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.

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.

Risk of infections in patients with pemphigus treated with rituximab vs. azathioprine or mycophenolate mofetil: a large-scale global cohort study.

BACKGROUND: The risk of infectious complications among patients with pemphigus managed by rituximab is yet to be precisely elucidated. OBJECTIVES: To evaluate the risk of infections in patients with pemphigus managed by rituximab vs. first-line corticosteroid-sparing agents [azathioprine and mycophenolate mofetil (MMF)]. METHODS: A global population-based cohort study compared patients with pemphigus initiating rituximab (n = 963) vs. azathioprine or MMF (n = 963) regarding the risk of 26 different infections. Propensity score matching was conducted to optimize comparability. RESULTS: During the initial 12 months following treatment, patients under rituximab experienced elevated risk of COVID-19 [hazard ratio (HR) 1.82, 95% confidence interval (CI) 1.06-3.14; P = 0.028], parasitic diseases (HR 3.22, 95% CI 1.04-9.97; P = 0.032) and cytomegalovirus (CMV) infection (HR 1.63, 95% CI 1.04-2.58; P = 0.033). When evaluating infections developing ≥ 12 months after drug initiation, rituximab was associated with greater risk of pneumonia (HR 1.45, 95% CI 1.00-2.10; P = 0.047), COVID-19 (HR 1.87, 95% CI 1.49-2.33; P < 0.001), osteomyelitis (HR 2.42, 95% CI 1.11-5.31; P = 0.023), herpes simplex virus (HR 2.06, 95% CI 1.03-4.11; P = 0.037) and CMV (HR 1.63, 95% CI 1.07-2.49; P = 0.023) infections. CONCLUSIONS: Within the first 12 months after treatment, patients under rituximab experience an elevated risk of COVID-19, parasitic and CMV infections. Rituximab is associated with pneumonia, osteomyelitis and viral diseases even beyond the first year after therapy. Pneumococcal vaccine and suppressive antiviral therapy should be considered even 1 year following therapy. There is no signal for elevated risk of tuberculosis, hepatitis B virus reactivation, Pneumocystis jiroveci pneumonia and progressive multifocal leukoencephalopathy.

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.

Isotretinoin and the risk of psychiatric disturbances: A global study shedding new light on a debatable story.

INTRODUCTION: Isotretinoin-related risk of depression and suicidal behavior is a topic of inconclusiveness. A crucial knowledge gap exists in defining the association of isotretinoin with other psychiatric comorbidities. OBJECTIVE: To evaluate the risk of psychiatric outcomes among patients with acne treated with isotretinoin versus oral antibiotics. METHODS: A global population-based retrospective cohort study enrolled 2 groups of patients with acne managed by isotretinoin (n = 75,708) and oral antibiotics (n = 75,708). Patients were compared regarding the risk of 9 psychiatric outcomes. RESULTS: Relative to those treated with oral antibiotics, patients prescribed isotretinoin experienced lower risk of depression (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.87-0.93; P < .001), but comparable risk of major depressive disorder (HR, 0.97; 95% CI, 0.92-1.03; P = .318). Risk of suicidal attempts was comparable between groups (HR, 0.97; 95% CI, 0.85-1.11; P = .663), despite the elevated risk of suicidal ideation in those under isotretinoin (HR, 1.41; 95% CI, 1.32-1.50; P < .001). Patients under isotretinoin had lower risk of post-traumatic stress disorder (HR, 0.75; 95% CI, 0.68-0.82; P < .001), anxiety (HR, 0.84; 95% CI, 0.82-0.87; P < .001), bipolar disorder (HR, 0.65; 95% CI, 0.59-0.72; P < .001), schizophrenia (HR, 0.60; 95% CI, 0.48-0.76; P < .001), and adjustment disorder (HR, 0.82; 95% CI, 0.77-0.87; P < .001). LIMITATIONS: Retrospective data collection. CONCLUSION: Isotretinoin confers lower risk of 6 psychiatric comorbidities and comparable risk of suicidal attempts.

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.

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.

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.

Management and treatment outcome of DRESS patients in Europe: An international multicentre retrospective study of 141 cases.

