroid administration is characterized by substantial adverse effects. Corticosteroid-sparing adjuvant therapies have been employed in the treatment of PV, aiming to reduce the necessary cumulative dose of corticosteroids. Specifically, immunosuppressive agents such as azathioprine and mycophenolate mofetil are widely used in PV. More recently, high-dose intravenous immunoglobulins, immunoadsorption, and rituximab have been established as additional successful therapeutic options. This review covers both conventional and emerging therapies in PV. In addition, it sheds light on potential future treatment strategies for this disease. Keywords: azathioprine, meycophenolate mofetil, rituximab, intravenous immunoglobulins, immunoadsporption, emerging

Objective: Our knowledge about the association between vitiligo and Parkinson's disease (PD) is sparse. We sought to investigate the bidirectional epidemiological association between vitiligo and PD., Methods: A population-based study was conducted using Clalit Health Services (CHS) database (2002-2019) using both a cohort study and a case-control study design. Adjusted hazard ratio (HR) and odds ratio (OR) were calculated by multivariate Cox and logistic regressions, respectively., Results: Overall, 20,851 vitiligo patients and 102,475 controls were included. The incidence of new-onset PD was 2.9 (95% CI, 2.1-4.1) and 4.3 (95% CI, 3.8-4.9) cases per 10,000 person-years among patients with vitiligo and controls, respectively. Patients with vitiligo had a significantly decreased risk of developing new-onset PD [adjusted HR, 0.62; 95% confidence interval (CI), 0.43-0.89, p = 0.009]. On the other hand, the likelihood of having vitiligo after a preexisting diagnosis of PD was not statistically different (adjusted OR, 0.80; 95% CI, 0.61-1.06; p = 0.117). Relative to the remaining patients with vitiligo, those with vitiligo and comorbid PD experienced an elevated risk of all-cause mortality (adjusted HR, 2.63; 95% CI, 1.82-3.80; p < 0.001) and higher prevalence of cardiometabolic comorbidities., Conclusion: Vitiligo is associated with a lower risk of developing PD. The presence of comorbid PD predisposes patients with vitiligo to elevated mortality and cardiometabolic outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kridin, Ofir, Weinstein and Badarny.)

Introduction: Uncertainty surrounds the optimal routine laboratory monitoring in acne patients treated with isotretinoin., Objective: Our aim was to evaluate the risk of mild and severe laboratory abnormalities in patients with acne starting isotretinoin versus oral antibiotic treatment., Methods: A global population-based retrospective cohort study assigned two groups of patients with acne-prescribed isotretinoin (n = 79,012) and oral antibiotics (n = 79,012). Comprehensive propensity-score matching was conducted., Results: Compared to acne patients treated with oral antibiotics, those under isotretinoin demonstrated an increased risk of grade ≥3 hypertriglyceridemia (hazard ratio [HR], 7.85; 95% confidence interval [CI], 5.58-11.05; P < 0.001) and grade ≥3 elevated aspartate transaminase (AST) levels (HR, 1.45; 95% CI, 1.13-1.85; P = 0.003) within the initial 3 months of treatment. The absolute risk of these abnormalities among isotretinoin initiators was 0.4% and 0.2%, respectively. The risk difference of these findings was clinically marginal: 3 and 1 additional cases per 1,000 patients starting isotretinoin, respectively. There was no significant risk of grade ≥3 impairment in cholesterol, alanine transaminase, gamma-glutamyl transferase, or creatinine levels under isotretinoin. Most laboratory abnormalities were documented 1-3 months after drug initiation in time-stratified analysis., Conclusion: Isotretinoin is associated with a clinically marginal increased risk of severe hypertriglyceridemia and hypertransaminasemia. Routine blood testing should be performed 1-3 months after commencing therapy., (© 2024 The Authors. International Journal of Dermatology published by Wiley Periodicals LLC on behalf of the International Society of Dermatology.)

