The term “celiac crisis” has been used to describe the acute, fulminant form of celiac disease (CD) associated with hypoproteinemia and edema (1). Celiac crisis, the most severe form of CD, has nearly disappeared from our experience and is a rare occurrence (2). We have entered into a new era with respect to our understanding of CD during the past 15 years. Previously it was believed that CD was an uncommon condition in the United States (3). Diagnostic techniques for obtaining small intestinal biopsy specimens such as the Crosby-Kugler capsule and the Rubin tube were laborious and fraught with technical problems. This resulted in the selection of pediatric patients who were the most symptomatic for investigation. As a result there was a pervasive low index of suspicion for CD. The development of sensitive serological markers for screening for CD has greatly facilitated diagnosis. The widespread availability of these screening markers has ushered in a new, modern era with respect to CD. There has been great emphasis on the subtle and often asymptomatic nature of CD as we have begun to expose the submerged part of the celiac “iceberg” (4,5).
Herein we present 2 patients with CD whose initial presentation was celiac crisis. These cases illustrate that celiac crisis still occurs. Furthermore, serological data can facilitate prompt diagnosis of celiac crisis in the acute setting. These cases also highlight the utility of corticosteroid therapy in the treatment of celiac crisis.
A 32-month-old girl was admitted to the hospital for the acute onset of severe diarrhea, lethargy, edema, and dehydration. The patient was in her usual state of good health before presenting to the emergency department with a 9-day history of watery diarrhea. There was no associated fever. Two days before admission she was evaluated by her pediatrician who diagnosed her with a viral gastroenteritis. Supportive treatment with oral rehydration solution was recommended. The patient became increasingly fatigued and on the day of admission was refusing to stand up. There were no previous hospital admissions. For the first 2 years of her life, the patient had been tracking along the 50th percentile in height and 75th percentile in weight. The family history was negative for CD, inflammatory bowel disease, irritable bowel syndrome, food allergies, liver disease, diabetes mellitus, and thyroid disease.
In the emergency department the patient's rectal temperature was 36.5°C, the pulse was 72 bpm, and the respiratory rate was 22 breaths per minute. Her blood pressure was 70/30 mmHg. Her weight was 11.8 kg (10th–25th percentile) and height 91.4 cm (25th percentile). She was noted to have significant periorbital and pedal edema as well as a distended abdomen. There was no organomegaly. She was moderately to severely dehydrated and received normal saline solution intravenously. Her abdominal radiograph revealed distended air-filled loops of small and large intestine without evidence of obstruction.
Her initial laboratory results are shown in Table 1. Stool examination for rotavirus, Salmonella species, Shigella species, Campylobacter species, Yersinia species, Escherichia coli 0157:H7, C difficile, and ova and parasites were negative. Serology for celiac disease was sent and noted to be abnormal (Table 2). A small intestinal biopsy showed subtotal villous atrophy with chronic duodenitis, numerous intraepithelial lymphocytes, and crypt hyperplasia (Marsh score 3b; Fig. 1). Despite a gluten-free diet and parenteral nutritional support, the patient continued to have severe diarrhea, anorexia, poor weight gain, and hypoalbuminemia. A diagnosis of celiac crisis was made. Methylprednisolone (2 mg · kg−1 · day−1) was started on hospital day 10. Within 48 hours, the patient's appetite returned to normal, she became more active, and her stool output markedly decreased.
She was discharged on a tapering dose of prednisone and a gluten-free diet. She has remained well and is thriving on a gluten-free diet for more than 1 year after hospital discharge.
A 3-year-old boy was admitted to the hospital for the sudden onset of profuse diarrhea and dehydration. He was in his usual state of good health until 7 days before admission when he began having as many as 6 to 7 episodes of explosive, watery stools daily. There were 2 episodes of emesis. There was no fever or known exposure to contagious illness. The patient had been seen by his pediatrician on the third day of illness, who recommended loperamide and increased oral fluid intake. On the day of admission the patient had become less active with decreased oral intake and urine output. His parents were also worried about his marked fatigue and irritability. The patient had an oral temperature of 36.3°C, a pulse of 102 bpm, and a respiratory rate of 23 breaths per minute. His blood pressure was 79/45 mmHg. His weight was 15 kg (50th percentile) and height was 103 cm (90th percentile). His mucus membranes and lips were dry and his abdomen was distended. There were no masses or organomegaly. He had pedal edema. He was estimated to be moderately dehydrated and received intravenous fluid resuscitation.
