Authors
Trahern W. ("TW") Jones, MD, Assistant Professor, Pediatric Infectious Diseases, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City
Anika S. D'Souza, BS, University of Utah School of Biological Sciences
Peer Reviewer
Catherine A. Marco, MD, FACEP, Professor, Department of Emergency Medicine, Penn State Health — Milton S. Hershey Medical Center, Penn State College of Medicine
Executive Summary
- Rickettsia rickettsii is an obligate intracellular gram-negative bacillus included in the broader category of spotted fever group rickettsioses (SFR), which also includes Rickettsia parkeri rickettsiosis, Pacific Coast tick fever, and rickettsialpox. It is transmitted via hard-bodied tick bites and has been documented in the American dog tick, the Rocky Mountain wood tick, and, most recently, the brown dog tick.
- It should be noted that discrete recollection of a tick bite is not uniformly encountered or noted. The absence of a known tick bite does not eliminate the possibility of Rocky Mountain spotted fever (RMSF) in suspected cases.
- Despite the name, RMSF is not limited to the western mountain regions of North America, and it has been reported in every U.S. state since 2019.
- Following inoculation via tick bite, the typical incubation period may range from two to 14 days until onset of symptoms. Patients most typically experience the onset of a sudden fever greater than 38.9°C (102°F), along with severe headache and malaise. Additionally, abdominal pain, vomiting, nausea, myalgia, and periorbital and hand edema may be reported within the first three days.
- Although the rash and its palmar and plantar involvement often are reported as defining features of RMSF, up to 12% of patients do not develop a rash at all, and the overall involvement of the palms and soles may vary from 36% to 82%.
- If inadequately treated, the symptoms and clinical manifestations of RMSF will continue to progress and lead to subsequent additional organ system involvement and failure. Patients will experience such adverse outcomes as skin necrosis, gangrene (subsequent amputation of the extremities), hepatomegaly, acute renal failure, respiratory compromise, cerebral edema, coma, and death.
- Fundamentally, the diagnosis of RMSF must be made clinically, with subsequent confirmatory testing after treatment is initiated. Patient survival depends on early recognition of the signs and symptoms of RMSF as well as immediate empiric therapy with doxycycline.
- It should be emphasized that antibody titers obtained in the acute period (in the first one to two weeks) often are negative. Confirmation of an RMSF diagnosis is established by the observation of a fourfold or greater rise in antigen-specific immunoglobulin G antibody titers between acute and convalescent sera.
- Patients may have a normal white blood cell count, mild anemia (in 5% to 30% of cases), but, most characteristically, thrombocytopenia may be prominent, even in patients with early disease or milder symptoms. Hyponatremia and hypoalbuminemia are also highly characteristic of the disease process.
- Doxycycline is the drug of choice in all age groups when treating RMSF, including children younger than 8 years of age.
Rocky Mountain spotted fever is an infectious disease that may be rapidly fatal if not rapidly recognized based on clinical findings and early institution of appropriate antibiotic therapy. The epidemiologic shift of this disease makes it important for all healthcare providers to be familiar with the current status, clinical presentation, and therapy for Rocky Mountain spotted fever.
— Ann M. Dietrich, MD, FAAP, FACEP, Editor
Case
A previously healthy 15-year-old girl presents to your facility in early autumn in Southern Arizona with a fever, headache, and rash. Her symptoms began two to three days ago, starting with a fever, and she notes that a headache developed soon after. Her mother noticed a rash today, and it has spread from her wrists and ankles to her trunk, palms, and soles. She describes the rash as innumerable spots of scarlet-red all over her extremities, with some spreading onto her abdomen, chest, and back. She denies any neck stiffness, altered mental status, seizures, or other central nervous system symptoms. Her mother notes that her daughter also has experienced nausea and has vomited twice today.
The girl is fully immunized, and she denies any recent sick contacts and any recent travel history outside of the region. However, she does live on a Native American reservation, and there are multiple peridomestic dogs around her home where she lives. She denies any sexual activity or intravenous drug use, and there is no significant family history for autoimmune disease.
