Case Quiz: An Unusual Diagnosis in a Young Woman With Abdominal Pain

A married 30-year-old woman with no past medical history presents to the emergency department with complaints of dull aching pain in the right upper quadrant of her abdomen and her lumbar region. The discomfort was initially associated with low-grade fevers that were relieved by over-the-counter antipyretics. Recently, the fevers have only temporarily been relieved with antipyretics. These symptoms are associated with nausea, vomiting, decreased appetite, yellowish discoloration of the sclera (shown), and a 10-kg weight loss. The patient denies any history of change in bowel habits, melena, clay-colored stools, hematemesis, or other symptoms.

Her medical history includes cholecystitis during pregnancy, which was managed with antibiotics. She subsequently had a caesarean section and cholecystectomy. She is a nonsmoker and doesn't consume alcohol. She denies any illicit drug use or any recent travel history and is a resident of Pakistan. On examination, she is a young, anxious-appearing woman, with a regular heart rate of 100 beats per minute, blood pressure of 110/70 mm Hg, respiratory rate of 24 breaths per minute, and a temperature of 102^oF. She is jaundiced. Abdominal examination reveals right upper quadrant tenderness on deep palpation with tender hepatomegaly. She has diminished breath sounds and dullness on auscultating the right lower lung. The rest of her physical examination is unremarkable.

The patient's laboratory results are shown. Which tests are abnormal?

The correct answer is total bilirubin of 25.0 μmol/L (normal: 5.1-17.0 μmol/L), alkaline phosphatase of 350 IU/L (normal: 20-140 IU/L), and erythrocyte sedimentation rate (ESR) of 70 mm/hr (normal: < 20 mm/hr).

The rest of her laboratory results are negative, including hepatitis A, B, C, D, and E; HIV; and syphilis. Her carcinoembryonic antigen (CEA) and alpha-fetoprotein are normal. Bacterial and fungal blood cultures are drawn.

An initial chest x-ray is ordered, which reveals what abnormality?

A. Focal infiltrate

B. Widened mediastinum

C. Abnormal calcifications over the right upper quadrant

D. Pleural effusion

There is a right-sided pleural effusion with blunting of the costophrenic angle (circled).

The pleural effusion is aspirated and sent to the laboratory for analysis. Pleural effusions may be either transudative or exudative. Light's criteria are used to differentiate between transudative and exudative processes.

Which of the following laboratory results is NOT needed to calculate Light's criteria?

A. Pleural lactate dehydrogenase (LDH)

B. Serum LDH

C. Serum protein

D. Pleural glucose

The correct answer is pleural glucose. According to Light's criteria, a pleural effusion is exudative if it meets one of the following criteria: pleural protein/serum protein > 0.5, pleural LDH/serum LDH > 0.6, pleural LDH > 200, or pleural LDH > 2/3 upper limit of normal serum LDH.

The patient subsequently underwent an abdominal ultrasound, which reveals a space-occupying lesion in the right lobe of the liver. A CT scan of the abdomen and pelvis is performed. Multiple representative images are shown.

What abnormalities are present on the CT scan images?

There are multiple hypodense lesions (circles) within the right lobe of the liver that likely correlate with the abnormality seen on ultrasound.

What is the most likely etiology of these hypodense lesions?

A. Abscess

B. Hepatocellular carcinoma

C. Hepatoma

D. Metastatic cancer

Abscess is the most likely diagnosis for multiple hypodense, interconnected lesions with well-defined walls.

Postcontrast images are shown, which reveal what additional abnormality?

There is a fluid collection extending posterolaterally in the perinephric space (yellow circle).

The patient undergoes an exploratory laparotomy with drainage of purulent material from the liver abscesses. The fluid is sent for Gram stain, culture and sensitivity, and acid-fast bacillus (AFB) smear. The abscess wall is sent for histopathology. While awaiting culture results, the patient is started on broad-spectrum antibiotic coverage.

What is the least likely etiology of this patient's abscess, given her clinical symptoms, radiologic appearance, age, medical history, and geographic location (see slide 2 for geography information)?

A. Amoebic liver abscess

B. Tuberculosis (TB)

C. Bacterial liver abscess

D. Toxoplasmosis

This patient has a TB liver abscess with perinephric extension. This was confirmed with a positive AFB on Ziehl-Neelsen stain. These findings were supported by the histopathology report of the liver abscess wall.

TB, in its varied forms, is widely prevalent in the tropics. It continues to be a leading cause of morbidity and mortality in the developing regions of the world, and globally there has been a resurgence as a result of the AIDS epidemic.^[1] More than 2 billion people, which is one third of the world's population, are infected with TB. This image of TB incidence in 2009 is shown courtesy of the World Health Organization (WHO).

