GENETIC STUDY OF PSORIASIS HIGHLIGHTS ITS CLOSE LINK WITH SOCIO-ECONOMIC STATUS AND AFFECTIVE SYMPTOMS.

Psoriasis is an inflammatory skin disease with an estimated heritability of around 70 %. Previous genome-wide association studies (GWASs) have detected several risk loci for psoriasis. To further improve the understanding of the genetic risk factors impacting the disease, we conducted a discovery GWAS in FinnGen and a subsequent replication and meta-analysis with data from the Estonian Biobank and the UK biobank; the study sample included 925 649 individuals (22 659 cases and 902 990 controls), the largest sample for psoriasis yet. In addition, we conducted downstream analyses to find out more about psoriasis' cross-trait genetic correlations and causal relationships. We report 6 risk loci to our knowledge previously unreported, most of which harbor genes related to nuclear factor kappa-light-chain-enhancer of activated B-cells-signaling pathway and overall immunity. Genetic correlations highlight the relationship between psoriasis and smoking, higher body weight, and lower education level. Additionally, we report causal relationships between psoriasis and mood symptoms, as well as two-directioned causal relationship between psoriasis and lower education level. Our results provide further knowledge on psoriasis risk factors, which may be useful in the development of future treatment strategies.

Identifying Atopic Dermatitis Risk Loci in 1,094,060 Individuals with Subanalysis of Disease Severity and Onset.

Atopic dermatitis (AD) is a common inflammatory skin disease highly attributable to genetic factors. In this study, we report results from a genome-wide meta-analysis of AD in 37,541 cases and 1,056,519 controls with data from the FinnGen project, the Estonian Biobank, the UK Biobank, the EAGLE Consortium, and the BioBank Japan. We detected 77 independent AD-associated loci, of which 10 were, to our knowledge, previously unreported. The associated loci showed enrichment in various immune regulatory processes. We further performed subgroup analyses of mild and severe AD and of early- and late-onset AD, with data from the FinnGen project. Fifty-five of the 79 tested variants in the associated loci showed larger effect estimates for severe than for mild AD as determined through administered treatment. The age of onset, as determined by the first hospital visit with AD diagnosis, was lower in patients with particular AD-risk alleles. Our findings add to the knowledge of the genetic background of AD and may underlie the development of new therapeutic strategies.

Adult Acne in Middle-age: Effects on Mental Health in General Population of the Northern Finland Birth Cohort 1966.

The impact of adult acne on patients' mental health has not been widely studied, and most studies have been conducted within specific patient populations. The current study examines the association between adult acne and psychological symptoms in the Northern Finland Birth Cohort 1966 (NFBC1966) (n = 1,907). The cohort members attended a health study at the age of 46 years, which comprised a whole-body examination performed by dermatologists to identify acne, and answering the Beck Depression Inventory II (BDI-II), Athens Insomnia Scale (AIS), Generalized Anxiety Disorder (GAD-7), State-Trait Anxiety Inventory (STAI) and 15-dimensional measure of health-related quality of life (15D HRQoL) questionnaires. The prevalence of adult acne was 7.9% (n = 150) with no statistical differences between the sexes. Cases with acne presented more (18.9%) depressive symptoms (BDI-II > 14 points) compared with those without acne (9.7%) (p < 0.001). In adjusted logistic regression analyses, those with acne had a 2-fold risk (odds ratio (OR) 2.08, 95% confidence interval (95% CI) 1.23-3.38) of having depressive symptoms compared with controls. In conclusion, when treating adult acne patients, it is important to recognize the increased risk of mental health symptoms.

Prevalence and Characteristics of Hidradenitis Suppurativa in the Northern Finland Birth Cohort 1986 Study: A Cross-sectional Study of 2,775 Subjects.

A negative stigmatization related to hidradenitis suppurativa may prevent patients from seeking care. Thus, a large proportion of patients with hidradenitis suppurativa may be missing from studies based on hospital data. The aim of this study was to examine the prevalence and characteristics of hidradenitis suppurativa among 2,775 subjects in the Northern Finland Birth Cohort 1986 Study (NFBC1986), who were in their mid-thirties. The prevalence of hidradenitis suppurativa was 4.0% (n = 110/2,775), being higher in females (4.8%) than in males (2.5%) (p < 0.01). Of those defined as having hidradenitis suppurativa in this study, only 4 cases (n = 4/110, 3.6%) were found to have a hidradenitis suppurativa diagnosis either in the hospital (Care Register for Health Care) or in the primary healthcare data. In an adjusted model in logistic regression analyses, hidradenitis suppurativa was significantly associated with obesity (body mass index 30-55 kg/m2) (odds ratio 3.81, 95% confidence interval 2.80-5.22), female sex (1.99, 1.53-2.61) and smoking (1.56, 1.21-2.00). In addition, there was an association between hidradenitis suppurativa and self-reported poor overall health status. Hidradenitis suppurativa seems to be common at the population level and only a minority of these patients seek care for the condition.

