1. Celiac Disease
Celiac disease is characterized by small intestinal malabsorption of nutrients after the ingestion of wheat gluten or related proteins from rye and barley, villus atrophy of the small intestinal mucosa, prompt clinical and histologic improvement following strict adherence to a gluten-free diet, and clinical and histologic relapse when gluten is reintroduced
Celiac disease exhibits a spectrum of clinical presentations. Atypical celiac disease is fully expressed gluten-sensitive enteropathy manifest only by extraintestinal symptoms and signs including short stature, anemia, osteoporosis, and infertility. Silent celiac disease is fully expressed gluten- sensitive enteropathy usually found after serologic screening in asymptomatic patients. The atypical and silent variants are more common than classic or typical celiac disease, which is fully expressed gluten-sensitive enteropathy found in association with the classic gastrointestinal symptoms of malabsorption.

2. Refractory celiac disease, also known as unclassified or intractable celiac sprue, is defined as symptomatic, severe small intestinal villus atrophy that mimics celiac disease but does not respond to at least six months of a strict gluten-free diet. This is a diagnosis of exclusion that is not accounted for by inadvertent gluten ingestion, other causes of villus atrophy, or overt intestinal lymphoma.
CLINICAL FEATURES
CHILDHOOD PRESENTATION
The classic presentation of celiac disease in infancy is not easily missed. The typical history is of steatorrhea with or without vomiting and occasional cramping abdominal pain that can occur anytime after weaning when cereals are introduced into the diet, but especially in the first and second years of life. Classically, the child fails to thrive, is apathetic and irritable, and has muscle wasting, hypotonia, and abdominal distention. Watery diarrhea or occasionally constipation may be reported.

3. ADULTHOOD PRESENTATION
In the past, celiac disease was perceived to be a pediatric disorder, but the diagnosis now is being made increasingly in adults; currently, the overall mean age at presentation is approximately 45 years. Typical symptoms are chronic watery diarrhea , steatorrhea, abdominal distention and bloating. Symptoms also have changed during the past 50 years. Diarrhea now is reported less often. A proportion of these adult patients have short stature or give a history consistent with unrecognized celiac disease in childhood. In many, however, there is nothing to suggest previous disease, and it is possible that celiac disease can develop for the first time in adult life. Celiac disease also is being diagnosed increasingly in later life, with approximately 25% of cases diagnosed in patients older than 60 years.Vague abdominal discomfort and especially abdominal bloating are extremely common and can lead to a mistaken diagnosis of irritable bowel syndrome (IBS).
EXTRAINTESTINAL FEATURES:
Anemia : is a common manifestation of celiac disease in children and adults and usually is caused by impaired iron or folate absorption from the proximal intestine; in severe disease with ileal involvement, vitamin B12 absorption also is impaired.

4. Evidence of hyposplenism of unknown cause, with thrombocytosis, deformed erythrocytes, and splenic atrophy, occurs in up to 50% of adults with celiac disease but only rarely is seen in children. In many patients, evidence of hyposplenism disappears with elimination of gluten from the diet.
Osteopenia
Osteopenia is the most common complication of celiac disease, and its prevalence increases with age at diagnosis. More than 70% of patients with untreated celiac disease have osteopenia, and osteoporosis occurs in more than one quarter of all celiac disease patients. Osteopenia develops as a result of impaired calcium absorption (secondary to defective calcium transport by the diseased small intestine), vitamin D deficiency (caused by impaired absorption of this fat-soluble vitamin), and binding of intraluminal calcium and magnesium to unabsorbed dietary fatty acids (forming insoluble soaps, which are then excreted in the feces). Patients can present with bone pain, especially of the lower back, rib cage, and pelvis. Calcium and magnesium depletion can cause paresthesias, muscle cramps, and even frank tetany with also increased risk of bone fractures.
Neurologic Symptoms:Celiac disease often is found in patients presenting with nonhereditary ataxia, and progressive gait and limb ataxia may be the sole manifestations of disease in some patients. These abnormalities, referred to as gluten ataxia, are believed to result from immunologic damage to the cerebellum, posterior columns of the spinal cord, and peripheral nerves. The associations of celiac disease and epilepsy, frequently complex partial seizures, and bilateral parieto-occipital cerebral calcification are well recognized.

