A 30 year old South-Asian female presented with 5 day history of high fever associated with severe myalgia, headache and yellowish discoloration of the skin. There was no history of contact with muddy water, alcohol consumption, or use of any drugs including antibiotics, anti-pyretics (acetaminophen) or antiemetics. Furthermore history of blood transfusion, sexual promiscuity or any other high risk behavior could not be elicited. She denied any pale stools or pruritus. At the time of admission, general examination revealed she was febrile and icteric but had no conjunctival hemorrhage, pallor, lymphadenopathy, rashes or scratch marks. The respiratory system was unremarkable and the abdominal examination did not elicit right hypochondrial tenderness, palpable gall bladder or abdominal guarding. The cardiovascular examination was normal and she had an initial blood pressure of 90 mmHg systole and 60 mmHg diastole, without a postural drop. She was conscious, alert, well oriented and nervous system examination was otherwise unremarkable.\nThe initial complete blood count revealed thrombocytopenia with a platelet count of 69 × 109/L (150–450), a normal white blood cell count (WBC) of 10.4 × 109/L (4–11) with a predominance of lymphocytes (55%) and a hemoglobin of 11.0 g/dL (11–17) . The blood picture mirrored the whole blood analysis and showed only thrombocytopenia, there was no neutrophil left shift or toxic granules and the red cell indices were normal. Liver functions showed a mildly elevated aspartate transaminase(AST) and alanine transaminase(ALT) which were 80 U/L(0–40) and 38 U/L (0–35 ) respectively with an elevated alkaline phosphatase(ALP) value of 450 U/L (100–360). Serum direct and total bilirubin levels were elevated at 6 mg/dL (0–0.3) and 9.1 mg/dL (0.3-1.9) respectively. Serum albumin was found to be reduced with a value of 2.3 g/dL (3.5 -5.5), with a normal international normalized ratio (INR). The renal functions were within normal reference range. The C- reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were also within normal parameters. The following day the platelet count continued to drop and her jaundice deepened. A positive dengue non- structural protein1antigen test (NS1) and a positive dengue IgM antibody ELISA test on day 6 confirmed the clinical suspicion and diagnosis of dengue fever. Hepatitis B surface antigen, hepatitis C antibody, hepatitis A and E antibodies, Ebstein Barr Virus antibody and a retroviral screening were all negative. Leptospira microscopic agglutination test (Lepto MAT) titres were insignificant at 1:200 on day 6 and the titre value remained unchanged when the repeat test was performed on day 12 of the illness (a four -fold rise in titre or a high titre >1:800 is the gold standard for diagnosis). Blood cultures remained repeatedly negative.\nThe platelet count continued to drop rapidly in the following days reaching the lowest nadir value of 3 × 109/L (150–450) with rising alkaline phosphatase and bilirubin levels (Table ). On day 6 of the illness the patient became afebrile. As per the local guidelines and WHO dengue guidelines on management of critical phase of dengue hemorrhagic fever, she was maintained on a fluid regimen tailored to her body weight, with strict monitoring of the blood pressure, pulse pressure, heart rate and urine output.\nOn day 7 the patient became mildly tachypnoeic, and examination revealed reduced air entry in the right lung base which was stony dull to percussion and deep icterus, further abdominal examination elicited a small shifting dullness, signifying ascites. An ultrasound scan was done and confirmed a small right sided pleural effusion, an enlarged liver of 16 cm, without intra or extra hepatic bile duct dilatation, a thickened gall bladder wall of 7 mm in the absence of any gall stones and a sonographic Murphy’s sign could not be elicited. Mild ascites was also noted. The blood pressure and urine output were maintained. A packed cell volume was done and showed only a mild rise. The fluid regimen was continued as per guidance, giving adequate fluids to maintain blood pressure and urine output.\nOn day 9 of the illness, the patient’s clinical status and jaundice improved. Serial complete blood counts showed rising platelet counts. Similarly liver function tests revealed normalizing alkaline phosphatase and bilirubin levels. The patient was discharged on the 15th day of illness with normal cell counts and liver function parameters.\nA 46 year old previously well South-Asian female, presented with six days of high fever, myalgia and jaundice. She too denied any history of contact with muddy water, recent drug usage, blood transfusion or any high risk behavior. On examination, she appeared ill, febrile to touch and deeply jaundiced. Abdominal examination revealed a mildly tender and firm hepatomegaly. The gallbladder was not palpable nor was there guarding or a positive Murphy’s sign. The respiratory system examination revealed reduced air entry on auscultation and stony dullness to percussion in the base of the right lung. The cardiovascular examination was unremarkable, with a blood pressure of 100mmHg systole and 70 mmHg without a postural drop. The nervous system examination was normal.