A Woman with Psychosis

Posted by • May 13th, 2016

2016-05-06_13-34-48The combination of malabsorption and autoimmunity strongly suggests the possibility of celiac disease, which is not always associated with gastrointestinal symptoms. Although neurologic and psychiatric symptoms of celiac disease are not widely recognized, they have been reported.

Examination of a 37-year-old woman with adult-onset psychosis revealed weight loss, a thyroid nodule, anemia, and micronutrient deficiencies. Diagnostic tests were performed. A new Case Records of the Massachusetts General Hospital summarizes.

Clinical Pearl

• What historical or clinical findings should make one consider celiac disease?

Celiac disease should be considered in patients with gastrointestinal symptoms and in patients with extraintestinal problems, such as iron-deficiency anemia that is unresponsive to treatment, arthritis, or elevated levels of liver enzymes; it should also be considered in high-risk patients, including those with a family history of celiac disease, those with type 1 diabetes mellitus, and those with autoimmune thyroid disease.

Clinical Pearl

• What serologic tests are useful when celiac disease is suspected?

Serologic tests — including tests for IgA tissue transglutaminase antibodies, endomysial antibodies, and deamidated gliadin peptide antibodies — help to identify persons who may benefit from duodenal biopsy. General consensus regarding these studies is that the test for IgA tissue transglutaminase antibodies is the most reliable and cost-effective.

Morning Report Questions

Q: What is the appropriate management when test results for IgA tissue transglutaminase antibodies are abnormal? 

A: Patients with abnormal test results for IgA tissue transglutaminase antibodies or those in whom celiac disease is highly suspected must be referred to a gastroenterologist for confirmatory testing with endoscopy and biopsy. The diagnostic standard for celiac disease is a biopsy of the small intestine. The patient must remain on a gluten-containing diet for testing to be accurate. A trial of a gluten-free diet is not appropriate unless celiac disease has been ruled out; once the patient is on a gluten-free diet, a clinician cannot distinguish between celiac disease and other gluten-related disorders, including nonceliac gluten sensitivity, because both can have extraintestinal manifestations. If a patient has initiated a gluten-free diet without having had the proper testing, a genetic test may be helpful to identify whether there is a need to reintroduce gluten for confirmatory testing for celiac disease.

Figure 1. Initial Biopsy Specimen of the Duodenum.

Figure 2. Subsequent Biopsy Specimen of the Duodenum (Hematoxylin and Eosin).

Q: Is there a connection between celiac disease and neuropsychiatric disease?

A: Celiac disease was classically described as a gastrointestinal condition that almost exclusively affects white children. Now celiac disease is described as an autoimmune disorder that can affect persons of any age or race and can involve any tissue or organ of the body. The typical gastrointestinal symptoms (diarrhea, bloating, failure to thrive, and weight loss) can be easily understood by the underlying intestinal damage caused by the autoimmune attack that occurs after the ingestion of gluten, but the many extraintestinal symptoms that patients with celiac disease often have are more difficult to explain. New insights on the pathogenesis of celiac disease suggest that it is truly a systemic disease that can spread from the intestine to any tissue or organ of the body. One of the most intriguing yet controversial clinical presentations of celiac disease involves the nervous system as a preferred target. Patients with celiac disease often have chronic headache, short-term memory loss, irritability, anxiety, and depression and more rarely have seizures, ataxia, autism, attention-deficit disorders, and psychosis. Although we do not have a definitive explanation of the way in which an inflammatory process in the intestine affects the brain, there is growing evidence of close functional and organic interactions between these two systems, which are typically described as the gut–brain axis.

Table 1. Extraintestinal Manifestations of Celiac Disease.

Table 2. Neuropsychiatric Symptoms Associated with Celiac Disease.

One Response to “A Woman with Psychosis”

  1. Willemina Rietsema says:

    All of the above-named neuropsychiatric disorders are consistent with vitamin B12 (B12) deficiency. [1-5] Patients with celiac disease are at increased risk of also having B12 deficiency. Firstly, celiac disease causes B12 malabsorption through inflammation of the small intestine. Secondly, auto-immune B12 deficiency (pernicious anaemia) occurs more frequently in patients who have other auto-immune disorders. [6] B12 deficiency is often not identified because the total serum B12 test has poor sensitivity. In a recent study sensitivity was only 11-36%, compared to holotranscobalamin and methylmalonic acid combined. [7] In the absence of a gold standard test for B12 deficiency, a therapeutic trial of B12 is justified as soon as B12 deficiency is suspected. Particularly since neurological deficit may become irreversible if treatment is delayed. [8] Careful recording of symptoms, signs, and the severity of these before and after 12 doses of 1 mg B12 over a month [3] or until no further improvement [8] is necessary to ascertain treatment response. If the therapeutic trial is proves positive, lifelong substitution of B12 is indicated.

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    2. Healton EB, Savage DG, Brust JCM, Garrett TJ, Lindenbaum J. Neurologic aspects of cobalamin deficiency. Medicine (United States) 1991;70:229-45.
    3. Savage DG, Lindenbaum J. Neurological complications of acquired cobalamin deficiency: clinical aspects. Baillieres Clin Haematol 1995;8:657-78.
    4. Solomon LR. Vitamin B12-responsive neuropathies: A case series. Nutr Neurosci 2016;19:162-8.
    5. Rietsema WJ. Unexpected recovery of moderate cognitive impairment on treatment with oral methylcobalamin. J Am Geriatr Soc 2014;62:1611-2.
    6. Osborne D, Sobczynska-Malefora A. Autoimmune mechanisms in pernicious anaemia & thyroid disease. Autoimmunity reviews 2015;14:763-8.
    7. Ward MG, Kariyawasam VC, Mogan SB, et al. Prevalence and Risk Factors for Functional Vitamin B12 Deficiency in Patients with Crohn’s Disease. Inflamm Bowel Dis 2015;21:2839-47.
    8. Devalia V, Hamilton MS, Molloy AM. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Br J Haematol 2014;166:496-513.