LATOI WALKER HAS BEEN IN PAIN FOR DAYS. It’s not the uncomfortable but livable pain of a backache, she says, nor the throbbing but temporary pain of a migraine. This pain is an excruciating, off-the-charts brand of awful, with no clear end in sight. “It’s the kind of pain you wouldn’t wish on your worst enemy,” says Walker, a pretty, round-faced 35-year-old who has been suffering through these bouts of agony for the past two decades.
Walker was diagnosed with sickle cell disease at age 3. For most of her childhood she was spared the intensely painful episodes known simply as “pain crises,” a hallmark of the disease. Then, around puberty, things took a horrifying turn. Suffering crises every few weeks, she missed lengthy chunks of high school. She managed to graduate, even to get college scholarships, only to have recurring cycles of deep, bony pain force her to quit soon after she started. Today she has set her sights on a career as a nail artist.
As she sits stiffly, her eyes staring motionless ahead as she describes each setback, it’s clear that the disease has taken a heavy emotional toll. But, she adds, none of these comes close to the searing humiliation she experienced each time she needed treatment for a crisis. Like most sickle cell patients, Walker has found that only the very strongest narcotics, delivered intravenously and usually in a hospital emergency room, take the edge off her pain. But the specter of a young, African American person insisting on high doses of narcotics doesn’t always bring out the best in the staffs of some emergency rooms she has visited.
Photograph by Jennifer Bishop
|Since her arrival here in 2000, Sophie Lanzkron has pushed to dramatically improve care and treatment for adults with sickle cell disease.
“In the ER, when we say we’re in pain, they say, ‘We just gave you some medicine. You’re drug-seeking.’ They look at us like we’re all drug users,” she says. “It’s not helpful because, one, it hurts our feelings, and two, we’re still in pain. I will go through excruciating pain because of the way I’m treated sometimes.”
Walker used to suffer in her Glen Burnie home, waiting until the pain reached an unbearable crescendo before she made her way to the nearest emergency room. Now, she has another option: In February 2008, the Johns Hopkins Hospital opened an infusion clinic especially for patients with sickle cell disease. Open Monday through Friday, the center is staffed by understanding caregivers who greet patients by name. Within 10 minutes of walking through the center’s doors, Walker is already feeling relief.
The infusion center isn’t the only long-awaited help Hopkins offers for those with sickle cell disease, a group that has in turn been ignored and scrutinized—often unsympathetically—by medical professionals. Hopkins researchers are currently investigating new ways to make life better for sickle cell patients, from working to find a cure (see “So Long to Sickled Cells,” below) to improving how patients and their doctors interact (see “An Eight-Minute Answer?” below).
WALKER US IBE OF ABOUT 100,000 PATIENTS patients with sickle cell disease here in the United States, with several millions more scattered worldwide. People with SCD produce an abnormal type of hemoglobin that causes their ordinarily round red blood cells to flatten and stiffen into a sickle shape when they become dehydrated, overly fatigued, or stressed—or sometimes, for no clear reason at all. Whereas normal red blood cells slip easily through blood vessels, the sickled cells stick to each other and clump together, blocking blood flow. Without blood, the body’s tissues begin to suffocate and starve, causing the immense pain of a crisis.
Researchers have known since the 1940s that people with SCD have two copies of a particular gene, one from each parent. Those with only a single copy of the gene, which makes a variety of the blood protein known as hemoglobin that carries oxygen, are more likely to survive severe malaria than people without any copies. Thus the sickle cell gene has flourished in areas of the world where malaria is endemic—particularly Africa, South and Central America, and the Middle East. As the peoples from these areas spread throughout the world, they took their genes, and sickle cell disease, with them. In the United States, the vast majority of sickle cell sufferers have African ancestors; about 1 in every 12 African Americans has one copy of the sickle cell gene, and about 1 in every 500 has sickle cell disease.
Over the last eight years, Sophie Lanzkron has heard many different descriptions of what the pain of an SCD crisis is like—almost as many descriptions as patients themselves. “The common thread is very simple: It’s bad,” says Lanzkron, who directs Hopkins’ Sickle Cell Center for Adults, which sees about 300 patients regularly.
