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21-Year-Old Woman With Flank Pain

      A previously healthy 21-year-old woman presented to her local emergency department with a 1-week history of nausea and vomiting and severe left lateral abdominal pain and costovertebral angle tenderness of 24 hours' duration. She was concurrently having menstrual cramping and bleeding but reported no fever, night sweats, chills, rigors, or weight loss. The patient was originally from Somalia but immigrated to the United States 9 years previously. At that time, a tuberculin skin test using purified protein derivative was administered, but the patient did not recall the result. She had no known exposures to persons who were ill or a history of travel to Africa since immigration.
      Physical examination revealed a young woman in no acute distress. Vitals signs were unremarkable: temperature, 36.3ϒC; blood pressure, 118/68 mm Hg; pulse rate, 63/min; respirations, 20/min; and oxygen saturation while breathing room air, 98%. Mild tenderness was noted in the left hemiabdomen and left costovertebral angle.
      Laboratory evaluation (reference ranges shown parenthetically) revealed a hemoglobin level of 12.3 g/dL, (12-15.5 g/dL) and a white blood cell count of 8.5 × 109/L (3.5-10.5 × 109/L) with a normal differential. The platelet count, electrolyte levels, coagulation factors, serum urea nitrogen concentration, and creatinine level were normal. Urinalysis revealed 1 to 3 red blood cells per high-power field, but the patient was currently menstruating. There was no evidence of pyuria, and qualitative β-subunit human chorionic gonadotropin testing yielded negative results.

      1.. Which one of the following would be the next most appropriate imaging study based on the patient's symptoms, physical examination findings, and laboratory test results?

      • a.
        Renal ultrasonography
      • b.
        Noncontrast abdominal computed tomographic (CT) renal stone protocol
      • c.
        Intravenous urography
      • d.
        Abdominal x-ray film
      • e.
        Abdominal magnetic resonance imaging
      Renal ultrasonography is generally insensitive for stones, especially those smaller than 2 mm and located at the ureteropelvic junction (UPJ) or mid ureter. Noncontrast abdominal CT is highly sensitive and specific in identifying urinary tract calcification and structural abnormalities such as hydronephrosis and urinary tract dilatation. It can easily differentiate between nonopaque stones, blood clots, and tumors and may suggest alternative diagnoses when urinary tract pathological abnormalities are not found. Thus, noncontrast CT would be the best imaging study at this time.
      Intravenous urography can identify urinary tract obstruction, but because its specificity in identifying renal calculi is lower than that of CT, it is not used routinely. Ninety percent of renal calculi are radiopaque,
      • Brenner BM
      and stones as small as 1 to 2 mm can be detected on plain abdominal x-ray film. However, cystine and uric acid stones are radiolucent and may not be evident on plain films. Abdominal magnetic resonance imaging is a poor choice because stones are not typically seen directly. Other important disadvantages of the modality include the time needed to acquire images, the greater expertise required for interpretation of the images, and the cost to perform.
      Concern about a urinary tract stone prompted performance of a CT renal stone protocol. No stone was identified, but the procedure showed multiple peripherally enhancing low-density masses ranging from 0.5 to 1.5 cm within the body and tail of the pancreas and the mesenteric root (Figure 1). Splenic vein thrombosis with isolated gastric varices was also noted. A low-density enhancing mass or fluid collection measuring 4.5 × 6.3 cm was seen within the right posterior psoas muscle, and multiple enhancing low-density masses were noted along the external iliac lymph node chain. Multiple small indeterminate subpleural nodules, the largest 0.5 cm, were also detected in the right lower lung.
      Figure thumbnail gr1
      FIGURE 1Abdominal computed tomographic scans on presentation showing peripancreatic cystic lesions (A), psoas abscess (B), and inguinal lymphadenopathy (C and D).
      The radiological findings were considered consistent with metastatic disease from an unknown primary tumor, most likely from a mucinous cystadenocarcinoma of the pancreas.

      2.. Which one of the following would be the next most appropriate step based on the CT findings?

