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What blood tests help diagnose celiac disease?
Histological confirmation of infiltrative lesions via small bowel biopsy is the gold standard for diagnosing celiac disease. Four serum antibody assays may serve as a first-step diagnostic tool to identify biopsy candidates: immunoglobulin A tissue transglutaminase (IgA tTG), IgA endomysial antibody (IgA EMA), IgA antigliadin antibody (IgA AGA), and IgG antigliadin antibody (IgG AGA). IgA tTG and IgA EMA offer the best diagnostic accuracy. Patients with selective IgA deficiency may have falsely negative IgA assays (strength of recommendation [SOR]: B, based on a systematic review, multiple small cross-sectional studies, and expert opinion).
The most reliable testing option is also the most cost-effective
Belinda Fu, MD
University of Washington, Seattle
When faced with a cryptic array of available serologic tests for celiac disease, and often pressed for time to look up which one is best, we are often quite tempted to simply check “Celiac Panel” on the lab order sheet and just order them all. However, the authors present us with an evidence-based rationale for limiting our lab testing to just one of the available serologic tests.
What a delight to find that the most reliable testing option is also the most cost-effective. At our university hospital, the billable cost of each serologic marker for celiac disease is approximately $50, and the entire panel—which includes IgA tTG, IgG tTG, IgA EMA, and IgA/G AGA—is $250. Rather than ordering the redundant panel (why include anti-AGA at all?), it is far better to start with IgA tTG or IgA EMA, and follow-up with IgG levels if necessary.
When ordering these tests, it is worth noting that some physicians recommend patients be on a gluten-containing diet for 2 to 4 weeks before serologic testing, to minimize the possibility of insufficient antibody titers.
Evidence summary
Celiac disease (also called celiac sprue, nontropical sprue, or gluten-sensitive enteropathy) is an autoimmune disorder classified by intestinal inflammation and malabsorption in response to dietary gluten—a storage protein component of wheat gliadins. Celiac disease patients—0.5% to 1.0% of the US population1—are often sensitive to other closely related grain proteins found in oats, barley, and rye.
Celiac disease’s classic histological finding is an infiltrative small intestine lesion characterized by villous flattening, crypt hyperplasia, and lymphocyte accumulation in the lamina propria.2 The American Gastroenterological Association’s (AGA) diagnostic criteria include confirmation of this abnormal mucosa and unequivocal improvement on repeat biopsy following a gluten-free diet.3 However, either clinical improvement or biopsy of dermatitis herpetiformis skin lesions (common occurrences in celiac disease) are often considered adequate for diagnosis without repeat intestinal biopsies.
Its reversible nature makes prompt diagnosis of celiac disease important. Three antibodies commonly appear in celiac disease patients: antibodies to tTG, antiendomysial antibodies, and antigliadin antibodies.4-6 AGA binds dietary gluten and EMA binds the enzyme tTG, which is found in connective tissue surrounding the smooth muscle cells in the intestinal wall.
The gluten-autoantibody interaction in the small intestinal lumen has IgA as its major component; IgG represents a longer-term immune response. Serum assays of the IgA and IgG forms of AGA and tTG are enzyme-linked immunosorbent assays (ELISA); EMA is measured by indirect immunofluorescence.5,6
In 2 studies of the diagnostic accuracy of IgA tTG, 95% to 98% of biopsy-proven celiac disease patients had positive tests, while only 5% to 6% of controls were positive.4,5 In a systematic review, there was no statistically significant difference between IgA EMA and IgA tTG—both had sensitivities greater than 90% and specificities greater than 95%.7 IgA AGA did not perform as well (sensitivity 80%–90%, specificity 85%–95%). The TABLE summarizes the diagnostic accuracy of the various tests.
TABLE
Diagnostic accuracy of serologic tests for celiac disease patients with normal IgA levels
| SEROLOGIC TEST | SN | SP | LR+ | LR– |
|---|---|---|---|---|
| IgA tTG | 95%–98% .95 | 94%–95% .94 | 16 | 0.05 |
| IgA EMA | >90% .91 | >95% .90 | 23 | 0.09 |
| IgA AGA | 80%–90% .85 | 85%–95% .90 | 8.5 | 0.17 |
| IgG tTG | 40% | 95% | 8 | 0.63 |
| IgG EMA | 40% | 95% | 8 | 0.63 |
| IgG AGA | 80% | 80% | 4 | 0.25 |
| Sn, sensitivity; Sp, specificity; LR+, likelihood ratio of a positive test result; LR–, likelihood ratio of a negative test result. | ||||
Two to 3% of patients with celiac disease have selective IgA deficiency.2 These patients often have falsely negative serum IgA assays (for EMA, tTG, and AGA), so IgG is a diagnostic alternative.8,9 In a cross-sectional study, 100% of 20 untreated celiac disease patients with IgA deficiency had positive IgG tests for tTG, AGA, and EMA despite negative IgA tests for the same antibodies.9 Eleven patients with celiac disease and no IgA deficiency all had positive tTG, AGA, and EMA tests, whether testing for the IgA or IgG forms.
Despite the performance of the IgG assays in this study, only IgG AGA has performed well in larger studies. In a systematic review, IgG tTG and IgG EMA had specificities of 95% but sensitivities of only 40%.7 IgG AGA has similar sensitivity to the IgA assay—approximately 80%—with a slightly lower specificity of 80%. The discrepancy in the sensitivity of IgG tTG and IgG EMA between studies occurs because of differing antibody levels with variations in dietary gluten.9,10 Therefore, testing for IgG tTG and IgG EMA should be reserved for patients with selective IgA deficiency.
