Authors: Jon Vivolo, DO (@PedalSkiClimbDr, Emergency Medicine Resident Physician, University of Kentucky) and Christopher I. Doty, MD (@PoppasPearls, University of Kentucky Emergency Medicine Program Director) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit, EM Chief Resident at SAUSHEC, USAF)

CASE

A 24 year-old male with no significant past medial history presents to the ED with a fever, diffuse muscle aches, headache, and vomiting for the past 2 days. You think his symptoms sound a lot like the flu, however it is summertime. History is unremarkable for sick contacts, family members with similar symptoms, or recent travel outside of the country. You do note he was recently on a backpacking trip in North Carolina. He is afebrile in the ED, with normal VS. Your physical exam is consistent with minimal to moderate dehydration and otherwise unremarkable. After Zofran and 1 liter of IV fluids, he feels better and is tolerating oral intake. He is discharged with instructions to alternate antipyretics and increase his clear fluid intake.

Five days later your fellow resident says “Do you remember that guy you saw in the ED last week with typical flu-like symptoms? He came back with a crazy rash all over his body.”

INTRO

– The constellation of fever, myalgias, headaches, nausea, vomiting along with a petechial rash involving the palms and soles are classic for Rocky Mountain Spotted Fever (RMSF).

– This is an illness with relatively low incidence; however, it has a high morbidity/mortality if it remains undiagnosed.

– RMSF is the leading killer among all of the tick-born illnesses.

EPIDEMIOLOGY

– RMSF (caused by R. rickettsii) is transmitted by the American Dog Tick, Brown Dog Tick, and Rocky Mountain Wood Rick.

– For disease transmission to occur, the tick must feed for a minimum of 4 hours.

– In the United States the reported annual incidence is over 6 cases per million; however, this number appears to be increasing and may be falsely low.

– Over 60% of cases have occurred in North Carolina, Oklahoma, Arkansas, Tennessee, and Missouri, but cases have been reported throughout the entire United States.

– Peak incidence occurs in the summer months, primarily June and July.

– In one study, 95 out of 96 people with confirmed RMSF reported being in a wooded area 14 days before symptom onset.3

– Average incubation from tick bite to symptom onset is 7 days.

ETIOLOGY/PATHOPHYSIOLOGY

– R. rickettsii is an intracellular bacteria.

– Once inoculation has occurred, bacteria spread into the vascular system through lymph channels causing a vasculitis.

– Endothelial cell damage leads to systemic inflammation, edema, hypovolemia, hypercoagulability, and ultimately end-organ damage.

ED EVALUATION

– Consider RMSF and other tick born diseases in patients presenting with viral symptoms during warmer months, even in the absence of a rash (up to 20% of confirmed cases).

– The most common symptoms in order are: fever (94-100%), headache (60-80%), myalgias, and abdominal pain.2

– A thorough history regarding possible exposure or known tick bite is important; however, in a review by Kirk et al., only slightly over half confirmed cases reported a recent bite.5

– If a rash is present, the exam findings show erythematous macules starting on the wrists and ankles. In the later stages the rash will spread proximally to palms, soles, trunk, and face. Around days 6-9 the rash will typically become petechial.1

– In severe cases there have been reported myocardial involvement,9 pulmonary edema,4 and acute renal failure.8

LABS

– CBC with differential: RMSF classically presents with a low to normal WBC with predominantly immature cells. Thrombocytopenia often occurs, typically in the range of 21,000-150,000.10

– CMP: Hyponatremia has been observed in about 20% of cases as well as elevated LFTs in up to 75%.6,7 BUN and creatinine may also be elevated.

– CSF: The most common findings are an unremarkable fluid analysis or that of aseptic meningitis. This may be reflected with elevated CSF WBC count (typically < 100 cells/microliter).5 Gram stain will be non-diagnostic for Rickettsia.11

– RMSF Serological Test: Confirmation of diagnosis is made with this (IgG and IgM antibodies); however, it typically takes several days for final results. Latex agglutination can be performed in 1-2 hours at certain labs, but its sensitivity is only 50-70%.12 Serological testing is not recommended for EM physicians secondary to poor test sensitivities in the first 2 weeks of symptom onset, slow lab result turnaround time, and difficulty distinguishing between current or previous infections.13

TREATMENT

– Confirming the diagnosis is difficult in RMSF given its common constellation of symptoms and lack of confirmatory testing for the ED practitioner. Therefore, it’s recommended to initiate antibiotics in those individuals with increased pre-test probability of the disease (24 year-old with a headache, fever, myalgias, who was recently backpacking in the middle of April).