On evaluation, she is tachycardic, with a heart rate of 112 beats per minute, but she has a normal blood pressure of 112/70 mmHg. She is tachypneic, with a respiratory rate of 34 breaths per minute. Her temperature is elevated to 39.3°C. Her oxygen saturation is normal at 98%. She is uncomfortable but nontoxic. Her physical exam is most noteworthy for diffuse, blanching, erythematous macules along all four extremities, including the palms and soles, with some involvement of the trunk but sparing the face.
Introduction
Rocky Mountain spotted fever (Rickettsia rickettsii) (RMSF) originally was described in outbreaks in Idaho and Montana in the early part of the 20th century (hence the source of its name).1 However, many providers know it better for its current endemicity in the southeastern United States and the Ozark range. In these regions, it classically is spread through the bites of the American dog tick (Dermacentor variabilis) and Rocky Mountain wood tick (Dermacentor andersoni).
Interestingly, in the past 20 years, R. rickettsii has illustrated the fundamental dynamicity of ecosystems and infectious diseases by situating itself in an entirely novel vector, the brown dog tick (Rhipicephalus sanguineus), and it has since found its way into the regions of southern Arizona and Northern Mexico.
Such radical shifts in epidemiology are an object lesson for infectious diseases experts and public health specialists, as well as a challenge to emergency and primary care providers who may encounter such cases in their facilities.
The diagnosis of RMSF can be confirmed through serological studies, but at the time of presentation, the diagnosis almost always must be clinical in nature. Thus, providers must maintain a relatively high index of suspicion in regions where the infection has spread. Ultimately, survival rests upon the swift empiric administration of the drug of choice, doxycycline.
This review will outline the currently understood epidemiology, vector life cycle, pathogenesis, and expected clinical manifestations associated with RMSF for emergency and primary care providers. Moreover, recommendations for diagnosis and treatment will be provided, although consultation with infectious disease specialists is recommended in all suspected cases.
Causative Agent and Tick Vectors
R. rickettsii is an obligate intracellular gram-negative bacillus included in the broader category of spotted fever group rickettsioses (SFR), which also includes Rickettsia parkeri rickettsiosis, Pacific Coast tick fever, and rickettsialpox.2 It is transmitted via hard-bodied tick bites and has been documented in the American dog tick, the Rocky Mountain wood tick, and, most recently, the brown dog tick.3
The American dog tick (commonly called a wood tick) is a hard-bodied tick found east of the Rocky Mountains and in coastal California in areas with little tree cover, such as dry grasslands.4 Its life cycle begins when adult ticks emerge in the spring to seek a host, most commonly a large mammal, such as a dog, deer, cow, or passing human.5 After attaching to the host and feeding for up to a week, adults mate and females lay eggs in the underbrush, then die.5 The eggs will hatch a month later, and a few larvae will immediately begin seeking a host, while others will seek cover in ground debris and seek a host the following spring.5 As the larvae seek a host, they often climb tall stems of grass, protruding branches of underbrush, or other prominences in the natural environment and extend their legs to await a passing mammal host — a behavior known as “questing.” If successful in grabbing onto a passing mammal, like a vole or mouse, larvae will attach themselves and feed for two to 14 days before dropping off and molting to become nymphs.5 Similar to the larval stage, some nymphs will quest for a host immediately while others will shelter until the next spring. Again, if questing is successful, the tick nymph will attach to a second host to feed for three to 10 days before falling off and molting into the adult stage of their life cycle.5 Newly emerged adults rarely seek hosts before the following spring, and then will subsequently feed, mate, reproduce, and die, as described earlier.5 The life cycle typically is completed in three years, but it can vary by a year or so depending on humidity, temperature, and success in finding hosts at each stage.5,6 (See Figure 1.)
