Typhoid Fever goes rogue: A rare & unusual case of concurrent typhoid hepatitis and splenic abscess in an immunocompetent adult

Abstract

Summary

This case report describes a rare instance of simultaneous typhoid hepatitis and splenic abscess in a 27-year-old immunocompetent male from India. The patient presented with high fever, jaundice, abdominal pain, and vomiting, and was mimicking acute viral hepatitis or disseminated tuberculosis finally diagnosed with Salmonella typhi infection following extensive diagnostic & therapeutic evaluations. Despite the seriousness of hepatic and splenic involvement, especially in the absence of underlying immunodeficiency, the patient responded well to appropriate antibiotic therapy. The report highlights the diagnostic challenges and clinical significance of atypical typhoid complications, emphasizing the importance of timely recognition and treatment to improve outcomes.

Introduction

In India, infection with Salmonella typhi, causing typhoid fever, is quite common. This may sometimes mimic other infectious diseases, complicating the diagnosis and management of these patients. Typhoid fever is a multisystem illness transmitted by the Feco-oral route, primarily through contaminated water and undercooked food, caused by Salmonella typhi and Salmonella paratyphi. It carries an important health concern, especially in tropical and developing countries. [1], [2] The gastrointestinal complications related to Salmonella typhi infection are Ileal perforation/ulceration, and may lead to obstruction and have been commonly reported. [1] Apart from that, involvement of the liver and spleen in typhoid fever is a serious concern. Here we are representing a case that presented with typhoid hepatitis and typhoid splenic abscess.

Case details

A 27-year-old male from Uttarakhand, India, presented with high-grade fever, chills, and rigor for 10 days. The fever only resolved with antipyretics. He also had yellowish discoloration of his eyes and urine, not linked to obstructive or cholestatic symptoms. Additionally, he experienced non-radiating upper abdominal pain and recurrent, non-bilious, non-projectile vomiting for 7 days. On arrival, he was conscious oriented, febrile (101 °F), and had a heart rate of 104/min with blood pressure at 108/70 mmHg. He appeared sick, cachectic, and icteric. The abdominal exam showed a scaphoid abdomen without visible lumps. Hepatomegaly with a liver span of 18 cm and right subcostal tenderness was found. Initial labs showed hemoglobin 9.8 gm/dL (MCV 90.5 fL), total leukocyte count 5400 × 103/uL (N42, L45, M12), and platelet count 155 × 103/uL. Liver function showed direct hyperbilirubinemia: total bilirubin 12.2 mg/dL and direct bilirubin 10.8 mg/dl. AST and ALT were 199 and 148 U/L; ALP and GGT were 268 and 125 U/L; total protein and albumin were 6.3 and 2.7 gm/dL; INR was 1.4. Kidney function was normal (creatinine 0.6 mg/dL, urea 16 mg/dL). Tests for acute viral hepatitis (HAV/HEV/HBV/HCV) and hepatotropic viruses (IgM for HSV/CMV/EBV) were negative. Blood culture was drawn before antibiotics, and later grew Salmonella typhi. Ultrasound showed an enlarged liver (18.2 cm) with a normal outline. Hepatic veins and portal vein were normal. The gall bladder was partially distended and smooth, with circumferential wall thickening and mild pericholecystic edema. The intra- and extrahepatic biliary system was normal. The spleen was enlarged (13.7 cm) with a well-defined, heterogeneously hypoechoic lesion at the inferior pole (1.9 × 2.1 cm) and a smaller lesion (∼9 × 8 mm) in the splenic parenchyma. Contrast CT confirmed an enlarged liver (∼19.7 cm), a prominent portal vein (13.2 mm), and a partially distended gall bladder with mild pericholecystic edema. Multiple peripherally placed hypodense, non-enhancing areas were in the spleen, the largest measuring 2.7 × 1.7 cm. Circumferential mural thickening with enhancement involved the ileocecal junction, terminal ileum, and ascending colon, with maximum thickness of ∼6.5 mm. Multiple enlarged, homogeneously enhancing right iliac lymph nodes were present, the largest measuring 2.7 × 1.4 cm. Mild peritoneal thickening was also observed, suggesting a likely tubercular etiology.

Fig. 1.

Coronal section of dual contrast CT scan of the abdomen showing showing enlarged liver, splenic abscess and mural thickening of ascending colon, terminal ileum ileoceacal thickening.

