#44 – Celiac Disease



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History of the Disease

The term “celiac” has Latin and Greek roots as Aretaeus of Cappadocia named this disease in the 1st century AD “koiliakos” meaning abdomen/abdominal in patients with chronic diarrhea.  The first modern medical description of the disease was in 1888 by Samuel Gee in an paper entitled “On the Coeliac Affection”. The specific medical term for Celiac Disease is “gluten-sensitive enteropathy”. It was still relatively unexplained until Willem Dicke, a Dutch pediatrician, noted improvement in his patient’s abdominal symptoms during bread and grain shortages of World War II.


Epidemiology

  • Primarily in northern European white
  • Prevalence is widely variable due to differing rates and types of population screening throughout the world


Pathophysiology

High association with genetic predisposition to gluten sensitivity, specifically HLA-DQ2 and/or DQ8, and because of these genetic changes, serum autoantibodies are produced that attack the endomysium of the enterocytes of the small bowel.


Signs and Symptoms

Originally thought to be a disease of infancy, it is being diagnosed later and later in life, with adults first being diagnosed as late as the fifth decade.  Often, this is in the setting of failure to thrive in an infant.

Common

  • Diarrhea
  • Steatorrhea
  • Malabsorption
    • Anemia (iron), weight loss, metabolic bone disease (vitamin D and calcium), vitamin deficiencies (B-complex vitamins)
      • Peripheral neuropathy, ataxia

Associated Clinical Findings

  • Dermatitis herpetifomis
    • Pruritic papules and grouped vesicles on the elbows, forearms, knees, scalp, back, and buttock.
    • 1:369 patients diagnosed with celiac disease
    • Diagnosed with biopsy histologic evidence of IgA deposition in basement membrane
  • Down Syndrome
    • As high as 16% association, which isa 20-fold increase compared with general public
  • Also associated with liver disease, diabetes, thyroid disease, inflammatory bowel disease

Screening and Diagnosis

  • Who should be screened?
    • Patients with chronic diarrhea, malabsorption, weight loss, or abdominal distension and bloating
    • Patients without other explanations for extraintestinal diseases such as anemia, elevated transaminases, peripheral neuropathy, ataxia, etc.
    • Patients with type 1 DM and signs or symptoms of celiac disease
    • Asymptomatic first-degree relatives of patients with confirmed celiac disease
  • Immunoglobulin A (IgA) anti-tissue transglutaminase (TTG) is the initial screening test of choice
    • If positive, then proceed with duodenal biopsy via endoscopy
    • If negative, HLA-DQ2/DQ8 testing is performed to evaluate for nonceliac gluten sensitivity
      • If negative, then celiac is ruled-out
      • If positive, then slow introduction of gluten-containing foods is started
        • If unable to tolerate, then proceed with biopsy
        • If serology changes to positive, then celiac disease is confirmed
  • Endoscopic biopsy is the confirmatory test of choice in patients with positive serologic screening and high probability of celiac disease.
    • Duodenal mucosa may appear atrophic with loss of folds, visible fissures, nodular folds, and/or scalloped appearance
  • Histologic features of small bowel biopsy include increased intraepithelial lymphocytes, flat mucosa with complete loss of villi and atrophy, and/or crypt hyperplasia

Classification

Celiac disease can present as a spectrum of signs and symptoms and thus, have different classifications.

  • Classic Disease
    • 3 key features
      • Villous atrophy
      • Symptoms of malabsorption
        • Steatorrhea, weight loss, nutrient deficiencies
      • Improvement in symptoms with withdrawal of gluten-containing foods
  • Atypical Disease
    • Minor gastrointestinal complaints
    • Anemia, osteoporosis, tooth enamel issues,
    • Severe mucosal damage is present on endoscopy
  • Asymptomatic (Silent) Disease
    • Incidental finding on screening without symptoms

Management

Six key elements of successful management of celiac disease and it has a nice acronym:

  • Consultation with a skilled dietician
  • Education about the disease
  • Lifelong adherence to a gluten-free diet
  • Identification and treatment of nutritional deficiencies
  • Access to an advocacy group
  • Continuous long-term follow-up by a multidisciplinary team

Cottage Physician

This is an excerpt from the pediatric disease section on diarrhea:



