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Chronic varioliform gastritis in childhood
Volume 115 Number 3
subdural fluid collection, was not performed in our patient. We chose the less invasive approach of performing the lumbar punctures at a higher vertebral interspace and confirmed that the C S F protein concentration was normal. The brief time between protein determinations argues against serial measurement of the same (subarachnoid) fluid and supports the presence of a collection of fluid in the subdural space. Our experience suggests that identification of an unexpected elevation in the C S F protein content of a child undergoing multiple lumbar punctures may be explained by the measurement of C S F in the subdural space. Consideration of this possibility may spare the child an overly aggressive evaluation (although myelography might be necessary to confirm the diagnosis should the subdural collection span multiple interspaces). Furthermore, injection of chemotherapeutic agents into the subdural space of
Clinical and laboratory observations
44 1
children with malignancies does not achieve the desired goal of prophylaxis or treatment of subarachnoid disease, which indicates the need for prompt attention to abnormal C S F protein values in these patients. We thank Dr. Jerome B. Posner for his helpful suggestions in the management of our patient and for his review of the manuscript. REFERENCES
1. Fishman RA. Cerebrospinal fluid in diseases of the nervous system. Philadelphia: WB Saunders, 1980. 2. Dohrman PJ, Elrick WL, Siu KH. Intracranial subdural hematoma after lumbar myelography. Neurosurgery 1983; 12:694-6. 3. Ruff RL, Dougherty JH. Complications of lumbar puncture followed by anti-coagulation. Stroke 1981;l 2:879-81. 4. Lasater GM. Primary intracellular hypotension: the low spinal fluid pressure syndrome. Headache 1970;10:63-6.
Chronic varioliform gastritis in childhood R i c h a r d Couper, MB, ChB, FRACP, B e r n a r d Laski, MD, FRCPC, B r e n d a n D r u m m , MB, BCh, FRCPC, D a v i d Stringer, BSc, MBBS, FRCR, FRCPC, a n d P e t e r Durie, MD, FRCPC From the Divisions of Gastroenterology and General Pediatrics, Department of Pediatrics, and the Department of Radiology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
Chronic varioliform gastritis is an uncommon, distinctive, inflammatory gastric mucosal disease of uncertain cause predominantly affecting middle-aged and elderly men? ,2 Many synonyms have been applied, including chronic erosive gastritis, complete erosions, dellengastritis, octopus sucker gastritis, and gastric aphthous ulcers2 ,2 Most patients have epigastric pain, nausea, and anorexia. The radiographic and endoscopic findings are characteristic. A double-contrast upper gastrointestinal tract series reveals discrete radiolucent haloes with central flecks of barium, and gastroscopy shows small, heaped-up, volcano-like mounds, pocked with a central crater, usually situated on hypertrophied rugae. In 1986 Caporali and Lucian@ reported a 10-year-old girl whose symptoms were similar to those in adult Submitted for publication Nov. 30, 1988; accepted Mar. 6, 1989. Reprint requests: Bernard Laski, MD, Division of General Pediatrics, The Hospital for Sick Children, University of Toronto, 555 University Ave., Toronto, Ontario M5G 1X8, Canada. 9/22/12292
patients. We report two further cases of CVG in children, one of whom had iron deficiency anemia, an uncommon presentation in adults. CASE REPORTS Patient 1. A 14-year-old girl without symptoms was found to have a hemoglobin level of 8 gm/day. Menses were regular and not excessive. Dietary and medication history were unremarkable. She had occasional hay fever and seasonalallergic rhinitis. Her
CVG DSCG
Chronic varioliform gastritis Disodium cromoglycate
[
grandmother required intramuscular injections of vitamin B~2 for pernicious anemia. A cousin had Crohn disease. Apart fi'om slight pallor, findings of the physical examination of the patient were normal. Blood smear analysis showed a microcytic, hypochromic anemia with the following values: hemoglobin 88 gm/L; mean corpuscular volume 57 fL; mean corpuscular hemoglobin 16.8 pg with a normal leukocyte count, no eosinophilia, reticulocyte count 52.3 X 109/L (normal 10 to 100.0 X 109/L), and erythrocyte
