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Published in: Digestive Diseases and Sciences 5/2019

01-05-2019 | Original Article

Epidemiology of Whipple’s Disease in the USA Between 2012 and 2017: A Population-Based National Study

Authors: Jamie Ann Elchert, Emad Mansoor, Mohannad Abou-Saleh, Gregory S. Cooper

Published in: Digestive Diseases and Sciences | Issue 5/2019

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Abstract

Objective

Prior studies on the epidemiology of Whipple’s disease are limited by small sample size and case series design. We sought to characterize the epidemiology of Whipple’s disease in the USA utilizing a large population-based database.

Methods

We queried a commercial database (Explorys Inc, Cleveland, OH), an aggregate of electronic health record data from 26 major integrated healthcare systems in the USA. We identified a cohort of patients with a diagnosis of Whipple’s disease based on systemized nomenclature of medical terminology (SNOMED CT) codes. We calculated the overall and age-, race-, ethnicity, and gender-based prevalence of Whipple’s disease and prevalence of associated diagnoses using univariate analysis.

Results

A total of 35,838,070 individuals were active in the database between November 2012 and November 2017. Of these, 350 individuals had a SNOMED CT diagnosis of Whipple’s disease, with an overall prevalence of 9.8 cases per 1 million. There was no difference in prevalence based on sex. However, prevalence of Whipple’s disease was higher in Caucasians, non-Hispanics, and individuals > 65 years old. Individuals with a diagnosis of Whipple’s disease were more likely to have associated diagnoses/findings of arthritis, CNS disease, endocarditis, diabetes, malignancy, dementia, vitamin D deficiency, iron deficiency, chemotherapy, weight loss, abdominal pain, and lymphadenopathy.