Another notable limitation of using serologic markers to diagnose celiac disease is poor sensitivity in patients with mild disease.11 Diagnosis in these patients may be particularly challenging. Patients with karyotype abnormalities and those with diabetes are also more likely to have false-negative serologic tests.2
Recommendations from others
The AGA recommends using serologic markers to screen patients with either non-specific symptoms or medical conditions that increase the risk of celiac disease.3 Patients whose clinical profile causes a high index of suspicion and negative IgA serologic markers should be tested for selective IgA deficiency. The AGA recommends relying on small intestinal biopsy for the final diagnosis.
Both the AGA and the North American Pediatric Society for Pediatric Gastroenterology state that tissue transglutaminase and endomysial antibodies are the most useful serologic tests. Antigliadin antibody tests are considered inferior in terms of diagnostic accuracy.
1. National Institutes of Health Consensus Development Panel on Celiac Disease. Celiac Disease. Bethesda, Md: US Department of Health and Human Services; 2004.
2. Hill ID, Dirks MH, Liptak GS, et al. Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr. 2005;40:1-19.
3. American Gastroenterological Association medical position statement: celiac sprue Gastroenterology 2001;120:1522-1525.
4. Dieterich W, Lang E, Schopper H, et al. Autoantibodies to tissue transglutaminase as predictors of celiac disease. Gastroenterology 1998;115:1317-1321.
5. Sulkanen S, Halttunen T, Laurila K, et al. Tissue transglutaminase autoantibody enzyme-linked immunosorbent assay in detecting celiac disease. Gastroenterology 1998;115:1322-1328.
6. Rostami K, Kerchkhaert J, Tiemessen R, von Blomberg BM, Meijer JW, Mulder CJ. Sensitivity of antiendomysium and antigliadin antibodies in untreated celiac disease: disappointing in clinical practice. Am J Gastroenterol 1999;94:888-894.
7. Rostom A, Dube C, Cranney A, et al. The diagnostic accuracy of serologic tests for celiac disease: a systematic review. Gastroenterology 2005;128(Suppl 1):S38-46.
8. Cataldo F, Marino V, Bottaro G, Greco P, Ventura A. Celiac disease and selective immunoglobulin A deficiency. J Pediatr 1997;131:306-308.
9. Cataldo F, Lio D, Marino V, Picarelli A, Ventura A, Corazza GR. IgG(1) antiendomysium and IgG antitissue transglutaminase (anti-tTG) antibodies in coeliac patients with selective IgA deficiency. Gut 2000;47:366-369.
10. Pyle GG, Paaso B, Anderson BE, et al. Low-dose gluten challenge in celiac sprue: malabsorptive and antibody responses. Clin Gastroenterology Hepatol 2005;3:679-686.
11. Tursi A, Brandimarte G, Giorgetti GM. Prevalence of antitissue transglutaminase antibodies in different degrees of intestinal damage in celiac disease. J Clin Gastroenterol 2003;36:219-221.
Histological confirmation of infiltrative lesions via small bowel biopsy is the gold standard for diagnosing celiac disease. Four serum antibody assays may serve as a first-step diagnostic tool to identify biopsy candidates: immunoglobulin A tissue transglutaminase (IgA tTG), IgA endomysial antibody (IgA EMA), IgA antigliadin antibody (IgA AGA), and IgG antigliadin antibody (IgG AGA). IgA tTG and IgA EMA offer the best diagnostic accuracy. Patients with selective IgA deficiency may have falsely negative IgA assays (strength of recommendation [SOR]: B, based on a systematic review, multiple small cross-sectional studies, and expert opinion).
The most reliable testing option is also the most cost-effective
Belinda Fu, MD
University of Washington, Seattle
When faced with a cryptic array of available serologic tests for celiac disease, and often pressed for time to look up which one is best, we are often quite tempted to simply check “Celiac Panel” on the lab order sheet and just order them all. However, the authors present us with an evidence-based rationale for limiting our lab testing to just one of the available serologic tests.
What a delight to find that the most reliable testing option is also the most cost-effective. At our university hospital, the billable cost of each serologic marker for celiac disease is approximately $50, and the entire panel—which includes IgA tTG, IgG tTG, IgA EMA, and IgA/G AGA—is $250. Rather than ordering the redundant panel (why include anti-AGA at all?), it is far better to start with IgA tTG or IgA EMA, and follow-up with IgG levels if necessary.
When ordering these tests, it is worth noting that some physicians recommend patients be on a gluten-containing diet for 2 to 4 weeks before serologic testing, to minimize the possibility of insufficient antibody titers.
Evidence summary
Celiac disease (also called celiac sprue, nontropical sprue, or gluten-sensitive enteropathy) is an autoimmune disorder classified by intestinal inflammation and malabsorption in response to dietary gluten—a storage protein component of wheat gliadins. Celiac disease patients—0.5% to 1.0% of the US population1—are often sensitive to other closely related grain proteins found in oats, barley, and rye.
Celiac disease’s classic histological finding is an infiltrative small intestine lesion characterized by villous flattening, crypt hyperplasia, and lymphocyte accumulation in the lamina propria.2 The American Gastroenterological Association’s (AGA) diagnostic criteria include confirmation of this abnormal mucosa and unequivocal improvement on repeat biopsy following a gluten-free diet.3 However, either clinical improvement or biopsy of dermatitis herpetiformis skin lesions (common occurrences in celiac disease) are often considered adequate for diagnosis without repeat intestinal biopsies.
