Case 29

Published on 18/02/2015 by admin

Filed under Allergy and Immunology

Last modified 22/04/2025

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CASE 29

PD is a 38-year-old woman whom you see in follow-up for investigation of abnormal results of liver function tests and vague chronic fatigue. During an otherwise uneventful pregnancy, 2 years earlier, some transient moderate increase (twofold to threefold) in liver enzymes was noted, with simultaneous complaints of abdominal cramps and bloating.

At that time, stool cultures for Clostridium difficile toxin were positive and her symptoms resolved after treatment with metronidazole. She is currently experiencing diarrhea of 2 weeks’ duration, with fatty foul-smelling stools and frequent abdominal cramps, but on questioning she admits that these symptoms have been essentially intermittent for 10 years or more. However, she does casually mention that when she is on a lactose-free diet the abdominal cramps are less frequent and less severe.

On questioning she is emphatic that there is no family history of inflammatory bowel disorders, that she is not a drug user and that she does not drink alcoholic beverages, has taken no medications, has not been exposed to hepatoxins (as far as she knows), and has not traveled. Blood work revealed a moderate elevation (twofold) in liver enzymes and a deficiency in production of clotting factors synthesized exclusively by the liver. Stool culture was normal, and B cell and T cell numbers and function were normal, as were serum immunoglobulin titers. An enzyme-linked immunosorbent assay (ELISA) for human immunodeficiency virus (HIV) was negative.

QUESTIONS FOR GROUP DISCUSSION

1. Our investigation should begin by considering the possible causes for diarrhea and increase in liver enzymes. Explain why each of the following is not a likely explanation.

(a) Clostridium difficile infection
(b) Intestinal malignancy
(c) Cystic fibrosis
(d) Primary biliary cirrhosis
(e) Amyloidosis

2. Given the chronic nature of the disorder, evidence for malabsorption, and the relapsing/remitting nature of the disease, an intestinal biopsy was performed. What did this biopsy reveal?
3. Based on the clinical history and the intestinal biopsy, PD was diagnosed with celiac sprue. What causes this disease?
4. Explain how you would confirm a diagnosis of celiac sprue (gluten-sensitive enteropathy).
5. What factor differentiates celiac sprue from other diseases that mimic it (parasitic infections and/or chronic duodenitis)?
6. What recommendations would you give to this patient?

RECOMMENDED APPROACH

Implications/Analysis of Family History

No family history of inflammatory bowel disorders was noted.

Implications/Analysis of Clinical History

The initial discovery of elevated liver function tests in the context of pregnancy was certainly potentially indicative of a pregnancy-related liver disease, including intrahepatic cholestasis, acute fatty liver, and disorders associated with preeclampsia and eclampsia. However, we are told the pregnancy itself was uneventful, and these pregnancy-related changes generally resolve after birth.

Infections

We are told that a previous infection with C. difficile has been eradicated; moreover, C. difficile infection is not associated with liver abnormalities. Infections would be a consideration for the diarrhea and altered liver function tests, particularly in immunocompromised individuals, but T cell and B cell numbers and function were normal. Tuberculosis, amebiasis, and schistosomiasis could all fit this picture (of gastrointestinal complaints and liver abnormalities), but the chronic course, lack of travel history, and negative stool cultures reduce their likelihood. Bacterial overgrowth in the upper intestine is a plausible consideration.

Disorders That Present Similarly

Intestinal malignancy could present this way, although again the lengthy history suggests this is an unlikely explanation. Cystic fibrosis would certainly fit this picture, although such a late presentation would be extraordinary. Primary biliary cirrhosis, an idiopathic disease generally affecting females of this age group, is a rare autoimmune-type disorder that fits this picture; in a male, sclerosing cholangitis is a disorder also associated with idiopathic inflammation of the bile ducts. A liver biopsy should be ordered to rule out this option (see Additional Laboratory Tests).

Chronic amyloidosis, another rare multisystemic immunologic disorder associated with overproduction and deposition (with induction of nonspecific inflammatory processes) of various proteins (e.g., serum amyloid protein) could also explain the picture. Biopsy would rule this out (also test for elevated serum amyloid protein).

Implications/Analysis of Laboratory Investigation

Blood work should include elimination of HIV infection and simple tests to exclude generalized immunodeficiency (e.g., T cell and B cell numbers/function; serum immunoglobulin). Given the chronic nature of the process, the evidence for malabsorption symptoms, and the relapsing/remitting nature of the disease, an intestinal biopsy is warranted (see Additional Laboratory Tests).

Additional Laboratory Tests

Liver and intestinal biopsies were performed. Liver biopsy was essentially normal. The intestinal biopsy reveals flattening of the crypts, villous atrophy, a lymphoplasmacytic infiltration of the mucosal wall, and increased intraepithelial lymphocytes (see Diagnosis).

Further confirmation of the diagnosis can be sought with tests for antigliadin antibodies. In addition, antiendomysial antibodies are increased in titer; these recognize a tissue transglutaminase that has gliadin as its preferred substrate.

DIAGNOSIS

The best diagnosis after the intestinal biopsy results and clinical history is celiac sprue, or gluten-sensitive enteropathy.

THERAPY

Eliminate gluten from the diet.

ETIOLOGY: CELIAC DISEASE

Celiac sprue, or gluten-sensitive enteropathy, is caused by immunologic reaction to wheat gliadin and similar proteins in the diet. The disease has an incidence of some 1:500 in Western Europeans. The importance of increased intraepithelial lymphocytes in this disorder has been stressed as a factor differentiating celiac sprue from other diseases that mimic it, including the altered histopathology and absorption that occurs in association with some parasitic infections and/or chronic duodenitis. These intraepithelial lymphocytes are, in general, cytotoxic T cells that decrease in number when gluten is withdrawn from the diet, rapidly recurring (within hours) with reintroduction of gluten in the diet. The relief of symptoms with elimination of gluten from the diet is also diagnostic.

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