The attacks came out of nowhere and brought life to a miserable standstill. And she had the scars to prove it.The 62-year-old woman shifted in her seat. The flight to Honolulu was full, the mood a little giddy. The unbroken ocean and sky filled the window. She and her daughter were four hours into the trip from Los Angeles to the wedding of a close family friend; it was going to be a great week. Then, she caught herself scratching lightly at a place on her forearm, just below the crease of her elbow. She lifted her arm to look at the spot. Nothing there. Immediately she was filled with dread.She reached over her head to touch the call button. She needed ice, lots of ice, and she needed it right away. The mild itch had already exploded into spasms of an intense sensation — it seemed wrong to call it an itch; surely there was a better word for it. The fierce intensity of the feeling shocked her. It was a feeling that insisted she scratch. Except scratching never helped. And she had the scars to prove it.She had suffered episodes of itching like this a few times in the past couple of years, though never quite as bad as it was on this flight. Her doctor back home had no idea what caused the crazy itch or what more she might do about it. These attacks came out of nowhere but immediately brought life to a standstill as she tried to ease the unbearable sensation. A bout could last for hours and almost always ended with her arm a bloody mess. When her daughter first saw her mother raking her nails over the invisible injury and the distress she felt fighting this unwinnable battle, she had offered her a Valium. And it helped. The itch was still there but the intensity somehow lessened.On the flight, the woman retrieved the pills she now carried with her all the time. The little bags of ice brought by the flight attendant melted slowly, numbing the hand that pressed them against her arm and easing the itch. She knew from experience that as soon as the ice was removed, the itch would roar back. The attendant brought an ice bucket. But within the hour, she needed more ice. More Valium. She was drenched with the condensation. Her clothes were dotted with blood. She didn’t care. She just had to get through it.The Valium and ice had done their job by the time the plane landed. The two women went to their hotel. The older woman went up to her room, closed the curtains and tried to manage the fear and the pain. The itch was gone, but her arm ached from the self-inflicted injuries. Two days later, the itch was back, this time on the other arm. She didn’t make it to the wedding. The unpredictable need to scratch was too grotesque for her to risk having to do it in public. Instead, she went to doctors. She saw four dermatologists during the trip. None had any idea of what was wrong or what she could do about it.A Doctor Who Loves Tough CasesShe had long since tried the usual remedies: antihistamine creams and pills; steroid creams; hot-pepper lotions; oatmeal baths; acupuncture. All completely useless.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

More than a decade after her original diagnosis, she suddenly had episodes of losing consciousness. Was this a different type of seizure? “I’m feeling a little stroke-y,” the 33-year-old woman said to her friend Clare as they stood in her kitchen making pizza one evening. Clare looked up from the crust she was stretching. Her words were slurred, and for a moment she just stood there, unmoving, knife in hand. Suddenly she threw the knife up in the air. Her body stiffened, and she teetered. Clare caught her, then eased her rigid body to the floor. The woman’s face was a terrible gray. Her eyes were open but unseeing. Clare crouched beside her, terrified and uncertain what to do. After what seemed an eternity but was probably less than a minute, the body on the floor blinked, then gasped. Color flooded back into her face. Clare almost wept with relief.“What was that?” she demanded.“I don’t know,” her friend answered slowly, still looking a little out of it. “I think it was a seizure.”Just over a decade earlier the young woman was diagnosed with epilepsy. But she’d had the strange episodes her doctors told her were seizures for many years. They were always the same: She would suddenly have a strong feeling of déjà vu, followed by a sense of impending doom and a sensation of falling, as if on an elevator dropping through space. Sometimes there was an odd chemical smell. She was awake throughout. She could hear everything and see everything, though sometimes she couldn’t speak. And then it would be over. The whole thing lasted less than a minute. The woman thought they were panic attacks, until she had one at work.She was teaching a swimming class when, in the middle of a sentence, she stopped speaking. She just stood there, not moving, for maybe 30 seconds. That was no panic attack, a fellow teacher stated flatly. She made an appointment to see her primary-care doctor in Vancouver, British Columbia, where she lived. He referred her to a neurologist. An EEG showed that the electrical activity was slower in her temporal lobe on the left. A scan of the brain was unrevealing, so she was started on an anti-seizure medication. And other than that, her life went on as before. She could play hockey, hike, climb and do the open-water swimming she loved.Every now and then, maybe two or three times a year, when she was very tired or stressed or she skipped a meal or two, she could still end up in that déjà vu, plunging-elevator moment. But she never lost consciousness — until two years earlier. She was with her mother when she suddenly stopped talking and slid off her chair. She woke almost immediately. Her mother took her to the emergency department at Vancouver General Hospital. The doctors there found nothing wrong. They weren’t sure what happened, but she seemed OK.She was sitting at her desk at work a few months later and the strange déjà vu and dread hit her. The next thing she knew, she was on the floor, her cheek throbbing from a rug burn. A few days later she got a call. The security camera had filmed something she needed to see. She sat in the security office and watched herself that day, sitting at her desk, then going completely limp and sliding out of her chair onto the floor. After about 15 seconds she saw her body jerk and then, again, nothing. Finally, after another 15 seconds or so, the body on the floor started to move. Slowly she sat up. Her movements were tentative, as if she were weak or drunk. Seeing this, the woman was scared. She called her neurologist. “Something bad happened,” she told the nurse. Her neurologist increased her anti-seizure medications and then referred her to the Epilepsy Clinic at Vancouver General Hospital.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