442
Clinical and laboratory observations
The Journal of Pediatrics September 1989 pylobacter pylori-like organisms were not identified or grown
Fig. t. Double-contrast, high-density barium radiograph shows multiple elevated nodules (straight arrows) throughout body of stomach, some of which have umbilicated central indentation in which barium collected (curved arrow). sedimentation rate 6 m m / h r (normal 1 to 10 mm/hr). The patient had reduced serum levels of iron (3 umol/L, normal 9 to 27 #mol/L) and ferritin (<2/zg/L, normal 16 to 300 #g/L) and an elevated total iron binding capacity (88 ~tmol/L, normal 45 to 72 umol/L). Serum total protein and albumin concentrations were normal. No occult blood was found in stool samples. Air-contrast barium enema demonstrated a normal colon and terminal ileum. A single-contrast upper gastrointestinal series was reported as normal. The patient received ferrous gluconate for 3 months, and her iron deficiency anemia resolved. Periodic cramping epigastric pain was the patient's only complaint during the next 3 years. Iron deficiency anemia recurred 3 years after presentation. A double-contrast upper gastrointestinal tract series of radiographs showed multiple, well-defined, circular filling defects, 5 to 9 mm in diameter, some with an umbilicated central crater, involving both the gastric body and the antrum (Fig. 1). Review of a postevacuation film from the prior barium study showed identical lesions with a similar distribution. At gastroscopy, numerous, small, friable, heaped, volcano-like lesions with an umbilicated central crater were seen in the body and the antrum. The lesions were friable but not ulcerated. The duodenum was normal. Histologic study of the antral lesion (Fig. 2) showed focal epithelial denudation and goblet cell depletion. Throughout the lamina propria there was a chronic inflammatory infiltrate extending focally into the muscularis mucosa; plasma cells and eosinophils were abundant. The body of the stomach showed mild infiltration of the lamina propria with inflammatory cells. Cam-
from biopsy cultures. Ferrous gluconate therapy was recommenced. The patient was reassessed 4 months later because of persistent abdominal cramps. Gastroscopy and an air-contrast barium study showed persistence of the lesions. Gastric histologic findings were unchanged. Immunofluorescent staining of an antral section revealed a marked increase in plasma cells, which stain positive for surface immunoglobulins, particularly IgA and IgE. The serum IgG concentration was 10.3 gm/L (normal 6 to 15 gm/L), the IgA level was 1.87 gm/L (normal 0.35 to 2.4 gm/L), and the IgE level was 56 I U / L (normal <41 IU/L). Serum C3 and C4 levels were normal, as was a fasting serum gastrin level. Antiparietal cell antibodies were absent. Two months of treatment with disodium cromoglycate, 200 mg orally twice a day, did not produce endoscopic or histologic improvement. Apart from periodic epigastric pain, the patient is symptom free and has maintained a normal hemoglobin level without oral iron therapy for the last year. Patient 2. A 10-year-old girl was examined after 7 days of nonbilious vomiting, which occurred two to four times a day and was associated with cramping lower abdominal pain. One day after the onset of the symptoms she underwent dental surgery, during which she received atropine, nitrous oxide, and local anesthetic. Urticaria developed and was treated with diphenhydramine but persisted for 3 days. Apart from periodic epigastric pain and belching for the prior 2 years, the history and physical examination were unremarkable. Anorexia, weight loss, abdominal pain, and vomiting persisted. Total parenteral nutrition was given for 3 weeks. A course of cyproheptaine and magnesium hydroxide had no effect. Singlecontrast barium radiographs showed coarse nodularity of the antrum and pylorus and markedly enlarged gastric and