A 22-year-old Hispanic man presents to the emergency department with headache, sore throat, and a non-productive cough. He explains that light sensitivity seems to be triggering his headaches, which, along with other symptoms and general malaise, began occurring about 2-weeks ago.
The patient’s medical history is unremarkable, aside from the unusual and variable constellation of symptoms that he has experienced over the past several weeks. These include intermittent fevers, fatigue, nausea, vomiting, occasional episodes of diarrhea, and nosebleeds. He explains that he decided to come to emergency when he developed a rash on his thighs about three to five days previously, which spread to involve his entire body.
Until this episode, he says he has been in good health – he doesn’t take any medications and has no allergies. The patient’s medical history is benign, with no dyspnea, chest pain, bloody stools, or neck stiffness.
He does report his suspicion that his home may be infested with fleas introduced by his pets, a cat and two dogs. He also claims to have seen rats in his home, although this is not confirmed. Further discussion reveals that he had just begun a new job as a taxidermist three days before his presentation at emergency.
Presenting vital signs
Assessment in the emergency department finds the patient is afebrile, with a blood pressure of 97/47 mm Hg, pulse rate of 136 beats per minute, and respiratory rate of 22 breaths per minute. Physical examination notes a petechial rash involving his trunk, and upper and lower extremities (Figure), but no nuchal rigidity.
Laboratory test findings
Diagnostic assay results were as follows (numbers in parentheses reflect the normal range):
- Sodium 126 mmol/L (135–145 mmol/L)
- Blood urea nitrogen 111 mg/dL (7–23 mg/dL)
- Creatinine 3.14 mg/dL (0.60–1.25 mg/dL)
- Aspartate transaminase 421 U/L (13–40 U/L)
- Alanine aminotransferase 135 U/L (9–51 U/L)
- Alkaline phosphatase 158 U/L (34–122 U/L)
- D-dimer 17.55 μg/mL (<0.41 μg/mL)
- Fibrinogen 94 mg/dL (214–470 mg/dL)
- Lactic acid 2.34 mmol/L (0.50–2.20 mmol/L)
- Platelets 35,000/mm3 (150,000–400,000/mm3)
- White blood cell count 13,830/mm3 (4,300–10,800/mm3)
Diagnosis and admission to hospital
The patient is admitted to the intensive care unit with a diagnosis of severe sepsis with disseminated intravascular coagulation (DIC). Treatment with vancomycin and ceftriaxone are initiated to address possible meningococcemia. Due to his thrombocytopenia, clinicians are unable to perform a lumbar puncture.
The patient is stabilized and assessed by an infectious disease specialist the following day, who proposes differential diagnosis of a possible viral infection, ehrlichiosis, or murine typhus.
Back to the lab
Further laboratory workup is ordered, including serological tests for Epstein-Barr virus viral capsid antibody, IgM, and IgG antibodies; parvovirus serology, including IgM and IgG antibodies; and a molecular assay for Ehrlichia DNA. Results of these tests are all negative.
Rickettsia typhi titers for IgM and IgG – requested a day after the patient was admitted to hospital – are positive.
Treatment and Outcome
To treat Rickettsia typhi infection, vancomycin is changed to doxycycline. Following consultation with hematology service regarding management of the patient’s coagulopathy, the patient is treated with cryoprecipitate to maintain his fibrinogen levels above 150 mg/dL.
The previous conditional diagnosis of DIC is excluded at this stage, based on the absence of red blood cell fragments (schistocytes) on the peripheral blood smear. Following treatment with doxycycline, the patient’s fever resolves. On day 3 of hospitalization, the patient is found to be hemodynamically stable enough to be transferred out of the intensive care unit.
On his fifth day in the hospital, followup serology shows residual high Rickettsia typhi serum antibody titers, and he remains negative for other infections. After five days of monotherapy with oral doxycycline 100 mg twice per day, his symptoms have improved sufficiently to allow the patient to be discharged.
