Hematological malignancy-associated pyoderma gangrenosum: evaluating the magnitude of the association.

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.

Differential risks of psoriatic arthritis development in patients with varied psoriasis manifestations: a sex- and ethnicity-specific analysis.

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.

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.

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.

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.

S2k guidelines on the management of paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome initiated by the European Academy of Dermatology and Venereology (EADV).

BACKGROUND: Paraneoplastic pemphigus (PNP), also called paraneoplastic autoimmune multiorgan syndrome (PAMS), is a rare autoimmune disease with mucocutaneous and multi-organ involvement. PNP/PAMS is typically associated with lymphoproliferative or haematological malignancies, and less frequently with solid malignancies. The mortality rate of PNP/PAMS is elevated owing to the increased risk of severe infections and disease-associated complications, such as bronchiolitis obliterans. OBJECTIVES: These guidelines summarize evidence-based and expert-based recommendations (S2k level) for the clinical characterization, diagnosis and management of PNP/PAMS. They have been initiated by the Task Force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology with the contribution of physicians from all relevant disciplines. The degree of consent among all task force members was included. RESULTS: Chronic severe mucositis and polymorphic skin lesions are clue clinical characteristics of PNP/PAMS. A complete assessment of the patient with suspected PNP/PAMS, requiring histopathological study and immunopathological investigations, including direct and indirect immunofluorescence, ELISA and, where available, immunoblotting/immunoprecipitation, is recommended to achieve a diagnosis of PNP/PAMS. Detection of anti-envoplakin antibodies and/or circulating antibodies binding to the rat bladder epithelium at indirect immunofluorescence is the most specific tool for the diagnosis of PNP/PAMS in a patient with compatible clinical and anamnestic features. Treatment of PNP/PAMS is highly challenging. Systemic steroids up to 1.5 mg/kg/day are recommended as first-line option. Rituximab is also recommended in patients with PNP/PAMS secondary to lymphoproliferative conditions but might also be considered in cases of PNP/PAMS associated with solid tumours. A multidisciplinary approach involving pneumologists, ophthalmologists and onco-haematologists is recommended for optimal management of the patients. CONCLUSIONS: These are the first European guidelines for the diagnosis and management of PNP/PAMS. Diagnostic criteria and therapeutic recommendations will require further validation by prospective studies.

Pruritus Is Associated with an Increased Risk for the Diagnosis of Autoimmune Skin Blistering Diseases: A Propensity-Matched Global Study.

Autoimmune bullous skin diseases (AIBDs), such as bullous pemphigoid (BP) and pemphigus, are characterized and caused by autoantibodies targeting structural proteins. In BP, clinical experience and recent systematic evaluation identified pruritus to be common and an important cause of impaired quality of life. Furthermore, chronic pruritus may be the sole clinical symptom of BP. In pemphigus, a retrospective study recently documented a high prevalence of pruritus. The temporal relation between pruritus and BP/pemphigus are, however, unknown. Likewise, the presence of pruritus in AIBDs other than BP and pemphigus is unknown. To address this, we performed propensity-matched retrospective cohort studies using TriNetX, providing real-world patient data to (i) assess the risk to develop AIBDs following the diagnosis of pruritus and (ii) vice versa. We assessed this in eight AIBDs: BP, mucous membrane pemphigoid (MMP), epidermolysis bullosa acquisita, dermatitis herpetiformis, lichen planus pemphigoides (LPP), pemphigus vulgaris, pemphigus foliaceous, and paraneoplastic pemphigus (PNP). For all AIBDs, pruritus was associated with an increased risk for the subsequent diagnosis of each of the eight investigated AIBDs in 1,717,744 cases (pruritus) compared with 1,717,744 controls. The observed hazard ratios ranged from 4.2 (CI 3.2-5.5; p < 0.0001) in MMP to 28.7 (CI 3.9-211.3; p < 0.0001) in LPP. Results were confirmed in two subgroup analyses. When restricting the observation time to 6 months after pruritus onset, most HRs noticeably increased, e.g., from 6.9 (CI 6.2-7.9; p < 0.0001) to 23.3 (CI 17.0-31.8; p < 0.0001) in BP. Moreover, pruritus frequently developed following the diagnosis of any of the eight AIBDs, except for PNP. Thus, all AIBDs should be considered as differential diagnosis in patients with chronic pruritus.

