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NME > Celiac disease and inflammatory bowel disease > Flashcards

Celiac disease and inflammatory bowel disease Flashcards

1
Q

What is Coeliac Disease?

A

Coeliac Disease is an immune-mediated small intestinal enteropathy triggered by exposure to dietary gluten in genetically predisposed individuals, leading to malabsorption.

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2
Q

What is gluten?

A

Gluten is a protein found in wheat, barley, and rye. Oats can be contaminated.

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3
Q

Does Coeliac disease affect more men or women?

A

Coeliac disease affects more women than men.

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4
Q

At what age can Coeliac disease occur?

A

Coeliac disease can occur at any age.

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5
Q

What are some conditions associated with a high prevalence of Coeliac disease?

A

Coeliac disease is associated with Down’s syndrome, Type I diabetes mellitus, auto-immune hepatitis, and thyroid gland abnormalities.

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6
Q

What is the genetic association with Coeliac disease?

A

Coeliac disease is associated with two genes in particular: the Human Leukocyte Antigen (HLA) DQ2 and DQ8 genes.

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7
Q

What are some common symptoms of Coeliac disease?

A

Coeliac disease presents with symptoms such as diarrhoea, steatorrhea (fatty floating stools), weight loss, anaemia, vague abdominal pains, glossitis, mouth ulcers, and a rash called dermatitis herpetiformis.

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8
Q

Can Coeliac disease be asymptomatic?

A

Yes, Coeliac disease is increasingly found in asymptomatic individuals, accounting for up to one-third of cases.

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9
Q

What are the endoscopic findings in Coeliac Disease?

A

In Coeliac Disease, the endoscopic findings may include decreased folds, villous atrophy, and scalloping of folds in the small bowel.

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10
Q

What are the endoscopic findings in a normal small bowel?

A

In a normal small bowel, the endoscopic findings show normal duodenal villi.

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11
Q

What is Dermatitis Herpetiformis?

A

Dermatitis Herpetiformis is an itchy, vesicular rash that appears on the extensor surfaces of the body.

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12
Q

What are some other clinical features associated with Coeliac Disease?

A

Other clinical features of Coeliac Disease include angular stomatitis (associated with iron or vitamin B12 deficiency), glossitis (associated with iron deficiency), and pallor (associated with anaemia).

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13
Q

What is the pathogenesis of Coeliac Disease?

A

The pathogenesis of Coeliac Disease involves the complexing of gliadin, a gluten by-product, with tissue transglutaminase (tTG) in the gut. This complex binds as an antigen (deaminated gliadin) to HLA-DQ2 on T cells, triggering an immune response that results in the production of anti-tTG IgA, anti-endomysial, and antigliadin antibodies in the blood, as well as inflammation through NK cells.

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14
Q

How does the pathogenesis of Coeliac Disease relate to dermatitis herpetiformis?

A

Tissue transglutaminase (tTG) cross-reacts with epidermal TG (eTG), leading to the development of dermatitis herpetiformis.

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15
Q

What are the normal appearances of small bowel villi?

A

The normal appearances of small bowel villi include finger-like projections called villi, which are responsible for absorbing nutrients from the bowel lumen.

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16
Q

What are the histopathological findings in Coeliac Disease?

A

The histopathological findings in Coeliac Disease include flattening of villi, the presence of chronic inflammatory cells such as intraepithelial lymphocytes and NK cells, and crypt hyperplasia.

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17
Q

How is Coeliac Disease diagnosed?

A

Coeliac Disease can be diagnosed through serology and endoscopy with biopsy.

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18
Q

What serological tests are used for diagnosing Coeliac Disease?

A

The serological tests used for diagnosing Coeliac Disease include anti-endomysial antibodies, IgA anti-tissue transglutaminase antibodies (or IgG anti-tTG in patients with IgA deficiency), and anti-gliadin antibodies.

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19
Q

What percentage of patients with Coeliac Disease have negative serology?

A

Approximately 6-22% of patients with Coeliac Disease have negative serology.