Conclusions

To our knowledge, this is the largest study to date examining the epidemiology of Whipple’s disease. In this large population-based study, the overall prevalence of Whipple’s disease in the USA is 9.8 cases per 1 million people. It affects men and women at similar rates and is more common in Caucasians, non-Hispanics, and people > 65 years old.
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Literature
1.
go back to reference Durand DV, Lecomte C, Cathebras P, Rousset H, Godeau P. Whipple disease. Clinical review of 52 cases. The SNFMI research group on whipple disease. Societe nationale francaise de medecine interne. Medicine. 1997;76:170–184.CrossRefPubMed Durand DV, Lecomte C, Cathebras P, Rousset H, Godeau P. Whipple disease. Clinical review of 52 cases. The SNFMI research group on whipple disease. Societe nationale francaise de medecine interne. Medicine. 1997;76:170–184.CrossRefPubMed
2.
go back to reference Schoniger-Hekele M, Petermann D, Weber B, Muller C. Tropheryma whipplei in the environment: Survey of sewage plant influxes and sewage plant workers. Applied and Environmental Microbiology. 2007;73:2033–2035.CrossRefPubMedPubMedCentral Schoniger-Hekele M, Petermann D, Weber B, Muller C. Tropheryma whipplei in the environment: Survey of sewage plant influxes and sewage plant workers. Applied and Environmental Microbiology. 2007;73:2033–2035.CrossRefPubMedPubMedCentral
3.
go back to reference Fenollar F, Trani M, Davoust B, et al. Prevalence of asymptomatic tropheryma whipplei carriage among humans and nonhuman primates. The Journal of Infectious Diseases. 2008;197:880–887.CrossRefPubMed Fenollar F, Trani M, Davoust B, et al. Prevalence of asymptomatic tropheryma whipplei carriage among humans and nonhuman primates. The Journal of Infectious Diseases. 2008;197:880–887.CrossRefPubMed
4.
go back to reference Ehrbar HU, Bauerfeind P, Dutly F, Koelz HR, Altwegg M. PCR-positive tests for tropheryma whippelii in patients without whipple’s disease. Lancet (London, England). 1999;353:2214.CrossRef Ehrbar HU, Bauerfeind P, Dutly F, Koelz HR, Altwegg M. PCR-positive tests for tropheryma whippelii in patients without whipple’s disease. Lancet (London, England). 1999;353:2214.CrossRef
5.
go back to reference Street S, Donoghue HD, Neild GH. Tropheryma whippelii DNA in saliva of healthy people. Lancet (London, England). 1999;354:1178–1179.CrossRef Street S, Donoghue HD, Neild GH. Tropheryma whippelii DNA in saliva of healthy people. Lancet (London, England). 1999;354:1178–1179.CrossRef
6.
go back to reference Zinkernagel AS, Gmur R, Fenner L, Schaffner A, Schoedon G, Schneemann M. Marginal and subgingival plaque–a natural habitat of tropheryma whipplei? Infection. 2003;31:86–91.CrossRefPubMed Zinkernagel AS, Gmur R, Fenner L, Schaffner A, Schoedon G, Schneemann M. Marginal and subgingival plaque–a natural habitat of tropheryma whipplei? Infection. 2003;31:86–91.CrossRefPubMed
8.
go back to reference Amsler L, Bauernfeind P, Nigg C, Maibach RC, Steffen R, Altwegg M. Prevalence of tropheryma whipplei DNA in patients with various gastrointestinal diseases and in healthy controls. Infection. 2003;31:81–85.CrossRefPubMed Amsler L, Bauernfeind P, Nigg C, Maibach RC, Steffen R, Altwegg M. Prevalence of tropheryma whipplei DNA in patients with various gastrointestinal diseases and in healthy controls. Infection. 2003;31:81–85.CrossRefPubMed
9.
go back to reference Marth T, Roux M, von Herbay A, Meuer SC, Feurle GE. Persistent reduction of complement receptor 3 alpha-chain expressing mononuclear blood cells and transient inhibitory serum factors in whipple’s disease. Clinical Immunology and Immunopathology. 1994;72:217–226.CrossRefPubMed Marth T, Roux M, von Herbay A, Meuer SC, Feurle GE. Persistent reduction of complement receptor 3 alpha-chain expressing mononuclear blood cells and transient inhibitory serum factors in whipple’s disease. Clinical Immunology and Immunopathology. 1994;72:217–226.CrossRefPubMed
10.
go back to reference Ectors N, Geboes K, De Vos R, et al. Whipple’s disease: A histological, immunocytochemical and electronmicroscopic study of the immune response in the small intestinal mucosa. Histopathology. 1992;21:1–12.CrossRefPubMed Ectors N, Geboes K, De Vos R, et al. Whipple’s disease: A histological, immunocytochemical and electronmicroscopic study of the immune response in the small intestinal mucosa. Histopathology. 1992;21:1–12.CrossRefPubMed
11.
