Jefferson doctors, and long-time patient, Julius Adams, ask others to listen and understand the pain of sickle cell disease.
Editor’s note: This article has been reviewed for accuracy from an earlier version posted in October 2021.
Imagine living, since you were an infant, with chronic and acute pain, exacerbated by stress, anxiety and depression, while trying to hold down a job and keeping up with economic and family responsibilities. All of this while facing the very real possibility that because of your disease, you could experience sudden organ damage and stroke.
Such is the life of patients born with sickle cell disease (SCD). This condition is largely incurable, and those who have it are oftentimes stigmatized because of their legitimate and frequent, though very worrisome, use of opioids to relieve severe pain. Compassionate and empathetic care are critical to ensuring patient compliance with regular screenings and treatments to manage SCD.
“Hopefully, some widely accessible cures for sickle cell disease may be on the horizon,” says internist Dr. David J. Axelrod. “But meanwhile, patients live tough lives, knowing not only that their life expectancy is lower than average, but also that they could die suddenly and unexpectedly. A lot of SCD patients have lived through the passing of family and friends. And many spend a lot of time in the hospital for pain crises, which can be very wearing. So, I think the main thing their friends, co-workers, neighbors and the medical community can do is to spend time talking with and listening more carefully to SCD patients. Show them compassion and don’t be judgmental of them for seeking supervised relief.”
Dr. Axelrod, whose concentrations are primary care and pain management, is one of the directors of Jefferson Health’s Comprehensive Sickle Cell Program, Philadelphia’s largest adult sickle cell program, which has been helping SCD patients since it was established in the 1970s. The other director is hematologist Dr. Sanaa Rizk, whose primary focus is providing standard care therapies as well as access to clinical trials for patients managing hematologic complications of SCD.
A Group of Genetic Diseases
SCD is an umbrella term used to describe a group of genetic diseases that affect hemoglobin, the protein in red blood cells that carries oxygen through the body. These cells are normally flexible and disc-shaped, so they can move through the blood vessels easily. But SCD causes red blood cells to harden and shape shift into crescent, or sickle, form. These changes make it far more difficult for red blood cells to circulate oxygen to important body organs, leading to organ damage.
Show [sickle cell disease patients] compassion and don’t be judgmental of them for seeking supervised relief. –Dr. Axelrod
SCD patients can experience chronic daily pain from necrosis of some of their joints, a disease which may cause a joint surface to collapse due to loss of blood supply. Patients may also have acute painful episodes in the chest, back, arms or legs that are known as sickle crises. These pain episodes require immediate care – usually in a hospital. Another aspect of SCD is anemia. Acute sickle cell complications can lead to pneumonia, acute chest syndrome and strokes – even in patients who are at a young age.
The most common and severe type of SCD is hemoglobin SS disease – better known as sickle cell anemia. It occurs when the hemoglobin S gene is inherited from both parents. – creating the worse symptoms of SCD.
The next-most common type is hemoglobin SC disease, occurring when the hemoglobin S gene is inherited from one parent and the hemoglobin C gene from the other. Though some symptoms may be less severe, it can cause painful sickle crises.
Other types of SCD include hemoglobin SB+ (beta) thalassemia, which is less severe, though complications can still develop, and hemoglobin SB O (Beta-zero) thalassemia, which is similar to hemoglobin SS when it comes to symptoms and complications.
SCD is most common among those whose ancestors come from sub-Saharan Africa, Spanish-speaking regions in the Western Hemisphere, Saudi Arabia and other Mediterranean countries. One theory as to why SCD impacts the Black population in the U.S. so disproportionately is that it’s an evolutionary trait developed originally in sub-Saharan Africa as protection from malaria.
Increased but Still Uncertain Life Expectancy
“SCD really used to be a pediatric disease,” says Dr. Axelrod. “Many patients didn’t survive into adulthood. That has radically changed in the past 20 to 30 years. For example, a study done in 1994 found the life expectancy of a person with sickle cell anemia to be 42 years for men and 48 years for women. More recent studies have life expectancy in the 50s for men and women. In developed countries, where antibiotics and immunizations are more plentiful, physicians can treat infections patients developed as children because of their SCD so that more of them survive well into adulthood.
“On the other hand, patients can still die unexpectedly. We had a sad case a couple of years ago of a patient in his 20s, who rarely had pain and therefore rarely came in for screenings. He died suddenly from acute chest syndrome, which can occur unpredictably.”
Pain and Anemia
Jefferson Health’s Comprehensive Sickle Cell Program recommends that patients come in every three months, or at least once a year, for various screenings that can detect silent killers caused by SCD, such as kidney damage. That’s important because patients can die even if they rarely show symptoms. Patients who have frequent pain episodes are at higher risk. If their pain crises are so great that they need inpatient hospital care more than three times, a year that is an indication of a likely early death.
“Our patients have had SCD since childhood,” says Dr. Axelrod. “A lot of them transition right from their pediatric program to us. Other patients, for a variety of reasons, take a pause from receiving care before coming to our program. Either way, they may have had stunted growth and development as children, and as adults they usually have a pattern of pain they are used to, such as in their limbs, back or chest, which can be more life-threatening. If they are experiencing a different pain crisis than usual, they know it and can tell us immediately, so that we can screen for other disorders that may be causing or contributing to their discomfort.”