Association of Rosacea with Depressive and Anxiety Symptoms: A General Population Study.

BACKGROUND: The association between rosacea and psychiatric comorbidity has been reported previously. However, there is a lack of general population studies about this subject area. OBJECTIVES: The aim of this study was to the association between rosacea with depressive and anxiety symptoms at the population level. METHODS: A clinical whole-body examination was performed by dermatologists for 1,932 subjects belonging to the Northern Finland Birth Cohort 1966 Study during the 46-year follow-up survey. The presence of depressive and anxiety symptoms was gathered by using validated Hopkins Symptom Checklist-25 (HSCL-25) included in the self-administered questionnaires. Binary logistic regression analysis was used to identify associations between rosacea and psychological symptoms. RESULTS: Rosacea was found in dermatological evaluation in 15.1% of the study subjects (n = 292). In logistic regression analyses, after adjusting for confounding factors, those with rosacea had 1.6-fold (OR 1.55, 95% CI: 1.02-2.32) risk for psychiatric symptoms according to HSCL-25 when compared with controls. In separate analyses of the HSCL-25 depression subscale, the risk was increased, especially for depressive symptoms (OR 1.56, 95% CI: 1.10-2.18). CONCLUSIONS: Patients with rosacea seem to have increased risk for depressive and anxiety symptoms in general population. Physicians treating patients with rosacea should pay more attention to the psychosocial health of patients.

Accurate diagnosis of bullous pemphigoid requires multiple health care visits.

Introduction: Accurate use of diagnostic codes is crucial for epidemiological and genetic research based on electronic health record (EHR) data. Methods: This retrospective study validated the International Classification of Diseases (ICD)-10 diagnostic code L12.0 for bullous pemphigoid (BP) using EHR data from two Finnish university hospitals. We found 1225 subjects with at least one EHR entry of L12.0 between 2009 and 2019. BP diagnosis was based on clinical findings characteristic of BP and positive findings on direct immunofluorescence (DIF), BP180-NC16A enzyme-linked immunosorbent assay (ELISA) or indirect immunofluorescence (IIF) assay. Results: True BP was found in 901 patients; the positive predictive value (PPV) for L12.0 was 73.6% (95% CI 71.0-76.0). L12.0 was more accurately registered in dermatology units than any specialized health care units (p<0.001). Including patients with multiple L12.0 registrations (≥3), increased the accuracy of the L12.0 code in both dermatology units and other settings. Discussion: One diagnostic code of L12.0 is not enough to recognize BP in a large epidemiological data set; including only L12.0 registered in dermatology units and excluding cases with <3 L12.0 record entries markedly increases the PPV of BP diagnosis.

The gut microbiome in bullous pemphigoid: implications of the gut-skin axis for disease susceptibility.

Bullous pemphigoid (BP) is an autoimmune blistering disease that primarily affects the elderly. An altered skin microbiota in BP was recently revealed. Accumulating evidence points toward a link between the gut microbiota and skin diseases; however, the gut microbiota composition of BP patients remains largely underexplored, with only one pilot study to date, with a very limited sample size and no functional profiling of gut microbiota. To thoroughly investigate the composition and function of the gut microbiota in BP patients, and explore possible links between skin conditions and gut microbiota, we here investigated the gut microbiota of 66 patients (81.8% firstly diagnosed) suffering from BP and 66 age-, sex-, and study center-matched controls (CL) with non-inflammatory skin diseases (132 total participants), using 16S rRNA gene and shotgun sequencing data. Decreased alpha-diversity and an overall altered gut microbial community is observed in BP patients. Similar trends are observed in subclassifications of BP patients, including first diagnoses and relapsed cases. Furthermore, we observe a set of BP disease-associated gut microbial features, including reduced Faecalibacterium prausnitzii and greater abundance of pathways related to gamma-aminobutyric acid (GABA) metabolism in BP patients. Interestingly, F. prausnitzii is a well-known microbiomarker of inflammatory diseases, which has been reported to be reduced in the gut microbiome of atopic dermatitis and psoriasis patients. Moreover, GABA plays multiple roles in maintaining skin health, including the inhibition of itching by acting as a neurotransmitter, attenuating skin lesions by balancing Th1 and Th2 levels, and maintaining skin elasticity by increasing the expression of type I collagen. These findings thus suggest that gut microbiota alterations present in BP may play a role in the disease, and certain key microbes and functions may contribute to the link between gut dysbiosis and BP disease activity. Further studies to investigate the underlying mechanisms of the gut-skin interaction are thus clearly warranted, which could aid in the development of potential therapeutic interventions.