Its reversible nature makes prompt diagnosis of celiac disease important. Three antibodies commonly appear in celiac disease patients: antibodies to tTG, antiendomysial antibodies, and antigliadin antibodies.4-6 AGA binds dietary gluten and EMA binds the enzyme tTG, which is found in connective tissue surrounding the smooth muscle cells in the intestinal wall.
The gluten-autoantibody interaction in the small intestinal lumen has IgA as its major component; IgG represents a longer-term immune response. Serum assays of the IgA and IgG forms of AGA and tTG are enzyme-linked immunosorbent assays (ELISA); EMA is measured by indirect immunofluorescence.5,6
In 2 studies of the diagnostic accuracy of IgA tTG, 95% to 98% of biopsy-proven celiac disease patients had positive tests, while only 5% to 6% of controls were positive.4,5 In a systematic review, there was no statistically significant difference between IgA EMA and IgA tTG—both had sensitivities greater than 90% and specificities greater than 95%.7 IgA AGA did not perform as well (sensitivity 80%–90%, specificity 85%–95%). The TABLE summarizes the diagnostic accuracy of the various tests.
TABLE
Diagnostic accuracy of serologic tests for celiac disease patients with normal IgA levels
| SEROLOGIC TEST | SN | SP | LR+ | LR– |
|---|---|---|---|---|
| IgA tTG | 95%–98% .95 | 94%–95% .94 | 16 | 0.05 |
| IgA EMA | >90% .91 | >95% .90 | 23 | 0.09 |
| IgA AGA | 80%–90% .85 | 85%–95% .90 | 8.5 | 0.17 |
| IgG tTG | 40% | 95% | 8 | 0.63 |
| IgG EMA | 40% | 95% | 8 | 0.63 |
| IgG AGA | 80% | 80% | 4 | 0.25 |
| Sn, sensitivity; Sp, specificity; LR+, likelihood ratio of a positive test result; LR–, likelihood ratio of a negative test result. | ||||
Two to 3% of patients with celiac disease have selective IgA deficiency.2 These patients often have falsely negative serum IgA assays (for EMA, tTG, and AGA), so IgG is a diagnostic alternative.8,9 In a cross-sectional study, 100% of 20 untreated celiac disease patients with IgA deficiency had positive IgG tests for tTG, AGA, and EMA despite negative IgA tests for the same antibodies.9 Eleven patients with celiac disease and no IgA deficiency all had positive tTG, AGA, and EMA tests, whether testing for the IgA or IgG forms.
Despite the performance of the IgG assays in this study, only IgG AGA has performed well in larger studies. In a systematic review, IgG tTG and IgG EMA had specificities of 95% but sensitivities of only 40%.7 IgG AGA has similar sensitivity to the IgA assay—approximately 80%—with a slightly lower specificity of 80%. The discrepancy in the sensitivity of IgG tTG and IgG EMA between studies occurs because of differing antibody levels with variations in dietary gluten.9,10 Therefore, testing for IgG tTG and IgG EMA should be reserved for patients with selective IgA deficiency.
Another notable limitation of using serologic markers to diagnose celiac disease is poor sensitivity in patients with mild disease.11 Diagnosis in these patients may be particularly challenging. Patients with karyotype abnormalities and those with diabetes are also more likely to have false-negative serologic tests.2
Recommendations from others
The AGA recommends using serologic markers to screen patients with either non-specific symptoms or medical conditions that increase the risk of celiac disease.3 Patients whose clinical profile causes a high index of suspicion and negative IgA serologic markers should be tested for selective IgA deficiency. The AGA recommends relying on small intestinal biopsy for the final diagnosis.
Both the AGA and the North American Pediatric Society for Pediatric Gastroenterology state that tissue transglutaminase and endomysial antibodies are the most useful serologic tests. Antigliadin antibody tests are considered inferior in terms of diagnostic accuracy.
Histological confirmation of infiltrative lesions via small bowel biopsy is the gold standard for diagnosing celiac disease. Four serum antibody assays may serve as a first-step diagnostic tool to identify biopsy candidates: immunoglobulin A tissue transglutaminase (IgA tTG), IgA endomysial antibody (IgA EMA), IgA antigliadin antibody (IgA AGA), and IgG antigliadin antibody (IgG AGA). IgA tTG and IgA EMA offer the best diagnostic accuracy. Patients with selective IgA deficiency may have falsely negative IgA assays (strength of recommendation [SOR]: B, based on a systematic review, multiple small cross-sectional studies, and expert opinion).
The most reliable testing option is also the most cost-effective
Belinda Fu, MD
University of Washington, Seattle
When faced with a cryptic array of available serologic tests for celiac disease, and often pressed for time to look up which one is best, we are often quite tempted to simply check “Celiac Panel” on the lab order sheet and just order them all. However, the authors present us with an evidence-based rationale for limiting our lab testing to just one of the available serologic tests.
What a delight to find that the most reliable testing option is also the most cost-effective. At our university hospital, the billable cost of each serologic marker for celiac disease is approximately $50, and the entire panel—which includes IgA tTG, IgG tTG, IgA EMA, and IgA/G AGA—is $250. Rather than ordering the redundant panel (why include anti-AGA at all?), it is far better to start with IgA tTG or IgA EMA, and follow-up with IgG levels if necessary.