Vitiligo and Crohn's disease form an autoimmune cluster: insights from a population-based study.

BACKGROUND: While the coexistence of vitiligo and Crohn's disease (CD) has been reported in individual patients, the epidemiological association between these autoimmune conditions remains inconclusive. OBJECTIVE: To assess the bidirectional association between vitiligo and CD. 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 CD. Adjusted hazard ratios (HRs) and adjusted odds ratios (ORs) were calculated by multivariable Cox regression and logistic regression, respectively. RESULTS: The incidence rate of new-onset CD was evaluated at 3.6 (95% CI, 2.7-4.9) cases per 10,000 person-years (PY) in patients with vitiligo and 2.4 (95% CI, 2.0-2.9) cases per 10,000 PY in controls. Patients with vitiligo experienced an elevated risk of CD (fully adjusted HR, 1.60; 95% CI, 1.10-2.34; p = 0.015). Congruently, a history of preexisting CD predicted elevated odds of having subsequent vitiligo (fully adjusted OR, 1.49; 95% CI, 1.15-1.93; p = 0.002). Compared to other patients with vitiligo, those with vitiligo and comorbid CD were older and had a higher prevalence of diabetes mellitus, hyperlipidemia, and hypertension but a comparable all-cause mortality rate. CONCLUSIONS: The current study depicts a robust bidirectional association between vitiligo and CD. This knowledge is of clinical implication for physicians managing patients with both conditions. The diagnostic threshold for CD should be lowered in vitiligo patients with compatible symptoms.

The risk of retinal vein occlusion among patients with neovascular age related macular degeneration: a large-scale cohort study.

PURPOSE: To examine the risk for retinal-vein-occlusion (RVO) in patients with neovascular age-related-macular-degeneration (AMD) as compared to age- and sex-matched controls. METHOD: This is a population-based, cohort study. The study encompassed 24,578 consecutive patients with neovascular AMD and 66,129 control subjects. Multivariate cox regression analysis was utilized to detect the risk of RVO among patients with neovascular AMD. Predictors of RVO in patients with neovascular AMD were identified using multivariate logistic regression analysis. Mortality of patients was assessed using Kaplan-Meier method. RESULTS: The incidence rate of RVO was estimated at 1.25 (95% CI, 1.06-1.45) per 1000 person-years among patients with neovascular AMD and 0.25 (95% CI, 0.20-0.31) per 1000 person-years among controls. Patients with neovascular AMD were associated with an increased risk of RVO (adjusted HR, 4.35; 95% CI, 3.34-5.66; P < 0.001). Among patients with neovascular AMD, older age (≥79.0 years) was associated with a decreased risk of RVO (adjusted OR, 0.50; 95% CI, 0.37-0.70; P < 0.001), whilst a history of glaucoma increased the likelihood of RVO (adjusted OR, 2.66; 95% CI, 1.94-3.65; P < 0.001). Patients with neovascular AMD and comorbid RVO had a comparable risk of all-cause mortality relative to other patients with neovascular AMD (HR, 0.90; 95% CI, 0.67-1.22; P = 0.500) CONCLUSIONS: An increased risk of RVO was found among patients with neovascular AMD. Younger age and glaucoma predicted the development of RVO in patients with neovascular AMD. Awareness of this comorbidity is of benefit for clinicians as patients with neovascular AMD might be carefully examined for RVO signs and complications.

Isotretinoin and the risk of inflammatory bowel disease and irritable bowel syndrome: A large-scale global study.

