What's causing a 7-month-old boy to be hospitalized for failure to thrive, recurrent wheezing, and bilateral infiltrates refractory to antibiotics?
Rochelle Hirschhorn, MD, professor of medicine, cell biology, and pediatrics at NYU Medical Center, New York, N.Y., provided invaluable assistance in determinations of adenosine deaminase (ADA) enzyme activity in specimens collected from the patient.
DR. GOLDBLATT is an attending physician in internal medicine and pediatrics at the Northern Navajo Medical Center, Shiprock, N.M.
DR. SIBERRY is an assistant professor of pediatrics in the divisions of general pediatric and adolescent medicine and pediatric infectious diseases at Johns Hopkins Hospital, Baltimore.
The authors and section editor have nothing to disclose in regard to affiliations with, or financial interests in, any organization that may have an interest in any part of this article.
On a Friday evening, in a tertiary care hospital, a pager that's been hotter than a Saharan mid-afternoon goes off, again. Seems like it's the hundredth call today. And, once again, it's all yours! You head to the nearest telephone. On the other end is a physician you know from a community hospital some 150 miles from your facility. She's requesting transfer of a 7-month-old boy who has been hospitalized for the past six weeks for failure to thrive, recurrent wheezing, and bilateral infiltrates refractory to antibiotics. You happily accept the patient and quickly relay the information you have to the on-call resident.
Despite the busy evening, there's time for your creative juices to begin to swirl as you await the transfer. A differential gathers. Respiration, you consider, can consume as much as two thirds of metabolic demand, resulting in failure to thrive. Will the baby's lungs be the key to a diagnosis? But what about the wheezing? As an "old doc" once told you, there are only a few general causes of wheezing: reactive airway disease (asthma, allergies, mastocytosis), infection (respiratory syncytial virus, human metapneumovirus), a foreign body, a structural defect (slings, rings, bronchiectasis), a genetic disorder (including cystic fibrosis), and heart failure.
Back to the business of fact-gathering
The patient arrives at your facility and the team begins its evaluation to gather a detailed understanding of his condition. His mother has accompanied him; she reports that he is the product of a full-term pregnancy that was complicated only by a case of genital warts. Delivery was vaginal. Birth weight was 3.3 kg.
The boy was hospitalized at 1 month of age for fever. A workup for sepsis was negative. He was seen by his pediatrician at 3 months of age for bronchiolitis. She reports that he had intermittent episodes of wheezing over following months.
During his sixth month, he was seen in the emergency department of the referring hospital three times for cough, low-grade fever, rhinorrhea, wheezing, thrush, and poor oral intake. The first two times, he was sent home on an antibiotic and an inhaled bronchodilator. At the third visit, he was admitted; over the course of one or two days before that hospitalization, the patient had a persistent fever (to 102° F), poor oral intake, increasing fatigue, and difficulty breathing-all despite nebulizer treatments, antipyretics, and multiple attempts to feed him. The chart from that admission notes desaturations in the 80% to 89% range while breathing room air; fever; bilateral infiltrates on a chest radiograph; and thrush.
The course of illness at that hospital was marked by a range of therapeutics: three weeks of parenteral ceftriaxone; 10 days of amoxicillin-clavulanate; two courses of azithromycin; courses of fluconazole and econazole nitrate; a short course of parenteral nutrition; a scheduled multivitamin; and scheduled nebulized budesonide (Pulmicort), albuterol, and ipratropium bromide (Atrovent).
Despite your knowledgeable colleague's treatments and extensive work-up, the baby continues to have thrush, wheezing, and respiratory difficulties and hasn't gained weight. You review the initial history that was taken upon presentation at the referring hospital when the baby was 5 months old. The notes describe a male full-term, African-American infant with a maternal complaint that the baby has had a life-long history of "cold"-like symptoms. As already reported by the mother and documented in the hospital record, the patient had been seen in the ED twice in the month before the 5-month-old admission, for intermittent "rattling cough," wheezing, low-grade fever (to 101°F) and poor oral intake without nausea, vomiting, or diarrhea. At each ED visit, he was sent home with a prescription for a course of oral antibiotic, and his mother was encouraged to treat him with the home nebulizer.
Five days before the baby was admitted at 5 months of age, he was seen by his pediatrician, who prescribed a course of ocular antibiotic drops for bilateral conjunctivitis, which, his mother tells you, resolved with treatment.
You obtain more history. The patient lives with his mother, father, and an older sister; there are no pets. Immunizations are up to date. He does not attend day care. Domestic water supply is from a municipal source. He has reached the developmental milestones of only a 4-month-old.