Sitting in her small office, the young Hopkins physician crosses her arms and leans in, recounting how one of her patients recently fell 20 feet at his construction job and broke several bones. When he saw her next, she asked him which pain was worse, his accident or a sickle cell crisis? There was no question, he’d said—definitely a crisis.
“It’s not just that the pain is awful, but it’s also so unexpected,” explains Lanzkron, an assistant professor of medicine and oncology. “Someone with sickle cell will just be doing whatever they’re doing, and then, boom—they’re in excruciating pain, and they really want to get treated right away.”
But that’s precisely the problem with many busy emergency rooms, she adds. While doctors are treating patients with heart attacks and gunshot victims, people with sickle cell disease are often triaged to the bottom of the list.
Lanzkron says pain relief isn’t just about comfort. While patients receive narcotics in their IVs, they typically also receive fluids that can help rehydrate them and turn a crisis around. As patients in crisis languish untreated in emergency rooms, tissues starved from oxygen gradually die. Blood vessel blockages and tissue death account for many of the complications sickle cell patients suffer, including cumulative damage to organs, strokes, and frequent infections.
Given these deeper consequences, Lanzkron says she’s not entirely sure why patients are often treated so suspiciously when they come to an emergency room. Perhaps ER staff don’t have the time to verify that a patient has sickle cell if they’re not already on the rolls. Physicians may also be hesitant to give drugs that are frequently abused. Though the vast majority of SCD patients are seeking treatment for their pain and not a fix, some SCD patients do abuse drugs or develop dependency issues from frequent narcotic treatments.
Additionally, it’s impossible to verify independently whether a patient is in crisis. No clinical test exists, leaving doctors to rely on a patient’s word. “I’ve heard patients told by doctors, ‘We’ve checked your labs, and you’re not in crisis,’” says Lanzkron. “There’s no way to check that, though.”
Lanzkron and others in the field suggest that, in the end, there may be elements of racism at play. But confirming that a racial health disparity exists is virtually impossible, since practically every patient with sickle cell disease belongs to a minority group. There is no racial majority with the same disease to look to for comparison.
Solving this problem for sickle cell patients nationwide seemed like an insurmountable challenge when Lanzkron arrived at Hopkins in 2000. At the time, though Hopkins had an excellent pediatric sickle cell program (like many states, Maryland diagnoses children with the disease at birth and provides for their care), no adult program existed. Many adult patients were receiving their only care for the disease when they showed up at emergency rooms.
Photograph by Jennifer Bishop
|Psychiatrist C. Patrick Carroll confronts the depression and hopelessness that often accompany the chronic pain of SCD.
Within two years, Lanzkron opened a sickle cell clinic two days a week that provides mainly preventive care, such as vaccinations (to ward off infections) and referrals for transfusions to replace sickle-prone blood with healthy blood. Transfusion therapy can be helpful, but it’s far from a perfect solution to treat SCD, Lanzkron explains. Receiving blood is time-consuming for patients, requires frequent exposures to blood products that might carry bacteria or contaminants, and can introduce too much iron into a patient’s bloodstream—a condition that can lead to heart and liver failure if it’s not managed correctly. Only about 10 percent of Lanzkron’s SCD patients currently receive monthly transfusions.
She also worked to get more patients on a drug called hydroxyurea, the only medication FDA-approved to treat SCD. It’s specifically approved only for those with the most severe form of the disease known as sickle cell anemia, which affects about 60 percent of patients. The drug works by boosting blood levels of a type of hemoglobin that makes cells more resistant to sickling. Hopkins researchers were among the first to study hydroxyurea’s effects on sickle cell anemia, finding in 1995 that it halved patients’ numbers of pain crises on average and reduced their need for transfusions. Though hydroxyurea is clearly beneficial, Lanzkron notes that many patients who are eligible still don’t take it. Although the data show no clear danger to taking the drug long term, the long-term safety of the drug hasn’t been officially proved either, she says.