Figure 1. Three-Host Life Cycle of Hard-Bodied Ticks |
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Source: Centers for Disease Control and Prevention. Ticks. Last reviewed Dec. 31, 2017. https://www.cdc.gov/dpdx/ticks/index.html |
D. andersoni, the Rocky Mountain wood tick, is another hard-bodied tick, but it is restricted to the mountainous regions of the western United States and Southwestern Canada.7 Like D. variabilis (see Figure 2), D. andersoni is a three-host tick in terms of its life cycle.7 The Rocky Mountain wood tick can complete its life cycle in less than a year in ideal conditions, but it usually takes two to three years to grow from egg to adult.7
Figure 2. Dermacentor Genus Tick |
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This is a female American dog tick (Dermacentor variabilis), although the Rocky Mountain wood tick (Dermacentor andersoni) is similar. Dermacentor adults can be identified by the ornate dorsal shield (DS), shortened mouthparts compared to other ticks, and festoons or ridges on the hindmost aspect of the dorsal shield. Source: Centers for Disease Control and Prevention. Ticks: Image gallery. Last reviewed Dec. 31, 2017. https://www.cdc.gov/dpdx/ticks/index.html |
Notable differences from the American dog tick include a longer questing season (ranging from February to November) and shorter feeding time in its larval stage (two to six days).7 Overall, the Rocky Mountain wood tick is most active from May to mid-summer, coinciding with high humidity and warm temperatures. The numbers of questing D. andersoni rapidly decline with temperatures higher than 20°C and humidity less than 20%.7
R. sanguineus, the brown dog tick, is the most recently identified vector for RMSF.8 (See Figure 3.) Its range is spread across the entirety of the continental United States, but it most recently has been found to harbor and spread the causative agent of RMSF in the southwestern United States and northwestern Mexico.8 R. sanguineus is capable of sustaining its entire life cycle indoors when there is a canine host population available, which multiplies the threat it poses to human populations living with domestic and peridomestic dogs.8-10 Similar to the other examples discussed earlier, it requires three blood meals throughout its life cycle, but it is unique in that all stages can use domestic or feral dogs as hosts, and multiple stages (larvae, nymph, and adult) can be found on a single host.9 The literature is unclear which stages are most culpable for human disease, because unlike D. variabilis and D. andersoni, the brown dog tick will feed on humans and dogs alike at any stage of life, and it is not restricted to small mammals in the larval and nymph stages.8,10 It should be noted that discrete recollection of a tick bite is not uniformly encountered or noted. The absence of a known tick bite does not eliminate the possibility of RMSF in suspected cases.
Figure 3. Brown Dog Tick (Rhipicephalus sanguineus) |
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Source: Centers for Disease Control and Prevention. Ticks: Image gallery. Last reviewed Dec. 31, 2017. https://www.cdc.gov/dpdx/ticks/index.html |
Epidemiology
Despite the name, RMSF is not limited to the western mountain regions of North America, and it has been reported in every U.S. state since 2019.2 (See Figure 4.) However, certain states and geographic regions bear a much higher incidence of transmission and disease; from 2017-2021, 50% of cases occurred in Arkansas, North Carolina, Alabama, Tennessee, and Missouri.2 These cases generally are reported in rural and suburban environments, which likely is because of the greater population of ticks and their sustaining wild mammal hosts in such areas.
Figure 4. Annual U.S. Incidence of Reported Spotted Fever Rickettsiosis for 2021 |
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Source: Centers for Disease Control and Prevention. Rocky Mountain spotted fever (RMSF): Epidemiology and statistics: Geography. Last reviewed Jan. 11, 2024. https://www.cdc.gov/rmsf/stats... |
Transmission typically is highest in the summer months (May through August), when ticks are most active and likely to come into contact with humans.2,11 However, it should be noted that RMSF cases can be observed year-round in many endemic areas, especially in regions where transmission is noted with the brown dog tick in the southwestern United States and northern Mexico.
