A Rare Occurance of Eosinophilic Ascites in Pregnancy

Eosinophilic ascites (EA) is an exceedingly rare disorder of unknown etiology characterized by elevated number of eosinophils in ascitic fluid. EA is the rarest subtype of eosinophilic gastroenteritis and is characterized by infiltration of eosinophils in serosal layer of gastrointestinal tract. EA usually occurs in female patients, is mostly associated with atopic disorders, and is easily treatable with corticosteroids. Association with pregnancy is rare and why it occurs in pregnant females is unknown. We report a case of EA which to our knowledge is the first case of idiopathic EA in a pregnant patient and was easily treatable with corticosteroids without adverse effect on fetus.


Introduction
Eosinophilic gastroenteritis, (EG) first described by Kaijser in 1937, is a rare disorder of unknown etiology characterized by eosinophilic infiltration of one or more layers of gastrointestinal wall. Klien et al. classify eosinophilic ascites (EA) as the rarest subtype of eosinophilic gastroenteritis, characterized by elevated number of eosinophils in ascitic fluid. Around 300 cases of EG and 15 cases of EA have been reported in literature, mostly in last decade due to increased diagnostic abilities. We report a case of EA which to our knowledge is the first case of idiopathic EA in a pregnant patient. A 29-year-old Hispanic female, gravida 5/para 4, 19 weeks pregnant, with a history of gestational diabetes and asthma, was admitted to our institution for nausea, vomiting, diffuse abdominal pain and loose non-bloody stools of 3-day duration. Nausea and vomiting were insidious in onset and preceded abdominal pain by one day. Vomitus was non-bilious, non-bloody and consisted of food she ate. Abdominal pain was diffuse, dull aching, and intermittent with no exacerbating or relieving factors. Vital signs in the emergency room were normal. Physical examination was remarkable for gravid uterus, generalized abdominal tenderness and shifting dullness. An ultrasound of the abdomen revealed hepatosplenomegaly, dilated portal vein and diffuse ascites (Figures 1 and 2).
A diagnosis of eosinophilic ascites was made. Prednisone 20 mg oral daily was started. Her symptoms improved rapidly and patient was discharged 2 days later. Unfortunately, the patient stopped steroids 6 weeks after discharge due to lack of insurance coverage.
After one week of stopping steroids, her symptoms recurred but with milder severity. A repeat ultrasound of the abdomen during follow-up showed improved organomegaly and ascites compared to previous exam.
She was restarted on prednisone 10 mg oral daily. Follow-up at 3 months revealed complete resolution of her symptoms, ascites and organomegaly. Peripheral eosinophilia also resolved. Rest of the pregnancy was uneventful and she delivered a healthy full term infant.

Discussion
Eosinophilic gastroenteritis (EG) is an uncommon disorder characterized by eosinophilic infiltration of gut wall and peripheral blood eosinophilia in the absence of a known cause for the latter, such as parasitic infestation, malignancy or allergy, etc. It can present with a wide spectrum of symptoms, may affect essentially any part and any or all layers of the gastrointestinal tract. Different subtypes of EG derive their nomenclature depending on the layer of the gut wall involved. Klein was the first to describe subtypes of eosinophilic gastroenteritis based on the depth of tissues involved [1]. Whereas involvement of the mucosal layer is the most common subtype (Table 1), eosinophilic ascites (EA) is probably the most unusual and rare presentation of EG that is generally associated with the serosal form of EGE. EA is seen in less than 10% of cases of EG [2,3]. Though most cases of EA are idiopathic, an association with other atopic or allergic diseases such as asthma or food allergy has occasionally been reported [4][5][6]. A few cases have been reported in children and also in post-partum women [7][8][9][10][11][12]. However, association of EG or EA by childbirth or pregnancy has not been reported in literature. Ours is the first case of eosinophilic ascites that developed during pregnancy and responded well to steroids.

