Basics
Description
- Life-threatening, small vessel vasculitis
- Caused by infection with Rickettsia rickettsii, an obligate intracellular gram-negative coccobacillus, transmitted by three species of ticks in the United States
- Member of spotted fever subgroup of rickettsial diseases
- Seasonal endemic disease but may occur in other areas and throughout the year
- Classic symptoms of fever, headache, and rash following tick exposure are often not present.
Epidemiology
- Most common rickettsial disease in the United States
- Seasonal: April " September accounts for 90% of cases.
- Geographic
- Restricted to countries of western hemisphere
- Cases reported from all states except Alaska, Hawaii, and Maine
- Occurs most often in southern Atlantic and south central regions: 1994 " 2003, >50% of cases in North Carolina, South Carolina, Tennessee, Oklahoma, Arkansas
- Less often seen in Rocky Mountain states
- Also occurs in southern Canada, Mexico, and Central and South America
- Single isolated cases most common in United States; clusters are reported infrequently in United States (4.4% familial) but are more typical in certain endemic areas (e.g., Brazil).
- Up to 2/3 of patients are <15 years old.
Incidence
- Annual incidence: 7 cases per million people (2002 " 2007); the highest recorded level in >80 years of national surveillance
- Cyclic fluctuations in incidence; 250 " 1,200 cases reported per year
- More often reported in American Indians, whites, males, and children; incidence highest in 5 " 9-year-olds
- Fatal outcome reported in 23% of untreated, and 5% of treated, cases
- Geographic variations in case fatality occur, likely due to different levels of pathogenicity, host factors, and delayed recognition in less endemic regions.
- 15% reported deaths in children <10 years of age
Prevalence
4 " 22% of children show significant antibody titers in endemic areas, likely representative of subclinical disease.
Risk Factors
R. rickettsii " infected tick exposure or rural environment or occupation increasing forest exposure in endemic region
General Prevention
- Avoid tick-infested areas; limit skin exposure with long, light-colored clothing, tucked-in socks, or boots; inspect frequently.
- Use tick repellants or impregnated clothing.
- DEET most effective
- Essential oils that offer natural alternatives considered safe (soybean, lemon eucalyptus, citronella, and clove)
- Remove ticks promptly.
- Do not crush; may increase transmission
- Avoid direct contact; remove with tweezers or gloved fingers close to skin.
- Apply steady upward traction until tick 's grip is released.
- Clean wound.
- Matches, petroleum jelly, nail polish, and rubbing alcohol are not effective for removal.
- Vaccine not available in the United States; may not prevent disease but does prevent deaths
Pathophysiology
- Transmission usually occurs from tick bite (reservoir):
- Usually >4 hours of attachment needed to transmit disease (often 24 hours)
- Can occur by transfusion or aerosol route
- Incubation period 2 " 14 days, average 7 days
- R. rickettsii spreads through the lymphatic system, causing a small vessel vasculitis that affects all organs, especially skin and adrenals; increased vascular permeability and focal areas of endothelial proliferation
- Causes hyponatremia, hypoalbuminemia, edema, and hypotension
- Immunity is conferred following disease.
Etiology
Wood tick (Dermacentor andersoni) in Rocky Mountain states and southwest Canada; dog tick (Dermacentor variabilis) in east central region and areas of Pacific coast; Rhipicephalus sanguineus in Arizona and northern Mexico; Amblyomma cajennense and Amblyommaaureolatum in Central and South America
Commonly Associated Conditions
- Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency account for a disproportionate number of deaths.
- Serious biologic weapon threat due to virulence causing severe disease; difficulty establishing diagnosis; low levels of immunity; agent available in nature; high infectivity; and feasibility of propagation, stabilization, and dispersal; thus development of a cross-protective vaccine against all Rickettsia is desirable for biodefense as well as for travel medicine.
Diagnosis
History
- History: classic triad of fever, headache, and rash seen in ’ Ό50% of cases
- Abdominal pain common mainly in children
- Symptoms usually appear 2 " 8 days after tick bite.
