After A Woman Was Prescribed A Common Medicine, Her Blood Suddenly Began Turning Blue

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When a woman in her mid-20s notices that her skin has taken on a blue tint, it’s not Halloween night, nor is she in a scene from a movie set in a world galaxies beyond ours. Her unusual skin tone is very real – and very troubling. So, the woman walks into a Rhode Island emergency room in seek of help from doctors who might be able to get to the bottom of her worrying problem. And, fortunately, medical professionals are able to make a diagnosis. Apparently, the patient’s bizarre appearance can be chalked up to a very uncommon medical condition – one that can be caused by a widely used medicine.

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The woman had more concerns than just her blue skin, in fact, although that symptom would be enough to scare just about anyone. As she told those at the hospital, she was also having trouble breathing and experiencing spells of acute tiredness. Naturally, though, it was the patient’s strange hue that initially stuck out to her attending doctors.

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But this cyanotic skin ultimately helped the doctors discern what had happened to the young Rhode Island woman. Thankfully, then, they were able to diagnose her condition. And in doing so, the medics realized something even more remarkable: the patient had gotten her blue tint from a very common health remedy that she’d administered the previous evening.

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Emergency room doctors Benjamin Blackwood and Otis Warren were the ones responsible for determining exactly what the woman was suffering from. And as Warren had previously seen a very similar case, he instantly knew the cause of the blue-hued skin. It turned out, you see, that the woman had a condition called methemoglobinemia.

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Methemoglobinemia affects the make-up of the body’s red blood cells by causing unusually high levels of methemoglobin to be produced. And as the amount of methemoglobin is raised, this makes it harder for hemoglobin – a protein contained within the red blood cells – to do its job.

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Hemoglobin has a vital function in the body, too, as it directs oxygen from the lungs – or gills, depending on the species in question – to the areas that need it. So, although hemoglobin is still able to perform this task if there is an excess of methemoglobin in the system, it cannot deposit the oxygen as efficiently in the parts of the body that require it.

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In those who don’t suffer from methemoglobinemia, methemoglobin makes up less than 1 percent of blood. Those with the condition, by contrast, have methemoglobin levels of at least 10 percent, although that total could ultimately be many times higher. And as is to be expected, the more methemoglobin is present in the body, the greater the health risks to those suffering from methemoglobinemia.

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What’s more, while methemoglobin levels as high as 15 percent often won’t cause problems in healthy individuals, a 10 percent methemoglobin content in the blood can cause the common symptoms of methemoglobinemia to show in those with other underlying conditions. Tiredness, disorientation and breathing difficulties can occur, as can cyanosis, which leads the skin to change from its normal hue to a shade of purple or blue.

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In particular, cyanosis takes place when tissue close to the skin doesn’t receive the required amounts of oxygen. And in more serious cases, methemoglobinemia patients have more to worry about than merely looking a little off-color. Should methemoglobin levels in the blood reach more than 50 percent, seizures and comas can occur, while at 70 percent or higher, the condition may prove fatal.

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And generally people acquire methemoglobinemia in one of two ways. For example, some come into the world with the condition owing to their relative lack of an enzyme named diaphorase I. Then, without a sufficient quantity of diaphorase I in the system, methemoglobin levels can increase, meaning babies can be born with bodies that are less capable of transporting oxygen than usual. Some of these infants come into the world looking blue in the skin, too.

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On occasion, then, the presence of methemoglobinemia can be traced back to a baby’s genetics. Should one parent have the gene responsible for causing blood to flow improperly, then the child won’t be born with bluish skin caused by oxygen deficiency. If two parents have the gene in question, though, the baby could come out with an indigo hue.

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In other cases, methemoglobinemia occurs after a person is born and has exhibited normal blood oxygen levels. Typically, this is due to a particular medication, although bromates, dyes, nitrates and chlorates can also trigger an increase in methemoglobin. And while protective enzymes in the blood would usually block such a rise, certain medicines can cause levels of methemoglobin to reach the point that the body’s natural systems become overcome.

