Auto-brewery syndrome in a 50-year-old woman

Discussion

Auto-brewery syndrome is a rare syndrome of endogenous alcohol fermentation. A 1948 report of a boy with a ruptured stomach whose contents smelled of alcohol was the first to describe gut fermentation.1 Auto-brewery syndrome as a diagnostic entity was first described in 1952 in Japan, where it bears the layman term Meitei-sho, which translates as “alcohol auto-intoxication syndrome.” 2 The first cases in North America were published in the United States in the 1980s.3^,4 A 2020 systematic review identified 20 patients reported in the English medical literature since 1974.5

Auto-brewery syndrome is thought to result when microorganisms capable of fermenting alcohol from carbohydrates outgrow normal gut flora.6 Although population-based studies have shown that gut alcohol fermentation with low levels of endogenous ethanol can occur even among healthy people, blood ethanol levels rarely reach concentrations high enough to cause intoxication.7 Auto-brewery syndrome is uncommon because it requires several host factors to interact with substantial overpopulation of fermenting microorganisms, and high carbohydrate consumption.6 Comorbidities such as diabetes, liver disease, gut dysmotility disorders, and inflammatory bowel disease are associated with auto-brewery syndrome through mechanisms contributing to increased levels of blood glucose and decreased ethanol metabolism.6^,7 Genetic predisposition for inactive aldehyde dehydrogenase enzyme and subsequent inefficient alcohol metabolism, may also play a role.6 In our patient, we suspect her recurrent antibiotics for UTI and dexlansoprazole use led to gut dysbiosis with potential contribution of genetics, resulting in auto-brewery syndrome.

Commonly implicated fungi responsible for outgrowing normal gut flora in auto-brewery syndrome are Saccharomyces cerevisiae and Candida species including C. albicans, C. tropicalis, and C. glabrata.2 Bacteria have also been cultured from patients with auto-brewery syndrome. Although the role of bacteria remains unclear, a recent case–control study proposed Klebsiella pneumoniae as an important culprit.7^–9

No standardized diagnostic algorithms are available for autobrewery syndrome and years of delay to diagnosis are common. 8^,9 When auto-brewery syndrome is suspected, the diagnostic framework includes performing a history (from the patient and close contacts), physical examination, blood work, glucose challenge test, and microbiological assessments (Figure 1). A CAGE screening questionnaire should be performed and blood ethanol and liver enzyme levels should be measured.3

Figure 1:

Diagnostic framework for suspected auto-brewery syndrome.

Protocols for glucose challenges include obtaining a baseline level of ethanol from blood or via a breathalyzer, followed by ingestion of a high load (100–200 g) of glucose. Ethanol levels are obtained at 1, 2, 4, 8, 16, and 24 hours after glucose ingestion. The glucose challenge should be conducted in a monitored setting to ensure no consumption of ethanol and safety in the event of intoxication.3^,8 Undetectable ethanol levels at baseline, followed by detection of ethanol after glucose ingestion, can confirm the diagnosis.

Fungal and bacterial cultures of gastrointestinal secretions obtained through esophagogastroduodenoscopy or colonoscopy can help identify culprit pathogens with antimicrobial susceptibility. 3 Stool fungal cultures can also be obtained as an adjunct test.6^,8 The diagnostic yield of the glucose challenge and microbiologic evaluations will decrease if these are conducted after administration of empiric antifungal agents, as with our patient. Therefore, prompt arrangements for these diagnostics are crucial when auto-brewery syndrome is suspected, as delays in treatment can prolong its physical, social, and financial ramifications.

Management of auto-brewery syndrome lacks established guidelines. Antifungal therapy and low-carbohydrate diets have been the primary treatments in documented cases. If a microbiologic diagnosis is established, an antifungal agent can be chosen based on susceptibility. Otherwise, fluconazole is a reasonable empiric choice given that S. cerevisiae and C. albicans are the most commonly implicated fungi.2^,7

Relapse after antifungal treatment, in the absence of dietary nonadherence, should prompt endoscopic evaluation for culture and susceptibility testing. Echinocandins, itraconazole, voriconazole, and amphotericin B have been successfully used in cases of relapse after fluconazole.7^,8 One patient who had refractory symptoms despite trials of several antifungals received a fecal microbiota transplant with effective symptom resolution.10

Clinical and biochemical resolution of auto-brewery syndrome has been reported with 3 weeks of fluconazole (100–150 mg/d).3^,7 Among patients with relapsing disease, antifungal durations of 6–8 weeks have been successful.3 In addition to antifungals, probiotics may provide benefit by replenishing gut bacteria as competitive flora to fungi.3^,8 Levofloxacin therapy resolved auto-brewery syndrome in a patient in whom K. pneumoniae was identified as a culprit pathogen.9 Management of auto-brewery syndrome should include evaluation for hepatic effects of ethanol similar to those with alcohol use disorder.

Auto-brewery syndrome carries substantial social, legal, and medical consequences for patients and their loved ones. Our patient had several ED visits, was assessed by internists and psychiatrists, and was certified under the Mental Health Act before receiving a diagnosis of auto-brewery syndrome, reinforcing how awareness of this syndrome is essential for clinical diagnosis and management.