She was involved in a minor car accident three months earlier. Could that somehow be the cause?“I feel just horrible, and no one knows what to do,” the 21-year-old woman sobbed to her father. In one hand, she held her phone, in the other, a red Solo cup. The pungent smell from the vomit-filled cup wafted through the room. Despite her best efforts, the strange lightness she felt when standing told her that she was dehydrated. And why wouldn’t she be? Everything she ate or drank came back minutes later in terrible heaves that tore at the aching muscles in her chest and abdomen. She filled the cup more than once during this call with her father. And maybe a dozen times earlier that day. And the day before. And the day before that.She paced around the room as she listened to her father. “You need to go to the emergency room,” he told her. She didn’t want to go. She already went seven times over the past three months since this vomiting became part of her daily routine. Most of the time they just gave her IV fluids and sent her home. They thought it was her anxiety. She was admitted twice. Both times they ran countless tests, then sent her home to vomit there — without any answers. Nevertheless, the woman took her father’s advice, and her roommate drove her to the Emory University Hospital emergency room in Atlanta. After getting some IV fluids and the anti-emetic Zofran, which hadn’t helped her in the past, she was discharged. She called her father as soon as she got back to her apartment, and he told her to come home to Cleveland. It was the week before Thanksgiving, and lots of flights were full, but she finally found one for that afternoon and packed her bag.Sideswiped and WhipsawedJust days after arriving in Atlanta that August to start her junior year at Emory University, she was in a car accident. Another car made an illegal turn and sideswiped hers, and she whipsawed against the door. She felt fine, though, and after they exchanged insurance information, she just went on with her day. But by the next day, she had started throwing up. Everything she ate or drank caused her to retch and vomit. She went to the E.R. Because the vomiting started right after her accident, the emergency-department doctor thought she had a concussion. He gave her some fluids and a medicine to stop the nausea. It should get better in a couple of days, he assured her. But it didn’t. She’d been vomiting every day since then. She felt fine until she ate or drank something — anything. Then, within minutes, she would have an overwhelming sense of nausea, and the wrenching spasms and vomiting would start. The flight to Cleveland was quick. Her father picked her up at the airport and drove directly to the Cleveland Clinic Children’s hospital. Her regular doctor, Ellen Rome, the head of the Center for Adolescent Medicine there, wasn’t in the office that holiday week but arranged for the young woman to see a pediatric gastroenterologist. She immediately admitted her to the hospital. The doctor who admitted her that night considered the possible causes of this kind of unremitting vomiting. The patient was taking medications for anxiety, so maybe the doctors in Atlanta were right — maybe this was psychogenic vomiting, caused by her longstanding psychiatric disorder. But there were other possibilities. Regular marijuana use could cause persistent vomiting. Hyperemesis gravidarum — excessive vomiting in pregnancy — was also possible. Those were easy to test for. Hyperthyroidism can cause this kind of vomiting as well. By the next morning results from the testing began to trickle in. She was not pregnant and had no evidence of marijuana in her system. Her thyroid was normal. So were the rest of the more routine studies.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

The 70-year-old man rapidly went from walking 10 to 15 miles a day to being nearly helpless. His wife wondered if he’d had a stroke. Surrounded by the detritus of a Thanksgiving dinner, the woman was loading the dishwasher when a loud thump thundered through the house. She hurried out of the kitchen to find her husband of 37 years sitting on the second-floor landing. Her son and son-in-law, an emergency-room doctor, crouched at his side. Her husband protested that he was fine, then began to scooch himself on his bottom into the bedroom. The two young men helped him to his feet. The man’s body shook with a wild tremor that nearly knocked him down again. “I was getting into bed and fell,” he explained — though the bed was too far away to make this at all likely. “Get some sleep,” the woman said gently once her husband was settled in the bed. “We’ll go to the hospital in the morning.”Her daughter and son-in-law had arrived that morning and already mentioned the change they noticed in the 70-year-old senior. The normally gregarious man was oddly quiet. And the tremor he had for as long as they could remember was much more prominent. His hands shook so much he had trouble using his fork and ended up eating much of his Thanksgiving dinner with his fingers. And now this fall, this confusion — they were worried.His wife was also worried. Just after Halloween, she traveled for business, and when she came back, her husband was much quieter than usual. Even more concerning: When he spoke, he didn’t always make sense. “Have you had a stroke?” she asked her first day home. He was fine, he insisted. But a few days later she came home from work to find his face covered with cuts. He was shaving, he said, but his hand shook so much that he kept cutting himself. “There is something wrong with me,” he acknowledged. It was Thanksgiving week, but she was able to get him an appointment at his doctor’s office the next day. They were seen by the physician assistant (P.A.). She was kind, careful and thorough. After hearing of his confusion, she asked the man what day it was. “Friday?” he offered uncertainly. It was Wednesday. Could he touch his finger to his nose and then to her finger, held an arm’s length away? He could not. His index finger carved jagged teeth in the air as he sought his own nose then stretched to touch her finger. And when she asked him to stand, his entire body wobbled dangerously. “It’s all happened so quickly,” the man’s wife said. The P.A. reviewed his lab tests. They were all normal. She then ordered an M.R.I. of the brain. That, she explained, should give them a better idea of what direction to take. But, she added, if he falls or seems unsafe at any point, you should take him to the emergency room. And so, early that Friday, the woman drove her husband to Danbury Hospital, the emergency room closest to the couple’s small Connecticut town. He walked in on his own. It was the last time he would walk without help for weeks. Many Pink PillsHe was admitted to the hospital. Neurology was consulted and did an extensive work-up: blood tests, CT scans, an M.R.I., an EEG, a spinal tap. While there were some abnormalities, nothing explained his rapid mental and physical decline. There was no sign of infection or tumor. No evidence of seizures. His vitamin levels were normal. And the gastritis he had earlier that spring was responding well to a daily acid-reducing medication, pantoprazole.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

