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“You are so yellow,” the physician assistant told the 39-year-old man. It was said as a simple statement of fact. In the bright lights of the CityMD Urgent Care center in Ronkonkoma, N.Y., the man could see that this was true; his normally light brown skin now had a distinctly saffron cast to it. You need more than this walk-in center can offer, the P.A. explained. Stony Brook University Hospital wasn’t far away. Would he like her to call an ambulance for him?

He could drive himself, he told her, although the thought of climbing back into his car and driving anywhere was unappealing. All he wanted to do was lie down and have someone tell him how he could make this terrible pain in his abdomen stop. Thank goodness for valet parking, he thought as he drove up to the emergency room. He left the key with the attendant and, holding his stomach, made his way to the crowded E.R.

He had experienced pain like this in the past, though never this bad. Once or twice a year, he would eat something that didn’t seem to agree with him. He would feel bloated, his stomach tight and achy. Burping sometimes helped. But the pressure would get so bad that he would often make himself throw up to relieve it. The pain came in waves. He would feel a little pressure and know that more was coming. It would ease a bit and then hours later come roaring back, lasting longer. That would continue, each wave more intense than the last, for a day, sometimes two. And once the pressure started, he couldn’t eat. Anything more than water was brutal. Only when the pain stopped could he add broth or juice and build up from that.

By the time he was called into the E.R. treatment area, his face and shirt were drenched with sweat. He could barely stand. Eventually he was helped onto a stretcher and placed in a cubicle. A half-dozen people came in, asked him questions, took his blood. He had a CT scan and an ultrasound, and within hours he had an answer: He had stones in his gallbladder. And one of them was stuck in the narrow tube that carries the digestive fluid known as bile from the gallbladder to the small intestine. That blockage was the source of the terrible pain. The stone would probably pass on its own — just as it did in all the painful episodes he had before. If not, it would have to be removed surgically. In any case, he was told, his gallbladder would be removed. He asked the many doctors he saw that night if this explained why he was so yellow. An unsatisfying “maybe” was all the answer he got.

The Yellow Matter

By morning, the man was feeling better — the jammed gallstone must have gotten loose and moved on. He was sitting up in bed, reading his phone, when he noticed a small group of doctors collecting outside his door. A young woman gave what he recognized as a description of his own presentation to the emergency room. Then an older doctor began talking about jaundice, the yellowing of the skin and eyes. The color came from a buildup of something known as bilirubin, a breakdown product of red blood cells. Normally there is a constant low level of this dark-colored waste created and disposed of as red blood cells are born and die. But there are diseases that can increase bilirubin levels — either because something happens to block its excretion or because more red blood cells are being broken down, causing more bilirubin to be made. In this patient’s case, the stuck gallstone blocked the flow of bilirubin into the gastrointestinal tract. But that doesn’t usually cause jaundice like this. The whites of a patient’s eyes might be a little yellow — it’s where jaundice is most easily seen — but this man was visibly yellow everywhere. He had far more bilirubin than would be expected in a blocked gallbladder. Our job, he explained to the doctors in training, is to figure out why.

“Do you think I’m hemolyzing?” the patient called out from his bed. Silence fell as every face turned toward him. Hemolyzing, they knew, was the destruction of red blood cells. But this wasn’t a word patients usually used. The patient got out of bed and ambled to the doorway. He could see the unasked question in their eyes. He went to medical school, he told the group, though he never went into practice.

Dr. Peter Braverman introduced himself and the three doctors in training on the team. Here’s something else interesting, he told the patient and the trainees. If you look at the blood-cell count, you can see that this young man has an anemia — a lower-than-usual number of red blood cells. That’s rare in a man. And the blood cells he does have are very, very small. Usually you see that only with a severe iron deficiency or with some anomaly in the shape of the red blood cells. Normal ones are shaped like SweeTarts candies — disc-shaped, with an indentation on each side. That shape allows the cells maximal flexibility in order to move through the narrowest capillaries in the body. Red blood cells with any other shape are destroyed at a much higher rate. That can give you jaundice, especially if the elimination of the extra bilirubin is blocked. Let’s reach out to the hematology service, the doctor said, to help us figure out the mysteries of this man’s blood.

Braverman, meanwhile, was curious. This young man had medical training. What did he make of his yellowed skin and eyes? The patient looked away uncomfortably. Actually, he hadn’t noticed it. During the pandemic, he moved in with his parents and was working from home. He had been quite isolated. Hadn’t been to his office. Hadn’t seen his friends. His parents, who were elderly, hadn’t said a word. And he didn’t look in the mirror much. In past years he noticed that the whites of his eyes sometimes had a yellow tint to them. Based on that, he had diagnosed himself with Gilbert’s syndrome, a benign condition that is caused by not having enough of the enzymes that break down bilirubin. People with Gilbert’s may have a yellowish cast to their eyes, especially during times of physical or emotional stress, when red blood cells are broken down more rapidly. But he never connected the yellow he sometimes saw in the mirror to the bouts of abdominal pains. And he had never been this yellow.

Stones and Sludge

Over the next several days, the yellow in the patient’s skin and eyes faded. He was taken to the operating room. The gallbladder the surgeons removed was filled with dark brown stones and sludge — some of the excess bilirubin accumulated in the sac as pea-size accretions, and the rest continued to the intestines to be eliminated. It’s bilirubin that gives stool its dark color.

While still in the hospital, the patient was seen by the hematology team. The small cells weren’t caused by a deficiency in iron. Indeed, he had plenty of iron. Instead, the specialists looked for some inherited abnormality in his red blood cells that caused them to be destroyed at a higher rate. He didn’t have sickle-cell disease. In this disorder, stress causes red blood cells to turn from SweeTarts to crescent moons that become trapped in the circulation and destroyed. Another common cause of the destruction of red blood cells is a deficiency of a protective enzyme called G6PD. Without this enzyme, infections, medications and even some foods can cause red blood cells to hemolyze. Thalassemia was a third possibility. Patients born with this inherited disorder make abnormal blood cells that are often destroyed at a much higher rate. Yet even before the patient left the hospital, his doctors knew he didn’t have any of these common inherited blood diseases.

The patient saw the hematology team in its office several weeks later. The specialist sent off a half-dozen more tubes of blood, looking for some of the rare causes of hemolysis. This batch provided an answer: He had hereditary spherocytosis, a disease in which the red blood cells were tiny spheres rather than the usual biconcave discs. This shape makes them much easier to damage as they flow through narrowing blood vessels and other blood pathways, just as a fully inflated balloon is a lot easier to pop than one only half full.

The patient asked how he could have inherited the disease. No one else in his very large family had it. Perhaps he was the first to have the mutation, the hematologist suggested. It wasn’t exactly the kind of first the man had imagined for himself. Still, he was glad to finally have an explanation for his episodes of abdominal pain. And really glad to know that now that he didn’t have a gallbladder, he wouldn’t have another.

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.