Overall, cases have steadily risen from 2000-2019, with a peak of 6,248 in 2017; however, cases dropped dramatically in 2020, when new standards for diagnosis were implemented to elucidate true cases of RMSF and SFR.2 Since the recategorization of RMSF into the larger group of SFR, case reports of SFR have increased while case severity has decreased, most likely because of the inclusion of less severe infections caused by R. parkeri.2
In the early 2000s, cases of RMSF were first reported in southern Arizona communities as well as throughout Sonora, Mexico.11 The first confirmed outbreak was reported in 2008 in the capital of Baja California, Mexicali. On Dec. 8, 2023, the Centers for Disease Control and Prevention (CDC) issued a health alert for those traveling to and from Tecate, Mexico, after five cases of RMSF were reported since July, leading to three deaths.12 The CDC notes that RMSF is now endemic to the Mexican states of Baja California, Sonora, Chihuahua, Coahuila, and Nuevo León.12 Compared to other outbreaks, the cases in northern Mexico and southern Arizona are in urban or semi-urban environments with large populations of stray and free-ranging dogs that sustain the population of R. sanguineus, leading to increased exposure and risk for the human population.11
Pathogenesis
R. ricketsii is introduced into the human host via feeding behaviors of the vector ticks discussed previously. After the tick attaches to the host during typical feeding behavior and ingests a blood meal, the warmth of the mammalian host reactivates dormant R. rickettsii bacteria in the tick's salivary glands.13,14 This process may require anywhere from six to 48 hours of continuous attachment and feeding. Very small inocula of pathogenic bacteria are required to induce disease. While the mean reported inoculum is 23 organisms, a single R. rickettsii bacillus may lead to symptomatic infection of a mammalian host.
Upon entry from the feeding site in the host’s skin, the bacteria subsequently travel along lymphatics and small blood vessels into the pulmonary and systemic circulation.13,14 The bacteria ultimately target the vascular endothelium of the host, where they induce phagocytosis by endothelial cells. This establishes innumerable foci of infection throughout the host, leading to many of the end-organ manifestations — the characteristic rash described later, as well as interstitial pneumonia, myocarditis, hepatitis, and myositis. As the vascular endothelium is injured and endothelial cells die, the host organism experiences rampant vascular permeability, leading to increased edema, hypovolemia, hypotension, hyponatremia, and hypoalbuminemia.14 Because of this pattern, RMSF essentially can be conceived of as a small-vessel vasculitis, providing a rationale for many of the clinical manifestations encountered.
Clinical Manifestations
Following inoculation via tick bite, the typical incubation period may range from two to 14 days until onset of symptoms. Patients most typically experience the onset of a sudden fever greater than 38.9°C (102 °F), along with severe headache and malaise. Additionally, abdominal pain, vomiting, nausea, myalgia, and periorbital and hand edema may be reported within the first three days.15,16 A rash occasionally may accompany this initial onset of symptoms, but it more commonly develops two to five days after the first symptoms are reported.
