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Cystic Fibrosis Discussants IVAN HARWOOD, MD; FERNANDO ROSAS, MD; DAVID K

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Cystic Fibrosis Discussants IVAN HARWOOD, MD; FERNANDO ROSAS, MD; DAVID K 62 im A Cystic Fibrosis Discussants IVAN HARWOOD, MD; FERNANDO ROSAS, MD; DAVID K. EDWARDS, MD; JOHN KELSO, MD; and WILLIAM L. NYHAN, MD, PhD I VAN HARWOOD, MD: * A starting point for the discussion of partial carbon dioxide pressure of 52 torr, and it was decided important topics in cystic fibrosis and its management in to insert an endotracheal tube for ventilation and to begin infants is provided by an informative case of a patient, which treatment with ribavirin. Klebsiella and Escherichia coli will be presented by Dr Rosas. From there we will discuss the were found on tracheal culture. rapidly developing advances in diagnosis and therapy. His course was stormy because of recurrent episodes of increased airway resistance and increased difficulty in ven- Case Presentation tilation, but his condition slowly improved, and the endo- Case 1 tracheal tube was removed about a week later. His weight was FERNANDO RoSAS, MD:t The mother was seen because of 2.3 kg. At 2 months of age, sufficient sweat could be collected polyhydramnios and other factors that led to the decision to for the first time for a sweat test, which was positive; the deliver the infant at 33 weeks by cesarean section. She was 30 chloride concentration was 95.7 mEq per liter and the spec- years old and the father 39. The first offive siblings died at the imen weighed 130 mg. age of 15 months of what was called intestinal infection, the Six weeks after admission, he was discharged weighing fourth was a fetal death at 20 weeks of gestation, and the fifth 2.7 kg and tolerating Pregestimil (Mead Johnson) formula died at 3 months of age of pneumonia. This pregnancy had supplemented with glucose polymers (Polycose [Ross]) to been complicated by a culture positive for herpesvirus three provide 238 calories per kg per day. He was readmitted four months before delivery. A sonogram one week before de- days later with pneumonia, respiratory distress, and diarrhea livery showed massive hydramnios. A screening test for toxo- and was treated with a regimen oftobramycin and piperacillin plasmosis, rubella, cytomegalovirus (CMV), and herpes (the sodium. "TORCH" screen) indicated a greatly elevated level of type Response was rapid, and he was discharged 2½/2 weeks II herpesvirus immunoglobulin and a mildly elevated type I, later. At 4 months of age his weight was 3.65 kg. At 6 months as well as substantially increased CMV titers. The culture for of age, he was readmitted because of increased cough, CMV was negative. wheezing, and the production of sputum. A sputum culture At birth the infant was found to have a very distended showed Staphylococcus aureus and E coli. He again re- abdomen. X-ray films showed diffuse calcifications essen- sponded to treatment with tobramycin and piperacillin and tially diagnostic of meconium peritonitis. He was taken to was discharged after three weeks, receiving cephradine and surgery for an exploratory laparotomy and lysis of adhesions. sulfamethoxazole-trimethoprim (Septra). There was diffuse meconium staining, but no perforation was His most recent outpatient visit was at 7 months of age. found. Postoperatively he did well and was discharged at 18 He was generally stable and weighed 5 kg, but he had a days of age. His weight at that time was 2.14 kg. chronic cough productive ofclear, thick sputum. During a month at home he had more or less continuous diarrhea. Three changes offormula from breast milk to Isomil DR HARWOOD: Thank you, Dr Rosas. Dr Edwards will de- Soy Protein Formula With Iron (Ross Laboratories) to Sim- scribe the x-ray findings. ilac With Iron Infant Formula (Ross) to ProSobee (Mead Johnson Nutritional Division) were without major effect. Radiologic Findings. Two weeks after discharge his weight was 2.19 kg. One DAVID K. EDWARDS, MD:* Prenatal sonography done six month after discharge he was seen in the emergency depart- days before delivery showed moderate hydramnios (Figure ment where he was described as flaccid and appearing ill. He 1). There was also evidence of fetal ascites and thickening of still had diarrhea and his weight was 2.44 kg. There were the abdominal soft tissues, findings that are suggestive of expiratory wheezes, occasional rales, and slight stridor. He nonimmune hydrops but in this case are probably a conse- was admitted and treated with a regimen of ampicillin and quence of fetal peritonitis. Ultrasound is generally relatively gentamicin sulfate. His respiratory status deteriorated despite insensitive to calcifications; in any event, no intra-abdominal the use of antibiotics and the addition of aminophylline. He calcifications were noted either at the time of sonogram or was found to have a partial oxygen pressure of 31 torr and a retrospectively. *Professor of Pediatrics and Chief of Pediatric Pulmonary Division, University of Following delivery, plain radiography showed scattered California, San Diego (UCSD). tFellow in Pediatric Pulmonary Disease. UCSD. *Associate Professor of Radiology