duodenal mucosal folds. Double-contrast barium examination revealed multiple, circular, well-defined, umbilicated filling defects, 8 mm in diameter, with central punctate flecks of barium. Gastroscopy showed the mucosa of the gastric body, antrum, and duodenum to be nodular and erythematous, with several heaped-up umbilicated lesions. Histologic study of the gastric body revealed a dense inflammatory infiltrate consisting of plasma cells, lymphocytes, neutrophils, and eosinophils. The antral biopsy findings were similar but included a sparse inflammatory cell infiltrate. Immunostaining revealed normal amounts of gastrin, somatostatin, and serotonin. Immunofluorescent staining showed an occasional plasma cell positive for IgG, IgM, and IgA and only one or two cells positive for IgE in each section viewed under high power. The hemoglobin level was 145 gm/L with a normal leukocyte count and no peripheral eosinophilia. The erythrocyte sedimentation rate was 6 mm/hr. Serum IgM, IgG, and IgA levels were normal, but the serum IgE level was mildly elevated (190 IU/L). A fasting serum gastrin level was normal. The serum albumin concentration fell to 30 gm/L by day 19. No occult blood was found in the stools, and electron microscopy did not reveal viral particles. With parenteral nutrition the patient's symptoms abated, and she resumed a normal diet. For the last 4 years she has been well
Volume 115 Number 3
Clinical and laboratory observations
443
Fig. 2. Focal epithelial denudation and goblet cell depletion are visible in section of antral mucosa. Chronic inflammatory cell infiltrate consisting of plasma cells and eosinophils is seen throughout lamina propria and extends into mascularis mucosa. (Hematoxylin and eosin stain, 125x.)
except for occasional abdominal pain. A repeat double-contrast upper gastrointestinal tract series 2V2 years after her initial examination showed persistence of the gastric lesions. DISCUSSION In adults, CVG is characterized by chronic epigastric pain, nausea, and anorexia) ,2 Less common complaints include protein-losing enteropathy, gastrointestinal bleeding, anemia secondary to occult bleeding, and extreme weight loss. Lambert et al. 1 noted that, of 90 patients, two had protein-losing cnteropathy, three had gastrointestinal tract hemorrhage, and three had anemia because of occult bleeding. One child with CVG has been reported; her symptoms conformed to the typical adult presentation. 4 Our two patients atypically had iron deficiency anemia and vomiting, respectively. The radiologic features of CVG persisted with minimal symptoms for at least 4 years in one patient and 272 years in the other. The differential diagnosis includes gastroduodenal Crohn disease, 3 eosinopbilic gastroenteritis: M6n6trier disease,6 herpesvirus infections (including cytomegalovirus), 3"6"7 candidiasis,3 and in adults, lymphoma or disseminated carcinoma. Gastroscopy identifies distinctive volcano-like mounds. Air-contrast barium radiographs show radiolucent filling defects 3 to 11 mm in diameter, with a central punctate fleck reflecting central superficial ulceration. These lesions are usually situated on hypertrophied antral rugae, although they can extend into the first part of the duodenum and the gastric body. Histologic studies
show antral gastric pit hyperplasia, mild edema, and infiltration of the lamina propria with chronic inflammatory cells, particularly polymorphonuclear leukocytes and plasma cells. Our patients had similar findings, although M~n6trier disease was considered in the second patient because of rugal hypertrophy. Eosinophilic gastroenteritis may be difficult to exclude. In the series by Lambert et al. l patients with CVG had both elevated serum IgE levels (40%) and peripheral eosinophilia (25%), as may be seen with eosinophilic gastroenteritis: Our patients had elevated serum IgE levels and increased mucosal infiltration with plasma cells staining for IgE, but no peripheral eosinophilia. Patient 1 had a history of allergy, and urticaria developed in patient 2. Eosinophilic gastroenteritis and other diagnoses are unlikely