Pancreatitis, malabsorption, and IgA deficiency in a child with diabetes

5 12

Brief clinical and laboratory observations

SUMMARY

The Journal of Pediatrics March 1971

REFERENCES

A 6-week-old infant with hypertonlc dehydration, uremia, and sepsis presented with bilaterally enlarged kidneys and thrombocytopenia. Following peritoneal dialysis the diagnosis of bilateral renal vein and inferior vena caval thrombosis was confirmed by angiography. Right nephrectomy and vena caval and left renal vein thrombectomy were performed and anticoagulation instituted. T h e infection responded to antibiotic therapy. Renal function returned to normal. T h e importance of angiography in the diagnosis of renal vein thrombosis is stressed. Because of the high mortality rate associated with the conservative therapy of bilateral renal vein thrombosis in infants, early surgery is considered the treatment of choice.

I. Miller, H. C., and Benjamin, J. A.: Acute idiopathic renal vein thrombosis in infants, Pediatrics 30: 247, 1962. 2. Verhagen, A. D., Hamilton, J. P., and Genel, M.: Renal vein in infants, Arch. Dis. Child. 40: 214, 1965. 3. Royer, P., Habib, R., and Mathieu, H.: Problems actuels de nephrologie infantile, Paris, 1963, t~ditions Medicales Flammarion. 4. Mauer, S. M., and Nogrady, M. B.: Renal papillary and cortical necrosis in a newborn infant: Report of a survivor with roentgenologic documentation, J. P~DIAT. 74: 750, 1969. 5. Wegner, G. P., Crummy, A. B., Flaherty, T. T., and Hipona, F. A.: Renal vein thrombosis, J'. A. M. A. 209: 1661, 1969. 6. Stark, H.: RenaI vein thrombosis in infancy, Amer. J. Dis. Child. 108: 430, 1964. 7. McFarland, J. B.: Renal vein thrombosis in children, Quart. J. Med. 34: 269, 1965.

We thank Drs. A. F. Michael, T. Nivens, J. Cich, and K. Amplatz for their assistance in the management of this patient.

Pancreatitis, malabsorption, and IgA deficiency in a chiM with diabetes R o b e r t Penny, Robert G. Thompson, Stephen H. Polmar, and Robert B. Schultz ~ BALTIMORE~

MD.

M A L A 13 S O R P T I O N is 21, well-known complication of diabetes mellitus in adults, 1, ~ but only recently has attention been drawn to the association of malabsorption and dia-

From the Department of Pediatrics, The Johns Hopkins University School of Medicine. Supported by United States Public Health Service Training Grant 2A-5219 and Grant HD-O1852. ~Address: Department o[ Pediatrics, Sinai Hospital, Belvedere and Greenspring Ave., Baltimore, Md. 21215.

betes mellitus in children, s-s T h e increased frequency of pancreatitis in diabetes has similarly been reported, G as has the absence of IgA in association with malabsorption. 7"~~ This report, however, deals with the unique occurrence of all these disorders in the same individual. CASE R E P O R T

Patient B. A., a 5 ~2-year-old Caucasian girl, initially presented to the Joslin Clinic at 2 2/12 years of age with a 2 week history of polyuria and polydipsia. She was found to have a blood sugar concentration of 342 rag. per cent with associated glycosuria and was diagnosed as having diabetes mellitus. Insulin requirements fluctuated and her course was punctuated by a number of hypoglycemic episodes. She usually received 1 U. of regular and 3 U. of NPH insulin in the morning and 1 U. of regular and 2 U. of NPH in the evening. At 3 ~ 2 years of age, there began an 11 month period of vague nonspecific abdominal pain, occasional bouts of emesis, bulky foul-smelling stools, abdominal protuberance, and a weight loss of 6 pounds during the first 8 months of this period. Subsequently she failed to gain weight. During this time there was