and Pediatrics, UCSD. (Harwood I, Rosas F, Edwards DK, et al: Cystic fibrosis [Specialty Conference]. West J Med 1988 Jan; 148:62-69) From the Departments of Pediatrics and Radiology, University of California, San Diego, School of Medicine, and University of California Medical Center, San Diego. Reprint requests to Ivan Harwood, MD, Division of Pediatric Pulmonary Disease, University of California, San Diego, School of Medicine, 4130 Front St, San Diego, CA 92103. o o o THlTHE WESTERNETR JOURNALORA OF MEDICINE JANUARY 1988 148 1 63 contrast material failed to show leakage into the peritoneum. ABBREVIATIONS USED IN TEXT It was professionally consoling that the surgeons similarly CF = cystic fibrosis failed to find a leak. The leak had closed CMV = cytomegalovirus evidently spontane- PON = paraoxonase ously. RFLP = restriction fragment length polymorphism Chest radiographs during the child's subsequent period of UCSD University of California, San Diego severe respiratory illness revealed shifting patches of atelec- tasis, areas suggesting pneumonia, and miscellaneous com- flecks of intraperitoneal calcification, findings virtually pa- plications related to endotracheal intubation. Following re- thognomonic of meconium peritonitis. It is our practice in covery, his chest films have become fairly typical of children such cases to seek the approximate site of perforation with an of this age with cystic fibrosis, showing mild hyperinflation upper gastrointestinal tract examination using a nonionic wa- and peribronchial thickening (Figure 3). ter-soluble contrast material (Figure 2). In the infants in whom the perforation is still patent at delivery, this technique Discussion often gives a surgeon a clue as to where the perforation is DR HARWOOD: Thank you, Dr Edwards. This patient had situated and at the same time excludes atresias, severe ste- meconium peritonitis, a prenatal consequence of cystic fi- noses, malrotation, and other abnormalities that may be asso- brosis. In about halfthe cases, the meconium peritonitis is due ciated with meconium peritonitis. to the meconium ileus of cystic fibrosis and in about half it is The scout film showed pneumoperitoneum, implying due to all the other causes of intestinal obstruction in a fetus, postnatal patency ofthe perforation, but the examination with including malrotation and valvular stenosis and atresia. Virtu- "ti .Hllm ally all patients who have meconium peritonitis with meco- 'k AVI WV VW Nu nium ileus have cystic fibrosis. Therefore, a diagnosis of meconium ileus is a presumptive diagnosis ofcystic fibrosis. Some 10% to 12% ofpatients with cystic fibrosis are born with meconium ileus. On examination during a surgical pro- ._ .:;- 0.s A. I4 ._~~~~~1 Figure 1.-A prenatal transverse sonogram of the fetal abdomen Figure 2.-The photo shows the final film from an upper gastrointes- shows abdominal wall soft-tissue thickening (solid arrows) and as- tinal series with nonionic water-soluble contrast material; no intraperi- cites (white arrow). toneal spill of contrast material was observed. The arrows indicate calcifications of meconium peritonitis. 6464 CYSTIC~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~CYSTIC FIBROSIS------FIBROSIS cedure, the typical appearance ofmeconium ileus is ofdilated tures were negative, but the hematocrit was 21.6%. The proximal loops and a dark, small, congested, and obstructed weight was 3.7 kg. The red cell indices were normal, the distal segment. leukocyte count was 4.5 x 103 per dl, and the platelets A few infants with meconium ileus experience sponta- 41 1,000 per Al. There was no evidence of hemolysis or gas- neous relief of the obstruction. Most require other measures. trointestinal bleeding. The baby was transfused and the he- In less than half, the obstruction can be relieved by an enema matocrit rose to 33 %. with N-acetylcysteine or diatrizoate meglumine (Gastro- Three weeks later the hematocrit was down to 25 % and grafin). Most require surgical relief of the intestinal obstruc- the baby had lost 0.45 kg. He weighed 3.62 kg at 3 months of tion. In this patient, no site of obstruction or continuing leak age. In addition, on physical examination there was pretibial was found at exploration. This case shows that there may be edema and the liver was palpable 2 cm below the costal other complications associated with meconium ileus prena- margin. Following admission the alkaline phosphatase level tally or postnatally, such as perforation and peritonitis. The was elevated, as was the -y-glutamyl transferase value. The distinctive meconium in meconium ileus is dehydrated, tarry, serum aspartate aminotransferase (glutamic-oxaloacetic and very sticky, and it has a high protein content. It is easy to transaminase) and serum alanine aminotransferase (glutam- understand why this material causes obstruction. ic-pyruvic transaminase) levels were normal. The serum al- Infants presenting with severe manifestations of cystic bumin value was 2.0 and the total protein 3.4 grams per dl. fibrosis so early in life have a high mortality rate, as much as The baby's sweat chloride concentration was 105 mEq per 30% within two months of birth.
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