go back to reference Marth T, Neurath M, Cuccherini BA, Strober W. Defects of monocyte interleukin 12 production and humoral immunity in whipple’s disease. Gastroenterology. 1997;113:442–448.CrossRefPubMed Marth T, Neurath M, Cuccherini BA, Strober W. Defects of monocyte interleukin 12 production and humoral immunity in whipple’s disease. Gastroenterology. 1997;113:442–448.CrossRefPubMed
12.
go back to reference Marth T, Kleen N, Stallmach A, et al. Dysregulated peripheral and mucosal Th1/Th2 response in whipple’s disease. Gastroenterology. 2002;123:1468–1477.CrossRefPubMed Marth T, Kleen N, Stallmach A, et al. Dysregulated peripheral and mucosal Th1/Th2 response in whipple’s disease. Gastroenterology. 2002;123:1468–1477.CrossRefPubMed
13.
go back to reference Schneider T, Stallmach A, von Herbay A, Marth T, Strober W, Zeitz M. Treatment of refractory whipple disease with interferon-gamma. Annals of Internal Medicine. 1998;129:875–877.CrossRefPubMed Schneider T, Stallmach A, von Herbay A, Marth T, Strober W, Zeitz M. Treatment of refractory whipple disease with interferon-gamma. Annals of Internal Medicine. 1998;129:875–877.CrossRefPubMed
14.
go back to reference Ectors NL, Geboes KJ, De Vos RM, et al. Whipple’s disease: A histological, immunocytochemical, and electron microscopic study of the small intestinal epithelium. The Journal of Pathology. 1994;172:73–79.CrossRefPubMed Ectors NL, Geboes KJ, De Vos RM, et al. Whipple’s disease: A histological, immunocytochemical, and electron microscopic study of the small intestinal epithelium. The Journal of Pathology. 1994;172:73–79.CrossRefPubMed
15.
go back to reference Bai JC, Sen L, Diez R, et al. Impaired monocyte function in patients successfully treated for whipple’s disease. Acta Gastroenterologica Latinoamericana. 1996;26:85–89.PubMed Bai JC, Sen L, Diez R, et al. Impaired monocyte function in patients successfully treated for whipple’s disease. Acta Gastroenterologica Latinoamericana. 1996;26:85–89.PubMed
16.
go back to reference Moos V, Schmidt C, Geelhaar A, et al. Impaired immune functions of monocytes and macrophages in whipple’s disease. Gastroenterology. 2010;138:210–220.CrossRefPubMed Moos V, Schmidt C, Geelhaar A, et al. Impaired immune functions of monocytes and macrophages in whipple’s disease. Gastroenterology. 2010;138:210–220.CrossRefPubMed
17.
go back to reference Maiwald M, von Herbay A, Persing DH, et al. Tropheryma whippelii DNA is rare in the intestinal mucosa of patients without other evidence of whipple disease. Annals of Internal Medicine. 2001;134:115–119.CrossRefPubMed Maiwald M, von Herbay A, Persing DH, et al. Tropheryma whippelii DNA is rare in the intestinal mucosa of patients without other evidence of whipple disease. Annals of Internal Medicine. 2001;134:115–119.CrossRefPubMed
18.
go back to reference Schinnerling K, Moos V, Geelhaar A, et al. Regulatory T cells in patients with whipple’s disease. Journal of Immunology (Baltimore, Md.: 1950). 2011;187:4061–4067.CrossRef Schinnerling K, Moos V, Geelhaar A, et al. Regulatory T cells in patients with whipple’s disease. Journal of Immunology (Baltimore, Md.: 1950). 2011;187:4061–4067.CrossRef
19.
go back to reference Schinnerling K, Geelhaar-Karsch A, Allers K, et al. Role of dendritic cells in the pathogenesis of whipple’s disease. Infection and Immunity. 2015;83:482–491.CrossRefPubMedPubMedCentral Schinnerling K, Geelhaar-Karsch A, Allers K, et al. Role of dendritic cells in the pathogenesis of whipple’s disease. Infection and Immunity. 2015;83:482–491.CrossRefPubMedPubMedCentral
20.
go back to reference Desnues B, Lepidi H, Raoult D, Mege JL. Whipple disease: Intestinal infiltrating cells exhibit a transcriptional pattern of M2/alternatively activated macrophages. The Journal of Infectious Diseases. 2005;192:1642–1646.CrossRefPubMed Desnues B, Lepidi H, Raoult D, Mege JL. Whipple disease: Intestinal infiltrating cells exhibit a transcriptional pattern of M2/alternatively activated macrophages. The Journal of Infectious Diseases. 2005;192:1642–1646.CrossRefPubMed
21.
go back to reference Desnues B, Ihrig M, Raoult D, Mege JL. Whipple’s disease: A macrophage disease. Clinical and Vaccine Immunology: CVI. 2006;13:170–178.CrossRefPubMed Desnues B, Ihrig M, Raoult D, Mege JL. Whipple’s disease: A macrophage disease. Clinical and Vaccine Immunology: CVI. 2006;13:170–178.CrossRefPubMed
22.
go back to reference Desnues B, Raoult D, Mege JL. IL-16 is critical for tropheryma whipplei replication in whipple’s disease. Journal of Immunology (Baltimore, Md.: 1950). 2005;175:4575–4582.CrossRef Desnues B, Raoult D, Mege JL. IL-16 is critical for tropheryma whipplei replication in whipple’s disease. Journal of Immunology (Baltimore, Md.: 1950). 2005;175:4575–4582.CrossRef
