Cutaneous manifestations of acute kidney injury.

Acute kidney injury (AKI) is a common medical problem with a multitude of aetiologies. Prompt diagnosis and management is key in the prevention of complications. Cutaneous signs can often give diagnostic clues of underlying systemic diseases causing AKI. This review summarizes cutaneous findings of diseases causing AKI in adults. Knowledge of such cutaneous signs could lead to earlier diagnosis of underlying kidney disease and facilitate management strategies in a timely manner. Acute interstitial nephritis, polyarteritis nodosa, Kawasaki's disease, granulomatosis with polyangiitis (previously Wegener's granulomatosis), microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis (previously Churg-Strauss syndrome), Henoch-Schönlein purpura, cryoglobulinaemia, Sjögren's syndrome, systemic sclerosis, nephrogenic systemic fibrosis, dermatomyositis, systemic lupus erythematosus, amyloidosis and cholesterol embolization syndrome were highlighted as diseases causing AKI with cutaneous manifestations.

Clinical and pharmacogenetic influences on response to hydroxychloroquine in discoid lupus erythematosus: a retrospective cohort study.

The recommended systemic therapy of choice for discoid lupus erythematosus (DLE) is the 4-aminoquinolone antimalarial hydroxychloroquine. There is limited published information on the likelihood of clinical response and, in particular, what factors influence outcome. We conducted a multicenter observational and pharmacogenetic study of 200 patients with DLE treated with hydroxychloroquine. The primary outcome was clinical response to hydroxychloroquine. We investigated the effects of disease attributes and metabolizing cytochrome P450 (CYP) polymorphisms on clinical outcome. Although the majority of patients responded to hydroxychloroquine, a significant proportion (39%) either failed to respond or was intolerant of the drug. Cigarette smoking and CYP genotype did not have any significant influence on response to hydroxychloroquine. Moreover, multivariate analysis indicated that disseminated disease (odds ratio (OR): 0.21; 95% confidence interval (CI): 0.08-0.52; P<0.001) and concomitant systemic lupus erythematosus (SLE; OR: 0.06; 95% CI: 0.01-0.49; P = 0.009) were significantly associated with lack of response to hydroxychloroquine. These findings suggest that baseline lupus severity and SLE are predictors of response to hydroxychloroquine. A prospective study is now required to further investigate the relationship between disease activity and response to hydroxychloroquine. This will have the potential to further inform the clinical management of this disfiguring photosensitive disease.

Null mutations in the filaggrin gene (FLG) determine major susceptibility to early-onset atopic dermatitis that persists into adulthood.

Atopic dermatitis (AD) is a common disease with a complex etiology in childhood and adult life. A significant proportion of childhood AD is transient, but in many cases it persists into adulthood. We have recently shown that null mutations in the filaggrin gene (FLG) are an important predisposing factor for childhood eczema and eczema-associated asthma, but persistence to adulthood has not been analyzed. Here we studied a cohort of adult patients with persistent AD, which had been present since early childhood. In this cohort, the combined allele frequency of the two common FLG null variants was 0.270 (cf. population frequency 0.046). This represents an odds ratio of 7.7 with 95% confidence interval of 5.3-10.9 and a chi2 P-value of 1.7 x 10(-53). Our data conclusively demonstrate that identification of FLG null alleles is an indicator of a poor prognosis in AD, predisposing to a form of eczema that starts in early infancy and persists into adulthood. This study helps to further define the nature of the AD phenotype associated with FLG null alleles.

Azathioprine dosed by thiopurine methyltransferase activity for moderate-to-severe atopic eczema: a double-blind, randomised controlled trial.

BACKGROUND: Atopic eczema affects 1-2% of adults, and can cause considerable morbidity. We aimed to assess the safety and efficacy of azathioprine as systemic monotherapy for moderate-to-severe atopic eczema, and the therapeutic importance of the thiopurine methyltransferase (TPMT) polymorphism (a key determinant of azathioprine-induced myelotoxicity) by using TPMT enzyme activity to establish azathioprine dose. METHODS: We did a parallel-group, double-blind, placebo-controlled trial in an outpatient setting. Minimisation was used to assign 63 patients with active disease despite optimum topical therapy to treatment with azathioprine (n=42) or placebo (n=21) for 12 weeks. As maintenance treatment, patients with heterozygous range TPMT activity received azathioprine 1.0 mg/kg daily, compared with 2.5 mg/kg daily in patients with normal TPMT activity. For the first 4 weeks, all participants received lower azathioprine doses (0.5 and 1.0 mg/kg daily, respectively) to reduce gastrointestinal side-effects. The primary measure of clinical response was disease activity assessed by the SASSAD (six area six sign atopic dermatitis) score. Analysis was by intention-to-treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN58943280. FINDINGS: 54 (86%) participants completed the study; two (3%) withdrew from the placebo group and seven (11%) from the azathioprine group. At week 12, there was a 37% (12.0 unit) improvement in mean disease activity with azathioprine compared with a 20% (6.6 unit) improvement with placebo (17% [5.4 unit] difference, 95% CI 4.3-29%). This finding was accompanied by significant improvements in patient-reported itch, area of involvement, global assessment, and quality of life. Between participants there was a wide variation in response to the drug. Generally, azathioprine was well tolerated, although two individuals developed drug hypersensitivity. Participants with heterozygous range TPMT activity responded to azathioprine in similar proportions to other participants, but none developed bone-marrow toxicity. TPMT-based dosing seemed to reduce predicted toxicity, and drug efficacy was maintained. INTERPRETATION: Treatment with azathioprine as systemic monotherapy produces clinically relevant improvement in moderate-to-severe atopic eczema that remains active despite optimum therapy with topical corticosteriods. We believe the study of azathioprine as systemic monotherapy for atopic eczema has major advantages, which should allow clarification of the relation between azathioprine effectiveness and metabolite profiles in other inflammatory diseases.

Phototherapy and systemic treatments.

A proportion of children and adults with moderate to severe atopic eczema are not adequately controlled with emollients and topical steroids, resulting in significant morbidity and disability. Studies indicate a significant placebo response, so randomized controlled trials of new treatments are vital. This article reviews the evidence for phototherapy and systemic treatments in atopic eczema.