Presented by: Supervised by:

Dr. Saleh Salman Dr.Adnan Al-Asosi

Mr. N I

Age : 48

Gender : male

Nationality : Bangladeshi

Date of admission : 16/8/2014

Date of discharge : 26/8/2014

Situation and background 48 years , male patient , previously healthy , non smoker , not

alcoholic , came to medical causality complaining of abdominal pain and vomiting .

this was the 4th visit to causality ( seen before by surgical and medical doctors ) .

The patient has history of five days duration of peri-umbilical abdominal pain of moderate severity , colicky in nature , associated with multiple episodes of vomiting ( 3 times per day in average )

there is no ( fever, weight loss , change in bowel habits , dysuria , melena , hematemesis , skin lesions, or joint pain …)

There is no clear aggravating or relaxing factors

There is no clear radiation

Assessment The patient vitally stable :

Bp= 143/95 HR=86 TEMP=36.6

He has no jaundice , pallor, or cyanosis…….

CVS: S1S2+ O

Chest : clear bilaterally

Abdomen : soft and lax , +ve bowel sounds, no rigidity or rebound , mild peri umbilical and RT iliac fosatenderness

CNS : no focal deficit , no abnormal movement , no abnormal behavior

LL: no edema , no signs of DVT , Intact perpheralpulsation

Initial investigation: X-ray chest : normal

X-ray abdomen : no air under diaphragm, no air fluid level

ECG : normal

7.40PH20000WBC

44Amylase33SEG

7.5Glu ( random)13LYM

99Cr5mono

138Na 42Eosin

3.8K8770

negativeTNT159Hgb

unremarkableUrine R\M312PLT

1.05INR

29APTT

SUGGESTION

Further work up

6ESRnegativeCRP

eosinophiliaBlood film

No parasite or ova seen WBC=0-1Stool R/M

41Alt38Alb

73Alk-pho304Uric acid

2.22Ca1.9T.G

4.3Cholesterol

22T bil

NegativeBrucellosis testNegative Widdal test

negativeSkin PPD test

During hospital stay :

the patient received empirical treatment for gastroenteritis as well as parasitic infection but still has abdominal pain and Eosinophilia

He received also supportive treatment with IV fluid, losec and anti-emetics

Surgical doctors was consulted again : no acute surgical emergency

In summary

48 years , male patient , previously healthy

complaining of abdominal pain and vomiting

Positive lab finding : eosinophilia

Imaging studies : suggestive for distal ileal inflammation

DIAGNOSIS?

Next step = endoscopy

Eosinophilic gastroentritis

INTRODUCTION Eosinophilic gastroenteritis (EG) represents one member of a

family of diseases that includes (eosinophilic esophagitis, gastritis, enteritis, and colitis ), collectively referred to as eosinophilic gastrointestinal disorders (EGIDs) .

Despite its rarity, eosinophilic gastroenteritis needs to be recognized by the clinician because this treatable disease can masquerade as irritable bowel syndrome. The diagnosis of EG is confirmed by a characteristic biopsy and/or Eosinophilic ascitic fluid in the absence of infection by intestinal parasites or other causes of intestinal eosinophilia.

Eosinophilic esophagitis is a distinct clinical entity and it is discussed elsewhere.

EG has a peak age of onset in the third decade .

The clinical features of EG are related to the layer(s) and extent of bowel involved with eosinophilicinfiltration: mucosa; muscle; and/or subserosa .

The prevalence of each subtype is unknown because of reporting and referral biases. Surgical series report a predominance of muscular disease with obstruction , while medical series primarily describe patients with mucosal involvement .

The disease can affect patients of any age, but typical presentations are in the third through fifth decade with a male predominance

MUCOSAL DISEASE Eosinophilic mucosal infiltration produces nonspecific symptoms

which depend upon the organ(s) involved. The entire gastrointestinal tract from esophagus to colon, including bile ducts, can be affected .

The previous suggestion that EG has a predilection for the distal antrum and proximal small bowel may have reflected a sampling bias because of the availability of these areas for biopsy .

In a retrospective study of 40 patients, the most common symptoms were abdominal pain, nausea, vomiting, early satiety, and diarrhea, suggesting a possible diagnosis of irritable bowel syndrome .

Only one-third of patients had a weight loss of 2.4 kg or more.

Patients with diffuse small bowel disease can develop malabsorption

Laboratory findings :

Peripheral eosinophil counts are usually elevated, ranging from 5 to 35 percent with an average absolute eosinophil count of 2000 cells/µL , but may be normal in about 20 % of patients .

The absolute eosinophil count rather than percent eosinophils is the best indicator to document eosinophilia.

Patients with malabsorption may have the typical laboratory findings of this disorder: abnormal D-xylose test, increased fecal fat excretion, prolonged prothrombin time, and reduced serum iron concentration.