Volume 78 Number 3

difficulty in her diabetic control as manifested by marked insulin sensitivity. In July, 1968, at the age of 4 ~ 2 years, she was admitted to the Johns Hopkins Hospital for evaluation of realabsorption. Her family and past medical history are of interest in that her father's first cousin developed diabetes at age 5, and her paternal grandmother had diabetes for 5 years prior to her death at 78. The patient had no history of recurrent infections. Physical examination on admission to Johns Hopkins Hospital revealed a thin, cooperative child who had little adipose or muscular tissue and was hirsute over her back and extremities. Blood pressure was 105/60 mm. Hg, pulse was 80 beats per minute, and respirations were 20 per minute; she was afebrile. Height was 3 9 ~ inches and weight was 31 pounds. There was abdominal distention with a prominent venous pattern above the umbilicus. No organomegaly was noted, but shifting dullness and a fluid wave were present. There was no abdominal tenderness. The remainder of the physical examination results were unremarkable. Paracentesis revealed ascitie fluid which contained 630 units of amylase; urine amylase activity also was found to be elevated (Table I). She had steatorrhea (stool fat of 8.25 Gin. per day with normal being less than 6 Gm. per day) and an equivocal D-xylose absorption test. Her upper gastrointestinal series was abnormal (Fig. 1 ). Pancreatitis was thought to be present; she was discharged on pancreatin, five 325 mg. tablets twice a day. During the initial 3 months of therapy, the character of the stools improved and she became relatively free of abdominal pain. However, there was no substantial weight gain. Because of this she was readmitted to the hospital in October, 1968. The only significant change in physical examination results was the absence of ascites. The abdomen was still protuberant, and weight was 31.9 pounds (+ 0.9 pounds in 3 months). A duodenal intubati0n with analysis of the aspirate for amylase, lipase, and trypsin showed them to be abnormal (Table I); a duodenal biopsy revealed changes consistent with celiac disease (Fig. 2). Moreover, she was found to have a deficiency of IgA, 3 rag. per 100 ml. (normal for age, 55 to 152 mg./100 ml. of serum). 11 She was discharged on pancreatin and a gluten-free diet. Two months after discharge (weight gain 2.8 pounds) pancreatin was discontinued. After 9 months of therapy she gained 6.8 pounds and grew 1.75 inches. In the 9 months

Brie[ clinical and laboratory observations

5 13

preceding therapy she had gained only 0.9 pounds and had grown only 1.0 inch. One year after initiation of the gluten-free diet she had gained 13 pounds. The weight gain was associated with a decrease in abdominal protuberance and an increase in insulin requirement (8 units regular and 10 units NPH insulin daily). The IgA levels did not become normal. DISCUSSION

Blumenthal and associates 6 concluded, in their study of the interrelationship of diabetes mellitus and pancreatitis, that pancreatitis is significantly more c o m m o n in diabetic than in nondiabetic subjects. T h e y considered small-vessel abnormalities and vascular infarcts as the probable cause of the pancreatitis. Katz and Spiro 2 observed that it is very likely that mild episodes of pancreatitis go undetected as a cause of abdominal pain in diabetes. T h e absence of signs of acute illness in our patient is not without precedent; H e n d r e n and associates 12 described a 3-year-old Negro female with abdominal distention, ascites, swelling of the hands and feet, and absence of signs of acute illness. As in our patient, the ascitic fluid amylase activity was elevated, whereas the serologic laboratory studies were normal. While the impaired pancreatic exocrine function found in our patient might be attributed to pancreatitis, impairment of pancreatic exocrine function in diabetic patients has been reported as a frequent finding. Chey and associates la evaluated 50 randomly selected diabetic adults and 13 children with diabetes and found a 33 per cent incidence of abnormal pancreatic exocrine function in the adult patients and a 77 per cent incidence in the juvenile patients. T h e r e was no correlation with duration or severity of the diabetes. Malabsorption with jejunal mucosal atrophy and a favorable response to a glutenfree diet in diabetic adults has been recognized for a n u m b e r of years. 1, e Recently attention has been drawn to the occurrence of this disorder in juvenile diabetic patients. H o o f t and associates 3 reported 12 cases, 3 females and 9 males, with ages ranging from 1 to 16 years. U p p e r gastrointestinal

5 1 4 Brief clinical and laboratory observations

The Journal of Pediatrics March 1971

T a b l e L S u m m a r y of l a b o r a t o r y investigation

Laboratory data Complete blood count Electrolytes Serum proteins SGOT SGPT Prothrombin time Bromsulphalein Sweat chloride

t

Preliminary

Pertinent admiss:on July admission [October i

Normal

All normal

Fasting blood sugar

65-455 rag. %

Urinalysis

Normal except for appropriate glycosuria

Amylase Urine Serum Ascitic fluid (10ml.; specific gravity 1.015)

6,520 U./100 ml. 120 U./100 ml. 630 U.

