Burden of disease and treatment patterns in patients with vitiligo: findings from a national longitudinal retrospective study in the UK.

BACKGROUND: UK studies examining vitiligo burden and vitiligo-related healthcare resource utilization (HCRU) are lacking. OBJECTIVE: To describe the incidence and prevalence of vitiligo, the demographic and clinical characteristics of patients with vitiligo, vitiligo burden, HCRU, incidence of mental health comorbidities and management strategies, including treatment patterns. METHODS: This retrospective study used UK Clinical Practice Research Datalink and Hospital Episode Statistics databases to analyse patients with vitiligo from 1 January 2010 to 31 December 2021. RESULTS: Among 17 239 incident patients, mean incidence of vitiligo was 0.16 (2010-2021) per 1000 person-years [PY; range 0.10 (2020-COVID-19) to 0.19 (2010/2013/2018)]; among 66 217 prevalent patients, prevalence increased from 0.21% (2010) to 0.38% (2021). The most common comorbidities recorded after vitiligo diagnosis were diabetes (19.4%), eczema (8.9%), thyroid disease (7.5%) and rheumatoid arthritis (6.9%). Mental health diagnoses recorded at any time included depression and/or anxiety (24.6%), depression (18.5%), anxiety (16.0%) and sleep disturbance (12.7%), and recorded after vitiligo diagnosis in 6.4%, 4.4%, 5.5% and 3.9%, respectively. Mental health comorbidities were more common in White (e.g. depression and/or anxiety 29.0%) than in Black (18.8%) and Asian (16.1%) patients. In adolescents, depression and/or anxiety was most commonly diagnosed after a vitiligo diagnosis than before (7.4% vs. 1.8%). Healthcare resources were used most frequently in the first year after vitiligo diagnosis (incident cohort), typically dermatology-related outpatient appointments (101.9/100 PY) and general practitioner consultations (97.9/100 PY). In the year after diagnosis, 60.8% of incident patients did not receive vitiligo-related treatment (i.e. topical corticosteroids, topical calcineurin inhibitors, oral corticosteroids or phototherapy), increasing to 82.0% the next year; median time from diagnosis to first treatment was 34.0 months (95% confidence interval 31.6-36.4). Antidepressants and/or anxiolytics were recorded for 16.7% of incident patients in the year after diagnosis. In 2019, 85.0% of prevalent patients did not receive vitiligo-related treatments. CONCLUSION: Most patients were not on vitiligo-related treatments within a year of diagnosis, with the time to first treatment exceeding 2 years, suggesting that vitiligo may be dismissed as unimportant. New effective treatments, early initiation and psychological intervention and support are needed to reduce the vitiligo burden on patients.

Vitiligo is a chronic disease in which cells that produce the skin pigment called melanin are attacked, resulting in white or pale patches of skin. It is diagnosed in an estimated 0.2­0.8% of people in Europe. This study aimed to describe how many new cases of vitiligo were recorded between 2010 and 2021 in the UK and the overall percentage of people with vitiligo. Linked national general practitioner (GP) and hospital-based records containing information on medical diagnoses, admissions and hospital visits were used. Records of other diseases and conditions, including mental health conditions, in combination with healthcare service use and treatment prescribed to patients with vitiligo, were studied to describe the impact of living with vitiligo. It was found that 0.16 new cases of vitiligo were recorded per 1000 person-years (for example, 0.16 new cases would have been recorded if 1000 people were followed for 1 year or if 100 people were all followed for 10 years) between 2010 and 2021. In 2021, 0.4% of the population studied had vitiligo. In the 5 years after a new diagnosis of vitiligo, the most common other diseases recorded were diabetes (19%), eczema (9%), thyroid disease (8%) and rheumatoid arthritis (7%), and the most common mental health conditions were depression and/or anxiety (25%). In the year after diagnosis, GP and dermatology outpatient visits were the most common type of medical services used. In 2019, 85% of all individuals with vitiligo were not receiving any vitiligo-related treatment (such as creams or phototherapy). It took approximately 34 months from diagnosis of vitiligo to the start of first treatment. The results suggest that new effective treatments and psychological interventions are needed to reduce the burden of vitiligo.

Temporal and geographical external validation study and extension of the Mayo Clinic prediction model to predict eGFR in the younger population of Swiss ADPKD patients.

BACKGROUND: Prediction models in autosomal dominant polycystic kidney disease (ADPKD) are useful in clinical settings to identify patients with greater risk of a rapid disease progression in whom a treatment may have more benefits than harms. Mayo Clinic investigators developed a risk prediction tool for ADPKD patients using a single kidney value. Our aim was to perform an independent geographical and temporal external validation as well as evaluate the potential for improving the predictive performance by including additional information on total kidney volume. METHODS: We used data from the on-going Swiss ADPKD study from 2006 to 2016. The main analysis included a sample size of 214 patients with Typical ADPKD (Class 1). We evaluated the Mayo Clinic model performance calibration and discrimination in our external sample and assessed whether predictive performance could be improved through the addition of subsequent kidney volume measurements beyond the baseline assessment. RESULTS: The calibration of both versions of the Mayo Clinic prediction model using continuous Height adjusted total kidney volume (HtTKV) and using risk subclasses was good, with R2 of 78% and 70%, respectively. Accuracy was also good with 91.5% and 88.7% of the predicted within 30% of the observed, respectively. Additional information regarding kidney volume did not substantially improve the model performance. CONCLUSION: The Mayo Clinic prediction models are generalizable to other clinical settings and provide an accurate tool based on available predictors to identify patients at high risk for rapid disease progression.

