Dermatology research team

More than skin deep: risk factors and co-morbidities of skin diseases in Finnish population

To understand better the life-course determinants and pathways to skin diseases we have performed full dermatologic status investigation of 1932 members of the Northern Finland Birth Cohort 1966 (NFBC 1966). NFBC 1966 is a longitudinal research program which included initially all 12058 children whose expected time of delivery was in the year 1966. The whole NFBC 1966 cohort has been followed on a regular basis since antenatal period by health care records, questionnaires and clinical examinations as well as data on their parents and offspring. During a 46-year follow-up survey, 1932 cohort members were evaluated by multidisciplinary examination including body index, blood pressure, heart echo recording, dental status and several other health measurements.

Another source for epidemiological data is the national registries. The Finnish Care Register for Health Care (CRHC), maintained by Finnish institute of Health and Welfare, is one of the longest-standing individual-level hospital discharge registries. It contains data from both hospitalized patients and those treated in the outpatient clinic of all hospitals across Finland. CRHC contains personal and hospital identification codes, data on age, gender, length of stay and subsidiary diagnoses. Data about all reimbursed medications purchased in Finland can also be found from national registry (KELA). By combining these registry data, we can study in nationwide-level the medication use and comorbidities in several skin diseases. Currently, we have built up three cohorts, in which we study comorbidities in atopic dermatitis, basal cell carcinoma and in hand eczemas.

In addition, we work as part of FinnGen-project. The FinnGen Research Project (https://www.finngen.fi/en) was designed to establish a resource that combines data from the Finnish national registers (CRHC, KELA) with genome-wide variant data from 500 000 Finns. The premise of the project is based on Finland’s high degree of genetic homogeneity, which is due to the country’s unique population history. This makes it easier to identify novel risk alleles in a relatively homogeneous population than it would be in a more genetically diverse one. New GWAS data releases are executed every 6 months.

Bullous pemphigoid: predisposing factors and mechanisms of autoimmunization

Bullous pemphigoid (BP) is an autoimmune blistering skin disease of elderly. Its symptoms include large blisters and severe pruritus. It is a chronic disease associated with heightened mortality rate. The incidence of BP has increased during the recent decade in several countries, including Finland. Type 2 diabetics with gliptin treatment and patients with multiple sclerosis (MS) have markedly increased risk for developing BP. The most important autoantigen in BP is collagen XVII (ColXVII) which is a transmembrane component of hemidesmosomes. Evidence for the pathogenic role of ColXVII autoantibodies comes from clinical findings and experimental BP mouse models, but the factors leading to the initiation of the autoimmunity in the aging skin are poorly understood.

Aside from the contribution of HLA class II allele variants, genetic factors predisposing to BP are largely unknown. We are utilizing the data from the FinnGen Research Project to obtain novel information concerning genetic susceptibility to BP. We believe that gliptin- and MS-associated BP provide a valuable model to investigate the breakdown of immune tolerance to BP180. Some gliptin users and MS patients without BP diagnosis have non-pathogenic autoantibodies against BP180. It is not known whether gliptin medication alone is sufficient to induce BP or if other factors are involved. It is also debated whether the gliptin treatment should be discontinued following a BP diagnosis. BP usually requires 1–2 years of treatment, 30 to 50% of patients experience a relapse within a few months of withdrawal. Nationwide data of reimbursed drugs from KELA allows us to determine whether some medications predispose to BP and to compare detailed real-life registry information on current treatment options. We are identifying the relapsing cases by finding BP patients with multiple periods of immunosuppressants and compare their co-morbidities, medication use and mortality to patients who have been treated with a single continuous course of treatment. The analysis of the longitudinal health register data of disease trajectories will also clarify the similarities and differences between gliptin-associated BP and “regular” BP.