References

  1. Impact – A Publication of the University of Chicago Celiac Disease Center. 2007;7(3):1-3. [article]
  2. Yan D, Holt PR. Willem Dicke. Brilliant clinical observer and translational investigator. Discoverer of the toxic cause ofceliac disease. Clinical and translational science. 2009; 2(6):446-8. [pubmed]
  3. Schuppan D. Current concepts of celiac disease pathogenesis. Gastroenterology. 2000; 119(1):234-42. [pubmed]
  4. Kagnoff MF. Celiac disease. A gastrointestinal disease with environmental, genetic, and immunologic components.Gastroenterology clinics of North America. 1992; 21(2):405-25. [pubmed]
  5. Dieterich W, Laag E, Schöpper H, et al.Autoantibodies to tissue transglutaminase as predictors of celiac disease.Gastroenterology. 1998; 115(6):1317-21. [pubmed]
  6. Sulkanen S, Halttunen T, Laurila K, et al.Tissue transglutaminase autoantibody enzyme-linked immunosorbent assay in detecting celiac disease. Gastroenterology. 1998; 115(6):1322-8. [pubmed]
  7. Fasano A, Catassi C. Clinical practice. Celiacdisease. The New England journal of medicine. 2012; 367(25):2419-26. [pubmed]
  8. Leonard MM, Sapone A, Catassi C, Fasano A.Celiac Disease and Nonceliac Gluten Sensitivity: A Review. JAMA. 2017;318(7):647-656. [pubmed]
  9. Guandalini S, Assiri A. Celiac disease: areview. JAMA pediatrics. 2014; 168(3):272-8. [pubmed]
  10. Bibbins-DomingoK, Grossman DC, et al. Screening for Celiac Disease: US Preventive Services Task Force Recommendation Statement. JAMA. 2017; 317(12):1252-1257. [pubmed]
  11. CarlssonA, Axelsson I, Borulf S, et al. Prevalence of IgA-antigliadin antibodies and IgA-antiendomysium antibodies related to celiac disease in children with Down syndrome. Pediatrics. 1998; 101(2):272-5. [pubmed]
  12. Rubio-TapiaA, Hill ID, Kelly CP, Calderwood AH, Murray JA, . ACG clinical guidelines:diagnosis and management of celiac disease. The American journal of gastroenterology. 2013; 108(5):656-76; quiz 677. [pubmed]
  13. ShahVH, Rotterdam H, Kotler DP, Fasano A, Green PH. All that scallops is not celiac disease. Gastrointestinal endoscopy. 2000; 51(6):717-20. [pubmed]
  14. OberhuberG, Granditsch G, Vogelsang H. The histopathology of coeliac disease: time for astandardized report scheme for pathologists. European journal of gastroenterology & hepatology. 1999; 11(10):1185-94. [pubmed]
  15. National Institutes of Health Consensus Development Conference Statement on Celiac Disease, June 28-30, 2004.Gastroenterology. 2005; 128(4 Suppl 1):S1-9. [pubmed]

Ep-PAINE-nym



Duct of Wirsung

Other known aliasesmain pancreatic duct

DefinitionThis is the main pancreatic duct that joins the pancreas to the common bile prior to the ampulla of Vater before emptying into the second portion of the duodenum

Clinical SignificanceHaving a single, major pancreatic duct is the most common anatomic variant for pancreatic anatomy, but some individuals may have an accessory duct that could be functional.  The issue with this, of course, is management of pancreatic pathology so imaging may be required prior to instrumentation or surgical management.

HistoryNamed after Johann Georg Wirsung (1589-1643), who was a German anatomist from Padua.  He made this discovery while dissecting a criminal (Zuane Viaro) who was recently hanged for murder in 1642.  Instead of formally publishing his findings, he engraved the sketch on a copper plate so numerous casting could be made and sent to the leading anatomists of the time.  This finding is not without controversy.  One year after this discovery, Wirsung was murdered in his house late at night by a Belgian student named Giacomo Cambier over a quarrel of first discovered this duct.  In a cruel twist of fate, 5 years after his death, one of Wirsung’s students who was assisting in the dissection, Moritz Hoffman, claimed it was he who discovered this duct in a turkey rooster a year before Wirsung.

Original copper plate etching
Painting of the murder of Wirsung

References

  1. Firkin BG and Whitwirth JA.  Dictionary of Medical Eponyms. 2nd ed.  New York, NY; Parthenon Publishing Group. 1996.
  2. Bartolucci S, Forbis P.  Stedman’s Medical Eponyms.  2nd ed.  Baltimore, MD; LWW.  2005.
  3. Yee AJ, Pfiffner P. (2012).  Medical Eponyms (Version 1.4.2) [Mobile Application Software].  Retrieved http://itunes.apple.com.
  4. Whonamedit – dictionary of medical eponyms. http://www.whonamedit.com
  5. Up To Date. www.uptodate.com
  6. Howard JM, Hess W, Traverso W. Johann Georg Wirsüng (1589-1643) and the pancreatic duct: the prosector of Padua, Italy. Journal of the American College of Surgeons. 1998; 187(2):201-11. [pubmed]

PAINE #PANCE Pearl – Gastrointestinal/Nutritional



Question

What vitamins have a higher potential for causing toxicity and why?



