Topical calcineurin inhibitors in eczema and cancer association: A cohort study.

INTRODUCTION: Cancer risk associated with topical calcineurin inhibitors (TCIs) remains unclear. OBJECTIVE: To evaluate the association between TCIs and cancer among patients with atopic and endogenous eczema. METHODS: Incident cancers were identified from the National Cancer Registry. Data were analyzed using the Cox proportional hazards model to estimate hazard ratios (HRs) and 95% confidence intervals. RESULTS: 880 unique cases of cancer developed in 66 176 patients from 2004 to 2012. The adjusted HRs for overall malignancy were 0.82 (95%CI 0.44-1.39) for tacrolimus-exposed and 1.30 (95%CI 0.59-2.45) for pimecrolimus-exposed. The only significant cancer association observed was lymphoid leukemia among the tacrolimus-exposed: HR 7.58 (95%CI 1.64-25.8). All affected patients had young-onset B-cell leukemia. Subgroup analysis of pediatric patients (≤16 years) showed significant association between tacrolimus use and B-cell leukemia: HR 26.4 (95%CI 4.77-146). CONCLUSIONS: In this first Asian study on the risk of TCIs and malignancies, we do not find an association between use of tacrolimus and pimecrolimus in atopic and endogenous eczema and the overall development of malignancies. However, the use of topical tacrolimus was found to be associated with the development of B-cell acute lymphoid leukemia in pediatric eczema patients; further studies are required to investigate if a true association indeed occurs.

Mortality of bullous pemphigoid in Singapore: risk factors and causes of death in 359 patients seen at the National Skin Centre.

BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune-mediated subepidermal blistering skin disease and is associated with significant morbidity and mortality. OBJECTIVES: To determine the 3-year mortality rate, risk factors and causes of death in patients with BP in Singapore, compared with the general population. METHODS: We conducted a retrospective cohort study of all newly diagnosed patients with BP seen at the National Skin Centre from 1 April 2004 to 31 December 2009. Demographic and clinical data on comorbidities and treatment were recorded. Mortality information was obtained from the National Registry of Diseases. RESULTS: In total 359 patients were included in our study. The 1-, 2-, 3-year mortality rates were 26·7%, 38·4% and 45·7%, respectively. The 3-year standardized mortality risk for patients with BP was 2·74 (95% confidence interval 2·34-3·19) times higher than for the age- and sex-matched general population. Parkinson disease, heart failure and chronic renal disease were associated with increased mortality, while combination treatment with low-to-moderate-dose corticoste-roids and immunomodulatory agents such as doxycycline and/or nicotinamide was associated with lower mortality. Overall, infections were the most common cause of death (59·8%), with the main causes of death being pneumonia (42·7%), cardiovascular disease (14·6%) and stroke (11·6%). CONCLUSIONS: This study confirms an increased 3-year mortality rate for patients with BP in Singapore. Risk factors for increased mortality include medical comorbidities, especially neurological, cardiac and renal diseases. Treatment with combination therapy, including the use of low-to-moderate-dose corticosteroid, appeared to decrease mortality risk in patients with BP.

Filaggrin mutations are associated with recurrent skin infection in Singaporean Chinese patients with atopic dermatitis.

BACKGROUND: Loss-of-function (null) mutations within the filaggrin (FLG) gene are a strong risk factor for atopic dermatitis (AD). We hypothesized that the absence or reduction of the filaggrin protein could compromise skin barrier and increase patients' susceptibility to recurrent skin infection. OBJECTIVES: To investigate the association between FLG-null mutations and the risk of recurrent skin infection among a series of patients with AD in Singapore. METHODS: This study included 228 Singaporean Chinese patients with AD with at least 1year of follow-up at the time of recruitment between January 2008 and December 2009 at the National Skin Centre in Singapore. Each patient had their medical records reviewed for history of skin infection in the preceding year and was genotyped for 22 FLG-null mutations. RESULTS: Compared with those without the FLG-null mutations, patients with AD who had FLG mutation(s) had approximately a seven times increased risk of more than four episodes of skin infection requiring antibiotics in the past year (odds ratio 6·74; 95% confidence interval 2·29-19·79). This risk was much greater in those with mild or moderate disease, and was present in both users and nonusers of oral steroids. CONCLUSION: This study highlights a novel association between FLG-null mutations and an increased susceptibility to recurrent bacterial skin infection among patients with AD.