The Herbst Triad: Report of Two Cases By P. Sacher and U.G. Stauffer
Zurich, Switzerland l We report two patients with hypoproteinemia and finger clubbing in whom the underlying gastroesophageal reflux was only detected after symptoms of esophageal stenosis became apparent. Ignorance of gastroesophageal reflux as a possible cause of these impressive symptoms led to complications and delayed surgery. @ 1990 by W. 8. Saunders Company. INDEX WORDS: Gastroesophageal enteropathy; finger clubbing.
I
reflux:
protein
losing
N 1976, HERBST
ET AL’ reported three children with hiatal hernia, protein-losing enteropathy, finger clubbing, severe reflux esophagitis, and iron deficiency anemia. Recently we observed two cases of gastroesophageal reflux (GER) in which hypoproteinemia and finger clubbing have been the leading symptoms. A thorough evaluation of these symptoms did not disclose any specific underlying disease. Only when symptoms of esophageal stenosis became apparent, was the presence of GER elucidated. In both cases ignorance of GER as a cause of hypoproteinemia and finger clubbing lead to a delayed surgical therapy. CASE
REPORTS
Case 1 A 4-year-old girl was admitted with recurrent vomiting, diffuse abdominal pains, increased tiredness, and impressive paleness. She had a story of rumination for the first year of life that ceased later on and physiotherapy was initiated because of leg-accentuated mild cerebral palsy. Her weight and height on admission were at the 25th percentile for age. Clubbing of the fingers was evident and a hypotrophy of the right leg was noted, reflexes were more accentuated on the right side than on the left side. The hemoglobine level was 5.3 g/100 mL, serum iron level was 267 pg/lOO mL, and feritin 4 pg/lOO mL. Total serum protein level was 4.1 g/100 mL, a cineesophagram showed a large esophagus with an irregular wall and a stenosis right above the diaphragm. The esophagoscopy showed confluent erosions and more distally circular superficial ulcers. The stenosis was dilated to a diameter of 11 mm. Gastric mucosa as well as duodenal mucosa did not show alterations. A blood transfusion was given and a medication with orai ferrous sulfate and Hz-blocking agents instituted. Recurrent endoscopy showed absent stenosis but unchanged signs of peptic esophagitis. A Nissen fundoplication was performed, the serum protein levels returned to normal values within 10 days. At follow-up 1 year later finger
From the Department of Surgery, Children’s University Hospital, Zurich, Switzerland. Address reprint requests to Dr P. Sacher, MD, Children’s University Hospital, Department of Surgery, Steinwiesstr 75, CH8032 Zurich, Switzerland. 0 I990 by W.B. Saunders Company. 0022-3468/90/2512-0011$03.00/0
i 238
clubbing had totally vanished and normal protein and serum iron levels have been measured
Case 2 A l%-year-old girl presented with refractory singultus and recurrent vomiting. The patient was pale. Head cocking and finger clubbing was noted. The hemoglobin level was 6.8 g/l00 mL and the hematocrit reading was 25%. The total serum protein level was 4.8 g/100 mL. The cineesophagram showed massive GER, no hiatal hernia, and ulcerations of the esophageal mucosa. Esophagoscopy showed circular and confluent lesions with superficial ulcers but no stenosis. A conservative treatment with oral ferrous sulphate therapy, Hz-blocking agents, as well as a prokinetic drug has been instituted. Vomiting vanished almost totally and head cocking was no longer observed, but anemia and low total serum protein concentrations did not improve. There was no weight gain during 4 months of conservative treatment. Recurrent esophagoscopy showed unchanged signs of peptic ulceration, and a Nissen fimdoplication was performed. At follow-up 6 months later the hemoglobin and total serum protein showed normal concentrations and finger clubbing was almost totally resolved.