      • a.
        Exploratory laparoscopy
      • b.
        Bronchoscopy with transbronchial biopsy of subpleural nodules
      • c.
        CT-guided fine-needle aspiration (FNA) of one of the masses
      • d.
        CT-guided drainage of the psoas fluid collection
      • e.
        Esophagogastroduodenoscopy with endoscopic ultrasonography (EUS) and FNA of the pancreatic mass
      Exploratory laparoscopy would allow direct visualization of the abdominal contents and collection of biopsy specimens. However, it is not the best choice because less invasive procedures can be performed to obtain tissue from any of the lesions in this patient.
      Bronchoscopy with transbronchial biopsy would not be useful because the burden of disease is clearly intra-abdominal. Biopsy of subpleural nodules would be technically difficult and would likely yield little valuable information.
      Computed tomography-guided FNA of the pancreatic lesions, lymph nodes, or psoas abscess is a reasonable approach but may be technically difficult. Fluid drained from the psoas abscess could be cultured for bacteria, mycobacteria, and fungus, but culture yield from abscess fluid is typically low for some organisms.
      In evaluating pancreatic masses, EUS has a higher sensitivity than CT (81% vs 56%) in determining nodal status and vascular involvement,
      • Midwinter MJ
      • Beveridge CJ
      • Wilsdon JB
      • Bennett MK
      • Baudouin CJ
      • Charnley RM
      Correlation between spiral computed tomography, endoscopic ultrasonography and findings at operation in pancreatic and ampullary tumours.
      information that is crucial in evaluating the resectability of a tumor. In addition, the accuracy of EUS-directed FNA in diagnosing a cystic neoplasm is as high as 83%,
      • Tamerisa R
      • Irisawa A
      • Bhutani MS
      Endoscopic ultrasound in the diagnosis, staging, and management of gastrointestinal and adjacent malignancies.
      and specimens can be subjected to pathological examination. Thus, EUS with FNA is the best choice in this patient.
      Endoscopic ultrasonography and FNA showed the pancreas to be diffusely enlarged with a partially cystic mass on the posterior wall. The mass was aspirated, and smears revealed necrotic material and occasional benign-appearing pancreatic cells. In addition, multiple large (>2 cm) cystic lymph nodes were detected adjacent to the stomach. Lymph node aspiration yielded creamy white-yellow fluid, and preliminary smears showed necrotic material with occasional lymphocytes. Acid-fast bacilli (AFB) smears were negative in both samples. Cultures grew Stomatococcus mucilaginosus, nonpathogenic Neisseria, and Streptococcus viridans. Treatment with amoxicillin-clavulanic acid was initiated.

      3.. Which one of the following is the most likely cause of this patient's positive FNA cultures?

      • a.
        Perforated bowel or gallbladder
      • b.
        Oral abscess with bacteremia
      • c.
        Endocarditis
      • d.
        Endoscopic contamination
      • e.
        Pelvic inflammatory disease
      The organisms that most commonly cause intra-abdominal infection from perforated bowel or gallbladder include Escherichia coli, Enterococcus, and Bacteroides; however, numerous other gram-negative or anaerobic bacteria can also cause such infections. Oral abscesses may cause bacteremia, but disseminated polymicrobial abscesses are extremely uncommon. Community-acquired polymicrobial endocarditis has not been associated with subsequent polymicrobial intra-abdominal infection.
      Stomatococcus, Neisseria, and S viridans all colonize the oral cavity, nasopharynx, and upper gastrointestinal (GI) tract. A polymicrobial culture from a single site such as a lymph node most likely represents contamination from instruments passed through the GI tract. Pelvic inflammatory disease is usually caused by organisms such as Neisseria gonorrhoeae, Chlamydia, Bacteroides, and Enterobacteriaceae. Organisms that usually colonize the upper GI tract are highly unlikely to cause pelvic inflammatory disease.
      Because further diagnostic testing was needed, a drain was placed in the psoas abscess with CT guidance. Purulent yellow fluid was aspirated and submitted for Gram stain, fungal stain, AFB smear, DNA probe for Mycobacterium tuberculosis, and bacterial, fungal, and mycobacterial cultures. The DNA probe was positive for M tuberculosis. A tuberculin skin test using purified protein derivative was positive with a reaction size of 18 mm. Abdominal tuberculosis was diagnosed, and treatment with isoniazid, rifampin, pyrazinamide, ethambutol, and pyridoxine was initiated.
      With the institution of therapy, the patient developed severe nausea and vomiting refractory to conservative measures. Laboratory studies yielded the following notable results: alkaline phosphatase, 148 U/L (52-144 U/L); aspartate aminotransferase (AST), 177 U/L (12-31 U/L) (increased from 37 U/L at presentation); alanine aminotransferase (ALT), 77 U/L (9-29 U/L) (increased from 27 U/L at presentation); total bilirubin, 1.6 mg/dL (0.1-1.0 mg/dL) (increased from 0.5 mg/dL at presentation); direct bilirubin, 1.1 mg/dL (0.0-0.3 mg/dL) (increased from 0.5 mg/dL at presentation); and international normalized ratio (INR), 1.3 (increased from 1.1 at presentation)

      4.. Which one of the following is the next most appropriate step in the management of this patient's condition?

