“Wow, brother, you look awful!” the middle-aged woman called out to the 48-year-old man as he made his way slowly to the table. The siblings were from a large, close-knit family, together (back before Covid-19 hit) to celebrate the birthday of their 8-year-old niece. The woman always described her brother as strapping or robust; he now looked neither. He limped toward the table as if his left leg was somehow too weak to carry him. His normally ruddy complexion looked gray. His face looked both thinner — as if he’d lost weight since she last saw him two weeks earlier — but also fatter, his cheeks chipmunk-swollen, especially strange in his otherwise bony face. One of his ears was the only spot of color on him, fire-engine red and oddly enlarged.
Yeah, not feeling great, her brother told her as he carefully lowered his body into a chair. Normally he never complained, so this was a big admission for him. He hadn’t felt well for the last two months. Sometime around Thanksgiving he came down with what he thought was a bad cold. He felt congested, and he couldn’t breathe through his nose at all. When it didn’t go away after a week, his wife insisted he go to the nearby walk-in clinic. Sinusitis, the doctor said, prescribing a week of antibiotics. When that didn’t help, he went to his regular doctor, who gave him more antibiotics and added some prednisone to relieve the congestion. With that, he felt better but not even close to well. His doctor gave him a third course of antibiotics and a little more prednisone. When he still felt sick, the doctor referred him to an ear, nose and throat specialist. It was nearly Christmas by then, so the earliest he could get in was after the holidays.
It was a long couple of weeks. The congestion became a pressure that started at the bridge of his nose and moved outward until it covered his entire face. His head ached as if it were being squeezed in a vise, and got even worse when he tried to lie down. Now he was sleeping in a chair. In the week between Christmas and New Year’s Day, his calves started to ache after he walked a couple of blocks. It seemed crazy that it took so little to make an active guy like him hurt so much.
He finally got to see the E.N.T. Definitely sinusitis, he was told. The swelling in his nose was so bad the specialist couldn’t even get the scope up there. His ears were filled with fluid. He got more antibiotics. More steroids. By then he’d been sick for months, but he wasn’t going to miss his niece’s birthday. After the candles were blown out and the cake was devoured, his sister confronted him and his wife. He needed to go to the hospital, she told them. Right then. He was a healthy guy — why was he so sick? No way, he told her. His wife joined the effort: At the very least he needed some blood tests, she suggested. OK, he said; he’d go to the walk-in clinic that evening and ask for blood tests.
When he told his sister the results, she got really worried. Every single result was abnormal. She called her sister-in-law, who then called her husband at work: He needed to go to the E.R. immediately. Amazingly, he agreed.
A Wide Diagnostic Net
When the nurse at the triage desk of the Yale New Haven Hospital asked him why he was there, he had a list: His ears hurt, his legs hurt and the results of some blood tests done the day before were abnormal. Before Thanksgiving he was completely healthy, the patient told the young emergency-department physician. Now everything hurt. On examination the patient didn’t look particularly sick. His right calf was a bit tender when the doctor squeezed it; everything else seemed fine.
When faced with a patient who doesn’t come in with a recognizable syndrome, a doctor has to cast a wide net. The patient reported that his leg pain got better with the prednisone. Steroids can have a pain-relieving quality, but that sort of improvement is also a characteristic of inflammatory or rheumatologic diseases like lupus or rheumatoid arthritis. The E.D. doctor ordered tests to look for systemic inflammation. The man had no fever or chills, just the congestion and a cough. The doctor ordered a chest X-ray to look for a pneumonia. The patient had night sweats and worked as an engineer, recently assigned to a temporary job at the local sewage plant. He also reported that one of his abnormal labs was an elevated white-blood-cell count. If not a pneumonia, could this be some other hidden infection? The doctor ordered blood cultures.
The results came back quickly. The inflammatory markers were crazy high — much higher than you’d see with most infections. Could this be some rheumatologic disease? And the chest X-ray showed patches of cloudy white scattered throughout both lungs, suggestive of an extensive pneumonia. Given these two abnormal results, the E.D. doctor decided to admit the patient for the treatment of his pneumonia and for further work-up.
Follow the Inflammation
Dr. Hannah Rosenblum was the physician in charge of the team caring for the patient in the hospital. As she entered his room, she was immediately struck by the man’s ears. They were bright red, and everything above the earlobes was hugely swollen. The rest of the patient’s exam was unremarkable. Even though he had what looked on the X-ray like a pretty bad pneumonia, he wasn’t having any problems breathing. Rosenblum was concerned about the wildly elevated inflammatory markers. Maybe it was an infection, but it seemed far more likely to be one of the many systemic inflammatory diseases. They are uncommon but potentially deadly — important not to overlook.
Rosenblum and her intern, Melissa Mariscal, went through everything they knew about the patient: He had chronic sinusitis and a pneumonia but no fevers or chills. The cartilage in his ears was red and swollen. There was blood in his urine. He had muscle pains that worsened with exertion but no evidence of muscle breakdown. And he had these incredibly high inflammatory markers. The fact that so many parts of his body were affected made a strong argument for some kind of rheumatologic disease. But which one?
As they spoke, the results from the patient’s CT scan came back. He had several masses (called granulomas) and some holes (called cavitations) in his lung tissue. Based on that finding, plus his history of sinusitis, the radiologist strongly suggested they consider the diagnosis of something known as Granulomatosis with polyangiitis (GPA). GPA is a disease of the small- and medium-size arteries in the body, which is a reason it can affect so many different parts. It is characterized by the development of granulomas — clumps of white cells and other tissues that form in reaction to infection or inflammation — in the lungs, in the upper respiratory tracts and in the kidneys. Untreated, the disease can kill, destroying the involved tissues.
Dialing Back the Immune System
Rosenblum and Mariscal immediately looked up GPA. Could it account for other parts of this patient’s presentation? The red ears: yes. The blood in the urine: yes. The muscle pains: yes. The chronic sinusitis: absolutely. The intern put in a referral to the rheumatology team to ask for help diagnosing this disease and treating it.
The rheumatology team recommended blood tests to look for evidence of GPA and rule out other possibilities. Treating GPA requires aggressive suppression of the inflammatory white blood cells, often for months at a time. Before starting this kind of treatment, they would have to make sure he didn’t have any hidden diseases, like tuberculosis, that could suddenly flare up if the white blood cells were taken out of action. He didn’t, and so when the test results came back positive, he was started on high-dose prednisone and a second immune-suppressing medication called rituximab. Treatment lasted months, but improvement started right away. As soon as he got his first dose of prednisone, he told me, he felt “like a million bucks.”
He’s still not much of a complainer. When I spoke to him, he told me he was 98 percent better. But his sister reports that he still tells her about his pain and stiffness at times, especially after sitting for a while. And episodes of congestion. “Does your doctor know?” she always asks him, and he promises to make the call. And, she tells me, maybe he does.