INTRODUCTION: Risk of inflammatory bowel disease under isotretinoin is a scope of a long-standing controversy. The burden of isotretinoin-related irritable bowel syndrome has not been investigated. OBJECTIVE: To evaluate the risk of Crohn's disease, ulcerative colitis (UC), and irritable bowel syndrome in patients with acne starting isotretinoin vs oral antibiotics treatment. METHODS: A global population-based retrospective cohort study assigned 2 groups of patients with acne initiating isotretinoin (n = 77,005) and oral antibiotics (n = 77,005). Comprehensive propensity-score matching was conducted. RESULTS: The lifetime risk of Crohn's disease (hazard ratio [HR], 1.05; 95% CI, 0.89-1.24; P = .583) and UC (HR, 1.13; 95% CI, 0.95-1.34; P = .162) was comparable between study groups, whereas the lifetime risk of irritable bowel syndrome was lower in isotretinoin-prescribed patients (HR, 0.82; 95% CI, 0.76-0.89; P < .001). In time-stratified analysis, isotretinoin-related risk of UC was significantly increased during the first 6 months following drug initiation (HR, 1.93; 95% CI, 1.29-2.88; P = .001), but decreased afterward to level the risk of the comparator group. The absolute risk difference within the first 6 months was clinically marginal (5.0 additional UC cases/10,000 patients starting isotretinoin; 95% CI, 2.5-7.7). LIMITATIONS: Retrospective data collection. CONCLUSION: Isotretinoin does not confer an elevated risk of Crohn's disease, whilst it might be associated with a slight and transient increase in UC risk.

Autoimmune pre-disease.

Approximately 5% of the world-wide population is affected by autoimmune diseases. Overall, autoimmune diseases are still difficult to treat, impose a high burden on patients, and have a significant economic impact. Like other complex diseases, e.g., cancer, autoimmune diseases develop over several years. Decisive steps in the development of autoimmune diseases are (i) the development of autoantigen-specific lymphocytes and (often) autoantibodies and (ii) potentially clinical disease manifestation at a later stage. However, not all healthy individuals with autoantibodies develop disease manifestations. Identifying autoantibody-positive healthy individuals and monitoring and inhibiting their switch to inflammatory autoimmune disease conditions are currently in their infancy. The switch from harmless to inflammatory autoantigen-specific T and B-cell and autoantibody responses seems to be the hallmark for the decisive factor in inflammatory autoimmune disease conditions. Accordingly, biomarkers allowing us to predict this progression would have a significant impact. Several factors, such as genetics and the environment, especially diet, smoking, exposure to pollutants, infections, stress, and shift work, might influence the progression from harmless to inflammatory autoimmune conditions. To inspire research directed at defining and ultimately targeting autoimmune predisease, here, we review published evidence underlying the progression from health to autoimmune predisease and ultimately to clinically manifest inflammatory autoimmune disease, addressing the following 3 questions: (i) what is the current status, (ii) what is missing, (iii) and what are the future perspectives for defining and modulating autoimmune predisease.

Chronic Spontaneous Urticaria in Patients With Interstitial Cystitis/Bladder Pain Syndrome: Insights From Big Data Analyses.

OBJECTIVE: To examine the association between chronic spontaneous urticaria (CSU) and interstitial cystitis/bladder pain syndrome (IC/BPS). METHODS: A population-based retrospective cross-sectional study was performed using the Clalit Health Services medical database. The prevalence of CSU was compared between patients diagnosed with IC/BPS and age- and gender-matched controls. Univariate analysis was performed using Chi-square and Student t test and a multivariable analysis was performed using a logistic regression model. RESULTS: The study included 681 patients with IC/BPS and 3376 demographically matched controls. The mean age of IC/BPS patients was 60 years old. The prevalence of CSU among patients with IC/BPS was higher as compared to the control group (20% vs 13.7%; P <.001). The adjusted OR for CSU in patients with IC/BPS was 1.58 (95% CI 1.28-1.97). Female gender and Jewish ethnicity were associated with the coexistence of these disorders (OR 1.7 95% CI 1.36-2.13, and 1.6 95% CI 1.28-2, respectively). CONCLUSION: A significant association was found between IC/BPS and CSU. This finding may support the presence of allergic/immune components in the pathogenesis of IC/BPS.

Psoriasis and hidradenitis suppurativa: A large-scale population-based study.