5. Gynecologic and Fertility Problems :Gynecologic and obstetric problems are common in women with untreated celiac disease. Amenorrhea occurs in one third of women of childbearing age and menarche is often delayed. Women with untreated celiac disease can present with infertility. Infertility secondary to impotence or an abnormally low sperm count can occur in men with untreated celiac disease.
Cutaneous:Increased skin pigmentation may be obvious in severely ill patients. In addition to dermatitis herpetiformis (DH) ( is a skin disease characterized by papulovesicular lesions that occur symmetrically over the extensor surfaces of the extremities and the buttocks, trunk, neck, and scalp. Unlike celiac disease, DH rarely is diagnosed in childhood and usually manifests in early or middle adult life. The diagnosis of DH requires demonstration by immunofluorescence of granular or speckled IgA deposits in an area of perilesional skin—that is, skin close to a lesion but not affected by blistering. DH is associated with a mild patchy enteropathy indistinguishable from celiac disease; because it has a patch distribution, multiple intestinal biopsies may be required for diagnosis. Thus, DH and celiac disease are two very closely related gluten-sensitive disorders but nonetheless distinct clinical disease entities. Most, if not all, patients with DH also have at least latent celiac disease, whereas less than 10% of patients with celiac disease have DH. Dapsone treatment at a dose of 1 to 2 mg/kg daily is effective and often diagnostic in its ability to heal the rash of DH and to relieve the pruritus rapidly, but the enteropathy associated with DH does not improve with dapsone. Six to 12 months of gluten withdrawal, however, usually reverses not only the intestinal but also the skin lesions in most patients with DH).
Ascites ,leg edema and anasarca may occur due to hypoproteinemia.

6. DIAGNOSIS:
Serum IgA EMA or tTG antibody and small intestinal biopsy are the most reliable diagnostic tests for celiac disease.
SEROLOGY:
Anti Endomysial Antibody and Tissue Transglutaminase Antibodies:IgA EMA has a sensitivity of 90%, specificity of 99%, and reproducibility of 93% and currently remains the gold standard. IgA antihuman tTG is slightly less reliable (sensitivity 93%, specificity 95%, reproducibility 83%).
Antigliadin Antibodies :Serum IgA and IgG AGA levels often are elevated in untreated celiac disease. Unfortunately, these tests have only moderate sensitivity and their specificity is substantially lower than those of IgA EMA or tTG tests.
SMALL INTESTINE BIOPSY
Although the diagnosis of celiac disease may be suspected on clinical grounds or as a result of abnormal serologic tests, biopsy of the small intestine has remained the standard test to establish the diagnosis. Scalloping or absence of duodenal folds has been noted in some patients with celiac disease .characteristic histology of celiac disease is villous atrophy with increased intraepithelial lymphocytes.
DX : S/S + SEROLOGY(EMA or tTG ) + SMALL INTESTINE BIOPSY .

7. TREATMENT
GLUTEN-FREE DIET :Removal of gluten from the diet is essential for treating patients with celiac disease . Avoid all foods containing wheat, rye, and barley gluten. Avoid all oats initially. After starting a gluten-free diet, most patients improve within a few weeks. In many, substantial symptomatic improvement is noticed within 48 hours, although it can take weeks or months to achieve full clinical remission.
DIETARY SUPPLEMENTS:In addition to the gluten-free diet, patients with newly diagnosed celiac disease should receive appropriate supplemental therapy to help correct nutritional deficiencies caused by malabsorption; iron deficiency is the most common. Deficiencies of vitamin D, vitamin B12, or folic acid are not uncommon. The risks of osteopenia and osteoporosis should be explained to all patients with celiac disease and general advice should be given about weight-bearing exercises, dietary calcium and vitamin D intake, If dietary calcium is inadequate, 500 to 1500 mg of supplemental calcium should be given. Vitamin D deficiency should be sought and treated .
GLUCOCORTICOIDS:glucocorticoids are not indicated in the routine management of celiac disease but are reserved for severely ill patients who present with acute celiac crisis manifested by severe diarrhea, dehydration, weight loss, acidosis, hypocalcemia, and hypoproteinemia.

8. NONRESPONSIVE CELIAC DISEASE
Nonresponsive celiac disease (NRCD) is a clinical diagnosis defined by the persistence of symptoms, signs, or laboratory abnormalities typical of celiac disease despite adherence to a gluten-free diet for at least six months.Ten percent of patients with celiac disease are nonresponsive either immediately after the initial diagnosis (primary NRCD) or following a period of response to the gluten-free diet (secondary NRCD). An approach to the evaluation of NRCD that is based on the early identification and correction of common causes and that culminates in the diagnosis of refractory celiac disease (which affects 1% of patients with celiac disease) . The single most common cause for NRCD is continued gluten ingestion, which is often inadvertent and occult. A persisting elevation of anti-tTG is strongly associated with ongoing gluten exposure. If no dietary causes can be identified, a small bowel biopsy should be repeated and the findings compared with the initial pretreatment biopsy. If repeat biopsies show ongoing changes consistent with active celiac disease, refractory celiac disease becomes likely. Other causes of a celiac- like enteropathy, however, should again be considered, including small bowel bacterial overgrowth, peptic duodenitis, hypogammaglobulinemia, tropical sprue, intestinal infections (e.g., giardiasis), Crohn's disease, and autoimmune enteropathy.
REFRACTORY CELIAC DISEASE
is defined as symptomatic, severe small intestinal villus atrophy that mimics celiac disease but does not respond to at least six months of a strict gluten-free diet and is not accounted for by other causes of villus atrophy or overt intestinal lymphoma, immunosuppressive therapy(corticosteroid with or without azathioprine) is considering in all patients with refractory celiac disease.

