It started withthe broken rib. Or at least that’s what made the 36-year-old physician consider the possibility that something was really wrong with her, she explained to Dr. James D. Katz, the rheumatologist her friends at work recommended. Right after the birth of her daughter 18 months earlier, she developed a cough. At first it was mostly when she exercised, but she still managed to complete a half marathon before her daughter was 6 months old. Her time wasn’t as good as it was in earlier races, but she was still pleased. After the race, though, the cough got worse. She would get these violent paroxysms so forceful that her ribs, especially the ones on the right, started to ache. It hurt to pick up her baby. It hurt to breathe. And it was excruciating to cough.
After a few months, when the cough persisted, she went to her doctor. He ordered an X-ray, which found what looked like a pneumonia. Because the cough had lasted too long to be a pneumonia, a CT scan was done the same day. The scan clearly showed a cracked rib.
She was prescribed prednisone, then antibiotics. Her lungs finally cleared up. The cough, however, remained. She was given a diagnosis of asthma and started on a bunch of inhalers and a high dose of prednisone. She felt better immediately. It didn’t take long to figure out that the benefit wasn’t from the inhalers; the prednisone was miraculous. And she’d been taking it — a lot of it — ever since. She knew it was too much, and yet when she was caring for patients in the intensive-care unit — something she did four or five months a year — she needed that high dose just to keep up with her life.
The medication eliminated the cough, and that was a blessing. But it did so much more. She had pain and stiffness in her joints that had been there so long she’d started to consider it normal. She figured this was just how her adult body felt. But with the prednisone, the pain and terrible stiffness disappeared. She was a physician; she knew that taking prednisone like this would hurt her. It could give her glaucoma, diabetes, osteoporosis and high blood pressure. But whenever she tapered the steroids, the pain, stiffness — and cough — all came roaring back. Right now, she told herself, taking that drug was the only way she could feel normal. That’s why she finally decided to see Katz.
Probing for Inflammation
James Katz was a senior research physician at the National Institute of Arthritis and Musculoskeletal and Skin Diseases at the National Institutes of Health in Bethesda, Md. After hearing the patient’s story, he stepped out of the exam room to give her a chance to change into a hospital gown. As he waited, Katz considered the possibilities. When he first heard that she had joint pains that resolved with prednisone, the specialist thought that she probably had rheumatoid arthritis (R.A.). It was one of the most common inflammatory joint diseases in women her age and could sometimes affect the lungs. But she needed extremely high doses of prednisone to manage her symptoms, and that was not typically necessary for treating R.A., which was usually exquisitely sensitive to the anti-inflammatory properties of steroids. Most patients with R.A. could be managed on five to 10 milligrams of prednisone. She needed 10 times that. No, Katz decided, this was probably something else.
At the top of his new list was a rare disease formerly called Churg-Strauss syndrome, now known as eosinophilic granulomatosis with polyangiitis (EGPA). This is a disease not of the joints — like R.A. — but of the blood vessels. A vasculitis like EGPA is dangerous because the involved blood vessels can be anywhere in the body. EGPA often starts in the lungs, frequently in patients who have asthma, but can then spread throughout the body. But in EGPA, patients have high levels of eosinophils, the white cells that drive the disease. Hers were normal. And EGPA usually causes more muscle pain than joint pain. So it wasn’t a great fit.
As the doctor examined the young woman, he paid special attention to her joints. If she had any sign of inflammation there — any redness or swelling or fluid in the joint space — it would make EGPA an even less likely diagnosis. Her knees looked normal — not red, not swollen — but they were quite tender. He had her straighten her legs and then gently but firmly pressed on her right thigh, a couple of inches above the knee, and moved his hand down the leg until he reached the kneecap. The joint space of the knee extends up into the thigh, and so if there is a small amount of fluid, it can be missed unless it’s collected together at the joint. He found no obvious fluid.
He then pressed gently on the outer aspect of the knee joint. If there was any fluid there, it would show up in the only space left, as a little swelling on the other side of the knee — the so-called bulge sign. Sure enough, there it was. Interesting. There was inflammation somewhere in the joint. If it was in the outer smooth surface where the joint came together, known as the synovium, then it probably was R.A. But what if it was in the cartilage that cushioned the joint? He then pressed on a spot on her chest where cartilage connects the ribs to the breastbone. The patient jumped back in pain. “I didn’t even know it hurt there,” she exclaimed.
To Katz, these two findings suggested a very rare disorder, a disease that causes inflammation and eventually destruction of cartilage. “Do you ever have pain in your ears when you wear a hat,” he asked, “or when you sleep on your side?” The patient was amazed. No one had ever asked that question. Yes, she replied. And did her nose ever get sore or red when she wore sunglasses? Again, she was amazed. Yes. Often. What in the world could that mean? She was a doctor, a specialist in intensive-care medicine and infectious diseases, and she’d never heard of either of these symptoms.
He was pretty sure that she had something called relapsing polychondritis (R.P.), he told the patient. R.P. is an autoimmune disease in which a patient’s white blood cells attack parts of her own body — in this case, the cartilage. The patient was astonished. She had learned about R.P. in med school, of course. The key symptom to look for, she — and most doctors — had been taught, was a grossly swollen and red ear. The ear lobe, however, will look normal because it has no cartilage. That or what’s known as a saddle-nose deformity, where the bridge of the nose dips because of the destruction of the cartilage there. It turns out that these classic symptoms are seen in only half of patients who are diagnosed with R.P.
What makes R.P. particularly hard to diagnose is that there is no single blood test to confirm the diagnosis. And even imaging may be unremarkable until the disease is advanced. Most patients have to be given the diagnosis based only on the symptoms they experience and what the doctor finds on examination. Because this patient had episodes of cartilage inflammation — in her ears, her nose, her chest and knee — that improved with steroids, she met the diagnostic criteria for the disease. Once he was convinced of the patient’s diagnosis, Katz started the patient on an immune-suppressing drug regimen.
A Shift in Specialization
Looking back, the patient recognized in herself something she often sees in her patients — denial. There was no outward sign of the pain she was feeling in her body — no redness, no swelling, just pain. And all the tests done to look for an autoimmune or inflammatory disease had been normal. To the patient it seemed clear that there couldn’t be anything wrong with her — that it was all in her head. The facts of her illness — the cough that was violent enough to break her rib, her need for huge doses of steroids to get out of bed — were confusing to her, as a doctor, so she ignored them.
She received her diagnosis six years ago. It took months for her to get her disease under control, and even now she has to take a long list of medications every day. Because of her diagnosis, she changed the direction of her career. She now cares for patients who, like her, live with this poorly understood, often devastating disease. And her research is focused on improving what we know about how to diagnose and treat it. This way, she hopes, patients will no longer suffer for years thinking it must all just be in their heads.
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 [email protected].