Serum reactivity in dermatitis herpetiformis: an international multicentre study.

BACKGROUND: Dermatitis herpetiformis (DH) is a rare gluten-induced skin disorder characterized predominantly by IgA autoantibodies against endomysium, tissue transglutaminase (TG2/tTG), epidermal transglutaminase (TG3/eTG) and deamidated gliadin. To date, circulating autoantibody reactivity has not been systematically described. OBJECTIVES: Characterization of serum reactivities in DH. METHODS: This multicentre international study analysed sera from 242 patients with DH taken at the time of initial diagnosis. DH-specific IgA and IgG serum autoantibodies were analysed by indirect immunofluorescence (IF) on monkey oesophagus, and by enzyme-linked immunosorbent assay (ELISA) based on recombinant TG2/tTG, TG3/eTG and deamidated gliadin (GAF3X). RESULTS: IgA indirect IF microscopy on monkey oesophagus revealed the highest reactivity (84.3%; specificity 100%) followed by IgA TG2/tTG ELISA (78.5%, specificity 99.0%), IgA TG3/eTG ELISA (72.7%, specificity 95.0%) and IgA GAF3X ELISA (69.0%, specificity 98.5%). CONCLUSIONS: Serum IgA and IgG autoantibodies against endomysium, TG2/tTG, TG3/eTG and deamidated gliadin are highly prevalent in DH. Indirect IF microscopy on monkey oesophagus (IgA) provides the highest diagnostic accuracy that can be further enhanced by 4.5% when combined with IgA TG2/tTG ELISA.

Anxiety and depression in patients with hand eczema: A population-based study among 853 middle-aged subjects.

BACKGROUND: Hand eczema (HE) is a common dermatological disorder with considerable effect on the health-related quality of life (HRQoL). The data on mental comorbidities of HE is sparse and mostly studied among selected patient groups. OBJECTIVES: We aimed to investigate symptoms of depression and anxiety in patients with HE in general population. METHODS: Study subjects (n = 6695) belonging to the Northern Finland Birth Cohort 1966 Study (NFBC1966) responded to an extensive health questionnaire including questions about HE. Depression and anxiety symptoms were evaluated according to the Hopkins Symptom Checklist-25 (HSCL-25). RESULTS: Having ever suffered from HE was reported by 853 (12.8%) study subjects. Symptoms scores of depression were significantly higher among (n = 172, 20.3%) HE subjects compared with (n = 884, 15.4%) subjects without HE (Odds ratio [OR] 1.40, 95% confidence interval [CI]: 1.17-1.68, P < 0.001). Correspondingly, symptoms scores of anxiety were also more common among (n = 90, 10.6%) HE subjects than among (n = 448, 7.8%) subjects without HE (OR 1.40, 95% CI: 1.10-1.78, P = 0.007). In an adjusted model, the associations remained statistically significant (OR 1.30, 95% CI: 1.08-1.57, P = 0.007 and OR 1.34, 95% CI: 1.04-1.72, P = 0.021, respectively). CONCLUSIONS: Symptoms associated with mental health should be taken into account when managing patients with HE.

Sexual behavioral factors of the subjects visiting the clinic of sexually transmitted infections in Northern Finland: A cross-sectional study among 775 subjects.

Background and Aims: Sexually transmitted infections (STI) are among the most common infections globally. However, the sexual behavioral factors and sexual history of people visiting STI clinics have only been surveyed in a few studies. We aimed to evaluate the characteristics of the patients visiting the open STI clinic. Methods: This is a prospective observational study performed in the STI clinic in the premises of Department of Dermatology, Oulu University Hospital. All individuals (n = 775) attending the STI clinic between February and August 2022 were included to the study and the profile of the patients was evaluated. Results: We found that the majority of the STI clinic attendees (58.5%) were female. Mean age of the study population was 28.9 years, with females being significantly younger than males (p < 0.001). Only one-third (30.6%) of the patients reported having symptoms at the time of attending. Most commonly, patients had had one sex partner in the last 6 months. However, one-fifth (21.7%) reported several sex partners (over four). Almost half of the patients (47.6%) reported using a condom only randomly. Those with heterosexual orientation had fewer multiple-sex partners (p < 0.001) than those with homo- or bisexual orientation (p < 0.05). Conclusion: It is important to increase knowledge about the profile of STI clinic visitors to effectively target STI prevention on the groups at the highest risk of STIs.

Cardiovascular and Metabolic Profile of Subjects with Acne in a Cohort of Middle-aged Patients: A General Population Study of 1,932 Subjects.