      • a.
        Change antituberculous therapy to pyrazinamide and ethambutol only
      • b.
        Continue all medications and add antiemetics
      • c.
        Increase the pyridoxine dosage
      • d.
        Obtain hepatitis serologies
      • e.
        Discontinue all medications
      Isoniazid, rifampin, and pyrazinamide are first-line antituberculous agents known to cause major hepatotoxicity, especially when administered together. The frequency of hepatotoxicity ranges from 1% to 10%.
      • Tost JR
      • Vidal R
      • Cayla J
      • et al.
      Severe hepatotoxicity due to antituberculosis drugs in Spain.
      Mild asymptomatic liver enzyme elevation (approximately 3 times the normal level) does not typically require discontinuation of the medications.
      • Tost JR
      • Vidal R
      • Cayla J
      • et al.
      Severe hepatotoxicity due to antituberculosis drugs in Spain.
      • Blumberg HM
      • Burman WJ
      • Chaisson RE
      • American Thoracic Society, Centers for Disease Control and Prevention, Infectious Diseases Society
      American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis.
      Treatment with only pyrazinamide and ethambutol would be inadequate and would likely promote resistance. Adding antiemetics would not address the primary pathology of hepatotoxicity caused by antibiotics. Pyridoxine is administered along with antituberculous therapy to prevent isoniazid-mediated neurotoxicity and would not be indicated for drug-induced hepatitis. The patient's clinical presentation is somewhat compatible with acute viral hepatitis; however, liver enzyme elevations in viral infections are typically much higher (ALT and AST usually >1000 U/L). In addition, the patient has no known history of or exposure to viral hepatitis. Although the ALT and alkaline phosphatase levels were not more than 3 times the normal levels, the AST level was extremely elevated, and the patient was symptomatic with intractable nausea and vomiting. Her elevated serum bilirubin and INR indicated hepatic dysfunction. Thus, it is most reasonable to discontinue all medications.
      • American Thoracic Society
      Targeted tuberculin testing and treatment of latent tuberculosis infection.
      The patient's INR peaked at 1.6, AST at 177 U/L, and ALT at 412 U/L. Hepatitis secondary to antituberculous therapy was diagnosed, and all medications were stopped. Once the patient was asymptomatic, rifampin, isoniazid, and ethambutol were reintroduced sequentially and were tolerated well. Cultures from the psoas abscess grew M tuberculosis, and susceptibility testing showed the organism to be resistant to isoniazid and rifampin.

      Which one of the following is true in light of the resistance pattern of the organism described above?

      • a.
        Second-line drugs are just as effective and less toxic
      • b.
        For a failing program, addition of a single secondary agent is usually adequate
      • c.
        The organism will most likely be cross resistant to rifabutin and rifapentine
      • d.
        Patients with suspected latent multidrug-resistant (MDR) tuberculosis can be treated successfully with isoniazid
      • e.
        Duration of treatment should be at most 12 months
      Multidrug-resistant tuberculosis is defined as an organism resistant to at least rifampin and isoniazid.
      • Di Perri G
      • Bonora S
      Which agents should we use for the treatment of multidrug-resistant Mycobacterium tuberculosis?.
      Resistance is typically generated by suboptimal antibiotic regimens, including erratic self-administration, monotherapy, and poor compliance.
      • Blumberg HM
      • Burman WJ
      • Chaisson RE
      • American Thoracic Society, Centers for Disease Control and Prevention, Infectious Diseases Society
      American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis.
      • Di Perri G
      • Bonora S
      Which agents should we use for the treatment of multidrug-resistant Mycobacterium tuberculosis?.
      • Sahbazian B
      • Weis SE
      Treatment of active tuberculosis: challenges and prospects.
      Second-line drugs for the treatment of MDR tuberculosis include amikacin, fluoroquinolones, cycloserine, para-aminosalicylic acid, ethionamide, and linezolid.
      • Blumberg HM
      • Burman WJ
      • Chaisson RE
      • American Thoracic Society, Centers for Disease Control and Prevention, Infectious Diseases Society
      American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis.
      As a class, these second-line agents are generally not as effective as first-line medications and are more toxic. The treatment of MDR tuberculosis requires 4 or 5 agents with in vitro activity. Adding a single second-line agent to an inadequate regimen is strongly discouraged and could cause further resistance.
      Rifampin, rifabutin, and rifapentine all belong to the rifamycin drug group. If an isolate is resistant to rifampin, cross-resistance to rifabutin and rifapentine would also occur as a class effect.
      • Blumberg HM
      • Burman WJ
      • Chaisson RE
      • American Thoracic Society, Centers for Disease Control and Prevention, Infectious Diseases Society
      American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis.
      Patients with latent tuberculosis who are from countries with a high incidence of MDR tuberculosis should be treated with at least 2 drugs for 6 to 12 months, not with isoniazid monotherapy.
      • American Thoracic Society
      Targeted tuberculin testing and treatment of latent tuberculosis infection.
      The choice of antimicrobials should be guided by the patient's known resistance patterns or epidemiological data. The duration of treatment of MDR tuberculosis with such drugs should be at least 18 to 24 months because they are typically less effective than first-line agents.
      • Blumberg HM
      • Burman WJ
      • Chaisson RE
      • American Thoracic Society, Centers for Disease Control and Prevention, Infectious Diseases Society
      American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis.
      Because the organism cultured from our patient was resistant to 2 of the 3 antibiotics she was receiving, another antibiotic regimen was formulated that consisted of ethambutol, pyrazinamide, moxifloxacin, amikacin, and cycloserine. At 3-month follow-up, repeated CT showed considerable decrease in the size of the pancreas lesion and partial resolution of intra-abdominal lymphadenopathy.