Background: The commensal skin bacterium Cutibacterium acnes plays a role in the pathogenesis of acne vulgaris and also causes opportunistic infections of implanted medical devices due to its ability to form biofilms on biomaterial surfaces. Poly- β -(1→6)- N -acetyl-D-glucosamine (PNAG) is an extracellular polysaccharide that mediates biofilm formation and biocide resistance in a wide range of bacterial pathogens. The objective of this study was to determine whether C. acnes produces PNAG, and whether PNAG contributes to C. acnes biofilm formation and biocide resistance in vitro ., Methods: PNAG was detected on the surface of C. acnes cells by fluorescence confocal microscopy using the antigen-specific human IgG1 monoclonal antibody F598. PNAG was detected in C. acnes biofilms by measuring the ability of the PNAG-specific glycosidase dispersin B to inhibit biofilm formation and sensitize biofilms to biocide killing., Results: Monoclonal antibody F598 bound to the surface of C. acnes cells. Dispersin B inhibited attachment of C. acnes cells to polystyrene rods, inhibited biofilm formation by C. acnes in glass and polypropylene tubes, and sensitized C. acnes biofilms to killing by benzoyl peroxide and tetracycline., Conclusion: C. acnes produces PNAG, and PNAG contributes to C. acnes biofilm formation and biocide resistance in vitro . PNAG may play a role in C. acnes skin colonization, biocide resistance, and virulence in vivo ., Competing Interests: JK serves as an advisor for, owns equity in, and receives royalties from Kane Biotech Inc., Winnipeg, Canada. This company is developing antibiofilm applications related to dispersin B. GP is an inventor of intellectual properties (human monoclonal antibody to PNAG and PNAG vaccines) that are licensed by Brigham and Women’s Hospital to Alopexx, Inc., an entity in which GP also holds equity. As an inventor of intellectual properties, GP also has the right to receive a share of licensing-related income (royalties, fees) through Brigham and Women’s Hospital from Alopexx, Inc. GP’s interests were reviewed and are managed by the Brigham and Women’s Hospital and Mass General Brigham in accordance with their conflict of interest policies. CC-B is an inventor of intellectual properties (use of human monoclonal antibody to PNAG and use of PNAG vaccines) that are licensed by Brigham and Women’s Hospital to Alopexx, Inc. As an inventor of intellectual properties, CC-B also has the right to receive a share of licensing-related income (royalties, fees) through Brigham and Women’s Hospital from Alopexx, Inc. NY, MS, and ME are employees of Kane Biotech Inc., manufacturer of dispersin B (DispersinB®), and own company stocks and stock options. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kaplan, Cywes-Bentley, Pier, Yakandawala, Sailer, Edwards and Kridin.)

Introduction: Since during the COVID-19 pandemic nail psoriasis was evaluated exclusively with teledermatology, dermatologists started to face the difficulty in rating it concurrent with other onycopathies (i.e., onychotillomania and onychophagy). Thus, we aimed to improve the existing severity scores and verify the value in different clinical settings (i.e., in person vs. teledermatology (video or picture))., Methods: This multicenter prospective observational study evaluated patients with nail psoriasis and screened them for onychophagy or onychotillomania in telemedicine from May 2020 to January 2021. For therapeutic purposes patients with nail psoriasis were followed and rated with the Nijmegen-Nail psoriasis Activity Index tooL (N-NAIL) for 9 months; at the same time, N-NAIL and a new dedicated index that monitor also the changes in nail dimension (Galeazzi-(G) N-NAIL) were tested for accuracy. We assessed inter- and intraobserver agreement for the three different settings (in person, video, and pictures)., Results: In our cohort of 382 patients with nail psoriasis after a clinical and dermatoscopic assessment we found 20 (5.24%) patients with onychophagy and 17 (4.45%) patients with onychotillomania. Analysis of the impact of nail psoriasis on patients revealed that onycholysis and crumbing, followed by subungual hyperkeratosis, were the clinical signs that prevalently bothered patients. N-NAIL score displayed moderate intra- and interobserver agreement. Over the 9 months follow-up, N-NAIL vs. GN-NAIL displayed a solid correlation at all the examined time points, i.e., baseline and after 3, 6, and 9 months., Conclusion: We created a new tool, the GN-NAIL capable of efficiently scoring nail psoriasis severity in complex cases, such as patients with onychotillomania and onychophagy, and monitor response to treatment during the COVID-19 pandemic., (© 2024. The Author(s).)

