Anti-BP180 autoantibody levels at diagnosis correlate with 1-year mortality rates in patients with bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is the most frequent autoimmune blistering disease mainly affecting elderly patients. Among several published risk factors, a recent post hoc analysis linked anti-BP180 autoantibodies (AABs) to fatal outcomes in BP. To date, this finding has not been confirmed independently. OBJECTIVE: To investigate the potential of anti-BP180-AAB levels as a marker of prognosis and to identify a cut-off level indicative of an increased risk for early death. Secondly, to characterize parameters associated with mortality. METHODS: Retrospective, single-centre study of BP patients diagnosed between 2001 and 2012. Analyses included epidemiological and patient- and disease-specific characteristics as well as immunological parameters at diagnosis and during follow-up. Standardized mortality ratios as well as uni- and multivariate regression analyses were calculated. RESULTS: One hundred patients (56 women, 44 men) with a median age of 81 years (interquartile range 74-86) were followed up for a median of 775 days (interquartile range 162-1617). One-year mortality rates were 25.0% implying a 2.4-fold increased risk of death compared with the general population. High anti-BP180 autoantibody levels at diagnosis (CI95 1.30-2.89; P = 0.001), dementia (CI95 1.13-6.72; P =0.03), length of hospitalization (CI95 1.16-2.41; P = 0.01) and age (CI95 1.23-4.19; P = 0.009) correlated significantly with 1-year mortality. BP180-AAB concentrations of ≥61 U/mL characterized a subgroup of patients with a particular higher risk for early death compared with the general population (CI95 1.81-3.81; P < 0.0001). CONCLUSION: In bullous pemphigoid, serum concentrations of BP180 autoantibodies at diagnosis could help to identify patients at risk for death within the first year after diagnosis (cut-off value 61 U/mL).

Carvedilol for reducing portal pressure in primary prophylaxis of variceal bleeding: a dose-response study.

BACKGROUND: Sequential measurements of hepatic venous pressure gradient (HVPG) are used to assess the haemodynamic response to nonselective betablockers (NSBBs) in patients with portal hypertension. AIMS: To assess the rates of HVPG response to different doses of carvedilol. METHODS: Consecutive patients with cirrhosis undergoing HVPG-guided carvedilol therapy for primary prophylaxis of variceal bleeding between 08/2010 and 05/2015 were retrospectively included. After baseline HVPG measurement, carvedilol 6.25 mg/d was administered and HVPG response (HVPG-decrease ≥20% or to ≤12 mm Hg) was assessed after 3-4 weeks. In case of nonresponse, carvedilol dose was increased to 12.5 mg/d and a third HVPG-measurement was performed after 3-4 weeks. We also assessed HVPG-response rates according to the Baveno VI consensus (HVPG decrease ≥10% or to ≤12 mm Hg) and changes in systolic arterial pressure (SAP). RESULTS: Seventy-two patients (Child A, 37%; B, 35%; C, 28%) were included. 28 (39%) patients achieved a HVPG-decrease ≥ 20% with carvedilol 6.25 mg/d and another 10 (14%) with carvedilol 12.5 mg/d. Forty (56%) patients had a HVPG decrease ≥10% with carvedilol 6.25 mg/d and 24 (33%) with carvedilol 12.5 mg/d. Thus, in total, a HVPG-response of ≥20% and ≥10% and was achieved in 38 (53%) and 55 (76%) and of patients respectively. Notably, 6 patients (n = 4 with ascites) did not tolerate an increase to 12.5 mg/d due to hypotension/bradycardia. However, none of the other patients had a SAP < 90 mm Hg at the final HVPG measurement. CONCLUSION: Carvedilol 12.5 mg/d was more effective than 6.25 mg/d in decreasing HVPG in primary prophylaxis. A total of 76% of patients achieved a HVPG-response of ≥ 10% to carvedilol 12.5 mg/d, however, arterial hypotension might occur, especially in patients with ascites.

Randomised clinical study: the effects of oral taurine 6g/day vs placebo on portal hypertension.

BACKGROUND: The amino sulphonic acid taurine reduces oxidative endoplasmatic reticulum stress and inhibits hepatic stellate cell activation, which might lead to reduction of portal pressure in cirrhosis. AIM: To assess the haemodynamic effects of taurine supplementation in patients with cirrhosis and varices. METHODS: Patients with hepatic venous pressure gradient (HVPG) ≥12 mm Hg were included in this prospective proof of concept study. Concomitant nonselective beta-blockers therapy was not allowed. Patients received either 4 weeks of oral taurine (6 g/day), or placebo, prior to evaluation of HVPG response. RESULTS: Thirty patients were screened and 22 included in the efficacy analysis (12 taurine/10 placebo; 64% male, mean age: 52 ± 11 years, Child A: 9%, B:64%, C:27%, ascites:68%). In the taurine group, mean HVPG dropped from 20 mm Hg (±4) at baseline to 18 mm Hg (±4) on day 28 (mean relative change: -12%, P = .0093). In the placebo group, mean HVPG increased from 20 mm Hg (±5) at baseline to 21 mm Hg (±5) on day 28 (mean relative change:+2%, P = .4945). Taurine had no significant effects on systemic haemodynamics. Seven of 12 patients (58%) on taurine achieved a HVPG response >10%, compared to none in the placebo group (P = .0053). In a multivariate linear model, HVPG reduction was significantly larger in the taurine group compared to placebo group (P = .0091 and P = .0109 for absolute and relative change respectively). Treatment-related adverse events included gastrointestinal discomfort and fatigue, and were usually mild and comparable between treatment groups. CONCLUSION: Taurine is safe and may reduce portal pressure in cirrhotic patients. More studies on the underlying mechanisms of action and long-term effects of taurine supplementation are warranted.

Testing patients with non-specific symptoms for antibodies against Borrelia burgdorferi sensu lato does not provide useful clinical information about their aetiology.

The aim of this study was to determine whether patients with antibodies against Borrelia burgdorferi sensu lato or who report a history of erythema migrans (EM) or tick bite are more likely to have non-specific symptoms such as musculoskeletal pain, fatigue, sensory disorder, and headache. The study group comprised 423 subjects with non-specific symptoms tested for antibodies against B. burgdorferi sensu lato between July 2012 and December 2014 because of suspicion of Lyme borreliosis (LB). Of these, 285 were females (67%) and 138 were males (33%); the median age was 53 years (range, 7-89 years). Patients with a confirmed diagnosis of LB and patients with a known underlying disease that could influence the development of the symptoms were excluded from the evaluation. Subjects were assigned to the seronegative group or to one of three seropositive groups, and the history of EM and tick bite was also recorded. Statistical analysis was performed with single chi-square tests of independence and multiple logistic regression models. No differences in the occurrence of non-specific symptoms were observed between patients grouped according to antibody status. A history of EM showed no significant effect on any of the non-specific symptoms. A history of tick bite was weakly correlated with joint pain and joint swelling (p <0.05). In conclusion, it is highly unlikely that the complaints are related to a previous infection with B. burgdorferi sensu lato. The results show that testing patients with non-specific symptoms for antibodies against B. burgdorferi sensu lato in the everyday clinical setting does not provide any useful information about their aetiology.