DISCUSSION
GER is known to be a cause of disorders, eg, chronic pulmonary disorders2 and sudden infant death syndrome,3 and a consequence of underlying diseases, eg, esophageal atresia4 and mental retardation.’ GER may be found with associated lesions, eg, in patients with cow’s milk protein allergy,6 torticollis,’ cystic fibrosis,8 and congenital heart disease.’ In 1976, Herbst et al’ reported additionally on three cases of GER with protein-losing enteropathy, finger clubbing, and iron deficiency anemia. Furthermore, one of these patients presented with cocking of the head. This abnormal posturing has been attributed to an attempt to decrease the pain of esophagitis resulting from GER.” The relationship between iron deficiency anemia and esophagitis is well known, as all gastrointestinal diseases with a mucosal damage may provoke this form of anemia. Finger clubbing has been associated with intrathoracic lesions, mainly chronic pulmonary diseases and congenital heart disease with a left-to-right shunt, as well as extrathoracic lesions, eg, liver diseases, mainly biliary cirrhosis and celiac disease. This symptom may also be associated with carcinoma of the esophagus.” We found only one additional syndrome with finger clubbing in the literature of the last 50 years, the idiopathic hypertrophic osteoarthropathia (FriedrichErb-Arnold-Uehlinger syndrome). This syndrome consists of finger clubbing with dermal alterations and no
Joma! of Pediatric Surgery, Vol 25. No 12 (December), 1990: pp
1238-1239
THE HERBST TRIAD
1239
cause is found.” In contradiction to the young children discussed here, the onset of this syndrome is puberty, and finger clubbing would of course not disappear after a Nissen fundoplication as it did in these two cases. Interestingly enough, disappearing of finger clubbing has been observed after vagotomy for peptic ulcer disease (Folkman J: Personal communication, May 1987). Hypoproteinemia may be due to reduced supply of substrates for synthesis or reduced hepatic production as well as increased losses, eg, nephrosis, burns, ascites, and numerous gastrointestinal tract disorders. In the three original patients described by Herbst et al, the site of protein loss was not detected but intestinal loss was shown by elevated levels of intravenously administered chrome Sl-labeled albumine in a 5-day stool
sample. Primary malnutrition leading to hypoproteinemia has been ruled out by the same studies.’ Normal intestinal biopsies, lack of specific radiological abnormalities of the stomach and the whole intestine, as well as a rapid increase of plasma protein levels after surgical correction strongly suggest that reflux esophagitis and protein-losing enteropathy are closely related. We think that a functional stenosis or decreased clearance of the esophagus may provoke stasis followed by bacterial contamination of the gut that would lead to alteration of the intestinal mucosa with resulting protein loss and hypoproteinemia. As in Sandifer’s syndrome, the presence of GER may be obscured by more apparent and impressive symptoms of the complicating lesions.
REFERENCES 1. Herbst JJ, Johnson DG, Oliveros MA: Gastroesophageal reflux with protein-losing enteropathy and finger clubbing. Am J Dis Child 130:1256-1258, 1976 2. Bergquist WE, Rachelefsky GS, Kadden M, et al: Gastroesophageal reflux associated recurrent pneumonia and chronic asthma in children. Pediatrics 68:29-35, 1981 3. Leape LL, Holder TM, Franklin JD, et al: Respiratory arrest in infants secondary to gastroesophageal reflux. Pediatrics 60:925928, 1977 4. LeUendertse-Verloop K, Tibbod D, Hazebroek FWJ, et al: Postoperative morbidity in patients with esophageal atresia. Pediatr Surg Int 2:2-5, 1987 5. Schgrli AF, Rumlova E: Der gastro-iisophageale Reflux im Kindesalter. Helv Chir Acta 47:733-747, 1980 6. Forget P, Arends JW: Cow’s milk protein allergy and gastrooesophageal reflux. Eur J Pediatr 144:298-300,1985
7. Sutcliffe J: Torsion spasms and abnormal postures in children with hiatus hernia: Sandifer’s syndrome. Progr Pediatr Radio1 2:190-197,1969 8. Scott RB, O’Loughlin EV, Gall DG : Gastroesophageal reflux in patients with cystic fibrosis. J Pediatr 106:223-227, 1985 9. Weesner KM, Rosenthal A: Gastroesophageal reflux in association with congenital heart disease. Clin Pediatr 22:424-426. 1983 10. Ramenofsky ML, Buyse M, Goldberg MJ, et al: Gastroesophageal reflux and torticollis. J Bone Joint Surg 60: 1140- 114 1, 1978 11. Maurice-Williams RS: Hypertrophic osteoarthropathy associated with carcinoma of the oesophagus. Postgrad Med J 45:743-744, 1969 12. Uehlinger E: Hyperostosis generalisata mit Pachydermie (Idiopathische familiare generalisierte Osteophytose Friedrich-ErbArnold). Virchow Arch Path01 Anat 308:396-444, 1942
Zurich, Switzerland l We report two patients with hypoproteinemia and finger clubbing in whom the underlying gastroesophageal reflux was only detected after symptoms of esophageal stenosis became apparent. Ignorance of gastroesophageal reflux as a possible cause of these impressive symptoms led to complications and delayed surgery. @ 1990 by W. 8. Saunders Company. INDEX WORDS: Gastroesophageal enteropathy; finger clubbing.
