Multimorbidity in bullous pemphigoid: a case-control analysis of bullous pemphigoid patients with age- and gender-matched controls.

BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune blistering disease in the elderly and is associated with increased mortality. The extent of multimorbidity in patients with BP and its impact on survival are unclear. OBJECTIVES: To describe the extent and spectrum of multimorbidity in patients with BP and to ascertain its impact on survival. METHODOLOGY: This was a case-control study conducted in the setting of an academic medical centre. Cases defined as newly diagnosed BP patients referred to the inpatient dermatology service between 2005 and 2014. For every case, three age- and gender-matched controls were randomly selected. Retrospective review of medical records was performed. Univariate and multivariate comparisons of cases and controls were performed using conditional logistic regression. RESULTS: A total of 105 cases and 315 controls were included in this study. Eighty-eight cases (84%) were multimorbid (≥2 chronic diseases) as compared to 205 controls (65%) (P < 0.001), while the mean number of comorbid conditions was 3.2 ± 1.6 in cases compared to 2.4 ± 1.6 in controls (P < 0.001). 43% of cases had ≥4 comorbidities compared to 27% in controls (P = 0.003). On multivariate analysis (adjusting for age, gender and comorbidities), neurological disease (OR 10.93; CI: 5.74, 20.79) and hypertension (OR 2.38; CI: 1.18, 4.77) were positively associated with BP. Charlson comorbidity index was 6.0 ± 2.5 in cases compared to 5.0 ± 2.1 in controls (P = 0.002), and the 1-year mortality of cases and controls was 32.4% and 17.8%, respectively. CONCLUSION: Our study has shown that a significant proportion of patients with BP are multimorbid and individually have a higher number of comorbidities compared to matched controls. Disease burden and multimorbidity may well impact the prognosis of patients with BP.

SAA1 polymorphisms are associated with variation in antiangiogenic and tumor-suppressive activities in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a cancer that occurs in high frequency in Southern China. A previous functional complementation approach and the subsequent cDNA microarray analysis have identified that serum amyloid A1 (SAA1) is an NPC candidate tumor suppressor gene. SAA1 belongs to a family of acute-phase proteins that are encoded by five polymorphic coding alleles. The SAA1 genotyping results showed that only three SAA1 isoforms (SAA1.1, 1.3 and 1.5) were observed in both Hong Kong NPC patients and healthy individuals. This study aims to determine the functional role of SAA1 polymorphisms in tumor progression and to investigate the relationship between SAA1 polymorphisms and NPC risk. Indeed, we have shown that restoration of SAA1.1 and 1.3 in the SAA1-deficient NPC cell lines could suppress tumor formation and angiogenesis in vitro and in vivo. The secreted SAA1.1 and SAA1.3 proteins can block cell adhesion and induce apoptosis in the vascular endothelial cells. In contrast, the SAA1.5 cannot induce apoptosis or inhibit angiogenesis because of its weaker binding affinity to αVß3 integrin. This can explain why SAA1.5 has no tumor-suppressive effects. Furthermore, the NPC tumors with this particular SAA1.5/1.5 genotype showed higher levels of SAA1 gene expression, and SAA1.1 and 1.3 alleles were preferentially inactivated in tumor tissues that were examined. These findings further strengthen the conclusion for the defective function of SAA1.5 in suppression of tumor formation and angiogenesis. Interestingly, the frequency of the SAA1.5/1.5 genotype in NPC patients was ~2-fold higher than in the healthy individuals (P=0.00128, odds ratio=2.28), which indicates that this SAA1 genotype is significantly associated with a higher NPC risk. Collectively, this homozygous SAA1.5/1.5 genotype appears to be a recessive susceptibility gene, which has lost the antiangiogenic function, whereas SAA1.1 and SAA1.3 are the dominant alleles of the tumor suppressor phenotype.

Graft-vs-tumor effect in patients with advanced nasopharyngeal cancer treated with nonmyeloablative allogeneic PBSC transplantation.

While nonmyeloablative peripheral blood stem cell transplantation (NST) has shown efficacy against several solid tumors, it is untested in nasopharyngeal cancer (NPC). In a phase II clinical trial, 21 patients with pretreated metastatic NPC underwent NST with sibling PBSC allografts, using CY conditioning, thymic irradiation and in vivo T-cell depletion with thymoglobulin. Stable lymphohematopoietic chimerism was achieved in most patients and prophylactic CYA was tapered at a median of day +30. Seven patients (33%) showed partial response and three (14%) achieved stable disease. Four patients were alive at 2 years and three showed prolonged disease control of 344, 525 and 550 days. With a median follow-up of 209 (4-1147) days, the median PFS was 100 days (95% confidence interval (CI), 66-128 days), and median OS was 209 days (95% CI, 128-236 days). Patients with chronic GVHD had better survival-median OS 426 days (95% CI, 194-NE days) vs 143 days (95% CI, 114-226 days) (P=0.010). Thus, NST may induce meaningful clinical responses in patients with advanced NPC.