Long-Term Trends in Esophageal Candidiasis Prevalence and Associated Risk Factors with or without HIV Infection: Lessons from an Endoscopic Study of 80,219 Patients

Abstract

BackgroundThe prevalence of candida esophagitis (CE) might be changing in an era of highly active antiretroviral therapy (HAART) among HIV-infected patients or today’s rapidly aging society among non-HIV-infected patients. However, few studies have investigated long-term CE trends, and CE risk factors have not been studied in a large sample, case-control study. This study aimed to determine long-term trends in CE prevalence and associated risk factors for patients with or without HIV infection.MethodsTrends in CE prevalence were explored in a cohort of 80,219 patients who underwent endoscopy between 2002 and 2014. Risks for CE were examined among a subcohort of 6,011 patients. In risk analysis, we assessed lifestyles, infections, co-morbidities, immunosuppressants, and proton-pump inhibitors (PPIs). All patients were tested for HIV, hepatitis B or C virus, and syphilis infection. For HIV-infected patients, sexual behavior, CD4 cell count, history of HAART were also assessed.ResultsCE prevalence was 1.7% (1,375/80,219) in all patients, 9.8% (156/1,595) in HIV-infected patients, and 1.6% (1,219/78,624) in non-HIV-infected patients. CE prevalence from 2002-2003 to 2012-2014 tended to increase in non-HIV-infected patients (0.6% to 2.5%; P<0.01) and decrease in HIV-infected patients (13.6% to 9.0%; P=0.097). Multivariate analysis revealed increasing age (odds ratio [OR], 1.02; p=0.007), HIV infection (OR, 4.92; p<0.001), and corticosteroid use (OR, 5.90; p<0.001) were significantly associated with CE, and smoking (OR, 1.32; p=0.085) and acetaminophen use (OR, 1.70; p=0.097) were marginally associated. No significant association was found with alcohol consumption, hepatitis B or C virus, syphilis, diabetes mellitus, cardiovascular disease, cerebrovascular disease, chronic kidney disease, liver cirrhosis, anticancer, or PPIs use. In HIV-infected patients, CD4 cell count <100/μL (OR, 4.83; p<0.001) and prior HAART (OR, 0.35; p=0.006) were independently associated with CE, but sexual behavior was not. Among corticosteroid users, CE was significantly associated with higher prednisone-equivalent dose (p=0.043 for trend test).ConclusionsThis large, endoscopy-based study demonstrated that CE prevalence increased in non-HIV-infected patients but decreased in HIV-infected patients over 13 years. Risk analysis revealed that increasing age, HIV infection, and corticosteroids use, particularly at higher doses, were independently associated with CE, but alcohol, other infections, diabetes, anticancer drugs, and PPIs use were not.

The diagnosis of clinically significant oesophageal Candida infections: a reappraisal of clinicopathological findings

“…Although this disease once showed a predilection for human immunodeficiency virus‐infected individuals and developed in up to 42% of these patients, improved retroviral therapy has resulted in decreased infection rates in this population 20 . Other risk factors for Candida oesophagitis include heavy alcohol consumption, hepatitis C viral infection, syphilis, and medications such as corticosteroids, non‐steroidal anti‐inflammatory drugs, acetaminophen, and proton pump inhibitors 6 . Recent use of antibiotic agents, motility disorders, uncontrolled diabetes mellitus, malnutrition and any process that diminishes host immunity, alters pH or modifies the microbial flora of the mucous membranes can also predispose to oesophageal candidiasis 1,3,5,14–16,21 …”

“…Infectious oesophagitis is the third leading cause of oesophagitis, following gastro‐oesophageal reflux and eosinophilic oesophagitis 1 . Candida infection, particularly with Candida albicans , is the most common cause of infectious oesophagitis, with an overall prevalence of 0.8–7.3% 2–11 . Candida is generally considered to cause an opportunistic infection, resulting in disease in patients with altered immunity due to immunodeficiency, diabetes mellitus, pregnancy, advanced age, and a number of other disorders associated with alterations in the normal components of the gastrointestinal flora.…”

Course of Esophageal Candidiasis and Outcomes of Patients at a Single Center

“…4 In a large study evaluating risk factors for esophageal candidiasis in 281 non-human immunodeficiency virus patients, corticosteroids, antibiotic use, herbal medications, and heavy drinking were identified as risk factors. 5 One of the important aspects of our study was the effect of treatment on symptoms and endoscopic followup evaluation. Symptomatic patients with a normal esophagus were approximately 3 times as likely to have resolution of their symptoms with treatment compared with untreated patients.…”

A Review of Esophagitis Due to Candida Species in Human Immunodeficiency Virus (HIV) Infected Patients

“…The incidence of EC demonstrated various ranges among HIV patients in different geographic areas because of antiretroviral therapy (ART). 6 The prevalence of EC had a decrease of about 25%-50% after one or two years of ART. Few studies investigated EC occurrence and risk factors in the last decades.…”