Incidence and remission rates of self-reported hidradenitis suppurativa - A prospective cohort study conducted in Danish blood donors.

BACKGROUND: A large discrepancy between physician-diagnosed and self-reported Hidradenitis suppurativa (HS) exists. Knowledge regarding incidence and remission rates of self-reported HS is missing, but may help bridge the gap in understanding between these two phenotypes. OBJECTIVES: To determine the incidence and remission rates of self-reported HS, and to what degree these are affected by sex, smoking and BMI. METHODS: A prospective cohort of 23 930 Danish blood donors. Information on self-reported HS, symptom-localisation, sex, age, BMI and smoking status was collected at baseline and study termination. Self-reported HS fulfilled clinical obligatory diagnostic criteria. Cox proportional hazards regression analyses were conducted for both incidence and remission rates providing a hazard ratio (HR) of risk for each variable in the regression. RESULTS: Incidence rate of self-reported HS was 10.8/1000 person-years (95% confidence interval (CI): 9.9-11.7), decreasing as a function of numbers of areas affected. Female BMI points above 25 (HR = 1.11, 95% CI: 1.09-1.13), male BMI points above 25 (HR = 1.07, 95% CI: 1.04-1.11), active smoking (HR = 1.72, 95% CI: 1.15-2.57), male sex (HR = 0.55, 95% CI: 0.45-0.67) and years of age above 25 (HR = 0.97, 95% CI: 0.96-0.97) were all statistically associated with the development of self-reported HS. Remission rate of self-reported HS was 256.7/1000 person-years (95% CI: 223.9-292.6), decreasing as a function of numbers of affected areas. Symptoms in ≥3 areas (HR = 0.54, 95% CI: 0.34-0.85), active smoking (HR = 0.49, 95% CI: 0.32-0.76) and female weight loss (every percentage drop in BMI: HR = 1.07, 95% CI: 1.05-1.11) all significantly affected the remission rate. CONCLUSIONS: Both incidence and remission rates of self-reported HS are high, indicating that many with self-reported HS are unlikely to be diagnosed, as they to a higher degree experience mild transient HS symptoms.

Evidence of gene-gene interaction in hidradenitis suppurativa: a nationwide registry study of Danish twins.

BACKGROUND: Hidradenitis suppurativa (HS) is a recurrent inflammatory skin disease that, apart from rare causative loss-of-function mutations, has a widely unknown genetic aetiology. OBJECTIVES: To estimate the relative importance of genetic and environmental factors underlying susceptibility to HS. METHODS: Via the Danish Twin Registry and the Danish National Patient Registry we pulled together information on zygosity with that of HS status. Cases of HS were identified by the International Classification of Diseases (ICD)-8 (705·91) and ICD-10 (L73·2). Heritability was assessed by the classic biometric model and the possibility of gene-gene interaction via the multilocus modelling approach. RESULTS: Among 100 044 registered twins, we found 170 twins (from 163 pairs) diagnosed with HS. The seven concordant pairs were all monozygotic. Monozygotic twins had a case-wise concordance rate of 28% [95% confidence interval (CI) 7-49], corresponding to a familial risk of 73 (95% CI 13-133) times that of the background population. The biometrical modelling suggested a heritability of 0·80 (95% CI 0·67-0·93), and the multilocus index estimate was 230 (95% CI 60-400). This is highly indicative of gene-gene interactions, with the possibility of up to six interacting loci. CONCLUSIONS: This twin study was substantially larger and employed a more valid phenotype than previous studies. Genetics account for the majority of HS susceptibility, and HS is most likely caused by gene-gene interactions rather than monogenetic mutations or solely additive genetic factors. New approaches aimed at assessing potential interactions at a single-nucleotide polymorphism (SNP)-SNP level should be implemented in future HS genome-wide association studies.

Convergent Validity of Suffering and Quality of Life as Measured by The Hidradenitis Suppurativa Quality of Life.

BACKGROUND: Hidradenitis suppurativa (HS) is a painful chronic, recurrent inflammatory skin disease with great impact on health-related quality of life (HRQOL). Recently, Hidradenitis SuppuraTiva cORe outcomes set International Collaboration (HISTORIC) established HRQOL as a core domain set for HS clinical trials and developed the Hidradenitis Suppurativa Quality of Life (HiSQOL) as a validated outcome measurement instrument. OBJECTIVES: To provide further convergent validity of HiSQOL by comparing it to Dermatology Life Quality Index (DLQI) and Pictorial Representation of Illness and Self Measure-Revised 2 (PRISM-R2). METHODS: In this cross-sectional study, 103 participants completed HiSQOL, PRISM-R2 and DLQI. PRISM-R2 is an instrument designed to measure suffering and reports the two measures, Illness Perception Measure (IPM) and Self-Illness Separation (SIS). Correlation analyses were performed including a sub-analysis for a subgroup of patients with high scores in the HS-specific domains of HiSQOL. RESULTS: A very strong correlation was found between HiSQOL and DLQI (ρ = 0.93, P < 2.2 × 10-16 , (95% CI: 0.89;0.95)), and moderately strong correlations were found between HiSQOL and SIS (ρ = -0.73, P < 2.2 × 10-16 , (95% CI: -0.81; -0.62)) and DLQI and SIS (ρ = -0.70, P < 2.2 × 10-16 , (95% CI: -0.79; -0.59)). IPM was positively associated with HiSQOL and DLQI and negatively with SIS. CONCLUSIONS: HiSQOL is a valid measure of quality of life for HS patients, and we suggest that HiSQOL can be used as a measure of suffering as well.

