September 1996
In the late 1980s, a physician prescribed penicillin for a man who worked for Yale University to treat a presumed strep throat. A rash developed, and an internist diagnosed it as an allergic reaction to penicillin. The internist admitted the man to an infirmary on campus.
Larry Kleinman, MD, a pediatrician on call at the infirmary, received a telephone call from a nurse who was concerned that the rash did not respond to diphenhydramine. Kleinman gave the patient a complete exam.
"He had this rip-roaring conjunctivitis," Kleinman recalled. The man also had pharyngitis and a maculopapular rash "that sort of became more confluent as it went down his body." Kleinman, who is 37 years old, suspected measles but, "In my training," he said, "I was told that if you ever see a rash and you think it's measles, it's not."
He looked again into the patient's mouth and saw little white spots inside his cheeks. Measles it was. "I couldn't quite believe it," Kleinman said.
Widespread use of vaccines has reduced the prevalence of once-common childhood illnesses, such as measles, to the point where physicians sometimes fail to consider the illnesses in the differential diagnosis.
Physicians also have misdiagnosed measles as Kawasaki disease, a rare illness that has certain clinical features in common with measles, including rash and fever.
Such a misdiagnosis occurred recently at Duke University, in Durham, N.C. As related by Samuel L. Katz, MD, Wilburt C. Davison Professor, department of pediatrics at the school, a child from Greece visited two clinics on successive days. A young physician at each clinic initially diagnosed a drug reaction and later diagnosed Kawasaki disease. Neither physician had ever seen a case of measles.
It wasn't until the third day that the child was brought to a general pediatrics clinic, where the attending pediatrician that day happened to be a woman 60 years old — old enough to remember what a case of measles looks like. "She recognized it instantly," Katz said.
According to Kleinman, missing a case of an uncommon illness may be understandable. "It's a rational part of clinical decision-making to consider what the probability is [for an illness to occur] before you start examining the patient," said Kleinman, who is a clinical assistant professor of pediatrics at the University of California, Los Angeles, and chief medical officer for Synergy Health Care, Wellesley Hills, Mass., a company that evaluates and measures health care quality.
Physicians who received their medical training in the United States in the past two or three decades may never have seen a case of measles, mumps, rubella, polio or diphtheria. In addition, the likelihood of physicians seeing cases of those illnesses may be diminishing because physicians are receiving more of their clinical training care in outpatient settings instead of hospitals, Kleinman said.
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Widespread use of Haemophilus influenzae type b (Hib) vaccine beginning in 1990 has led to a rapid decrease in Hib disease and one of its most frightening manifestations, acute epiglottitis. Unfamiliar with epiglottitis, physicians may misdiagnose it as croup and aggravate the condition, potentially leading to suffocation, Kleinman said. Hib cellulitis also has become relatively rare.
If the varicella vaccine that became commercially available in 1995 comes into widespread use, chickenpox could join the list of obscure childhood illnesses.
A physician's inability to spot contagious illnesses can have serious consequences. In California, Katz said, a rash and fever developed in a child who had undergone a bone marrow transplant. Physicians thought the rash was a sign of graft vs. host reaction. Physicians admitted the child to the bone marrow transplant unit and two weeks later an outbreak of measles occurred among all the children in the unit, Katz said.
Katz called the measles virus "the most clever of all the viruses. If there are only two susceptible children in a high school of 1,000, it'll find those two."
Measles, polio, tuberculosis and other communicable diseases continue to vex pediatric populations around the world. Foreigners with these illnesses could enter the United States and catch unsuspecting pediatricians by surprise. "Polio is probably the worst of all," Katz said, "because we haven't had any outbreaks of wild polio in this country for nearly 40 years." Some cases of vaccine-related polio have taken two, three and four years to be diagnosed, he said.
Epidemic diphtheria continues to occur in parts of the world, including the Independent States of the former Soviet Union. In patients who present with diphtheria's characteristic sore throat and pharyngeal membrane, physicians should ask about travel outside of the United States, Katz warned.
Most physicians have never seen a case of diphtheria. No more than five cases of diphtheria have been reported annually in the United States since 1980, according to the Centers for Disease Control and Prevention. No culture-confirmed cases involving transmission within the United States have been reported since 1988.
Vaccine-preventable diseases are not the only diseases to decrease in prevalence so much that physicians sometimes fail to consider them in their differential diagnoses. Tuberculosis is among those diseases. The prevalence of tuberculosis has declined precipitously since the early 1900s, thanks in large part to improvements in living conditions and nutrition, and the debut of anti-TB drugs. Consequently, medical schools provide little instruction in TB, and pediatricians may not think to ask whether patients with respiratory complaints have had contact with somebody who has or might have TB, according to pediatric TB specialist Jeffrey R. Starke, MD, associate professor of pediatrics at Baylor College of Medicine, Houston.
"TB is not distinct clinically," Starke said. "If a child comes in with pneumonia, the key piece of information that it's TB is going to be that there is some adult in the child's environment who has [TB] risk factors or actually has tuberculosis."
Some childhood illnesses have become so rare in the United States that medical educators frequently have to use photographs to show medical students the clinical features of those illnesses. The appearance of a real-life case of measles can be an important teaching event, as it is at Children's Hospital in Denver. "When we see a case of measles, we usually take that opportunity to have a lot of people come to see the case," said Mary P. Glodé, MD, director of the hospital's pediatric residency program.
Through their approach to the differential diagnosis, physicians can compensate for never having seen a case of a particular illness first-hand, according to Glodé, who also is professor of pediatrics at the University of Colorado, Denver. Physicians should consider as suspects even rare illnesses that could be explained by patients' signs and symptoms and ask the right questions when obtaining a patient history, she said. Information about recent foreign travel, vaccination status and illnesses in household contacts can be important tipoffs.
So that residents can get a first-hand look at unusual diseases, Glodé encourages them to spend time in foreign countries where those diseases are more prevalent than they are in the United States. Many faculty members have professional relationships with physicians in other countries and could arrange for residents to work under the tutelage of foreign physicians, she said.
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