because of the distinctive lesions seen with radiology and gastroscopy. The etiology of CVG is an enigma. Nonsteroidal antiinflammatory drugs have been associated with the development of symptoms in a small number of patients, 1 but their widespread use in older patients makes this association difficult to interpret. Cytomegalovirus has been detected occasionally in both nodular gastritis and M+n&rier dise a s e : : Whether this agent is implicated in CVG is not resolved. The most popular hypothesis invokes an immunologic mechanism, as suggested by raised serum IgE levels, peripheral eosinophilia, and infiltration of plasma cells bearing IgE surface markers: Radioallergic immunosorbent testing of serum has not demonstrated any association with dietary antigens) DSCG (a mast cell stabilizer) has
444
Clinical and laboratory observations
been used successfully to treat this disorder. In a doubleblind, placebo-controlled trial involving a very small patient cohort, D S C G improved symptoms and endoscopic findings and reduced the number of plasma cells staining for surface IgE in histologic sections. 8 Paganelli et al. 9 have demonstrated that DSCG may reduce antigen entry and consequent immune complex formation in atopic individuals. However, the finding that gut-associated mast cells release histamine in the presence of D S C G leaves the question of antigen entry and the exact effect of D S C G unresolved. 1~ Caporali and Luciano 4 have claimed an excellent response to D S C G in their pediatric patient. We did not demonstrate any effect of D S C G in our first patient and thought therapeutic trials were not warranted. Treatment of CVG must be individualized. A patient with mild symptoms needs no specific therapy. Therapy with D S C G may be tried in patients with persistent and troublesome symptoms. Steroids were effective in four elderly patients but should be reserved for severe manifestations." Antacids, cimetidine, carbenoxolone, and bismuth salts have occasionally been effective. 1,2,8 The longterm outlook for patients with CVG is uncertain. Adult patients may have significant morbidity associated with many years of dyspeptic symptoms. Although CVG is probably rare in childhood, it should be considered in children with unexplained anemia or chronic dyspepsia. The typical radiographic, endoscopic, and microscopic appearances are so characteristic that other diagnoses seem unlikely.
The Journal of Pediatrics September 1989
REFERENCES
1. Lambert R, Andr6 C, Moulinier B, and Bugnon B. Diffuse varioliform gastritis. Digestion 1978;17:159-67. 2. Gallagher CG, Lennon JR, Crowe JP. Chronic erosive gastritis: a clinical study. Am J Gastroenterol 1987;82:302-6. 3. McLean AM, Paul RE Jr, Philipps E, et al. Chronic erosive gastritis--clinical and radiological features. J Can Assoc Radiol 1982;33:158-62. 4. Caporali R, Luciano S. Diffuse varioliform gastritis. Arch Dis Child 1986;61:405-7. 5. Marshak RH, Lindner A, Maklansky D, Gelb A. Eosinophilic gastroenteritis. JAMA 1981;245:1677-80. 6. Chouraqui JP, Roy CC, Brochu P, Gregoire H, Morin C, Weber A. M6n6trier's disease in children: report of a patient and review of sixteen other cases. Gastroenterology 1981; 80:1042-7. 7. Henson D. Cytomegalovirus inclusion bodies in the gastrointestinal tract. Arch Pathol 1972;93:477-82. 8. Andre C, Gillon J, Moulinier B, Martin A, Farger MC. Randomized placebo-controlled double-blind trial of two dosages of sodium cromoglycate in treatment of varioliform gastritis: comparison with cimetidine. Gut 1982;23:348-52. 9. Paganelli R, Levinsky R J, Brostoff J, Wraith DG. Immune complexes containing food proteins in normal and atopic subjects after oral challenge and effect of sodium cromoglycate on antigen absorption. Lancet 1979;1:1270-2. 10. Pearce FL, Befus AD, Gauldie J, Bienenstock J. Mucosal mast cells. II. Effects of antiallergic compounds on histamine secretion by isolated intestinal mast cells. J Immunol 1982; 2481-6. 11. Farthing MJG, Fairclough PD, Hegarty JE, Swarbrick ET, Dawson AM. Treatment of chronic erosive gastritis with prednisolone. Gut 1981;22:759-62.
