On Thursday we challenged Well readers to unravel the case of a 67-year-old healthy retiree who suddenly developed knife-like chest pain and a worsening cough. Maybe this case was too easy because more than a quarter of you figured it out.
The correct diagnosis is:
Eosinophilic pneumonia, caused by the antibiotic daptomycin (brand name Cubicin)
The first reader to make this not-quite-as-tough-as-I-thought diagnosis was Francis Graziano, a second-year medical student at Georgetown University School of Medicine. He had just learned about daptomycin and recalled that there were some pretty dramatic side effects linked to it. And the time course seemed right. So he went to the Wikipedia page on the drug and saw that this type of pneumonia was a known adverse reaction to it. Francis is another two-time winner, having solved another tough case two years ago. Well done, Francis.
Daptomycin is an antibiotic used primarily to treat drug-resistant staph infections. It was approved by the Food and Drug Administration in 2003.
The first report suggesting a link between this antibiotic and pneumonia was made in 2007. An 87-year-old man who, like this patient, was being treated with daptomycin for an infection after knee surgery lost 15 pounds over the course of just a few weeks and became increasingly fatigued. A CT scan of his chest revealed multiple nodules, and when these nodules were biopsied, the patient was found to have a pneumonia.
But it was an unusual pneumonia. Instead of finding bacteria or the usual infection-fighting white blood cells in the lungs, the sample showed a handful of eosinophils (or eos), a type of white blood cell that normally fights off parasites (like intestinal worms) but can also be seen in allergic reactions. The doctors suspected that the pneumonia was an allergic reaction to the daptomycin. They stopped the drug, and the pneumonia resolved.
As a result of this case report, the F.D.A. put eosinophilic pneumonia on the list of possible adverse reactions. By 2011, 11 cases had been reported, enough to convince the F.D.A. that the link was real.
Eosinophilic pneumonia is an unusual disorder and is usually caused by exposure to certain drugs or toxins or radiation therapy. The most common trigger is cigarette smoke, and the illness may occur in those who recently started or restarted smoking. More than 300 different medications have been linked to eosinophilic pneumonia; antibiotics and nonsteroidal anti-inflammatory drugs such as ibuprofen are most commonly cited.
How or why this pneumonia develops is not clear. Men are more likely to be affected than women. In the cases of eosinophilic pneumonia associated with daptomycin, patients were all over age 60.
How the Diagnosis Was Made
Dr. Robert Centor was the doctor on call when the patient was admitted to the hospital. The patient was seen by the resident on his team, who called to tell him about the 67-year-old man with the infected knee and a week-long pneumonia.
Dr. Centor was intrigued. Why would a pretty healthy guy on antibiotics for one infection develop a second infection? He was getting his antibiotics through an intravenous catheter than ran from a vein in his arm into his heart. Could some type of skin bug have traveled up the catheter into his heart, and from there into his lungs?
He asked the resident to make sure that the patient had a CT scan of his chest to look for tiny pieces of infection, known as septic emboli, which might be clogging up the blood vessels in his lungs. The patient got the scan, which showed only the fluffy clouds dotted throughout his lungs.
The next morning, Dr. Centor went to the radiology suite to review the chest X-ray and CT scan with the radiologist. No septic emboli were present. After confirming what he’d already heard the night before, the internist headed up to see the patient with his team.
Looking for Answers
After talking to the patient and examining him, Dr. Centor was certain of two things. First, that the patient was seriously ill. Second, that he wasn’t sure why. It didn’t make any sense at all that this youthful 67-year-old retiree should suddenly develop a whopping double pneumonia.
Certainly bad things can happen to healthy people, but Dr. Centor liked to understand why. In this case, “I was completely befuddled,” Dr. Centor told me in his thoughtful Southern twang. We were old friends; he had been a wonderful teacher and mentor to me. “But whenever I am befuddled, I just talk to other people,” he told me.
I know from my own experience that often enough, just posing a case to a colleague as a question can prompt you to see it in a different light and reveal an answer you hadn’t considered. And if you’re really lucky, the answer comes from asking someone who has previously come across a similar case. So Dr. Centor, who was the dean of his residency program, headed to the cafeteria, where he grabbed a cup of coffee and scanned the room for familiar faces. He settled down at a table full of doctors and residents and quickly outlined the case.
The Right Place, the Right Time
Mohamed Raja, a resident in his second year of training, listened carefully to the case. “It was a matter of being in the right place at the right time,” he told me. Because as soon as Dr. Centor mentioned the name of the antibiotic the patient had been getting, the resident realized with a jolt that he knew the diagnosis.
Well, he said to Dr. Centor, he had been reading up on Cubicin just the week before. And there was this rare complication associated with the drug that had caught his attention. It was an allergic reaction that manifests itself as a terrible and painful pneumonia, caused not by an infection but by the patient’s own white blood cells, the eosinophils.
Hearing of this unusual reaction, Dr. Centor quickly pulled out his cellphone and looked up Cubicin and eosinophilic pneumonia. Sure enough, this unusual side effect, first described just a few years earlier, seemed to fit his patient exactly.
The only way to know for certain was to get a lung doctor to put a scope into the patient’s lungs and see if these specialized cells, the eosinophils, were there. They shouldn’t be. But first he had to stop the medication.
Dr. Centor called the nurses to make certain the patient didn’t get his next scheduled dose. Then he went upstairs to tell his team and the patient.
Waiting for Watson
It is the nature of medical knowledge that no one knows everyone. We doctors all learn the same basics, and what we add depends on the patients we see and the interests we pursue. One of the key skills all doctors must hone is how to recognize and supplement these almost inevitable gaps.
The Internet has made this kind of supplementation much, much easier. For example, when Dr. Centor first told me about this case, he gave me the outline and asked what I thought was going on – a game we often play. I didn’t know, but what I call “test logic” told me that if he was telling me the name of the antibiotic, it had to be part of the answer. So I Googled the terms “daptomycin” and “pneumonia” and whammo, I got the answer immediately.
Last fall, IBM announced that it is developing a health care business based on its supercomputer, Watson. Using the same data-accumulating skills that allowed Watson to conquer “Jeopardy!” in 2011, the goal is to master all medical knowledge – new and old – so that we won’t have to. But until then, doctors must continue to rely on their own data accumulating skills.
Dr. Centor turned first to the traditional method, the who-wants-to-be-a-millionaire option of phoning a friend, before turning to other sources. Will Watson – or any of the other emerging databases – fully replace human recall and thought? They haven’t so far.
How the Patient Fared
The patient had the bronchoscopy the next day. He had eosinophils and no signs of infection. He was started on high-dose steroids to calm the allergic reaction, and the Cubicin was replaced with another antibiotic for the last weeks of treatment.
It’s been four months since his scary pneumonia episode, and the patient tells me he feels just fine. He’s resigned to the fact that his knee may never be perfect. But breathing? No problem.
As for his fishing camp, it’s closed for the winter. But he’ll be back as soon as the weather, and his knee, allow.