When ordering these tests, it is worth noting that some physicians recommend patients be on a gluten-containing diet for 2 to 4 weeks before serologic testing, to minimize the possibility of insufficient antibody titers.
Evidence summary
Celiac disease (also called celiac sprue, nontropical sprue, or gluten-sensitive enteropathy) is an autoimmune disorder classified by intestinal inflammation and malabsorption in response to dietary gluten—a storage protein component of wheat gliadins. Celiac disease patients—0.5% to 1.0% of the US population1—are often sensitive to other closely related grain proteins found in oats, barley, and rye.
Celiac disease’s classic histological finding is an infiltrative small intestine lesion characterized by villous flattening, crypt hyperplasia, and lymphocyte accumulation in the lamina propria.2 The American Gastroenterological Association’s (AGA) diagnostic criteria include confirmation of this abnormal mucosa and unequivocal improvement on repeat biopsy following a gluten-free diet.3 However, either clinical improvement or biopsy of dermatitis herpetiformis skin lesions (common occurrences in celiac disease) are often considered adequate for diagnosis without repeat intestinal biopsies.
Its reversible nature makes prompt diagnosis of celiac disease important. Three antibodies commonly appear in celiac disease patients: antibodies to tTG, antiendomysial antibodies, and antigliadin antibodies.4-6 AGA binds dietary gluten and EMA binds the enzyme tTG, which is found in connective tissue surrounding the smooth muscle cells in the intestinal wall.
The gluten-autoantibody interaction in the small intestinal lumen has IgA as its major component; IgG represents a longer-term immune response. Serum assays of the IgA and IgG forms of AGA and tTG are enzyme-linked immunosorbent assays (ELISA); EMA is measured by indirect immunofluorescence.5,6
In 2 studies of the diagnostic accuracy of IgA tTG, 95% to 98% of biopsy-proven celiac disease patients had positive tests, while only 5% to 6% of controls were positive.4,5 In a systematic review, there was no statistically significant difference between IgA EMA and IgA tTG—both had sensitivities greater than 90% and specificities greater than 95%.7 IgA AGA did not perform as well (sensitivity 80%–90%, specificity 85%–95%). The TABLE summarizes the diagnostic accuracy of the various tests.
TABLE
Diagnostic accuracy of serologic tests for celiac disease patients with normal IgA levels
| SEROLOGIC TEST | SN | SP | LR+ | LR– |
|---|---|---|---|---|
| IgA tTG | 95%–98% .95 | 94%–95% .94 | 16 | 0.05 |
| IgA EMA | >90% .91 | >95% .90 | 23 | 0.09 |
| IgA AGA | 80%–90% .85 | 85%–95% .90 | 8.5 | 0.17 |
| IgG tTG | 40% | 95% | 8 | 0.63 |
| IgG EMA | 40% | 95% | 8 | 0.63 |
| IgG AGA | 80% | 80% | 4 | 0.25 |
| Sn, sensitivity; Sp, specificity; LR+, likelihood ratio of a positive test result; LR–, likelihood ratio of a negative test result. | ||||
Two to 3% of patients with celiac disease have selective IgA deficiency.2 These patients often have falsely negative serum IgA assays (for EMA, tTG, and AGA), so IgG is a diagnostic alternative.8,9 In a cross-sectional study, 100% of 20 untreated celiac disease patients with IgA deficiency had positive IgG tests for tTG, AGA, and EMA despite negative IgA tests for the same antibodies.9 Eleven patients with celiac disease and no IgA deficiency all had positive tTG, AGA, and EMA tests, whether testing for the IgA or IgG forms.
Despite the performance of the IgG assays in this study, only IgG AGA has performed well in larger studies. In a systematic review, IgG tTG and IgG EMA had specificities of 95% but sensitivities of only 40%.7 IgG AGA has similar sensitivity to the IgA assay—approximately 80%—with a slightly lower specificity of 80%. The discrepancy in the sensitivity of IgG tTG and IgG EMA between studies occurs because of differing antibody levels with variations in dietary gluten.9,10 Therefore, testing for IgG tTG and IgG EMA should be reserved for patients with selective IgA deficiency.
Another notable limitation of using serologic markers to diagnose celiac disease is poor sensitivity in patients with mild disease.11 Diagnosis in these patients may be particularly challenging. Patients with karyotype abnormalities and those with diabetes are also more likely to have false-negative serologic tests.2
Recommendations from others
The AGA recommends using serologic markers to screen patients with either non-specific symptoms or medical conditions that increase the risk of celiac disease.3 Patients whose clinical profile causes a high index of suspicion and negative IgA serologic markers should be tested for selective IgA deficiency. The AGA recommends relying on small intestinal biopsy for the final diagnosis.
Both the AGA and the North American Pediatric Society for Pediatric Gastroenterology state that tissue transglutaminase and endomysial antibodies are the most useful serologic tests. Antigliadin antibody tests are considered inferior in terms of diagnostic accuracy.
1. National Institutes of Health Consensus Development Panel on Celiac Disease. Celiac Disease. Bethesda, Md: US Department of Health and Human Services; 2004.
2. Hill ID, Dirks MH, Liptak GS, et al. Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr. 2005;40:1-19.
3. American Gastroenterological Association medical position statement: celiac sprue Gastroenterology 2001;120:1522-1525.
4. Dieterich W, Lang E, Schopper H, et al. Autoantibodies to tissue transglutaminase as predictors of celiac disease. Gastroenterology 1998;115:1317-1321.