In addition, Lanzkron worked with ER staff to reduce wait times for patients in crisis, cutting six-hour waits to 2.5 hours. Yet for patients in crisis, says Lanzkron, even two hours can be too much. So in 2005, she began researching the possibility of a clinic where patients could get immediate pain relief and hydration.
Since this new clinic might also catch patients whose sole source of care had been the ER, Lanzkron reasoned that it might present an even bigger opportunity: to help improve not just their physical health but their emotional and social well-being. She envisioned a place staffed not just with doctors, physicians assistants, and nurses but also a psychiatrist to tend to the mental health issues that can complicate treatment of a chronic disease, and a social worker to help patients work through common emotional problems, such as unemployment, money issues, and family troubles.
Lanzkron’s dream became a reality when the Johns Hopkins Sickle Cell Infusion Center opened its doors about a year ago, launched with $500,000 in funding from Hopkins—and support from medical insurance companies, including Hopkins-owned Priority Partners. Those companies’ bottom-line rationale: financially supporting better pain crisis management will stave off potentially more costly health complications down the line.
The facility, located in a group of converted rooms in Hopkins’ Carnegie building, has a cheery waiting room with bright lights and colorful green chairs.
“They ask you how you’re feeling. If you don’t feel like talking, you just sign in,” reports Latoi Walker, who gestures toward the clipboard on the receptionist’s desk as a television overhead broadcasts a chatty morning talk show.
Inside the treatment area, the scene turns decidedly more somber. Four patients, separated by green hanging drapes, recline on medical grade easy chairs in darkness. As they receive a steady drip of medication and fluids through their IVs, the only sounds are the sporadic conversations among caregivers and the soft hum of CNN on a large-screen television.
Patients stay for as long as it takes to relieve their pain—usually a few hours—until they either head home or check into the hospital for further treatment. However, that’s not where the story ends.
“When someone comes in to see us in crisis, it’s a bump in the road, but it’s also an opportunity,” says psychiatrist C. Patrick Carroll, who works closely with many patients at the Infusion Center.
Carroll, a burly young doctor with a light brown beard, wanted to be a psychiatrist for as long as he could remember. But he’d never planned on working with sickle cell patients. In medical school, the feedback he’d received from other doctors wasn’t favorable. “If you’d say ‘sickle cell,’” he remembers, “their eyes would roll back in their heads. The impression that floats around is that these patients are very tough, that there’s lots of bad behavior, that they’re too interested in opiates.”
Rather than seeing SCD merely as a series of crises, Carroll sees it as a chronic condition that requires treating the whole person. Carroll’s work starts when Lanzkron and her colleagues notice something in one of their patients that looks like it’s “more” than just SCD—maybe the patient stops coming to appointments, starts getting into arguments with his health care providers, or just looks depressed or burned out. Carroll meets with the patient to try to get at the root of the problem, then develops a comprehensive, step-by-step plan to address the problem fully.
It’s the rare sickle cell patient who has everything going for him except the disease, Carroll explains. Many people he sees are like a recent patient—a young, African American man who had dropped out of high school and remained unemployed due to his sickle cell pain. His family—many members crammed into a tiny, drafty house—relied on his meager disability check to pay the bills. He didn’t have a car, so he had to walk to his appointments, a journey that could take two hours because of his chronic pain. The patient’s previous doctors complained that he frequently missed appointments. But from the patient’s point of view, the situation was hopeless—he was in chronic pain, and his doctors weren’t helping.
“He was depressed out of his mind, but he had never been diagnosed with depression,” says Carroll. “We started working on that.”
This patient has made significant progress, Carroll adds. Though many problems in his personal and family life will take time to improve, he’s now coming to more appointments—a step in the right direction.
Carroll says he’s seen many patients take better care of themselves and their sickle cell disease once their underlying issues have been addressed—a process that can take years, rather than a few hours or days. “At a really pragmatic level, it’s just irrational to give up,” he says. “If you do something, there is some chance it will work—maybe it’s slim, but if you give up, you’ve decided on certain failure.”
