What is the name for this collection of events?

BUDD, THE PRESIDENT OF OUR MEDICAL GROUP, TOLD ME A FEW WEEKS AGO, “IT IS MY GOAL NEVER TO BECOME AN INTERESTING PATIENT.”

I hadn’t seen Sheryl in 19 months when she showed up for an appointment in March 1998. In the interim, she had developed an interesting physical attribute: enormous cheeks. Doctors recognize such moon facies as an obnoxious side effect of long-term use of corticosteroids, anti-inflammatory hormones our bodies make in response to physiologic stress. Physicians prescribe these steroids to treat problems that produce pain, pus, pruritis (itching), burning, or mucus. Hay fever, poison oak, asthma, and hemorrhoids are common examples. When possible, we give the medicine for a short time and we put the medicine right where it’s needed, via ointments, nasal sprays, inhalers, or injections, so that people don’t get the systemic side effects, which can include diabetes, osteoporosis, hirsutism, cataracts, psychosis, and increased susceptibility to infections.

Sheryl has systemic lupus erythematosus, an immune-system disorder in which one’s antibodies attack his or her own connective tissue. In mid-1996, before I had met her, a rheumatologist had figured out that lupus was causing her intermittent joint pains, fevers, and rashes and had started her on a high dose of prednisone, an oral corticosteroid. Sheryl had continued to take prednisone for almost two years, during which time she had made sporadic visits to emergency rooms for diarrhea and vomiting but did not see any physician on a regular basis for ongoing supervision of her care.

She returned to see me, with her cherub cheeks and extra fat around the middle, looking like a 34-year-old African-American infant. Her problems had an infantile ring to them: diarrhea, vomiting, and urinary incontinence. The diagnosis, however, was a very adult one: pancreatitis.

The pancreas is the body’s equivalent of a nuclear reactor. The substances it produces and stores cause mayhem if they escape their proper containers. Powerful enzymes (proteins that break down carbohydrates and other proteins into their simpler sugar and amino-acid components) made in the pancreas travel through the pancreatic duct to the small intestine, where they digest the food we eat. Damage to the pancreas from trauma, toxins (alcohol is the most common of these), or obstruction within the bile duct system (from gallstones, cancers, or fats) allows the release of these enzymes into the abdomen, where they begin to digest the pancreas itself and the surrounding abdominal organs. This causes terrible pain and gastrointestinal malfunction.

“It bothers me right in here,” she told me in March, pointing to her central lower abdomen, below the usual location for pain from pancreatitis, “and it goes into my back.” Situated deep in the abdomen, the pancreas often sends pain into the back when it is inflamed.

Fixing a diseased pancreas begins with the same first step as fixing a damaged reactor shutting it down. This means putting the gastrointestinal tract to rest by not having anything to eat or drink. When pancreatitis is mild, as Sheryl’s was, we can give the patient intravenous fluids, while making her fast for a few days as the pancreas mends itself, and then gradually introduce oral fluids and food. Once the patient tolerates oral nutrition and we eliminate what caused the damage, usually by removing gallstones or stopping alcohol intake, the patient can go home.

Shutting down Sheryl’s pancreas proved to be difficult. Obese and addicted to food, she could not keep herself from eating. She persuaded those who visited her at the hospital to sneak food into her room. Her inability to control her oral intake and our difficulty identifying the cause of her pancreatitis frustrated me and her. We could never get her to stop eating long enough to heal her pancreas, and the only possible cause my consulting gastroenterologists and rheumatologists and I could find was presumed pancreatic blood-vessel inflammation (vasculitis) due to lupus.

Predictably, she bounced in and out of the hospital, requiring admission about every six weeks because of pancreatitis. Rather than jnform me early when she developed worsening pain, diarrhea, and/or vomiting, she always waited until she was unable to eat or drink and would then go to the emergency room. I would admit her to the hospital, write orders for her to be MPO (nothing by mouth), start intravenous fluids, and often give her TPN (total parenteral nutrition, or intravenous food) until her pancreas allowed her to eat again. TPN allows us to give nutrition to patients whose gastrointestinal tracts do not function. Even though she ate without our permission, her condition always gradually improved enough so that she could go home. We even gave her TPN at home a few times, although this upset her because it gave her leg cramps.

After her first admission, I started her on methotrexate, a powerful immunosuppressant we use in advanced autoimmune disease and for cancer chemotherapy, in order to get her off of prednisone. We did succeed in cutting her prednisone use by about a third, but since we thought every pancreatitis episode represented a lupus flare-up, we pulsed her with high steroid doses upon admission to the hospital and tapered them down as she improved each time. An unexpected benefit was that her urinary incontinence, for which my consulting urologist and I could not find a cause, improved when we gave her steroids.

But we didn’t make any great progress until January 1999, when Marcus, a local gastroenterologist who has given up most of his clinical responsibilities to serve as a high-level insurance administrator, consulted on her case and suggested that microscopic gallstones were a much more likely pancreatitis cause than lupus vasculitis and recommended we treat her with a medicine that helps dissolve gallstones.

It worked. Sheryl didn’t get sick for four months, until she let her medicine run out Just the latest example of her characteristic passive, noncompliant approach to her multiple illnesses, this choice to “see what would happen” annoyed me. As usual, she denied feeling depressed or angry. “I just don’t like taking pills,” she explained with a shrug that implied, “and I don’t think this is such a big deal,” even though just three weeks had elapsed between her stopping the medicine and landing in the hospital.