His mouth always tasted like metal and he vomited several times a week. Nothing seemed to help. Then his sister got him the help he needed.“We were thinking about going bowling with the kids tomorrow,” the woman told her 43-year-old brother as they settled into their accustomed spots in the living room of their mother’s home in Chicago. It was late — nearly midnight — and he had arrived from Michigan to spend the days between Christmas and New Year’s with this part of his family. She and her husband and her brother grew up together and spent many late nights laughing and talking. She knew her brother was passionate about bowling. He had spent almost every day in his local alley two summers ago. So she was taken by surprise when he answered, “I can’t do that anymore.”Certainly, her brother had had a tough year. It seemed to start with his terrible heartburn. For most of his life, he had what he described as run-of-the-mill heartburn, usually triggered by eating late at night, and he would have to take a couple of antacid tablets. But that year his heartburn went ballistic. His mouth always tasted like metal. And the reflux of food back up the esophagus would get so bad that it would make him vomit. Nothing seemed to help. He quit drinking coffee. Quit drinking alcohol. Stopped eating spicy foods. He told his doctor, who started him on a medication known as a proton pump inhibitor (P.P.I.) to reduce the acid or excess protons his stomach made. That pill provided relief from the burning pain. But he still had the metallic taste in his mouth, still felt sick after eating. He still vomited several times a week. When he discovered that he wouldn’t throw up when he drank smoothies, he almost completely gave up solid foods. When he was still feeling awful after weeks on the P.P.I., his gastroenterologist used a tiny camera to take a look at his esophagus. His stomach looked fine, but the region where the esophagus entered the stomach was a mess. Normally the swallowing tube ends with a tight sphincter that stays closed to protect delicate tissue from the harsh acid of the stomach. It opens when swallowing, to let the food pass. But his swallowing tube was wide open and the tissue around the sphincter was red and swollen. He had, he was told, something called Barrett’s esophagus — a precancerous condition — caused by the injury done by the stomach acid. He was put on higher doses of the P.P.I. Even that wasn’t enough. So the day after Thanksgiving, he had surgery to prevent that reflux of acid up his throat. And it worked — mostly. The vomiting stopped. He could eat solid foods. But the metallic taste and the nausea were still there. The patient restarted the P.P.I., and that helped a little. But he had what he thought were side effects: He felt off-balance and uncoordinated. It was better on the lower dose, he told his sister. But he still felt too unstable to go bowling. His sister, a neurologist, knew some of this medical back story, but her brother was not much of a complainer. Besides, for the past year or so, many of their conversations had to do with his and his wife’s efforts to have a baby. They were trying in vitro fertilization, and that had been tough for both of them. Now, hearing that her brother’s balance was off, she was worried. She asked him something that, until that night, she could not have imagined asking: “May I examine you?” Photo illustration by Ina JangWe are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

Shortly after he retired, the man’s health began to fail him. An accidental finding on a CT scan revealed the true culprit.The couple couldn’t quite remember when the 61-year-old man started to get sick. Was it before he retired the previous spring? No — it was later, the man insisted. But both men agreed that they knew something was seriously wrong the day the recent retiree fell going up the stairs. He was carrying his new laptop when his right leg suddenly buckled. If he hadn’t had the computer, he might have been able to catch himself. Instead, holding his new machine aloft, he fell forward and slid down a couple of steps. He scraped his shins and forearms; blood seeped from the shallow wounds. And he was too weak to get up. “I need help,” he called to his partner upstairs. The man, already on his feet after hearing the thump, appeared almost instantly at his side. He hefted his partner to his feet and half-carried him into the upstairs bathroom. “You really need to call your doctor,” he murmured as he dabbed the scrapes. He had been urging him to do this for weeks, ever since he noticed how easily his partner bruised, how strangely thin his skin looked. And there were other changes. He was quieter. His easy laugh had all but disappeared. Most worrisome, he seemed confused and forgetful; sometimes he didn’t make sense. They had been together for more than 40 years; the man knew his partner well. These changes scared him. By the time the man agreed to see the doctor, he could barely move the leg that gave way on the stairs. His walk was an awkward shuffle, and he had to hold on to his partner as they made their way from the car to the medical center in Durham, Conn. The doctor on duty that day basically took one look at the bruised and limping man and sent him to Yale New Haven Hospital. At the very least the patient was going to need a scan. He would probably need more. In the emergency room, a physical exam revealed that the muscles in his right thigh weren’t working at all. And the skin there was numb. His blood chemistries were out of whack — his potassium dangerously low. An M.R.I. of his entire spine provided no answers. He lived in a wooded area, not far from Lyme. Had he noticed a tick bite? Or a rash? No bites, but a friend had pointed out a rash earlier that summer. It was in a spot he couldn’t see, though, and he just forgot about it. A blood test and then a spinal tap confirmed the diagnosis: He had Lyme disease. Both men felt a shudder of relief. He would need a full month of antibiotics, but once he was treated, he should get better. The IncidentalomaBut he didn’t. A month later he was still weak, still bruising and bleeding. He was tired; his thinking remained foggy. And his blood pressure was out of control. He had a history of hypertension, but it had always been well controlled on a single medication. Suddenly, it wasn’t. His primary-care doctor put him on a second drug, then a third, but his blood pressure remained higher than it had ever been. His doctor sent him to a cardiologist, who put the patient on even stronger blood-pressure medications. He also ordered an ultrasound of the man’s heart to make sure it was beating normally. It was, but the aorta looked strange. A CT scan reassured him that the man’s aorta was normal but did reveal an unexpected finding: On top of his left adrenal gland was a golf-ball-size mass.Accidental findings on CT scans are so common they have a name — incidentalomas. Up to 7 percent of imaging studies of the abdomen will reveal an incidentaloma on one of the adrenal glands. Most of these masses are benign and don’t make any of the hormones normally produced by the adrenal gland. Still, all need to be evaluated. The cardiologist called the patient with the news and referred him to an endocrinologist at Yale. Between the difficulty of scheduling an appointment with a subspecialist and an unexpected snowstorm, it was months before the patient was able to see the endocrinologist. But finally, on a chilly, overcast day in April, he and his partner found themselves in an exam room at Yale New Haven Hospital. The brisk, smiling endocrinologist strode in and introduced herself. The two men