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TEACHING TOPICS from the New England Journal of Medicine
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Teaching Topics | December 20, 2012
Celiac Disease: What are the risk factors for celiac disease?
Alcoholism, Seizures, and Agitation: What is an alcohol withdrawal syndrome “type indicator”?
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Teaching Topic
Celiac Disease
Clinical Practice
A. Fasano and C. Catassi
  
Celiac disease is a systemic immune-mediated disorder triggered by dietary gluten in genetically susceptible persons. Gluten is a protein complex found in wheat, rye, and barley. Celiac disease is characterized by a broad range of clinical presentations, a specific serum autoantibody response, and variable damage to the small-intestinal mucosa.
Clinical Pearls
 What is the prevalence of celiac disease?
Celiac disease affects 0.6 to 1.0% of the population worldwide, with wide regional differences in Europe (e.g., the prevalence is 0.3% in Germany and 2.4% in Finland) for reasons that are unclear. Celiac disease is also common in developing countries, particularly in North Africa and the Middle East. In India, celiac disease is observed mainly in the northwestern part of the country, where wheat is a staple food. Cases of celiac disease also have been described in China. The frequency of celiac disease is increasing in many developing countries because of westernization of the diet, changes in wheat production and preparation, increased awareness of the disease, or a combination of these factors.
What are the risk factors for celiac disease?
The prevalence of celiac disease is 1.5 to 2 times as high among women as among men and is increased among persons who have an affected first-degree relative (10 to 15%), type 1 diabetes (3 to 16%), Hashimoto’s thyroiditis (5%) or other autoimmune diseases (including autoimmune liver diseases, Sjögren’s syndrome, and IgA nephropathy), Down’s syndrome (5%), Turner’s syndrome (3%), and IgA deficiency (9%).
Genetic background plays a key role in the predisposition to the disease. The HLA-DQ2 haplotype (DQA1*0501/DQB1*0201) is expressed in the majority of patients with celiac disease (90%), whereas it is expressed in one third of the general population. In another 5% of patients with celiac disease, the HLA-DQ8 haplotype (DQA1*0301/DQB1*0302) is expressed, whereas almost all the remaining 5% of patients have at least one of the two genes encoding DQ2 (DQB1*0201 or DQA1*0501).
Morning Report Questions
Q. What are the symptoms and signs of celiac disease?
A. Frequent symptoms and signs include chronic diarrhea, weight loss, and abdominal distention (in 40 to 50% of patients). Other manifestations include iron deficiency with or without anemia, recurrent abdominal pain, aphthous stomatitis, short stature, high aminotransferase levels, chronic fatigue, and reduced bone mineral density. Unusual manifestations of celiac disease include dermatitis herpetiformis, a blistering rash with pathognomonic cutaneous IgA deposits; gluten ataxia, a sporadic form of ataxia with positive serologic markers for gluten sensitization (although the association with celiac disease is still debated); and celiac crisis, a rare life-threatening syndrome, mostly observed in children, that is characterized by severe diarrhea, hypoproteinemia, and metabolic and electrolyte imbalances. Clinically silent celiac disease has been increasingly detected by means of serologic screening.
Q. What is the most useful laboratory test for the diagnosis of celiac disease?
A. Measurement of serum IgA anti–tissue transglutaminase antibodies is recommended for initial testing in persons who do not have concomitant IgA deficiency because of its high sensitivity (94%), high specificity (97%), and excellent standardization; IgG anti–tissue transglutaminase antibodies can be measured in persons with IgA deficiency. Measurement of IgA anti-endomysial antibodies is nearly 100% specific for active celiac disease, but it should be used only as a confirmatory test in the case of borderline positive or possibly false positive results of tests for anti–tissue transglutaminase antibodies, as occurs in other autoimmune diseases, including type 1 diabetes. Measurement of deamidated gliadin peptide antibodies of the IgG class, which has recently been introduced as an alternative test, is reported to have better sensitivity and specificity than measurement of IgG anti–tissue transglutaminase antibodies as a screening test for celiac disease in IgA-deficient patients. The sensitivity of serologic testing is markedly reduced in patients with a gluten-restricted diet; patients should therefore not restrict their diet before testing.