– The drug of choice for all patients including children is Doxycycline with a recommended dose of 100 mg q 12 hours for adults and 2-4 mg/kg/day divided BID for children with a duration between 7-10 days.

– Chloramphenicol was a popular treatment modality in the past; however, it has fallen out of favor secondary to its side effect profile and efficacy of doxycyline. Doxycycline is contraindicated during first and second trimester of pregnancy; Chloramphenicol remains the drug of choice.

DISPOSITION

– Poor prognosis and ICU consideration is associated with the following: >40 years old, symptom onset > 5 days, altered mental status, AST > 500, Cr > 2.0, Na < 130, Billirubin > 3.0.8

– Decision for admission should be largely based on clinical gestalt. Strong consideration should be made for likely cases of RMSF via signs & symptoms. Patients with probable RMSF and abnormal vital signs, inability to tolerate oral intake, etc. should be admitted.

– Those who are discharged on oral Doxycycline should have close follow-up within 2-3 days. If possible the first dose of antibiotics should be administered in the ED.

PEARLS

– Consider tick-born disease, particularly RMSF in patients who present with symptoms consistent with viral syndrome in warmer months.

– Don’t let the absence of a classic rash or geographical location influence your consideration of RMSF.

– If RMSF is probable based on signs/symptoms, initiate Doxycycline treatment and arrange for close follow-up if considering discharge.

– Serology testing is often not helpful or recommended for the ED practitioner.

References / Further Reading

Kostman JR. Laboratory Diagnosis of Rickettsial Diseases. Clinical Dermatology 1996;14:301-306. Dalton MJ, Clarke MJ, Holman RC, et al. National Surveillance for Rocky Mountain Spotted Fever, 1981- 1991: Epidemiologic Summary and Evaluation of Risk Factors for Fatal Outcome. American Journal of Tropical Medicine Hygiene 1995;52:405-413. Wilfert CM, MacCormack JN, Kleeman K. Epidemiology of Rocky Mountain Spotted Fever as Determined by Active Surveillance. Journal of Infection Disease 1984;150:469-479. Roggli VL, Keener S, Bradford WD et al. Pulmonary Pathology of Rocky Mountain Spotted Fever in Children. Pediatric Pathology 1985;4:47-57. Kirk JL, Fine DP, Sexton DJ, et al. Rocky Mountain Spotted Fever A Clinical Review Based on 48 Confirmed Cases, 1943-1986. Medicine 1990;69:35-45. Razzaq S, Schurtze GE. Rocky Mountain Spotted Fever: A Physicians Challenge. Pediatric Review 2005;26:125- 129. Centers for Disease Control. Lyme Disease Symptoms. 13 October 2005. http://www.cdc.gov/ncidod/dvbid/lyme/ld_humandisease_ symptoms.htm Conlon PJ, Procop GW, Fowler V, et al. Predictors of Prognosis and Risk of Acute Renal Failure in Patients with Rocky Mountain Spotted Fever. American Journal of Medicine 1996;101:621-626. Bradford WD, Hackel DB. Myocardial Involvement in Rocky Mountain Spotted Fever. Archives Pathology Laboratory Medicine. 1978;102:357-9. Hall GW, Schwartz RP. White Blood Cell Count and differential in Rocky Mountain Spotted Fever. North Carolina Medical Journal. 1979;40:212-214. Abedon ST. Eubacterial Classification. 14 May 1998. http://www.mansfield.ohiostate.edu/~sabedon/biol3018.htm Greene CE, Marks MA, Lappin MR. Comparison of Latex Agglutination, Indirect Immunofluorescent Antibody, Enzyme Immunoassay Methods for Serodiagnosis of Rocky Mountain Spotted Fever in Dogs. American Journal of Veterinary Medicine. 1993;54:20-28. Hechemy KA. Correspondence. American Journal of Tropical Medicine and Hygiene 1987;37:205-207. http://www.ncbi.nlm.nih.gov/pubmed/21293226 http://www.cdc.gov/rmsf/index.html

Photos from: http://www.wildmedcenter.com/blog/american-dog-tick-brown-dog-tick-rocky-mountain-wood-tick-borne-diseases