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Those most often affected by methemoglobinemia, meanwhile, are very young children aged six months or under. That said, people who drink privately sourced water should also be wary. Without the necessary regulation, independent wells could develop dangerously large amounts of nitrates, which in turn can cause methemoglobin spikes – especially in babies.

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Thankfully, though, if someone is experiencing methemoglobinemia, doctors have plenty of ways to remedy the situation. Typically, medics administer an intravenous solution of methylene blue and oxygen that restores tissue to breathable levels. And, fortunately, most methemoglobinemia patients feel better shortly after this treatment is given.

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This method works, moreover, because methylene blue returns iron back to the hemoglobin. But although this particular treatment is often effective in acquired cases of methemoglobinemia, congenital sufferers need a more permanent solution to the problems posed by their oxygen-poor blood.

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And as it turns out, doctors treat these patients with methylene blue, too, as taking the compound orally each day can keep oxygen flowing through the blood healthily. Methylene blue may also help boost enzymes’ methemoglobin-fighting powers, while vitamin C is handy at warding off the blue-tinted skin that is caused by cyanosis.

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Before such treatments for methemoglobinemia were developed, however, people with the condition simply had to live with their blue skin. And as such, some became famous for their unusual appearances. Take, for example, the Fugate family, who once dwelled in the Kentucky hills and made a name for themselves through their methemoglobinemia.

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When Martin Fugate and Elizabeth Smith tied the knot, you see, they didn’t just join in holy matrimony; they also brought together the methemoglobinemia gene that each of them carried. A neighboring family whose members many of the Fugates’ children would marry also carried the blue-skin-causing gene.

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So, from the early 19th century onward, the Fugate-Smith union produced blue-tinted children, who in turn produced more blue-tinted kids. Much of the extended family clustered in districts such as Ball Creek and Troublesome Creek, remaining in their indigo communities until the 20th century. And over time, people began referring to them as the Blue People of Kentucky.

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Then, in the 20th century, word of the Fugates’ condition started to spread further afield. And, fortunately, the right doctor would hear about the family’s strange predicament. Hematologist Madison Cawein III subsequently studied the Fugates and their family line to better understand why they may have turned such an unusual shade. Ultimately, Cawein also gave the clan methylene blue – the remedy still used in modern-day cases of methemoglobinemia.

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And as time went on, the Fugates started to settle further afield, which in turn thinned out the blue-tinged population that had gathered in their corner of Kentucky. This meant that the recessive gene left the area, too, thus causing fewer and fewer blue births to occur. The last known descendant of the family born with methemoglobinemia, Benjamin Stacy, came into the world in 1975, and his skin has faded into a more natural color over the years.

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Intriguingly, though, not all cases of blue skin can be traced back to methemoglobinemia. You see, a condition called argyria can also change a person’s pigment to a bluish or purplish color. Sufferers may see small patches with these characteristics pop up, although in certain cases the entirety of the skin can change its hue.

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And perhaps one of the most famous argyria sufferers was Paul Karason, whose skin became so remarkably blue that images of him went viral and earned him the nickname “Papa Smurf.” Furthermore, unlike those with methemoglobinemia, Karason apparently didn’t have any options when it came to muting the bluish tone in his skin, as it had permanently changed color.

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Karason had suffered from dermatitis, which causes the skin to itch, become dehydrated and sometimes break into a rash. To remedy the situation, then, he’d applied a compound mixed with silver for more than ten years. And there may have been some medical basis for that decision, as the metal does in fact have antibacterial qualities. These properties in turn once made treatments that contained silver very popular.

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However, over the course of time medical professionals opted to use superior antibacterials such as penicillin. And in the late 1990s the FDA banned the use of silver in medications entirely, owing to the propensity of the metal to build up in the body. The darkly pigmented remains of silver metal and sulfides turns the skin a purplish color, thus causing argyria.