650 U./100 ml.

350 U./100 ml.

Stool fat

8.25 Gm./day x 3 days

< 6 Gm./day

Xylose absorption (Abnormal ~ 15% ; equivocal 15-25%)

Excreted 20.7% of dose in urine

>25%

Duodenal aspirate Time (min.) 30 ~ 60 ~ Amylase (U.)

3,425 2,800 3,060

Lipase (U.)

0.20 0.15 0.25

Trypsin (U.)

476 287 164

Immunoglobulin (rag./100 ml.; mean-+ 1 S.D.) IgG IgM IgA

980 76 3

920 -+ 228 56 +- 18 93 + 27

eThese studies were kindly performed by the Division of Gastroenterology of the Department of Medicine, the Johns Hopkins Hospital, The values were determined after the administration of a metracal load. Normal: amylase should increase 6 or more units per kilogram above base line, Lipase should increase to 0.4 units or more, and Trypsin should quadruple in concentration.

studies were a b n o r m a l in 5 of 8 patients. Eleven of the 12 h a d increased steatorrhea a n d fecal glucose excretion. F o u r of the children h a d chronic diarrhea, a n d one h a d i n t e r m i t t e n t diarrhea. T h e others were clinically asymptomatie. O n e child h a d a small

bowel biopsy a n d 2 were treated with a gluten-free diet. W a l k e r - S m i t h a n d Grigor 4 a n d K o m r o w e r ~ each r e p o r t e d a case of m a l a b s o r p t i o n in a diabetic child, an 8-yearold girl a n d a 3 8 9 boy, respectively. Both subjects h a d small bowel biopsies which

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C

showed a flat mucosa, a n d both h a d a favorable response to a gluten-free diet. Several adults 7, 8 have been r e p o r t e d with malabsorption, isolated I g A deficiency, flat mucosa on small bowel biopsy, a n d a favorable response to a gluten-free diet. I m m o nen 9 r e p o r t e d a 4-year-old child with isolated I g A deficiency a n d malabsorption. West a n d associates 1~ m e n t i o n e d the coincidence of I g A deficiency a n d m a l a b s o r p t i o n in childhood. T h e y studied 13 children, ages 1 89 to 15 years, with isolated I g A deficiency. Six of the children h a d r e c u r r e n t m i n o r infections a n d fevers of u n k n o w n origin, 5 h a d central nervous system d a m a g e a n d 2

Brie/ clinical and laboratory observations

5 15

Fig. 1. Early films from the upper gastrointestinal series. A, Frontal film. The dark bands across the jejunum (open arrow) and the spiculated margins (closed arrows) are caused by widened mucosal circular folds. B, Oblique film. "/?he mucosal folds are greatly thickened in the duodenum also (arrows). C, Frontal film. One half hour later. The jejunum is mildly dilated; the ileum is moderately dilated and there is a transient small bowel intussusception (between the arrows). The thick circular folds give the small bowel an unusual coarse appearance.

Fig. 2. Duodenal biopsy showing absence of villi, increased chronic inflammation, and damaged surface epithelium. Plasma cells were present in large numbers within the lamina propria.

5 16

Brie[ clinical and laboratory observations

(a l ~ - y e a r - o l d female and a 2 ~ - y e a r - o l d female) had malabsorption. However, isolated IgA deficiency also has been described in apparently normal subjects? 4 O u r patient is remarkable in that she has the unique triad of pancreatitis, malabsorption, and IgA deficiency in association with juvenile diabetes. Whether the association represents more than a chance l~henomenon is not clear, nor is the etiology of the association explainable.

