Tugas 9 November 2021

1. Selesaikan kasus ini

2. Tinjauan pustaka anemia

A 24-Year-Old Man With Symptomatic Anemia

Background
A 24-year-old Caribbean man who is currently incarcerated presents with symptomatic
anemia. He is primarily complaining of exertional dyspnea, generalized fatigue, and some
mild chronic nausea. He has no known history of hematemesis, melena, rectal bleeding, or
hemoptysis.
His family history is significant for sickle cell anemia in both his grandmother and sister. His
medical history is limited to asthma that is controlled with salbutamol and beclomethasone
inhalers and to previous admissions for symptomatic idiopathic anemia, for which he has
been maintained on iron supplementation.
The patient is a nonsmoker and does not drink alcohol. He has no history of nonsteroidal anti-
inflammatory drug or aspirin use. His diet is varied and nonvegetarian.

Physical Examination and Workup

Upon physical examination, the patient appears to be well, although he does exhibit
significant conjunctival pallor. His pulse is regular, at 88 beats/min, and his blood pressure is
110/64 mm Hg. No lymphadenopathy, jaundice, clubbing, or edema is noted. A soft,
pansystolic murmur is detected over the tricuspid and aortic valves, without any stigmata of
endocarditis.
The respiratory examination is unremarkable. No masses, tenderness, or hepatosplenomegaly
are noted on the abdominal examination. A rectal examination reveals no masses, gross
blood, or melena. The stool is brown and heme-negative.
The patient has had multiple admissions in the past 5 years for symptomatic anemia, all with
similar presentations. Each time, he was noted to have iron deficiency anemia, with a
hemoglobin level between 6 g/dL and 7 g/dL, as well as low mean corpuscular volume and
low serum ferritin. He has never had documented episodes of gastrointestinal (GI) or extra-GI
blood loss. He has complained intermittently of nausea but has not had any vomiting.

Figure 1.
Figure 2.

Numerous investigative procedures were completed during these previous admissions; the
findings of these procedures included normal endoscopic findings (however, no D2 biopsies
were done) and negative tissue transglutaminase, with normal levels of immunoglobulin A.
Autoantibody findings (antinuclear antibody, antineutrophil cytoplasmic autoantibodies,
double-stranded DNA, and small nuclear ribonucleoprotein Sm) were all negative. A direct
Coombs test result was also negative. In addition, hemoglobin electrophoresis was normal,
eliminating the possibility of sickle cell anemia.

During the current admission, another series of tests is performed. The results are as follows:
 Hemoglobin level: 6.5 g/dL
 Mean corpuscular volume: 64.5 μm3
 White blood cell count: 4.2 × 103 cells/μL
 Platelet count: 405 × 103 cells/μL
 Neutrophil count: 1.6 × 109 cells/L
 Lymphocyte count: 2.1 × 109 cells/L
 Eosinophil count: 1 × 109 cells/L
 Ferritin level: 9 ng/mL
 C-reactive protein level: <5 mg/L

Tests for autoantibodies (immunoglobulin), celiac serology, liver function, hemoglobin

electrophoresis, vitamin B12, and folate all return normal results.
Colonoscopy is performed and is normal to the terminal ileum, with no underlying cause of
anemia established. The patient undergoes a repeat endoscopy (having already had a normal
endoscopy 1 year earlier). The appearance of the esophagus and duodenum is unremarkable.
Patches of the gastric mucosa however, have an odd, nodular appearance (Figure 1). The area
is biopsied; the histology is shown here (Figure 2).

What is the underlying etiology of the patient's anemia?

Hint: The histologic examination reveals florid infiltration of specific cells. Also, carefully
consider the white blood cell count differential
A. Celiac sprue
B. Idiopathic eosinophilic gastroenteritis
C. Eosinophilic granuloma (histiocytosis X)
D. Crohn disease
Discussion
The patient was diagnosed with idiopathic eosinophilic gastroenteritis on the basis of the
diffuse eosinophilic infiltrate seen on the histologic samples taken from the nodular area of
his gastric antrum (Figure 2).