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare but potentially fatal drug hypersensitivity reaction. OBJECTIVE: To explore treatment approaches across Europe and their impact on the disease course, as well as prognostic factors and culprit drugs. METHODS: In this retrospective European multicentric study, we included patients with probable or certain DRESS (RegiSCAR score ≥ 4) between January 2016 and December 2020. Independent associations between clinical parameters and the risk of intensive care unit admission and mortality at three months were assessed using a multivariable-adjusted logistic regression model. RESULTS: A total of 141 patients from 8 tertiary centres were included. Morbilliform exanthem was the most frequent cutaneous manifestation (78.0%). The mean affected body surface area (BSA) was 67%, 42% of the patients presented with erythroderma, and 24.8% had mucosal involvement. Based on systemic involvement, 31.9% of the patients had a severe DRESS. Anticonvulsants (24.1%) and sulphonamides (22.0%) were the most frequent causative agents. In all, 73% of the patients were treated with systemic glucocorticoids, and 25.5% received topical corticosteroids as monotherapy. Few patients received antiviral drugs or anti-IL5. No patients received intravenous immunoglobulins. The overall mortality was 7.1%. Independent predictors of mortality were older age (≥57.0 years; fully adjusted OR, 9.80; 95% CI, 1.20-79.93; p = 0.033), kidney involvement (fully adjusted OR, 4.70; 95% CI, 1.00-24.12; p = 0.049), and admission in intensive care unit (fully adjusted OR, 8.12; 95% CI, 1.90-34.67; p = 0.005). Relapse of DRESS and delayed autoimmune sequelae occurred in 8.5% and 12.1% of patients, respectively. CONCLUSIONS: This study underlines the need for diagnostic and prognostic scores/markers as well as for prospective clinical trials of drugs with the potential to reduce mortality and complications of DRESS.

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.

Vitiligo and systemic sclerosis: Are they associated?- Lessons from a population-based study.

BACKGROUND: The epidemiological relationship of vitiligo with systemic sclerosis (SSc) remains to be precisely evaluated. OBJECTIVE: To investigate the bidirectional association between vitiligo and SSc. METHODS: A population-based study was carried out 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 SSc. Adjusted hazard ratios (HRs) and adjusted odds ratios (ORs) were calculated by the Cox regression and logistic regression, respectively. RESULTS: The incidence rate of new-onset SSc was calculated at 2.4 (95% CI, 1.6-3.4) and 0.4 (95% CI, 0.3-0.6) cases per 10,000 person-years among patients with vitiligo and controls, respectively. Patients with vitiligo had an increased risk of SSc (fully adjusted HR, 5.37; 95% CI, 3.03-9.54; p < 0.001). Correspondingly, a history of SSc predicted elevated odds of developing vitiligo (fully adjusted OR, 2.09; 95% CI, 1.23-3.55; p = 0.006). Relative to other patients with vitiligo, those with vitiligo and comorbid SSc were older and had a higher prevalence of ischaemic heart disease, hyperlipidaemia, and hypertension. CONCLUSIONS: A robust bidirectional association exists between vitiligo and SSc. This knowledge is valuable for physicians managing patients with both conditions. Patients with vitiligo and comorbid SSc might be monitored for cardiovascular and metabolic comorbidities.

Sexually Transmitted Diseases in Northern Israel: Insights From a Large Referral Laboratory.

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.

The risk, predictors and outcomes of amyloidosis in ankylosing spondylitis: a longitudinal population-based cohort study.

OBJECTIVES: The risk of amyloidosis during the course of AS is yet to be firmly established. We aimed to evaluate the risks, predictors and prognostic outcomes of amyloidosis among patients with AS. METHODS: A population-based cohort study was conducted comparing AS patients (n = 5911) with age-, sex- and ethnicity-matched control subjects (n = 29 007) with regard to incident cases of amyloidosis. Hazard ratios (HRs) and odds ratios (ORs) were estimated by Cox regression and logistic regression analyses, respectively. RESULTS: The incidence rate of amyloidosis was 2.15 (95% CI 1.09, 2.82) and 0.35 (95% CI 0.16, 0.66) per 10 000 person-years among patients with AS and controls, respectively. The risk of incident amyloidosis was >6-fold higher among patients with AS relative to control subjects [adjusted HR 6.16 (95% CI 2.43, 15.62); P < 0.001]. A higher comorbidity burden [OR 1.36 (95% CI 1.08, 1.73); P = 0.010] was found to predict an increased susceptibility to amyloidosis in AS patients. Compared with other patients with AS, those with AS and comorbid amyloidosis had a 14-fold increased risk of end-stage renal disease necessitating dialysis [adjusted HR 14.7 (95% CI 2.0, 107.2); P = 0.008], but comparable risk of all-cause mortality [adjusted HR 2.16 (95% CI 0.69, 6.71); P = 0.174]. CONCLUSIONS: Patients with AS are at an increased risk of amyloidosis. AS-associated amyloidosis is associated with an elevated risk of dialysis dependence. Awareness of the burden and consequences of this complication may be of help for rheumatologists managing patients with AS.

