Sickle cell disease: The forgotten survivors

In 2010, Clarence Anderson IV told his mother, Evangeline, “OK, Mama, you did take care of everybody. Time for you to be happy.”

It was her 44^th birthday.

He said, “What’s gonna be is gonna be.”

“You’re right,” she joked, as if she would ever wash her hands of her baby boy, after everything she had done to keep him healthy and living a full life. Seven months later, at age 21, he was dead.

Looking back now, she thinks he knew his end was coming. But it was a death that wasn’t foretold. Clarence wasn’t dying. His illness — sickle cell disease — had meant a lot of physical pain, strokes and time spent in hospitals.  But it wasn’t terminal, and it hadn’t stopped him from doing anything, including playing football for a season in high school.

Sickle cell disease (SCD) is a group of inherited red blood cell disorders that take their name from the irregular sickle shape of those cells in individuals with the disease. Healthy red blood cells are round, which makes it easy for them to move through small blood vessels, carrying oxygen throughout the body. But in individuals with the disease, the sickle shape prevents the cells from carrying out their function. They can become hard and sticky, getting stuck in small blood vessels and blocking the flow of blood and oxygen to organs in the body. This causes repeated episodes of severe pain, organ damage, serious infections or even stroke. Sickle cells also die early, resulting in a constant shortage of red blood cells.

The CDC estimates that SCD affects 90,000 to 100,000 people in the United States, which makes it a rare disease here. But globally, it isn’t, affecting millions of people throughout the world.  (It is particularly common in sub-Saharan Africa, South America, the Caribbean, Central America, Saudi Arabia, India and Mediterranean countries such as Turkey, Greece, and Italy.)

Similarly, while the rate of occurrence is low in the total U.S. population, it’s not rare when measured within the specific racial or ethnic groups it affects: Among African-Americans, the disease occurs in about one out of every 500 births, and among Hispanic-Americans, in one out of every 36,000 births.

In addition, about one in 12 African-Americans carries what is called sickle cell trait (SCT), which occurs when a person inherits one sickle cell gene and one normal gene. People with SCT usually do not have any of the symptoms of sickle cell disease (SCD) but can pass the trait on to their children. They can also experience heat stroke and muscle breakdown during intense exercise under very high or very low temperatures. (The sudden deaths on the field of several student athletes who unknowingly had SCT prompted the NCAA in April 2010 to require Division I institutions to perform testing for SCT on all incoming team members. Similar policies were extended to Divisions II and III schools in January 2011 and 2013, respectively. The policy  includes an opt-out provision for students who can provide results from a prior test or for those who are willing to sign a liability waiver.) 

“It’s rare depending on where you live because the disease is not equally distributed; for example, maybe in New Hampshire there are few cases, but there are places — like Atlanta — where the burden is crippling. The health system has to be able to adapt to that fact,” says Dr. Grant of the CDC.

To date, the only cure for SCD is a bone marrow or stem cell transplant, which includes risks of serious side effects, even death.  The current focus in SCD treatment is on relieving pain and preventing infections and strokes, a range of symptoms that vary from patient to  patient.

Treatments can include receiving blood transfusions — which Clarence did; avoiding dehydration by drinking eight to 10 glasses of water each day; and, once in pain, receiving intravenous therapy and medications. In 1998, the FDA approved the use for SCD of a cancer drug, hydroxyurea, which for many people has reduced the number of painful crises.

As individuals age, the effects of chronic sickling means more severe pain more frequently, and patients accumulate complications such as organ damage, renal disease, cardiovascular issues, stroke and priapism, or painful and long-lasting erections.  And like all adults, sickle cell patients face other health challenges as they age.

One of the main reasons care for SCD adults isn’t as good as pediatric care is because there simply aren’t enough hematologists specializing in sickle cell disease treatment for adults. Dr. Wally Smith, professor of internal medicine and scientific director of the Virginia Commonwealth University Center on Health Disparities, estimates there are as few as 300 adult SCD specialists across the country.

Doctors who could specialize in sickle cell disease are those who complete a fellowship in hematology and oncology after their internal medicine residency. When it comes to choosing a field after the fellowship, oncology is often the far more attractive career option.

“The tremendous infrastructure and financial support to incentivize people to pursue research or care in oncology” does not exist for SCD, says Dr. Michael DeBaun, director of Vanderbilt-Meharry Center for Excellence in Sickle Cell Disease. “So there’s not this allure, no constant interaction, where medical students, then residents, then fellows are introduced to the field.”

