Risk and timing of isotretinoin-related laboratory disturbances: a population-based study.

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.

Telemedicine in Nail Psoriasis: Validation of a New Tool to Monitor (In-Person, In-Picture, and In-Video) Nail Psoriasis Severity in Patients with Concurrent Onychophagia and Onychotillomania.

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.

Comparing the risk of death, major adverse cardiac events, and relapse in bullous pemphigoid patients treated with systemic or topical corticosteroids.

BACKGROUND: According to current guidelines, systemic or topical corticosteroids are recommended as first-line treatments for bullous pemphigoid (BP). There is evidence suggesting 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 BP patients treated with systemic or topical corticosteroids. METHODS: A population-based retrospective cohort study was performed in the TriNetX US Collaborative Network. As a measure against bias, propensity-score matching for age, sex, ten diseases and six medications, and three sensitivity analyses were conducted. RESULTS: All-time risk of death was increased in US BP patients exposed to any dose of systemic corticosteroids (n=2,917) compared to topical clobetasol propionate treated patients (n=2,932, hazard ratio [HR], 1.43, 95% confidence interval [CI] 1.28-1.58, p<0.0001). This was consistent in time-stratified analysis (1- and 3-year mortality rates), and in analysis contrasting prednisone (equivalent) does of 1-10 mg (low) or 30-100 mg (medium-high) systemic corticosteroid to topical treatment. The increased risk of death in US BP patients exposed to any dose of systemic corticosteroids compared to topical treatment was accompanied by increased risks for MACE (HR 1.33, CI 1.08-1.64, p=0.0075) and infections (HR 1.33, CI 1.15-1.54, p=0.0001). The risk of continued disease or relapse was decreased in patients treated with systemic as opposed to topical corticosteroid (HR 0.85, CI 0.77-0.94, p=0.0016). Results regarding mortality and continued disease or relapse persisted in three of three sensitivity analyses. Potential limitations are the retrospective data collection, bias for treatment selection and miscoding. CONCLUSION: Pending validation in prospective studies, where feasible, and despite the heightened risk of relapse, topical corticosteroid treatment may be advantageous compared to systemic corticosteroid treatment due to its significantly lower risk of death.

Poly-ß-(1→6)-N-acetyl-D-glucosamine mediates surface attachment, biofilm formation, and biocide resistance in Cutibacterium acnes.

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-ß-(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.

Increased cardiovascular risks and mortality in prurigo nodularis: a global cohort study.

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.

Are interleukin 17 and interleukin 23 inhibitors associated with malignancies?-Insights from an international population-based study.

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.

The Prevalent Comorbidome at the Onset of Psoriasis Diagnosis.

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.

A history of asthma is associated with susceptibility to hidradenitis suppurativa: a population-based longitudinal study.

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.

Improvement in Endothelial Function in Men Taking Phosphodiesterase Type 5 Inhibitors for Erectile Dysfunction.

BACKGROUND: The purpose of this research was to explore the mechanistic protective cardiovascular effects of phosphodiesterase-5 inhibitors (PDE5-Is) in males with erectile dysfunction. Erectile dysfunction and endothelial dysfunction both precede clinical atherosclerosis. Studies have shown that treatment for erectile dysfunction with PDE5-Is decreased death, heart failure, myocardial infarction, and revascularization in males with erectile dysfunction who had previous myocardial infarction, and cardiovascular events. METHODS: This was a pilot study that recruited 5 men with erectile dysfunction without cardiovascular disease. Endothelial function (flow-mediated percent change of the diameter of the brachial artery), erectile dysfunction grade, high-sensitivity C-reactive protein, and body mass index were measured before and 3 months after starting treatment with tadalafil, 5 mg daily. Pearson's analysis was performed to study a correlation between the change in erectile dysfunction and the change in endothelial function. RESULTS: A significant correlation was found between changes in flow-mediated percent change of the diameter of the brachial artery and changes in erectile dysfunction following the administration of tadalafil (P = .010; Pearson correlation coefficient = 0.959). No change was observed in C-reactive protein or weight. CONCLUSIONS: Erectile dysfunction and endothelial dysfunction are risk factors for cardiovascular disease. Our study showed that PDE5-Is improved endothelial function and erectile dysfunction (with a significant correlation). Improving endothelial function could be the mechanism that leads to a reduction in cardiovascular events and death in men with erectile dysfunction treated with PDE5-Is.