Initial laboratory results are shown in Table 1. Stool examination for Salmonella species, Shigella species, Campylobacter species, Yersinia species, E coli 0157:H7, Giardia species, Cryptosporidium species, Isospora species, C difficile, rotavirus, adenovirus-41, fecal leukocytes, and reducing substances were negative. An abdominal ultrasound examination revealed ascites and an abdominal and pelvic computed tomography showed ascites and small bilateral pleural effusions. He received 2 infusions of albumin. The diarrhea persisted and his albumin level decreased to 1.2 g/dL. Celiac crisis was suspected. Serological markers are shown in Table 2. Biopsies of the duodenum revealed total villous atrophy and were consistent with a Marsh score of 3c (Fig. 2). The patient was started on parenteral nutrition. Attempts to feed with a nasogastric infusion of Peptamen Junior (Nestle Nutrition, Glendale, CA) at low volumes resulted in marked diarrhea. On hospital day 14, the patient was started on a regimen of methylprednisolone (2 mg · kg−1 · day−1). He began to tolerate a full energy volume of nasogastric feeding and was advanced to a lactose-free, gluten-free diet. His appetite improved, as did his activity, and he was passing formed stools. His weight increased to 15.65 kg and the serum albumin level to 4.3 g/dL by discharge. He was discharged on a tapering prednisone regimen after 8 days of solumedrol treatment and was to continue a gluten-free diet.
We describe 2 previously healthy, thriving toddlers who presented with the acute onset of severe diarrhea, dehydration, and metabolic sequelae as their initial presentation of celiac disease. Both patients presented in a state of celiac crisis. Celiac crisis is the term that has been applied to patients with CD of acute onset that is severe enough to be potentially fatal. It may arise in patients with established CD or, as in our patients, it may be the initial presentation of their disease. Celiac crisis may not respond to a gluten-free diet alone.
The acute presentation of CD has been included in some of the earliest descriptions of the affliction. Gee, in 1888, stated of CD that “the onset is usually gradual so that the time of onset is hard to fix. Sometimes the complaint sets in suddenly, like an accidental diarrhea” (6). In 1952 Anderson and di'Sant-Agnese followed the clinical course of 58 children with CD (7). They observed 35 episodes of celiac crisis and 3 fatalities among these patients. In 1951 Adlersberg et al reported that the use of corticosteroids in adults with CD was effective therapy but relapse occurred when treatment was withdrawn (8). The dramatic success of the gluten-free diet all but eliminated the use of corticosteroids for the treatment of CD.
In 1972 Lloyd-Still described 3 cases of celiac crisis in children who presented with profound diarrhea, dehydration, metabolic abnormalities, and weight loss (9). They were successfully treated with corticosteroids. More recently, Baranwal et al reported celiac crisis in a 5-year old girl with chronic intermittent diarrhea and gastrointestinal complaints who was treated with corticosteroids (10). Walia and Thapa were the first to describe a pediatric patient with celiac crisis whose diagnosis was supported by a markedly increased anti-tissue transglutaminase immunoglobulin A antibody (11). Their patient was a 7-year-old boy who had been having recurrent watery stools since 18 months of age (12). Celiac crisis has also been described in adults (13,14).
A great deal has been learned about the pathogenesis of CD in recent decades. We know there is an inflammatory response to the ingestion of gluten that ultimately results in morphological changes in the small intestine and subsequent clinical manifestations of CD (15). Our patients presented with severe gastrointestinal manifestations of CD and were not responding to the withdrawal of gluten from their diet. The response to a course of corticosteroids was dramatic.
It is not clear why celiac crisis has become a rare event during the past 50 years. It may be because of the changing nature of CD in general (ie, toward a more subtle and indolent disease). This may be the result of natural selection. One of the symptoms of CD is male and female infertility (15), which may deselect a subset of people with more severe CD. It has also been hypothesized that factors such as the increased incidence of breast-feeding in our society, the delayed introduction of baby food in general, and the introduction of gluten-containing cereals at an older age have contributed to the changing nature of CD. Finally, in some patients, the lesions of CD may be extensive and may therefore result in more severe symptoms.
In summary, we believe it is important to recognize that CD may present in “crisis.” CD should be considered in the differential diagnosis of patients who present with the acute onset of severe diarrhea and hypoproteinemia. Intestinal biopsies in cases caused by infections or those secondary to protein allergy may show nonspecific villous atrophy and crypt hyperplasia and may be indistinguishable from biopsies of patients with CD. By performing screening tests for CD, a more accurate and specific diagnosis of celiac crisis may be made, allowing for prompt treatment. Corticosteroids should be considered in those cases of celiac crisis when a rapid response to a gluten-free diet does not occur.
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