subdural fluid collection, was not performed in our patient. We chose the less invasive approach of performing the lumbar punctures at a higher vertebral interspace and confirmed that the C S F protein concentration was normal. The brief time between protein determinations argues against serial measurement of the same (subarachnoid) fluid and supports the presence of a collection of fluid in the subdural space. Our experience suggests that identification of an unexpected elevation in the C S F protein content of a child undergoing multiple lumbar punctures may be explained by the measurement of C S F in the subdural space. Consideration of this possibility may spare the child an overly aggressive evaluation (although myelography might be necessary to confirm the diagnosis should the subdural collection span multiple interspaces). Furthermore, injection of chemotherapeutic agents into the subdural space of
Clinical and laboratory observations
44 1
children with malignancies does not achieve the desired goal of prophylaxis or treatment of subarachnoid disease, which indicates the need for prompt attention to abnormal C S F protein values in these patients. We thank Dr. Jerome B. Posner for his helpful suggestions in the management of our patient and for his review of the manuscript. REFERENCES
1. Fishman RA. Cerebrospinal fluid in diseases of the nervous system. Philadelphia: WB Saunders, 1980. 2. Dohrman PJ, Elrick WL, Siu KH. Intracranial subdural hematoma after lumbar myelography. Neurosurgery 1983; 12:694-6. 3. Ruff RL, Dougherty JH. Complications of lumbar puncture followed by anti-coagulation. Stroke 1981;l 2:879-81. 4. Lasater GM. Primary intracellular hypotension: the low spinal fluid pressure syndrome. Headache 1970;10:63-6.
Chronic varioliform gastritis in childhood R i c h a r d Couper, MB, ChB, FRACP, B e r n a r d Laski, MD, FRCPC, B r e n d a n D r u m m , MB, BCh, FRCPC, D a v i d Stringer, BSc, MBBS, FRCR, FRCPC, a n d P e t e r Durie, MD, FRCPC From the Divisions of Gastroenterology and General Pediatrics, Department of Pediatrics, and the Department of Radiology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
Chronic varioliform gastritis is an uncommon, distinctive, inflammatory gastric mucosal disease of uncertain cause predominantly affecting middle-aged and elderly men? ,2 Many synonyms have been applied, including chronic erosive gastritis, complete erosions, dellengastritis, octopus sucker gastritis, and gastric aphthous ulcers2 ,2 Most patients have epigastric pain, nausea, and anorexia. The radiographic and endoscopic findings are characteristic. A double-contrast upper gastrointestinal tract series reveals discrete radiolucent haloes with central flecks of barium, and gastroscopy shows small, heaped-up, volcano-like mounds, pocked with a central crater, usually situated on hypertrophied rugae. In 1986 Caporali and Lucian@ reported a 10-year-old girl whose symptoms were similar to those in adult Submitted for publication Nov. 30, 1988; accepted Mar. 6, 1989. Reprint requests: Bernard Laski, MD, Division of General Pediatrics, The Hospital for Sick Children, University of Toronto, 555 University Ave., Toronto, Ontario M5G 1X8, Canada. 9/22/12292
patients. We report two further cases of CVG in children, one of whom had iron deficiency anemia, an uncommon presentation in adults. CASE REPORTS Patient 1. A 14-year-old girl without symptoms was found to have a hemoglobin level of 8 gm/day. Menses were regular and not excessive. Dietary and medication history were unremarkable. She had occasional hay fever and seasonalallergic rhinitis. Her
CVG DSCG
Chronic varioliform gastritis Disodium cromoglycate
[
grandmother required intramuscular injections of vitamin B~2 for pernicious anemia. A cousin had Crohn disease. Apart fi'om slight pallor, findings of the physical examination of the patient were normal. Blood smear analysis showed a microcytic, hypochromic anemia with the following values: hemoglobin 88 gm/L; mean corpuscular volume 57 fL; mean corpuscular hemoglobin 16.8 pg with a normal leukocyte count, no eosinophilia, reticulocyte count 52.3 X 109/L (normal 10 to 100.0 X 109/L), and erythrocyte