Evaluating the risk of infections under interleukin 23 and interleukin 17 inhibitors relative to tumour necrosis factor inhibitors - A population-based study.

BACKGROUND: The risk of infections among patients with psoriasis undergoing interleukin (IL)-23 inhibitors (IL-23i) and IL-17 inhibitors (IL-17i) is yet to be exhaustively determined. OBJECTIVE: To assess the risk of infectious complications in patients with psoriasis managed by IL-23i and IL-17i with tumour necrosis factor inhibitors (TNFi) as a comparator. METHODS: A global cohort study comprised two distinct analyses comparing patients with psoriasis under different therapeutic modalities; (i) new users of IL-23i (n = 5272) versus TNFi (n = 5272) and (ii) new users of IL-17i (n = 15,160) versus TNFi (n = 15,160). Study groups were compared regarding the risk of 26 different infections. Propensity score matching was conducted to optimize between-group comparability. RESULTS: Patients under IL-23i had a lower risk of otitis media (HR, 0.66; 95% CI, 0.44-0.97), encephalitis (HR, 0.18; 95% CI, 0.04-0.78), herpes zoster (HZ; HR, 0.58; 95% CI, 0.41-0.82), hepatitis B virus (HBV) reactivation (HR, 0.24; 95% CI, 0.12-0.47), cytomegalovirus (HR, 0.25; 95% CI, 0.07-0.86), influenza (HR, 0.52; 95% CI, 0.38-0.71) and parasitic diseases (HR, 0.78; 95% CI, 0.64-0.95). IL-17i was associated with a decreased risk of pneumonia (HR, 0.76; 95% CI, 0.68-0.85), septicaemia (HR, 0.84; 95% CI, 0.72-0.97), upper respiratory tract infection (HR, 0.84; 95% CI, 0.77-0.92), HZ (HR, 0.79; 95% CI, 0.67-0.92), HBV (HR, 0.59; 95% CI, 0.46-0.76) and hepatitis C virus (HR, 0.71; 95% CI, 0.57-0.88) reactivation, cytomegalovirus (HR, 0.58; 95% CI, 0.36-0.93), Epstein-Barr virus (HR, 0.38; 95% CI, 0.19-0.75), influenza (HR, 0.70; 95% CI, 0.61-0.81) and parasitic diseases (HR, 0.80; 95% CI, 0.72-0.88). CONCLUSION: Compared with TNFi, IL-23i and IL-17i are associated with decreased risk of several infectious diseases. These agents might be preferred in patients with susceptibility to infections.

Cutaneous lupus erythematosus is associated with an increased risk of cardiac and vascular diseases: a large-scale, propensity-matched global retrospective cohort study.

BACKGROUND: Autoimmune skin diseases can expedite various systemic sequelae involving other organs. Although limited to the skin, cutaneous lupus erythematosus (CLE) was noted to be associated with thromboembolic diseases. However, small cohort sizes, partially discrepant outcomes, missing data on CLE subtypes, and incomplete risk assessment limits these findings. METHODS: The Global Collaborative Network of TriNetX provides access to medical records of more than 120 million patients worldwide. We used TriNetX to elucidate the risk for cardiac and vascular diseases after diagnosis of CLE, and its subtypes chronic discoid (DLE) and subacute cutaneous lupus erythematosus (SCLE). We included 30,315 CLE, 27,427 DLE, and 1613 SCLE patients. We performed propensity-matched cohort studies determining the risk to develop cardiac and vascular diseases (ICD10CM:I00-99) following diagnosis of CLE, DLE, or SCLE. Patients with systemic lupus erythematosus were excluded. FINDINGS: We document that CLE and its subtype DLE but less so SCLE are associated with a higher risk for various cardiac and vascular diseases. This included predominantly thromboembolic events such as pulmonary embolism, cerebral infarction, and acute myocardial infarction, but also peripheral vascular disease and pericarditis. For example, the hazard ratio of arterial embolism and thrombosis was 1.399 (confidence interval: 1.230-1.591, p < 0.0001) following CLE diagnosis. The study is limited by retrospective data collection and reliance on ICD10-disease classification. INTERPRETATION: CLE and its major subtype DLE are associated with an increased risk for the development of a wide range of cardiac and vascular diseases. FUNDING: This research was funded by Deutsche Forschungsgemeinschaft (EXC 2167, CSSL/CS01-2022) and the Excellence-Chair Program of the State of Schleswig-Holstein.