Approach

Rocky Mountain spotted fever (RMSF) is a notifiable disease. Clinicians should prescribe antibiotic therapy (doxycycline) once the diagnosis is reasonably considered, without waiting for results of confirmatory tests. Early consideration of the diagnosis and initiation of therapy is important as the case fatality rate increases considerably after 5 days of illness. This presents a challenge, as no constellation of signs and symptoms definitely confirms or excludes the diagnosis, and fever with headache is a common presentation of many illnesses.

History

During the spring and summer in endemic areas, RMSF should be seriously considered in any patient with fever and headache, regardless of the tick exposure history. A detailed history of recent recreational or occupational outdoor activities may reveal potential tick exposures that were unknown to the patient. A history of tick bite may not be elicited in up to 45% of cases. An inoculation eschar at the site of the tick bite is rarely present.[1]

Clinical presentation

In most cases, clinical features begin 3 to 12 days after the bite attachment of an infected tick.[16]​ Because RMSF is a multi-system vasculitis, its manifestations can be related to virtually any organ. Approximately two-thirds of patients present with fever, rash, and headache, and almost all patients will have fever with headache.[1][12][13][16]​​[17]​​​​ Myalgia and malaise are usually present. Other reported clinical features include nausea, vomiting, abdominal pain, and diarrhoea.[12][13][16]​ 

Initial symptoms are vague and non-specific, and the rash is only present in less than 50% of adults in the first 3 days of illness. It can, however, manifest earlier in the disease course in children. Therefore, it is important to consider the diagnosis in patients with signs and symptoms that support the diagnosis, even if a rash is not present. The rash typically occurs 2-4 days after the onset of fever, and approximately 90% of patients will eventually get a rash.[16]​ The rash typically begins as small (1-5 mm), blanching erythematous macules on the ankles and wrists which then spreads proximally to the arms and legs, and palms and soles before involving the trunk. The face is usually spared. Over a few days the rash becomes maculopapular and subsequently petechial. Purpura fulminans is a late finding of severe infection. Classic petechiae usually appear by day 5 or 6 and are associated with severe disease. It should be noted that the rash may be absent altogether in a small proportion of adults and children with RMSF. The presence of a maculopapular or petechial rash markedly increases the likelihood of RMSF; however, the absence of a rash does not exclude the diagnosis.[1][Figure caption and citation for the preceding image starts]: Child's right hand and wrist displaying the characteristic spotted rash of Rocky Mountain spotted feverCDC Image Library; used with permission [Citation ends].com.bmj.content.model.Caption@559840a7

Less frequently noted findings that may occur later in the presentation include mental status impairment, meningismus/meningitis, conjunctivitis, lymphadenopathy, periorbital or peripheral oedema, hepatosplenomegaly, or jaundice. Abdominal pain mimicking appendicitis, or gastroenteritis, may be observed and is more common in children. Uncommon findings include pneumonitis, focal neurologic deficits, coma, seizures, shock, arrhythmias, or myocarditis.[12][13][16]

It is important to note that the clinical presentation of cases in Arizona may differ from the usual presentation in the US, and may have higher case fatality rates, particularly among children.[4]​​

While RMSF is the most common and severe spotted fever rickettsiosis in the US, it can easily be confused with other spotted fevers as the presentation is similar. While other spotted fevers may present with signs of an eschar, this is not common in cases of RMSF.[16]

CDC: timeline of RMSF signs and symptoms Opens in new window

Laboratory investigations

FBC, electrolytes, LFTs, and blood culture should be evaluated in patients with suspected RMSF. Hyponatraemia, thrombocytopenia, and mildly elevated AST and ALT are all suggestive of RMSF; however, absence of any of these does not exclude the diagnosis.[1][18]​​

Blood culture should be performed, because meningococcaemia (or, rarely, bloodstream infections with other pyogenic bacteria) can present with similar signs and symptoms.

Cerebrospinal fluid (CSF) examination is not necessary in most cases of suspected RMSF, but may be performed as part of the diagnostic evaluation of patients with fever and abnormal sensorium or other neurological findings. The CSF of patients with RMSF typically demonstrates mononuclear cell pleocytosis (<100 cells/microlitre), elevated protein concentration, and normal glucose concentration.

Findings of disseminated intravascular coagulation are rare.

Chest and abdominal imaging may suggest pulmonary oedema, systemic vasculitis, or can be useful for excluding other diagnoses such as appendicitis.

Serology

Patients with RMSF do not usually demonstrate a serological response against Rickettsia rickettsii until at least 7 to 10 days into the course of illness. Thus, serological testing is done for confirmation purposes only; clinicians should prescribe therapy as soon as the diagnosis is reasonably considered, without waiting for the results of confirmatory tests.[1][18]​​

Indirect immunofluorescent antibody (IFA) is the preferred serological test, and IFA from paired acute and convalescent serum collected 2-10 weeks apart is the reference standard.[1][18][19]​​

Other options include enzyme immunoassay, complement fixation (CF), latex agglutination (LA), indirect haemagglutination (IHA), and microagglutination (MA) tests.

If the single serum titre is ≥1:64 by IFA, ≥1:16 by CF, or ≥1:128 by LA, IHA, or MA in a patient with a compatible clinical illness, there is a probable diagnosis of RMSF. If results are negative in a patient in the first week of illness, serology should be repeated. Early therapy with doxycycline might impair development of RMSF antibodies.

Confirmation of the diagnosis requires a 4-fold or greater change in titre between acute-phase and convalescent-phase serum specimens.[19]​

The Weil-Felix serological test, which measures responses to Proteus vulgaris OX-19 and OX-2 agglutinins, is inferior to currently available specific anti-rickettsial serological tests and is no longer recommended.[1][11]​​

Serological diagnosis does not differentiate between spotted fever group Rickettsia species in most laboratories.[1][19]​​[20]​​​​​

Other investigations

Immunohistochemistry can confirm the diagnosis early in the illness course by demonstrating the presence of rickettsiae in skin biopsy samples, but it is not commonly used. This technique has a reported diagnostic sensitivity of about 70% and specificity of 100% but is time consuming and available only in specialised research laboratories and at the Centers for Disease Control and Prevention (CDC).[1][18][19]​​​​​

Polymerase chain reaction can confirm the diagnosis early in the illness course by demonstrating the presence of Rickettsia rickettsii DNA in blood or biopsy specimens, but it is not commonly used. This technique is not adequately sensitive to exclude the diagnosis due to low numbers of rickettsia in circulating blood in patients with less severe disease. A negative result does not rule out the diagnosis. It is currently available only in specialised research laboratories and at the CDC.[1][18]​​​[19]

CDC: rickettsial disease diagnostic testing and interpretation Opens in new window

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