How much does AIDS increase the risk of developing active TB (compared with a non-HIV/AIDS-infected person)?

A. 2 x

B. 5-10 x

C. 10-20 x

D. 20-40 x

Patients with AIDS have a 20-40 times increase in the risk of developing active TB.^[2]

HIV infection and AIDS are very large risk factors in the development of TB. TB is the leading cause of death worldwide among patients infected with HIV. In Africa, HIV infection is the single most important factor contributing to the risk of developing TB. This image of HIV prevalence in new cases of TB is shown courtesy of the WHO.

Although abdominal TB is thought to be frequently associated with active pulmonary TB, evidence of active pulmonary TB occurs in only 6%-38% of reported cases.^[3] Abdominal TB most commonly affects the intestinal tract, lymph nodes, and peritoneum. Up to two thirds of patients with abdominal TB have abdominal lymphadenopathy or peritoneal disease in addition to intestinal involvement. The abdominal x-ray shown demonstrates diffuse calcified mesenteric lymphadenopathy in a patient with abdominal TB. One third of patients may have extraintestinal involvement as well. Isolated hepatobiliary or pancreatic TB is rare and the preoperative diagnosis is difficult.^[3]

How often does TB involve the liver?

A. < 1% of cases

B. 1%-5% of cases

C. 5%-10% of cases

D. 10%-15% of cases

Hepatic TB is extremely rare and occurs in less than 1% of all cases of TB.

Isolated hepatic TB is extremely rare with less than 30 cases reported in the literature.^[4] Jaundice is extremely rare and occurs as a result of lymphadenopathy creating biliary tract obstruction at the porta hepatis, obstruction in the common bile duct, or by portal inflammatory stricture. The low oxygen tension within the liver, which makes it an unfavorable environment for mycobacterial growth, has been cited as an explanation for the rarity of isolated hepatic TB.

Laboratory evaluation is nonspecific with elevated alkaline phosphatase in the setting of normal ALT and AST. Granulomas (shown) in the liver are associated with a myriad of disorders, the prevalence of which depends upon geographic location and the specific population. They may also be an incidental finding on otherwise normal liver biopsy specimens.^[6] Indeed, cases of hepatic TB mimicking hepatocellular carcinoma and cholangiocarcinoma have been described in the literature.^[4,7]

Microscopically, hepatic TB typically shows epithelioid cell granulomas. Langerhans-type giant cells (arrow) are often present with a mixed inflammatory infiltrate including plasma cells and lymphohistiocytic cells. Tubercular granulomas in the diffuse form are located in the hepatic lobules, in contrast to the localized form, wherein the granulomas are predominantly portal in location.^[8] Other nonspecific histologic findings may include Kupffer cell hyperplasia, focal hepatocyte necrosis with round-cell infiltration, and portal inflammation.

In Ziehl-Neelsen stains, AFB are stained bright red, which causes them to stand out against a blue background (arrows).

In a patient with suspected hepatic TB, which are the most sensitive and specific diagnostic battery of tests?

A. AFB smear alone

B. AFB smear with histopathology finding of granulomas

C. AFB smear, ESR, and histopathology findings of granulomas

D. Polymerase chain reaction (PCR), AFB smear, and histopathology findings of granulomas

Maximum sensitivity and specificity is achieved by the combined use of clinical diagnosis, positive AFB smear (arrows), histopathology, and PCR.

Imaging studies can pose a diagnostic challenge for abdominal TB because there are a large number of potential diagnoses. Tuberculous abscesses usually appear as round hypo- and hyperechoic areas on ultrasonography, while CT scans demonstrate hypodense lesions.^[9] These diagnostic findings in the setting of an indolent presentation with mainly constitutional symptoms can easily lead the differential diagnosis toward malignancies and, therefore, a definitive noninvasive diagnosis is difficult, with up to 90% of cases requiring a laparotomy to establish a definitive diagnosis.

You have just diagnosed a patient with hepatic TB using the above-mentioned diagnostic battery of tests. Which of the following is the optimal treatment regimen?

A. Isoniazid and rifampin for 1 year

B. Surgical drainage of the abscess

C. Quadruple therapy with isoniazid, rifampin, pyrazinamide, and ethambutol for 1 year

D. Isoniazid and rifampin for 1 year and surgical drainage

Treatment of hepatic TB is by quadruple therapy consisting of isoniazid, rifampin, pyrazinamide, and ethambutol for 1 year, although there are often signs of clinical improvement within 2-3 months. Dosing instructions are shown courtesy of the WHO.