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20
Q

What are the histological findings seen in the small bowel during endoscopy for Coeliac Disease diagnosis?

A

The histology of the small bowel in Coeliac Disease shows raised intraepithelial lymphocytes, crypt hyperplasia, and villous atrophy according to the Marsh Criteria.

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21
Q

What is the main treatment for Coeliac Disease?

A

The main treatment for Coeliac Disease is a Gluten-Free Diet, which includes avoiding gluten-containing foods such as wheat, barley, and rye. Oats are generally considered safe for most individuals with Coeliac Disease.

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22
Q

What vaccination is recommended for individuals with Coeliac Disease?

A

Vaccination against pneumococcus is recommended for individuals with Coeliac Disease.

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23
Q

How should osteoporosis be managed in patients with Coeliac Disease?

A

Osteoporosis screening and prevention measures should be implemented in patients with Coeliac Disease. This may include calcium supplementation with a recommended intake of 1 gram of calcium per day.

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24
Q

What supplements may be necessary for individuals with Coeliac Disease?

A

Iron, vitamin B12, and folate supplementation may be necessary for individuals with Coeliac Disease to address any deficiencies that may arise due to malabsorption.

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25
Q

What other autoimmune diseases should be monitored in individuals with Coeliac Disease?

A

Individuals with Coeliac Disease should be monitored for the development of other autoimmune diseases such as autoimmune thyroiditis (such as Graves disease) and autoimmune hepatitis.

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26
Q

How frequently should blood monitoring be conducted for individuals with Coeliac Disease?

A

Annual blood monitoring is recommended for individuals with Coeliac Disease to assess their nutritional status, detect any deficiencies or complications, and monitor overall health.

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27
Q

What is Inflammatory Bowel Disease (IBD)?

A

Inflammatory Bowel Disease is a chronic inflammatory condition that affects the bowel.

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28
Q

When was Inflammatory Bowel Disease first recognized?

A

Inflammatory Bowel Disease was recognized as early as the 17th century.

29
Q

What is Crohn’s Disease (CD)?

A

Crohn’s Disease is a form of Inflammatory Bowel Disease characterized by patchy, transmural ulceration that can affect any part of the digestive tract from the mouth to the anus.

30
Q

What is Ulcerative Colitis (UC)?

A

Ulcerative Colitis is a form of Inflammatory Bowel Disease characterized by continuous inflammation limited to the mucosal layer of the colon.

31
Q

How do Crohn’s Disease (CD) and Ulcerative Colitis (UC) look different?

A

Crohn’s Disease (CD) is characterized by deep ulcers and patchy inflammation, whereas Ulcerative Colitis (UC) is characterized by shallow ulcers and continuous inflammation.

32
Q

What are the histological features that differentiate Crohn’s Disease (CD) from Ulcerative Colitis (UC)?

A

Crohn’s Disease (CD) is associated with transmural inflammation, meaning that all layers of the bowel wall can be affected. It may also exhibit the presence of granulomas. On the other hand, Ulcerative Colitis (UC) is associated with mucosal inflammation, and while crypt abscesses may be seen, granulomas are not typically present.

33
Q

What are granulomas?

A

Granulomas are aggregations of macrophages around foreign substances they want to eliminate. They can be seen in a range of conditions such as tuberculosis (TB) and sarcoidosis.

34
Q

What are some differences between Crohn’s Disease (CD) and Ulcerative Colitis (UC)?

A

It was first described by Bernard Burhill Crohn in the 1930s after reports of a disease causing terminal ileitis.
It predominantly affects younger adults and children.
There is a strong predisposition to smokers.
Fistulas, strictures, and perianal disease may be seen, indicating complications (refer to the next slide).
Penetrating disease can occur, where inflammation tracks across the bowel wall to adjacent bowel or organs and may cause localized abscess formation.

35
Q

What are some hallmarks of Crohn’s Disease (CD)?

A

Some hallmarks of Crohn’s Disease include the presence of granulomas and inflammation of the ileum. It can also be associated with complications such as strictures, fistulas, and perianal disease.

