Eduardo Valle, MD, a second-year medical resident in Brazil, was sitting in the hospital cafeteria with his fellow residents in late December when they heard news of the emergency department's newest patient. A middle-aged man with abdominal pain, vomiting, constipation, and unexplained acute kidney injury had just arrived from a smaller hospital 80 miles away. 160 miles to the north, the man's son-in-law was in the intensive care unit of another hospital in the city of Belo Horizonte with symptoms that were identical but progressing faster than the older man's, a fellow resident told Valle. The son-in-law was showing signs of quadriplegia and required mechanical ventilation. The residents scattered from the cafeteria to relay the news to their attendings. In what seemed like minutes, their hospital in the city of Juiz de Fora was abuzz with talk of the unexplained illness. "We thought it could be contagious," Valle told Medscape. "Fear was in the air." Valle volunteered to help the nephrology team research the case. Testing showed the older man had normal blood cell counts, elevated lactic acid, and hepatitis without liver dysfunction. His cranial CT scans appeared normal. After a few days, none of the team's leads had panned out and the father's limbs started to lose function. Meanwhile, three other people from the son-in-law's neighborhood were also admitted to the ICU in Belo Horizonte with similar symptoms. The strange, linked cases were the start of a medical mystery that took the doctors' intense collaboration to solve as they tried to save their patients. Seeking help, Valle posted the case on Medscape Consult, a global crowdsourced social media platform on which clinicians share and discuss real cases. "Is this an unknown infection or intoxication?" he wrote. "Any thoughts?" Doctors from around the world responded to his case suggesting botulism, rhabdomyolysis, and lead poisoning, but none of the suggestions could fully explain the patients' symptoms. Then the patients' family mentioned that the men had shared some beer over the Christmas holiday. A WhatsApp discussion between the doctors in Juiz de Fora and Belo Horizonte confirmed that all five patients drank the same brand of beer before their symptoms started. The doctors began rapidly sharing contamination case studies via the WhatsApp channel until one case of nausea, acute kidney injury, and cranial nerve palsy following a "mystery drink" seemed to match what they were seeing. A toxicology investigation by police confirmed their suspicion: Diethylene glycol, a poisonous industrial solvent used in antifreeze, was found in beer bottles from the patients' homes and blood samples from four of the patients. But the resolution came too late for Valle's patient. The man died; his kidney biopsy showed acute tubular necrosis and his blood contained diethylene glycol. The man Valle treated was one of more than 30 reported cases and 6 deaths from the diethylene glycol poisoning outbreak in Brazil's state of Minas Gerais, where Juiz de Fora and Belo Horizonte are located. Police identified the source as a craft brewer, Belorizontina Backer. Brazil's Ministry of Agriculture called the contamination "systemic" in a statement and stopped all production at the brewery until it could be remedied. A Rare and Tricky Diagnosis The most well-known diethylene glycol poisoning in the US occurred in 1937, when a pharmaceutical company, S.E. Massengill Co, used it as a solvent in a liquid formulation of the antibiotic sulfanilamide. More than 100 people in the US died after ingesting it, and public outcry prompted the 1938 Federal Food, Drug, and Cosmetic Act that authorized the US Food and Drug Administration to require evidence of safety for new drugs, issue standards for food, and conduct factory inspections. The cases in Brazil were the first recorded diethylene glycol poisonings in the country's history, Valle said. Renal failure and severe neurological symptoms are pretty typical of diethylene glycol poisoning, Andrew Stolbach, MD, MPH, a medical toxicologist at Johns Hopkins University in Baltimore, Maryland, told Medscape. But because there's no direct test for the substance and such poisonings are rare, the diagnosis can be tricky for most doctors, he said. "I've only been involved in one case, and that's probably more than most people," Stolbach said. In 2006, he treated a patient who ingested the toxic alcohol via an expectorant that she brought back from Panama. Early detection is essential to treating diethylene glycol poisoning and preventing its devastating neurologic symptoms. But to do that, "you have to have a high degree of suspicion," Stolbach said. In the early stages, patients will appear drunk, though perhaps more quickly than usual, according to Eric Judd, MD, a nephrologist at the University of Alabama in Birmingham. The first evidence of diethylene glycol poisoning is a gap in blood osmolarity — one significantly greater than in ethanol intoxication. Running a metabolic panel and doing some calculations to find an osmolarity gap is one way to detect diethylene glycol poisoning before dangerous symptoms set in, Judd said. Essentially, you'd only find it if you were looking, he said. After a reported outbreak, doctors nearby need to be acutely mindful of anyone in the ER who appears intoxicated and may have gastrointestinal issues, Judd said. If spotted early, it's possible that a dose of the alcohol dehydrogenase inhibitor fomepizole could be enough to treat diethylene glycol poisoning, Stolbach said. Preventing the breakdown of diethylene glycol shields the body from its metabolites, which are far more dangerous than the toxic alcohol itself. The severity of symptoms increases as the body metabolizes diethylene glycol, Stolbach told Medscape. "Once you've made the acid metabolites, we are concerned that you're now on your way to renal failure and stopping new production of metabolites [with fomepizole] won't change that," Stolbach said. At that point, the patient will require hemodialysis, which will only protect against further symptoms if diethylene glycol and its metabolites are filtered out before they damage the nervous system, he said. Because of the delay between ingestion and symptoms, it can take a while for doctors and public health workers to figure out why and how an outbreak is happening. But "even if we can't offer much to those with advanced neurological symptoms," these poisonings rarely occur as single cases, Stolbach said. There are likely others that physicians will be able to help. The son-in-law of Valle's patient was diagnosed late. He remains in critical condition in the ICU relying on hemodialysis, mechanical ventilation, and a vasopressor. For more than 2 weeks he showed only discreet eye movement, his nephrologist Fabricio Marques, MD, told Medscape. "So, his ability to nod and communicate is a great victory. If he manages to survive he will most likely have neurological sequelae." Soon after diethylene glycol was identified as the culprit in Valle's patient, the Minas Gerais State Society of Nephrology issued a warning to all doctors about the risk of contamination and potential symptoms. No other people with diethylene glycol poisoning came to the hospital in Juiz de Fora. Marques saw three other patients with the poisoning and was involved indirectly with at least seven other patients at different hospitals in the city. For Valle, the takeaway of the case was more than clinical. He observed his advisors modeling collaboration on the cusp of a crisis. The WhatsApp group between the doctors treating the father and those who treated the son-in-law was critical to the case, helping identify the beer as a common exposure and allowing the doctors to discuss a myriad of possible diagnoses before pinpointing the toxin. "I learned when we don't know what's happening with our patient, we have to ask for help," Valle said. Source