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Blue skin also changed Karason’s life, as he spent much of his days with argyria as a recluse. And in 2013 Karason’s estranged wife told Today that he didn’t always like being addressed as “Papa Smurf,” although sometimes it did bring him joy. She said, “That was a nickname he didn’t appreciate, depending on who said it.”

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“If it was a kid who ran up to him saying, ‘Papa Smurf,’ it would put a smile on his face,” Karason’s former spouse added. “But if it was an adult, well…” In 2008 Karason even emerged from seclusion to speak to Today about his skin condition and to explain how he had gotten it.

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Unfortunately, though, as is the case with methemoglobinemia, argyria brings with with it some health implications; it could impair a person’s vision at night, for example, or cause damage to their kidneys. Yet when Karason passed away in 2013 at the age of 62, his death apparently wasn’t caused by his argyria. Instead, he had a heart attack, after which he contracted pneumonia then suffered a major stroke.

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And although “Papa Smurf” Karason, the Fugates and others have risen to fame for their strange hues, methemoglobinemia isn’t a common condition by any means. In fact, emergency-room physician Warren, who treated the 25-year-old woman with blue skin, has since tried to explain the condition’s rarity.

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In 2019 Warren told CNN that, in all of his time working as an ER physician, he’d only seen one other blue patient prior to the Rhode Island woman. He also went on to explain the chances of any doctor encountering even a single instance of methemoglobinemia. Warren said, “It’s one of those rare cases that we’re taught about, [that] you study for [and] take tests on, but you rarely ever see.”

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Fortunately for Warren – and the young woman who needed his help – he was one of the few doctors who’d witnessed methemoglobinemia in person. So, as soon as he saw his second blue patient at the hospital in Rhode Island, he knew exactly what she had – and precisely how to treat her.

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It turned out, moreover, that the woman’s case of methemoglobinemia came from an interesting source. She hadn’t had the condition since birth, of course; instead, she reported to Warren and Blackwood – the other attending medic – that she’d applied a common anti-pain medication the previous evening. The patient had used so much of the treatment, however, that she had caused herself to turn cyanotic, as her doctors put it.

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In a study that Warren and Blackwood published in the New England Journal of Medicine in September 2019, they revealed that the patient had suffered a toothache the night before she ended up in the emergency room. The doctors added that in order to soothe her pain, the woman in question had used “large amounts of topical benzocaine.”

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Benzocaine has a long history as a pain reliever, in fact, as it was given the green light for medical application at the turn of the 20th century. And since then, it’s made its way into a slew of over-the-counter remedies for common complaints. The brand Orajel, for instance, uses benzocaine to dull toothaches.

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Benzocaine also appears in other topical pain relievers, such as formulas meant to treat oral ulcers, and can be an ingredient in anesthetic ointments and cough drops. In fact, the effective pain suppressant is used for a whole slew of issues – among them sore gums, denture irritation, earaches and even cold sores. Some medical professionals additionally use benzocaine for localized anesthesia before any surgical procedures.

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So, it seemed that the Rhode Island woman with acquired methemoglobinemia had had a reaction to using too much benzocaine. And while doctors noted that the patient’s response to the pain reliever was very rare, the Food & Drug Administration (FDA) nevertheless issued a warning after her treatment concluded. In particular, the FDA cautioned the public against giving benzocaine-based treatments to children under two with teething pains.

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Regardless, though, methemoglobinemia remains both a rare condition and an uncommon side effect of benzocaine usage. At the time of the Rhode Island woman’s diagnosis, the FDA had only counted 319 cases in which the drug had caused such a reaction – and just three of those instances had ended in death.

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Yet even with the FDA’s findings and infant-centric warning, many use benzocaine without knowing its potential drawbacks. And according to a September 2019 report in The Sun, Warren pointed out the need for education on this medication, saying, “People have no idea that something very specific and very dangerous can happen. It is not a mild side effect.”