I
reflux:
protein
losing
N 1976, HERBST
ET AL’ reported three children with hiatal hernia, protein-losing enteropathy, finger clubbing, severe reflux esophagitis, and iron deficiency anemia. Recently we observed two cases of gastroesophageal reflux (GER) in which hypoproteinemia and finger clubbing have been the leading symptoms. A thorough evaluation of these symptoms did not disclose any specific underlying disease. Only when symptoms of esophageal stenosis became apparent, was the presence of GER elucidated. In both cases ignorance of GER as a cause of hypoproteinemia and finger clubbing lead to a delayed surgical therapy. CASE
REPORTS
Case 1 A 4-year-old girl was admitted with recurrent vomiting, diffuse abdominal pains, increased tiredness, and impressive paleness. She had a story of rumination for the first year of life that ceased later on and physiotherapy was initiated because of leg-accentuated mild cerebral palsy. Her weight and height on admission were at the 25th percentile for age. Clubbing of the fingers was evident and a hypotrophy of the right leg was noted, reflexes were more accentuated on the right side than on the left side. The hemoglobine level was 5.3 g/100 mL, serum iron level was 267 pg/lOO mL, and feritin 4 pg/lOO mL. Total serum protein level was 4.1 g/100 mL, a cineesophagram showed a large esophagus with an irregular wall and a stenosis right above the diaphragm. The esophagoscopy showed confluent erosions and more distally circular superficial ulcers. The stenosis was dilated to a diameter of 11 mm. Gastric mucosa as well as duodenal mucosa did not show alterations. A blood transfusion was given and a medication with orai ferrous sulfate and Hz-blocking agents instituted. Recurrent endoscopy showed absent stenosis but unchanged signs of peptic esophagitis. A Nissen fundoplication was performed, the serum protein levels returned to normal values within 10 days. At follow-up 1 year later finger
From the Department of Surgery, Children’s University Hospital, Zurich, Switzerland. Address reprint requests to Dr P. Sacher, MD, Children’s University Hospital, Department of Surgery, Steinwiesstr 75, CH8032 Zurich, Switzerland. 0 I990 by W.B. Saunders Company. 0022-3468/90/2512-0011$03.00/0
i 238
clubbing had totally vanished and normal protein and serum iron levels have been measured
Case 2 A l%-year-old girl presented with refractory singultus and recurrent vomiting. The patient was pale. Head cocking and finger clubbing was noted. The hemoglobin level was 6.8 g/l00 mL and the hematocrit reading was 25%. The total serum protein level was 4.8 g/100 mL. The cineesophagram showed massive GER, no hiatal hernia, and ulcerations of the esophageal mucosa. Esophagoscopy showed circular and confluent lesions with superficial ulcers but no stenosis. A conservative treatment with oral ferrous sulphate therapy, Hz-blocking agents, as well as a prokinetic drug has been instituted. Vomiting vanished almost totally and head cocking was no longer observed, but anemia and low total serum protein concentrations did not improve. There was no weight gain during 4 months of conservative treatment. Recurrent esophagoscopy showed unchanged signs of peptic ulceration, and a Nissen fimdoplication was performed. At follow-up 6 months later the hemoglobin and total serum protein showed normal concentrations and finger clubbing was almost totally resolved.
