Chinese Journal of Digestive Diseases 2005; 6; 206–208
Hypereosinophilic syndrome presenting with eosinophilic colitis, enteritis and cystitis
MA Amin et al. Blackwell Oxford, The CDD 2005 1443-9611 July O 4 6 Hypereosinophilic riginal Chinese 2005 Chinese UK Article Publishing, Journal Medical syndrome ofLtd. Association Digestive Diseases Shanghai Branch
Mona A AMIN,* Magdy Abdel HAMID† & Sleman SABA‡ Departments of *Internal Medicine, †Cardiology, and ‡Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt
Idiopathic hypereosinophilic syndrome (HES) refers to a group of leukoproliferative disorders characterized by an overproduction of eosinophils that result in organ damage. Peripheral eosinophilia with tissue damage has been recorded for approximately 80 years, but Hardy and Anderson first described the specific syndrome in 1968. The three features required for a diagnosis of HES were defined in 1975 by Chusid et al.1: (i) a sustained eosinophil count greater than 1500/mm3 that persists for longer than 6 months; (ii) no other etiologies for eosinophilia are present; and (iii) patients must have signs and symptoms of organ involvement. Thus, this last requirement excludes benign eosinophilia, which may exist for years with no associated pathology.
CASE REPORT
Hypereosinophilic syndrome is a heterogeneous disease process; thus, multiple manifestations may occur simultaneously or individually. The presenting symptoms may be sudden and dramatic, which sometimes occurs with cardiac, neurological, or thrombotic complications, but more often the onset is insidious. In one series, 12% of patients with HES discovered it as an incidental finding. Virtually any organ system can be involved.
On admission, the patient appeared conscious, vitally stable, afebrile, not cyanosed, with reddish small macular rash over the chest wall and stria rubra over the abdominal wall and the thigh. Auscultation revealed bilateral diffuse rhonchi over the chest and hyperaudible intestinal sounds, with no organomegaly detected.
The gastrointestinal manifestations can include: •
diarrhea (a relatively common complaint, occurring in approximately 20% of patients)
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nausea and abdominal pain (also common)
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small bowel necrosis due to microthrombi (can occasionally occur)
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splenomegaly (occurs in 40% of patients)
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liver and gall bladder dysfunction and ascites
Correspondence to: Mona A AMIN, Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt. Email:
[email protected]
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A 37-year-old male smoker presented with diffuse colicky abdominal pain, repeated vomiting and frequent loose motions with mucus and tenesmus of 3 weeks duration. The condition was associated with dysuria and frequency of micturation, but no hematuria or fever. The patient had a history of recurrent asthmatic attacks during the preceding 2 years, for which monthly longacting steroid injections were given. Percutaneous transluminal coronary angioplasty (PTCA) and stenting of the right coronary artery was carried out because of ischemic chest pain.
Investigations revealed that the erythrocyte sedimentation rate (ESR) was 4 mm at the end of 1 h, hemoglobin (Hb) was 18.7 g/L, the total leucocyte count was 15.300 cell/cmm (eosinophils 14%, polymorphs 64%, and lymphocytes 21%) and the platelet count was 337.000/ cmm. A peripheral blood smear indicated eosinophilia, with the absolute eosinophil count being 2142/cmm. A bone marrow examination revealed hypercellular bone marrow, a myeloid series showed marked eosinophilia with normal morphology, an erythroid series showed normal morphology and maturation, and megakaryocytes were normal with respect to number, lobulation, granulation and platelet budding. A stool examination showed 30–40/high power field (HPF) pus cells and 0–1/HPF red blood cells, with no growth on stool culture. Repeated stool examinations
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Figure 1. Endoscopic findings in the terminal ileum. Note diffuse hyperemia of the mucosa of the terminal ileum.