442
Clinical and laboratory observations
The Journal of Pediatrics September 1989 pylobacter pylori-like organisms were not identified or grown
Fig. t. Double-contrast, high-density barium radiograph shows multiple elevated nodules (straight arrows) throughout body of stomach, some of which have umbilicated central indentation in which barium collected (curved arrow). sedimentation rate 6 m m / h r (normal 1 to 10 mm/hr). The patient had reduced serum levels of iron (3 umol/L, normal 9 to 27 #mol/L) and ferritin (<2/zg/L, normal 16 to 300 #g/L) and an elevated total iron binding capacity (88 ~tmol/L, normal 45 to 72 umol/L). Serum total protein and albumin concentrations were normal. No occult blood was found in stool samples. Air-contrast barium enema demonstrated a normal colon and terminal ileum. A single-contrast upper gastrointestinal series was reported as normal. The patient received ferrous gluconate for 3 months, and her iron deficiency anemia resolved. Periodic cramping epigastric pain was the patient's only complaint during the next 3 years. Iron deficiency anemia recurred 3 years after presentation. A double-contrast upper gastrointestinal tract series of radiographs showed multiple, well-defined, circular filling defects, 5 to 9 mm in diameter, some with an umbilicated central crater, involving both the gastric body and the antrum (Fig. 1). Review of a postevacuation film from the prior barium study showed identical lesions with a similar distribution. At gastroscopy, numerous, small, friable, heaped, volcano-like lesions with an umbilicated central crater were seen in the body and the antrum. The lesions were friable but not ulcerated. The duodenum was normal. Histologic study of the antral lesion (Fig. 2) showed focal epithelial denudation and goblet cell depletion. Throughout the lamina propria there was a chronic inflammatory infiltrate extending focally into the muscularis mucosa; plasma cells and eosinophils were abundant. The body of the stomach showed mild infiltration of the lamina propria with inflammatory cells. Cam-
from biopsy cultures. Ferrous gluconate therapy was recommenced. The patient was reassessed 4 months later because of persistent abdominal cramps. Gastroscopy and an air-contrast barium study showed persistence of the lesions. Gastric histologic findings were unchanged. Immunofluorescent staining of an antral section revealed a marked increase in plasma cells, which stain positive for surface immunoglobulins, particularly IgA and IgE. The serum IgG concentration was 10.3 gm/L (normal 6 to 15 gm/L), the IgA level was 1.87 gm/L (normal 0.35 to 2.4 gm/L), and the IgE level was 56 I U / L (normal <41 IU/L). Serum C3 and C4 levels were normal, as was a fasting serum gastrin level. Antiparietal cell antibodies were absent. Two months of treatment with disodium cromoglycate, 200 mg orally twice a day, did not produce endoscopic or histologic improvement. Apart from periodic epigastric pain, the patient is symptom free and has maintained a normal hemoglobin level without oral iron therapy for the last year. Patient 2. A 10-year-old girl was examined after 7 days of nonbilious vomiting, which occurred two to four times a day and was associated with cramping lower abdominal pain. One day after the onset of the symptoms she underwent dental surgery, during which she received atropine, nitrous oxide, and local anesthetic. Urticaria developed and was treated with diphenhydramine but persisted for 3 days. Apart from periodic epigastric pain and belching for the prior 2 years, the history and physical examination were unremarkable. Anorexia, weight loss, abdominal pain, and vomiting persisted. Total parenteral nutrition was given for 3 weeks. A course of cyproheptaine and magnesium hydroxide had no effect. Singlecontrast barium radiographs showed coarse nodularity of the antrum and pylorus and markedly enlarged gastric and duodenal mucosal folds. Double-contrast barium examination