The rash itself begins as blanching erythematous macules at the wrists and ankles, followed by extension to the soles of the feet and palms before progressing to a maculopapular rash with central petechiae on the limbs and trunk.16 (See Figures 5 and 6.) Petechiae usually are not reported until day 5 or 6 of the disease and can be a sign of severe disease.15 Although the rash and its palmar and plantar involvement often are reported as defining features of RMSF, up to 12% of patients do not develop a rash at all, and the overall involvement of the palms and soles may vary from 36% to 82%.16,17
Figure 5. Characteristic Rash in the Early Stages of Rocky Mountain Spotted Fever |
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Source: Centers for Disease Control and Prevention. Rocky Mountain spotted fever (RMSF): Signs and symptoms. Last reviewed Feb. 19, 2019. https://www.cdc.gov/rmsf/healthcare-providers/signs-symptoms.html |
Figure 6. Early Rocky Mountain Spotted Fever on Arm |
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Source: Centers for Disease Control and Prevention. Rocky Mountain spotted fever (RMSF): Signs and symptoms. Last reviewed Feb. 19, 2019. https://www.cdc.gov/rmsf/healthcare-providers/signs-symptoms.html |
Although RMSF usually presents with the classical clinical triad of fever, headache, and malaise, it may involve only some or none of the usual symptoms in conjunction with more atypical presentations.15,16 Patients older than 15 years of age more frequently have atypical disease presentations, including greater prominence of neurological and ocular involvement, in addition to arrhythmias, stupor, delayed onset rash, and pneumonia.18 It also has been noted that Black patients with RMSF may develop a rash less frequently than other patient populations, but this also may be because of inadequate diagnosis of erythematous macules on dark skin tones.18,19 Uncommon neurological symptoms include lethargy, photophobia, meningismus, amnesia, and behavioral changes. Ocular manifestations may include conjunctivitis, optic disk edema, arterial occlusion, and retinal vasculitis.16
If inadequately treated, the symptoms and clinical manifestations of RMSF will continue to progress and lead to subsequent additional organ system involvement and failure. Patients will experience such adverse outcomes as skin necrosis, gangrene (subsequent amputation of the extremities), hepatomegaly, acute renal failure, respiratory compromise, cerebral edema, coma, and death.15,16
Although children younger than 10 years of age represent just 6% of RMSF cases in the United States, they account for 22% of fatalities and are five times more likely to die of RMSF than adults. Children are less likely to report headache but more frequently report abdominal pain and gastrointestinal symptoms in addition to periorbital and hand edema.15
Overall, one of the most important and preventable risk factors for adverse outcomes is delayed treatment. For this reason, immediate initiation of empiric therapy with doxycycline is always warranted if RMSF is included on the differential diagnosis of a patient with compatible symptoms and geographic risk factors. Finally, glucose-6-phosphate dehydrogenase deficiency is reported as an additional risk factor for adverse outcomes and mortality.15
Diagnosis
Patient survival depends on early recognition of the signs and symptoms of RMSF as well as immediate empiric therapy with doxycycline.20 Fundamentally, the diagnosis of RMSF must be made clinically, with subsequent confirmatory testing after treatment.14,21 Because of this (and the potential rapid progression of the disease), practitioners should never delay presumptive therapy to establish the diagnosis with confirmatory testing. Practitioners should err on the side of caution when considering RMSF in their differential diagnosis; any individual with compatible signs and symptoms and exposure to areas with ticks should be treated as a potential case, and life-saving empiric therapy with doxycycline should be considered.20
Serologic testing for immunofluorescence antibodies to R. rickettsii antigen remains the mainstay of confirmatory diagnosis.14,21 Patients will begin to seroconvert and generate immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies after seven to 10 days of illness. IgM antibodies are less specific and may lead to false-positive diagnoses; therefore, the presence of IgG antibodies is regarded as the gold standard. However, even RMSF IgG antibody testing may cross-react with prior exposure to other spotted-fever group Rickettsiae, and low-level positive antibody titers sometimes are seen in the general population of various regions. Thus, when encountering cases of suspected RMSF, providers should obtain IgG and IgM antibodies during the acute phase of illness (at the outset of starting presumptive therapy, in the first week of symptoms), followed by convalescent IgG and IgM antibody titers two to four weeks later — after completing presumptive therapy, recovery, and, presumably, when the serologic response has had time to generate an antibody response.20 It should be emphasized that antibody titers obtained in the acute period (in the first one to two weeks) often are negative. Confirmation of an RMSF diagnosis is established by the observation of a fourfold or greater rise in antigen-specific IgG antibody titers between acute and convalescent sera.20,21 Patients may continue to demonstrate high-level IgG titers for years after successful therapy and cure.20
Adjunctive tests to help establish the diagnosis early on include compatible, characteristic laboratory data. Patients may have a normal white blood cell count, mild anemia (in 5% to 30% of cases), but, most characteristically, thrombocytopenia may be prominent, even in patients with early disease or milder symptoms.14 Coagulopathy, as measured by increased coagulation times or decreased concentrations of fibrinogen, is not expected. Fundamentally, the pathophysiology rests on endothelial injury and dysfunction, rather than interruption of the clotting cascade.14 Likewise, disseminated intravascular coagulation is not expected in RMSF. However, hyponatremia and hypoalbuminemia are highly characteristic of the disease process.