      DISCUSSION

      This case highlights the difficulties in diagnosing and treating extrapulmonary tuberculosis. On the basis of abdominal CT findings, the disorder was initially thought to be neoplastic, but subsequent FNA indicated an infection. In addition, the culture results obtained from the FNA specimens misdirected treatment, and several specimens had to be obtained to determine the diagnosis. Once treatment was initiated, the patient developed complications and was discovered to have a resistant organism that further complicated her treatment.
      M tuberculosis is a slow-growing acid-fast bacillus that is a major cause of morbidity and mortality worldwide. Endemic in developing nations, the incidence of tuberculosis has also increased in developed countries because of increased immigration and greater numbers of immunosuppressed patients. It is estimated that nearly 9 million new cases of active tuberculosis occur each year, and most US cases occur in non-US-born individuals.
      • Di Perri G
      • Bonora S
      Which agents should we use for the treatment of multidrug-resistant Mycobacterium tuberculosis?.
      • Blumberg HM
      • Leonard Jr, MK
      • Jasmer RM
      Update on the treatment of tuberculosis and latent tuberculosis infection [published correction appears in JAMA. 2005;294:182].
      On CT, pancreatic tuberculosis may manifest as an enlarged pancreas with a hypodense lesion and occasionally an irregular septated cystic lesion, but these findings are typically nonspecific and may be mistaken for a cystic pancreatic neoplasm or other abdominal malignancy.
      • Liu Q
      • He Z
      • Bie P
      Solitary pancreatic tuberculous abscess mimicking pancreatic cystadenocarcinoma: a case report.
      • Claro I
      • Leitao CN
      • Oliveira P
      • et al.
      Tuberculous mesenteric lymphadenitis mimicking pancreatic carcinoma.
      When intra-abdominal infection occurs, the lymph nodes and the terminal ileum are the most common sites. However, infection may involve any part of the GI tract, peritoneum, liver, or spleen.
      • Liu Q
      • He Z
      • Bie P
      Solitary pancreatic tuberculous abscess mimicking pancreatic cystadenocarcinoma: a case report.
      • Rezeig MA
      • Fashir BM
      • Al-Suhaibani H
      • Al-Fadda M
      • Amin T
      • Eisa H
      Pancreatic tuberculosis mimicking pancreatic carcinoma: four case reports and review of the literature.
      • Ozden I
      • Emre A
      • Demir K
      • Balci C
      • Poyanli A
      • Ilhan R
      Solitary pancreatic tuberculosis mimicking advanced pancreatic carcinoma.
      • Demir K
      • Kaymakoglu S
      • Besisik F
      • et al.
      Solitary pancreatic tuberculosis in immunocompetent patients mimicking pancreatic carcinoma.
      The patient may present with a variety of symptoms, including abdominal pain, obstruction, peritonitis, fever of unknown origin, GI bleeding, or splenic vein thrombosis.
      Even in endemic countries, tuberculosis affecting the pancreas is relatively uncommon, occurring in as few as 5% of patients with miliary tuberculosis in autopsy studies.
      • Liu Q
      • He Z
      • Bie P
      Solitary pancreatic tuberculous abscess mimicking pancreatic cystadenocarcinoma: a case report.
      • Demir K
      • Kaymakoglu S
      • Besisik F
      • et al.
      Solitary pancreatic tuberculosis in immunocompetent patients mimicking pancreatic carcinoma.
      • Franco-Paredes C
      • Leonard M
      • Jurado R
      • Blumberg HM
      • Smith RM
      Tuberculosis of the pancreas: report of two cases and review of the literature.
      The development of abdominal tuberculosis is typically independent of pulmonary disease, but coexisting disease has been reported in 5% to 38% of cases.
      • Liu Q
      • He Z
      • Bie P
      Solitary pancreatic tuberculous abscess mimicking pancreatic cystadenocarcinoma: a case report.