23.
go back to reference Moos V, Kunkel D, Marth T, et al. Reduced peripheral and mucosal tropheryma whipplei-specific Th1 response in patients with whipple’s disease. Journal of Immunology (Baltimore, Md.: 1950). 2006;177:2015–2022.CrossRef Moos V, Kunkel D, Marth T, et al. Reduced peripheral and mucosal tropheryma whipplei-specific Th1 response in patients with whipple’s disease. Journal of Immunology (Baltimore, Md.: 1950). 2006;177:2015–2022.CrossRef
24.
go back to reference Trotta L, Weigt K, Schinnerling K, et al. (2017). Peripheral T-cell reactivity to heat shock protein 70 and its cofactor GrpE from tropheryma whipplei is reduced in patients with classical whipple’s disease. Infection and Immunity, 85(8), https://doi.org/10.1128/iai.00363-17. Print 2017 Aug. Trotta L, Weigt K, Schinnerling K, et al. (2017). Peripheral T-cell reactivity to heat shock protein 70 and its cofactor GrpE from tropheryma whipplei is reduced in patients with classical whipple’s disease. Infection and Immunity, 85(8), https://​doi.​org/​10.​1128/​iai.​00363-17. Print 2017 Aug.
25.
go back to reference Schneider T, Moos V, Loddenkemper C, Marth T, Fenollar F, Raoult D. Whipple’s disease: New aspects of pathogenesis and treatment. The Lancet. Infectious Diseases. 2008;8:179–190.CrossRefPubMed Schneider T, Moos V, Loddenkemper C, Marth T, Fenollar F, Raoult D. Whipple’s disease: New aspects of pathogenesis and treatment. The Lancet. Infectious Diseases. 2008;8:179–190.CrossRefPubMed
26.
go back to reference Fenollar F, Puechal X, Raoult D. Whipple’s disease. The New England Journal of Medicine. 2007;356:55–66.CrossRefPubMed Fenollar F, Puechal X, Raoult D. Whipple’s disease. The New England Journal of Medicine. 2007;356:55–66.CrossRefPubMed
27.
go back to reference Dobbins WO III. Whipple’s Disease. Springfield: Charles C Thomas; 1987. Dobbins WO III. Whipple’s Disease. Springfield: Charles C Thomas; 1987.
28.
go back to reference von Herbay A, Otto HF, Stolte M, et al. Epidemiology of whipple’s disease in germany. Analysis of 110 patients diagnosed in 1965–95. Scandinavian Journal of Gastroenterology. 1997;32:52–57.CrossRef von Herbay A, Otto HF, Stolte M, et al. Epidemiology of whipple’s disease in germany. Analysis of 110 patients diagnosed in 1965–95. Scandinavian Journal of Gastroenterology. 1997;32:52–57.CrossRef
29.
go back to reference Marth T. Systematic review: Whipple’s disease (tropheryma whipplei infection) and its unmasking by tumour necrosis factor inhibitors. Alimentary Pharmacology and Therapeutics. 2015;41:709–724.CrossRefPubMed Marth T. Systematic review: Whipple’s disease (tropheryma whipplei infection) and its unmasking by tumour necrosis factor inhibitors. Alimentary Pharmacology and Therapeutics. 2015;41:709–724.CrossRefPubMed
30.
go back to reference Lagier JC, Lepidi H, Raoult D, Fenollar F. Systemic tropheryma whipplei: Clinical presentation of 142 patients with infections diagnosed or confirmed in a reference center. Medicine. 2010;89:337–345.CrossRefPubMed Lagier JC, Lepidi H, Raoult D, Fenollar F. Systemic tropheryma whipplei: Clinical presentation of 142 patients with infections diagnosed or confirmed in a reference center. Medicine. 2010;89:337–345.CrossRefPubMed
31.
go back to reference Moos V, Schneider T. Changing paradigms in whipple’s disease and infection with tropheryma whipplei. European Journal of Clinical Microbiology & Infectious Diseases: Official Publication of the European Society of Clinical Microbiology. 2011;30:1151–1158.CrossRef Moos V, Schneider T. Changing paradigms in whipple’s disease and infection with tropheryma whipplei. European Journal of Clinical Microbiology & Infectious Diseases: Official Publication of the European Society of Clinical Microbiology. 2011;30:1151–1158.CrossRef
32.
go back to reference Gunther U, Moos V, Offenmuller G, et al. Gastrointestinal diagnosis of classical whipple disease: Clinical, endoscopic, and histopathologic features in 191 patients. Medicine. 2015;94:e714.CrossRefPubMedPubMedCentral Gunther U, Moos V, Offenmuller G, et al. Gastrointestinal diagnosis of classical whipple disease: Clinical, endoscopic, and histopathologic features in 191 patients. Medicine. 2015;94:e714.CrossRefPubMedPubMedCentral
33.
go back to reference Mori K, Ando I, Kukita A. Generalized hyperpigmentation of the skin due to vitamin B12 deficiency. The Journal of Dermatology. 2001;28:282–285.CrossRefPubMed Mori K, Ando I, Kukita A. Generalized hyperpigmentation of the skin due to vitamin B12 deficiency. The Journal of Dermatology. 2001;28:282–285.CrossRefPubMed