Other diagnostic methods typically are less useful in the clinical environment. Polymerase chain reaction (PCR) testing from the serum often is negative earlier in illness and does not become positive until high levels of rickettsial deoxyribonucleic acid are circulating as endothelial injury progresses and the patient’s situation becomes more dire.14,20,21 PCR-based tests can be employed if skin biopsies of the characteristic rash are obtained; but, again, presumptive therapy should never be delayed for the sake of such testing. Tissue specimens obtained at autopsy also can be usefully interrogated via PCR for establishing cause of death.20
While R. rickettsii has been successfully cultured in research settings, this modality generally is not viewed as clinically useful. Culture and immunohistochemistry assays can be performed on biopsy specimens and tissue obtained at autopsy through specialized centers.20
Lastly, additional diagnoses to be considered in patients with signs and symptoms compatible with RMSF, depending on geographic risk factors and other demographic or patient data, include other rickettsial diseases (SFR or typhus), ehrlichiosis, anaplasmosis, measles, rubella, meningococcemia, disseminated gonococcal infection, secondary syphilis, leptospirosis, immune thrombocytopenic purpura, thrombotic thrombocytopenic purpura, and drug reactions.14 Providers should apply appropriate testing for such entities while also bearing in mind the need for empiric doxycycline therapy if RMSF is a pertinent consideration.
Treatment
Doxycycline is the drug of choice in all age groups when treating RMSF, including children younger than 8 years of age.14,21,22 Prior to the introduction of tetracyclines and chloramphenicol, mortality rates of RMSF were as high as 20% to 80%. However, with appropriate treatment, mortality is as low as 3%.14,21
Early and prompt treatment with doxycycline in adults and children of all ages is lifesaving, and it should be added to the empiric antibiotic regimen as soon as RMSF is considered as a reasonable item in the differential diagnosis of an ill patient.
Adults should receive doxycycline 100 mg every 12 hours, orally or intravenously, for a minimum course of therapy of five to seven days.21,22 Children should receive doxycycline 2.2 mg/kg (to a maximum dose of 100 mg) every 12 hours, orally or intravenously, likewise for a minimum course of five to seven days. Therapy should be continued for at least three days following defervescence.21,22 While the usual duration usually does not exceed seven days, longer durations may be considered in more severe cases. Importantly, doxycycline is most effective if started within five days of symptom onset; treatment started after this crucial period is less likely to be lifesaving or to prevent severe complications.21
It bears repeating that while doxycycline normally is contraindicated in children younger than 8 years of age and pregnant patients, the benefits of this drug are thought to outweigh the risks in this potentially fatal illness.14,22 Therefore, providers are recommended to choose this therapy above all others in any demographic. Studies regarding the risk of permanent teeth staining or enamel dysplasia in young children receiving doxycycline for RMSF have found that short courses of this antibiotic are unlikely to have any ill effects.23 While the risk of teratogenicity with doxycycline use in pregnancy is thought to be low, the risk cannot be said to be zero, and thus pregnant patients should be counseled regarding this possibility.22 Patients with severe doxycycline allergy may undergo rapid desensitization procedures in an inpatient setting, but consultation with infectious diseases specialists and allergists should be pursued to consider risks vs. benefits in such cases.22
Chloramphenicol is considered to be a viable and well-studied alternative agent; however, it is not available in the United States as an oral formulation.21
Prevention
The only reliable method to prevent RMSF is avoidance of tick bites.14,24 If a tick bite is discovered, prophylactic treatment with doxycycline is not known to be effective, nor is it recommended.25
Families should be counseled to be conscious of entering areas where ticks exhibit questing behavior, specifically wooded and grassy areas in the warm summer months. Ticks are not only found in undeveloped wilderness areas, but also near human settlements, such as public parks or private yards. Most importantly, families should be counseled to avoid walking through underbrush or tall grass, where questing ticks may latch onto a passing hiker’s clothing.
