Case ReportA Case of Typhoid Fever with Hepatic Granulomas and Enteritis
Shraddha Narechania,1 Marc Duran,2 Vidhya Karivedu,1 and K. V. Gopalakrishna3
1Fairview Hospital, Cleveland, OH 44111, USA2Internal Medicine Residency, Atlanta Medical Center, 303 Parkway Drive NE, Atlanta, GA 30312, USA3Internal Medicine Residency Program, Fairview Hospital, Cleveland, OH 44111, USA
Correspondence should be addressed to Shraddha Narechania; [email protected]
Received 16 November 2014; Accepted 12 January 2015
The common histopathologic hepatic manifestations in patients infected with Salmonella include cloudy swelling and balloondegeneration with vacuolation of the hepatocytes and steatosis. Hepatic granulomas are a very rare finding, so far reported invery few cases. We report a 64-year-old patient with Salmonella enteritis who was found to have multiple 1.4 to 1.6 cm hypoechoicliver masses on ultrasound of the abdomen which on biopsy revealed hepatic granulomas. This case highlights the importance ofkeeping the differential diagnosis of Salmonella typhi (S. typhi) in mind in a patient with hepatic granulomas.
1. Introduction
Typhoid is an infection seen in developing countries causedby the bacterium S. typhi. It is rare in developed countries likeUnited States. As per CDC, approximately 5700 cases of S.typhi occur in the United States every year. Out of these mostcases (75%) are acquired while travelling internationally.Route of transmission is through feck-oral route. Infectionwith S. typhi is known to cause hepatitis with findings offocal hepatocellular necrosis and nonspecific inflammationon liver biopsy. Granulomas are extremely rare to find inhepatitis caused by S. typhi and have been reported only ina few cases till date.
Objective. To describe a rare case of typhoid fever withgranulomas in the liver.
2. Case Report
A 64-year-old Cambodian female presented with a two-weekhistory of abdominal pain, bloody diarrhea, nausea, poor oralintake, and mild fever. Her past medical history includedarterial hypertension, hypercholesterolemia, and type twodiabetes mellitus. There was no history of inflammatorybowel disease or colon cancer in her family. Her medications
included metoprolol, simvastatin, and metformin. She hadtravelled to Cambodia recently but had no exposure tosick contacts. Clinical exam presented an ill, pale appearingwoman with blood pressure 124/60mmHg, heart rate 115beats per minute, respiratory rate 16 per minute, and tem-perature 99.7∘C. She later developed a temperature max of39.4∘C (103∘F). She had right-upper quadrant and epigastrictenderness. No hepatosplenomegaly could be appreciatedand Murphy’s sign was negative. Laboratory studies showedwhite blood cell count of 7640/𝜇L, hemoglobin of 10.8 gm/dL,and hematocrit of 31.1% with serum potassium of 3.1mmol/Land serum calcium 7.9mg/dL. Liver profile showed totalbilirubin of 0.4mg/dL, total protein of 6.4 g/dL, albuminof 2.9 g/dL, AST of 218U/L, ALT of 131 U/L, and alkalinephosphatase of 209U/L. Blood, urine, and stool specimenswere collected and sent for culture. Stool studies werenegative for Shigella, Yersinia, Campylobacter, E. coli, andC. diff. Blood cultures were taken and all 4 bottles ofthe 2 sets grew S. typhi. Ultrasonography showed multiplehypoechoic liver masses of 14 to 16mm in size along withgallbladder sludge and otherwise normal biliary tree. Com-puted tomography of the abdomen showed a homogenousenhancement without any focal abnormality in the liverand wall thickening involving the terminal ileum withoutsurrounding inflammatory changes. It was reported that the
Hindawi Publishing CorporationCase Reports in PathologyVolume 2015, Article ID 745461, 3 pageshttp://dx.doi.org/10.1155/2015/745461
2 Case Reports in Pathology
Figure 1: H&E staining of biopsy specimen showing hepaticgranuloma in 20x magnification.