34.
go back to reference Louis ED, Lynch T, Kaufmann P, Fahn S, Odel J. Diagnostic guidelines in central nervous system whipple’s disease. Annals of Neurology. 1996;40:561–568.CrossRefPubMed Louis ED, Lynch T, Kaufmann P, Fahn S, Odel J. Diagnostic guidelines in central nervous system whipple’s disease. Annals of Neurology. 1996;40:561–568.CrossRefPubMed
35.
go back to reference Matthews BR, Jones LK, Saad DA, Aksamit AJ, Josephs KA. Cerebellar ataxia and central nervous system whipple disease. Archives of Neurology. 2005;62:618–620.CrossRefPubMed Matthews BR, Jones LK, Saad DA, Aksamit AJ, Josephs KA. Cerebellar ataxia and central nervous system whipple disease. Archives of Neurology. 2005;62:618–620.CrossRefPubMed
36.
go back to reference Elkins C, Shuman TA, Pirolo JS. Cardiac whipple’s disease without digestive symptoms. The Annals of Thoracic Surgery. 1999;67:250–251.CrossRefPubMed Elkins C, Shuman TA, Pirolo JS. Cardiac whipple’s disease without digestive symptoms. The Annals of Thoracic Surgery. 1999;67:250–251.CrossRefPubMed
37.
go back to reference Gubler JG, Kuster M, Dutly F, et al. Whipple endocarditis without overt gastrointestinal disease: Report of four cases. Annals of Internal Medicine. 1999;131:112–116.CrossRefPubMed Gubler JG, Kuster M, Dutly F, et al. Whipple endocarditis without overt gastrointestinal disease: Report of four cases. Annals of Internal Medicine. 1999;131:112–116.CrossRefPubMed
38.
go back to reference Fenollar F, Lepidi H, Raoult D. Whipple’s endocarditis: Review of the literature and comparisons with Q fever, bartonella infection, and blood culture-positive endocarditis. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 2001;33:1309–1316.CrossRef Fenollar F, Lepidi H, Raoult D. Whipple’s endocarditis: Review of the literature and comparisons with Q fever, bartonella infection, and blood culture-positive endocarditis. Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 2001;33:1309–1316.CrossRef
39.
go back to reference Lepidi H, Fenollar F, Dumler JS, et al. Cardiac valves in patients with whipple endocarditis: Microbiological, molecular, quantitative histologic, and immunohistochemical studies of 5 patients. The Journal of Infectious Diseases. 2004;190:935–945.CrossRefPubMed Lepidi H, Fenollar F, Dumler JS, et al. Cardiac valves in patients with whipple endocarditis: Microbiological, molecular, quantitative histologic, and immunohistochemical studies of 5 patients. The Journal of Infectious Diseases. 2004;190:935–945.CrossRefPubMed
40.
go back to reference Altman D. Practical statistics for medical research. London: Chapman and Hall; 1991. Altman D. Practical statistics for medical research. London: Chapman and Hall; 1991.
42.
go back to reference Dobbins WO III. Whipple’s disease: an historical perspective. Q J Med.. 1985;56:523–531.PubMed Dobbins WO III. Whipple’s disease: an historical perspective. Q J Med.. 1985;56:523–531.PubMed
43.
go back to reference Enzinger FM, Helwig EB. Whipple’s disease. Whipple’s Disease. 1963;336:238. Enzinger FM, Helwig EB. Whipple’s disease. Whipple’s Disease. 1963;336:238.
44.
46.
go back to reference Nadkarni PM, Darer JA. Migrating existing clinical content from ICD-9 to SNOMED. Journal of the American Medical Informatics Association: JAMIA. 2010;17:602–607.CrossRefPubMed Nadkarni PM, Darer JA. Migrating existing clinical content from ICD-9 to SNOMED. Journal of the American Medical Informatics Association: JAMIA. 2010;17:602–607.CrossRefPubMed
47.
go back to reference Kaelber DC, Foster W, Gilder J, Love TE, Jain AK. Patient characteristics associated with venous thromboembolic events: A cohort study using pooled electronic health record data. Journal of the American Medical Informatics Association: JAMIA. 2012;19:965–972.CrossRefPubMed Kaelber DC, Foster W, Gilder J, Love TE, Jain AK. Patient characteristics associated with venous thromboembolic events: A cohort study using pooled electronic health record data. Journal of the American Medical Informatics Association: JAMIA. 2012;19:965–972.CrossRefPubMed
Metadata
Title
Epidemiology of Whipple’s Disease in the USA Between 2012 and 2017: A Population-Based National Study
Authors
Jamie Ann Elchert
Emad Mansoor
Mohannad Abou-Saleh
Gregory S. Cooper
Publication date
01-05-2019
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 5/2019
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-018-5393-9

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