Hypoalbuminemia and anemia can be induced by a protein-losing enteropathy, impaired iron absorption, and occult gastrointestinal bleeding.

The ESR is usually normal , but can be elevated modestly in about 25 percent of patients .

Serum IgE levels can be elevated, especially in children, and up to 50 percent may be atopic or have a history of food intolerance or allergy.

Barium studies of the gastrointestinal tract may suggest the diagnosis but are neither sensitive nor specific. They typically reveal thickening or nodularity in the antrum and a thickened or "saw-tooth" mucosa in the small bowel .

Diagnosis :

The diagnosis of mucosal EG is typically confirmed by endoscopic biopsies, which reveal ≥20 to 25 eosinophils per high power field on microscopic examination. Upper endoscopy with biopsy of the stomach and small intestine is diagnostic in at least 80 percent of patients . Typical endoscopic findings in mucosal disease include nodular or polypoid gastric mucosa, erythema, or erosions .

There are specific recommendations with respect to the diagnosis

Biopsies should be taken from both normal and abnormal appearing mucosa because even normal appearing mucosa can demonstrate eosinophilic inflammation .

Multiple biopsy samples (at least four to five biopsies per site) should be taken from both the stomach and small intestine including areas with visual abnormalities to overcome sampling error . Biopsies that reveal increased eosinophils in sheets in conjunction with mucosal architectural abnormalities are diagnostic in the appropriate clinical setting.

On the other hand, given its patchy mucosal involvement, even multiple normal mucosal biopsy specimens cannot exclude the diagnosis of EG in some patients.

In one series, surgical biopsy of the terminal ileum was positive for mucosal involvement in five of six patients . Whether colonoscopic biopsies of the terminal ileum would be equally diagnostic is unknown. In two small series, colonoscopicbiopsies revealed the disease in 6 of 11 patients

MUSCLE LAYER DISEASE Eosinophilic infiltration of the muscle layer of the gastrointestinal

tract results in a thickened, rigid gut and symptoms of intestinal obstruction such as nausea, vomiting, and abdominal distention .

Pseudo-achalasia, esophageal stricture, perforation, or obstruction of the gastric outlet, small bowel, or rarely the colon can occur depending on the site of infiltration.

Food intolerance or allergic history IS NOT usually present in patients with this form of eosinophilic gastroenteritis (EG).

Patients may present with a peripheral eosinophilia with absolute eosinophil counts averaging 1000 cells/µL .

Muscle involvement has been demonstrated in eosinophilicesophagitis in which it probably contributes to dysphagia by impairing esophageal motility

Diagnosis :

The diagnosis of muscle layer disease is typically made after resection of small bowel for obstruction.

In less acute presentations, Barium studies usually reveal irregular luminal narrowing, especially in the distal antrumand proximal small bowel. These findings can mimic those induced by cancer, lymphoma, or other malignancies.

Endoscopic biopsies should be performed, but they are oftennondiagnostic because mucosal involvement is lacking.

In these cases, laparoscopic FULL THICKNESS biopsy is usually necessary to exclude malignancy, thereby avoiding unnecessary radical resectional surgery by confirming the diagnosis

SUBSEROSAL DISEASE Patients with subserosal eosinophilic gastroenteritis (EG)

present with isolated ascites or ascites in combinationwith symptoms characteristic of mucosal or muscular EG .

The diagnostic feature is a marked eosinophilia, up to 88 percent, in the ascitic fluid.

Patients in this subgroup may have an allergic history and

peripheral eosinophil counts as high as 8000 cells/µL .

An eosinophilic pleural effusion may also be present

PATHOGENESIS

The pathogenesis of eosinophilic gastroenteritis (EG) is not well understood. Several epidemiologic and clinical features suggest an allergic component:

Approximately one-half of patients have allergic disease, such as asthma, defined food sensitivities, eczema, or rhinitis

Some patients have elevated serum IgE levels.

The role of food allergy as a stimulus to EG has not been as clearly defined as for eosinophilic esophagitis. However, several reports have described an allergic response to food allergens with improvement in disease activity with allergen avoidance with an elemental or elimination diet .

In allergic EG patients, but not those with conventional anaphylactic food allergy, a population of IL-5 expressing food allergen specific T cells have been characterized . This suggests that food exposure activates IL-5+ T cells in EG, leading to gut eosinophilia.

As a result, a thorough allergy history and workup are important in management of this illness.

Although food hypersensitivity plays an important role in EG pathogenesis, no food allergy test (skin, patch, or RAST/ImmunoCAP test) has been shown to effectively identify specific culprit foods leading to clinical improvement.