described their strange journey over the previous nine months. It started, they explained, that summer with what turned out to be Lyme disease. He was treated but never got better. Indeed, he felt even worse now. He was weak — he stopped going to the gym because he could no longer do the workout. The muscles on his arms and legs seemed to evaporate. He put on weight, but none of it was muscle. He had never had a belly like this. And he was exhausted even though he slept 10 to 12 hours a night. The endocrinologist had already reviewed the man’s CT scan, as well as the M.R.I. done the summer before, and so she knew what she was looking for. This had nothing to do with his recent Lyme infection. The adrenal glands are responsible for providing several hormones, including the fight-or-flight hormones like adrenaline; cortisol, the hormone that regulates metabolism; and the fluid-balance hormone aldosterone. Excesses of any one of these could be responsible for his high blood pressure. His easy bruising and fragile skin suggested an excess of cortisol. His low potassium and elevated sodium could be caused by an excess of aldosterone. His rapid heart rate could be a sign of excess stress hormones. As the doctor examined him, she looked for clues to help her determine which hormone was being overproduced. His body was covered with bruises. His arms and legs were thin and the muscles wasted. His belly, in contrast, was soft and obese. He had pads of fat at the top of each shoulder and his face was puffy, red and round. This unusual collection of symptoms was classic for Cushing’s syndrome — caused by an excess of the metabolic hormone cortisol. Photo illustration by Ina JangA Puzzling ContradictionOne aspect of his illness, however, was puzzling. These adrenal tumors usually grow slowly, taking years to create this much physical discord. But this man described symptoms that appeared suddenly and worsened quickly. And the tumor itself seemed to be growing fast. Although it wasn’t noticed at the time, a smaller version of the tumor was visible on the M.R.I. done the summer before. A cancer could grow this rapidly. Was this adrenal carcinoma? These aggressive cancers are rare — with only one or two cases found per million people each year — but they can be deadly.The endocrinologist ordered a CT scan to be done that day. If this was a cancer, it should have grown in the months since his last scan. But even if it wasn’t cancer, it clearly needed to come out, and soon. She referred him to a surgeon. He had been sick with this growth long enough. The labs confirmed what the endocrinologist suspected. The man’s level of cortisol was sky high — 25 times the normal amount. The CT scan showed no growth in the tumor size. That was a relief. Adrenal cancers often spread beyond the gland itself, and once that happens the chance of living more than five years plummets. He had his surgery a month later. The response was immediate. The next day his blood pressure and heart rate were back to normal. His blood chemistries, including his cortisol level, were in the normal range. The overactive tumor had taken over the production of cortisol; his remaining adrenal gland was now on vacation, and it would take time for it to recover. In the meantime, he would need to take hydrocortisone. The mass was examined in the lab. The endocrinologist was surprised to find that it was adrenal carcinoma after all. Both doctor and patient were relieved when a PET scan showed no signs of spread. The rest of his recovery was slow. The bruises faded. His muscles reappeared and his endurance returned. By the end of the year he was able to start running again. He went for scans every few months, and after four and a half years he got what was supposed to be his final scan. But that scan showed a new lesion, on his spine. It was treated with radiation. The next year, just this fall, he had a hint of another lesion. A new metastasis. He and his doctors are discussing next steps. I spoke with the patient recently. He has a good life, he told me. He feels great. When asked about the new lesion, he was thoughtful but optimistic. He’ll take care of these problems as they come up, he said. In the meantime, he will continue to enjoy the life he and his partner have together. He asked: What else can any of us do?Lisa Sanders, M.D., is a contributing writer for the magazine. Her latest book is “Diagnosis: Solving the Most Baffling Medical Mysteries.” If you have a solved case to share, write her at Lisa.Sandersmdnyt@gmail.com.

“Go to the emergency room,” the doctor told him after hearing of his trip and fever, rash and whole-body weakness. “You need to be seen.”The 57-year-old man looked up the long staircase that led to his rooms in the rectory, the residence he shared with three other priests. He gripped the handrail on either side of the stairs and forced his foot onto the first step. Slowly he pulled himself up the two flights of stairs to his rooms. His trip home to Boston from a conference in Asunción, Paraguay, had been rough. It was an overnight trip, but he hadn’t been able to sleep at all. Now all he wanted to do was take off his Roman collar and lie down.When he finally made it to his rooms, he looked into his bathroom mirror. His face was bright red and shiny with sweat. The red continued down his chest and onto his belly. His whole body ached. He crawled gratefully beneath his covers. What he really needed was a good night’s sleep, he told himself. But as sleep continued to elude him, he suddenly felt cold. He shivered uncontrollably. The shaking chills confirmed what he already suspected: He was sick. And that worried him.Six years earlier he felt this bad after a flight. He went to the hospital and was diagnosed with non-Hodgkin’s lymphoma. Treatment had been brutal. The seven months of chemotherapy killed the cancer but also destroyed his body’s ability to make any blood for himself. He was rescued with stem cells — the cells that create the blood he needed — harvested from his own body before he started the treatment. He had been disease-free since then but knew that recurrence was possible. It was a low-level anxiety he faced with every subsequent symptom. Before the cancer, he might have just toughed it out. Not now.He called Dr. Peter Zuromskis, his longtime primary care physician. He hated to bother him on a Saturday, but he thought this was important enough to merit the call. “Go to the emergency room,” the doctor told him after hearing of his trip and fever, rash and whole-body weakness. “You need to be seen.”Photo illustration by Ina JangTrouble Carrying His Suitcase One of his housemates drove him to the emergency department at Beth Israel Deaconess Medical Center. It was dark outside by the time he passed through the busy E.D. and into a room in the hospital. He repeated his story a half-dozen times to various doctors, nurses and trainees as he was poked, prodded, stuck and imaged for hours. The priest was grateful for the quiet of the small room where he was finally able to rest.Dr. Martin Kaminski was the hospitalist on the night shift. He introduced himself and asked the patient to tell his story, listening as the man described his trip, his weakness, his rash, his fever. His temperature