UNUSUAL CAUSE OF ABDOMINAL DISTENSION

From Dr. S. Balasubramanian’s unit, Dr.S.Srinivas (Ped. GE Dept.)

K.K.C.T.H

Dr.Aparna

CASE SCENARIO

6 year old male:

• Progressive abdominal distension x 3 years

• Diarrhea & vomiting x 15 days

• Normal appetite and activity and no other complaints

Contd….

• Hospitalised for diarrhoea at 9/12

• Treatment for tuberculosis at 2 years for 6 months

• Normal Family history

• Normal development

• North Indian (Marwari from Rajasthan)

• Wheat based diet from early infancy

On examination:

• Grade 2 clubbing, not anemic

• BMI-12.04 - Underweight

• Distended abdomen, visible bowel loops

• No organomegaly or free fluid

Grade 2 clubbing

Possibilities considered:

• IBD

• Coeliac disease

• Tropical sprue

• Tuberculous abdomen

Investigations :• Normal counts, RFT,LFT

• Normal urine and stool routine (Occult blood –ve)

• ESR 80 (1 hr)

• Ig profile- IgG-2145,IgA-267,IgM-259,IgE-552

• Gastric juice for AFB negative

• Barium meal study revealed mild malabsorption pattern

Contd….• Tissue transglutaminase Ig A >800

• Antiendomysial antibody +ve

• Upper GI scopy - mild scalloping of the duodenal mucosa

• HPE revealed total villous atrophy

COELIAC DISEASE

On follow up after 2 weeks of GFD

Coeliac disease

Review of literature

HISTORY

• Greek physician in the first century AD- “The Coeliac Affection.” - Greek word “koelia” (abdomen): “If the stomach be irretentive of the food and if it pass through undigested and crude, and nothing ascends into the body, we call such persons coeliacs”.

• “a child who was fed upon a quart of the best Dutch mussels daily, throve wonderfully, but relapsed when the season for mussels was over; next season he could not be prevailed upon to take them.” Thus documenting improvement following the introduction of a gluten-free diet, and the relapse after reintroduction of gluten.

• Breakthrough- Dicke - noticed that during bread shortages in the Netherlands caused by World War II, children with celiac disease improved. He also saw that when Allied planes dropped bread into the Netherlands, they quickly deteriorated.

Coeliac disease:• Autoimmune enteropathy caused by a permanent

intolerance to gluten.

• Gluten-main storage protein of wheat. The alcohol-soluble fraction (prolamin) of gluten, gliadin, is toxic in celiac disease, as are similar proteins in barley (hordein) and rye (secalin) .

• Associated with maldigestion and malabsorption of nutrients, vitamins, and minerals in the gastrointestinal tract.

Celiac disease

PATHOGENESIS

• Approximately 97%- genetic markers on chromosome 6p21- HLA-DQ2 and HLA-DQ 8

• The immune response involves CD4+ T cells in the lamina propria that recognize specific immunogenic gluten peptides, processed and presented by antigen-presenting cells.

• Gluten antigens are modified enzymatically by tissue transglutaminase (tTG).

• tTG is the target of endomysial autoantibodies it deamidates glutamine residues in gliadin by converting them to glutamic acid residues.

• more antigenic than native gluten peptides and usually adhere to the binding grooves of HLA-DQ2 and HLA-DQ8 molecules.

• stimulate production of autoantibodies in the form of anti-tTG and antiendomysial antibodies

• CD4+ T lymphocytes infiltrate the lamina propria, T cells produce proinflammatory cytokines, and consequently destruction of the surface epithelium occurs. Flattening of the mucosa ensues.

Gastrointestinal manifestations

• Diarrhea, steatorrhea, flatulence, abdominal distension and weight loss or FTT

• Diarrhea – episodic

• Nocturnal or early morning diarrhea is common.

• High fat content -light tan or grayish and greasy

• Typical form presents with GI

symptoms, characteristically appear at

age 9-24 months.

• Behavioral changes common- irritability

,introverted attitude.

• Celiac crisis - explosive watery

diarrhea, marked abdominal distension,

dehydration, hypotension, and

lethargy, electrolyte abnormalities,

including severe hypokalemia.

EXTRA INTESTINAL MANIFESTATIONS

• Hematopoetic- anaemia, haemorrhage

• Skeletal- osteopenia, pathological fractures

• Muscular- atrophy, tetany, weakness

• Nervous-peripheral neuropathy, ataxia

• Endocrine- 2o Hyperparathyroidism

• Others-edema, dermatitis herpetiformis

Atypical presentation

• 70% atypical

• Infants and Toddlers- GI symptoms and FTT predominate

• Childhood- minor GI symptoms, inadequate rate of weight and height gain, and delayed puberty more common.