SUMMARY A 52A2-year-old diabetic girl developed signs and symptoms of malabsorption one year after the onset of diabetes. She was found to have atrophic mucosa on small bowel biopsy and responded favorably to a gluten-free diet. H e r evaluation also demonstrated the presence of pancreatitis and isolated I g A deficiency. REFERENCES 1. Vinnick, I. E., Kern, F., Jr., and Struthers, J., Jr.: Malabsorption and the diarrhea of diabetes mellitus, Gastroenterology 43: 507, 1962. 2. Katz, L. A., and Spiro, H. M.: Gastrointestinal manifestaqons of diabetes, New Eng. J. Med. 275: 1350, 1966. 3. Hooft, C., Devos, E., Kriekemans, J., and VanDamme, J.: Malabsorption and diabetes mellitus in children, Helv. Pediat. Acta 23: 478, 1968.

Neonatal thrombocytopenia and chorangioma Luz A. Froehlieh, M.D., and

Mary Housler, R.N. BETHESDA, MD. From the Perinatal Research Branch, National Institute o[ Neurological Diseases and Stroke, National Institutes o[ Health, and The Children's Hospital o[ Buffalo. The Collaborative Study of Cerebral Palsy, Mental Retardation, and Other Sensory Disorders of In[ancy and Childhood is supported by the National Institute of Neurological Diseases and Stroke. Reprint address: PerinatatResearch Branch, Institute of Neurological Diseasesand Stroke, National Institutes ~( Health.

The Journal of Pediatrics March 1971

4. Walker-Smith, J. A., and Grigor, W.: Celiac disease in a diabetic child, Lancet h 1021, 1969. 5. Komrower, G. M.: Celiac disease in a diabetic child, Lancet h 1215, 1969. 6. Blumenthal, H. T., Probstein, J. G., and Berns, A. W.: Interrelationship of diabetes mellitus and pancreatitis, Arch. Surg. 87: 844, 1963. 7. Hermans, P. E., Huizenga, K. A., Hoffman, H. W., Brown, A. L., Jr., and Markowitz, I-I.: Dysgammaglobutinemla associated with nodular lymphoid hyperplasia of the small intestine, Amer. J. Med. 40: 78, 1966. 8. Crabli, P. A., and Heremans, J. F.: Selective IgA deficiency with steatorrhea, Amer. J. Med. 42: 319, 1967. 9. Immonen, P.: Levels of the serum immunoglobulin A, G, and M in the malabsorption syndrome in children, Ann. Pediat. Fenn. 13: 115, 1967. 10. West, C. D., Hong, R., and Holland, N. H.: Immunoglobulin levels from the newborn period to adulthood and in immunoglobulin deficiency states, J. Clin. Invest. 41: 2054, 1962. 11. Stiehn, E. R., and Fudenburg, H. H.: Serum levels of immune globulins in health and disease, Pediatrics 37: 715, 1966. 12. Hendren, W. H., Creep, J. M., and Patton, A. S.: Pancreatitis in childhood: Experience with 15 cases, Arch. Dis. Child. 40: 132, 1965. I3. Chey, W. Y., Shay, tt., and Shuman, C. Q.: External pancreatic secretion in diabetes mellitus, Ann. Intern. Med. 59: 812, I963. 14. Rocky, J. H., Hanson, L. A., Heremans, J. F., and Kunkel, H. G.: Beta-2A aglobulinemia in two healthy men, J. Lab. Clin. Med. 63: 205, 1964.

THROMBOGYTOPENIG PURPURA and giant hemangiomas, particularly of the skin, have been a well-recognlzed combination 1"~ since the first case report by K a s a b a c h and Merritt 1~ in 1940. A few instances of splenic h e m a n g i o m a associated with thrombocytopenic purpura, in which recovery followed splenectomy, have also been described?l, 12 It has been presumed that platelets are sequestered in the hemangioma, hence the thrombocytopenia. T h e r a p y has included x-ray, radium implantation, surgical excision when feasible, splenectomy (particularly in splenic h e m a n g i o m a ) , corticosteroid therapy, and injection of sclerosing agents, with varying results. It is generally conceded, however, that removal or significant regression of the t u m o r has resulted in