Ever since SCD was first described in the Western literature a century ago,23
understanding of the disease mechanisms and sequelae has been important to guide care of people with the disease. There was a time when SCD was considered primarily a pediatric condition because of extremely high childhood morbidity and mortality. In the 1960s, only 50% of SCD patients survived to age 20;24
however, in the first decade of the twenty-first century, the probability of survival to adulthood has improved to nearly 95%,25
with a parallel reduction in life-threatening complications. These improvements can be attributed to a number of medical advances, including the introduction of penicillin prophylaxis for prevention of pneumococcal infections,26, 27
vaccines in early childhood; universal newborn screening for hemoglobinopathies;31, 32
and prevention of primary strokes.33, 34
Currently, newborn screening for hemoglobinopathies is practiced in all 50 states. Hence, in contrast to previous years, the parents of virtually all SCD patients in this country become aware of their child’s condition shortly after birth. Upon being informed for the first time of the diagnosis of SCD in their newborn child, parents face a multitude of issues. Although most have heard of SCD, unless they or another family member also have the disease, parents are likely to have little understanding of the condition or its potential impact on the health and life expectancy of their children. Many new parents are surprised to learn that they were at risk of having a child with SCD, and were unaware that they and/or their partner were carriers of a genetic abnormality. In addition to feeling guilt for having passed on a genetic illness to their child, they may feel helpless or uncertain for the future.
From early in life and throughout their lives, people with SCD have great need for palliative care. Although a child with SCD is asymptomatic at birth (due to high levels of fetal hemoglobin), by three to six months of age the child is at risk for early complications of the disease. Frequently, dactylitis or “hand-and-foot syndrome” is the first clinical manifestation in an infant or toddler with SCD. Dactylitis is characterized by swelling of the dorsum of the hands or feet, or swelling of the fingers or toes. Progressive loss of splenic function begins in infancy and leads to a lifelong risk for potentially deadly bacterial infections, such as septicemia, pneumonia, meningitis, and osteomyelitis. Because of infection risk, young children with SCD are frequently hospitalized when they develop a fever. Infants or young children may develop potentially fatal splenic sequestration crises, due to trapping of the blood by the dysfunctional spleen, or aplastic crises associated with common viral infections (e.g., parvovirus). In these situations, red blood cell transfusions may be life-saving. Parents may feel ambivalent or fearful of the risks of transfusions, or may have religious objections, lending further emotional trauma to such situations. Families find themselves needing to adapt their lifestyles to accommodate frequent visits to the doctor or hospital, daily medications, blood tests and other medical procedures.
In addition to infections, the risk for certain complications of SCD begins early in life and continues throughout life. Examples35
include painful vaso-occlusive crises and acute chest syndrome, which is an acute illness characterized by fever and respiratory symptoms in an SCD patient and accompanied by a new pulmonary infiltrate on a chest X-ray.36
This syndrome of pulmonary infarction may arise from a variety of causes, including bacterial or viral pneumonitis, pulmonary infarction, fat embolus from marrow necrosis during vaso-occlusive crisis, or acute respiratory compromise. Although more common in young children, the condition is much more likely to be fatal in adults.37
School-aged children with SCD face additional challenges. Painful crises or hospitalizations may lead to frequent school absences, with difficulty in maintaining school performance and passing grades. Risk for debilitating strokes is high throughout the school years, with a peak incidence for cerebral infarction at about 7 years of age.38
The vascular pathology leading to infarctive strokes in SCD children is incompletely understood, but frequently involves the large cerebral arteries. In this case, inflammatory endothelial damage results from adherent sickle cells or the products of hemolysis in conjunction with high blood flow rates due to anemia and vasoconstriction from nitric oxide depletion. Intimal hyperplasia ensues, the caliber of the affected vessels narrows, and a thrombus ultimately occludes the vessel.39
A child having a stroke or found through screening to be at high risk for a stroke may start a chronic red blood cell transfusion program. This involves transfusions approximately monthly; this is about 90% effective in reducing stroke risk.33
Because discontinuing a program of regular transfusions is associated with return of high stroke risk,40
chronic transfusion therapy may be maintained for many years. This is not without risks. Chronic transfusion therapy leads to excessive iron accumulation in body organs (transfusional hemosiderosis), which results in liver, cardiac or endocrine abnormalities, and potentially contributes to premature mortality.41
In addition to overt strokes, a different CNS lesion known as “silent infarction” may be found in children with SCD.42
These children may experience attention deficit, hyperactivity or various learning disabilities. Silent infarcts, which can be diagnosed based upon characteristic brain lesions seen on MRI,43, 44
may progress to overt stroke.45
Neuropsychiatric testing and development of an individualized education plan at school may help a child perform to his or her fullest potential.
Children and teens with SCD face additional physical and social challenges. The renal damage caused by SCD leads to loss of urinary-concentrating ability during childhood.46
As a result, young people with SCD have a high incidence of primary enuresis, which may be embarrassing. Body image issues are common in adolescents and teens with SCD; these frequently include short stature and delayed puberty,47
as well as chronic jaundice. Participation in sports and physical activities is frequently limited. Not only do chronic anemia and propensity to dehydration limit the exercise capacity of SCD patients, but also painful crises may be triggered by vigorous exercise or environmental extremes, including summer heat, swimming in cold water, or travel to high altitudes. Despite these limitations, physical activity may be beneficial in SCD patients48
and should be judiciously encouraged. Denial, or a desire to be like other teens, may induce a patient with SCD to engage in risky behaviors,49
or to forgo his or her medications or medical treatments, sometimes with serious consequences.