Fig. 2.

Coronal section of CT abdomen showing showing splenic abscess

Fig. 3.

Coronal section of CT abdomen showing showing multiple splenic abscess

Fig. 4.

Contrast CT scan of the abdomen showing showing multiple splenic abscess

Fig. 5.

Contrast CT scan of the abdomen showing showing multiple splenic abscess

Guided pus aspiration was done. A GeneXpert test for Mycobacterium tuberculosis was negative. Culture and sensitivity showed Salmonella typhi, sensitive to ceftriaxone, chloramphenicol, and azithromycin. The patient received ceftriaxone and azithromycin according to clinical guidelines. His condition improved gradually. At discharge, his liver function tests were better (Total bilirubin/Direct bilirubin: 2.8/2.2 mg/dL; AST/ALT: 73/71 U/L; ALP/GGT: 285/80 U/L; INR: 1.35).

Discussion

Hepatic involvement in typhoid fever

Hepatic involvement in typhoid fever has been recognized since it was first reported by William Osler in 1899. [3] Clinical manifestations commonly include hepatomegaly and mild elevation of hepatic transaminases, which are observed in approximately 21–60 % of typhoid infections. [4], [5] Although hepatitis and cholestasis [6] are rare consequences of Salmonella infection, [6], [7] severe hepatic dysfunction that mimics acute viral hepatitis is exceedingly uncommon. [8] There have been occasional reports of typhoid fever leading to acute liver failure. [2]

Prevalence and contributing factors of salmonella typhi-induced acute hepatitis

Acute hepatitis resulting from infection with Salmonella typhi is observed with notable frequency in tropical regions. These areas are often characterized by the endemic presence of malaria and a heightened incidence of viral hepatitis. Within these settings, several factors contribute to the development of Salmonella hepatitis. The virulence of the Salmonella typhi pathogen plays a significant role, as more aggressive strains are associated with increased risk and severity of hepatic involvement. Furthermore, delays in the initiation of appropriate treatment can exacerbate the progression of the disease, underscoring the importance of prompt medical intervention. The overall health status of individuals affected by the infection also influences the likelihood and severity of hepatitis, with compromised general health potentially predisposing patients to more severe manifestations of typhoid fever.

Profound hyperbilirubinemia in cases of enteric hepatitis is rare and typically arises in the presence of co-infection with hepatitis A virus (HAV) or hepatitis E virus (HEV), which may subsequently progress to fulminant hepatitis. [9] While Salmonella typhi is an extremely rare cause of acute liver failure, cases have been documented in the United States. [2]

The retrospective studies by El-Newihi et al. showed the comparative analysis of clinical & biochemical parameters, along with outcome comparisons of acute hepatitis caused by Salmonella & viruses, revealed both were frequently indistinguishable. [10]

Histopathological and molecular mechanisms of hepatic injury in typhoid fever

Histopathological examination of the liver in cases of typhoid fever reveals several characteristic findings. Notably, typhoid nodules are present, accompanied by ballooning degeneration of hepatocytes and focal infiltration by mononuclear cells. [4] These features reflect the underlying pathological processes triggered by infection with Salmonella typhi. Additionally, cultures obtained from liver biopsy specimens, as well as immunohistochemical analysis of liver parenchyma, have demonstrated the presence of Salmonella typhi bacilli within hepatic tissue. [11]

At the molecular level, hepatitis is induced by typhoid toxin, which leads to DNA damage in hepatocytes. This damage activates both apoptotic and necrotic pathways, contributing to liver cell injury and death. Furthermore, phagocyte proliferation, stemming from the host's immune response, results in the formation of typhoid nodules. [12] This proliferation serves as an additional mechanism of hepatocyte injury. The typhoid nodules themselves are indicative of reticuloendothelial cell hyperplasia. This hyperplasia has the potential to obstruct the hepatic microvasculature, thereby contributing to hepatocyte necrosis. [12]

Other intra-abdominal complications, such as hepatic and splenic abscesses, are other rare complications reported in the past.

