UK experience of liver transplantation for erythropoietic protoporphyria

Erythropoietic protoporphyria (EPP) is characterised by excess production of free protoporphyrin from the bone marrow, most commonly due to deficiency of the enzyme ferrochelatase. Excess protoporphyrin gives rise to the cutaneous photosensitivity characteristic of the disease, and in a minority of patients leads to end-stage liver disease necessitating liver transplantation (LT). There is limited information regarding the timing, impact and long-term outcome of LT in such patients, thus we aimed to identify the indications and outcomes of all transplants performed for EPP in the UK using data from the UK Transplant Registry. Between 1987 and 2009, five patients underwent LT for EPP liver disease. Median follow-up was 60 months, and there were two deaths at 44 and 95 months from causes unrelated to liver disease. The remaining recipients are alive at 22.4 years, 61 months and 55 months after transplant. A high rate of postoperative biliary stricturing requiring multiple biliary interventions was observed. Recurrent EPP-liver disease occurred in 4/5 (80%) of patients but graft failure has not been observed. Given the role of biliary obstruction in inducing EPP-mediated liver damage, we suggest that consideration should be given for construction of a Roux loop at the time of transplant. Thus we demonstrate that although EPP liver transplant recipients have a good long-term survival, comparable to patients undergoing LT for other indications, biliary complications and disease recurrence are almost universal, and bone marrow transplantation should be considered where possible

Erythropoietic protoporphyria

Erythropoietic protoporphyria (EPP) is an inherited disorder of the haem metabolic pathway characterised by accumulation of protoporphyrin in blood, erythrocytes and tissues, and cutaneous manifestations of photosensitivity. EPP has been reported worldwide, with prevalence between 1:75,000 and 1:200,000. It usually manifests in early infancy upon the first sun exposures. EPP is characterised by cutaneous manifestations of acute painful photosensitivity with erythema and oedema, sometimes with petechiae, together with stinging and burning sensations upon exposure to sunlight, without blisters. These episodes have a variable severity depending on the exposure duration and may result in chronic permanent lesions on exposed skin. As protoporphyrin is a lipophilic molecule that is excreted by the liver, EPP patients are at risk of cholelithiasis with obstructive episodes, and chronic liver disease that might evolve to rapid acute liver failure. In most patients, EPP results from a partial deficiency of the last enzyme of the haem biosynthetic pathway, ferrochelatase, EC 4.99.1.1/FECH (encoded by the FECH gene). EPP appears to be inherited as an autosomal dominant disease, the clinical expression of which is modulated by the presence of the hypomorphic FECH IVS3-48C allele trans, but recessive inheritance with two mutated FECH alleles has also been described. In about 2% of patients, overt disease was recently shown to be caused by gain-of-function mutations in the erythroid-specific aminolevulinic acid synthase 2 (ALAS2/ALAS, EC 2.3.1.27) gene and named X-linked dominant protoporphyria. Diagnosis is established by finding increased levels of protoporphyrin in plasma and red blood cells, and detection of a plasma fluorescence peak at 634 nm. Investigations for hepatic involvement, ferrochelatase activity level, genetic analysis (FECH mutations, presence of the hypomorphic FECH IVS3-48C allele trans and ALAS2 mutations) and family studies are advisable. Differential diagnosis includes phototoxic drug reactions, hydroa vacciniforme, solar urticaria, contact dermatitis, angio-oedema and, in some cases, other types of porphyria. Management includes avoidance of exposure to light, reduction of protoporphyrin levels and prevention of progression of possible liver disease to liver failure. As the major risk in EPP patients is liver disease, a regular follow-up of hepatic involvement is essential. Sequential hepatic and bone marrow transplantation should be considered as a suitable treatment for most severe cases of EPP with hepatic involvement. EPP is a lifelong disorder whose prognosis depends on the evolution of the hepatic disease. However, photosensitivity may have a significant impact on quality of life of EPP patients

Association Between Body Mass Index and Clinical and Endoscopic Features of Eosinophilic Esophagitis

BACKGROUND: Because eosinophilic esophagitis (EoE) causes dysphagia, esophageal narrowing, and strictures, it could result in low body mass index (BMI), but there are few data assessing this. AIM: To determine whether EoE is associated with decreased BMI. METHODS: We conducted a prospective study at the University of North Carolina from 2009–2013 enrolling consecutive adults undergoing outpatient EGD. BMI and endoscopic findings were recorded. Incident cases of EoE were diagnosed per consensus guidelines. Controls had either reflux or dysphagia, but not EoE. BMI was compared between cases and controls and by endoscopic features. RESULTS: Of 120 EoE cases and 297 controls analyzed, the median BMI was lower in EoE cases (25 kg/m(2) vs. 28 kg/m(2), p=0.002). BMI did not differ by stricture presence (26 kg/m(2) vs. 26 kg/m(2), p=0.05) or by performance of dilation (26 kg/m(2) vs. 27 for undilated; p=0.16). However, BMI was lower in patients with narrow caliber esophagus (24 kg/m(2) vs. 27, p<0.001). EoE patients with narrow caliber esophagus also had decreased BMI compared to controls with narrow caliber esophagi (24 kg/m(2) vs. 27, p=0.001). On linear regression after adjustment for age, race, and gender, narrowing decreased BMI by 2.3 kg/m(2) [95% CI −4.1, −0.6]. CONCLUSIONS: BMI is lower in EoE cases compared to controls, and esophageal narrowing, but not focal stricture, is associated with a lower BMI in patients with EoE. Weight loss or low BMI in a patient suspected of having EoE should raise concern for esophageal remodeling causing narrow caliber esophagus