Patients with sickle cell anemia have, until recently, spent their short lives mostly under the care of pediatricians. Now that patients are living into their 40s and beyond, internists are more likely to see adults with sickle cell anemia. (Editor's Note: See Ann Intern Med. 1998; 128:882-4 for information on other childhood diseases being seen in adults.)
The transition from pediatric care to adult care can be difficult for young adult patients. Adolescents are accustomed to their parents communicating with the physician and managing their day-to-day health care. As patients approach their 20s, that responsibility shifts from the parent to the patient. "It's a big change, and it can be scary for the patients," said Chris Brunson, MD, assistant professor in the division of hematology/oncology at the Medical University of South Carolina. The transition requires open communication and some reeducation for young adult patients.
As recently as the early 1970s, most people with sickle cell anemia did not live beyond their early 20s. Many died before age 5, often from pneumococcal sepsis. Now, with early testing (most states test newborns for sickle cell anemia) and daily penicillin prophylaxis, the life-threatening infections that were once the leading cause of death for children with the disorder have been reduced by 85%. One often-cited study found that 50% of patients survive beyond their fifth decade (N Engl J Med. 1994; 330:1639-44).
The acute chest syndrome and severe painful events, or crises, are the most common acute complications for adults with sickle cell anemia. The acute chest syndrome is characterized by hypoxemia, chest pain, fever, and dyspnea. Chest radiography generally shows new pulmonary infiltrates in one or more lobes. However, diagnosis can be difficult because infiltrates may take several days to appear on radiographs, and symptoms sometimes mimic myocardial infarction or angina.
"Acute chest syndrome is considered a true medical emergency," said Kathryn Hassell, MD, associate director of the Colorado Sickle Cell Treatment and Research Center at the University of Colorado Health Sciences Center in Denver. In adults, acute chest syndrome usually results from intrapulmonary sickling, bacterial or viral infection, or emboli of sickled red blood cells, she said. The acute chest syndrome strikes some patients several times a year.
Although painful events are commonly thought to occur when sickled erythrocytes cause vaso-occlusion, Graham R. Serjeant, FRCP, of the MRC Laboratories at the University of West Indies in Jamaica, contends that bone pain, which can be most severe in early adulthood, results from shunting of blood away from active bone marrow, thereby inducing bone marrow necrosis (Lancet. 1997; 350:725-30). Despite these opposing theories, Serjeant and others agree on the therapeutic approach. In some cases, a patient can manage the pain at home with rest, increased fluids, mild analgesia (such as aspirin), and a warm environment. If pain persists or fever develops, the patient needs more aggressive management.
"One of the biggest problems we see is patients being undermedicated for painful events," Brunson emphasized. "The patients sometimes get labeled as drug seeking, but they're not." Undermedication is especially common among young adult patients making the transition from pediatric specialists to adult primary care physicians, according to Brunson. Adolescents fear that health care providers for adults will not believe them when they say their pain is severe.
Patients who experience three or more painful events or episodes of the acute chest syndrome per year are at the greatest risk for death before age 40, said Duane Bonds, MD, leader of the Sickle Cell Disease Scientific Research Group at the National Heart, Lung, and Blood Institute (NHLBI) in Bethesda, Maryland. For such severely affected patients, oral hydroxyurea has been shown to reduce the incidence of painful events, the acute chest syndrome, and the need for blood transfusions by 50%, according to a 1995 clinical alert issued by the NHLBI. Hydroxyurea is believed to work by stimulating the production of fetal hemoglobin, which can prevent the sickled cells from becoming rigid.
A hematologist familiar with sickle cell anemia should be involved in the initial administration of hydroxyurea, Hassell cautioned. "You need to push it to the maximum tolerated dose, and blood counts need to be taken every 2 weeks. So the patient really needs to be monitored first by a hematologist."
The chronic effects of sickle cell anemia can be just as damaging as the acute conditions. Chronic hemolytic anemia and vaso-occlusion that cause ischemic tissue injury and end-stage organ damage are hallmarks of the disease in adults.
"In many cases, it's a subclinical process," Hassell emphasized. "If you're not looking for the signs, you're not going to see them until the damage is already done. The lungs, liver, and kidneys are especially vulnerable."
"Even patients who never have acute chest syndrome are at high risk for lung injury," she continued. "We see pulmonary hypertension, cor pulmonale, and hepatic failure. All this can happen even if a person says he never had any problems with his lungs."
Evaluating for end-stage organ damage every 3 to 6 months, depending on the severity of the disease, is critical. By closely monitoring patients, a physician can identify early signs of organ damage and take steps to treat it before more serious complications develop.
New therapeutic approaches are under development for sickle cell anemia and its complications. In September 1997, the NHLBI announced that therapy using periodic erythrocyte transfusions to maintain a level of HbS below 30% reduced the rate of cerebral infarction by 90% in children with elevated transcranial Doppler velocities. Bonds emphasized that, although no randomized, controlled trial has been done to evaluate the efficacy of the therapy for adults, it is not known if discontinuation of transfusions begun during childhood is safe when the patient transfers from pediatric to adult care. On the other hand, although bone marrow transplantation has been successful on an experimental basis for some children with sickle cell anemia, it has not been successful in adults. There is a narrow window of opportunity in which transplantation may be advantageous, Hassell noted.
Some of the most direct treatment approaches involve developing drugs that prevent cells from sickling or that increase fetal hemoglobin production for the same end result. Use of chelation methods to diminish iron overload in patients who receive frequent transfusions is also being studied. The current chelation method requires nightly subcutaneous administration of deferoxamine, usually 5 nights a week over several months.
According to the NHLBI, an estimated 72 000 people in the United States, mostly African Americans, have sickle cell anemia. The disease occurs in about 1 in every 500 African-American births and 1 in every 1000 to 1400 Hispanic-American births. About 1 in 12 African Americans carries the sickle cell trait.
"A child born today with sickle cell disease can expect to live well into adulthood," Hassell stated. "You couldn't say that 20 years ago."
-Laurie Jones
A book of guidelines for physicians entitled The Management and Therapy of Sickle Cell Disease is available free of charge from the NHLBI at 301-435-0055 or on the World Wide Web (http://www.nhlbi.nih.gov).
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