Approach to Gluten Sensitivity - Stein

Question 1

What type of hypersensitivity reaction is seen in Wheat allergy?

What sites can it affect?

How common is it?

Answer 1

Type I.

The skin, GI tract, and respiratory tract.

Prevalence is less than 2% (note that symptomology can vary widely)

Question 2

How can wheat allergy manifest?

How is it diagnosed?

Answer 2

Baker’s asthma, rhinitis, contact urticaria, wheat-dependent exercise-induced anaphylaxis (WDEIA).

Pin-prick testing for allergies.

Question 3

What is non-celiac gluten sensitivity?

How common is it?

Answer 3

A (patient-driven) claim of improved symptoms on a GFD, always in the absence of celiac disease.

Around 5% in the US!

Question 4

Is there evidence to support the notion that non-celiac gluten sensitivity is “real”?

How can it be explained?

Answer 4

Some; a few double-blind studies have found improved symptoms on those placed on GFDs.

Gluten-free diets have fewer fermentable fructans (indeed, it tends to match FODMAP diets). Patients were probably getting more fruits & veg…

Question 5

What are the shortcomings of gluten-free diets?

Answer 5

Potentially decreased iron, calcium, and vitamins B & D. Fiber, too.

Price and inconvenience.

Oh, and most beers are made from barley.

Question 6

Where is environmental enteropathy seen?

How does it present?

Answer 6

In developing countries where malnutrition abounds.

Stunted growth, diarrhea, and histological features similar to those of celiac disease.

Question 7

How is environmental enteropathy thought to arise?

How is it treated?

Answer 7

Malnutrition, which contributes to “a cycle of mucosal injury, infection, and inflammation”.

Supplementary feeding and vitamins.

Question 8

Give four major symptoms associated with “classis celiac disease”

Why is ‘classic’ somewhat of a misnomer?

Answer 8

• Diarrhea
• Bloating
• Abdominal pain
• Weight loss

“Classic” presentation is actually an atypical presentation - most patients with celiac disease do not show this exact pattern

Question 9

What are some possible symptoms/findings associated with “Atypical” sprue? Name 6.

Answer 9

• Iron deficiency (unexplained IDA in 3% to 15% of patients)
• Folic acid or B12 deficiency
• Osteoporosis
• Dermatitis herpetiformis
• IBS
• DM type 1
• Elevated LFTs (unexplained, 2% to 9% of patients)

Question 10

If a patient has celiac disease, what is the approximate risk of this disease for:

• HLA-identical siblings?
• First-degree relatives?
• Monozygotic sibling?
• Second-degree relative

Answer 10

• 40%
• 10%
• 70-80%
• 1 in 39 (<2.6%)

Question 11

Iron deficiency anemia is a common problem in celiac disease. Why?

Answer 11

The duodenum is the most commonly affected part of the GI tract. This may be because the duodenum experiences the highest concentration of gluten of all segments of the bowel. Incidentally, iron is also absorbed here - inflammation and malabsorption in the duodenum can lead to IDA.

Question 12

Which immunoglobulin class is sometimes deficient in celiac disease patients?

What other immune dysfunctions might be associated with celiac disease?

Answer 12

IgA (2-5% of all CD patients)

Autoimmine disorders: T1DM, thyoid (Hashimoto’s), Addison disease, PBC, Sjogren’s, autoimmune hepatitis

Question 13

Name two major chromosomal abnormalities associated with celiac disease

Answer 13

Turner Syndrome

Down Syndrome

Question 14

What skin condition, characterized by pruritic papulovesicles on the extensor surfaces and trunk, is associated with celiac disease?

What is the main treatment approach?

Answer 14

Dermatitis Herpetiformis (85% will have CD)

Gluten-free diet (GFD), even if they’re in the 15% that don’t have CD.

Question 15

What is the most common non-GI presentation of CD?

Answer 15

Osteopenia/osteoporosis

Question 16

Give (7) neurological symptoms associated with CD

Answer 16

Ataxia (B12 deficiency)

Night blindness (Vitamin A)

Headaches

Epilepsy

Mood disturbances

Peripheral neuropathies

Question 17

Infertility and amenorrhea is common with CD. What important fact is important to communicate to female CD patients upon beginning a gluten-free diet?

Answer 17

Infertility is often resolved upon commencing a GFD. It is fairly common to become pregnant shortly after commencing a GFD (and possibly not notice for awhile either due to amenorrhea associated with untreated CD).

Question 18

What are the three more useful serological tests for diagnosing CD?

Which antibody found in CD is not necessarily useful in clinical diagnosis? Why?

Answer 18

Useful tests:

• EMA - IgA Endomysial antibody
• tTG - Tissue transglutaminase
• IgA and IgG deamindated gliadin antibodies

Anti-gliadin antibodies are not particularly useful as they can be falsely elevated or elevated in other conditons (i.e. not specific for CD)

IgA level may be useful because some CD patients have IgA deficiency, but this is not diagnostic.

Question 19

If the GI tract is biopsied to confirm suspicion of CD, approximately how many biopsies should be taken?

Describe some basic gross and histological findings you’d expect with CD.

Answer 19

6-8 biopsy sites

Gross: scalloping or ‘notching’ of the small bowel folds. Villi not visualizable grossly.

Histo: villous atrophy, intraepithelial lymphocytosis, crypt hyperplasia

Question 20

After beginning a GFD, how long does it take antibody levels to fall? Why is this a problem clinically?

In the setting of IgA deficiency, what is the most useful serological test for CD?

Answer 20

Antibody levels fall within days to weeks (6-8). This can mask diagnosis (false negative)

If IgA deficient, use IgG deaminated gliadin antibody test (IgA tests are useless in this situation)

Question 21

What are the major pitfalls of biopsy for diagnosis if CD?

What else might cause villous atrophy?

Answer 21

Pitfalls:

• Were enough biopsies taken
• Logistical issues with jejunum and ileum biopsy (these locations are difficult to biopsy, so we often don’t bother considering CD is usually also in the duodenum)

Not all villous atrophy is CD…

• NSAID injury
• Infections
• IBD

Question 22

Nearly 100% of CD patients have what two genetic markers? Which is the most common?

Why is this useless diagnostically? For whom might it be useful?

Answer 22

DQ2 (95%) and DQ8 (5%)

~40% of persons of European anscestry are DQ2 or DQ8 positive (a positive result is of little value diagnostically). However, it has great **negative **predicitive value - i.e. if a CD patient doesn’t have these markers, they almost certainly don’t have CD after all and can discontinue GFD

Question 23

Why is beer bad for CD patients?

Answer 23

The malted barley used in beer brewing contains gluten. Therefore, beer is not a part of a gluten-free diet. However, some gluten-free beers are available that are made with alternative gluten-free malted grains.

Question 24

Say you have an ansymptomatic CD patient. Why might you still recommend GFD?

Answer 24

Long-term prognosis: the hazard ratio for CVD and malignancy is increased for CD patients, even those who are generally asymptomatic. This risk can be relieved (normalized) through GFD.

Question 25

What is enteropathy-associated T-cell lymphoma

Answer 25

An rare, but aggressive high-grade T-cell NHL with a low survival rate (5-year: ~10%). It occurs 20X more frequently in CD patients.

Risk for CD patients normalizes on GFD

Question 26

Besides normalizing CVD and malignancy risks, what other non-GI benefits are there for CD patients on GFD?

Answer 26

Things that improve on GFD

• Osteoporosis - at least partial improvement/prevention
• IDA
• Rashes
• Avoidance of other autoimmune diseases
• Fertility