Anemia is also something many of Jefferson Health’s SCD patients have struggled with throughout their lives. Early symptoms are low-energy and fatigue. In the long run, anemia can lead to cardiac failure or shock. To ease anemia, patients may receive a lot of blood products throughout their lives that will cause increased iron in their organs, leading to organ failure and even death if untreated.
“Each patient’s experience is different,” notes Dr. Rizk. “Some patients rarely get pain, while others experience it every week – it really varies. Some may have little or no discomfort as young children but then begin having it as they become teenagers and become stressed more frequently because of increasing responsibilities such as school, planning their careers and starting a family. As they grow older, they also become independent from their parents’ supervision and may lose medical coverage for a while, which can lead to lack of compliance with doctor visits or therapy.”
Although approved by the FDA in 1967 as a chemotherapeutic agent for treatment of various cancers, hydroxyurea, a capsule taken orally, was subsequently approved in 1998 for treatment of SCD. Hydroxyurea, supplemented with folic acid, is the standard of care for all sickle cell patients because it has been shown to decrease mortality and the frequency and severity of pain crisis. In 1992-96, Jefferson participated in the seminal multicenter clinical trial that established hydroxyurea’s efficacy in treating pain from SCD.
Between 2017-19, some medications developed specifically for the treatment of SCD have come onto the market, including:
- L-glutamine oral powder – works to increase the amount of free glutamine circulating in the blood, enabling red blood cells to regain the flexibility necessary to travel through blood vessels and capillaries so they can carry oxygen to tissues throughout the body.
- crizanlizumab-tmca – an infusion therapy that decreases the frequency of patients’ chronic painful crises and hospital admissions. Jefferson participated in its phase 2 clinical trial.
- voxelotor – an oral medication that decreases breakdown of red blood cells and increases hemoglobin to improve anemia. Jefferson participated in the HOPE Trial that helped to establish this treatment.
“The only known cure for SCD right now is bone marrow, or stem cell, transplant – but it is rarely employed,” says Dr. Rizk. “It is primarily used for children with stroke or other severe disease manifestations. In most centers, few patients meet the criteria, including identification of an HLA-matched sibling donor – that is, a sibling whose tissues match those of the patient. Novel approaches such as using low-dose chemotherapy and/or radiotherapy regimens are also being studied.”
Next in the development pipeline is gene therapy. A few companies are using different gene-editing techniques, such as CRISPR, to increase normal hemoglobin production or increase fetal hemoglobin expression to red blood cells from sickling and destruction.
“Instead of being judgmental of them, take the time to listen to them,” Dr. Rizk urges. “When you listen to their stories, you can feel their emotional pain, which is sometimes bigger than their physical pain because of how they’re often treated by communities and by hospital emergency departments.”
Passionate Patient Advocate
One such patient of Dr. Axelrod’s who is a passionate advocate for compassionate and non-judgmental treatment of those with SCD is Julius Adams, 56, a Philadelphia native who currently lives in Berlin, NJ.
When he was two years old, Adams began receiving care for his hemoglobin SC disease at Children’s Hospital of Philadelphia. In 1983, when he turned 16, he transferred to Jefferson’s adult Comprehensive Sickle Cell Program, where he was originally under the care of noted clinician and researcher Dr. Samir Ballas; Adams has been a patient of Dr. Axelrod’s for the past 17 years.
“I wouldn’t wish this on my worst enemy!” says Adams of the pain he has experienced. “It’s hit me in different areas – my shoulders, knees, thighs and back. The pain has been so unbearable at times that it’s had me crying like a newborn baby and put me in a fetal position for comfort.”
Adams currently takes acetaminophen-codeine and methadone pills daily for his pain. He hasn’t been in the hospital due to a pain crisis for 15 years. But when he was younger, his pain was so bad that when he was unable to obtain additional medications at various ERs to ease his pain, he sought relief through other avenues.
“I became highly addicted,” Adams candidly admits. “There was no way around it – how could there be when I’d been taking prescribed opioids all my life to manage the pain? I used to overhear nurses talking about me disrespectfully. I would say to them, ‘Please don’t do that. I didn’t choose to have sickle cell – sickle cell chose me! If you knew what this pain was like, your thinking would be totally different.’”
Fortunately, Adams is now able to effectively manage his pain by carefully following the daily regimen Dr. Axelrod has prescribed for him. In fact, Adams has frequently talked about his SCD journey on panels put together by Dr. Axelrod for the benefit of his medical students. During those discussions, he talks about the importance of understanding SCD and of the patient’s right to understanding, respect and compassion.
“So many hospitals, healthcare workers and others in the community are blind to the realities of sickle cell disease and its impact on patients. It saddens me,” says Adams. “I speak out about SCD to get my message heard: Please educate yourselves before you judge us.”
Today, Adams is happily employed as an executive director at a senior living facility, and enjoys a wonderful relationship with his five children and partner. He is committed to sharing his story so that others – SCD patients and care providers alike – can learn and benefit from his experience in managing this debilitating disease.