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Warren explained, too, that while the woman in his ER had refuted having applied her entire supply of benzocaine at once, he believed that she had nevertheless “used a whole lot of it.” This treatment in turn had caused the blue tinge to her skin and nails – along with a dark indigo tint to her blood. Luckily for the patient, though, she had a knowledgeable medical team to count on.

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And in the end, the woman who was treated in Rhode Island walked away unscathed after her temporary skin complaint, with a couple of measures of methylene blue curing her. Indeed, according to Warren, methemoglobinemia is thankfully as simple to treat as it is unusual to encounter. The doctor added, “In my field, emergency medicine, when you can cure a patient with a single antidote – that’s a rare thing for us.”

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Most people would agree that this woman and her blue skin are up there with some of the most bizarre medical cases around. But another patient who undoubtedly makes the cut is a man from North Carolina. You see, Greg Phillpotts struggled to shake off what initially seemed to be a simple runny nose – but it turned out to be the sign of a life-threatening condition.

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Like a lot of other people throughout the years, you see, Phillpotts was suffering from a runny nose. But by February 2018, he’d been dealing with the issue for around half a decade. And during that period, a number of medics had found it difficult to pinpoint precisely what the problem was.

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In fact, the experts told Phillpotts that his ailment was either bronchitis or pneumonia. Yet no one could give the man a definitive explanation for his problems. So he continued to assume that his runny nose was being caused by allergies. And while that is somewhat irritating, the grandfather appeared to have a handle on the condition until early 2018 – at which point something changed.

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One night in February, Phillpotts couldn’t shake a nasty cough – and this left him feeling increasingly worried. So after the incident had passed, he decided to visit Mount Sinai Hospital, located in his old home city of New York. And at that point, the North Carolina resident was at last given the answers he’d been looking for. The problem was a lot more serious than a simple allergy, however.

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For some of us, of course, certain periods of the year can be daunting due to allergies. And while people are often able to avoid some of the direct physical causes of an allergic reaction, such as a particular animal or food item, other irritants can’t be sidestepped so easily. Pollen, for example, is one of the biggest problems in this regard.

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A form of powder usually found in plants, pollen can cause allergies such as hay fever to flare up during the summer months. And as a result, those who are prone to the condition have to be alert to pollen levels – especially if they’re outside. Sometimes that just isn’t enough, though, so many people simply can’t avoid enduring the unpleasant symptoms of hay fever.

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One of the most common hay fever symptoms is a runny nose, too, as the pollen can inflame your nasal passage. In addition to that, though, sufferers are also prone to excessive sneezing and blocked noses, while their eyes can be affected as well. This allergy isn’t a particularly recent problem, mind you.

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Hay fever appeared in texts as far back as the 10th century, in fact, when a Persian doctor named Rhazes described its effects. Hundreds of years later, in 1859, British physician Charles Blackley discovered the significant connection between pollen and the allergy.

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And today a significant number of people across the world still have to deal with the condition. In America alone, for example, nearly 20 million adults in 2017 had been afflicted with hay fever over the preceding 12 months. More than five million children received the same diagnosis during that time frame as well.

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So in 2013 Greg Phillpotts appeared to be yet another victim of a troublesome allergy. He had started to display one of the condition’s symptoms, after all. Yes, the grandfather had to deal with a runny nose – but thought little of it. As we’ve heard, though, unfortunately for him the issue continued for quite some time.

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In 2016 Phillpotts packed his bags for Johnston County, North Carolina, following the retirement of his spouse. As he left New York behind, however, he still couldn’t shift the irritation in his nose. And according to Phillpotts, keeping it under control proved to be a real challenge.

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“You could be anywhere,” Phillpotts said of his symptoms during an interview with WTVD in November 2018. “You could be on the airplane, you could be talking to anybody, and this thing just drains out of your face. I was stuffing tissues up my nose.” He then revealed a little more about the condition’s cycle.

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Just like a typical allergy, Phillpotts’ ailment would flare up during a particular period of the year. “I have an annual allergy that comes [on] around February,” he continued. “Sometimes it won’t go away. And then I gotta go find some Jamaican roots to drink! Anything just to knock the cough down.”