Splenic abscess in typhoid fever

Though Salmonella typhi causing splenic abscess is a rare clinical presentation, an earlier study suggested an incidence between 0.29 % and 2 %, [13] However, the incidence of splenic abscesses in typhoid fever decreased in the pre-antibiotic era to less than 1 % post introduction of effective antibiotics. [14] It is generally caused by septic foci metastasis, which carries a mortality rate of 40 % if untreated. [14] In typhoid fever, a splenic abscess forms due to septic foci metastasis and consequently an In typhoid fever, the development of a splenic abscess arises from the spread of septic foci, leading to an overwhelming immunogenic response within the spleen. [15] This process results in the formation of localized, contained areas of infection within the organ. Splenic abscess is considered a potentially life-threatening complication and is more likely to occur in the later stages of a delayed or particularly severe infection. [16] Several factors contribute to the risk of developing a splenic abscess in the setting of typhoid fever, including splenic infarction, an immunocompromised state, trauma, and delays in initiating appropriate treatment for the infection. [17]

Mechanism and diagnosis of splenic abscess in typhoid fever

Pathogenesis of splenic abscess

The development of a splenic abscess in typhoid fever involves a sequence of distinct steps. Initially, Salmonella typhi is ingested and disseminates via the bloodstream. Infected macrophages then transport the bacteria to the spleen, seeding the reticuloendothelial tissues. Abscess formation occurs when the host’s immune response is compromised and the bacterial load becomes overwhelming, which leads to tissue necrosis. Subsequently, a fibrous capsule forms around the necrotic tissue and bacteria, encapsulating the abscess within the spleen. [18]

Ultrasonography (USG) and computed tomography (CT) are the most effective imaging techniques for diagnosing splenic abscesses. Of these, CT is considered more specific than USG, providing precise details regarding the location and characteristics of the abscess. [19]

Management of typhoid splenic abscess

The optimal approach to treating typhoid splenic abscess continues to be a topic of discussion, primarily because of the absence of randomized controlled trials. Current management strategies are based on evidence from small case series and individual case reports.

Conservative management

Recent publications have shifted away from routinely performing splenectomy, instead recommending conservative, spleen-preserving therapies when the clinical scenario allows. In stable patients presenting with solitary, unilocular abscesses, percutaneous drainage is advised. This less invasive method, combined with prolonged antibiotic therapy and image guidance (either ultrasound or CT), has demonstrated a success rate as high as 68 %. [19]

Surgical intervention

Despite the trend toward organ preservation, surgical intervention in the form of splenectomy remains necessary in certain complicated situations. These include cases where there is abscess rupture, the presence of multiple or multiloculated abscesses, or when conservative treatment fails to resolve the infection. A review by Ganesan et al. noted that splenectomy was performed in 7 out of 33 cases between 2001 and 2024, underscoring its continued relevance for select clinical presentations. [20]

The presented case was peculiar, involving both liver and spleen, and presented with viral mimicking acute hepatitis and splenic abscess. The differential could be disseminated tuberculosis workup for tuberculosis was done, and was negative for the same. We treated that patient with the ceftriaxone and azithromycin combination as per guidelines for 5 days after getting culture-positive blood & splenic abscess aspirate.

This case was notable for the simultaneous involvement of both the liver and spleen. The patient exhibited symptoms consistent with acute hepatitis that closely resembled those of a viral infection. Additionally, a splenic abscess was identified. Given the unusual presentation, disseminated tuberculosis was considered as a possible differential diagnosis. A comprehensive workup for tuberculosis was conducted; however, the results were negative, effectively ruling out tuberculosis as a cause. Upon confirmation of Salmonella typhi via culture from both blood samples and aspirate from the splenic abscess, the patient was treated according to established guidelines. A combination therapy of ceftriaxone and azithromycin was administered for five days, targeting the identified pathogen.

Ethical approval

Not required, as the article is a case report.

sources of funding

No funding from any sources.

Author contribution

Dr Chandan Kumar Baranwal reports a relationship with Graphic Era Institute of Medical Sciences that includes: employment. Manish Thakur reports a relationship with Graphic Era Institute of Medical Sciences that includes: employment. Kanika soni reports a relationship with Graphic Era Institute of Medical Sciences that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Consent

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request”.

CRediT authorship contribution statement

thakur manish: Data curation. Chandan Kumar Baranwal: Writing – original draft, Conceptualization. soni kanika: Writing – review & editing.

Declaration of Competing Interest

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr Chandan Kumar Baranwal reports a relationship with Graphic Era Institute of Medical Sciences that includes: employment. Manish Thakur reports a relationship with Graphic Era Institute of Medical Sciences that includes: employment. Kanika soni reports a relationship with Graphic Era Institute of Medical Sciences that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.