Celiac disease
Celiac disease
• Celiac sprue (CS)
• Gluten enteropathy
• Life-long illness of both children and adults, occuring in all the countries of the world
• It is an auto-immune disease, where the trigger (gliadin), its close genetic bond to HLA-DQ2 or HLA-DQ8 and a specific humoral auto-immune response (autoantibodies against
transglutaminasis) is known
CS
• Occurs as a result of inadequate T-cell-
mediated auto-immune reaction to fission products of gluten.
• Manifests in small intestine mucosa,
where we find diminishing or flattened villi, hypertrophy of Liebermann crypts,
enterocyte maturation disorders, oedema and infiltration of the mucosa tissue
CS – characteristics
• Typical inflammatory changes of small intestine mucosa
• Absorption disorder of all nutrients
• Obvious condition improvement after introducing a no-glutene diet
CS – history
• 1888 described in children, a dietary poison considered a cause
• 1932 described in adults
• 1950 gluten was described as a cause
• 1954 mucosal changes from surgically resected material described
• 1957 Crosby’s capsule
Incidence of CS
• 1: 70- 1:550.
• Very common disease with prevalence close to 1:100 in total population
• In CR 1:200 cca, ie. 40 thousand patients with CS
• In first degree relatives, co-occurrence is 8-18%. In single-egg twins up to 70%
CS – mortality
• 10-30 % before introducing residue-free diet
• Less than 1% with gluten-free diet and early diagnostics
Gluten
• Protein complex localized on surface part of cereal corns
• Is responsible for stickiness of the batter
• Gluten may be divided in alcohol to soluble PROLAMINS and insoluble GLUTENS.
• Prolamins of wheat are gliadins, of rye – secalins, of oat – avenins and of barley – hordeins.
CS
• Prolamins may invoke imflammatory
changes of bowel mucosa in genetically susceptible individuals.
• All of them are toxic to some extent and their molecular weight is 20-75 kD
CS - pathological findings
• The maximum of mucosal changes occurs in proximal small intestine, diminishing in aboral direction
• So-called atrophic jejunitis
• No villi visible here
• Histologically, qualitative and quantitative reduction of absorption surface is proven
• Increased basophilia of enterocytes with multiple deficits of their enzymatic equipment
CS - pathological findings
• Electron microscopy – changes and lowering the amount of microvilli, increased amount of
ribosomes, defects of gap junctions between cells, higher mucosa permeability etc.
• Oedema, plasmocyte inflammatory infiltration with higher production of immunoglobulins of all three classes
• Increased percentage of intraepithelial lymphocytes
• An extensive layer of collagen may be found,
which does not respond to gluten exclusion from the diet
CS - pathological findings
• In patients with progressed disease, pathological fingings may be found in other organ systems, namely
• Bone
• Skin
• Muscular
• Endocrine
• Haematopoietic
• Nervous
Clinical findings
• Clinical manifestation differs according to extent and intensity of intestinal lesion
• Improvement frequent in children and
adolescents, with later manifestation at around age 30-40
• Women affected twice more often
• Exacerbation in adulthood often bound to stress situations (“trigger mechanisms”), e.g. infection, pregnancy, childbirth, breast-feeding, operation, trauma.
Clinical findings
• Diarrhea with marks of steatorrhea
• Weight loss
• General weakness, anemia
• Prominent abdomen, muscular atrophies,
(triangular face), percussional darkening above the hypogastrium (stasis of bowel contents)
• Oligosymptomatic, monosymptomatic, and latent forms exist.
• Anorexia is not present.
Clinical findings - forms
• Typical
• Subclinic – atypical extraintestinal symptoms – positive histology
• Silent – no syptoms, positive biopsy
• Latent form – positive antibodies, increase in IEL
• Potencial form – no syptoms, increase in IEL, this form can turn in other forms
Extraintestinal symptoms
• Frequent
• The nutrient absorption defect may affect all organ systems
• Anemia — deficiency of haemopoietic factors / folic acid, cobalamine, iron, pyridoxin, proteins – most often macrocyte anemia
• Bleeding – low coagulation factor (prothrombine) level due to malabsorption of vitamine K
Extraintestinal symptoms
• Clinical image of bone involvement – bone pain, spontaneous fractures
• Ca and Mg deficiency leads to paresthesias, muscle spasms and manifest tetany.