5. Sulkanen S, Halttunen T, Laurila K, et al. Tissue transglutaminase autoantibody enzyme-linked immunosorbent assay in detecting celiac disease. Gastroenterology 1998;115:1322-1328.
6. Rostami K, Kerchkhaert J, Tiemessen R, von Blomberg BM, Meijer JW, Mulder CJ. Sensitivity of antiendomysium and antigliadin antibodies in untreated celiac disease: disappointing in clinical practice. Am J Gastroenterol 1999;94:888-894.
7. Rostom A, Dube C, Cranney A, et al. The diagnostic accuracy of serologic tests for celiac disease: a systematic review. Gastroenterology 2005;128(Suppl 1):S38-46.
8. Cataldo F, Marino V, Bottaro G, Greco P, Ventura A. Celiac disease and selective immunoglobulin A deficiency. J Pediatr 1997;131:306-308.
9. Cataldo F, Lio D, Marino V, Picarelli A, Ventura A, Corazza GR. IgG(1) antiendomysium and IgG antitissue transglutaminase (anti-tTG) antibodies in coeliac patients with selective IgA deficiency. Gut 2000;47:366-369.
10. Pyle GG, Paaso B, Anderson BE, et al. Low-dose gluten challenge in celiac sprue: malabsorptive and antibody responses. Clin Gastroenterology Hepatol 2005;3:679-686.
11. Tursi A, Brandimarte G, Giorgetti GM. Prevalence of antitissue transglutaminase antibodies in different degrees of intestinal damage in celiac disease. J Clin Gastroenterol 2003;36:219-221.
1. National Institutes of Health Consensus Development Panel on Celiac Disease. Celiac Disease. Bethesda, Md: US Department of Health and Human Services; 2004.
2. Hill ID, Dirks MH, Liptak GS, et al. Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr. 2005;40:1-19.
3. American Gastroenterological Association medical position statement: celiac sprue Gastroenterology 2001;120:1522-1525.
4. Dieterich W, Lang E, Schopper H, et al. Autoantibodies to tissue transglutaminase as predictors of celiac disease. Gastroenterology 1998;115:1317-1321.
5. Sulkanen S, Halttunen T, Laurila K, et al. Tissue transglutaminase autoantibody enzyme-linked immunosorbent assay in detecting celiac disease. Gastroenterology 1998;115:1322-1328.
6. Rostami K, Kerchkhaert J, Tiemessen R, von Blomberg BM, Meijer JW, Mulder CJ. Sensitivity of antiendomysium and antigliadin antibodies in untreated celiac disease: disappointing in clinical practice. Am J Gastroenterol 1999;94:888-894.
7. Rostom A, Dube C, Cranney A, et al. The diagnostic accuracy of serologic tests for celiac disease: a systematic review. Gastroenterology 2005;128(Suppl 1):S38-46.
8. Cataldo F, Marino V, Bottaro G, Greco P, Ventura A. Celiac disease and selective immunoglobulin A deficiency. J Pediatr 1997;131:306-308.
9. Cataldo F, Lio D, Marino V, Picarelli A, Ventura A, Corazza GR. IgG(1) antiendomysium and IgG antitissue transglutaminase (anti-tTG) antibodies in coeliac patients with selective IgA deficiency. Gut 2000;47:366-369.
10. Pyle GG, Paaso B, Anderson BE, et al. Low-dose gluten challenge in celiac sprue: malabsorptive and antibody responses. Clin Gastroenterology Hepatol 2005;3:679-686.
11. Tursi A, Brandimarte G, Giorgetti GM. Prevalence of antitissue transglutaminase antibodies in different degrees of intestinal damage in celiac disease. J Clin Gastroenterol 2003;36:219-221.
Evidence-based answers from the Family Physicians Inquiries Network
Which vaccinations are indicated after splenectomy?
Immunization against encapsulated bacterial pathogens decreases the incidence of post-splenectomy sepsis. Pneumococcal, meningococcal, and Haemophilus influenzae (Hib) vaccinations are indicated for patients after splenectomy. These immunizations should be given at least 14 days before a scheduled splenectomy, or given after the fourteenth postoperative day (strength of recommendation [SOR]: A, based on systematic review of RCTs for the pneumococcal vaccine; SOR: B, based on systematic review of clinical trials for meningococcal and Hib vaccines).
Don’t forget those on prednisone, immunosuppressants, or undergoing chemotherapy
David Cravens, MD
University of Missouri–Columbia
This is an important and often overlooked component of preventive care—what to do with an asplenic patient? Individuals with functional asplenia from sickle-cell disease or other causes should also probably be included in this vaccination/revaccination schedule.
Another patient group that may require a more considered approach is those residing in long-term care facilities. Attention to immunizations may be even more important to a frail elder’s health in an institutional setting: vaccinations historically have been overlooked in this group, and certainly revaccination could be even more easily missed. I have occasionally discovered I was caring for an asplenic patient in the nursing home upon reviewing that patient’s medical history with a close family member or caregiver.
Additionally, elders on chronic immunosuppressant therapy or prednisone for rheumatoid arthritis or other autoimmune disorders, and those on chemotherapy for malignancies should also be revaccinated with pneumococcal vaccine approximately every 5 years.