Once eosinophils are recruited to the gastrointestinal tract, they are able to persist through the release of eosinophilactive cytokines such as interleukin-3, interleukin-5, and granulocyte macrophage-colony stimulating factor (GM-CSF)

Eotaxin, a chemokine, appears to have a central role in the recruitment of eosinophils into the small intestine in response to antigen challenge .

Eosinophils may cause local inflammation by release of eosinophil major basic protein, a cytotoxic cationic protein .

DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS

Eosinophilic gastroenteritis (EG) should be suspected in any patient with

gastrointestinal symptoms

associated with peripheral eosinophilia.

It should also be considered before making a diagnosis of irritable bowel syndrome. As noted above, the diagnosis of EG can be made in almost all cases by suspicion in the appropriate clinical context and endoscopic or full thickness biopsy or paracentesis.

Other diseases in which gastrointestinal symptoms are associated with peripheral eosinophilia usually can be distinguished from EG with simple laboratory tests and/or endoscopic biopsies:

Intestinal parasites ( such as Ancylostoma, Anisakis, Ascaris,

Strongyloides, Toxocara, Trichiura, Capillaria, and Trichinella ) all cause eosinophilia and should be excluded with careful examination of the stool for ova or parasites and/or appropriate serologic testing. Such stool examination may reveal Charcot-Leyden crystals, which are the product of eosinophil granules. Infection with the dog hookworm, Ancylostoma caninum, mimics EG clinically and pathologically with eosinophilic infiltration of the gut wall and even ascites. Although reported so far only from Australia, the worm has a worldwide distribution and is easy to overlook even on pathologic specimens .

Malignancies, such as lymphoma, gastric cancer, and colon cancer, can present with intestinal obstruction, masses on barium radiography, and eosinophilia. They can be differentiated

from EG by endoscopic or full thickness biopsy.

Conversely, EG can mimic some of the features of a MALT lymphoma, with bowel wall thickening and marked retroperitoneal lymphadenopathy.

Crohn's disease can usually be differentiated by the typical architectural distortion that is not found in EG. Rarely, Crohn'sdisease or ulcerative colitis may be associated with peripheral eosinophilia and/or an eosinophil rich tissue infiltrate.

Polyarteritis nodosa is associated with systemic manifestations, a markedly elevated ESR , and perivasculareosinophilia .

Hypereosinophilic syndrome (HES) is an idiopathic condition associated with marked peripheral eosinophilia

and may rarely present with predominantly gastrointestinal symptoms. Many EG patients may formally fulfill the diagnostic criterion for HES (AEC ≥1500 cells/mL present for

over six months). However, HES, in contrast to EG, involves other organs such as the heart, lungs, brain, and kidneys and generally has a progressively fatal course . Because of the potential for confusion, patients with EG should be counseled that their prognosis is generally good and that they do not have HES.

Eosinophilic granuloma (Langerhans cell histiocytosis), which can present as an antral mass, is diagnosed by its typical GRANULOMATOUS appearance on biopsy specimens .

An eosinophilic gastroenteritis, characterized by abdominal pain, diarrhea, gastrointestinal bleeding, and colitis, may precede or coincide with the vasculitic phase of the Churg-Strauss syndrome. Asthma is the cardinal feature of this disorder (occurring in more than 95 percent of patients) and usually precedes the vasculitic phase by approximately 8 to 10 years.

PROGNOSIS AND TREATMENT

Data on the natural history and therapy of (EG) are limited to case reports and retrospective series of less than 20 patients.

Untreated patients with EG may rarely remit spontaneously or progress to severe malabsorption and malnutrition .

There have been no prospective, randomized therapeutic clinical trials. Thus, treatment is empiric and based upon the severity of the clinical manifestations.

Patients who are SYMPTOMATIC or have evidence of MALABSORPTION may be treated with systemic glucocorticoids. Micronutrient deficiencies should be sought and replaced as needed. [ In cases of severe malabsorption, a dietary consultation may be valuable to help identify nutritional deficits] .

Although food hypersensitivity plays an important role in EG pathogenesis, no food allergy test (skin, patch or allergen specific IgE) has been shown to effectively identify specific culprit foods leading to clinical improvement of EG symptoms or tissue eosinophilia.

Thus, at present there is no evidence base to support routine food allergy testing of EG patients for use in clinical decision making.

A prospective trial in adults with EG has demonstrated clinical remission with a six-week course of dietary elimination. In this study, three of seven adults undergoing an empiric six food elimination diet and six of six adults undergoing elemental diet had significant reduction in symptoms, complete histologic remission, endoscopic improvement and normalization of peripheral eosinophilia within six weeks .

The empiric elimination diet is similar to the six-food elimination diets employed in EoE, with the patient avoiding soy, wheat, corn, egg, milk, peanut, and seafood .

While empiric dietary elimination and elemental diets have also demonstrated success in pediatric EoE patients, limitations exist due to patient tolerance.

