Long-term steroid therapy can result in secondary adrenal insufficiency due to suppression of the hypothalamic-pituitaryadrenal axis. Systemic intercurrent illness can often precipitate adrenal crisis in such patients if steroid therapy is not increased temporarily to tide over the period of metabolic stress.The aetiology of adrenal insufficiency can be differentiated by checking serum ACTH which is high in Addison's disease and suppressed in secondary adrenal failure due to hypothalamic or pituitary causes. Adrenocortical autoantibodies to 21-hydroxylase are positive in 80% of patient's with Addison's disease. 4 Our patient had taken prednisolone for seven years and presented with incipient adrenal crisis six months after this was discontinued. Secondary adrenal failure due to long-term adrenal suppression was initially considered as the cause of adrenal failure but the generalised hyperpigmentation and positive adrenal antibodies suggest a diagnosis of autoimmune Addison's disease. Our patient was fortuitously being partially treated for Addison's disease while on prednisolone for presumed polymyalgia rheumatica, but developed overt adrenal insufficiency when this was discontinued. We are aware of at least one other case in which primary adrenocortical failure was masked by exogenous steroid administration. 5 Our patient subsequently developed primary autoimmune hypothyroidism and this, along with the history of pernicious anaemia, supports a common autoimmune aetiology.The ubiquitous long-term use of oral glucocorticoids to treat a variety of respiratory, rheumatological and haematological disorders carries the risk of causing adrenal insufficiency. Signs and symptoms of adrenal insufficiency in such patients should be anticipated and treated with 'crisis' dose steroid replacement during metabolic stress. Primary autoimmune Addison's disease often presents with non-specific symptoms and diagnosis is often delayed. A high index of suspicion remains the cornerstone of diagnosis. lesson of the month (2)Lesson A malnourished 82-year-old woman was referred to the emergency department with an extensive, painful rash. This had worsened despite two weeks treatment for herpes zoster. A month prior to admission she had undergone patellar surgery with a brief interruption of warfarin treatment. Warfarinisation had been commenced a year previously for a postoperative pulmonary embolus. Examination revealed extensive tender and malodorous erythematous plaques with a violacious hue. Central necrotic eschars and vesiculobullous changes were evident and there was involvement of the face, breasts, trunk and limbs (Fig 1). Warfarin-induced skin necrosis (WISN) was suspected necessitating the cessation of warfarin, and administration of vitamin K and low molecular weight heparin. Broad-spectrum antibiotics, enteral feeding and a three-day course of methylprednisolone, as vasculitis could not be excluded, were commenced. Biopsy of involved skin showed vascular thrombi, patchy necrosis and recent haemorrhage consistent with WI...

ATB mainly affects young South Asian and African patients, with difficulties in confirming diagnosis despite a range of non-invasive and invasive diagnostic tests.

Variants in ATP8B1, ABCB11, and ABCB4 underlie the most prevalent forms of progressive familial intrahepatic cholestasis. We aim to describe variants in these genes in a cohort of patients with adult-onset liver disease, and explore a genotype-phenotype correlation. Patients with onset of liver disease aged above 18 who underwent sequencing of cholestasis genes for clinical purposes over a 5-year period were identified. Bioinformatic analysis of variants was performed. Liver histology was evaluated in patients with variants.Of the 356 patients tested, at least one variant was identified in 101 (28.4%): 46 ABCB4, 35 ABCB11, and 28 ATP8B1. Patients with ABCB4 variants had chronic liver disease (71.7%) and pregnancy-associated liver dysfunction (75%), with a younger age of onset in more severe genotypes (p = 0.046).ABCB11 variants presented with pregnancy-associated liver dysfunction (82.4%) and acute/episodic cholestasis (40%), with no association between age of onset and genotype severity. ATP8B1 variants were associated with chronic liver disease (75%); however, they were commonly seen in patients with an alternate etiology of liver disease and variants were of low predicted pathogenicity. In adults with suspected genetic cholestasis, variants in cholestasis genes were frequently identified and were likely to contribute to the development of liver disease, particularly ABCB4 and ABCB11. Variants were often in heterozygous state, and they should no longer be considered recessive Mendelian traits. Sequencing cholestasis genes in selected patients with adult-onset disease should be considered, with interpretation in close collaboration with histopathologists and geneticists.

Background. The use of once-daily extended-release tacrolimus (ERT) is associated with improved long-term graft and patient survival when compared with twice-daily tacrolimus (BDT), but the underlying reasons for differential survival are unclear. The aim of the study was to compare clinical outcomes known to impact on posttransplant survival for de novo BDT and ERT in liver transplantation (LT) recipients. Methods. We conducted a single-center, prospective sequential cohort analysis of adult patients undergoing LT during a change in protocol from de novo BDT to ERT, with a 6-month post-LT follow-up. Results. A total of 160 transplanted patients were evaluated; 82 were in the BDT group and 78 were in the ERT group. The cohorts were matched for standard variables and a similar proportion in each group received induction interleukin-2 receptor antibody (36% and 31%). There were no significant differences in the measured outcomes of patient and graft survival, biopsy-proven acute rejection episodes, post LT diabetes, and toxicity. A significantly lower number of patients developed chronic kidney disease Stage3–4 in the ERT cohort compared with BDT cohort. In patients with pre-LT renal dysfunction who received antibody induction, estimated glomerular filtration rate decreased significantly in the BDT but not the ERT group. Conclusions. We show that once-daily ERT is as safe and efficacious as BDT in de novo LT but optimally conserves renal function post-LT.