• Teenagers and young adults- anemia

• Adults and elderly- GI symptoms are more prevalent, although minor.

• Associated autoimmune disorders -Rheumatoid arthritis , SLE, autoimmune liver disease, Addison’s disease, alopecia areata, Sjögren’s syndrome , cholangitis, primary biliary cirrhosis, autoimmune hepatitis, peripheral neuropathy, psoriasis, and cardiomyopathy

• Small bowel malignancies, adenocarcinoma, and enteropathy-associated T-cell lymphoma can occur if untreated

Clinical presentation

Compared to West, celiac disease in India has later onset

of disease

India

• Mean age of onset of symptoms is 2.5 – 3 yrs

• Mean age at diagnosis is 6 - 8

West

• Mean age of onset of symptoms is 9 – 18 mos

• Diagnosed by 2 yrs of age

Modified ESPGHAN criteria 1990

1. Abnormal jejunal biopsy while on gluten

2. Clinical improvement on GFD

If age < 2 yrs of age, gluten challenge is suggested as there may be other causes of villous atrophy like CMPI, viral diarrhea

Which serological test?

Antibody testing in Indian children with celiac disease

SK Yachha, R Aggarwal, Srinivas S, A Srivastava, SK Somani, S Itha

Indian J Gastroenterol. 2006 May-Jun;25(3):132-5.

Sensitivity Specificity Accuracy

EMA 82.6% 94.7% 88.1%

IgA tTG 73.9% 100% 85.7%

IgA AGA 60.8% 60.8% 73.8%

IgG AGA 73.9% 26.3% 52.4%

Modified Marsh criteria

Type 0 : Normal mucosa

Type I : Infiltrative - normal mucosa with increased IELs

Type II : Hyperplastic- in addition has crypt hperplasia

Type III : Destructive - diagnostic lesion of celiac disease

– A. partial VA

– B. sub-total VA

– C. total VA

Type IV : Hypoplastic

Rostami Am.J.Gastro. 1989; 94: 888

Guideline for the Diagnosis and Treatment of Celiac Disease

in Children: NASPGHAN recommendations

• The diagnosis of CD is considered definitive when there

is complete symptom resolution after treatment with a

strict GFD in a previously symptomatic individual with

characteristic histologic changes on small intestinal biopsy

• A positive serological test that reverts to negative after

treatment with a strict GFD in such cases is further

supportive evidence for the diagnosis of CD

JPGN Jan 2005 40:1–19

• INDIAN PEDIATRICS-VOLUME 42-NOVEMBER 17, 2005

Dr.Malathi Sathiyasekeran, Dr.S.Shivbalan

reported 3 cases seen in Chennai with characteristics features of CD who responded well to gluten free diet (GFD).

Management• Strict lifelong adherence to a

gluten-free diet.

• Growth and development in children returns to normal with adherence to the gluten-free diet

• Antibody levels may revert to normal in 6 to 12 months

• Complete histological resolution may take up to 2 years .

The National Institutes of Health Consensus Development Panel on celiac disease identified six elements essential to managing individuals affected by celiac disease:

C Consultation with a skilled dietitian;

E Education about celiac disease;

L Lifelong adherence to a gluten-free diet;

I Identification and treatment of nutritional deficiencies;

A Access to an advocacy group; and

C Continuous long-term follow-up.

New and developing therapies for

celiac disease

• Emerging research: decrease gluten exposure, to modify intestinal permeability and to modulate immune activation.

• Enzymes designed to digest gluten and the use of inhibitors to decrease the migration of gluten peptides into the lamina propria.

• Other potential therapeutic maneuvers include -binding of gluten by polymers, use of tissue transglutaminase (TTG) inhibitors and DQ2 or DQ8 blockers, or modulation of cytokine production.

Gluten-free grains and starches

• Amaranth • Arrowroot• Buckwheat • Corn• Flax • Flours made from • nutsbeans and seeds• Millet • Montina™• Potato starch• Potato flour • Quinoa• Rice• rice bran • Sago• Sorghum • Soy (soya)• Tapioca • Teff

Take home message

• Reportedly high prevalence of 1 in 310 in Punjab school children.

• Good history, high index of suspicion will help in early diagnosis and in management of this disease

THANK YOU