was 102 when he arrived at the hospital but had come down with acetaminophen and IV fluids. When the patient got to the end, Kaminski had a few more questions. Had he used insect repellent while in South America? No, the priest recalled. A fellow priest gave him a wristband that was supposed to keep the mosquitoes away. He hadn’t felt any bites while there. He drank only bottled water, he added. Did he leave the city or go for hikes in wooded areas? Had he been in contact with any domestic or farm animals? No, he was too busy to leave the hotel where the conference was held.Kaminski asked if he had any body aches. He did. And earlier, his right hand felt achy and a little weak. He had trouble carrying his suitcase. On the ride home, his neck felt strangely weak, as if his head had suddenly gotten much heavier. His neck still felt sore and stiff. The doctor asked him if he could put his chin on his chest. A stiff neck could suggest meningitis. But the patient demonstrated that he could. He was worried, the priest told Kaminski. He had felt this sick only once in his life — and that time was diagnosed with lymphoma. Could it have come back? In the E.D., the hematology-oncology team recommended a CT scan of his chest, abdomen and pelvis, but he hadn’t had it yet. Kaminsky told the anxious man that he thought an infection was much more likely than cancer. But they would know more after the CT scan.A Bite on His Ankle?As he examined the priest, Kaminski noted that his rash was on his back and arms as well as his chest. It looked like a sunburn, and the red skin paled to near-white when Kaminsky pressed his finger into the bright-colored skin on his chest, indicating that it was some kind of inflammation in the skin rather than blood leaking from the vessels below it. There was a tender red nodule on his ankle — possibly a bite. Otherwise, his exam was unremarkable. The lymph nodes in his neck and groin and those under his arms were not enlarged. If he had lymphoma, it wasn’t obvious. Infection was still the most likely cause of his misery.According to the Centers for Disease Control and Prevention, the doctor told the priest, there was an outbreak of chikungunya fever — a viral infection spread by mosquitoes — in Paraguay. And most of the cases had been reported where he’d been, in Asunción. The disease usually isn’t fatal but can cause an arthritis that can last months or even years after the infection is gone.Of course, there were other possibilities, Kaminski added. It could be dengue, another viral disease — spread by the same mosquito. Dengue can cause high fevers and body aches so severe the illness is called breakbone fever. And it can be deadly. While patients infected the first time are often just miserable, those unlucky enough to catch it a second time are at risk of developing a hemorrhagic version of the infection. Each infection is common throughout South America. Each is a virus, spread by the same mosquito. Chikungunya is famous for its abrupt onset and short incubation period, and so that was first on his list. Another possibility was that it was something he caught before he left his home in the Northeast. Maybe some tick-borne disease — like Lyme or anaplasmosis. They should have the answer within the week.Lingering Aches and FatigueThe patient felt better by the next day and was eager to go home. The fever and weakness were gone, and the rash was fading. Only the achiness remained. His doctors still weren’t sure what he had. The only thing known at that point was that this was not a recurrence of his lymphoma. The CT scan showed a couple of enlarged lymph nodes in his chest, but the radiologist thought those were most consistent with an infection. The scans of his abdomen and pelvis, where his original cancer had been located, looked fine.In the days after the priest’s discharge, Kaminski watched as the test results came back. The test for chikungunya was negative. So was the test for dengue. It wasn’t any of the other diseases that he and the infectious-disease doctors had looked for.As for the patient, although the fever was gone by the time he left the hospital, the fatigue and body aches hung on. His head felt cloudy; even reading was hard. Over the following weeks he felt better, but not well. He went to see Zuromskis and described his persistent malaise. What else could this be? Zuromskis smiled. He was confident this was chikungunya. But the test was negative, the patient reminded him. “That test was negative then,” he replied. If he repeated the test now, the doctor felt certain it would be positive.Those first results showed the priest’s immune response to each of the infections they looked for. If he had ever been exposed to that bug before, the test looking for the antibody would read positive immediately; the template to fight off that bug would have already been made by his immune system and stored away. If, instead, this was a first infection, it would take days for the body to gear up and create the bespoke antibodies, tailored to this specific invader. It might have been negative while he was in the hospital, but Zuromskis was sure it wouldn’t be negative now. He sent the tests for the suspected viruses. The results came back a few days later. Only one was positive. Very positive. He had chikungunya fever.The trip to Paraguay was eight months ago. Full recovery was slow. The stiffness and joint pains lasted for months. It’s only recently that he has been able to take on the stairs with his old vigor and speed. And yet, despite the infection and his history of cancer, he is, he tells me, a healthy man. Lisa Sanders, M.D., is a contributing writer for the magazine. Her latest book is “Diagnosis:Solving the Most Baffling Medical Mysteries.” If you have a solved case to share, write her atLisa.Sandersmdnyt@gmail.com.

It started with a bout of dry, itchy skin. Soon everything hurt. A specialist found a way to find some relief.The 49-year-old woman knew as soon as she got out of bed that something was very wrong. A quick survey of her body revealed the source: Sprinkled around her bellybutton were a half dozen blisters. They were small — the largest maybe the size of a pencil eraser — and painful. They looked like the kind of blister you might get on your heel after wearing a new pair of shoes. Except they were on her belly. She dressed carefully, choosing a pair of slacks that were a little loose around the middle. She put a long T-shirt under her sweater and hoped for the best. It was hard to concentrate at her job: The fleshy bubbles shot painful reminders every time she shifted position. When she got home, she immediately changed into a loosefitting dress. One of the blisters had ruptured, leaving an angry-looking raw red mark. She tried not to worry about it. It was September 2021; this was her first week back in the office after months of working at home, and she had too much on her mind already. But the next day, there were a couple of more blisters. And the day after that. By the end of the week, her back and belly were dotted with a dozen of these odd bubbles. Another dozen had burst, leaving sores that seeped a clear fluid. At night, the opened blisters soaked through the gauze she applied, then through her