Evidence summary
Asplenic individuals are known to be at an elevated risk for infection with encapsulated bacteria. The lifetime risk of post-splenectomy sepsis is estimated to be approximately 1% to 2%. The overwhelming majority of these cases are caused by Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitides.1-4
In 2 recent RCTs, the 23-valent pneumococcal polysaccharide vaccine was tested on patients 1, 7, 14, and 28 days after splenectomy.1,2 The studies demonstrated that the immunogenicity of the vaccine was best when given at or after day 14 after the operation. In both studies, patients immunized at day 14 had immunoglobulin G (IgG) antibody levels approaching those of control subjects with intact spleens. There were no differences in antibody levels among those patients immunized at day 14 compared with those immunized on day 28. However, those subjects immunized on days 1 and 7 had significant lower antibody levels than the control subjects or those immunized on day 14.
In another study, 130 asplenic individuals were compared with 48 age-matched controls after receiving a meningococcal vaccine.3 The majority (93%) achieved bactericidal immunoglobulin levels following immunization. This study demonstrated the need to have antibody titers drawn to ensure immunization response, as 20% of the subjects required a second dose of vaccine to achieve adequate levels. No clear evidence supports the timing of the meningococcal vaccine post-splenectomy.
Two recent studies look at the immunogenicity of the Hib for asplenic patients. The first study demonstrated increased antibody titers to Hib at 2, 6, 12, 24, and 36 months after immunization.4 Fifty of the 57 patients in the study (88%) maintained adequate antibody titers 3 years after immunization. No symptomatic infections were observed during the 3-year study period. In a study of 561 Danes, those vaccinated within 14 days of splenectomy (before or after) had a significantly higher need for revaccination than those who were vaccinated more than 14 days before or after surgery.5
Recommendations from others
The most common infections occurring among asplenic patients are due to encapsulated organisms. The incidence is 10 to 50 times higher than in the general population.
The Advisory Committee on Immunization Practices for the Centers for Disease Control and Prevention (CDC) and the Society of Surgery for the Alimentary Tract recommends all patients that undergo splenectomy have the pneumococcal polysaccharide vaccine.6-7 In addition, this organization also recommends that all asplenic patients receive meningococcal vaccination and be considered for the Hib vaccine. Both groups recommend that these vaccinations occur at the same time as the pneumococcal vaccine.6-8
The CDC also recommends annual influenza vaccine in addition to the pneumococcal, meningococcal, and Hib vaccines, because secondary bacterial infections can lead to severe disease in this patient population. Boosters are recommended for all the bacterial vaccines every 5 years for asplenic patients.
1. Shatz DV, Schinsky MF, Pais LB, Romero-Steiner S, Kirton OC, Carlone GM. Immune responses of splenectomized trauma patients to the 23-valent pneumococcal polysaccharide vaccine at 1 versus 7 versus 14 days after Splenectomy. J Trauma 1998;44:765-766.
2. Shatz DV, Romero-Steiner S, Elie CM, Holder PF, Carlone GM. Antibody responses in postsplenectomy trauma patients receiving the 23-valent pneumococcal polysaccharide vaccine at 14 versus 28 days postoperatively. J Trauma 2002;53:1037-1042.
3. Balmer P, Falconer M, McDonald P, et al. Immune response to meningococcal serogroup C conjugate vaccine in asplenic individuals. Infect Immun 2004;72:332-337.
4. Cimaz R, Mensi C, D’Angelo E, et al. Safety and immunogenicity of a conjugate vaccine against haemophilus influenzae type b in splenectomized and nonsplenectomized patients with Cooley anemia. J Infect Disease 2001;183:1819-1821.
5. Konradsen HB, Rasmussen C, Ejstrud P, Hansen JB. Antibody levels against streptococcus pneumoniae and haemophilus influenzae type B in a population of splenectomized individuals with varying vaccination status. Epidemiol Infect 1997;119:167-174.
6. Recommended Adult Immunization Schedule United States October 2004–September 2005. The Advisory Committee on Immunizations Practices. Department of Health and Human Services. Centers for Disease Control and Prevention. Available at: www.cdc.gov/nip/recs/adult-schedule.pdf. Accessed on July 6, 2006.
7. National Guideline Clearinghouse Surgical Treatment of Disease and Injuries of the Spleen. Society for Surgery of the Alimentary Tract (SSAT). 2004 Feb. Available at: www.guideline.gov/summary/summary.aspx?view_id=1& doc_id=5698. Accessed on July 6, 2006.
8. Davies JM, Barnes R, Milligan D. Update of guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen. Clin Med 2002;2:440-444.
Immunization against encapsulated bacterial pathogens decreases the incidence of post-splenectomy sepsis. Pneumococcal, meningococcal, and Haemophilus influenzae (Hib) vaccinations are indicated for patients after splenectomy. These immunizations should be given at least 14 days before a scheduled splenectomy, or given after the fourteenth postoperative day (strength of recommendation [SOR]: A, based on systematic review of RCTs for the pneumococcal vaccine; SOR: B, based on systematic review of clinical trials for meningococcal and Hib vaccines).
Don’t forget those on prednisone, immunosuppressants, or undergoing chemotherapy
David Cravens, MD
University of Missouri–Columbia
This is an important and often overlooked component of preventive care—what to do with an asplenic patient? Individuals with functional asplenia from sickle-cell disease or other causes should also probably be included in this vaccination/revaccination schedule.
Another patient group that may require a more considered approach is those residing in long-term care facilities. Attention to immunizations may be even more important to a frail elder’s health in an institutional setting: vaccinations historically have been overlooked in this group, and certainly revaccination could be even more easily missed. I have occasionally discovered I was caring for an asplenic patient in the nursing home upon reviewing that patient’s medical history with a close family member or caregiver.