revealed multiple, circular, well-defined, umbilicated filling defects, 8 mm in diameter, with central punctate flecks of barium. Gastroscopy showed the mucosa of the gastric body, antrum, and duodenum to be nodular and erythematous, with several heaped-up umbilicated lesions. Histologic study of the gastric body revealed a dense inflammatory infiltrate consisting of plasma cells, lymphocytes, neutrophils, and eosinophils. The antral biopsy findings were similar but included a sparse inflammatory cell infiltrate. Immunostaining revealed normal amounts of gastrin, somatostatin, and serotonin. Immunofluorescent staining showed an occasional plasma cell positive for IgG, IgM, and IgA and only one or two cells positive for IgE in each section viewed under high power. The hemoglobin level was 145 gm/L with a normal leukocyte count and no peripheral eosinophilia. The erythrocyte sedimentation rate was 6 mm/hr. Serum IgM, IgG, and IgA levels were normal, but the serum IgE level was mildly elevated (190 IU/L). A fasting serum gastrin level was normal. The serum albumin concentration fell to 30 gm/L by day 19. No occult blood was found in the stools, and electron microscopy did not reveal viral particles. With parenteral nutrition the patient's symptoms abated, and she resumed a normal diet. For the last 4 years she has been well
Volume 115 Number 3
Clinical and laboratory observations
443
Fig. 2. Focal epithelial denudation and goblet cell depletion are visible in section of antral mucosa. Chronic inflammatory cell infiltrate consisting of plasma cells and eosinophils is seen throughout lamina propria and extends into mascularis mucosa. (Hematoxylin and eosin stain, 125x.)
except for occasional abdominal pain. A repeat double-contrast upper gastrointestinal tract series 2V2 years after her initial examination showed persistence of the gastric lesions. DISCUSSION In adults, CVG is characterized by chronic epigastric pain, nausea, and anorexia) ,2 Less common complaints include protein-losing enteropathy, gastrointestinal bleeding, anemia secondary to occult bleeding, and extreme weight loss. Lambert et al. 1 noted that, of 90 patients, two had protein-losing cnteropathy, three had gastrointestinal tract hemorrhage, and three had anemia because of occult bleeding. One child with CVG has been reported; her symptoms conformed to the typical adult presentation. 4 Our two patients atypically had iron deficiency anemia and vomiting, respectively. The radiologic features of CVG persisted with minimal symptoms for at least 4 years in one patient and 272 years in the other. The differential diagnosis includes gastroduodenal Crohn disease, 3 eosinopbilic gastroenteritis: M6n6trier disease,6 herpesvirus infections (including cytomegalovirus), 3"6"7 candidiasis,3 and in adults, lymphoma or disseminated carcinoma. Gastroscopy identifies distinctive volcano-like mounds. Air-contrast barium radiographs show radiolucent filling defects 3 to 11 mm in diameter, with a central punctate fleck reflecting central superficial ulceration. These lesions are usually situated on hypertrophied antral rugae, although they can extend into the first part of the duodenum and the gastric body. Histologic studies
show antral gastric pit hyperplasia, mild edema, and infiltration of the lamina propria with chronic inflammatory cells, particularly polymorphonuclear leukocytes and plasma cells. Our patients had similar findings, although M~n6trier disease was considered in the second patient because of rugal hypertrophy. Eosinophilic gastroenteritis may be difficult to exclude. In the series by Lambert et al. l patients with CVG had both elevated serum IgE levels (40%) and peripheral eosinophilia (25%), as may be seen with eosinophilic gastroenteritis: Our patients had elevated serum IgE levels and increased mucosal infiltration with plasma cells staining for IgE, but no peripheral eosinophilia. Patient 1 had a history of allergy, and urticaria developed in patient 2. Eosinophilic gastroenteritis and other diagnoses are unlikely because of the distinctive lesions