pajamas and into the sheets. Every movement she made ripped open the weeping wounds that had dried, marrying flesh to fabric.After a week of this, she took a sick day and began searching online for a dermatologist; after many calls, she found a practice where she could be seen the next day. The physician assistant who saw her was immediately concerned. After 40 years in practice, she had mastered the routine stuff — and this wasn’t routine. The patient told the P.A. that her skin had been extremely dry and itchy for months, but these blisters were new. As the P.A. examined the woman, she saw a few intact blisters but much of the woman’s torso was dotted with open splotches. This could be acne, she said. She would give her a cream for that. But it could also be a skin infection, and for that she prescribed an antibiotic. The patient should follow up in a couple of weeks so she could make sure things were moving in the right direction.They weren’t. At the woman’s next appointment, her skin hadn’t improved. The P.A. brought in one of the dermatologists. This was clearly some kind of blistering disease, the doctor said. Possibly a type of disseminated infection called eczema herpeticum, which is caused by the herpes simplex virus. The doctor prescribed a potent steroid cream along with an antiviral medication to be taken for a week. That should clear things up, she told the woman confidently. Blisters EverywhereBut over the next week, the blisters and the seeping spots that followed kept appearing. A second antibiotic was prescribed. More steroid creams. At this point, everything she did hurt. The blisters were everywhere: on her arms, her legs and all over her back and stomach. They were even in her mouth and on her scalp. Sitting down was impossible. All she could do was perch at the very edge of the chair. When she went back, the determined P.A. brought in another dermatologist. He examined the woman closely and said: “I think this may be something called bullous pemphigoid. If it is, we can treat you.” The P.A. explained that bullous pemphigoid (B.P.) is a rare autoimmune disease in which the body’s white blood cells create antibodies that attack the connection between the skin and the tissue below, causing these blisters. B.P. is treated with high-dose steroids, and when the disease cools off and blisters stop appearing, the steroids can be tapered down and sometimes stopped completely. The disease often resolves in a few months but can last for years. She started taking 60 milligrams of prednisone every day. The drug was awful. She couldn’t sleep. She felt constantly hungry but at the same time bloated and full. She was weak. Her legs felt like each weighed 100 pounds. But the results were amazing. There were fewer new blisters. And the raw spots marking where old blisters had once been started healing. She took the prednisone for two months. Her skin got better, but she gained more than 20 pounds, and the weakness was so profound she could hardly get out of bed in the morning. The weight gain was depressing, but the weakness was intolerable. Seeing how disabled she was, and how much her skin had improved, the P.A. lowered her dose. Almost immediately new crops of blisters arose. The P.A. increased the dose, but this woman clearly needed a different approach. She needed a doctor who specialized in these kinds of autoimmune diseases. There are internet groups for patients with B.P., the P.A. told the patient. They will know the best doctors for you. She was right. Through the International Pemphigus and Bullous Pemphigoid Foundation, she found a group of fellow sufferers online who lived not far from her on Long Island. They were unanimous in their recommendation: Dr. Allireza Alloo, an associate professor and attending physician at the Zucker School of Medicine at Hofstra/Northwell. Photo illustration by Ina JangHitting the Reset ButtonWhen Alloo entered the exam room to meet his new patient, he could see how tired she was. And frustrated. She had been uncomfortable in her own skin for months, and the treatment was almost as bad as the disease. It started with the itch, she reported. She always suffered from dry skin in the icy depths of winter, but a couple of years earlier her skin got that same dry itchiness while she was vacationing with friends in balmy Hawaii. She bought her usual wintertime creams — moisturizers and low-dose steroid creams — and slathered herself at regular intervals. It helped, but the itch never went away completely. Then she started getting canker sores — huge and painful ones. It hurt to eat. When one erupted in her mouth, she had to limit her diet to soups and shakes. And then the blisters started. Alloo had her change into a gown and then did a full exam of her skin. Her blisters ranged from the size of a BB pellet to the size of a quarter. He could push down on them and they wouldn’t rupture or spread outward, as you might see with bullous pemphigoid. The skin over these blisters was thin, almost translucent. And they were delicate. Alloo could understand why the first dermatologists had thought she had B.P. That disease often starts with an intense itchiness before the blisters appear. But the disrupted tissue is deep, so the skin forming the blisters is thicker. And the blisters themselves are tense and not soft like these. This wasn’t B.P. “You have pemphigus vulgaris,” Alloo told her, “and you are going to get better.” Pemphigus gets its name from the Greek word for blister. It was first described in the 18th century, and until the 20th century, with all its advances, every disease that caused blisters (and there are many) was called pemphigus. Pemphigus vulgaris is an autoimmune disorder, like B.P., but even rarer. In this disease, antibodies attack the connection between cells in the topmost layers of the skin so that it is easily separated from the layers below. An old test for the disease, called the Nikolsky test, was to rub the normal-appearing skin next to the blisters. In pemphigus, that skin often sheers off in thin sheets. Mouth sores are usually the disorder’s first symptom. Until recently the diagnosis was made solely by biopsy. Now a blood test can help identify the specific antibodies that do the damage. As with B.P., Alloo explained to the patient, pemphigus can often be treated with steroids. But when these are not sufficient or cause intolerable side effects, the next step is often a medication called rituximab. This powerful immune-suppressing drug destroys the antibody-producing white blood cells. When the next generation of these cells are created, they no longer make the abnormal antibodies. It’s like hitting the reset button at a cellular level.The patient had her first two doses of rituximab soon after that. Over the next few months her skin began to clear. It has been a year and a half since she started treatment, and she still hasn’t fully recovered; she expects she’ll need a couple of more doses of rituximab. But she is confident Alloo was right. She is going to get well again.Lisa Sanders, M.D., is a contributing writer for the magazine. Her latest book is “Diagnosis: Solving the Most Baffling Medical Mysteries.” If you have a solved case to share, write her at Lisa.Sandersmdnyt@gmail.com.