BACKGROUND: The coexistence of psoriasis and hidradenitis suppurativa (HS) has been described, but the association between these conditions is yet to be firmly established. OBJECTIVE: To study the association between psoriasis and HS by using a large-scale real-life computerized database. METHODS: A cross-sectional study was conducted to compare the prevalence of HS among patients with psoriasis with that among age-, sex- and ethnicity-matched control subjects. RESULTS: A total of 68,836 patients with psoriasis and 68,836 controls were included in the study. The prevalence of HS was increased in patients with psoriasis versus in those in the control group (0.3% vs 0.2%, respectively; odds ratio, 1.8; 95% confidence interval, 1.5-2.3; P < .001). In a multivariate analysis adjusting for smoking, obesity, and other comorbidities, psoriasis was still associated with HS (odds ratio, 1.8; 95% confidence interval, 1.4-2.2; P < .001). Patients with coexistent psoriasis and HS were significantly younger (39.0 ± 15.7 vs 42.6 ± 21.2 years [P = .015]) and had a higher prevalence of obesity (35.1% vs 25.3% [P = .001]) and smoking (58.5% vs 37.3% [P < .001]) compared with patients with psoriasis alone. LIMITATIONS: Retrospective data collection. CONCLUSIONS: A positive association was observed between HS and psoriasis. Further longitudinal observational studies are necessary to establish these findings in other study populations.

Hidradenitis suppurativa: Evaluating activity patterns and predictors of recalcitrant course-A population-based study.

BACKGROUND: Epidemiological evidence regarding the course and activity patterns of hidradenitis suppurativa (HS) is yet to be delineated. OBJECTIVE: To identify activity patterns of HS throughout the time axis and to outline predictors of recalcitrant disease course. METHODS: A population-based retrospective cohort study was performed to follow patients with HS (n = 4417) throughout the initial 10 years following their diagnosis. The disease was considered active in a certain month if one of the following criteria was fulfilled: (i) purchase of an HS-related drug, (ii) admission to a dermatological ward and (iii) referral to a dermatological consultation in an emergency room. Patients with a recalcitrant disease were defined as those with ≥5 years of follow-up with ≥6 'active months' each. Patients with an indolent course were defined as those experiencing ≥9 years of follow-up with ≤1 'active months' each. RESULTS: The average (SD) number of months in which patients had an active disease was 1.37 (1.28) months per year. While 98 (2.2%) patients pursued a recalcitrant course, 1390 (31.5%) went through an indolent disease course. Older age (≥38 years; adjusted OR, 6.17; 95% CI, 3.33-11.43), Arab ethnicity (adjusted OR, 2.04; 95% CI, 1.20-3.48), low socioeconomic status (adjusted OR, 1.64; 95% CI, 1.03-2.60), obesity (adjusted OR, 3.47; 95% CI, 2.25-5.34) and smoking (adjusted OR, 2.65; 95% CI, 1.57-4.47) were found to independently predict recalcitrant course of HS. CONCLUSIONS: Mild course is more frequently encountered than severe course among Israeli patients with HS. Modifiable risk factors of recalcitrant course should be carefully addressed.

Antihistamines-refractory chronic pruritus in psoriatic patients undergoing biologics: aprepitant vs antihistamine double dosage, a real-world data.