36
Q

What is the epidemiology of Crohn’s Disease (CD)?

A

Crohn’s Disease has a high prevalence in the Western world, with an increased incidence in patients of Jewish origin. There is also an increasing incidence in Africa, South America, and Asia. It has a bimodal presentation with peaks in the teens-20s and 60-70-year age groups.

37
Q

What is the cause of Crohn’s Disease (CD)?

A

The exact cause of Crohn’s Disease is unknown. It is believed to involve a combination of genetic, infectious, immunologic, environmental, dietary, vascular, smoking, NSAIDs, and psychological factors. Defects in mucosal barriers that allow pathogens and other antigens have also been implicated.

38
Q

What is the genetic component of Crohn’s Disease (CD)?

A

There is strong scientific evidence for genetic predisposition to Crohn’s Disease. First-degree relatives of individuals with CD have a 13-18% increased risk of developing the condition, with a 50% concordance in monozygotic twins. CD does not follow classical Mendelian inheritance patterns but is polygenic. The NOD2 (nucleotide-binding domain) on chromosome 16 is the most well-known variant associated with CD predisposition, although over 200 other variants have been identified.

39
Q

What is the aim of medical treatment for Crohn’s Disease (CD)?

A

The aim of medical treatment for Crohn’s Disease is to prevent excessive surgery and the development of short bowel syndrome. Approximately 50% of patients with CD will require surgery, and 70% of those will need a second operation within 5 years of the first. Surgery may be necessary for abscess drainage or treatment of fibrostenotic strictures.

40
Q

What are some characteristics of Ulcerative Colitis (UC)?

A

Ulcerative Colitis is more common in females and non-smokers. It has a bimodal age distribution, affecting people in their 20s and 60s. Like Crohn’s Disease, genetics play a significant role, with a high concordance rate among monozygotic twins. Flares of UC can be triggered by NSAIDs.

41
Q

What is the risk associated with the behavior of Ulcerative Colitis (UC) in the colon?

A

While UC affects only the colon and involves only the mucosal layer of the bowel wall, this behavior itself poses a risk for complications such as Toxic Megacolon, which is the dilatation of the colon and can lead to colonic perforation in cases of severe inflammation.

42
Q

What is the lifetime risk of colectomy in Ulcerative Colitis (UC)?

A

The lifetime risk of colectomy (removal of the colon) in UC is approximately 20-30%.

43
Q

What is the significance of the location of the disease in Ulcerative Colitis (UC)?

A

The location of the disease, whether it is proctitis (limited to the rectum), left-sided disease (involving the left side of the colon), or pancolitis (affecting the entire colon), is a risk factor in UC.

44
Q

What is the progression of disease seen in Ulcerative Colitis (UC)?

A

Within one year, approximately one-third of patients with UC will go into remission on treatment, one-third will have some symptoms, and one-third will progress to more extensive disease.

45
Q

What are the treatment options for chronic IBD (UC and CD)?

A

Mesalazines (not typically used in CD)
Biologics
Thiopurines
Repeated courses of corticosteroids in cases of worsening disease

46
Q

What are corticosteroids?

A

Corticosteroids are naturally occurring hormones that regulate the immune response. They are also used as a treatment for inflammatory conditions such as IBD and asthma.

47
Q

What is the intravenous formulation of corticosteroids used for acute flares of IBD?

A

Hydrocortisone is used as the intravenous formulation for acute flares of IBD.

48
Q

What is the oral formulation of corticosteroids used for IBD treatment?

A

Prednisolone is used as the oral formulation of corticosteroids for IBD treatment.

49
Q

What are Mesalazines?

A

Mesalazines are 5-aminosalicylic acids (5-ASAs) commonly used in the treatment of chronic inflammatory conditions such as IBD.

50
Q

In what forms are Mesalazines available?

A

Mesalazines are available in different preparations, including oral formulations, rectal suppositories, and enemas.

51
Q

What are some brand names of Mesalazines?

A

Some brand names of Mesalazines include Pentasa, Octasa, Asacol, Balsalazide, and Mezavant.