Acne vulgaris is one of the most common inflammatory skin diseases, but there are few studies of adult acne and its association with general health. The aim of this study was to examine the prevalence and clinical characteristics of adult acne at the population level among 1,932 subjects belonging to the Northern Finland Birth Cohort 1966 Study. In addition, cardiovascular and metabolic profiles of acne cases and their controls were analysed. The prevalence of adult acne was 7.9% (n = 150) with no statistical difference between the sexes. The majority of subjects presented with papulopustular acne (77.1%). Comedo acne (10.8% of all subjects) was more common in females than in males (p < 0.005). Males with acne had more abnormality in their metabolic factors than did acne-free controls; plasma glucose and insulin levels at 60 min after the 75 g glucose load were higher in males with acne than in controls (p < 0.01 for both). Corresponding associations were not seen in females. In conclusion, adult acne is common in middle-age, presenting a slightly different clinical picture in females than in males. In addition, male subjects with acne may have a higher risk of metabolic disturbances than do controls, and thus, comprehensive evaluation of patients with adult acne is needed.

Characteristics, comorbidities, and treatment practices of lichen planus in Northern Finland: A register-based study among 619 subjects.

Background and Aims: Lichen planus (LP) is a common itching skin disease where lesions appear on the skin and mucous membranes. However, the epidemiology of LP is not yet sufficiently understood. The aim of this study was to retrospectively map out the characteristics, comorbidities and treatments of patients diagnosed with LP. Methods: This is a retrospective hospital patient registry-based study performed between 2009 and 2021 in a secondary care hospital (Oulu University Hospital) in Northern Finland. All patients with recorded diagnosis of LP were included in the study. Characteristics, comorbidities, and treatments of LP patients were studied. Results: In total, 619 patients were verified from the hospital health records. The mean age of patients was 54.2 years and the majority were female (58.3%). Most of the patients had symptoms in more than two skin areas (mean 2.7 skin areas), lower limbs being the most common site (74.0%). A third of patients (34.7%) had oral LP lesions. Nearly fifth (19.4%) of the subjects had a history of previous LP. Of comorbidities found among LP subjects, obesity (22.5%), malignancies (19.4%), depression (12.8%), and thyroiditis (12.4%) were seen more often than in general Finnish population. The most used form of treatment was topical corticosteroids (97.6%), followed by phototherapy 26.8%. Systemic treatments such as prednisolone and methotrexate had been used in 7.6% and 1.1% of the patients, respectively. Conclusion: LP patients had a heightened risk for several comorbidities, which should be considered when managing patients with LP.

Comorbidities and Medication Use in Finnish Patients with Psoriasis: A Population-Based Registry Study.

Therapeutic options for psoriasis vulgaris have changed during recent decades with the introduction of biologics. Few nationwide studies are available on psoriasis treatment patterns, and those from Finland predate the use of biologics. The aim of this retrospective, population-based registry study was to identify patients with psoriasis vulgaris and their treatment patterns in the secondary care setting in Finland. The study cohort included 41,456 adults with a diagnosis of psoriasis vulgaris in the public secondary healthcare setting from 2012 through 2018. Data on comorbidities, pharmacotherapy, and phototherapy were collected from nationwide healthcare and drug registries. Patients in the cohort had a wide range of comorbidities, with 14.9% having psoriatic arthritis. Treatment was based largely on topical and conventional systemic medications. Conventional medications were used by 28.9% of patients, and methotrexate was the most common option (20.9%). Biologics were used by 7.3% of patients, mostly as second- and third-line treatment. The use of conventional systemic medications, topical treatments, and phototherapy decreased after the initiation of biologics. This study of psoriasis vulgaris in Finland provides a framework for the development of future care practices.

Association between Pruritus and Psychosocial Well-being: A Population-based Study among 6,809 Subjects.

Pruritus has an extensive impact on functional, social and psychosocial behaviour. The association between pruritus and psychological well-being has mostly been studied among selected patient groups, whereas population-based studies are lacking. The aim of this study was to determine the association between pruritus and insomnia, quality of life, depression and anxiety at the population level in the general population. A cross-sectional population-based study was conducted in 2012 to 2013. Study subjects (n = 6,809) belonging to the Northern Finland Birth Cohort 1966 Study participated in a large follow-up study at the age of 45-47 years. They completed an extensive health questionnaire including questions on pruritus and several previously validated questionnaires regarding symptoms of psychosocial well-being. Pruritus affected 19.9% of the study subjects weekly, being more common in women than in men (p < 0.001). A significant association was found between both localized and generalized pruritus and symptoms of insomnia, depression, anxiety and decreased quality of life. The association was seen even in those with mild psychological symptoms/insomnia, and it affected both sexes. The severity of psychological symptoms increased with increasing frequency of pruritus. In conclusion, pruritus has a multiple effect on psychosocial well-being. Physicians should consider possible psychosocial symptoms in patients with pruritus.