This time, it was a big deal. I noted that her admission blood work showed a significant change in her kidney function, and within three days her kidneys were on the verge of failure. Methotrexate was the most likely culprit, so we stopped it 1 then went on a two-week vacation to Brazil. While I was away, the consulting nephrologists biopsied one of her kidneys; the ensuing microscopic examination showed that lupus and methotrexate had both played a role in her kidney damage.

When I returned, her kidneys had begun to recover, but now it was her bone marrow’s turn to shut down. Our bone marrow, tucked inside our biggest bones, manufactures blood cells: red cells to carry oxygen, white cells to fight infection, and platelets to start blood clots. Sheryl’s red blood cell quantity measurement (hematocrit) dropped from 31.5 when I left to 19.9 (normal for a menstruating woman is 36), and her platelets plunged from 186,000 to 86,000 per cubic milliliter (150,000 is normal).

She had more problems. She had gained ten pounds. The small amounts of food she sneaked past the nurses could not be blamed for that much weight, so I looked at her legs. I pushed my index finger into the front of her leg where the flat anterior shaft of the tibia runs down the center and watched it sink into her flesh, leaving the defining impression that we identify as “pitting edema,” a common sign of water retention in the legs. I postulated that lupus or methotrexate had punched holes in Sheryl’s basement membranes, the filters in the kidney that are supposed to prevent the loss of protein, blood cells, and other essential blood elements. This would cause Sheryl to lose large quantities of protein into her urine, which would lead to a protein shortage in her blood. Proteins are an important source of oncotic pressure, the force that keeps the blood’s liquid portion (serum) from diffusing out of our veins. Lowering protein levels in blood results in leakage of serum into the surrounding tissues, which would explain Sheryl’s swollen, heavy legs. In response to the low protein levels, the liver cranks up its protein production and its cholesterol production, sending serum fat levels way above normal. Continuing the maladaptive chain of events, the body constricts its arteries, attempting to maintain adequate blood flow and pressure despite a perceived volume depletion due to the fluid leakage. The undesirable result is high blood pressure.

Nephrotic syndrome, the name for this collection of events, therefore consists of edema, protein in the urine, and elevated blood fats. I ordered a check of Sheryl’s blood fats and a 24-hour urine collection for total protein to confirm my suspicions. She spilled nine grams of protein in 24 hours, way above the normal one-tenth of a gram, and her cholesterol registered high at 308.

And she still had pancreatitis. "l’m a mess,” was how she greeted me my first day back; I had to nod in agreement. One of my most challenging patients ever, she was now sicker than I had ever seen her. But after reviewing everything in her chart, I saw a few changes I could make, and whenever there’s something that can be done, I, like most people, can remain hopeful even in dismal situations.

Perhaps the most important thing to do when a patient is taking a downward turn is to anticipate what the next catastrophe could be and to do whatever you can to prevent it. Sheryl’s anemia and hypertension threatened to overstress her heart, which continued to pump blood forward against her high blood pressure while receiving far less than a normal oxygen supply due to the reduced number of red blood cells in her blood. These circumstances can cause heart muscle death (heart attack) or an inability to pump all of the blood that comes to the heart (congestive heart failure).

So she needed more blood, a goal which we could attain by restoring her bone-marrow function and by giving a blood transfusion. She also needed a lower blood pressure, preferably with an accompanying loss of her extra fluid. I knew that we had

been giving her furosemide (Lasix), a strong diuretic that infrequently causes bone-marrow suppression and is not absorbed well when the intestines are swollen from such conditions as congestive heart failure and nephrotic syndrome.

I ordered a two-unit transfusion of packed red blood cells and a change from oral furosemide to intravenous bumetanide. Over the next five days, she lost 20 pounds of fluid, her bloodcell counts increased to their baseline levels, her blood pressure dropped into the normal range, her kidney function returned to about 75 percent of normal, and her pancreatitis resolved. “I feel better than I have in years,” she gushed on the day I discharged her from the hospital.

The speed of her recovery startled me, and I couldn’t help but feel good about and responsible for the turnaround in her condition. When she returned to my office one week later for her follow-up visit, I entered the exam room proudly.

“God spoke to me last week and told me I was cured” was how she opened our conversation. “So I stopped taking all of my pills,” including the steroids she needed to keep her lupus quiet. My attempts to convince her to think of her medicines as God’s tools failed, so I did what I always do when I can’t help someone: I referred her. “Please discuss this with your pastor,” I pleaded. “These issues and decisions are so important. I really think you need to go over them with someone who understands.” Her agnostic physician had run out of ideas. I don’t impose my agnosticism on my patients because the truth is that religious people sometimes get more help from their church than they do from me. She compromised with me on one point: she agreed to more frequent office visits.

So she came back once a week for the next three weeks, and she looked so well during these visits that she made me wonder if I hadn’t been reduced to the role of innocent bystander while some other force was working a miracle. She was eating a healthy diet for perhaps the first time in her adult life, and she had no abdominal pain nor swelling in her legs. Her cherub cheeks radiated happiness.

“I feel great,” she told me, but I remained troubled. Lupus doesn’t just go away, and her resting pulse was 120, so something wasn’t right.

Seven weeks later, she was back in the hospital with kidney failure, and this time it was permanent. Lupus had won its battle with her kidneys and my medicines, leaving her to wonder what God’s role was. I haven’t asked her about this yet. For now, she is accepting medical treatment, including the hemodialysis that she needs to remain alive. I’m accepting that this occurred in spite of my best efforts and contributed to my education about the levels of complexity my job has. Her spiritual instincts had defeated my medical knowledge. “She’s a really interesting patient,” her new nephrologist enthused to me over the phone after meeting her in the emergency room. I would add: and a humbling one.