52
Q

How does the pH-dependent capsules of Mesalazines work?

A

The pH-dependent capsules of Mesalazines are designed to release the medication in specific regions of the intestine and colon based on the pH levels.

53
Q

How do maintenance and treatment doses of Mesalazines vary?

A

The maintenance and treatment doses of Mesalazines can vary based on the severity of the condition being treated and the individual patient’s response.

54
Q

What are Thiopurines?

A

Thiopurines are a commonly used drug therapy for IBD (Inflammatory Bowel Disease).

55
Q

In which conditions are Thiopurines commonly used as treatment?

A

Thiopurines are considered second-line therapy for ulcerative colitis (UC) and first-line therapy for Crohn’s disease (CD).

56
Q

What are the two commonly used Thiopurine medications?

A

The two commonly used Thiopurine medications are Azathioprine and Mercaptopurine.

57
Q

How long does it take for Thiopurines to take effect?

A

Thiopurines typically take around 6 weeks to show their therapeutic effect.

58
Q

Who developed Thiopurines and for what purpose?

A

Thiopurines were developed by Gertrude Elion in the 1940s as antimetabolites to nucleic acids. They were initially used to prevent renal transplant rejection and childhood leukemia.

59
Q

What is the role of the enzyme TPMT in Thiopurine metabolism?

A

Thiopurine metabolism is influenced by an enzyme called thiopurine methyltransferase (TPMT).

60
Q

What is the significance of TPMT activity in Thiopurine therapy?

A

TPMT activity exhibits a trimodal distribution in the population based on genotype. Around 1 in 300 people have no TPMT activity, which puts them at risk of severe side effects such as bone marrow suppression. Routine checking of TPMT activity is performed for all patients.

61
Q

What are the active metabolites of Thiopurines and how do they work?

A

The active metabolites of Thiopurines, known as thioguanine nucleotides, incorporate the sulfur moiety into the phosphoribosyl backbone of DNA. This incorporation prevents DNA unwinding.

62
Q

What is the mechanism of action of Anti-TNF Agents (Biologics)?

A

Anti-TNF Agents (Biologics) block the body’s natural response to the Tumor Necrosis Factor cytokine, which plays a role in inflammation.

63
Q

What are examples of common Anti-TNF Agents (Biologics)?

A

Infliximab and Adalimumab are common examples of Anti-TNF Agents (Biologics).

64
Q

How is Infliximab used in treatment?

A

Infliximab can be given acutely in patients for whom steroids are not effective. It is administered intravenously and can provide a quicker response compared to Thiopurines, which take more than 6 weeks to work. Infliximab is typically given as 8 weekly infusions, and subcutaneous preparations are also available.

65
Q

How is Adalimumab administered?

A

Adalimumab is a subcutaneous drug administered every two weeks.

66
Q

What is the success rate of induction and maintenance of remission with Anti-TNF Agents (Biologics)?

A

The success rate for induction and maintenance of remission in IBD with Anti-TNF Agents (Biologics) is approximately 60%.

67
Q

What are some other Biologics used in the treatment of IBD?

A

Other Biologics used in the treatment of IBD include Vedolizumab (specific to the gut, blocking α4ß7 integrins), Tofacitinib (the first oral molecule), Ustekinumab, and Golimumab.

68
Q

What are the treatment options for acute Crohn’s Disease (CD)?

A

Nil by mouth (NPO) to rest the bowel.
Intravenous antibiotics if there are abdominal abscesses.
Modulen, a liquid nutritionally complete diet, for those who can tolerate it.
Intravenous hydrocortisone (corticosteroid) for anti-inflammatory effect.
Biologics such as infliximab.

69
Q

What are the treatment options for acute Ulcerative Colitis (UC)?

A

Intravenous hydrocortisone for anti-inflammatory effect.
Low molecular weight heparin.
Early surgical review for cases that may require surgical intervention.
Biologics such as infliximab or ciclosporin (a calcineurin inhibitor with anti-inflammatory properties) for patients who fail to respond to steroids

NME (49 decks)

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