Psoriasis and Renal Disorders: A Large-Scale Population-Based Study in Children and Adults.

BACKGROUND: Psoriasis is a systemic disease with associated comorbidities. An association between renal diseases and psoriasis has previously been reported in adult patients, but little is known about renal diseases in pediatric patients. OBJECTIVE: To determine whether there is an association between psoriasis and renal comorbidities in adult and pediatric patients. METHODS: This cross-sectional study analyzed the database of the largest health care maintenance organization in Israel. Logistic regression was used to calculate odds ratios to compare 68,836 psoriatic patients and 68,836 controls with respect to renal comorbidities. RESULTS: In adults, an inverse association emerged between psoriasis and dialysis (OR, 0.69; 95% CI, 0.58-0.83) and kidney transplantation (OR, 0.60; 95% CI, 0.43-0.83), a positive association with other kidney diseases (OR, 1.09; 95% CI, 1.05-1.13), and no association between psoriasis and chronic kidney disease (OR, 1.03; 95% CI, 0.98-1.09). Comparing 9,127 pediatric patients and 9,478 controls, no association was found between psoriasis and renal comorbidities, chronic kidney disease (OR, 0.90; 95% CI, 0.33-2.48), dialysis (OR, 2.06; 95% CI, 0.19-22.69), kidney transplantation (OR, 0.34; 95% CI, 0.04-3.29), or other kidney diseases (OR, 0.98; 95% CI, 0.79-1.23), even after a multivariate analysis adjusting for putative confounders. CONCLUSION: As opposed to adult patients, pediatric patients with psoriasis were not shown at risk of kidney diseases.

Alopecia Areata as a Proximal Risk Factor for the Development of Comorbid Depression: A Population-based Study.

Alopecia areata and depression tend to co-occur; however, their temporal association has not been comprehensively investigated. The aim of this study was to examine the temporal association between alopecia areata and depression. The study included only cases with a comorbid presentation of alopecia areata and depression (n = 1,936), extracted from the databases of the Clalit Health Services, Israel. Survival analyses were used to assess the cumulative probability of receiving alopecia areata as comorbid diagnosis in the years following depression, and vice versa, compared with the opposite trajectory. The results indicate that patients with alopecia areata had greater odds of subsequent depression within 2 years from alopecia areata diagnosis, and showed a steeper increase in cumulative probability of depression as time progressed (log-rank =336.38, p < 0.001), compared with the opposite trajectory. All patients with alopecia areata had comorbid depression within 10 years of alopecia areata, compared with 70% of depression patients receiving diagnoses of comorbid alopecia areata within the same time-frame.

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.

DNA chip-based diagnosis of onychomycosis and tinea pedis.

BACKGROUND AND OBJECTIVES: Onychomycosis (OM) and tinea pedis (TP) are common fungal infections. Currently, diagnosis is based on direct microscopy and culture that have a low to moderate sensitivity and/or require up to 3-4 weeks until results are obtained. PCR techniques have emerged for the diagnosis of fungal infections, but little is known about their sensitivity and specificity in diagnosing. Here, we compared the diagnostic value of a DNA-chip technology, that detects 56 fungal pathogens, in a single-center prospective diagnostic study with microscopy and culture in suspected OM/TP. PATIENTS AND METHODS: Microscopy, culture and DNA microarray assays were performed on scraping material from patients with suspected OM (n = 67) or TP (n = 73). To test whether swabs can be used as an alternative for scraping, PCR yields were compared in a further 13 patients with OM and 11 patients with TP. RESULTS: DNA microarrays had the highest sensitivity. Combination of DNA-chip technology with microscopy further increased the sensitivity, and results from this combined laboratory diagnosis can be obtained within 24 hours. Comparison of sampling techniques (scraping, dry or wet swab) for DNA-chip assays showed similar results in suspected OM or TP. CONCLUSIONS: DNA-chip technology shows high sensitivity for OM and TP diagnosis, especially when combined with microscopy.

DNA-Chip-basierte Diagnose der Onychomykose und Tinea pedis.