Eosinophilic gastroenteritis is a rare inflammatory disorder characterized by eosinophilic

infiltration of the GI tract, without any known cause of eosinophilia. The gastric antrum and
duodenum are primarily involved, but it can also affect the esophagus and colon. It was first
described by Kaijser in 1937.[1] Although more than 300 cases have been reported worldwide,
the true incidence is unclear. A confounding factor in its characterization is the lack of
diagnostic precision.[2]
This condition is an uncommon GI disease that affects adults and children. It usually presents
between the third and fifth decades of life; however, it may present in patients of any age. It
appears to be slightly more common in white males. A coexistent history of atopy (in
approximately 50% of cases), such as asthma (as seen in this case), hay fever, eczema, or
food intolerances, is common.

Although the precise underlying pathophysiologic mechanism remains unknown, the most
widely accepted theory involves mast cell activation by possible allergenic insult, leading to
histamine and cytokine release, which causes eosinophil activation. Allergens (eg, food,
virus, immunoglobulin) initially enter the GI tract via the compromised integrity of the gut
mucosa. The subsequent activation of eosinophils by the allergen leads to the release of
platelet-activating factor, histamines, toxic proteins, and leukotrienes, which results in
mucosal damage and inflammation. Few reports have described death resulting from this
condition; however, malnutrition and intestinal perforation may be seen.[2,3,4,5,6,7]
The time between the initial presentation and the diagnosis may be months or years, as a
result of the broad spectrum of presenting symptoms. The fact that the presenting features
may overlap with those of other, more common underlying GI diseases (such
as inflammatory bowel disease) can lead to misdiagnosis and unnecessary therapy.[2,4]

For a definitive diagnosis of eosinophilic gastroenteritis, the following four criteria must be
met[2,6]:
 Presence of GI symptoms
 Demonstration of eosinophilic infiltration (>20 eosinophils per high-power field) in
one or more areas of the GI tract
 Absence of alternative causes of eosinophilia
 No involvement outside of the GI tract (ie, no systemic eosinophilic pathology)

Histologic subclassification of eosinophilic gastroenteritis is determined according to the

layer of the GI tract involved (mucosa, muscularis, or serosa). The clinical manifestations are
also dependent on the affected area. Patients presenting with vomiting, abdominal pain,
diarrhea, bloody stools, failure to thrive, and iron deficiency anemia often have mucosal
infiltration. Patients with obstructive symptoms or dysphagia tend to have muscular
involvement. Serosal involvement presents with eosinophilic ascites, which has been well
described in the literature.[2,4]

The differential diagnosis includes all conditions with presenting features similar to those
described above (ie, inflammatory bowel disease), as well as those that produce eosinophilia.
Eosinophilic infections include parasitic infections (Ancylostoma
caninum, giardiasis, strongyloidosis, and other zoonoses), connective tissue diseases
(scleroderma, dermatomyositis, polymyositis), vasculitis (Churg-Strauss
syndrome, polyarteritis nodosa), drug reactions (sulfonamides, penicillin, cephalosporin,
carbamazepine, azathioprine, L-tryptophan, gold salts), celiac disease, and lymphoma.[2]
Investigations must center on confirmation of peripheral eosinophilia, evidence of increased
eosinophil counts in GI tissue (defined variably as 10-50 eosinophils per high-power field),
and the exclusion of alternative diagnoses. Imaging may help demonstrate the extent of bowel
involvement, but it cannot distinguish this condition from alternative, more common
diagnoses (eg, Crohn disease, ulcerative colitis).