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This self-described “annual allergy” proceeded to make an unwelcome appearance during Thanksgiving in 2017 – causing a big problem for Phillipotts’ family. “I was preparing a meal and standing in the kitchen, and it just added itself to the ingredients,” he told the television station. “It screwed up the whole dinner.”

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As a result of exasperating moments like that, no doubt, Phillpotts had tried to get some answers by visiting a number of different doctors down the years. Incredibly, though, the medics couldn’t pinpoint what the issue was – despite checking him over. That subsequently led to varying diagnoses, one of which was bronchitis.

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“Bronchitis is an infection of the main airways of the lungs (bronchi), causing them to become irritated and inflamed,” reads a description of the condition on the U.K.’s NHS website. “Most cases of bronchitis develop when an infection irritates and inflames the bronchi, causing them to produce more mucus than usual. Your body tries to shift this extra mucus through coughing.”

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Alongside the coughing, though, one of the other signs that you might have bronchitis is a runny nose, due to the surfeit of mucus in your system. Given that Phillpotts described having a cough as well, then, it seemed to be a reasonable diagnosis. Yet he received contrasting information from another doctor, who instead claimed Phillpotts had pneumonia.

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“Pneumonia is swelling (inflammation) of the tissue in one or both lungs,” the NHS website states. “It’s usually caused by a bacterial infection. At the end of the breathing tubes in your lungs are clusters of tiny air sacs. If you have pneumonia, these tiny sacs become inflamed and fill up with fluid.”

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Much like bronchitis, then, pneumonia causes you to develop a nasty cough that sometimes brings up mucus. But as the uncertainty about his ailment continued, Phillpotts went on with his life as usual and tried as best he could to endure the symptoms. In February 2018, though, that all changed after he received a real scare.

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“It became normal up until February, because I was up all night coughing,” Phillpotts told WTVD. “You’re sitting here, you’re a family man. You don’t want to check out of the picture when it’s something someone could readily fix.” So the grandfather looked to solve the mystery once and for all.

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Phillpotts therefore booked an appointment at one of the hospitals under the Mount Sinai Health System – located back in New York. First established in 2013, the health network boasts in excess of 6,000 doctors. And Phillpotts was due to meet Dr. Alfred Iloreta in the hope of finding some firm answers to his questions.

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Thankfully for Phillpotts, then, he appeared to be in capable hands. “Alfred Marc Iloreta is an Assistant Professor of Otolaryngology and member of the Division of Endoscopic Skull Base Surgery at Mount Sinai School of Medicine,” reads a post on the hospital’s website. “He received his medical degree from the University of Kansas School of Medicine.”

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Dr. Iloreta’s accolades don’t end there, either, as he continued his medical training after graduating. “[He] completed his internship and residency at Mount Sinai Medical Center, and a fellowship in Skull Base Surgery and Rhinology at Thomas Jefferson University,” the post added. Off the back of that, the physician started to focus on various “clinical interests.”

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Dr. Iloreta in fact began to specialize in issues relating to the neck and head, with a particular focus on certain types of tumors. And while he continues to work at the hospital three days a week, that hasn’t stopped him from broadening his horizons. Even now, Dr. Iloreta’s still compiling personal studies.

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“[Dr. Iloreta’s] current research is focused on health outcomes following skull base surgery, sinus surgery and rhinoplasty,” reads the post on the hospital website. “Dr. Iloreta has authored textbook chapters and published manuscripts in peer-reviewed journals in rhinology, facial plastic surgery, neurosurgery and otolaryngology. He has been invited to teach at skull base courses around the country.”

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So, back at the facility in the Big Apple, Dr. Iloreta met Phillpotts and examined him. And following those tests, the Mount Sinai practitioner was able to pinpoint what the issue was – bringing the five-year mystery to an end. Few people could’ve predicted the eventual diagnosis, however.

