Circling Back for the Diagnosis Joseph Rencic, M.D., Mengyu Zhou, M.D., Gerald Hsu, M.D., Ph.D., and Gurpreet Dhaliwal, M.D.
Total Page：16
File Type：pdf, Size：1020Kb
The new england journal of medicine Clinical Problem-Solving Caren G. Solomon, M.D., M.P.H., Editor Circling Back for the Diagnosis Joseph Rencic, M.D., Mengyu Zhou, M.D., Gerald Hsu, M.D., Ph.D., and Gurpreet Dhaliwal, M.D. In this Journal feature, information about a real patient is presented in stages (boldface type) to an expert clinician, who responds to the information, sharing his or her reasoning with the reader (regular type). The authors’ commentary follows. From the Department of Medicine, Tufts A 28-year-old man presented to the emergency department with abdominal pain, Medical Center, Boston (J.R., M.Z.); and nausea, and vomiting. The patient reported that he had had intermittent pain in the the Department of Medicine, University of California, San Francisco, and the right upper and right lower quadrants of the abdomen for 6 weeks. The pain wors- Medical Service, San Francisco Veterans ened when he ate food and usually abated within 1 to 2 hours after he took antacids. Affairs Medical Center — both in San On this occasion, the pain was severe and had lasted for 8 hours. Intake of food had Francisco (G.H., G.D.). Address reprint requests to Dr. Rencic at 800 Washington worsened the pain and was followed by an episode of nonbloody, nonbilious emesis. St., Box 398, Boston, MA 02111, or at He did not have fever or chills. jrencic@ tuftsmedicalcenter . org. N Engl J Med 2017;377:1778-84. Recurrent, limited bouts of pain on the right side of the abdomen after meals are DOI: 10.1056/NEJMcps1701742 characteristic of biliary colic and peptic ulcer disease. The increased severity and Copyright © 2017 Massachusetts Medical Society. persistence of the pain at the time of the patient’s current presentation could rep- resent evolution into acute cholecystitis or ulcer perforation. Other causes of pain on the right side of the abdomen include appendicitis, hepatitis, colitis, nephroli- thiasis, and renal infarction, although these disorders seem to be unlikely on the basis of the recurrent and previously limited nature of the pain. The patient had received a diagnosis of Gilbert’s syndrome 2 years earlier when his primary care physician noted that he had isolated indirect hyperbilirubinemia. He was obese (body-mass index [the weight in kilograms divided by the square of the height in meters], 33) and had nonalcoholic fatty liver disease. He reported that he had never used tobacco or recreational drugs and that he seldom drank alcohol. On physical examination, the temperature was 37.1°C, the heart rate 84 beats per minute, the blood pressure 145/90 mm Hg, the respiratory rate 18 breaths per min- ute, and the oxygen saturation 100% while he was breathing ambient air. He ap- peared to be uncomfortable because of the abdominal pain. Scleral icterus was pres- ent. Cardiac and pulmonary examinations were normal. There was mild tenderness in the right upper and right lower quadrants of the abdomen, with no rebound or guarding. There were no stigmata of chronic liver disease. The most common causes of isolated indirect hyperbilirubinemia in an adult are Gilbert’s syndrome and hemolysis. Nonalcoholic fatty liver disease may be associated with dull discomfort in the right upper quadrant but does not cause severe pain. Obesity and hemolysis predispose patients to the formation of gallstones (choles- terol and pigment gallstones, respectively). The patient’s jaundice and the tender- ness on the right side of the abdomen suggest a hepatobiliary disorder such as hepa- titis, hepatic infiltration, hepatic congestion, cholecystitis, or choledocholithiasis. The white-cell count was 19,800 per cubic millimeter (86% neutrophils, 5% lympho- cytes, 8% monocytes, and zero bands), the hemoglobin level 16.0 g per deciliter, and 1778 n engl j med 377;18 nejm.org November 2, 2017 The New England Journal of Medicine Downloaded from nejm.org by LUIS ERNESTO GONZALEZ SANCHEZ on November 7, 2017. For personal use only. No other uses without permission. Copyright © 2017 Massachusetts Medical Society. All rights reserved. Clinical Problem-Solving the platelet count 196,000 per cubic millimeter. bin level was 19.5 mg per deciliter (334 μmol per The levels of electrolytes, blood urea nitrogen, liter), and the direct bilirubin level 11.2 mg per creatinine, and glucose were normal. The total deciliter (192 μmol per liter). The alanine amino- bilirubin level was 6.7 mg per deciliter (115 μmol transferase level was 519 U per liter, the aspartate per liter; reference range, 0.2 to 1.1 mg per decili- aminotransferase level 188 U per liter, and the ter [3 to 19 μmol per liter]), and the direct biliru- alkaline phosphatase level 171 U per liter. bin level was 2.6 mg per deciliter (44 μmol per Testing for hepatitis B surface antibody was liter; reference range, 0.0 to 0.3 mg per deciliter [0 to positive. Hepatitis B surface antigen and antibodies 5 μmol per liter]). The alanine aminotransferase to hepatitis A (IgM), hepatitis C, and hepatitis B level was 185 U per liter (normal value, <54), the core antigen were not detected. The ceruloplas- aspartate aminotransferase level 157 U per liter min level was normal. Testing for antinuclear and (normal range, 10 to 42), and the alkaline phos- antimitochondrial antibodies was negative. Ultra- phatase level 101 U per liter (normal range, 40 to sonography of the abdomen revealed a sludge- 130). The albumin level was 4.7 g per deciliter. filled gallbladder with wall thickening and peri- The international normalized ratio was 1.1. The cholecystic fluid, findings that are consistent lipase level was normal. Computed tomography with acute cholecystitis (Fig. 1A). There was no (CT) of the abdomen revealed a normal-sized hepatic or common bile-duct dilatation or choledo- liver with mild steatosis and splenomegaly (16 cm cholithiasis. Magnetic resonance cholangiopan- in the sagittal diameter) but no gallstones, biliary- duct dilatation, or evidence of cholecystitis. The A appendix was not visualized. The patient was admitted to the hospital, and intravenous ad- ministration of meropenem was initiated. The predominantly indirect hyperbilirubinemia suggests that Gilbert’s syndrome or hemolysis ** may be accompanying the acute illness. However, pain on the right side of the abdomen, leukocy- tosis, and an elevated direct bilirubin level (pro- portional to the other liver biochemical values) arouse concern about cholecystitis or choledocho- lithiasis. The CT results suggest neither condi- B tion, but ultrasonography is more sensitive for the detection of gallstones within the gallbladder, and magnetic resonance cholangiography would detect or rule out choledocholithiasis more de- finitively. Although physiologic stress and dehy- dration may contribute to leukocytosis, ruling out cholangitis is essential. Hemolysis sometimes causes a modest eleva- tion of aminotransferase levels (particularly the aspartate aminotransferase level) in addition to indirect hyperbilirubinemia. The normal hemo- Figure 1. Ultrasonographic and Magnetic Resonance globin level does not support a diagnosis of hemo- Cholangiopancreatography of the Gallbladder. lysis, but the patient may have hemoconcentration An ultrasonographic image of the abdomen (Panel A) or fully compensated hemolysis. A peripheral- shows a gallbladder filled with sludge (arrow), with blood smear and reticulocyte count should be gallbladder-wall thickening (asterisks) and a small obtained. amount of pericholecystic fluid (arrowheads). A T2- weighted magnetic resonance image with fat suppres- sion (Panel B) shows gallbladder-wall thickening and On the second hospital day, the abdominal pain irregularity with associated pericholecystic fluid (arrow- abated and the white-cell count decreased to heads) and a moderate amount of dependent sludge 14,200 per cubic millimeter, but the values on the in the gallbladder (arrow). liver biochemical tests increased. The total biliru- n engl j med 377;18 nejm.org November 2, 2017 1779 The New England Journal of Medicine Downloaded from nejm.org by LUIS ERNESTO GONZALEZ SANCHEZ on November 7, 2017. For personal use only. No other uses without permission. Copyright © 2017 Massachusetts Medical Society. All rights reserved. The new england journal of medicine creatography (MRCP) confirmed these findings able to portal hypertension, given the normal (Fig. 1B). Fatty infiltration of the liver and spleno- albumin level, international normalized ratio, megaly were noted on both studies. The portal and platelet count. Splenomegaly could arise and hepatic veins were patent, and normal flow from infiltration (e.g., infection or cancer) or the was observed on ultrasonography. accumulation of abnormal red cells in the con- text of hemolysis. The acute rise in the direct bilirubin level can be explained by acute cholecystitis and transient On the third hospital day, the abdominal pain biliary-duct obstruction superimposed on the pa- resolved, and the patient remained afebrile. The tient’s chronic liver disease (i.e., nonalcoholic fatty total bilirubin level was 5.7 mg per deciliter liver disease). The ultrasonographic and MRCP (97 μmol per liter), and the direct bilirubin level findings are consistent with acute cholecystitis, 2.5 mg per deciliter (43 μmol per liter). The ala- which can cause mild jaundice even in the ab- nine aminotransferase level was 292 U per liter, sence of common bile-duct obstruction. Con- the aspartate aminotransferase level 89 U per li- comitant choledocholithiasis causes more sub- ter, and the alkaline phosphatase level 174 U per stantial jaundice, although the direct bilirubin liter. Meropenem was discontinued. The patient level is typically less than 10 mg per deciliter. It was discharged home, referred to surgery for an is possible that sludge or a gallstone transiently elective cholecystectomy, and scheduled for an obstructed the common bile duct before the more appointment in the general medicine clinic the sensitive imaging methods for the detection of next day. choledocholithiasis were performed on the sec- ond hospital day; the reduction in pain would The clinical picture is consistent with acute cho- support that hypothesis.