Full exome sequencing of 11 families with Hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is not a well-studied or easily treated disease. Genetic information is essential for advances in the understanding and treatment of HS. This study aims to examine mutations in the gamma-secretase complex, the Notch signalling pathway and to perform a Mendelian analysis of genetic variants that segregated with disease in a full exome sequencing of 11 families with HS. METHOD: Whole-exome sequencing and Mendelian analysis of 11 families with HS from Denmark. Patients with a clinical diagnosis of active HS and a positive family history of HS were recruited. Consenting family members were enrolled and examined for HS as well. We included 11 families, with a total of 51 participants, 24 with HS and 27 without. Whole-exome sequencing using HiSeq platform as paired-end 2 × 150 bases was used. RESULTS: We found mutations in the Notch pathway for all families. We found mutations in the PSENEN and APH1B of the gamma-secretase genes. We also report 161 variants of unknown significance that segregated with the disease within these families. CONCLUSIONS: We did not find causative mutation for each family in this study, supporting the theory that HS is rarely caused by single-gene mutations. We suggest that future genetic studies should be focused on genome-wide association with thousands of cases, as this technique is better suited for suspected polygenic diseases.

Factors predicting the self-evaluated health of hidradenitis suppurativa patients recruited from an outpatient clinic.

OBJECTIVES: In recent years, Hidradenitis suppurativa has received increased attention but still lack well-defined, robust patient-reported outcome measures. Such measures are likely to be influenced by contextual factors. We, therefore, aim to describe the association of biological and other factors with HS patient's self-evaluated health as reflected by the EQ5D VAS score. METHODS: This cross-sectional study measured basic information, Dermatology Life Quality Index, Major Depression Inventory and Euro-QoL-5D. Information obtained through questionnaires was used to create a model showing the relation between biological factors, questionnaire results and self-evaluated health using the stepwise method for linear regression. Patients with HS (n = 805) registered at our department were invited to participate. A total of 503 (62.5%) patients replied to this survey. There was no difference in basic demographics between responders and non-responders. RESULTS: Possible predictors for this study were DLQI, MDI, BMI, smoking, gender. A final model for correlation with self-evaluated health was obtained. Significant predictors for the model were DLQI (P < 0.05), BMI points above 25 and active smoking (both: P < 0.01) and MDI (P < 0.001). CONCLUSION: As this is a cross-sectional study, it reveals several clinically relevant correlations. Smoking appears to correlate with the highest change in VAS score, but an MDI of 10 (lower than study average) or a BMI of 40 influences the results more. This study provides an assessment of how much BMI and smoking, in relation to other factors, correlate to the self-evaluated health state of patients with HS. These may, therefore, be relevant contextual factors to the construction and interpretation of specific patient-reported outcome measures. To improve QoL, we advocate smoking cessation and weight loss, and advice active screening for depression as over 10% of our patients qualify for a depressive diagnosis according to ICD-10.

Self-reported minor infections in patients with hidradenitis suppurativa and healthy controls.

BACKGROUND: Patients with hidradenitis suppurativa (HS) often report opportunistic infections such as herpes and urinary tract infections. AIM: To compare opportunistic infections in patients with HS against a group of healthy controls (HCs). METHODS: In total, 99 patients with HS and 109 HCs were recruited at random to this retrospective case-control study. We devised a questionnaire to explore the frequency of minor infections, general practitioner (GP) visits and sick days experienced during the past 6 months. Additionally, participants were asked if they felt unwell more often compared with their peers. RESULTS: Patients with HS felt unwell more often than did HCs (26.3% vs. 7.3%, P < 0.001). Although there was no difference between the groups in five of the seven diseases studied, patients with HS had a higher frequency of the common cold (P < 0.01) and genital herpes (P < 0.01). Number of pack-years of smoking did not affect risk of infections (Pearson correlation, P = 0.51). Subgroup analysis of nonsmokers found the same differences in frequency of minor infections, common cold and genital herpes between patients with HS and controls. CONCLUSIONS: Patients with HS appear to experience more frequently symptoms compatible with minor infections in general, and the common cold and genital herpes specifically. This results in more GP visits and more sick days. Further research is needed to determine if this is caused by an immunological hyper-reactive state in these patients or a reduced threshold for minor infections.