BACKGROUND: Psoriasis-related pruritus (PRP) in patients under systemic treatment is challenging. The risk to switch anti-psoriatic drugs and to lose response to previous therapy is high, thus dermatologists prefer to add an anti-pruritic agent. OBJECTIVES: To evaluate the effect of anti-histamines and aprepitant in treating PPR of psoriatic patients undergoing systemic anti-psoriatic therapies. METHODS: A pilot observational open-label study was performed on responsive psoriatic patients with PPR under treatment. Initial therapy included oral rupatadine (10 mg/day for 30 days). In case of the Epworth Sleepiness Scale (ESS) was above 14, patients were switched to aprepitant (80 mg/day for 7 days), otherwise, rupatadine dosage was increased (20 mg/day for 7 days). Clinical evaluation was performed at the baseline (T0) and after 7 days (T7). RESULTS: We enrolled 40 patients with PPR, 20 in each group. Age, gender, Psoriatic arthritis (PsA) and the itch - VAS, were matched. At T7, aprepitant displayed higher improvements than rupatadine (itch - VAS = 4 [3-5] vs 8.5 [8-9], p < .01, DLQI = 14 [13-16] vs. 18 [16-21], p < .01 and ESS = 5 [4-7] vs 15 [14-16], p < .01). Doubling the rupatadine dosage from 10 mg to 20 mg/day only slightly improve itch (itch - VAS = 9 [8-10] vs 9 [8-9], p = .03), conversely no modifications in the quality of life (DLQI = 18 [17-20] vs 18 [17-21], p = .73) and increased sleepiness (ESS = 10 [9-11] vs 15 [14-16], p < .01). CONCLUSIONS: Aprepitant may be a valid alternative in PPR patients with ESS >14 under antihistamines.

Melanoma is associated with an increased risk of bullous pemphigoid: a large population-based longitudinal study.

The association between bullous pemphigoid (BP) and melanoma is yet to be investigated. We aimed to assess assess the bidirectional association between BP and melanoma and to delineate the epidemiological features of patients with both diagnoses. A population-based cohort study was performed comparing BP patients (n = 3924) with age-, sex- and ethnicity-matched control subjects (n = 19,280) with regard to incident cases of melanoma. A case-control design was additionally adopted to estimate the risk of BP in individuals with a preexisting diagnosis of melanoma. The prevalence of preexisting melanoma was higher in patients with BP than in control subjects (1.5% vs. 1.0%, respectively; P = 0.004). A history of melanoma confers a 50% increase in the risk of subsequent BP (OR 1.53; 95% CI 1.14-2.06). This risk was higher among males (OR 1.66; 95% CI 1.09-2.54) and individuals older than 80 years (OR 1.63; 95% CI 1.11-2.38), and persisted after adjustment for multiple putative confounders including PD-1/PDL-1 antagonists (adjusted OR 1.53; 95% CI 1.14-2.06). Conversely, the risk of melanoma among patients with BP was slightly elevated, but did not reach the level of statistical significance (adjusted HR 1.13; 95% CI 0.73-1.74). Patients with a dual diagnosis of BP and melanoma were older at the onset of BP and had lower body mass index. A history of melanoma is associated with a 50% increase in the incidence of subsequent BP. Physicians managing patients with both conditions should be aware of this association. Further research is warranted to reveal the underlying mechanism of these findings.

The association between alopecia areata and anxiety, depression, schizophrenia, and bipolar disorder: a population-based study.

Although Alopecia areata (AA) has been found to be associated with psychological distress, the scope and nature of this association has not been fully delineated. The current study sought to examine the association of AA with anxiety, depression, schizophrenia, and bipolar disorder, utilizing a large-scale matched controlled cohort design. Patients suffering from AA (n = 41,055) were matched to control cases (n = 41,055) by age, sex, and socioeconomic status (SES). The prevalence of the four major mental disorders was assessed while stratifying the sample by age and sex, and after adjusting for marital status, smoking, BMI, hypertension, and diabetes. Data were accessed via the Clalit Health Services (CHS) database, a comprehensive health registry utilized by the largest managed healthcare company in Israel. Anxiety was independently and positively associated with AA (OR 1.22, 95% CI 1.13-1.31, p < 0.001), across all age groups above 30, with similar rates in males and females. Depression was also independently and positively associated with AA (OR 1.09, 95% CI 1.01-1.17, p < 0.005), particularly in the 30-49 age group, with a higher association among females. A negative association was found between AA and schizophrenia (OR 0. 71, 95% CI 0.61-0.83, p < 0.001). No association was found between AA and bipolar disease. Patients with AA are at risk for anxiety and depression, with female patients, and patients in the 30-49 age group being particularly vulnerable to develop a co-occurring mental disorder. Medical treatment should therefore include psychiatric evaluation and appropriate care.