AMONG THE SICKLE CELL PATIENTS who defy the odds, Carlton Haywood is a standout.
|Photograph by Jennifer Bishop
|"This issue of trust [between patient and physician] may be a huge barrier to whether patients get appropriate pain management when they're in the middle of a pain crisis." - newly minted PhD Carlton Haywood, himself a SCD sufferer.
Haywood, who joined the faculty here last October as an assistant professor of medicine in the Division of Hematology, also holds an appointment at Hopkins’ Berman Institute of Bioethics. Tall and clean-cut, he displays a stiff stride that testifies to tissue damage in his hips caused by sickle cell. Haywood was diagnosed with the disease at age 2, and has logged dozens of crises during his 32 years. Some have been mild enough to treat at home, he says, but others are severe enough to land him in the hospital for days.
“Think about the worst pain you’ve ever had, and think about a severe thunderstorm. The steady beating rain is like the pain beating all over your body, and there’s also lightning flashes in the midst of this pain storm,” he says. Unlike a real storm, however, the pain of a crisis can span over days or even weeks without letting up.
Haywood remembers a childhood marked by frequent trips to the hospital. When he wasn’t in the hospital or home sick, he was often sitting at a desk outside his classrooms, making up work he’d missed while his classmates went on with their normal routine.
Such experiences lead many young SCD sufferers to eventually drop out of school. But Haywood was lucky. His parents pushed him to continue with his education, and he went on to complete his undergraduate degree at the University of Virginia. He was also blessed with a team of doctors who encouraged him to advocate for his own care. “They instilled in me that I have a certain expertise about my condition, what works for me and what doesn’t, so I understood what treatment I needed and felt comfortable asking for it,” he says.
As he headed into adulthood, Haywood began to notice that many of his fellow sickle cell sufferers hadn’t been as fortunate as he’d been with his providers. Patients in support groups he’s attended have described a myriad of mistreatments.
When Haywood began to consider a career in public health, he immediately saw his calling in helping others with SCD. He focused his doctoral research at Hopkins’ Bloomberg School of Public Health on the concept of “patient centeredness,” the idea of treating patients as individuals with different experiences that need unique considerations, rather than taking a cookie-cutter approach. A key component to making this work is communication, he explains.
Haywood wanted to see whether sickle cell patients’ ratings of how well they communicate with their care providers had any bearing on the trust they had in the medical profession in general. In a study here led by associate professor Mary Catherine Beach, he asked SCD patients to answer questions based on dealings with their doctors within the past year. Were their doctors really listening to them? Explaining everything clearly? Showing respect for what they had to say?
Not surprisingly, the researchers found that patients who gave low ratings to their doctors’ quality of communication also had little trust in doctors in general. This lack of trust probably runs both ways, Haywood adds, with doctors often having little confidence that their SCD patients aren’t drug seekers or that they’ll participate in their own care. Haywood plans to examine doctors’ trust in his next study, then go a step further to see how attitudes on either side affect patients’ ultimate care for sickle cell disease. “This issue of trust might be a huge barrier to whether patients get appropriate pain management when they’re in the middle of a crisis,” he says.
Haywood has big ideas for many more SCD-related research projects. He recently joined a national steering committee charged with exploring the scientific, ethical, and policy issues involved in developing a system to register and track patients with hemoglobin-related diseases, including SCD. If researchers succeed in developing this system, Haywood says, they could get a much better idea of how many people in the U.S. have SCD, where they live, and how they’re doing.
Haywood also talks with Hopkins first-year medical students each year to describe what it’s like to have this disease and how important it is for doctors and patients to communicate well.
With his health holding steady, he hopes to make big strides in this field for years to come. The average life expectancy for those with the most common form of SCD, which Haywood has, is thought to be in the mid-40s. Though his parents were told he wouldn’t live past childhood, Haywood says he’s still relatively healthy, despite chronic hip and back pain. He has the occasional crisis, but since he started taking hydroxyurea in 1995, the frequency of his crises has greatly decreased.
As the storm of his sickle cell disease has lightened, Haywood says his desire to help other patients has grown.
