Case Presentation: A 27-year-old male presented to the hospital after developing jaundice with elevated transaminases on routine labs. Patient described preceding two-week febrile illness characterized by general malaise, chills, and myalgias. He received two courses of antibiotics without resolution of symptoms. To manage fever, he consumed 7 grams/day of acetaminophen consecutively for 5 days. His last dose was 3 days before presentation. During evaluation, he is asymptomatic with resolution of febrile illness. Other than mild tachycardia, vitals were normal. Physical exam showed a young obese man in no acute distress with scleral icterus, but no petechiae, abdominal tenderness, hepatomegaly, palpable splenomegaly, nuchal rigidity, or asterixis. Initial BMP and CBC were normal, AST/ALT was 284 and 301 U/L, respectively, and total bilirubin was 2.9 mg/dL. APAP level was < 2 mcg/mL and INR was 1.1. Abdominal CT showed splenomegaly with no biliary disease. He was started on the N-acetylcysteine protocol over the next 21 hours given his recent APAP use. Liver enzymes remained elevated. Initial Infectious work up was negative including respiratory viral panel, hepatitis, HIV, and EBV serologies. Given preceding febrile illness with myalgias, murine typhus was suspected and serologies were sent. The patient had no reported exposure to dogs with fleas. The patient was discharged given clinical stability and Rickettsia typhi serologies resulted positive with an IgM titer > 1:1024. Repeat liver function panel several weeks later were normal.
Discussion: This case illustrates the challenge in diagnosing murine typhus. Rickettsia typhi is an intracellular gram-negative organism that is spread by fleas (Xenopsylla cheopis) to mammals including rats, dogs, opossums, and humans (1). The disease is found worldwide but most cases in the United States occur in Texas and California (2). Clinical symptoms are non-specific; fever, malaise, headache, and body aches occur in 60-70% of cases (1). Rash, usually maculopapular, occurs in 48% of patients (1). Although uncommon, hepatic involvement with jaundice is present in up to 12% of cases (3). The diagnosis is confirmed with a 4-fold rise in antibody titers 2-4 weeks after initial diagnosis; however, admission IgM levels titers greater than 1:800 have more than 90% specificity for the diagnosis of acute murine typhus (4). Treatment is with 7-day course of doxycycline which shortens duration of illness and severity. Treatment is generally indicated when acute infection is suspected prior to awaiting diagnostic results (1). However, spontaneous recovery typically occurs over two weeks in untreated patients as it did for our patient.
Conclusions: Early recognition of Rickettsia typhi infection can prevent delayed diagnosis and unnecessary utilization of healthcare resources. The patient’s preceding febrile illness resolved and the lack of infectious symptoms on presentation resulted in diagnostic anchoring on the history of APAP overuse. However, the previous 2-week febrile illness that did not improve after two courses of antibiotics and lack of response to NAC raised suspicion for an atypical infection. Had treatment been initiated earlier in clinical course, patient may have avoided hospitalization altogether.