seen with radiology and gastroscopy. The etiology of CVG is an enigma. Nonsteroidal antiinflammatory drugs have been associated with the development of symptoms in a small number of patients, 1 but their widespread use in older patients makes this association difficult to interpret. Cytomegalovirus has been detected occasionally in both nodular gastritis and M+n&rier dise a s e : : Whether this agent is implicated in CVG is not resolved. The most popular hypothesis invokes an immunologic mechanism, as suggested by raised serum IgE levels, peripheral eosinophilia, and infiltration of plasma cells bearing IgE surface markers: Radioallergic immunosorbent testing of serum has not demonstrated any association with dietary antigens) DSCG (a mast cell stabilizer) has
444
Clinical and laboratory observations
been used successfully to treat this disorder. In a doubleblind, placebo-controlled trial involving a very small patient cohort, D S C G improved symptoms and endoscopic findings and reduced the number of plasma cells staining for surface IgE in histologic sections. 8 Paganelli et al. 9 have demonstrated that DSCG may reduce antigen entry and consequent immune complex formation in atopic individuals. However, the finding that gut-associated mast cells release histamine in the presence of D S C G leaves the question of antigen entry and the exact effect of D S C G unresolved. 1~ Caporali and Luciano 4 have claimed an excellent response to D S C G in their pediatric patient. We did not demonstrate any effect of D S C G in our first patient and thought therapeutic trials were not warranted. Treatment of CVG must be individualized. A patient with mild symptoms needs no specific therapy. Therapy with D S C G may be tried in patients with persistent and troublesome symptoms. Steroids were effective in four elderly patients but should be reserved for severe manifestations." Antacids, cimetidine, carbenoxolone, and bismuth salts have occasionally been effective. 1,2,8 The longterm outlook for patients with CVG is uncertain. Adult patients may have significant morbidity associated with many years of dyspeptic symptoms. Although CVG is probably rare in childhood, it should be considered in children with unexplained anemia or chronic dyspepsia. The typical radiographic, endoscopic, and microscopic appearances are so characteristic that other diagnoses seem unlikely.
The Journal of Pediatrics September 1989
REFERENCES
1. Lambert R, Andr6 C, Moulinier B, and Bugnon B. Diffuse varioliform gastritis. Digestion 1978;17:159-67. 2. Gallagher CG, Lennon JR, Crowe JP. Chronic erosive gastritis: a clinical study. Am J Gastroenterol 1987;82:302-6. 3. McLean AM, Paul RE Jr, Philipps E, et al. Chronic erosive gastritis--clinical and radiological features. J Can Assoc Radiol 1982;33:158-62. 4. Caporali R, Luciano S. Diffuse varioliform gastritis. Arch Dis Child 1986;61:405-7. 5. Marshak RH, Lindner A, Maklansky D, Gelb A. Eosinophilic gastroenteritis. JAMA 1981;245:1677-80. 6. Chouraqui JP, Roy CC, Brochu P, Gregoire H, Morin C, Weber A. M6n6trier's disease in children: report of a patient and review of sixteen other cases. Gastroenterology 1981; 80:1042-7. 7. Henson D. Cytomegalovirus inclusion bodies in the gastrointestinal tract. Arch Pathol 1972;93:477-82. 8. Andre C, Gillon J, Moulinier B, Martin A, Farger MC. Randomized placebo-controlled double-blind trial of two dosages of sodium cromoglycate in treatment of varioliform gastritis: comparison with cimetidine. Gut 1982;23:348-52. 9. Paganelli R, Levinsky R J, Brostoff J, Wraith DG. Immune complexes containing food proteins in normal and atopic subjects after oral challenge and effect of sodium cromoglycate on antigen absorption. Lancet 1979;1:1270-2. 10. Pearce FL, Befus AD, Gauldie J, Bienenstock J. Mucosal mast cells. II. Effects of antiallergic compounds on histamine secretion by isolated intestinal mast cells. J Immunol 1982; 2481-6. 11. Farthing MJG, Fairclough PD, Hegarty JE, Swarbrick ET, Dawson AM. Treatment of chronic erosive gastritis with prednisolone. Gut 1981;22:759-62.