In addition, vector ticks can live on both domestic and wild animals, and care should be taken to minimize contact with potential hosts.24 Dogs should be properly shampooed with anti-tick products, and known infestations of peridomestic dogs should be addressed.
When time is spent outside in tick-heavy areas, pretreating clothing with permethrin can offer an important element of protection.24 Additionally, wearing light-colored, long-sleeved shirts and pants instead of shorts will decrease the amount of available/exposed skin for ticks to latch onto and allows for better visualization of ticks attached to clothing.26 Environmental Protection Agency-approved insect repellents, such as DEET, picaridin, and oil of lemon eucalyptus can protect exposed skin from attachment by vector ticks.24
When returning from outdoor recreation, it also is important to check clothing and body alike for ticks, as well as pets or children that were also outside. Special attention should be paid to the underarms, ears, inside the navel, backs of the knees, in and around the hair, groin, and waist.24 Long hair also can be a risk factor for failure to detect the attachment of a host tick, so special care should be given to the scalps of long-haired patients.
If an attached tick is discovered, removing it immediately is important. Removal can be accomplished by grasping the head of the arthropod with tweezers and steadily pulling upward. Alternative removal methods (such as holding a flame near the tick or coating it in petroleum jelly) should be avoided, since these may cause the tick to regurgitate its blood meal back into the host, potentially inoculating pathogenic R. rickettsii or other bacteria into the patient.27 The bite area then should be washed with soap and water. Special care should be taken to not crush the tick; the tick can be saved in a plastic bag or submerged in rubbing alcohol to determine whether it is a known vector species.27 However, commercial diagnostic tests of the arthropod vector itself are not available.
Conclusion
R. rickettsii has demonstrated the dynamic interchange of arthropod vectors, hosts, and geography over the past 20 to 30 years, subjecting new regions to risk for RMSF. Because of RMSF’s rapid progression and high fatality rate if treated inappropriately, practitioners must remain vigilant and maintain a high index of suspicion for this serious diagnosis.
When considering patients who live in or who have traveled through known endemic regions, the constellation of fever, headache, myalgias, and petechial rash should trigger a deeper investigation and strong consideration of initiating doxycycline. Antibiotic therapy cannot be delayed; empiric therapy must be started right away, and confirmatory testing then can be pursued with acute and convalescent serologic titers. As mentioned, the treatment of choice in all age groups and demographics remains doxycycline — even among the very young or pregnant, for whom this drug normally is contraindicated. Tick bite prevention is pertinent and sound advice for all individuals living in and traveling through endemic regions.
Case Conclusion
A laboratory evaluation is initiated. A complete blood cell count reveals a normal white blood cell count, a hemoglobin of 10.2 g/dL, and thrombocytopenia with a platelet count of 90k per microliter. A complete metabolic panel shows hyponatremia, with sodium levels of 130 mmol/L, along with some renal dysfunction, with a serum creatinine of 1.4 mg/dL. Notably, her serum albumin is low (at 2.9 g/dL), and she has some mild elevation to her transaminases, with aspartate transferase of 101 U/L and alanine aminotransferase of 99 U/L.
Based on recent reports of RMSF in the region, suspicion is raised for this clinical entity. Additionally, the providers caring for her consider the possibility of early sepsis and meningococcemia. Blood cultures are quickly drawn, and after a discussion over the telephone with a regional pediatric infectious disease specialist, RMSF IgG and IgM antibodies are sent to a reference laboratory. There is no delay in starting antibiotics, and the patient is started on an empiric regimen of intravenous vancomycin, ceftriaxone, and doxycycline. She subsequently is admitted for further evaluation and treatment.