Dietary therapy should be pursued in motivated patients under the guidance of a dietitian trained in eosinophilicgastrointestinal disorders.

If dietary measures do not result in decreased symptoms and tissue eosinophilia, we suggest a trial of prednisone (typically 20 to 40 mg/day).Improvement usually occurs within two weeks regardless of the layer of bowel involved . Prednisone should then be taperedrapidly over the next two weeks. However, some patients require more prolonged therapy (up to several months) to produce resolution of symptoms .

Patients not responding to prednisone can be tried on intravenous glucocorticoids.

The subsequent course is variable.

Some patients have no recurrences , or only require periodic glucocorticoid bursts, while most experience recurrent symptoms during or immediately after the Predniaon taper. The latter patients may require long-term, low-dose maintenance therapy with prednisone (eg, 5 to 10 mg/day). Other patients experience periodic flares months to years after the initial episode. They can be treated with another short course of oral prednisone, 20 to 40 mg/day, followed by a rapid taper

Several other approaches have been described in case reports or small series:

Successful transition from oral, conventional

glucocorticoids to budesonide(non-entericallycoated) was described in patients with EG involving the gastric antrum and small intestine . It should be noted that the formulation of budesonide currently available for gastrointestinal use is in controlled ileal release capsules, which largely bypass the upper gastrointestinal tract.

Oral cromolyn (800 mg/day in four divided doses) has been effective for short- and long-term management in some , but not all case reports. This agent works by preventing the release of mast cell mediators, including histamine, platelet-activating factor, and leukotrienes, and also is thought to reduce absorption of antigens by the small intestine.

Ketotifen (Zaditen), an H1-antihistamine, has been helpful in individual cases . The drug is approved for treatment of urticaria in Canada, Europe, and Japan, but is not available in the United States. In adults, it is administered at a starting dose of 1 mg at night and increased to 2 to 4 mg per day for one to four months.

The leukotriene antagonist,montelukast , was effective in some reported cases, but not in others

A clinical response to suplatast tosilate (a novel antiallergic drug that suppresses cytokine production including interleukin-4 and interleukin-5 from T helper 2 cells) was described in a single patient .

In a preliminary report of four patients, treatment with a

humanized anti-interleukin-5 antibody was associated with reduced peripheral and tissue eosinophilcounts but had NO effect on symptoms . Rebound eosinophilia has been observed after the drug was discontinued .

A report of nine patients treated with omalizumab( which is a recombinant humanized IgG1 monoclonal antibody that binds IgE with high affinity and has been developed for the treatment of allergic diseases described significant improvement in symptoms and measures of IgE mediated allergy . Tissue eosinophilia was reduced but results were not statistically significant.

SUMMARY AND RECOMMENDATIONS

The signs and symptoms of eosinophilic gastroenteritis (EG) are related to the layer(s) and extent of bowel involved with eosinophilic infiltration: mucosa; muscle; and/or subserosa.

Eosinophilic mucosal infiltration produces nonspecific symptoms, which depend upon the organ(s) involved. Most common symptoms are abdominal pain, nausea, early satiety, vomiting, diarrhea, and weight loss.

Eosinophilic infiltration of the muscle layer of the gastrointestinal tract results in a thickened, rigid gut and symptoms of intestinal obstruction such as nausea, vomiting, and abdominal distention.

Patients with subserosal EG present with isolated ascites or ascites in combination with symptoms characteristic of mucosal or muscular EG.

We suggest the following approach, which is based upon observational data and clinical experience:

In patients who are symptomatic or have evidence of malabsorption, we suggest an initial attempt at an empiric elimination diet, an elemental diet, or a six-food elimination diet for six weeks. This approach is similar to dietary interventions used to treat eosinophilic esophagitis.

If a dietary approach is undertaken, patients should be referred to a dietitian to obtain proper education on the foods to avoid. If a history of environmental allergens is identified, these should be treated in conjunction with the diet.

If the dietary changes are successful at reducing symptoms, peripheral eosinophilia, and tissue eosinophilia, foods can be added back slowly in a systematic fashion from least allergenic to most allergenic.

We follow patients based upon their symptoms and the changes in peripheral eosinophilia. We perform a repeat endoscopy when there is uncertainty regarding the response to treatment and/or degree of ongoing disease activity.

In patients who decline a dietary approach or whose symptoms, tissue and peripheral eosinophilia do not improve after the diet, we suggest a trial of prednisone (20 to 40 mg/day).

Improvement usually occurs within two weeks regardless of the layer of bowel involved. Prednisone should then be tapered rapidly over the next two weeks. However, some patients require more prolonged therapy (up to several months) to produce resolution of symptoms. Patients who relapse immediately after steroid cessation may need chronic low dose steroids or transition to budesonide or other agents as outlined above.

Refference

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