Additionally, elders on chronic immunosuppressant therapy or prednisone for rheumatoid arthritis or other autoimmune disorders, and those on chemotherapy for malignancies should also be revaccinated with pneumococcal vaccine approximately every 5 years.
Evidence summary
Asplenic individuals are known to be at an elevated risk for infection with encapsulated bacteria. The lifetime risk of post-splenectomy sepsis is estimated to be approximately 1% to 2%. The overwhelming majority of these cases are caused by Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitides.1-4
In 2 recent RCTs, the 23-valent pneumococcal polysaccharide vaccine was tested on patients 1, 7, 14, and 28 days after splenectomy.1,2 The studies demonstrated that the immunogenicity of the vaccine was best when given at or after day 14 after the operation. In both studies, patients immunized at day 14 had immunoglobulin G (IgG) antibody levels approaching those of control subjects with intact spleens. There were no differences in antibody levels among those patients immunized at day 14 compared with those immunized on day 28. However, those subjects immunized on days 1 and 7 had significant lower antibody levels than the control subjects or those immunized on day 14.
In another study, 130 asplenic individuals were compared with 48 age-matched controls after receiving a meningococcal vaccine.3 The majority (93%) achieved bactericidal immunoglobulin levels following immunization. This study demonstrated the need to have antibody titers drawn to ensure immunization response, as 20% of the subjects required a second dose of vaccine to achieve adequate levels. No clear evidence supports the timing of the meningococcal vaccine post-splenectomy.
Two recent studies look at the immunogenicity of the Hib for asplenic patients. The first study demonstrated increased antibody titers to Hib at 2, 6, 12, 24, and 36 months after immunization.4 Fifty of the 57 patients in the study (88%) maintained adequate antibody titers 3 years after immunization. No symptomatic infections were observed during the 3-year study period. In a study of 561 Danes, those vaccinated within 14 days of splenectomy (before or after) had a significantly higher need for revaccination than those who were vaccinated more than 14 days before or after surgery.5
Recommendations from others
The most common infections occurring among asplenic patients are due to encapsulated organisms. The incidence is 10 to 50 times higher than in the general population.
The Advisory Committee on Immunization Practices for the Centers for Disease Control and Prevention (CDC) and the Society of Surgery for the Alimentary Tract recommends all patients that undergo splenectomy have the pneumococcal polysaccharide vaccine.6-7 In addition, this organization also recommends that all asplenic patients receive meningococcal vaccination and be considered for the Hib vaccine. Both groups recommend that these vaccinations occur at the same time as the pneumococcal vaccine.6-8
The CDC also recommends annual influenza vaccine in addition to the pneumococcal, meningococcal, and Hib vaccines, because secondary bacterial infections can lead to severe disease in this patient population. Boosters are recommended for all the bacterial vaccines every 5 years for asplenic patients.
Immunization against encapsulated bacterial pathogens decreases the incidence of post-splenectomy sepsis. Pneumococcal, meningococcal, and Haemophilus influenzae (Hib) vaccinations are indicated for patients after splenectomy. These immunizations should be given at least 14 days before a scheduled splenectomy, or given after the fourteenth postoperative day (strength of recommendation [SOR]: A, based on systematic review of RCTs for the pneumococcal vaccine; SOR: B, based on systematic review of clinical trials for meningococcal and Hib vaccines).
Don’t forget those on prednisone, immunosuppressants, or undergoing chemotherapy
David Cravens, MD
University of Missouri–Columbia
This is an important and often overlooked component of preventive care—what to do with an asplenic patient? Individuals with functional asplenia from sickle-cell disease or other causes should also probably be included in this vaccination/revaccination schedule.
Another patient group that may require a more considered approach is those residing in long-term care facilities. Attention to immunizations may be even more important to a frail elder’s health in an institutional setting: vaccinations historically have been overlooked in this group, and certainly revaccination could be even more easily missed. I have occasionally discovered I was caring for an asplenic patient in the nursing home upon reviewing that patient’s medical history with a close family member or caregiver.
Additionally, elders on chronic immunosuppressant therapy or prednisone for rheumatoid arthritis or other autoimmune disorders, and those on chemotherapy for malignancies should also be revaccinated with pneumococcal vaccine approximately every 5 years.
Evidence summary
Asplenic individuals are known to be at an elevated risk for infection with encapsulated bacteria. The lifetime risk of post-splenectomy sepsis is estimated to be approximately 1% to 2%. The overwhelming majority of these cases are caused by Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitides.1-4
In 2 recent RCTs, the 23-valent pneumococcal polysaccharide vaccine was tested on patients 1, 7, 14, and 28 days after splenectomy.1,2 The studies demonstrated that the immunogenicity of the vaccine was best when given at or after day 14 after the operation. In both studies, patients immunized at day 14 had immunoglobulin G (IgG) antibody levels approaching those of control subjects with intact spleens. There were no differences in antibody levels among those patients immunized at day 14 compared with those immunized on day 28. However, those subjects immunized on days 1 and 7 had significant lower antibody levels than the control subjects or those immunized on day 14.
In another study, 130 asplenic individuals were compared with 48 age-matched controls after receiving a meningococcal vaccine.3 The majority (93%) achieved bactericidal immunoglobulin levels following immunization. This study demonstrated the need to have antibody titers drawn to ensure immunization response, as 20% of the subjects required a second dose of vaccine to achieve adequate levels. No clear evidence supports the timing of the meningococcal vaccine post-splenectomy.