As teens grow into adulthood, the transition to being an adult living with a chronic medical condition is difficult.50
The young adult must leave the familiar setting of the pediatric physicians and nurses who have cared for the patient for his or her entire life, and establish a relationship with an unfamiliar medical care team. In addition, the responsibility for managing the patient’s medical condition, taking medicines, making appointments, etc., is transferred from the parent to the patient. Medicaid or parental private insurance coverage terminates at the age of majority, and the patient must secure new medical coverage through an employer, Medicare or SSI (Supplemental Security Income) disability. If the pediatric sickle cell center has a transition program, that program may be a valuable resource in guiding the patient through this process.51
Certain medical complications of SCD become increasingly frequent in the teenage to young adult years. Because of sickle vasculopathy and poor wound healing, cutaneous leg ulcers may arise from apparently trivial injury, such as insect bites or minor abrasions.52
Ulcers may become large and debilitating, sometimes lasting for years. Avascular necrosis of bones occurs, most frequently in the femoral head, leading to chronic hip disease.53, 54
The patient ultimately may need a hip replacement in order to relieve pain and restore function. Avascular necrosis also may occur in the humeral head, leading to shoulder dysfunction. Collapse of infarcted vertebral bodies may lead to chronic back pain. Vasculopathy also leads to sickle retinopathy,55
which includes retinal hemorrhages, neovascularization and retinal detachment, and may lead to blindness. This complication is particularly frequent in patients with hemoglobin SC disease.56
Frequent eye exams are essential to identifying and treating retinal vascular lesions early.57
Cholelithiasis is a frequent complication of SCD. If asymptomatic, no intervention is required; however, cholelithiasis may progress to symptomatic cholecystitis requiring cholecystectomy.58
Priapism, a painful, prolonged involuntary erection, is a potentially serious condition in teens and young men with SCD. It may occur repeatedly; recurrent priapism leads to lifelong impotence in many cases.59
Priapism frequently begins at night, and prompt interventions that patients may try at home include voiding, ejaculation, warm baths and analgesics.60
However, the occurrence of a painful erection lasting more than two hours should be considered an emergency, and the patient should seek medical attention immediately, in order to reduce the risk for impotence. There is no universal approach to the medical management of priapism, but intervention may include oral vasoactive agents, transfusion, penile aspiration and injection with epinephrine or phenylephrine, and surgical shunting.59
Although many women with SCD can safely bear children, pregnancy is considered high-risk61
due to a high frequency of sickling complications, as well as spontaneous miscarriage, preeclampsia, premature delivery and low birth weight infants. Teens and young adults should be counseled to use effective methods of birth control to avoid unintended pregnancies. When they become pregnant, women should initiate prenatal care promptly from an obstetrician experienced in the management of SCD. Teens and young adults with SCD should receive genetic counseling, in order to understand the risk of having children with SCD. Their partners should also be tested for a hemoglobinopathy; this testing should be by means of hemoglobin electrophoresis or HPLC (high-performance liquid chromatography), and not merely a sickle prep, as the latter will miss other hemoglobinopathies such as hemoglobin C or beta thalassemia.
Due to chronic pain, physical disabilities, frequent acute pain episodes or other complications resulting in hospitalization, SCD patients may be fired for excessive job absences, and may have difficulty in securing employment. Employed patients should be encouraged to file federal Family and Medical Leave Act papers with their employer, to protect their jobs whenever possible. Similarly, patients may experience difficulties with marital and other personal relationships.
Despite medical advances, SCD in adults is a debilitating disorder leading ultimately to premature mortality. The Cooperative Study of SCD (CSSCD), a national study of the natural history of SCD, found in 1994 that patients with persistently high levels of fetal hemoglobin (Hb F) had prolonged survival compared to those with low Hb F. The protective effect of Hb F has been observed for many years62
and forms the basis for the treatment of patients with hydroxyurea,63
a chemotherapy agent capable of inducing Hb F production in some SCD patients. Long-term follow-up of patients who participated in a definitive trial of hydroxyurea therapy64
has provided some preliminary evidence that use of this drug may prolong survival. Patients often succumb to chronic organ failure, dying from an illness that under other circumstances would not be fatal. Common causes of death include pulmonary hypertension, sudden death due to unknown causes, renal failure, ACS or acute multi-organ failure, often in the context of hospitalization for painful crisis, sepsis, cardiac disease, thromboembolism, stroke, or iron overload.65
Frequently, more than one of these conditions contributes to the death.
Despite the multitude of challenges facing persons living with SCD and their loved ones, many adults are able to lead successful careers and fulfilling family lives. Such patients’ optimism has been eloquently expressed by the late Linda Collins, a beloved and respected Chicago sickle cell activist, UIC patient and the founder of the Have a Heart for Sickle Cell Foundation, whose motto was, “SCD is not who you are; it is what you have.” With the focus on the person with SCD, effective management of the pain and other symptoms of the disease is important for patient-centered and family-focused care and central to high quality of life, as advocated by a palliative care approach to SCD management.