Unfortunately, there are a growing number of cases of TB unresponsive to standard therapy, termed multidrug-resistant TB (MDR-TB). These patients have a much higher mortality rate and require a unique drug regimen with a longer duration of therapy. Data from the WHO showing historical and predicted cases of MDR-TB are shown in 'surveyed' (grey) and 'to be surveyed' (blue) countries.

This patient was started on a quadruple-drug regimen after drainage of the liver abscess for a period of 1 year. Fortunately, she did not have MDR-TB. She showed marked clinical improvement within 2 months, and a repeat CT scan showed complete resolution of the abscess. Image courtesy of the WHO.

More Slideshows

• Can't-Miss Common-to-Rare Skin Conditions in Infancy
• Case Quiz: A Can't-Miss Abdominal Catastrophe
• Case Quiz: The Febrile Traveler
• The Shattered Pelvis
• Thoracentesis Best Practices
• Other Slideshows

For more information, see the following resources:

• eMedicine, Emergency Medicine: Tuberculosis
• eMedicine, Infectious Diseases: Tuberculosis
• eMedicine, Pediatrics: General Medicine: Tuberculosis

Contributor Information

Authors
Ismaa G. Kiani, MBBS, MCPS, FCPS
Fellow, Department of Nephrology, Military Hospital
Rawalpindi, Pakistan

Disclosure: Ismaa G. Kiani, MBBS, MCPS, FCPS, has disclosed no relevant financial relationships.

Craig A. Goolsby, MD
Director, eMedicine Case of the Week
Staff Physician, Department of Emergency Medicine, Wilford Hall Medical Center, Lackland Air Force Base
San Antonio, Texas

Disclosure: Craig A. Goolsby, MD, has disclosed no relevant financial relationships.

Contributor Information

Mark P. Brady, PA-C
Chief Physician Assistant
Department of Emergency Medicine
Cambridge Hospital
Cambridge Health Alliance
Cambridge, Massachusetts

Disclosure: Mark P. Brady, PA-C, has disclosed no relevant financial relationships.

Lars Grimm, MD, MHS
House Staff
Department of Internal Medicine
Duke University Medical Center
Durham, North Carolina

Disclosure: Lars Grimm, MD, MHS, has disclosed no relevant financial relationships.

Editor
Burke A. Cunha, MD
Professor of Medicine, State University of New York School of Medicine at Stony Brook, Stony Brook, New York;
Chief, Infectious Disease Division, Winthrop-University Hospital
Mineola, New York

Disclosure: Burke A. Cunha, MD, has disclosed no relevant financial relationships.

References

1. Arora R, Sharma A, Bhowate P, Bansal VK, Guleria S, Dinda AK. Hepatic tuberculosis mimicking Klatskin tumor: a diagnostic dilemma. Indian J Pathol Microbiol. 2008;51:382-385.Medline: [18723964]

2. WHO. Fact Sheet 104. World Health Organization. Available at http://www.who.int/mediacentre/factsheets/fs104/en/index.html Accessed October 13, 2010.

3. Saluja SS, Ray S, Pal S, et al. Hepatobiliary and pancreatic tuberculosis: a two decade experience. BMC Surg. 2007; 7:10. Medline: [17588265]

4. Bikhchandani J, Malik VK, Kumar V, Sharma S. Hepatic tuberculosis mimicking carcinoma gall bladder. Indian J Gastroenterol. 2005;24:25.Medline: [15778524]

5. Levine C. Primary macronodular hepatic tuberculosis: US and CT appearances. Gastrointest Radiol. 1990;15:307–309. Medline: [2210202]

6. Drebber U, Kasper HU, Ratering J, et al. Hepatic granulomas: histological and molecular pathological approach to differential diagnosis--a study of 442 cases. Liver Int. 2008;28:828-834. Medline: [18312287]

7. Brookes MJ, Field M, Dawkins DM, Gearty J, Wilson P. Massive primary hepatic tuberculoma mimicking hepatocellular carcinoma in an immunocompetant host. MedGenMed. 2006;8:11. Medline: [17406153]

8. Hersch C. Tuberculosis of the liver. A study of 200 cases. S Afr Med J. 1964;38:857-863. Medline: [14212648]

9. Hayashi M, Yamawaki I, Okajima K, Tomimatsu M, Ohkawa S. Tuberculous liver abscess not associated with lung involvement. Intern Med 2004;43:521-523. Medline: [15283192]