Background: Prurigo nodularis (PN) presents with intensely itchy hard nodules. Despite being limited to the skin, PN was noted to be associated with systemic diseases including diabetes and chronic renal failure. In previous smaller retrospective studies, several cardiac and vascular diseases were found more frequently in patients with PN. However, small cohort sizes, partially discrepant outcomes, missing data, and incomplete risk assessment limit these findings., Methods: Electronic health records (EHR)s of 64,801 patients (59.44% females) with PN and an equal sized propensity-matched control group were retrieved. In these cohorts, the risks to develop cardiac and vascular diseases and mortality following the diagnosis of PN were determined. Sub-analyses included stratification for sex, ethnicity, and treatments., Findings: PN was associated with a higher risk for a broad range of acute cardiac events including heart failure and myocardial infarction. For example, the hazard ratio of myocardial infarction was 1.11 (95%-CI: 1.041-1.184, p = 0.0015) following PN diagnosis. Also, all-cause mortality was higher in patients with PN. Further, chronic vascular as well as structural heart diseases, e.g., peripheral arterial disease, chronic ischaemic heart disease and valval disorders were found more frequently following a PN diagnosis. Risks were more pronounced in white and female patients. Having established an increased risk for death and cardiovascular disease, we next addressed if dupilumab that has been recently licenced for use in this indication can modulate these risks. The risk of death but not of any cardiovascular disease was slightly reduced in patients with PN treated with dupilumab as opposed to those treated with systemic therapies other than dupilumab. The study is limited by retrospective data collection and reliance on ICD10-disease classification., Interpretation: PN is associated with higher mortality and an increased risk for the development of a wide range of cardiac and vascular diseases. Health care professionals should take this into account when managing patients with PN., Funding: This work was supported by the University of Lübeck, the Deutsche Forschungsgemeinschaft and the State of Schleswig-Holstein., Competing Interests: Declaration of interests The authors declare that this study was designed and conducted in the absence of any financial or commercial relationships that could be construed as a potential conflict of interest. HZ received travel honoraria and support for meeting attendance from TriNetX, Pfizer, UCB Pharma, Almirall and Janssen unrelated to the current work., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The association of autoimmune bullous diseases (AIBDs) with thyroid disorders remains to be profoundly investigated. Objective: To evaluate the epidemiological association between six AIBDs and thyroid disorders. Methods: A population‐based cross‐sectional study enrolled patients with bullous pemphigoid (BP), mucous membrane pemphigoid (MMP), epidermolysis bullosa acquisita (EBA), pemphigoid gestationis (PG), pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Patients with these six AIBDs were compared with six age‐ and sex‐matched control groups regarding the prevalence of thyroiditis and hyperthyroidism. Logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI) for thyroid disorders. Results: The study population included 1,743, 251, 106, 126, 860 and 103 patients with BP, MMP, EBA, PG, PV and PF respectively. The corresponding control groups consisted of 10,141, 1,386, 606, 933, 5,142 and 588 matched controls respectively. A significant association was found between thyroiditis and BP (OR, 1.98; 95% CI, 1.18–3.35; P = 0.010), MMP (OR, 7.02; 95% CI, 1.87–26.33; P = 0.004) and PV (OR, 2.73; 95% CI, 1.45–5.15; P = 0.002). With regards to hyperthyroidism, PF was the only AIBD to demonstrate significant comorbidity (OR, 2.42; 95% CI, 1.13–5.21; P = 0.024). EBA and PG were not found to cluster with any of the investigated thyroid conditions. Conclusion: Patients with BP, MMP, PV and PF experience an elevated burden of thyroid disorders. Patients with these AIBDs presenting with suggestive symptoms may be carefully screened for comorbid thyroid disorders. [ABSTRACT FROM AUTHOR]