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As it turned out, Phillpotts was suffering from cerebrospinal fluid leak – better known as a CSF leak. So what he thought was just a runny nose was actually fluid leaving his brain. Dr. Iloreta subsequently gave a detailed description of the condition and the dangers it can pose if left untreated.

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“It’s the leakage of fluid that surrounds the brain to cushion it primarily to protect it from shock or trauma or anything like that,” Dr. Iloreta told WTVD. “Sometimes when you have this leakage of the fluid from the brain, it can evolve into what we call an ascending infection. So bacteria can travel from the nose to the brain, resulting in meningitis.”

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While many diseases and other medical conditions were first written about hundreds of years ago, the same can’t be said for CSF leaks. This particular ailment was actually only initially studied by a German named Georg Schaltenbrand in the late 1930s. The Mayo Clinic’s Dr. Henry Woltman then conducted further research more than a decade later.

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The condition itself is very rare, though, with just 0.005‬ percent of individuals suffering its effects annually. Yet Phillpotts wasn’t the only person in the U.S. to be diagnosed with a CSF leak in 2018. In fact, a woman from Omaha, Nebraska, had experienced very similar symptoms to him before getting to the bottom of her ailment.

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“When it first started out, I just thought it was my allergies or a runny nose,” Kendra Jackson told CNN in May 2018. “Like the beginning of a fresh cold. When it didn’t go away, I kept going back and forth to the doctors, and they prescribed every kind of medicine you can think of. And my nose just kept on running.”

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Much like Phillpotts, Jackson had also suffered with her runny nose for a significant period of time. In fact, the Omaha resident had felt the effects for around two years. She then visited Nebraska Medicine in 2018 in the hope of discovering the real cause of the problem – and finally received some answers.

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So after undergoing a scan, Jackson was told that she had a little hole in her cranium that had caused a CSF leak. And she had an idea as to how that might’ve happened. A couple of years before the symptoms had started, you see, Jackson had survived a bad accident in her vehicle during which she’d banged her head on the dashboard.

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And according to Jackson’s physician, Dr. Christine Barnes, her suggestion could’ve been correct. “She was rear-ended and had head trauma, so it’s certainly possible,” the doctor said. “It may have caused a bit of a thin area there. Her symptoms actually started a little bit after [the accident], so for her, I think there’s probably a combination of both the trauma and the increased pressure.”

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To solve the issue, Jackson required an operation, with Dr. Barnes looking to close the hole up. For that to happen, though, Barnes first needed to take different pieces of tissue away from Jackson’s body. And after completing that procedure, the tissue was used to fix Jackson’s skull, which stopped the CSF leak.

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“I used tissue from the inside of [Jackson’s] nose to plug the leak,” Dr. Barnes told CNN. “I also borrowed some abdominal fat. It makes a great plugging agent in this location. So with just a tiny bit of fat, I was able to plug the leak.” And as Barnes suggested, the surgery was a success – much to Jackson’s delight.

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After two frustrating years, then, Jackson’s nose is now back to normal. “I don’t have the nasal drip anymore, but I still have the headaches,” she said a few weeks on from the operation. “I actually feel pretty good, and I’m able to get a little bit of sleep.”

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Jackson also had a message for those who might be experiencing similar symptoms to her. “For people who hear my story, if they’re tasting a very salty taste and something’s draining in the back of your throat, it’s probably something other than allergies,” she said. “So get to the doctor.”

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As for Phillpotts, he required a similar operation to Jackson’s in order to close his CSF leak. And just like Dr. Barnes had done for Jackson, a group of surgeons removed a piece of tissue from the grandparent’s anatomy and used it to fix the issue. Thankfully for Phillpotts, too, the procedure cleared everything up.

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After the surgery, Phillpotts tried his best to describe how he felt now that his nose was completely clear of the fluid. “Have you ever been so congested that you can’t breathe?” the North Carolina resident asked a WTVD reporter. “All of sudden you can breathe again – and what a relief that was!”

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