• Neurological symptoms – in severe forms of the disease
• Muscle weakness, paresthesias, taxia disorders, deep sensory disorders, cerebellar atrophy
Extraintestinal symptoms
• Hyposplenism with thrombocytosis, disc- like erythrocytes and spleen atrophy
occurs in about ½ of patients – permanent stimulation of their immune system
• Metabolic osteopathy – due to calcium,
vitamin and aminoacid absorption disorder – mixed character of bone involvement,
porose and malatia
Extraintestinal symptoms
• Disorders of menstruation, fertility, potency, malnutrition, disorder of hypothalamic-pituitary regulations
CS – diagnostics
• Serum antibodies
• Against gliadin
• Against endomysium
• Against transglutaminasis
• Positive antibodies indicates intestinal biopsy
• Negative anti-gliadin antibodies non responding to gliadin-free diet lead to suspection of a
different illness
• Antibodies quickly disappear after the diet (compliance checking)
• Antibody examination does not replace intestinal biopsy
CS – diagnostics
• Lab:
• Decrease in total protein, albumin, cholesterol, TCG, Fe, Ca, K
• Increase in ALP, AST, ALT
• Anemia, decrease in INR, APTT
CS – radiodiagnostics
• Enteroklysis
• X-ray: signs of dysfunction – disorder of intestinal tonus, hypo- and hypertonic segments, widening of spaces between plicae, angular contour of bowel
(“cogwheel sign”), incoherent contrast filling – segmentation, flocculation,
vanishing of the mucosa relievo
• X-ray of skeleton, bone densitometry.
CS - diagnostics
• Biopsy of small intestine mucosa
• Capsule
• Endoscopical, during gastroscopy or enteroscopy
CS - diagnostics
biopsy of intestinal mucosa
• Endoscopy of distal duodenum under Vater’s papilla
• Lowering or loss of plicae of Kerckring, mosaic image, denticulated plicae with visible vessels
• Endoscopic biopsy followed by histological diagnostics
CS – diagnostics, Marsh classification
• Type 0 – preinfiltrative – normal musoca
• Type 1 – infiltrative – increase in IEL
• Type 2 – hyperplastic – increase in IEL + crypt hyperplasia
• Type 3 – destructive – partial villous atrophy, crypt hyperplasia, uncomplete maturation of
enterocytes, edema and infiltration mucosa with inflammatory cells
• Type 4 – hypoplastic – diffuse atrophy, dense infiltration, colagen deposits
CS – associated diseases
• Dermatitis herpetiformis Duhring
• IDDM. Prevalence of CS is 4% in patients with IDDM
• Auto-immune thyreoiditis, IgA nefropathy, sclerotising cholangoitis, primary biliary cirrhosis, Down syndrome.
CS differential diagnostics
• Diffuse lymphoma
• Gastrinoma
• Eozinophilic gastroenteritis
• Cow milk intolerance
• Viral gastroenteritis
• Whipple’s disease
CS – complications
• Is a significant precancerosis.
• Malignant illness, occuring in about 10% of patients, is a complication of a long-term CS
• The cause is weakening of immune system, gluten-free diet is a protection against
malignancy
• The most often found tumor is
• LYMPHOMA – intestinal and extraintestinal generally out of T-cells, adenocarcinoma of
small intestine and esophageal squamous cell carcinoma
CS – complications
• Refractory sprue
- disease which responses to gluten-free diet for some period, then relapses even under full
gluten-free regime
• Collagenous sprue. Histologically, deposits of collagen in the muscularis propria of mucosa, under a basement membrane
• Hard to influence therapeutically, even using corticosteroids and immunosuppresion.
CS – complications
• Ulcers and stenoses of small intestine
• May cause diarrhea, abdominal pain, bleeding, obstruction
CS – therapy
• GLUTEN-FREE DIET
• Exclusion of all meals made with flour
• Improvement occurs within weeks
• Usually, the lactase deficiency also occurs – limit of milk intake
• Corticoids work against inflammation and suppress autoimmune response
• To be administered in a short-time period
(couple of weeks) with initial dosis of 40 mg daily then subtracting cca 5-10 mg each week.
CS – therapy
• In case of refractory sprue, long-term corticoid use is indicated
• Immunosuppresant use also possible – azathioprin, cyclosporine
• Substitution therapy - Fe, folic acid, vitamins K, B12 and D, calcium
CS – prognosis
• All patients have to be followed up.
• The course of pregnancy is normal in 70%
of women with CS, but relaps of disease during or after pregnancy is frequent
Dermatitis herpetiformis Duhring
• Chronical disese, foci of itching papulovesicular dermatitis with
predilecting distribution around elbows, knees, buttocks and scalp.
• In 1960s, the affection of small intestine same as in CS was described. It is also susceptible to gluten-free diet.
Dermatitis herpetiformis Duhring
• Clinical findings – in 95% without any digestive disorders
• At enterobiopsy, 80% show intestinal changes
• Diagnosis is made according to skin
biopsy, changes occur even outside lesion
• Therapy: DDS sulphons - Dapson, gluten- free diet
CS – children’s specialties
• Dropping number of heavy forms (breast- feeding is longer now, gluten becomes part of the diet later)
• Active disorder
intestinal symptoms prevail in the first 7-24 months, the child stops to grow, large
abdomen, large-volume stools, psychical changes – celiac crisis may occur,
vomiting, constipation
CS – children
• Have no acute clinical symptoms, or their severity is minimal
• Diagnosis is difficult
• Anorexia, returning abdominal pains, sloppy stool, slow growth, late onset of puberty.
• DH - versus atopic eczema
• Corticoids are not administered to children