Two recent studies look at the immunogenicity of the Hib for asplenic patients. The first study demonstrated increased antibody titers to Hib at 2, 6, 12, 24, and 36 months after immunization.4 Fifty of the 57 patients in the study (88%) maintained adequate antibody titers 3 years after immunization. No symptomatic infections were observed during the 3-year study period. In a study of 561 Danes, those vaccinated within 14 days of splenectomy (before or after) had a significantly higher need for revaccination than those who were vaccinated more than 14 days before or after surgery.5
Recommendations from others
The most common infections occurring among asplenic patients are due to encapsulated organisms. The incidence is 10 to 50 times higher than in the general population.
The Advisory Committee on Immunization Practices for the Centers for Disease Control and Prevention (CDC) and the Society of Surgery for the Alimentary Tract recommends all patients that undergo splenectomy have the pneumococcal polysaccharide vaccine.6-7 In addition, this organization also recommends that all asplenic patients receive meningococcal vaccination and be considered for the Hib vaccine. Both groups recommend that these vaccinations occur at the same time as the pneumococcal vaccine.6-8
The CDC also recommends annual influenza vaccine in addition to the pneumococcal, meningococcal, and Hib vaccines, because secondary bacterial infections can lead to severe disease in this patient population. Boosters are recommended for all the bacterial vaccines every 5 years for asplenic patients.
1. Shatz DV, Schinsky MF, Pais LB, Romero-Steiner S, Kirton OC, Carlone GM. Immune responses of splenectomized trauma patients to the 23-valent pneumococcal polysaccharide vaccine at 1 versus 7 versus 14 days after Splenectomy. J Trauma 1998;44:765-766.
2. Shatz DV, Romero-Steiner S, Elie CM, Holder PF, Carlone GM. Antibody responses in postsplenectomy trauma patients receiving the 23-valent pneumococcal polysaccharide vaccine at 14 versus 28 days postoperatively. J Trauma 2002;53:1037-1042.
3. Balmer P, Falconer M, McDonald P, et al. Immune response to meningococcal serogroup C conjugate vaccine in asplenic individuals. Infect Immun 2004;72:332-337.
4. Cimaz R, Mensi C, D’Angelo E, et al. Safety and immunogenicity of a conjugate vaccine against haemophilus influenzae type b in splenectomized and nonsplenectomized patients with Cooley anemia. J Infect Disease 2001;183:1819-1821.
5. Konradsen HB, Rasmussen C, Ejstrud P, Hansen JB. Antibody levels against streptococcus pneumoniae and haemophilus influenzae type B in a population of splenectomized individuals with varying vaccination status. Epidemiol Infect 1997;119:167-174.
6. Recommended Adult Immunization Schedule United States October 2004–September 2005. The Advisory Committee on Immunizations Practices. Department of Health and Human Services. Centers for Disease Control and Prevention. Available at: www.cdc.gov/nip/recs/adult-schedule.pdf. Accessed on July 6, 2006.
7. National Guideline Clearinghouse Surgical Treatment of Disease and Injuries of the Spleen. Society for Surgery of the Alimentary Tract (SSAT). 2004 Feb. Available at: www.guideline.gov/summary/summary.aspx?view_id=1& doc_id=5698. Accessed on July 6, 2006.
8. Davies JM, Barnes R, Milligan D. Update of guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen. Clin Med 2002;2:440-444.
1. Shatz DV, Schinsky MF, Pais LB, Romero-Steiner S, Kirton OC, Carlone GM. Immune responses of splenectomized trauma patients to the 23-valent pneumococcal polysaccharide vaccine at 1 versus 7 versus 14 days after Splenectomy. J Trauma 1998;44:765-766.
2. Shatz DV, Romero-Steiner S, Elie CM, Holder PF, Carlone GM. Antibody responses in postsplenectomy trauma patients receiving the 23-valent pneumococcal polysaccharide vaccine at 14 versus 28 days postoperatively. J Trauma 2002;53:1037-1042.
3. Balmer P, Falconer M, McDonald P, et al. Immune response to meningococcal serogroup C conjugate vaccine in asplenic individuals. Infect Immun 2004;72:332-337.
4. Cimaz R, Mensi C, D’Angelo E, et al. Safety and immunogenicity of a conjugate vaccine against haemophilus influenzae type b in splenectomized and nonsplenectomized patients with Cooley anemia. J Infect Disease 2001;183:1819-1821.
5. Konradsen HB, Rasmussen C, Ejstrud P, Hansen JB. Antibody levels against streptococcus pneumoniae and haemophilus influenzae type B in a population of splenectomized individuals with varying vaccination status. Epidemiol Infect 1997;119:167-174.
6. Recommended Adult Immunization Schedule United States October 2004–September 2005. The Advisory Committee on Immunizations Practices. Department of Health and Human Services. Centers for Disease Control and Prevention. Available at: www.cdc.gov/nip/recs/adult-schedule.pdf. Accessed on July 6, 2006.
7. National Guideline Clearinghouse Surgical Treatment of Disease and Injuries of the Spleen. Society for Surgery of the Alimentary Tract (SSAT). 2004 Feb. Available at: www.guideline.gov/summary/summary.aspx?view_id=1& doc_id=5698. Accessed on July 6, 2006.
8. Davies JM, Barnes R, Milligan D. Update of guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen. Clin Med 2002;2:440-444.
Evidence-based answers from the Family Physicians Inquiries Network