An Unusual Cause of Acute Gastroenteritis, Ascites, and Eosinophilia in a 29-Year-Old Woman

Abstract

Question: A previously healthy 29-year-old woman presented to the gastroenterology department with a 1-month history of abdominal pain, abdominal distention, nausea, vomiting, and watery diarrhea. She had no reported history of allergies and recent drug use or travel. Before we saw her, she went to a clinic first and was prescribed antibiotics based on a diagnosis of acute gastroenteritis. However, the antibiotic therapy was ineffective. Then, she was referred to a local tertiary hospital. A routine blood test showed leukocytosis (14.33 × 109/L, normal 3.5–9.5), neutrophilia (9.02 × 109/L, normal 1.8–6.3), and eosinophilia (3.16 × 109/L, normal 0.02–0.52). Autoantibodies tests for rheumatoid immune diseases including systemic lupus erythematosus and systemic sclerosis were all normal. Except for slightly elevated serum immunoglobulin E (141 IU/mL, normal 0–100), levels of immunoglobulin A, immunoglobulin M, immunoglobulin G, complement C3, and complement C4 were all within normal ranges. Echocardiography showed no abnormality. Gastroscopy showed normal esophagus, chronic antral gastritis (Figure A), and bulb duodenitis (Figure B). Pathology of the biopsy specimen from duodenal bulb mucosa revealed the villi were significantly reduced and shortened, accompanied by diffuse inflammatory cell infiltration, in which a small number of eosinophils were seen (Figure C). Transabdominal ultrasonography indicated massive ascites. She received diuretic treatment, but abdominal discomfort was not improved. On physical examination, she was very weak with a heart rate of 74 beats per min, and a blood pressure of 108/83 mm Hg. She was afebrile. Her abdomen was soft and bulging without tenderness or rebound pain. Shifting dullness was positive. The blood routine examination showed leukocytosis (16.58 × 109/L, normal 3.5–9.5) associated with eosinophilia (6.74 × 109/L, normal 0.02–0.52). The concentration of D-dimer was increased (11.24 μg/mL, normal 0–0.50). The stool examination was negative for parasitic and bacterial infections. The levels of C-reactive protein, erythrocyte sedimentation rate, and serum procalcitonin were normal. Liver, renal, and thyroid functions showed no abnormality. Tumor markers were all normal except for markedly elevated carbohydrate antigen 125 (508 U/mL, normal 0–35). The antineutrophil cytoplasmic antibodies were within normal ranges. Tests for Epstein–Barr virus, human immunodeficiency virus, viral hepatitis, and tuberculosis were negative. However, the treponema pallidum–specific antibody test was positive (40.748 signal to cut-off ratio [S/CO], normal 0–1.0), and the toluidine red unheated serum test (TRUST) for syphilis was positive (1:1). A computed tomography (CT) scan of the thorax, abdomen, and pelvis showed massive ascites with significant edema of the lower esophagus and small intestine, presenting as a halo sign and an araneid limb-like sign (Figures D, E, F, and G). Subsequently, a diagnostic paracentesis was done. Routine and biochemical tests of ascites were performed (Tables 1 and 2). The serum-ascites albumen gradient was 6.9 g/L. The acid-fast stain and culture for bacteria and fungi of ascites were negative. Histopathologic examination of the ascitic fluid revealed plentiful eosinophils with a proportion of about 60% (Figure H). In addition, the serum immunofixation electrophoresis and immunoglobulin G4 tests showed no abnormality. The test for TEL-PDGFRB, a receptor tyrosine kinase fusion gene that causes chronic myeloid malignancies associated with hypereosinophilia, was negative.Table 1Routine Test for AscitesColorPropertyLeukocyte count (×106/L)Erythrocyte count (×106/L)Mononuclear cell (%)Multinuclear cell (%)Specific gravityRivalta testYellowMuddy4522.001500.000.080.921.015Positive Open table in a new tab Table 2Biochemical Test of AscitesProtein (g/L)Albumen (g/L)Globulin (g/L)Adenosine deaminase (U/L)Glucose (mmol/L)Lactate dehydrogenase (U/L)Amylase (U/L)Carcinoembryonic antigen (ng/mL)50.932.718.25.54.9418312＜0.30 Open table in a new tab What is the most possible diagnosis? See the Gastroenterology website (www.gastrojournal.org) for more information on submitting to Gastro Curbside Consult. Based on