HINTERGRUND UND ZIELE: Onychomykose (OM) und Tinea pedis (TP) sind häufige Pilzinfektionen der Haut. Aktuell basiert die Diagnose vornehmlich auf mikroskopischem Direktnachweis und/oder Kultur. Beide Methoden haben jedoch eine geringe bis mäßige Sensitivität und benötigen teilweise mehrere Wochen, bis endgültige Laborergebnisse vorliegen. Um die Diagnose kutaner Pilzinfektionen zu verbessern, wurden PCR-basierte Methoden entwickelt. Hier haben wir hier die Sensitivität und Spezifität einer Chip-basierten Multiplex-PCR mit mikroskopischen Direktnachweis und verglichen. PATIENTEN UND METHODIK: In einer monozentrischen, prospektiven Studie wurden bei Patienten mit Verdacht auf OM (n  =  67) oder TP (n  =  73) Schuppenpräparate entnommen und mittels mikroskopischem Direktnachweis, Kultur und DNA-Chip-Technologie der Erregernachweis durchgeführt. In einem weiteren Ansatz wurde überprüft, ob Abstriche als Alternative zur Entnahme eines Schuppenpräparates verwendet werden können. Hierfür wurden 24 weitere OM/TP-Patienten rekrutiert und die Ergebnisse der DNA-Chip-Technologie aus Abstrichen mit denen aus den Schuppenpräparaten verglichen. ERGEBNISSE: Im Vergleich aller Methoden hatte die DNA-Chip-Technologie die höchste Sensitivität, eine Kombination von DNA-Chip-Technologie mit mikroskopischem Direktnachweis erhöhte dies weiter. Ergebnisse dieser kombinierten Labordiagnostik sind innerhalb von 24 Stunden verfügbar. Der Vergleich der Probenentnahmetechniken (Abstrich beziehungsweise Schuppenpräparat) zeigte vergleichbare Ergebnisse. SCHLUSSFOLGERUNGEN: Die molekulare Diagnostik (mittels DNA-Chip-Technologie) hat eine hohe Sensitivität für die OM- und TP-Diagnostik, insbesondere in Kombination mit dem mikroskopischen Direktnachweis.

The role of Dipeptidyl Peptidase-4 in cutaneous disease.

Dipeptidyl peptidase-4 (DPP4) is a multifunctional, transmembrane glycoprotein present on the cell surface of various tissues. It is present in multiple molecular forms including cell surface and soluble. The role of DPP4 and its inhibition in cutaneous dermatoses have been a recent point of investigation. DPP4 exerts a notable influence on T-cell biology, the induction of skin-specific lymphocytes, and the homeostasis between regulatory and effector T cells. Moreover, DPP4 interacts with a broad range of molecules, including adenosine deaminase, caveolin-1, CXCR4 receptor, M6P/insulin-like growth factor II-receptor and fibroblast activation protein-α, triggering downstream effects that modulate the immune response, cell adhesion and chemokine activity. DPP4 expression on melanocytes, keratinocytes and fibroblasts further alters cell function and, thus, has crucial implications in cutaneous pathology. As a result, DPP4 plays a significant role in bullous pemphigoid, T helper type 1-like reactions, cutaneous lymphoma, melanoma, wound healing and fibrotic disorders. This review illustrates the multifactorial role of DPP4 expression, regulation, and inhibition in cutaneous diseases.

Hidradenitis suppurativa and atopic dermatitis: A 2-way association.

BACKGROUND: The coexistence of hidradenitis suppurativa (HS) and atopic dermatitis (AD) had been reported but, to our knowledge, was not investigated in controlled studies. OBJECTIVE: To evaluate the bidirectional association between HS and AD. METHODS: A population-based retrospective cohort study was conducted to compare the incidence rate of AD among patients with HS (n = 6779) and age-, sex-, and ethnicity-matched control individuals (n = 33,260). Adjusted hazard ratios (HRs) and adjusted odds ratios were estimated. RESULTS: The incidence of AD was 2.51 (95% confidence interval [CI], 2.07-3.02) and 1.24 (95% CI, 1.10-1.40) per 1000 person-years among patients with HS and control individuals, respectively. Patients with HS were twice as likely to develop AD as control individuals (HR, 2.06; 95% CI, 1.64-2.58). Furthermore, the prevalence of pre-existing AD was higher in patients with HS than in control individuals (2.5% vs 1.8%, respectively; P < .001). A history of AD was associated with a 40% increase in the odds of HS (odds ratio, 1.41; 95% CI, 1.19-1.67). Relative to patients with isolated HS, those with a dual diagnosis of HS and AD were younger and had a female predominance, lower prevalence of smoking, and lower body mass index. LIMITATIONS: Retrospective data collection. CONCLUSIONS: A bidirectional association between HS and AD was observed. Dermatologists should be aware of this association.