In 1528, Henry VIII slept in a different bed every night—and not in the way you might think. He did have a mistress, his wife’s lady-in-waiting Anne Boleyn. But it was fear of disease that drove him to move almost daily that summer. The king was terrified of sweating sickness, a deadly epidemic that is nearly forgotten today.

Scientists are still fascinated by the mysterious disease, which swept through Europe multiple times during the Tudor period. Beginning in 1485, five epidemics plagued England, Germany and other European countries. But the epidemic’s origins and even the identity of the disease are still murky.

There was good reason to be scared of sweating sickness. It came on without any warning and did not seem preventable. People would feel a sudden sense of dread, then be overtaken with headache, neck pains, weakness and a cold sweat that covered the entire body. Fever, heart palpitations and dehydration followed. Within three to 18 hours, 30 to 50 percent of people afflicted with the illness were dead.

It’s unclear who first contracted sweating sickness, but some historians believe it was brought to England by the mercenaries Henry’s father hired to seize England’s throne for him and his son. The controversial move ended the War of the Roses in 1487, but questions about Henry VII’s legitimate claim to the throne—and whether the foreign soldiers he imported to England to fight on his behalf brought sweating sickness with them—persist to this day.

Regardless of who contracted it first, sweating sickness soon became a regional epidemic. It was “a new kind of sickness,” wrote Richard Grafton, the king’s printer, “which was so sore, so painful, and sharp, that the like was never heard of to any man’s remembrance before that time.”

That wasn’t exactly true. England had already survived history’s most fearful epidemic. Between 1346 and 1353, the Black Death—an unprecedented wave of bubonic plague—wiped out as much as 60 percent of the world’s population and killed over 20 million people in Europe alone. But sweating sickness does not seem to have been related to plague. It had no skin symptoms and it popped up randomly in different locations, always after a period of extended rainfall or flooding and usually in the very rich or the very poor.

In a time before modern medicine, people had no way of knowing whether sweating sickness would strike or how it spread. That didn’t stop doctors from trying to find out, though, and the epidemic made an unlikely celebrity out of a man named John Kays. He saw the disease as an opportunity—especially because it seemed to strike rich noblemen. He gave himself the more impressive-sounding moniker Johannus Caius and began to treat wealthy Englishmen who, like their monarch, were paranoid of the disease.

Caius figured out another way to profit from sweating sickness: writing about it. In 1552, he publishedThe Sweating Sickness: A boke or counseill against the disease commonly called the sweate or sweatyng sicknesse. Now considered a medical classic, it lays out the doctor’s observations of the disease’s symptoms, prevention and cure. Reflecting the medical knowledge of his time, Caius advised people to avoid evil mists and rotten fruit and to exercise frequently. He recommended that people who were afflicted with the sickness drink herbal concoctions, sweat as much as possible and avoid going outdoors.

Not that his advice worked: “Despite most of Caius’s patients still ending up dead, he was eventually rich enough to make a splendid endowment to his old Cambridge college,” writes biomedical researcher Derek Gatherer. A college at Cambridge still bears Caius’ name today.

Caius and other doctors were unable to explain or stop the disease. But the fact that royals flocked to physicians for help speaks to the impact of the epidemics. Henry VIII remained scared of it throughout his entire reign. Members of his court were stricken, including Henry’s advisor Cardinal Wolsey, who survived multiple bouts of sweating sickness. And Henry’s older brother Arthur is suspected to have died from it. “One is safer on the battlefield than in the city,” wrote Henry VIII’s advisor Thomas More. (Given that he was eventually executed for refusing to recognize Henry’s divorce, that may not have been true.)

Sweating sickness stopped as quickly as it started. The last epidemic was in 1551. About 150 years later, a seeming variant called the Picardy Sweat popped up in France, but neither strain has reappeared. That makes it difficult for modern-day scientists and historians to study. They must rely on accounts of the time and primitive public health information to reconstruct the epidemics. Though it’s clear thousands died overall, the exact figure is uncertain due to spotty record keeping and lost data. And the jury’s still out on what sweating sickness actually was. Some scientists think it was a form of hantavirus, a rare disease also known as Seoul virus, others wonder if flu, food poisoning or a condition called relapsing fever were to blame.

No matter what its cause, sweating sickness left its mark. When William Shakespeare wrote Henry IV, Part 2 in 1600, a half-century after the last English epidemic, he had one of his most famous characters, Falstaff, die of “a sweat.” Did the bard mean a sexually transmitted infection or sweating sickness? That’s another longstanding historic debate—but the fact that it’s still being argued is a testament to the lasting horror of the still-mysterious disease.