Flexible Sigmoidoscopy Rather than Colonoscopy Is Adequate for the Diagnosis of Ipilimumab-Associated Colitis.

OBJECTIVES: Treatment with ipilimumab, a cytotoxic T lymphocyte antigen-4 approved for metastatic melanoma can result in clinically significant immune-mediated drug injury in the form of colitis. Timely diagnosis and response are essential for optimal management. The aims of our study were to determine the percentage of our patients with ipilimumab-associated colitis in which the colitis could be diagnosed by flexible sigmoidoscopy only and to describe the variations in endoscopic and histologic findings as well as the patients' clinical courses. METHODS: We retrospectively reviewed 244 patients with metastatic melanoma, treated them with ipilimumab, and characterized the endoscopic and histologic features for those who developed colitis. RESULTS: Of the 68 patients who presented with diarrhea, 33 were diagnosed as having ipilimumab-associated colitis. Endoscopically, all of them had involvement of the left side of the colon; none of the patients were noted to have isolated right colon involvement. CONCLUSIONS: Ipilimumab-associated colitis can be diagnosed with a flexible sigmoidoscopy alone, obviating the need for full colonoscopy.

Acute porphyrias in the USA: features of 108 subjects from porphyrias consortium.

BACKGROUND: Recent descriptions of the clinical and laboratory features of subjects with acute porphyrias in the US are lacking. Our aim was to describe clinical, biochemical, and genetic features of 108 subjects. METHODS: Between September 2010 and December 2012, 108 subjects with acute porphyrias (90 acute intermittent porphyrias, 9 hereditary coproporphyrias, 9 variegate porphyrias) were enrolled into an observational study. Genetic testing was performed at a central genetic testing laboratory and clinical information entered into a central database. Selected features were compared with data for adults in the US. RESULTS: Most subjects (88/108, 81%) were female, with self-reported onset of symptoms in the second through fourth decades of life. The most common symptom was abdominal pain. Appendectomies and cholecystectomies were common before a diagnosis of porphyria. The diagnosis was delayed by a mean of 15 years. Anxiety and depression were common, and 18% complained of chronic symptoms, especially neuropathic and other pains. The incidences of systemic arterial hypertension, chronic kidney disease, seizure disorders, and psychiatric conditions were markedly increased. Mutations of the known causative genes were found in 102/105 of those tested, with novel mutations being found in 37, including in 7/8 subjects with hereditary coproporphyria. Therapy with intravenous hematin was the most effective therapy both for treatment of acute attacks and for prevention of recurrent attacks. CONCLUSIONS: Acute porphyrias often remain undiagnosed for more than a decade after first symptoms develop. Intravenous hematin is the treatment of choice, both for treatment of acute attacks and for prevention of recurrent attacks.

Circadian rhythms in acute intermittent porphyria--a pilot study.

BACKGROUND: Acute intermittent porphyria (AIP) is an inherited disorder of haem synthesis wherein a partial deficiency of porphobilinogen (PBG) deaminase (PBGD) with other factors may give rise to biochemical and clinical manifestations of disease. The biochemical hallmarks of active AIP are relative hepatic haem deficiency and uncontrolled up-regulation of hepatic 5-aminolevulinic acid (ALA) synthase-1 (ALAS1) with over-production of ALA and PBG. The treatment of choice is intravenous haem, which restores the deficient regulatory haem pool of the liver and represses ALAS1. Recently, haem has been shown to influence circadian rhythms by controlling their negative feedback loops. We evaluated whether subjects with AIP exhibited an altered circadian profile. MATERIALS AND METHODS: Over a 21-h period, we measured levels of serum cortisol, melatonin, ALA, PBG and mRNA levels (in peripheral blood mononuclear cells) of selected clock-controlled genes and genes involved in haem synthesis in 10 Caucasian (European-American) women who were either postmenopausal or had been receiving female hormone therapy, six of whom have AIP and four do not and are considered controls. RESULTS: Four AIP subjects with biochemical activity exhibited higher levels of PBG and lower levels and dampened oscillation of serum cortisol, and a trend for lower levels of serum melatonin, than controls or AIP subjects without biochemical activity. Levels of clock-controlled gene mRNAs showed significant increases over baseline in all subjects at 5 a.m. and 11 p.m., whereas mRNA levels of ALAS1, ALAS2 and PBGD were increased only at 11 p.m. in subjects with active AIP. CONCLUSIONS: This pilot study provides evidence for disturbances of circadian markers in women with active AIP that may trigger or sustain some common clinical features of AIP.

Liver transplantation for acute liver failure at 11-week gestation with successful maternal and fetal outcome.

Acute liver failure (ALF) during pregnancy is very uncommon. Pregnancy-specific liver conditions like hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome and acute fatty liver of pregnancy can cause ALF at term or postpartum, but, typically occur during the third trimester. Most of these patients recover spontaneously after delivery, but, on occasion, they require liver transplantation in the postpartum period. However, ALF during the first and second trimester of pregnancy requiring antepartum liver transplantation is rare. Only fifteen cases of liver transplantation during pregnancy have been reported, and very few occurred during the first trimester. We report a Woman who developed acute liver failure during the first trimester of pregnancy and underwent successful liver transplantation at 11-week gestation, followed by successful delivery of the fetus at 30 weeks. To our knowledge, this is the earliest case of successful liver transplantation during pregnancy followed by successful fetal outcome. We discuss management of the patient and fetus before, during, and after liver transplantation and review the literature on antepartum liver transplant in pregnancy.