gastrointestinal symptoms, blood eosinophilia with unknown causes, eosinophilic ascites, patchy eosinophils in the duodenal biopsy, and multisegmented edema of the gastrointestinal tract, we made an initial diagnosis of serosal eosinophilic gastroenteritis. Meanwhile, the positive results of the treponema pallidum–specific antibody test and TRUST proved that she had syphilis. On learning the diagnosis of syphilis, she admitted to a history of sexual behaviors with her boyfriend, who was also tested for syphilis but refused to provide the result. We speculated that she might have gotten syphilis through sexual contact. Initially, we thought that syphilis and serosal eosinophilic gastroenteritis were concurrent and irrelevant. However, the patient’s unexpectedly good response to syphilis treatment changed our view. She was treated with an intramuscular dose of 2.4 million units of benzathine penicillin weekly for 3 successive weeks. The routine blood test on the next day after each benzathine penicillin treatment showed that the eosinophil count gradually decreased (4.79 × 109/L, 2.69 × 109/L, 1.71 × 109/L, normal 0.02–0.52). After treatment for syphilis, her abdominal discomfort was completely resolved. She underwent a CT scan again. We found that the ascites disappeared, and the gastrointestinal tract edema was also relieved (Figures I, J, K, and L). The eosinophil count decreased close to the normal range (0.93 × 109/L, normal 0.02–0.52), and the TRUST was converted to negative although the treponema pallidum–specific antibody test was still positive (44.771 S/CO, normal 0–1.0). She remained symptom-free at a 9-month follow-up. Therefore, the final diagnosis was syphilis masquerading as serosal eosinophilic gastroenteritis. This case is presented as an eosinophil-associated gastrointestinal disease. Eosinophilic gastrointestinal disorders can be classified as primary eosinophilic disorders (eosinophilic esophagitis, eosinophilic gastroenteritis, eosinophilic colitis, and hypereosinophilic syndrome with gastrointestinal involvement), secondary eosinophilic disorders (infections [mainly parasites], food hypersensitivity, drug hypersensitivity, neoplasia, connective tissue diseases, and vasculitis), and gastrointestinal diseases associated with eosinophilia (eg, functional dyspepsia, gastro-esophageal reflux disease, and inflammatory bowel diseases).1Walker M.M. Potter M. Talley N.J. Eosinophilic gastroenteritis and other eosinophilic gut diseases distal to the oesophagus.Lancet Gastroenterol Hepatol. 2018; 3: 271-280Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar Obviously, the features of this patient do not tally with eosinophilic esophagitis, eosinophilic colitis, and gastrointestinal diseases associated with eosinophilia. Eosinophilic gastroenteritis, hypereosinophilic syndrome, and secondary eosinophilic disorders should be carefully identified. Considering no history of allergies, drug use, or recent travel and the negative result of stool screening for parasites, we can exclude the possibility of hypersensitivity to food or drugs and parasitic infections. There is no evidence of malignancy in serologic and ascitic tests, CT scan, and gastroscopy. So, neoplasia can be removed from the spectrum of differential diagnoses. Furthermore, the suspicion of connective tissue diseases and vasculitis can also be eliminated according to the normal autoimmune antibodies and antineutrophil cytoplasmic antibodies tests, and no findings of angiitis on duodenal bulb biopsy. Hypereosinophilic syndrome is a primary eosinophilic disease characterized by an absolute blood eosinophil count of more than 1.5 × 109/L for more than 1 month associated with multiorgan system infiltration by eosinophils. The heart and nervous system are commonly involved. The patient’s clinical performance of single-organ system involvement of the gastrointestinal tract does not conform to the hypereosinophilic syndrome. Also, the negative result of the fusion gene TEL-PDGFRB test does not indicate the myeloproliferative form of hypereosinophilic syndrome. Eosinophilic gastroenteritis is a rare primary gastrointestinal eosinophilic disease with unclear pathogenesis and nonspecific gastrointestinal symptoms. It can affect any part of the gastrointestinal tract; the stomach and small intestine are most frequently involved. Three types of eosinophilic gastroenteritis are described: mucosal, mural, and serosal. Among them, serosal eosinophilic gastroenteritis is the rarest and characterized by eosinophilic ascites. The halo sign and araneid limb-like sign on CT are valuable features for the diagnosis of eosinophilic gastroenteritis.2Huang X. Liao X. Xiao Z. et al.Halo sign and araneid limb-like sign in eosinophilic enteritis.Lancet Gastroenterol Hepatol. 