A 42-year-old man presented to the emergency room with intermittent diarrhea for over four months and progressive lower extremity edema for three months. He had 5–6 bowel movements per day, with no obvious fever or abdominal discomfort. Progressive pitting edema of the bilateral legs was noticed one month later, accompanied by a decline in exertional tolerance. The patient lost approximately 15 kg over this period of time. A series of echocardiographic examinations had revealed a growing mass in his left atrium of uncertain origin, which grew from 25 × 22 to 60 × 54 mm within 3 months. His previous medical history was remarkable for poorly controlled type 2 diabetes mellitus complicated by diabetic nephropathy, retinopathy and peripheral neuropathy. He also had a five-year history of major depressive disorder without regular treatment. He lived with his mother and sister in the city of Qingdao, Shandong Province, and denied any recent travel history. The patient’s sister reported that he had intermittently consumed raw river fish for as long as 6–7 years before onset of this episode. Due to the mental status of the patient, his medical history was also obtained and confirmed by his mother and sister who lived with him. On admission, the patient appeared emaciated and anemic. He was afebrile, his blood pressure was 93/67 mmHg, and heart rate 102 bpm. He was moody, disoriented, and slightly hypoxemic with an oxygen saturation of 90% at room air. A grade II diastolic rumbling murmur was heard at the apex. Examination of his lungs and abdomen was otherwise unremarkable. Decreased myodynamia of the bilateral limbs was appreciated, more significant on the left side, with a positive left Babinski sign. Initial laboratory assessment revealed peripheral eosinophilia (eosinophils 6.64 × 109/L) and anemia (hemoglobin 85 g/L). The level of gamma-glutamyl transpeptidase was elevated at 1093 U/L, and alkaline phosphatase was 666 U/L, with no apparent hyperbilirubinemia. Serial of electrocardiograms showed paroxysmal atrial fibrillation. A bedside echocardiogram was immediately arranged, and a space-occupying lesion measuring 60 × 54 mm was identified in the left atrium with a slight pericardial effusion. The left ventricular ejection fraction (LVEF) was moderately reduced at the level of 55%. The initial chest CT showed scattered bilateral pulmonary infiltrations and pleural effusion, with a cavity in the right upper lobe. Abdominal CT scan showed intrahepatic bile duct dilatation with no obvious obstruction. A CT scan of the head was also preformed due to recurrent episodes of seizures during hospitalization, and showed low density lesions in bilateral corona radiate. The initial differential diagnosis included infectious endocarditis, Löffler endocarditis, hypereosinophilic syndrome, parasitic infection and hypersensitive reactions to recent medication. Although no evidence of fungus was identified from qualified sputum samples, sulperazon and caspofungin were initiated empirically based on the CT manifestation and history of uncontrolled diabetes. Supportive care was also initiated. A multi-disciplinary discussion was held, and consensus was achieved regarding the urgency of cardiac surgery, both to alleviate progressive heart failure and to obtain a tissue specimen for diagnostic purposes. The patient underwent the surgery two weeks following admission. Surprisingly, the cardiac mass turned out to be an endocardial hematoma, possibly due to mechanical perforation of the left ventricular posterior wall close to the base of posterior mitral valve. The valves were otherwise intact. Pathological review of the specimen revealed nonspecific inflammation and all pathogenic examinations turned out to be unremarkable. The surgical findings largely ruled out endocarditis of infectious or autoimmune origin, nor did they reveal any evidence of eosinophilic infiltration. Given the systemic involvement and the dietary habits mentioned by his family, we began to consider the possibility of parasitic infection with systemic involvement. A more detailed history confirmed raw or half-raw consumption of freshwater fish and shrimps, frogs, tadpoles and snake gall bladders nearly every month in recent years as a result of his altered mental status. Further tests were warranted. Multiple stool samples were sent for microscopic examination by direct fecal smear, and various eggs were identified. Eggs of Clonorchis sinensis were first identified (measuring 27-30 μm × 16-18 μm, Fig. d), at a count of 3–5/low-power (LP) field. Clonorchiasis was therefore confirmed, which partially explained the patient’s chronic diarrhea and dilatation of intrahepatic bile ducts. However, this liver fluke rarely causes such widespread organ damage. A few days later, another type of egg smaller than that of C. sinensis was identified, which was morphologically most consistent with that of heterophyid trematodes (measuring 23-26 μm × 13-15 μm, Fig. d). The eggs of Heterophyidae were much fewer in number, and required 10–20 LP field to find one. Moreover, several large-sized eggs were also observed (measuring 100-110 μm × 60-70 μm), consistent with those of the Echinostomatidae family. Approximately five eggs of the Echinostomatidae could be identified per fecal smear. Further evaluations included a contrast-enhanced cerebral magnetic resonance imaging test with angiography, which revealed multiple long T2 densities in the centrum semiovale with no obvious vascular involvement. Lumbar puncture was performed and showed moderately elevated intracranial pressure at 210 mmH2O and a slightly elevated protein level in the cerebral spinal fluid. A colonoscopy was apparently normal, but deposition of C. sinensis eggs was later observed on ileocecal squash slides. Specific PCR band patterns of C. sinensis were later observed in samples of the ileocecal tissues and stool, but not in the sputum or heart tissues. DNA of heterophyid trematodes was not detected from any obtained samples. The primers of PCR were designed according to previous studies (Additional file: Table S1). Once the diagnosis of triple trematodiases was established, treatment with praziquantel was started. Due to the comprehensive involvement and the concern for hypersensitivity reaction, a reduced oral dose of praziquantel at 25 mg/kg/d was initiated for the first 10 days combined with low-dose dexamethasone. The patient tolerated this regimen well and received the full dose of 75 mg/kg/d for ten days each month for another consecutive two months. His diarrhea gradually resolved with a steady improvement in nutritional status and cardiac function. Continuous surveillance of his stool samples revealed no further trematode eggs since the second month of treatment. Follow-up CT scans showed remission of pulmonary and liver lesions, while enhanced MRI showed absorption of previous abnormal signals in centrum semiovale.