A 33-year-old woman presents with complaints of fever, headache, and rash for the past several days. She lives in Los Angeles and works as a physician’s assistant (PA) in an Internal Medicine office. She often volunteers with a city outreach clinic, providing basic on-site medical care for homeless people. She has no significant past medical history, no recent travel outside Los Angeles, takes no medications, does not smoke or drink alcohol, and has been in a monogamous relationship for the past several years. She recalls no recent insect or tick bites, and aside from occasionally seeing rats at various outreach sites, she has had no contact with animals.
History of Present Illness – about five days ago she recalls developing a fever, with mild chills, malaise, and a headache, which was more intense behind her eyes. Because of her many ill contacts related to her work, she thought she was developing a cold or flu, and aside from taking oral hydration and an occasional Tylenol dose, she ignored her symptoms. One to two days later, she developed worsening fevers, increased retro-orbital headache, and diffuse muscle aches. This was soon followed by a rash, first over her abdomen, then on her arms and legs.
Exam – ill-appearing; T – 38.8⁰C; P – mild tachycardia; BP, RR, and O2 sat – normal; skin – erythematous, maculopapular rash over the abdomen, and extremities; no other focal finding or abnormalities
Labs – normal CBC, basic chemistries and U/A; rapid flu test – negative
Discussion
Acute febrile illness has a broad differential diagnosis, which requires close attention to the patient’s underlying health status (e.g. immune status, prior illness history), work and travel history, exposures, and other epidemiologic factors. Given this patient’s presentation and the fact that she resides in a subtropical region, consideration should be given to arthropod-borne viruses (arboviruses). The list of possibilities is extensive and is made even longer given that she works with a transient population, many of which have unknown medical and travel histories. The Los Angeles County Department of Public Health’s statistics show West Nile virus has been the most common arbovirus infection in Los Angeles County for the past few years. Some other arboviruses present in southern California include St. Louis encephalitis, Zika virus, dengue fever, chikungunya, and western equine encephalitis.
This case is also consistent with many other infectious etiologies, including leptospirosis, coccidioidomycosis, measles, EBV infection – and despite her reported sexual history, consideration should also be given to acute HIV, disseminated gonococcal infection, and secondary syphilis. Given the lack of nuchal rigidity and normal neurologic exam, meningococcal meningitis is less likely. Non-infectious etiologies, such as autoimmune disease (e.g. lupus), and neoplastic conditions are also possibilities.
This clinical picture, in a patient working on city streets, in proximity to rats, places a specific rickettsial disease near or at the top of the differential diagnosis. While tick-borne rickettsia such as Rocky Mountain spotted fever should be ruled out in this case, rickettsia carried by rat fleas is more likely, especially as there have been reports of increasing numbers of such cases in Los Angeles over the past several years.
Murine Typhus
Murine typhus, also known as endemic typhus or flea-borne typhus, is caused by Rickettsia typhi, a gram-negative, obligate, intracellular bacillus. Fleas ingest R. typhi while biting an infected animal (host), typically a rat or opossum. The bacterium is spread when the flea bites another host. The flea defecates while feeding, and the host will unwittingly scratch the infected feces into a pruritic flea bite wound. Human infections are incidental, as the main vector cycles are either rat-flea-rat or opossum-cat flea-opossum.
The incubation period for murine typhus is one to two weeks. The most common symptoms are fever, headaches, and malaise. The “classic triad” of fever, headache, and rash only occurs in about one-third of cases. Severe complications include meningitis, focal neurologic changes, respiratory failure, acute renal failure, and septic shock. The majority of cases, however, are relatively mild, and the case fatality rate, even without antibiotic therapy, is low. Increased mortality is associated with older age and immune compromise.
Given the clinical overlap observed among rickettsial diseases, PCR and/or indirect immunofluorescence assays (IFA) can be done to discriminate between them (and other etiologies). Prior to the return of specific diagnostic lab assays, empiric antibiotic therapy includes doxycycline due to its effectiveness against rickettsial infections.
References
CDC, Flea-borne (murine typhus), (2019), Retrieved from https://www.cdc.gov/typhus/murine/ (Accessed 07 August 2019).
Chu, J.T., Hossain, R., et al. Case 22-2017 – A 21-year-old Woman with Fever, Headache, and Myalgias. N Engl J Med 2017; 377:268-78. doi: 10.1056/NEJMcpc1616399
Flea-Borne (Endemic) Typhus, (2019), Retrieved from www.publichealth.lacounty.gov/acd/VectorTyphus.htm (Accessed 07 August 2019).
Stern, R.M., Luskin, M.R., et al. A Headache of a Diagnosis. N Engl J Med 2018; 379:475-79. doi: 10.1056/NEJMcps1803584
West Nile Virus and Other Arbovirus Diseases: 2017 Los Angeles County Epidemiology Final Report May 1st, 2018, (2018), Retrieved from publichealth.lacounty.gov/acd/docs/Arbo2017.pdf (Accessed 07 August 2019).
West Nile Virus Testing, (2019), Retrieved from www.publichealth.lacounty.gov/lab/wnv.htm (Accessed 07 August 2019).