23↓
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 possi-
bilities. When he fi rst 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 infl ammatory
joint diseases in women her age and could
sometimes aff ect the lungs. But she need-
ed 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-infl ammatory properties of steroids.
Most patients with R.A. could be managed
on fi ve 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 vas-
culitis like EGPA is dangerous because
the involved blood vessels can be any-
where 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 fi t.
As the doctor examined the young
woman, he paid special attention to her
joints. If she had any sign of infl ammation
there — any redness or swelling or fl uid
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
fi rmly pressed on her right thigh, a cou-
ple 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 fl uid, it can be missed
unless it’s collected together at the joint.
He found no obvious fl uid.
He then pressed gently on the outer
aspect of the knee joint. If there was any
fl uid 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. Interest-
ing. There was infl ammation 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 fi ndings suggested
a very rare disorder, a disease that causes
infl ammation 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 some-
thing called relapsing polychondritis
(R.P.), he told the patient. R.P. is an auto-
immune disease in which a patient’s whiteblood 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 confi rm 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 fi nds on examination. Because this
patient had episodes of cartilage infl am-
mation — 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 infl ammatory 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 dis-
ease 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 poor-
ly 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 suff er 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 Baffl ing
Medical Mysteries.’’
If you have a solved case
to share, write her
at Lisa.Sandersmd
@gmail.com.