Answer

Fat soluble vitamins can be stored in the adipose tissue instead of excreted if in excess.  As a result, vitamins A, D, E, and K can cause toxicity if patients take too much (in this order of incidence as well).

  • Hypervitamintosis A can result in ataxia, hepatotoxicity, visual impairments, and orange skin.
  • Hypervitamintosis D can result in hyperphosphatemia and hypercalcemia.
  • Hypervitamintosis E can block vitamin K absorption and leads to easy bleeding and bruising
  • Hypervitamintosis K is very rare and really only seen in infants receiving newborn injections after birth.

References

Ep-PAINE-nym



Morison’s Pouch

Other known aliaseshepatorenal recess/fossa, right posterior subhepatic space

Definitiona potential space between the liver and the right kidney

Clinical SignificanceThis a space where fluid can accumulate in the setting of ascites or abdominal trauma and be seen on CT or ultrasound.  It is one of the view of a Focused Assessment of Sonography in Trauma (FAST) exam. Typically, 30-40mL of fluid needs to be present to be visualized.

Ultrasound
Computed Tomography

HistoryNamed after James Rutherford Morison (1853-1939), a British surgeon who received his medical degree from the University of Edinburgh in 1874.  He was also an assistant and “surgical dresser” for Joseph Lister early in his career and later founded a school of surgery at the University of Durham where he made his name as a prolific instructor of surgery.  He is well known as a pioneer of modern surgery with several of his contemporaries noting he was twenty years ahead of his time and was a driving force of he surgical arts in Great Britain at the turn of the 20th century. 


References

  1. Firkin BG and Whitwirth JA.  Dictionary of Medical Eponyms. 2nd ed.  New York, NY; Parthenon Publishing Group. 1996.
  2. Bartolucci S, Forbis P.  Stedman’s Medical Eponyms.  2nd ed.  Baltimore, MD; LWW.  2005.
  3. Yee AJ, Pfiffner P. (2012).  Medical Eponyms (Version 1.4.2) [Mobile Application Software].  Retrieved http://itunes.apple.com.
  4. Whonamedit – dictionary of medical eponyms. http://www.whonamedit.com
  5. Up To Date. www.uptodate.com
  6. http://livesonline.rcseng.ac.uk/biogs/E004690b.htm

Ep-PAINE-nym



Zenker’s Diverticulum

Other Known Aliasespharyngeal diverticulum

Definitionsac-like outpouching of the mucosa and submucosa through Killian’s triangle, which is the area of structural weakness between the cricopharyngeus and lower inferior constrictor muscles.

Clinical SignificanceThere are actually three different types of diverticulae that can form in this region and are based on anatomic location:

  • Zenker’s – immediately above the upper esophageal sphincter
  • Traction – near midpoint of the esophagus
  • Epiphrenic – immediately above the lower esophageal sphincter

Signs and symptoms of a Zenker’s diverticulum are pretty awful and include dysphagia, pulmonary aspiration, and halitosis from partially rotting food in the outpoaching.  It is diagnosed via barium swallow under flouroscopy. The majority of the patients are male and present after the age of 60.  Management is surgical resection.

HistoryNamed after Friedrich Albert von Zenker (1825-1898), who was German physician and pathologist and received his medical doctorate at Leipzig in 1851.    He held numerous teaching posts including chief prosector and professor of general pathology and anatomy at Dresden city hospital.  Dr. Zenker, along with Hugo Wilhelm von Ziemssen, published a case series and literature review on his eponymous diverticulum in 1867 entitled “Krankheiten des Oesophagus”. He also was the first to document and describe trichinosis in a girl who died in 1860, proving that the once thought harmless parasite could cause severe disease.

Friedrich Albert von Zenker

References

  1. Firkin BG and Whitwirth JA.  Dictionary of Medical Eponyms. 2nd ed.  New York, NY; Parthenon Publishing Group. 1996.
  2. Bartolucci S, Forbis P.  Stedman’s Medical Eponyms.  2nd ed.  Baltimore, MD; LWW.  2005.
  3. Yee AJ, Pfiffner P. (2012).  Medical Eponyms (Version 1.4.2) [Mobile Application Software].  Retrieved http://itunes.apple.com.
  4. Whonamedit – dictionary of medical eponyms. http://www.whonamedit.com
  5. Up To Date. www.uptodate.com
  6. F. A. Zenker and Hugo Wilhelm von Ziemssen:
    Krankheiten des Oesophagus. Leipzig, 1867
  7. Ueber die Trichinenkrankheit des Menschen. Virchows Archiv für pathologische Anatomie und Physiologie und für klinische Medizin, Berlin, 1860, 18: 561-572.