Background: The risk of gout amid patients with acne keloidalis nuchae (AKN) has not been investigated in the past., Objective: To assess the risk of developing gout among patients with AKN relative to control subjects., Methods: A population-based retrospective study followed patients with AKN (n = 2677) and age-, sex-, and ethnicity-matched control subjects (n = 13 190). The incidence of new-onset gout was compared between the two groups. Hazard ratio (HR) for the risk of gout was obtained using a multivariate Cox regression model., Results: The incidence rate of gout was 1.12 (95% CI, 0.68-1.76) and 0.48 (95% CI, 0.34-0.66) per 1000 person-years among patients with AKN and controls, respectively. The crude risk of developing gout was significantly higher in patients with AKN (HR, 2.27; 95% CI, 1.26-4.10; p = 0.007). After controlling for age, sex, and ethnicity, AKN emerged as an independent risk factor of gout (adjusted HR, 2.34; 95% CI, 1.29-4.22; p = 0.005). When adjusting for other confounders such as body mass index, diabetes mellitus, hypertension, and dyslipidemia, the risk of gout in AKN fell out of significance (adjusted HR, 1.39; 95% CI, 0.73-2.65; p = 0.311), CONCLUSION: Patients with AKN experience an increased risk of gout. The risk is not independent and is mainly mediated through the metabolic comorbidities typifying AKN. We recommend screening for gout in patients with suggestive complaints., (© 2022 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Objectives: The aims of the study are to investigate the distribution and frequency of different sexually transmitted diseases (STDs) among a large study population of individuals undergoing STD investigation both in inpatient and STD clinic settings and to evaluate influence of test anonymity on the positivity rate of pathogens., Material and Methods: A retrospective study retrieved epidemiologic data from the following 3 sources: a secondary referral hospital and 2 STD clinics in Northern Israel. Positivity rate of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Mycoplasma genitalium , and Trichomonas vaginalis (TV) was assessed and stratified based on age, sex, site of sampling, and anonymity of test. Adjusted odds ratios (ORs) were calculated by multivariable logistic regression., Results: Overall, 3,753 assays were performed on 2,407 patients who were screened for STD. Chlamydia trachomatis (4.8%) was the most frequently detected STD, followed by NG (2.1%), MG (1.9%), and TV (0.6%). Mycoplasma genitalium (OR, 4.32; 95% CI, 1.70-10.97; p = .001) and NG (OR, 6.08; 95% CI, 2.18-16.96; p < .001) were significantly associated with male sex, while TV was more frequently encountered among female individuals (OR, 4.34; 95% CI, 1.49-12.50; p = .003). Mycoplasma genitalium infection was detected most commonly by urine samples, while rectal swabs were the leading source of positive tests for CT. Compared with fully identified patients, those tested anonymously were 6-fold more likely to be tested positive for TV (adjusted OR, 6.49; 95% CI, 2.06-20.42; p = .001)., Conclusions: Chlamydia trachomatis and NG are the leading non-HIV STDs in Northern Israel. Anonymous tests predict higher positivity of TV. Rectal sampling should be increasingly used because of its efficacy in detecting CT infections., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2022, ASCCP.)