DISCUSSION
GER is known to be a cause of disorders, eg, chronic pulmonary disorders2 and sudden infant death syndrome,3 and a consequence of underlying diseases, eg, esophageal atresia4 and mental retardation.’ GER may be found with associated lesions, eg, in patients with cow’s milk protein allergy,6 torticollis,’ cystic fibrosis,8 and congenital heart disease.’ In 1976, Herbst et al’ reported additionally on three cases of GER with protein-losing enteropathy, finger clubbing, and iron deficiency anemia. Furthermore, one of these patients presented with cocking of the head. This abnormal posturing has been attributed to an attempt to decrease the pain of esophagitis resulting from GER.” The relationship between iron deficiency anemia and esophagitis is well known, as all gastrointestinal diseases with a mucosal damage may provoke this form of anemia. Finger clubbing has been associated with intrathoracic lesions, mainly chronic pulmonary diseases and congenital heart disease with a left-to-right shunt, as well as extrathoracic lesions, eg, liver diseases, mainly biliary cirrhosis and celiac disease. This symptom may also be associated with carcinoma of the esophagus.” We found only one additional syndrome with finger clubbing in the literature of the last 50 years, the idiopathic hypertrophic osteoarthropathia (FriedrichErb-Arnold-Uehlinger syndrome). This syndrome consists of finger clubbing with dermal alterations and no
Joma! of Pediatric Surgery, Vol 25. No 12 (December), 1990: pp
1238-1239
THE HERBST TRIAD
1239
cause is found.” In contradiction to the young children discussed here, the onset of this syndrome is puberty, and finger clubbing would of course not disappear after a Nissen fundoplication as it did in these two cases. Interestingly enough, disappearing of finger clubbing has been observed after vagotomy for peptic ulcer disease (Folkman J: Personal communication, May 1987). Hypoproteinemia may be due to reduced supply of substrates for synthesis or reduced hepatic production as well as increased losses, eg, nephrosis, burns, ascites, and numerous gastrointestinal tract disorders. In the three original patients described by Herbst et al, the site of protein loss was not detected but intestinal loss was shown by elevated levels of intravenously administered chrome Sl-labeled albumine in a 5-day stool
sample. Primary malnutrition leading to hypoproteinemia has been ruled out by the same studies.’ Normal intestinal biopsies, lack of specific radiological abnormalities of the stomach and the whole intestine, as well as a rapid increase of plasma protein levels after surgical correction strongly suggest that reflux esophagitis and protein-losing enteropathy are closely related. We think that a functional stenosis or decreased clearance of the esophagus may provoke stasis followed by bacterial contamination of the gut that would lead to alteration of the intestinal mucosa with resulting protein loss and hypoproteinemia. As in Sandifer’s syndrome, the presence of GER may be obscured by more apparent and impressive symptoms of the complicating lesions.
REFERENCES 1. Herbst JJ, Johnson DG, Oliveros MA: Gastroesophageal reflux with protein-losing enteropathy and finger clubbing. Am J Dis Child 130:1256-1258, 1976 2. Bergquist WE, Rachelefsky GS, Kadden M, et al: Gastroesophageal reflux associated recurrent pneumonia and chronic asthma in children. Pediatrics 68:29-35, 1981 3. Leape LL, Holder TM, Franklin JD, et al: Respiratory arrest in infants secondary to gastroesophageal reflux. Pediatrics 60:925928, 1977 4. LeUendertse-Verloop K, Tibbod D, Hazebroek FWJ, et al: Postoperative morbidity in patients with esophageal atresia. Pediatr Surg Int 2:2-5, 1987 5. Schgrli AF, Rumlova E: Der gastro-iisophageale Reflux im Kindesalter. Helv Chir Acta 47:733-747, 1980 6. Forget P, Arends JW: Cow’s milk protein allergy and gastrooesophageal reflux. Eur J Pediatr 144:298-300,1985
7. Sutcliffe J: Torsion spasms and abnormal postures in children with hiatus hernia: Sandifer’s syndrome. Progr Pediatr Radio1 2:190-197,1969 8. Scott RB, O’Loughlin EV, Gall DG : Gastroesophageal reflux in patients with cystic fibrosis. J Pediatr 106:223-227, 1985 9. Weesner KM, Rosenthal A: Gastroesophageal reflux in association with congenital heart disease. Clin Pediatr 22:424-426. 1983 10. Ramenofsky ML, Buyse M, Goldberg MJ, et al: Gastroesophageal reflux and torticollis. J Bone Joint Surg 60: 1140- 114 1, 1978 11. Maurice-Williams RS: Hypertrophic osteoarthropathy associated with carcinoma of the oesophagus. Postgrad Med J 45:743-744, 1969 12. Uehlinger E: Hyperostosis generalisata mit Pachydermie (Idiopathische familiare generalisierte Osteophytose Friedrich-ErbArnold). Virchow Arch Path01 Anat 308:396-444, 1942