9. ULCERATIVE JEJUNOILEITIS
is a rare but serious complication of celiac disease characterized by ulceration and strictures of the small intestine. Ulcerative jejunoileitis should be suspected in patients with celiac disease who present with weight loss, abdominal pain, and diarrhea that do not respond to a gluten-free diet. Typically, patients also experience recurrent episodes of intestinal ulceration and obstruction with gradual weight loss despite surgery and strict adherence to a gluten-free diet. Areas of intestinal ulceration and stricture formation typically cause hemorrhage and obstruction. perforation with peritonitis also can occur. Diagnosis is made by enteroscopy, contrast studies of the small intestine, abdominal CT, capsule endoscopy, or laparotomy.
COLLAGENOUS SPRUE: is characterized by the development of a subepithelial collagen band thicker than 10 mm in the small intestine.
Small bowel lymphoma( T cell).
CA of small bowel and esophagus.

10. SMALL INTESTINAL BACTERIAL OVERGROWTH:
Short Bowel Syndrome:
characterized by malabsorption due to insufficient intestinal surface area, occurs in adults in whom less than 200 cm of small intestine is present. The major causes of SBS in adults are Crohn's disease for which multiple intestinal resections have been performed; mesenteric infarction from venous or arterial thrombosis, arterial embolism, or midgut volvulus; massive enterectomy performed to manage traumatic injuries or tumor resection, and radiation injury.
SMALL INTESTINAL BACTERIAL OVERGROWTH:
The upper small intestine is an environment of relatively low bacterial counts because of the combined effects of gastric acid and peristalsis. Bacterial counts in aspirates from the normal upper small intestine generally are less than 1000/mL.
The gold standard test for the diagnosis of SIBO is aspiration of small intestinal fluid with culture and bacterial counts of the aspirate; presence of more than 105 CFU/mL of duodenal aspirate is considered diagnostic.
A variety of noninvasive tests have been developed for diagnosing SIBO. The 14C-glycocholic acid breath test was one of the first breath tests used for this purpose and is based on the ability of bacteria to deconjugate bile salts. 14C-glycine is produced and metabolized, resulting in a peak of 14CO2 in the expired air.The currently used breath tests are based on the ability of bacteria to produce hydrogen or radiolabeled carbon dioxide after metabolizing a substrate such as glucose, lactulose, or xylose. Breath tests are simple and noninvasive and therefore are more attractive than is duodenal intubation or endoscopy for collecting intestinal aspirates.

11. Tropical Diarrhea and sprue:
Vitamin B12 deficiency is caused by bacterial utilization of the vitamin within the intestinal lumen before it can be absorbed across the mucosa.
Causes:
Anatomic abnormalities:Blind loop (Billroth II gastrectomy, end-to-side anastomosis), Small intestinal diverticulosis
,Small intestinal stricture (Crohn's disease, radiation enteritis, focal segmental ischemia).
Motility disorders:Diabetes mellitus, Scleroderma.
Reduced gastric acid secretion:Acid-lowering medication, Atrophic gastritis.
Abnormal connection between colon and proximal bowel:Gastrocolic or enterocolic fistula, Resection of ileocecal valve.
Tropical Diarrhea and sprue:
Diarrhea and malabsorption are common in the tropics and most often result from infectious causes. Enteric infections that cause diarrhea are common in tropical countries, a result both of deficient sanitation and the ambient temperature that fosters proliferation of infectious organisms in water and food. Tropical diarrhea affects not only the indigenous population but also visitors to the tropics.
Tropical sprue is a primary (i.e., not caused by other known disease) malabsorption syndrome that occurs in visitors to or residents of the tropics.

12. In contrast to celiac disease, in which involvement of the proximal small intestine predominates and, therefore, serum folate levels are low and vitamin B12 levels are normal, tropical sprue affects the distal small intestine and terminal ileum; as a result, serum folate levels are normal and vitamin B12 levels are low.
Malabsorption commonly is established by testing for fecal fat, measuring serum levels of vitamin B12 and folate, and testing for d-xylose absorption. Fecal examination for occult blood and for parasites is essential.
Whipple's disease: is a chronic systemic infection caused by a Gram-positive bacterium, Tropheryma whipplei. The small intestine is affected most often, but a variety of other organs also may be involved, including the joints, the central nervous system (CNS), and the heart. Clinical symptoms and findings are protean and include weight loss, diarrhea, malabsorption, fever, arthralgias, skin hyperpigmentation, and dementia.