focal masses seen on ultrasound were thought to be atypicalhemangiomas. Magnetic resonance imaging showed dur-ing the arterial phase innumerable hyperenhancing massesthroughout the liver. A hepatobiliary iminodiacetic acid(HIDA) scan reported normal hepatocellular function, patentcystic duct, common bile duct, and sphincter of Oddi. Upperendoscopy showed diffuse stomach erythema with small 4× 4mm ulcer in the antrum and a superficial ulcer in theduodenal bulb along with a deep 1 × 1 cm ulcer in the apexof the bulb that were both cauterized. Colonoscopy showeddeep clean-based ulcerations in the cecum and ascendingcolon and scattered superficial ulcerations in the transversecolon. Gastric biopsy reported minimal superficial chronicgastritis without activity. Duodenal biopsy reported focalactive duodenitis. Colon biopsy reported focal active enteritisin the terminal ileum with patchy active colitis in the cecumascending and transverse colon. There was no evidenceof viral inclusions, dysplasia, or malignancy. A focal cryptrupture granuloma was seen in the transverse colon but notrue mucosal granulomas were seen. Liver biopsy (A, B)reported normal lobular architecture without fibrosis. Bileducts appeared normal in number and morphology andhepatic vasculature was unremarkable. Portal tracts showa mixed inflammatory infiltrate consisting of lymphocytes,histiocytes, and occasional scattered plasma cells and neu-trophils. Numerous suppurative granulomas were scatteredthroughout the hepatic lobules. The patient initially receivedIV Ciprofloxacin 400mg every 12 hours and IV Ceftriaxone2 gm every 24 hours for a total of 2 weeks each while shewas in the hospital and was eventually discharged on IVCeftriaxone 2 grams every 24 hours for a total of 6 weeks.
3. Discussion
The etiology of hepatic granulomas can be divided intoinfectious, noninfectious (immune), foreign body reactions,drugs, and neoplasia. Well-reported causes of hepatic granu-lomas in developed countries include sarcoidosis, tuberculo-sis, primary biliary cirrhosis, drug reactions, andmalignancy[1]. Our patient was suffering from typhoid enteritis buther clinical status was transformed to typhoid fever andhepatitis due to her immunocompromising risk factor of
Figure 2: H&E staining of biopsy specimen showing hepaticgranuloma in 40x magnification.
diabetes mellitus. This case highlights and further describesthe manifestations that can be associated with S. typhiand typhoid fever, specifically hepatic and GI involvement.Association between typhoid and systemic granulomas hasbeen reported in very few cases. To our knowledge, only 5cases of hepatic granulomas have been reported so far inthe English language literature. Pais [2] reported the first 2cases of typhoid hepatitis with hepatic granulomas in 1984.The third case of typhoid associated hepatic granulomas wasreported by Satti et al. [3] in 1990. They reviewed 59 cases ofpatients with hepatic granulomas out of which 1 case was dueto S. typhi. Mert et al. [4] reported 2 more cases of typhoidfever in 2004 with hepatic granulomas who also had splenicand bone marrow granulomas, respectively. The first caseshowednoncaseating granulomas and the secondone showeda single microgranuloma on liver biopsy. Typhoid cases withgranulomas in other sites like ileum, colon, ovaries, and breasttissue have also been reported.The present case would be thesixth case reported of a patient with typhoid having hepaticgranulomas (Figures 1 and 2). In all the previously reportedcases, the biopsy showed very few or one granuloma whichwas nonnecrotizing. Our case showed multiple suppurativenecrotizing granulomas. In our case, the AFB stain doneon Liver biopsy samples was negative. Sarcoidosis can alsopresent as hepatic granulomas but our patient did not haveany other manifestations suggestive of sarcoidosis. Crohn’sdisease rarely causes hepatic granulomas; however, in ourpatient, positive blood cultures for S. typhi and recent travelto an endemic region support the diagnosis of Salmonellainfection. Mainstay of diagnosis for S. typhi infection is withblood cultures. Histologic findings of typhoid fever includemacrophage aggregates found commonly in the intestines,mesenteric lymph nodes, spleen, liver, and bone marrow.Liver biopsy in these individuals shows cloudy swelling andballoon degenerationwith vacuolation of the hepatocytes andsteatosis.
Hepatic granulomas have been reported rarely, only in 5cases until now.The present case is the 6th case reported. It ishard to say if this is really a rare manifestation of S. typhi orif it is under reported. S. typhi is an infection seen mainly indeveloping countries whereas our patient was diagnosed in adeveloped country where extensive measures are undertakento characterize a patient’s disease.
Case Reports in Pathology 3
Conflict of Interests
The authors declare that there is no conflict of interestsregarding the publication of this paper.
References
[1] S. M. Lagana, R. K. Moreira, and J. H. Lefkowitch, “Hepaticgranulomas: pathogenesis and differential diagnosis,” Clinics inLiver Disease, vol. 14, no. 4, pp. 605–617, 2010.
[2] P. Pais, “A hepatitis like picture in typhoid fever,” BritishMedicalJournal, vol. 289, no. 6439, pp. 225–226, 1984.
[3] M. B. Satti, H. Al-Freihi, E. M. Ibrahim et al., “Hepaticgranuloma in Saudi Arabia: a clinicopathological study of 59cases,”The American Journal of Gastroenterology, vol. 85, no. 6,pp. 669–674, 1990.
[4] A. Mert, F. Tabak, R. Ozaras, R. Ozturk, H. Aki, and Y. Aktuglu,“Typhoid fever as a rare cause of hepatic, splenic, and bonemarrow granulomas,” Internal Medicine, vol. 43, no. 5, pp. 436–439, 2004.