“I really consider myself lucky, as patients go,” he says. “My parents’ financial situation was such that I’ve never been without health care coverage. They supported my educational efforts, and I had support from clinicians and friends.
“I personally feel that it is my responsibility to take advantage of the good fortune I’ve been given,” he says, “to try to improve conditions for others with the disease.”
So-Long to Sickled Cells
There’s currently no way to relieve sickle cell patients of the faulty genes that cause their disease. However, there is a way to permanently rid patients of their sickled blood cells: by swapping their bone marrow, the body’s blood-making factory, with marrow from a healthy person, which produces only normal, healthy blood cells.
Doctors have been performing such bone marrow transplants in people with sickle cell disease for two decades. However, says Robert Brodsky, director of Hopkins’ Division of Hematology, it’s not a perfect treatment. Since sickle cell patients can accumulate massive organ damage as they age into adulthood, doctors typically perform bone marrow transplants only in children, whose organs are young and healthy enough to withstand the chemotherapy necessary to prep their bodies for treatment. Even then, less than 1 percent of patients with the disease have a suitable “matching” donor, usually a full sibling whose immune cells share the exact same group of proteins to prevent rejection of the new marrow.
Brodsky and his colleagues at Hopkins have a possible solution for both problems. They have been testing a procedure that gives patients bone marrow transplants that are just a half-match, allowing a bigger pool of donors that includes parents and even half-siblings. They’re also giving patients less chemotherapy. Both conditions usually make it riskier for a transplant to work. However, the doctors also give these patients a high dose of a drug called cyclophosphamide (a regimen known as “Hi-Cy”), which “reboots” their immune systems, making it less likely that the donor marrow will be rejected or that immune cells in the new marrow will attack the patient.
Brodsky and his colleagues have tried their new approach in just two patients. One, a 45-year-old Baltimore woman named Pamela Newton, has been completely cured of her disease. Brodsky says that the other patient, a 19-year-old man, wasn’t as lucky—his donor bone marrow didn’t engraft. Brodsky and his fellow researchers plan to enroll up to five more sickle cell patients in a clinical trial over the next year to continue to study their new technique. —CB
An Eight-Minute Answer?
Mary Catherine Beach had long been aware of the difficult personal interactions between doctors and sickle cell patients.
After conducting a small study at Hopkins in 2006, which found that most SCD patients in crisis reported insufficient pain management, far from what hospital guidelines suggest, Beach considered doing a second, bigger study. But she quickly changed her mind. “I couldn’t spend more of my efforts trying to document how bad things are in the rest of Maryland, in California, in Florida,” she says. “Everyone already knows things are bad. We should move on to finding a solution.”
So she came up with a novel idea. Why not use film to allow patients to share their own searing stories? “I felt doctors would be moved by that to give better pain management and be more compassionate,” says Beach, an associate professor of medicine and the researcher who led Carlton Haywood’s initial study on patient trust.
Beach considers herself the creative type—she’s a skilled amateur photographer—but admits that she knew “absolutely nothing” about creating a film. She found an unusually perfect resource in a fellow mom from her child’s school: Nina Noble, the executive producer of the popular HBO police drama The Wire. Noble referred Beach to her father-in-law, Nigel Noble, an Academy Award-winning documentary maker, who graciously volunteered his expertise, time, and equipment. A small grant provided by Hopkins’ Osler Center for Clinical Excellence covered Noble’s expenses.
Over the course of two days, Beach, Noble, and others at Hopkins filmed sickle cell patients at the hospital and in their homes. The resulting film, currently an eight-minute pilot version, captures a vivid array of patient experiences. Those featured include a wife and mother of three, who tearfully recounts how she spends each visit to the ER warily watching the clock, afraid that she won’t receive the next dose of medication on schedule to ward off the terrible ache of her crises.
Beach and her colleagues plan to use the pilot film for a study aimed at measuring physician response. Will doctors and nurses who view the film be more likely to follow hospital guidelines for pain relief when treating sickle cell patients?
“You may ask, how could eight minutes of our film change the behavior of a doctor or nurse? We’re not sure that it can,” says Beach. “But we have to start somewhere.” —CB