Subtype Characteristic
Mucosal form most frequent form [6], involves mucosa and submucosa, but not the muscularis propria [1]; symptoms are related to dysfunction of the mucosa with malabsorption and possible protein-losing enteropathy (diarrhea, steatorrhea, weight loss, hypoalbuminemia, peripheral edema, occult fecal bleeding, iron-deficiency anemia); more frequently associated with a history of allergy or high total IgE levels (atopy) [13] Muscular form involves the muscularis propria; consequent thickening of the wall results in sub-occlusive signs (colicky pain, nausea, and/or vomiting) Serosal form isolated or associated involvement of the serosa; observed in less than 10% of cases; eosinophilic ascites is pathognomic; typical in women of childbearing age.

Pathophysiology
Long thought as an idiopathic disorder, EG (and it's all subtypes) is now believed to occur as a result of a complex interaction of genetic, environmental and immune systems [14][15][16]. A defective mucosal barrier allows environmental allergens to pass through, activating both humoral and cell-dependent immune response [2,6,17]. Activated lymphocytes and mast cells secrete interleukin-5 (IL-5), a cytokine which attracts and activates eosinophils [18]. Once activated, eosinophils recruit themselves in an autocrine manner, secreting several pro-inflammatory cytokines such as transforming growth factor, granulocyte-macrophage colony stimulating factor, IL-3 and IL-5 [18,19]. This theory is further supported by the observation that mast cell stabilizer sodium cromoglycate have been effective in some cases of EG [20][21][22]. This autocrine cycle continues and IL-5 and eosinophils together help potentiate immune response. Desreuxmaux et al. found an increase in total serum IgE levels with RAST positive for food allergens, and an increased number of lymphocytes and eosinophils in patients with EA as compared to normal population [23]. Paracentesis in these patients shows a sterile exudative effusion containing as many as 95% eosinophils [24,25].

Diagnosis
Diagnostic criteria for EA include: a) presence of gastrointestinal signs and symptoms (as described above), b) absence of other known causes of eosinophilia like malignancy, parasitic and fungal infections, autoimmune diseases, drug reactions, cholesterol embolism and hyperimmunoglobulin syndrome, c) eosinophilic infiltration in serosal layer of gut wall and ascitic fluid [2,31,32]. Diagnosis is made by analysis of ascitic fluid, CBC and EGD with biopsy. There is no literature on how many eosinophils should be seen in ascitic fluid to make the diagnosis but usually 10 eosinophils per high power field is cutoff in our practice. Peripheral eosinophilia is seen in 50%-90% patients but is not essential for diagnosis [4,33,34]. Magnitude of peripheral eosinophilia is directly proportional to the severity of symptomatology [5,35]. Around 80% of the cases are associated with atopic disorders and 16% have an affected immediate family member [36]. Although EG is more common in males, EA has predominantly been diagnosed in females [37].

Treatment
Corticosteroids are the mainstay of therapy and the response is excellent [38]. There are no consensus guidelines for dose and duration of steroid treatment. Patients can usually be started on 40 mg of oral prednisone and gradually tapered off over two weeks [6,31,39,40]. Alternative therapy with a mast cell stabilizer (sodium cromoglycate) has been tried successfully in several patients with the mucosal form but has not been well studied in patients with the serosal form. Pérez-Millán et al. reported complete resolution of EA in a young patient after sodium cromoglycate treatment with no recurrence at one year [22]. It is yet to be determined whether other alternative measures including ketotifen [41][42][43], montelukast [39,44,45] and elimination diet [46][47][48][49] are useful in any form of EG at all. Only three cases of eosinophilic ascites have been reported in literature which improved without medical therapy [50]. General consensus is that prognosis is excellent [21,51] but the disease can easily progress into a chronic or relapsing-remitting form [52].

Conclusion
Eosinophilic ascites in our patient appeared during pregnancy and did not recur after delivery. It is unclear what could have triggered this idiopathic incidence. A fetal antigen or an altered immune status during pregnancy in this patient with a history of an atopic disorder (asthma) may be postulated. Though our patient needed longer than recommended duration of steroids, her disease showed excellent response to therapy even though that incomplete treatment with steroids led to a relapse of the disease in her case. There were no adverse effects on pregnancy or fetus. In the future, it would be interesting to know if pregnancy alters the course of EA in a patient with a previous diagnosis of EA or EG or atopic disorders.