Discussion
This case report describes a patient presenting with the classic triad of symptoms – fever, headache, and rash – that characterizes about one-third of murine typhus infections.1
This usually rare condition has seen a resurgence that began in Galveston, Texas in 2012. Most cases have been reported in the coastlines states of California, Hawaii, and southeast Texas, and have occurred primarily during warmer months.
Murine typhus is caused by infection with Rickettsia typhi – its re-emergence is thought to be due to increasing transmission from cat and opossum fleas. Of 12 opossums studied recently, eight had Rickettsia typhi antibodies, and all 12 opossums had fleas.2
As physicians reporting this case note, murine typhus can present with a range of non-specific symptoms of varying severity; these include malaise, chills, myalgia, anorexia, arthralgia, nausea, and vomiting. Thus, awareness of this rare infection is important to prevent it from being misdiagnosed as a viral infection.
In one in three patients with murine typhus, clinical examination of the skin will detect a rash is macular or maculopapular. The rash typically spreads outward from the trunk to involve the rest of the body, except for the palms and soles.
Laboratory abnormalities can include elevated liver enzymes, elevated lactate dehydrogenase, hypoalbuminemia, an increased erythrocyte sedimentation rate, thrombocytopenia, increased alkaline phosphatase, and hyponatremia.
Symptoms differ in children
In children, murine typhus is more likely to be marked by abdominal pain, diarrhea, and sore throat, with a higher frequency of anemia, a lower frequency of hypoalbuminemia, hematuria, and proteinuria and a much lower rate of complications.
Suspected cases of murine typhus should be checked for serum IgG antibodies to Rickettsia typhi with an indirect fluorescent antibody test. Notably, antibodies are often not present in the first week of illness. A fourfold antibody titer rise in convalescent serum samples confirms diagnosis.3,4
Risk factors
Murine typhus should be considered in patients with the symptoms described here, particularly if they have been around animals, exposed to fleas, spent time in a coastal state, or they live in an area where the disease is prevalent.5 Patients who may be at risk can be educated with this brochure.
Additionally, a retrospective analysis of 32 cases of murine typhus diagnosed from 2008 to 2010 found that all of the infections had occurred in travelers, returning primarily from Africa and Southeast Asia.6
Murine typhus can be a self-limiting illness – untreated, the fever may last from 12–21 days. Treatment with tetracyclines can reduce the duration of the disease significantly, with doxycycline reported to resolve the fever in 1.5–4 days. Similarly, treatment with the antibiotic chloramphenicol – used during pregnancy – can reduce the duration of fever to 2.5–4 days.
Conclusion
Given its increasing prevalence in coastal cities, murine typhus should be included in differential diagnosis in patients with non-specific findings, including in patients who present when critically ill, case authors noted. Awareness of this infection can assist in early diagnosis and treatment, thus hastening patient recovery and reducing morbidity.
References
1. Tsioutis C et al. Clinical and laboratory characteristics, epidemiology, and outcomes of murine typhus: A systematic review. Acta Trop, 2017; 166: 16–24
2. Blanton LS et al. Opossums and cat fleas: New insights in the ecology of murine typhus in Galveston, Texas. Am J Trop Med Hyg, 2016; 95(2): 457–61
3. Blanton LS et al. Re-emergence of murine typhus in Galveston, Texas, USA, 2013. Emerg Infec Dis, 2015; 21(3): 484–86
4. Arup Laboratories. Rickettsia typhi (typhus fever) Antibodies, IgG & IgM by IFA. Available from: URL: http://ltd.aruplab.com/Tests/Pub/0050384
5. Centers for Disease Control and Prevention (CDC): Outbreak of Rickettsia typhi infection – Austin, Texas, 2008. Morb Mortal Wkly Rep, 2009; 58: 1267
6. Walter G et al. Murine Typhus in Returned Travelers: A Report of Thirty-Two Cases. Am J Trop Med Hyg 2012;86(6):1049-1053
No disclosures reported.
Source: MedicalNewsToday.com