Bullous pemphigoid is an autoimmune blistering disease caused by autoantibodies against components of the cutaneous basement membrane zone. Autoantibodies lead to complement-dependent and -independent inflammation and blistering. Blister fluid is a valuable biologic resource, as it provides insight into both systemic and local microenvironment responses. Here, we utilized liquid chromatography with tandem mass spectrometry to characterize the bullous pemphigoid blister fluid proteome. We then depleted exosomes to better understand the exosomal versus non-exosomal proteome. We identified 339 proteins in the blister fluid of bullous pemphigoid patients. Gene ontology demonstrated enrichment of several key biologic processes including innate immune response, neutrophil degranulation, platelet degranulation, and complement activation. Exosome depletion resulted in a significant decrease in normalized reporter intensities of 192 proteins, consistent with our observation of a large number of exosomal proteins found in the blister fluid. We then compared the bullous pemphigoid blister fluid proteome to prior proteomic datasets in suction blister fluid, snake bites, and thermal burns, identifying 76 proteins unique to bullous pemphigoid. These include major basic protein, eosinophil peroxidase, galectin-10, and the immunoglobulin epsilon heavy constant region, consistent with tissue eosinophilia. We lastly validated several previously reported blister fluid exosomal components. Blister fluid in bullous pemphigoid contains a mixture of numerous biologic processes. While many of these processes are shared with blistering from alternative causes, we have identified several notable features unique to bullous pemphigoid., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Cancer risk after long-term exposure to interleukin (IL)-23 inhibitors (IL-23i) and IL-17 inhibitors (IL-17i) remains to be delineated., Objective: To evaluate the risk of malignancies in patients with psoriasis treated with IL-23i and IL-17i relative to those prescribed tumour necrosis factor inhibitors (TNFi) during the first 5 years following drug initiation., Methods: A global population-based cohort study included two distinct analyses comparing patients with psoriasis under different therapeutic modalities; (i) new users of IL-17i(n = 15,331) versus TNFi (n = 15,331) and (ii) new users of IL-23i (n = 5832) versus TNFi (n = 5832)., Results: Patients prescribed IL-17i experienced a decreased risk of non-Hodgkin lymphoma (NHL; HR, 0.58; 95% CI, 0.40-0.82; p = 0.002), colorectal cancer (HR, 0.68; 95% CI, 0.49-0.95; p = 0.024), hepatobiliary cancer (HR, 0.68; 95% CI, 0.58-0.80; p < 0.001), ovary cancer (HR, 0.48; 95% CI, 0.29-0.81; p = 0.005), melanoma (HR, 0.52; 95% CI, 0.37-0.73; p < 0.001), and basal cell carcinoma (BCC; HR, 0.57; 95% CI, 0.48-0.67; p < 0.001). IL-23i was associated with a reduced risk of NHL (HR, 0.39; 95% CI, 0.19-0.78; p = 0.006), hepatobiliary cancer (HR, 0.44; 95% CI, 0.31-0.62; p < 0.001) and BCC (HR, 0.76; 95% CI, 0.57-0.99; p = 0.046). In a sensitivity analysis comparing patients managed by IL-17i and IL-23i with their biologic-naïve counterparts, these classes were associated with decreased risk of several malignancies., Conclusion: IL-17i and IL-23i are associated with decreased risk of several malignancies. These findings should be considered prior to the prescription of biologics., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Competing Interests: Conflicts of interest None disclosed.