At first, it seemed like an exercise injury. But it wouldn’t go away.“My hip hurts most of the time now,” the 20-year-old woman explained to Dr. Samantha Smith, a sports-medicine doctor at Yale New Haven Hospital and the second specialist she had seen since the pain in her left hip started two years earlier. She ran her hand down the side of her hip and over the thigh to her knee. It used to just happen at night, she continued. And only every now and then. But these past few months, the pain was present just about every day and absolutely every night. It started sometime in the first flush of the pandemic in 2020. She was 18 and stuck at home. Her social life was limited, and she and her high school pals would work out together over FaceTime, moving to the beat of one of the exercise videos that went viral that summer. Her favorite was a brutal 20-minute drill of lunges and squats designed to build a better butt. At first, she wondered if she just pulled a muscle. The pain was dull and came on slowly as she lay in bed. She couldn’t pinpoint the exact location — it seemed as if her whole hip ached — but when she woke the next day, the pain was gone. She changed videos, and the pain went away, but not for long. After weeks of this on-and-off ache, she mentioned it to her parents. They were doctors, and they peppered her with questions. It probably was some muscle injury, they agreed. She should take a few days off. And she did. But the pain kept its irregular nocturnal schedule. When rest didn’t work, she tried physical therapy. But the pain kept coming. Not every night, but often. And strangely, never in the daytime. That fall she started college at Vassar. The excitement made her forget all about the pain — until just after Halloween, when her nights were interrupted once more. She signed up for more P.T. It didn’t help. The only thing that did help, she discovered, was ibuprofen. Indeed, a dose of that drug right before bed practically guaranteed a good night’s sleep. Just before the Thanksgiving break, she had a video visit with her pediatrician. She moved her leg as her doctor instructed, rotating, lifting, kicking this way and that. All looked fine. She pressed and squeezed the various muscles. Again, fine. Her doctor sent her for an X-ray: normal. The doctor encouraged her to continue with P.T. With the help of the prophylactic doses of ibuprofen, she made it through her first semester. But just as spring greened the branches of the Poughkeepsie campus, her nighttime pain drifted into her days. It wasn’t every day. It wasn’t all day. But it was now an intense pain. She carried her ibuprofen with her all the time. As the hours of her pain expanded, so too did its location. It crept from her hip down her thigh to her knee. And on really bad days, it strayed almost to her foot. Walking somehow made it better. If this was an injury, she thought, that didn’t make any sense. But really nothing about this pain made sense. The girl’s mother was worried. During school breaks, she took her daughter to her pediatrician and to lots of physical-therapy appointments. It had to be a muscle problem. But why was she getting worse? One of the girl’s legs was slightly longer than the other. Was that the problem? Probably not, doctors and therapists assured her. Her daughter described an occasional clicking sensation in that hip when she stretched. Was it snapping-hip syndrome? If so, why hadn’t the therapy helped? Finally one friend had a recommendation: “You should take her to see Sam Smith.” Smith trained in both adult and pediatric medicine at Yale New Haven Hospital and had followed that up with a year focused on sports medicine at the Hospital for Special Surgery in Manhattan before coming back to New Haven. “She is really the best doctor I know,” the friend said. Photo illustration by Ina JangAn Overlooked AbnormalityAnd so now, just a few weeks later, mother and daughter were in with Smith. Smith noticed that the patient had some tenderness at the top of the thigh bone, over the part of the bone that stuck out farthest, a prominence known as the greater trochanter. She was also tender down the side of her thigh, over what is known as the IT band, a thick strip of tissue that extends from the top of the hip bone — known as the iliac crest — down to the upper tip of the tibia. The IT band provides stability to the leg during strenuous activities like running and can be irritated by rubbing against the bony hip prominence. Smith tested each of the muscles of the young woman’s hips and legs. The right leg was completely normal. But there was subtle weakness on the left. When asked to do a squat using only the right leg, the patient could do it easily, but she wobbled noticeably on the left. Smith gave the young woman a series of exercises designed to strengthen the specific muscles that were weak and scheduled her to come back in a month, just before she left for a semester abroad in England. At the end of August, when mother and daughter returned, Smith was surprised to see that although the girl’s muscles were stronger, the pain hadn’t changed. So it wasn’t greater trochanteric pain syndrome; what else could it be? The mother mentioned that there was an abnormality in one of the blood tests done when the pain first started. It was a marker of inflammation known as a C-reactive protein, or more familiarly, CRP. There are many reasons this protein can spike — physical trauma can do it; so can a minor infection. But a persistently elevated CRP would suggest something more than a muscle or ligament issue. That can be seen in autoimmune diseases or chronic infections, even cancer. No one knew what to make of it at the time, given that the X-ray was normal and the blood tests sent to look for infectious and rheumatologic causes of this kind of inflammation came back normal as well. That could be an important clue, Smith said. She ordered a new X-ray and repeated the test. The results came back the following day: The X-ray again read as normal. But the CRP was now three times the level it had been. A whole new list of possibilities sprang to mind. Smith called the patient. She needed to get an M.R.I. of that hip. The patient had her scan three days later. When she emerged, the technician told her that her doctor would be in touch. There was something on the M.R.I., Smith told her. A tumor. She was pretty sure it was not malignant, but to be certain, the patient would need a CT scan. Smith explained that she thought the young woman had something known as an osteoid osteoma — an inflammatory tumor that can be seen in people her age. It hadn’t been what she was looking for, and an M.R.I. was not the best way to diagnose it. The young woman looked up the M.R.I. report on her electronic medical record. What she saw scared her. It was, as Smith said, a small tumor, but the report listed other, scarier possibilities as well. Most prominent on that list: cancer. An infection in the bone was also possible. The benign tumor that Smith suspected wasn’t even mentioned. The CT scan was mercifully quick, and Smith called right away with the answer: It was an osteoid osteoma. Although these poorly understood tumors will resolve on their own after several years, most people who have them end up having them removed. The tumors are quite painful, and the treatment is simple and safe. Under CT guidance, a tiny catheter is introduced through the skin to the tumor, and a probe blasts the tumor with heat. Because the procedure is painful, it is usually done under general anesthesia. Smith told me that she had seen three patients who had osteoid osteomas. Each time, she discovered it while looking for something else. The tumor is called the great mimicker because it looks like so many other possibilities that are more common or more dangerous. The patient chose to defer the procedure until after her semester abroad. Then, just at the start of Hanukkah, she went to the operating room. Once the pain medicine she received at the hospital wore off, her hip hurt as it had never hurt before. Her parents discouraged her from using the opiates the surgeon had prescribed, and she survived on ibuprofen and acetaminophen for her first week at home. By the second week, she was fine. “I was lucky,” she told me. Her parents were doctors. They knew how to get her the specialists and tests she needed. Still, it took two years to figure this out. It must, she said, be so much harder for those without these advantages.Lisa Sanders, M.D., is a contributing writer for the magazine. Her latest book is “Diagnosis: Solving the Most Baffling Medical Mysteries.” If you have a solved case to share, write her at Lisa.Sandersmdnyt@gmail.com.

