LAUSR

Diseases such as psoriasis, atopic dermatitis, hidradenitis suppurativa, alopecia areata, vitiligo, bullous pemphigoid and rosacea have different aetiologies, but are sometimes studied together as ‘chronic inflammatory skin diseases’ or ‘immunemediated inflammatory skin diseases’. A growing body of literature has led to recognition that these conditions are frequently associated with other diseases that extend beyond the skin. While most comorbidity research on inflammatory skin diseases has focused on links to cardiovascular disease, cancer, infections and mental health conditions, a growing body of literature examines links to kidney disease. In this issue of the BJD, Schonmann et al. use routinely collected primary care data from the UK to explore the association between chronic kidney disease (CKD) stages 3–5 and inflammatory skin diseases. They found that patients with CKD were more likely to have a history of atopic eczema [odds ratio (OR) 1 14, 99% confidence interval (CI) 1 11–1 17], psoriasis (OR 1 13, 99% CI 1 08–1 19) and hidradenitis suppurativa (OR 1 49, 99% CI 1 19–1 85) in a case–control analysis. The effect sizes were larger among patients with moderate-to-severe atopic eczema and psoriasis than among patients with mild disease, and did not appear to be mediated through hypertension, cardiovascular disease (i.e. ischaemic heart disease, chronic heart failure and peripheral arterial disease) or nephrotoxic drugs (i.e. ciclosporin, methotrexate or mycophenolate mofetil). There was no evidence for an association with rosacea. A challenge to studying CKD is that early disease is usually asymptomatic and routine screening is not recommended for the general population. Therefore, the results of the case– control analysis in the study by Schonmann et al. (and most studies using routinely collected data) may be biased if participants with inflammatory skin disease are more likely to see providers and have blood or urine testing. To address this potential ascertainment bias, the authors also performed a cohort analysis among patients with diabetes as guidelines recommend that all patients with diabetes are routinely monitored for CKD. They did not find an increased risk of incident CKD among patients with atopic eczema or psoriasis. However, their study may have been underpowered for this cohort analysis because a very large sample size and duration of follow-up may be required to detect an increase in risk over the high background risk of incident CKD among those with diabetes. It is unclear whether the discrepancy in results is due to ascertainment bias in the case–control analysis or statistical power issues in the cohort analysis. Additional evidence regarding a potential link between inflammatory skin disease and kidney disease comes from data pertaining to cause of death. Patients with atopic dermatitis, psoriasis and hidradenitis suppurativa have an increased risk of death owing to urogenital disease, which can be up to twofold to fivefold greater according to some studies. Urogenital disease encompasses multiple conditions and CKD can result from different pathologies. Thus, the specific types of urogenital diseases potentially linked to inflammatory skin diseases and their mechanisms warrant additional study. The increasing availability of large databases with routinely collected data has enabled studies of inflammatory skin disease comorbidities, but specific challenges warrant discussion. Firstly, quantitative measures of disease activity and severity are rarely recorded and most studies using routinely collected data rely on treatment patterns to ascertain severity, which makes it difficult to disentangle the impact of disease severity from potential side-effects of treatment. Moreover, some treatments can introduce ascertainment bias through the need for frequent lab monitoring as described above. Secondly, inflammatory skin diseases are often treated with nonprescription products, which are rarely linked to medical records. Thirdly, inflammatory skin diseases may be impacted by behavioural and lifestyle factors such as activity, sleep and diet, which are rarely well captured in large administrative databases. A final challenge to studying inflammatory skin disease comorbidities is variability in the age of presentation and the episodic natural history, which can make it difficult to identify temporal associations with other conditions. Despite these challenges, there has been substantial progress in our understanding of inflammatory skin disease comorbidities resulting from the use of routinely collected data. Comorbidity research on inflammatory skin diseases is important. These diseases collectively impact up to 20% of the population and may represent a group that warrants targeted screening. In the case of CKD, early treatment can help to prevent progression to end-stage renal disease. Although evidence remains insufficient to support clear recommendations for screening in most current guidelines, future work should evaluate the potential impact of screening and treatment among patients with inflammatory skin disease.