2020; 5: 954Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar Although prominent eosinophil infiltration in the gastrointestinal wall is necessary to diagnose eosinophilic gastroenteritis, the presence of eosinophilic ascites, when present, is also important in clarifying the diagnosis. When confronted with this case, clinicians who do not have a high index of suspicion for syphilis are prone to misdiagnosis as serosal eosinophilic gastroenteritis. Fortunately, despite the initial misdiagnosis, we treated syphilis before empirical corticosteroid therapy for eosinophilic gastroenteritis. The subsequent good therapeutic effect helped us rule out eosinophilic gastroenteritis and confirm the final diagnosis. Syphilis is a chronic infectious disease caused by Treponema pallidum with a sharply increased incidence over the past 2 decades. It is endemic in low-income countries and less common in middle-income and high-income countries. Except for congenital syphilis, syphilis is spread mainly through sexual contact and blood transfusion. As a great imitator, syphilis can be a diagnostic challenge for physicians because it can affect almost every organ of the body with variable clinical presentations.3Hook 3rd., E.W. Syphilis.Lancet. 2017; 389: 1550-1557Abstract Full Text Full Text PDF PubMed Scopus (238) Google Scholar The skin, genitalia, bone, central nervous system, and cardiovascular system are often involved. In contrast, the gastrointestinal tract is rarely affected. Gastrointestinal syphilis has been described mainly in case reports and manifests with atypical abdominal discomfort symptoms and various endoscopic appearances, such as mucosal edema, erosions, superficial ulcers, nodularity, rugal hypertrophy, and ulcerative mass lesions. To our best knowledge, this is the first case report of syphilis mimicking serosal eosinophilic gastroenteritis. Two features overlooked by us might hint that the true diagnosis is not eosinophilic gastroenteritis. First, eosinophilic gastroenteritis frequently affects the stomach and small intestine, and seldomly involves the esophagus in adults.1Walker M.M. Potter M. Talley N.J. Eosinophilic gastroenteritis and other eosinophilic gut diseases distal to the oesophagus.Lancet Gastroenterol Hepatol. 2018; 3: 271-280Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar Whereas in this case, the esophagus and small intestine were affected, and the stomach was exempt. Second, eosinophils did not dominate inflammatory cell infiltration on duodenal bulb biopsy. Eosinophils, as the normal constituents of the gut,1Walker M.M. Potter M. Talley N.J. Eosinophilic gastroenteritis and other eosinophilic gut diseases distal to the oesophagus.Lancet Gastroenterol Hepatol. 2018; 3: 271-280Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar participate in almost all inflammatory processes. Only infiltration of excessive eosinophils in the gut indicates eosinophilic gastroenteritis, although the exact number of eosinophils to attain a diagnosis is not well defined.1Walker M.M. Potter M. Talley N.J. Eosinophilic gastroenteritis and other eosinophilic gut diseases distal to the oesophagus.Lancet Gastroenterol Hepatol. 2018; 3: 271-280Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar She completely recovered after syphilis treatment. She is very healthy now. Long-term monitoring and follow-up will be continued for her. In conclusion, we present a rare case of syphilis masquerading as serosal eosinophilic gastroenteritis. Clinicians should carefully inquire about sexual history and prompt a screen for syphilis when encountering similar patients with gastrointestinal complaints and eosinophilia. If syphilis is confirmed to be present, treatment for syphilis should be initiated, and evaluation of response facilitates differential diagnosis.