The association of hidradenitis suppurativa (HS) and asthma remains to be investigated. To assess the bidirectional association between HS and asthma. A population-based study was conducted to compare HS patients (n = 6779) with age-, sex-, and ethnicity-matched control subjects (n = 33,259) with regard to the incidence of new onset and the prevalence of preexisting asthma. Adjusted hazard ratios (HRs) and adjusted odds ratios (ORs) were calculated. The prevalence of preexisting asthma was higher in patients with HS relative to controls (9.6% vs. 6.9%, respectively; P < 0.001). The odds of HS were 1.4-fold greater in patients with a history of asthma (fully adjusted OR 1.41; 95% CI 1.27-1.55; P < 0.001). The incidence rate of new-onset asthma was estimated at 9.0 (95% CI 6.3-12.7) and 6.2 (95% CI 5.1-7.5) cases per 10,000 person-years among patients with HS and controls, respectively. The risk of asthma was not statistically different in patients with HS and controls (fully adjusted HR 1.53; 95% CI 0.98-2.38; P = 0.062). Relative to other patients with HS, those with HS and comorbid asthma were younger at the onset of HS (30.7 [14.7] vs. 33.3 [15.1], respectively; P < 0.001) and had a comparable risk of all-cause mortality (adjusted HR 0.86; 95% CI 0.44-1.68; P = 0.660). A history of asthma confers susceptibility to subsequent development of HS. This observation is of importance for clinicians managing both patients with HS and asthma. Further research is warranted to elucidate the pathomechanism underlying this finding., (© 2023. The Author(s).)

Background: Although bullous pemphigoid (BP), atopic dermatitis (AD), and allergic rhinitis (AR) are associated with shared pathogenic mechanisms the epidemiological relationship between these conditions remains to be investigated., Objective: To evaluate the bidirectional association of BP with AD and AR., Methods: A population-based retrospective cohort study was performed comparing BP patients (n = 3924) with age-, sex-, and ethnicity-matched control subjects (n = 19,280), with respect to incident cases of AD and AR. A case-control design was additionally adopted to assess the odds of BP in individuals with a preexisting diagnosis of AD and AR., Results: The odds of BP was increased after a preexisting diagnosis of AD (fully adjusted odds ratio, 1.76; 95% confidence interval [CI], 1.44-2.15; P < 0.001) and AR (fully adjusted odds ratio, 1.13; 95% CI, 1.01-1.28; P = 0.047). Patients with BP were at an increased risk of subsequent AD (fully adjusted hazard ratio, 2.00; 95% CI, 1.60-2.51; P < 0.001) but not AR (fully adjusted hazard ratio, 1.00; 95% CI, 0.83-1.20; P = 0.997). Compared with other patients with BP, those with BP and comorbid AD and AR were more frequently managed by adjuvant drugs and long-term systemic and topical corticosteroids and had decreased all-cause mortality., Conclusions: A history of AD and AR confers susceptibility to the development of BP. Awareness of this association may be of help for physicians managing patients with these diseases., Competing Interests: The authors have no funding or conflicts of interest to declare., (Copyright © 2021 American Contact Dermatitis Society. All Rights Reserved.)

Background: The association of vitiligo with psoriasis is inconsistent in the current literature., Objective: To assess the bidirectional association between vitiligo and psoriasis., Methods: A population-based study was performed to compare vitiligo patients (n = 20,851) with age-, sex- and ethnicity-matched control subjects (n = 102,475) regarding the incidence of new-onset and the prevalence of preexisting psoriasis. Adjusted hazard ratios (HRs) and adjusted odds ratios (ORs) were calculated by cox regression and logistic regression, respectively., Results: The incidence rate of new-onset psoriasis was estimated at 7.9 (95% CI 6.4-9.7) and 4.7 (95% CI 4.1-5.3) cases per 10,000 person-years among patients with vitiligo and controls, respectively. Patients with vitiligo experienced an increased risk of psoriasis (fully-adjusted HR 1.71; 95% CI 1.35-2.17; P < 0.001). On the other hand, the odds of vitiligo were only marginally elevated among patients with preexisting psoriasis (fully-adjusted OR 1.19; 95% CI 1.01-1.40; P = 0.051). Compared to other patients with vitiligo, those with vitiligo and comorbid psoriasis were older at the onset of the disease and had a greater prevalence of metabolic and cardiovascular comorbidities., Conclusions: A diagnosis of vitiligo predisposes individuals to develop subsequent psoriasis. Clinicians managing dermatologic patients ought to be aware of this comorbidity. Further research is required to explicate the pathomechanism underlying this epidemiological observation., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)