And while cancer care is financially lucrative, many SCD sufferers are on Medicaid and their treatment is not fully reimbursable.

In addition to paying less, Dr. Smith says that the limited treatment options in SCD can make it less intellectually rewarding than treating cancer, where constant developments in drugs and therapies make the field dynamic. 

Treating SCD often involves giving high dosages of opiates to relieve the excruciating pain patients can experience, which have a diminishing effect the more they are used.

“That lack of supply of willing and trained and available adult practitioners — that is problem No. 1,” says Smith. “Even if they are trained, they may not be willing or may not want to take care of these patients. They don’t want to be in the business of just giving painkillers; they don’t want to be a dope dealer.”

However, pharmaceutical companies have begun to take some interest in SCD. A couple of recently developed drugs that might help improve patients’ lives and also make the field more interesting to specialists are currently in FDA trial stages.

“There’s no simple solution, no silver bullet for this; you can’t change the number of sub-specialties in a quick turnaround,” says Dr. W. Keith Hoots, director of the Division of Blood Diseases and Resources at the National Heart, Lung, and Blood Institute (NHLBI), part of the NIH. 

It will require, he explains, “a concerted effort across training care systems in the U.S. as well as strategic changes in things like reimbursement so that doctors who go into it will get compensated.”

According to SCD activist Friend, health care professionals who have little knowledge or experience with the disease are often prejudiced. “Once you walk into the ER and start talking with the doctors, they judge you by what they see, and because I don’t look like a sick person, they think you can’t be in as much pain as you say. But when you have lived in pain for as long as you can remember, you can deal with it to a certain extent,” she says. “They think you are a drug seeker because you know 4 milligrams of a strong painkiller won’t cut it for you.”

Furthermore, Friend adds, “it’s definitely race-related, and it’s worse for African-American men; they are really stigmatized and made to suffer, and to doubt their own pain.”

Recognizing that the shortage in SCD specialists will take years to change, the conversation has shifted toward strategies that would make those primary care physicians and ER doctors who do end up providing that care better equipped to treat the disease.

The NIH is currently developing guidelines for primary care physicians that are projected to be available this summer, even though the amount of scientific evidence behind them is less than ideal, according to Johns Hopkins bioethics professor Dr. Carlton Haywood Jr., whose research focuses on SCD.

“So much of this is tied into the inequities in the amount of research and resources directed to SCD, compared to other disease, that we don’t even have the appropriate amount of research-based evidence to develop guidelines,” he says. “But we have reached a point where the NIH said, ‘Regardless, we have to do something.’”

For Vanderbilt’s DeBaun, the guidelines are only a first step.

“Simply having guidelines available doesn’t mean people use them. There have to be other strategies to reinforce the importance of the guidelines.”

At Vanderbilt, DeBaun decided to take specialized medical care off-campus, out of the academic center, and into a federally qualified health center located in an African-American neighborhood in Nashville. That way, by having a specialist available to work “shoulder to shoulder” with the primary care physician, he or she is able to gain greater understanding and experience with treating the disease.

DeBaun’s work is supported in part with a Health Resources and Services Administration (HRSA) grant, which champions the idea of a “medical home” in general and specifically for SCD patients.

Such a model envisions local primary care providers supported by a partnership with a regional specialist so that wherever a patient lives, both they and their primary care provider can have some kind of access to an expert if there isn’t one locally. This helps the primary care doctors feel as if they aren’t alone and makes them more willing and able to care for patients with specialized needs, all of which benefits the patient.

“We think this could be the long-term strategy,” says Dr. Edward Ivy, director of HRSA's Sickle Cell Disease Treatment Demonstration Program.

And from the patient side, Haywood, who also suffers from the disease, says efforts should focus on getting doctors thinking about transition from pediatric to adult care earlier and empowering them to ask the right questions and getting the answers. He also believes that conversation should start well before the child is on the cusp of transitioning into adulthood.

“It’s a particularly dangerous time,” he says. “Because no one is following them, they can easily get lost in the process.”

After Clarence turned 18, he was unable to find a specialist to care for him, so he stopped having regular transfusions, which were critical to minimizing the amount of strokes he suffered. When he had a pain crisis, he would end up in the ER, lost among all the other emergencies and attended to by doctors and nurses who weren’t trained to treat SCD. And because he was an adult and had moved away from home, he had lost his best advocate, his mother.