      The diagnosis of abdominal tuberculosis often requires tissue sampling, including FNA, biopsy, or cyst or abscess drainage. Samples should be subjected to AFB smear, mycobacterial culture, histological analysis, and polymerase chain reaction for M tuberculosis. Polymerase chain reaction is particularly useful when the initial AFB smear, microscopy, or culture results are negative. However, tuberculosis should remain an option, especially when clinical suspicion is high, because false-negative results have been reported.
      • Ozden I
      • Emre A
      • Demir K
      • Balci C
      • Poyanli A
      • Ilhan R
      Solitary pancreatic tuberculosis mimicking advanced pancreatic carcinoma.
      Another less meritorious option involves initiating a trial of antituberculous therapy and evaluating the patient's clinical response.
      • Liu Q
      • He Z
      • Bie P
      Solitary pancreatic tuberculous abscess mimicking pancreatic cystadenocarcinoma: a case report.
      Cultures and sensitivity studies should be obtained in all patients to determine resistance patterns and to tailor therapy.
      Treatment of drug-susceptible tuberculosis usually includes rifampin, isoniazid, pyrazinamide, and ethambutol for an intense initiation phase of 2 months, followed by a continuation phase of 4 to 7 months with isoniazid and rifampin.
      • Sahbazian B
      • Weis SE
      Treatment of active tuberculosis: challenges and prospects.
      • Blumberg HM
      • Leonard Jr, MK
      • Jasmer RM
      Update on the treatment of tuberculosis and latent tuberculosis infection [published correction appears in JAMA. 2005;294:182].
      When revising therapy, adding a single drug to a failing regimen simply breeds resistance to the new agent.
      • Blumberg HM
      • Burman WJ
      • Chaisson RE
      • American Thoracic Society, Centers for Disease Control and Prevention, Infectious Diseases Society
      American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis.
      • Di Perri G
      • Bonora S
      Which agents should we use for the treatment of multidrug-resistant Mycobacterium tuberculosis?.
      • Sahbazian B
      • Weis SE
      Treatment of active tuberculosis: challenges and prospects.
      Optimal design of re-treatment requires an infectious or thoracic disease specialist and should involve at least 2 medications that the patient has not taken previously.
      • Sahbazian B
      • Weis SE
      Treatment of active tuberculosis: challenges and prospects.
      The cure rate is invariably decreased and requires a longer duration of treatment (up to 18-24 months) compared to that for drug-susceptible tuberculosis.
      • Blumberg HM
      • Burman WJ
      • Chaisson RE
      • American Thoracic Society, Centers for Disease Control and Prevention, Infectious Diseases Society
      American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis.
      • Di Perri G
      • Bonora S
      Which agents should we use for the treatment of multidrug-resistant Mycobacterium tuberculosis?.
      At least 3, and preferably 4 or 5, drugs with proven in vitro activity should be administered, with preference given to first-line agents that are still active.
      • Blumberg HM
      • Burman WJ
      • Chaisson RE
      • American Thoracic Society, Centers for Disease Control and Prevention, Infectious Diseases Society
      American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis.
      • Di Perri G
      • Bonora S
      Which agents should we use for the treatment of multidrug-resistant Mycobacterium tuberculosis?.

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        Which agents should we use for the treatment of multidrug-resistant Mycobacterium tuberculosis?.
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        Treatment of active tuberculosis: challenges and prospects.
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        Update on the treatment of tuberculosis and latent tuberculosis infection [published correction appears in JAMA. 2005;294:182].
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        Solitary pancreatic tuberculous abscess mimicking pancreatic cystadenocarcinoma: a case report.
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