Radiographic findings may be nonspecific or totally absent. Thickened intestinal walls and
lymphadenopathy may be seen on ultrasonography and CT. Endoscopic findings are
nonspecific and varied, but histologic demonstration of eosinophils in tissue samples is the
criterion standard. If serosal involvement with ascites is noted, an ascitic tap that is rich in
eosinophils is diagnostic.[2,3,4]
Once the diagnosis of idiopathic eosinophilic gastroenteritis has been confirmed, the
mainstay of treatment is primarily oral glucocorticoids, such as prednisone, to halt the
inflammatory process and control symptoms. Budesonide has also been used successfully as
an alternative.
Some researchers have investigated the elimination of possible allergenic foci (eg, dietary
components, including milk, eggs, wheat and/or gluten, soy, and beef), as well as the use of
skin testing to identify allergens; however, the effectiveness of this has yet to be proven. [2,7] In
addition, mast cell stabilizers and other immunosuppressants (eg, montelukast, ketotifen,
suplatast tosilate, mycophenolate mofetil) have been used in some cases; however, the
success of these therapies has varied. Herbal therapies and Chinese medicine have also been
evaluated, but no definite benefit has been shown to date. Surgery may be necessary in
treatment-resistant cases, but this is generally considered a last resort, unless it is necessary to
relieve persistent pyloric or small-bowel obstruction.[2,3,7]

The aim of early diagnosis and treatment is to prevent long-term complications, such as
refractory ascites, bowel obstruction, perforation, recurrent iron deficiency anemia, and
(rarely) premature death.[2]
In view of the histologic findings, the patient in this case was prescribed budesonide (9 mg
daily). After the first month, the dose was reduced to 6 mg, and then to 3 mg for the third and
final month. After budesonide was initiated, the eosinophilia apparently dropped.
After completion of a course of reduced-dose budesonide over 3 months, the patient remained
well, and on laboratory examination had an eosinophil count at the higher end of the normal
range. He did not require any further admissions for management of his symptomatic anemia
and did not experience any other known complications. He was followed on a quarterly basis.
A plan for the reinstatement of budesonide treatment should the patient develop additional
complications was established.

This case highlights the diagnostic challenge of a condition that presents with common
symptoms and apparently normal investigations. These findings should motivate and
encourage the clinician to consider rarer diagnoses and pay special attention to seemingly
unimportant clues, no matter how small, that may have been present all along. In this case,
the patient had low-grade eosinophilia at the very first presentation, which was confirmed on
review of previous examinations.
Question 1 of 2
Which of the following is not required for the diagnosis of idiopathic eosinophilic
gastroenteritis?
Absence of extra-GI involvement
Demonstration of eosinophilic infiltration in the GI tract
History of atopy
GI symptoms
Absence of an alternative cause of eosinophilia

Question 2 of 2
Which of the following may be recommended as a primary treatment for eosinophilic
gastroenteritis?
Corticosteroids
Mycophenolate mofetil
Chinese medicine
Elimination diets
Infliximab

1. Kaijser R. Zur Kenntnis der allergischen Affektionen des Verdauungskanals von

Standpunkt des Chirurgan aus. Arch Klin Chir. 1937;188:36-64.
2. Nguyen MT, Szpakowski JL. Eosinophilic gastroenteritis. Medscape Drugs &
Diseases. January 11, 2017. http://emedicine.medscape.com/article/174100-
overview Accessed February 22, 2017.
3. Kristopaitis T, Neghme C, Yong SL, Chejfec G, Aranha G, Keshavarzian A. Giant
antral ulcer: a rare presentation of eosinophilic gastroenteritis—case report and review
of the literature. Am J Gastroenterol. 1997;92:1205-1208. Medline
4. Steffen RM, Wyllie R, Petras RE, et al. The spectrum of eosinophilic gastroenteritis.
Report of six pediatric cases and review of the literature. Clin Pediatr (Phila).
1991;30:404-411. Medline
5. Scolapio JS, DeVault K, Wolfe JT. Eosinophilic gastroenteritis presenting as a giant
gastric ulcer. Am J Gastroenterol. 1996;91:804-805. Medline
6. Klein NC, Hargrove RL, Sleisenger MH, Jeffries GH. Eosinophilic gastroenteritis.
Medicine (Baltimore). 1970;49:299-319. Medline
7. Chehade M. IgE and non-IgE-mediated food allergy: treatment in 2007. Curr Opin
Allergy Clin Immunol. 2007;7:264-268. Medline