Building a network of ADPKD reference centres across Europe: the EuroCYST initiative.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic inherited kidney disease, affecting an estimated 600 000 individuals in Europe. The disease is characterized by age-dependent development of a multiple cysts in the kidneys, ultimately leading to end-stage renal failure and the need of renal replacement therapy in the majority of patients, typically by the fifth or sixth decade of life. The variable disease course, even within the same family, remains largely unexplained. Similarly, assessing disease severity and prognosis in an individual with ADPKD remains difficult. Epidemiological studies are limited due to the fragmentation of ADPKD research in Europe. METHODS: The EuroCYST initiative aims: (i) to harmonize and develop common standards for ADPKD research by starting a collaborative effort to build a network of ADPKD reference centres across Europe and (ii) to establish a multicentric observational cohort of ADPKD patients. This cohort will be used to study factors influencing the rate of disease progression, disease modifiers, disease stage-specific morbidity and mortality, health economic issues and to identify predictive disease progression markers. Overall, 1100 patients will be enrolled in 14 study sites across Europe. Patients will be prospectively followed for at least 3 years. Eligible patients will not have participated in a pharmaceutical clinical trial 1 year before enrollment, have clinically proven ADPKD, an estimated glomerular filtration rate (eGFR) of 30 mL/min/1.73 m(2) and above, and be able to provide written informed consent. The baseline visit will include a physical examination and collection of blood, urine and DNA for biomarker and genetic studies. In addition, all participants will be asked to complete questionnaires detailing self-reported health status, quality of life, socioeconomic status, health-care use and reproductive planning. All subjects will undergo annual follow-up. A magnetic resonance imaging (MRI) scan will be carried out at baseline, and patients are encouraged to undergo a second MRI at 3-year follow-up for qualitative and quantitative kidney and liver assessments. CONCLUSIONS: The ADPKD reference centre network across Europe and the observational cohort study will enable European ADPKD researchers to gain insights into the natural history, heterogeneity and associated complications of the disease as well as how it affects the lives of patients across Europe.

Long-term effect of coffee consumption on autosomal dominant polycystic kidneys disease progression: results from the Suisse ADPKD, a Prospective Longitudinal Cohort Study.

BACKGROUND: Previous in vitro experiments of human polycystic kidney disease (PKD) cells reported that caffeine is a risk factor for the promotion of cyst enlargement in patients with autosomal dominant PKD (ADPKD). The relentless progression of ADPKD inclines the majority of physicians to advocate minimization of caffeine consumption despite the absence of clinical data supporting such a recommendation so far. This is the first clinical study to assess prospectively the association between coffee consumption and disease progression in a longitudinal ADPKD cohort. METHODS: Information on coffee consumption and disease progression was collected at each follow-up visit using standardized measurement methods. The main model for the outcomes, kidney size (height-adjusted total kidney volume, htTKV) and kidney function (estimated glomerular filtration rate, eGFR), was a linear mixed model. Patients entered the on-going Swiss ADPKD study between 2006 and June 2014 and had at least 1 visit every year. The sample size of the study population was 151 with a median follow-up of 4 visits per patient and a median follow-up time of 4.38 years. RESULTS: After multivariate adjustment for age, smoking, hypertension, sex, body mass index and an interaction term (coffee*visit), coffee drinkers did not have a statistically significantly different kidney size compared to non-coffee drinkers (difference of -33.03 cm3 height adjusted TKV, 95% confidence interval (CI) from -72.41 to 6.34, p = 0.10). After the same adjustment, there was no statistically significant difference in eGFR between coffee and non-coffee drinkers (2.03 ml/min/1.73 m2, 95% CI from -0.31 to 4.31, p = 0.089). CONCLUSION: Data derived from our prospective longitudinal study do not confirm that drinking coffee is a risk factor for ADPKD progression.

Urinary biomarkers at early ADPKD disease stage.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by a decline in renal function at late disease stage when the majority of functional renal parenchyma is replaced by cystic tissue. Thus, kidney function, assessed by estimated glomerular filtration rate (eGFR) does not well represent disease burden in early disease. Here, we investigated various urinary markers for tubular injury and their association with disease burden in ADPKD patients at early disease course. METHODS: ADPKD patients between 18 and 40 years with an eGFR greater or equal to 70 ml per min per 1.73m2 were eligible for this cross-sectional study. Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney Injury Molecule-1 (KIM-1), and Uromodulin (UMOD) were investigated by Enzyme-Linked Immunosorbent Assay. Clara Cell Protein 16 (CC16) was investigated by Latex Immuno Assay. Cryoscopy was performed to assess urine osmolality and Urinary Albumin-to-Creatinine Ratio (UACR) was calculated. The association and the predictive properties of the markers on eGFR and height adjusted total kidney volume (htTKV) was evaluated using multiple regression analysis, incorporating different control variables for adjustment. Internal bootstrapping validated the obtained results. RESULTS: In 139 ADPKD patients (age 31 ±7 years, mean eGFR of 93 ± 19 ml per min per 1.73 m2) the total kidney volume was negatively correlated with eGFR and UMOD and positive associated with age, UACR, KIM-1 and urine osmolality after adjustment for possible confounders. Urine osmolality and htTKV were also associated with eGFR, whereas no association of CC16, NGAL and UMOD with eGFR or htTKV was found. CONCLUSION: UACR and urinary KIM-1 are independently associated with kidney size but not with renal function in our study population. Urine osmolality was associated with eGFR and kidney volume following adjustment for multiple confounders. Despite statistical significance, the clinical value of our results is not yet conceivable. Further studies are needed to evaluate the property of the aforementioned biomarkers to assess disease state at early ADPKD stage.