for ova or cysts were negative for common parasitic infections. A urine examination showed 9–10/HPF pus cells and 3–5/HBF red blood cells with no growth on culture. There was no biochemical evidence of hepatic or renal dysfunction. Ultrasonography of the abdomen and pelvis revealed a thickened wall of the urinary bladder (6 mm) and dilated bowel loops. Chest X-ray showed a hyperinflated chest. The results of electrocardiography and echocardiography were normal. Barium meal analysis revealed non-specific malabsorption, with thickened wall of the duodenum and the jejunum. Colonoscopy was carried out up to the cecum and terminal ileum; the cecum and terminal ileum showed hyperemic mucosa but no ulcers, with a small 0.5-cm sessile polyp in the sigmoid colon, of which biopsies were taken (Figure 1). Microscopic examination of the colonic biopsies revealed eosinophilic colitis with hyperplasic polyps (Figure 2). The buffy coat preparation for microfilaria and the serology for filarial antigen were both negative. Tests for rheumatoid factor and antinuclear antibodies were negative. Because no cause attributable to hypereosinophilia was found, a diagnosis of idiopathic HES was made. The patient received a full dose of prednisone (1 mg/kg per day) and was followed up with a complete hemogram, including a peripheral blood smear examination. A marked improvement in the patient’s symptoms (abdominal colic, diarrhea and dysuria) was noted within 2 days of starting steroid therapy, and improve-
Figure 2. Microscopic findings of the colonic mucosal biopsy. (a) Note the colonic mucosa with minimally distorted glands, lamina propria with moderate edema, congestion, and infiltration by lymphocytes, plasma cells and many eosinophils. (b) Few polymorphs were seen disrupting the crypts.
ments were noted with respect to the hemogram 1 week after initiation of steroid treatment. DISCUSSION A case of HES was first reported in 1968 by Hardy and Anderson but no details were available.1,2 Chusid and coworkers later defined the condition and set criteria for the diagnosis of HES as persistent eosinophilia of more than 1500 cells/cmm for at least 6 months, or death before 6 months with signs or symptoms of HES, plus lack of evidence for any recognized cause of eosinophilia, plus signs or symptoms of multi-organ system involvement.1–5 HES can occur at any age, but most cases occur between 20 and 50 years.3,6 The characteristic features of HES are the eosinophilic tissue
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damage related to the release of the major basic proteins eosinophil peroxidase, eosinophil cationic protein, and eosinophil-derived neurotoxin.2 The conversion of idiopathic HES to acute leukemia is rare. Eosinophilic enteropathy is a condition in which one or more layers of the gastrointestinal tract are infiltrated with eosinophils, and is given a more specific name corresponding with the area that contains the most eosinophils:
occurs, followed by alternate day therapy. If clinical improvement occurs, the dose should be tapered off gradually.8 A very low dose steroid can also be used with good results. Symptomatic patients non-responsive to steroids should be offered chemotherapeutic agents. Common chemotherapeutic drugs used include hydroxyurea, vincristine, 6-mercaptoputine (6-MP), busulfan and chlorambucil. Hydroxyurea is used frequently, because of its absence of leukemogenic effect and convenience of oral administration. Hematological remission can be achieved and maintained with vincristine alone, or in combination with 6-MP and 6-thioguanine. αInterferon and cyclosporine have also been found to be useful in the treatment of HES.9
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eosinophilic esophagitis (EE) is when a large number of eosinophils occur only in the esophagus
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eosinophilic gastroenteritis (EG) is when a large number of eosinophils are found only in the stomach and small intestine
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eosinophilic duodenitis (ED) is when a large number of eosinophils are found in above normal numbers only in the duodenum (upper small intestine)
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eosinophilic colitis (EC) is the occurrence of large numbers of eosinophils only in the large intestine.
Cromolyn sodium (Gastrocrom) has been used with some success for EG, but does not work in all cases. Some patients have found that they can reduce the severity of an attack if they take long-acting-non-drowsy antihistamines (such as Claritin, Allegra or Zyrtec), but no clinical trails have been done on EG, EE, or EC with such medications.
Some physicians may give a diagnosis of eosinophilic enteritis when only the small intestine is involved, eosinophilic ileitis if only the last part of the small intestine is involved, or eosinophilic gastritis if only the stomach is involved.7
Finally, a new class of asthma medications known as leukotriene inhibitors have been producing some mixed results in clinical trials for asthma patients, and have been used experimentally in cases of EG and EE, but again with mixed results.
Diagnosis can be difficult, even with the best current technology, because the eosinophils occur in irregular patches instead of continuous areas in the digestive system, therefore confirmation of the diagnosis often requires many tissue samples or biopsies. Also, eosinophils in larger numbers may only occur in deeper layers of the digestive system that cannot be seen on a normal biopsy, and therefore a full thickness or surgical biopsy may be needed in order to establish or confirm the diagnosis. A further complicating factor is that there are a number of other conditions that may mimic the symptoms of eosinophilic disorders, such as inflammatory bowel disease (IBD).
REFERENCES
Because there is no known cure for EE, EG or EC, medications are used for controlling symptoms and the prevention of full-blown attacks (or ‘flare-ups’). The only known medication to successfully stop eosinophilic inflammation in EE, EC and EG is prednisone. Symptomatic patients should be treated with prednisone therapy (1 mg/kg per day) until clinical improvement
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