\nWhole blood analysis on presentation demonstrated thrombocytopenia with a platelet count of 10 × 109/L (150–450) and a lymphocytic predominant (51%) white cell count of 7.8 × 109/L (4–11) with a haemoglobin value of 11.6 g/dl with a packed cell volume of 34%. The liver enzymes were elevated with the AST more than the ALT which were 242 U/L (0–40) and 120 U/L(0–35) respectively. The alkaline phosphatase was mildly elevated with a value of 400 U/L (100 – 360), with a high direct bilirubin fraction of 12 μmol/L (0–3.4) and total bilirubin of 23 μmol/L (5–21). Albumin was found mildly reduced at 31 g/L (36–48). The INR was normal. The renal functions were normal. The ultrasound scan of the abdomen and chest confirmed an enlarged liver, with a cranio-caudal length of 16 cm. The gallbladder wall was thickened and measured 6 mm, a negative sonographic Murphy’s sign was noted and no gall stones were visualized. Leakage was confirmed as there was mild ascites and a pleural effusion in the right hemithorax. The ESR was 19 mm for the first hour and the CRP was mildly elevated with a value of 7 mg/L (0.0 – 5.0). The dengue IgM antibody was positive. A Lepto MAT was performed twice on day 7 and day 11 of the illness, and showed a titre of 1:400 (a four -fold rise in titre or a high titre >1:800 is the gold standard for diagnosis) without further rise. A hepatitis screen was performed and was found negative. EBV antibody was also negative. This patient was similarly managed with a fluid regimen tailored to her body weight as per guidance, with strict monitoring of hemodynamic parameters and urine output.\nThe platelet count continued to drop reaching a nadir of 5 × 109/L (150–450) on day 8 of the illness, and subsequently began to rise. The alkaline phosphatase and bilirubin continued to rise till day 10 of the illness, after which the liver functions began to normalize (Table ). The patient was discharged on day 12 of the illness, being afebrile for 4 days with a platelet count of 128 × 109/L (150–450) and a near normal bilirubin level.
A 73-year-old man, farmer from Gorgan, a city in the north of Iran, who came because of fever and icterus since 1 week before presentation. He had no obvious symptoms since 1 week before admission when he developed progressive jaundice and episodic right upper quadrant pain especially after meal but unrelated to position or respiration. He also reported mild fever, anorexia, and generalized body pain during this period. To analyze his problem, abdominal sonography was performed in outpatient setting, which showed an increased liver echogenesity without the dilation of bile ducts and gall stone. Based oh the abovementioned symptoms, his primary care physician made a diagnosis of viral hepatitis, but the patient eventually developed constant high-grade fever and right upper quadrant pain. Therefore, he was referred to our hospital and was admitted. At the time of hospitalization, the temperature was 39.5°C, the pulse was 90 beats/min, and the respiratory rate was 18 breaths/min. The blood pressure was 110/65 mm Hg. On physical examination, the patient did not appear to be in severe pain, and there was mild jaundice. The lungs and heart sounds were normal. The abdomen was flat, and the bowel sounds were present. There was tenderness in the right upper and quadrant, with mild guarding but without rebound tenderness. No mass or hernia was detected. The arms and legs were well perfused. No abnormalities were found on rectal examination. His sonography at admission revealed minimal intrahepatic and mild extrahepatic biliary dilation, while other organs were normal and no stones were observed. Blood tests revealed mild normocytic normochromic anemia, while white blood cell and absolute eosinophil count were normal in the patient. The erythrocyte sedimentation rates were high (90 mm/h) and serum chemical analysis revealed the following values: albumin, 3.4 g/dl; alkaline phosphatase, 170 U/l (normal range, 53–128); alanine aminotransferase, 73 U/l (normal range, 10–35); aspartate aminotransferase, 54 U/l (normal range, 14–50); and total bilirubin, 8.9 mg/dl (normal range 0.3–1.2), with a direct bilirubin level of 5.7 mg/dl (normal,< 0.2). The white-cell count was 11 400/mm3, with 84% neutrophils and 1% eosinophils. The urine was orange and was positive for bile (++), protein (+), and urobilinogen (+). Because of the endemicity of leptospirosis, serologic test (indirect hemagglutination test) was done, which revealed negative result. A urine culture and multiple blood cultures were negative. Assays for the presence of hepatitis B antigen and antibody, hepatitis C antibody, and antimitochondrial antibodies were negative. Chest radiographs showed no abnormalities. Endoscopic retrograde cholangiopancreatography (ERCP) demonstrated extrahepatic biliary dilatation; the common bile ducts (CBDs) were about 12–15 mm in diameter, with a small filling defect in the distal part [].\nSerologic test for showed high titer against that (positive titer 1/80), and the detection of ova in stool documented infestation with this liver fluke. After diagnosis, triclabendazole was administered at a dose of 10–12 mg/kg for 1 or 2 days, after which the symptoms disappeared and biochemical values soon returned to normal, and the patient was discharged with good condition. During the follow-up, her jaundice subsided, and ultrasonography revealed an almost normal CBD in our patient.