Table 1. Serum Tests for the Diagnosis of Celiac Disease.
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Teaching Topic
Alcoholism, Seizures, and Agitation
Case Records of the Massachusetts General Hospital
S.H. Nejad and Others
The differential diagnosis of altered mental status with seizures consists of two basic categories — intrinsic seizures (as in epilepsy) and acute symptomatic seizures (i.e., provoked seizures). The differential diagnosis of provoked seizures includes acute neurologic illness (e.g., stroke, traumatic brain injury, meningitis or encephalitis, or anoxia); acute medical illness, such as metabolic derangement (e.g., hypoglycemia, hyponatremia, or hypocalcemia); and intoxication or a withdrawal state.
Clinical Pearls
What is alcohol withdrawal delirium and what are the associated risk factors?
Alcohol withdrawal delirium is a clinical diagnosis and is characterized by the presence of hyperarousal, confusion, hallucinations, hypertension, tachycardia, fever, diaphoresis, and agitated behavior in a patient with an abrupt reduction in alcohol consumption or sudden abstinence from alcohol. Symptoms of withdrawal can differ widely among patients with active alcohol dependence and even among different withdrawal episodes in the same person. The strongest risk factor for the development of alcohol withdrawal delirium is previous episodes of alcohol withdrawal delirium; other risk factors include seizures related to alcohol withdrawal (past and recent), increased length of time since last drink, a long history of heavy drinking, an age older than 40 years, and an elevated ratio of aspartate aminotransferase to alanine aminotransferase (>1.5:1).
What is an alcohol withdrawal syndrome “type indicator”?
An alcohol withdrawal syndrome “type indicator” is a symptom-based assessment tool used to guide treatment decisions and monitor clinical response. The type indicator groups symptoms into categories. Type A symptoms are characterized by central nervous system excitation (e.g., anxiety and restlessness) caused by γ-aminobutyric acid (GABA) withdrawal. Type A symptoms are generally treated with GABA agonists, most commonly benzodiazepines. Type B symptoms (e.g., fever, diaphoresis, tremor, and elevated blood pressure and heart rate) are caused by adrenergic excess from activation of the locus coeruleus due to a hyperglutamatergic state. Before treating a patient for type B symptoms, other acute causes should be ruled out, such as volume depletion, blood loss, or pain. Type C symptoms (e.g., confusion, hallucinations, paranoia, and agitation) are caused by excess dopamine release through the mesolimbic tract and are treated with dopamine antagonists.
Morning Report Questions
Q. What is the most appropriate medication to use for the treatment of alcohol withdrawal?
A. Benzodiazepines are generally considered first-line treatment for alcohol withdrawal syndromes and for the prevention of seizures related to alcohol withdrawal. There is no consensus as to the best benzodiazepine to use; however, long-acting benzodiazepines with active metabolites, such as diazepam, may allow a smoother course of withdrawal, lower the chance of recurrent seizures, and provide greater efficacy in the prevention of delirium than other benzodiazepines. Benzodiazepines with an intermediate half-life, such as lorazepam, may have a safer profile in patients with hepatic dysfunction.
Q. What other medications may be useful in the context of refractory symptoms of alcohol withdrawal in an ICU setting?
A. Antipsychotic therapy is commonly used as an adjunct to benzodiazepines. In patients in whom treatment with these medications is not adequate, phenobarbital and propofol have both been used successfully to treat refractory symptoms. Dexmedetomidine is an α2-adrenergic agonist that has been approved for use as a sedative in critically ill patients. It has the advantage of alleviating symptoms of agitation while causing less respiratory depression than other agents and therefore can be given without mechanical ventilation. Dexmedetomidine has been used successfully to reduce symptoms of severe agitation in some patients with alcohol withdrawal. However, since this regimen has not been well studied, use of this drug should be undertaken with great care.
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