The man always loved to bask in the sun. Now, at 80, the rays were making his skin red and itchy. “Come in out of the sun,” the woman shouted to her 80-year-old husband. “You’re turning red!” The man reluctantly trudged toward the house. It was late afternoon — the end of a glorious summer day in Orange, Conn. But when he glanced down at his exposed arms, he could see that she was right. He was a bright pink, and soon he knew his arms and probably the back of his neck would be red and itchy. It was time to go inside. He suspected that it gave his wife kind of a kick for him to be suddenly as sensitive to the sun as she had always been. He loved the sun and until recently thought it loved him back, turning his olive skin a deep brown that seemed to him a signal of health. But that spring he started to get red wherever the sun hit him. It wasn’t exactly a sunburn, or at least not the kind of burn his wife used to get that made her skin turn red and peel and hurt for days. His sunburn was itchy, not painful, and lasted an hour or two, sometimes a little more. It certainly never lasted long enough for his dermatologist, Dr. Jeffrey M. Cohen, to see it. He told his doctor about the rash that spring when he went in for his annual skin exam. Cohen said he might be allergic to the sun and suggested an antihistamine and a strong sunscreen. He took the pills when he thought of it and slathered on the sunscreen some of the time, but he wasn’t sure it did much. Besides, who ever heard of being allergic to the sun? Clearly Not a SunburnHe made an appointment with his dermatologist just before Christmas. It was one of those warm, sunny days in December, before winter really sets in, so he decided to make sure his doctor had a chance to see the rash. He arrived early and parked in the lot. He took off his jacket and stood in the sunshine that poured weakly over the building. After about 10 minutes he could see that he was getting pink, so he headed into the office. “I’ve got something to show you,” he told Cohen with a smile when the doctor entered the brightly lit exam room. He unbuttoned his shirt to reveal his chest. It was now bright red. The only places on his torso that looked his normal color were those covered with a double layer of cloth — the placket strip beneath the shirt buttons, the points of his collar, the double folds of fabric over his shoulders. Palest of all was the area underneath his left breast pocket where his cellphone had been. Cohen was amazed. This was clearly not a sunburn. To Cohen, it looked like a classic presentation of what’s called a photodermatitis — an inflammatory skin reaction triggered by sunlight. Most of these unusual rashes fall into one of two classes. The first is a phototoxic reaction, often seen with certain antibiotics such as tetracycline. When someone is taking these drugs, the sun can cause an immediate and painful sunburnlike rash that, like a regular sunburn, can last for days, causing blistering and even scarring. Clearly this patient had an immediate reaction to the sun, but he insisted his rash didn’t hurt. It just itched like crazy. And it was gone within hours. His reaction was more like a photoallergic dermatitis, in which sunlight causes hives — raised red patches that are intensely itchy and last less than 24 hours. But that didn’t quite fit either; photoallergic reactions aren’t immediate. They usually take one or two days to erupt after exposure to light. Each reaction is triggered by medications. Cohen reviewed the patient’s extensive med list. Amlodipine, an antihypertensive drug, was known to cause this kind of photosensitivity, but the patient had started this medicine recently, months after he first mentioned the rash. Hydrochlorothiazide, another of his blood-pressure medicines, could sometimes do this. The patient had taken this drug for years and been fine, but at least in theory, this unusual type of reaction could start at any point. Cohen explained his thinking to the patient. He would need to get a biopsy to confirm a diagnosis. The pathology would help him distinguish the inflammation of hives from the more destructive phototoxic reaction, which destroys the skin cells. And it would help him rule out other possibilities such as systemic Lupus erythematosus, an autoimmune disease that is most common in middle-aged women but can occur in men and women at any age. A couple of days later, Cohen had his answer. It was hives — medically known as urticaria. This was a photoallergic reaction. And it was probably triggered by his hydrochlorothiazide. He should ask his primary-care doctor to stop the medication, Cohen told his patient, and after a few weeks he should stop getting the rash. Photo illustration by Ina JangThrough the WindowThe man returned to Cohen’s office three months later. The rash was unchanged. After a few minutes in the sun he would be itchy and pink, even in the dead of winter. Cohen went back to the patient’s med list. None of the others had been linked to this type of reaction. “Tell me about this rash again,” he said. The patient went through his story once more. Any time sun hit his skin, even if the sun was coming through the window, he would turn red. When he was driving, the warm touch of the sun on his arm would cause an aggravating itch. And by the time he reached his destination that skin would be bright red. Hearing this description, Cohen suddenly realized he had it right the first time. The patient had developed an allergy to sunshine — a condition known as solar urticaria. Cohen explained that this was not a sunburn. Sunburns are caused by light in shorter wavelengths known as ultraviolet B or UVB. That form of light cannot penetrate glass. The fact that he could get this reddening through his window indicated that his reaction was triggered by light with a longer wavelength, known as UVA. This is the form of light that causes skin to tan and to age, the form used in tanning salons. Solar urticaria, he explained, is a rare disorder and not well understood. When sunshine penetrates the skin, it interacts in different ways with different cells. The most familiar are those cells that, when exposed, produce a pigment known as melanin, which tans the skin and offers some protection from other effects of the sun. In those with solar urticaria, the body develops an immediate allergic reaction to one of the cellular components changed by sunlight. How or why this change occurs is still not known. The allergy can start in young adulthood and may last a lifetime. And it’s hard to treat. Sunscreen, Cohen told him, is a must — even when indoors. He would also need to take a higher dose of the antihistamine that he was prescribed — at least double the usual recommended dose. Patients are also advised to wear protective clothing. Solar urticaria can be dangerous. Extensive exposure to sunlight can trigger severe reactions and, rarely, a potentially lethal anaphylactic event.The patient received the diagnosis just over a year ago and has been using sunscreen with an SPF of 50 ever since. He doubled the dose of his antihistamine. And most of the time, the medication plus long pants and sleeves and a hat keep him safe. Most of the time. And when he forgets, he knows he can count on his wife to let him know that he’s starting to turn red again.Lisa Sanders, M.D., is a contributing writer for the magazine. Her latest book is “Diagnosis: Solving the Most Baffling Medical Mysteries.” If you have a solved case to share, write her at Lisa.Sandersmdnyt@gmail.com.