Over the first 48 hours of her hospitalization, she experiences a marked improvement. Her fever abates, and the rash fades quickly. She feels much better by the end of the second day. Her blood cultures remain negative, and soon, empiric ceftriaxone and vancomycin are discontinued. Her laboratory markers improve, demonstrating normalization of her platelet count, sodium, albumin, and renal function. She is discharged home with a prescription to complete a seven-day course of oral doxycycline and follow up with her primary care provider. Her outpatient course is uneventful, and she returns to school the following week feeling well with no further sequelae.
Her initial R. rickettsii serum antibody titers result as < 1:64, which are normal. However, four weeks later the IgG antibody titer is repeated. This time the result is 1:512, which is confirmatory of her previous working diagnosis of RMSF.
References
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- Centers for Disease Control and Prevention. Rocky Mountain spotted fever: Epidemiology and statistics. Last reviewed Jan. 11, 2024. https://www.cdc.gov/rmsf/stats/index.html
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- Zazueta OE, Armstrong PA, Márquez-Elguea A, et al. Rocky Mountain spotted fever in a large metropolitan center, Mexico-United States border, 2009-2019. Emerg Infect Dis 2021;27:1567-1576.
- Centers for Disease Control and Prevention. Severe and fatal confirmed Rocky Mountain spotted fever among people with recent travel to Tecate, Mexico. Published Dec. 8, 2023. https://emergency.cdc.gov/han/2023/han00502.asp
- Walker DH. Rocky Mountain spotted fever: A disease in need of microbiological concern. Clin Microbiol Rev 1989;2:227-240.
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- Sangha AM. Dermatological conditions in skin of color: Managing atopic dermatitis. J Clin Aesthet Dermatol 2021;14(3 Suppl 1):S20-S22.
- Centers for Disease Control and Prevention. Rocky Mountain spotted fever: Clinical and laboratory diagnosis. Last reviewed March 26, 2021. https://www.cdc.gov/rmsf/healthcare-providers/ClinLab-Diagnosis.html
- American Academy of Pediatrics. Rocky Mountain Spotted Fever. In: Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH, eds. Red Book: 2021 Report of the Committee on Infectious Diseases. American Academy of Pediatrics;2021:641-644.
- Centers for Disease Control and Prevention. Rocky Mountain Spotted Fever (RMSF): Prevention. Last reviewed May 27, 2021. https://www.cdc.gov/rmsf/prevention/index.html
- Centers for Disease Control and Prevention. Rocky Mountain spotted fever: Research on doxycycline and tooth staining. Last reviewed Feb. 19, 2019. https://www.cdc.gov/rmsf/doxycycline/index.html
- Osterloh A. The neglected challenge: Vaccination against Rickettsiae. PLOS Negl Trop Dis 2020;14:e0008704.
- Centers for Disease Control and Prevention. Rocky Mountain Spotted Fever (RMSF): Treatment. Last reviewed Feb. 19, 2019. https://www.cdc.gov/rmsf/healthcare-providers/treatment.html#:~:text=Post%2Dtick%20bite%20antibiotic%20prophylaxis,two%20weeks%20of%20tick%20bite
- United States Environmental Protection Agency. Tips to prevent tick bites. Last reviewed May 2, 2023. https://www.epa.gov/insect-repellents/tips-prevent-tick-bites#:~:text=Keep%20ticks%20away%20from%20exposed,to%20see%20ticks%20more%20easily
- Centers for Disease Control and Prevention. Ticks: Tick removal. Last reviewed May 13, 2023. https://www.cdc.gov/ticks/removing_a_tick.html
Rocky Mountain spotted fever is an infectious disease that may be rapidly fatal if not rapidly recognized based on clinical findings and early institution of appropriate antibiotic therapy. The epidemiologic shift of this disease makes it important for all healthcare providers to be familiar with the current status, clinical presentation, and therapy for Rocky Mountain spotted fever.
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