- Gradual fever onset to >40 °C (104 °F), often unresponsive to antipyretics
- Headache: intense, retrobulbar or frontal, persistent and difficult to treat; young children may not describe
- Cough, dyspnea
- Nausea, vomiting, abdominal pain, diarrhea
- Tick bite is reported in only 50 " 60% of cases.
Physical Exam
- Fever and rash present in 85% of patients.
- Skin
- Rash: usually appears by illness days 2 " 3, may be >6th day; 10 " 15% never develop rash so absence should not delay therapy.
- Usually small, irregular, erythematous blanching macules, become maculopapular then petechial and confluently hemorrhagic
- Usually on wrists and ankles first, spreads within hours to trunk, neck, and face; may involve palms, soles, and scrotum
- May appear first on trunk or diffusely; can progress to necrosis of ears, nose, scrotum, fingers, or toes
- Difficult to detect in people with dark skin
- CNS: meningismus, restlessness, irritability, apprehension, confusion, delirium, lethargy, stupor, coma, ataxia, opisthotonos, aphasia, papilledema, seizures, cortical blindness, central deafness, spastic paralysis, cranial nerve palsy
- Cardiac: CHF, myocarditis, arrhythmias, hypovolemic vascular collapse
- Pulmonary: pneumonitis, dyspnea, pulmonary edema, hypoxemia, pleural effusions, alveolar infiltrates
- GI: diarrhea, hepatomegaly, splenomegaly, anorexia, jaundice, mild pancreatitis
- Ocular: conjunctivitis, venous engorgement, papilledema, cotton wool spots, retinal hemorrhages, retinal artery occlusion, uveitis
- Other: edema, myalgias (especially calf or thigh), parotitis, orchitis, pharyngitis
Diagnostic Tests & Interpretation
Presumptive diagnosis based on signs, symptoms, exposure history, and epidemiologic considerations rather than laboratory aids
Lab
- Nonspecific
- CBC: anemia (30%), thrombocytopenia (from consumptive coagulopathy); normal or low leukocytes days 4 " 5, subsequent leukocytosis associated with secondary bacterial disease; bandemia common
- Electrolytes: hyponatremia
- Elevated BUN, creatinine, liver function tests, bilirubin, creatine kinase
- Screen for disseminated intravascular coagulation (rare), prolonged prothrombin time, decreased fibrinogen (consumption).
- Arterial blood gases: acidosis
- Hypoalbuminemia
- CSF: usually clear (leukocyte count <10), may see pleocytosis in 1/3 and increased protein in 1/2 of patients
- Specific serologic tests
- No early specific laboratory tests; serologic data reliable by days 10 " 12 of illness; negative results do not exclude diagnosis.
- All test results normalize with early intervention.
- Indirect immunofluorescence assay (IFA)
- Best and most widely available method
- 2 serum samples obtained weeks apart showing 4-fold increase in IgG and IgM anti " R. rickettsii antibody titers
- Positive 6 " 10 days after onset of disease, sensitivity increases to 94% with convalescence serum sample from days 14 to 21 days; specificity 100%
- PCR, immunohistochemical staining, and culture are best done on biopsy specimen (of rash site or at autopsy) due to low circulating organism levels.
- Routine hospital blood cultures will not detect; available only at specialty labs
- Weil-Felix test: oldest specific test but nonspecific and insensitive; no longer recommended
Imaging
Chest radiograph, ECG, and echocardiogram are recommended. Distinctive features on MR images (brain and spinal cord) may lead to early diagnosis; CT findings are less often present.
Differential Diagnosis
Measles, meningococcemia, ehrlichiosis, typhoid fever, leptospirosis, rubella, scarlet fever, disseminated gonococcal disease, infectious mononucleosis, secondary syphilis, rheumatic fever, enteroviral infection, immune thrombocytic purpura, thrombotic thrombocytopenic purpura, immune complex vasculitis, drug hypersensitivity reaction, murine typhus, rickettsialpox, and recrudescent typhus
Alert
Do not exclude diagnosis even if there is no history of tick bite, no rash present, and/or results of serologic tests are negative. Treatment should be started presumptively and postponement of therapy while awaiting laboratory confirmation or presence of rash.
Treatment
Medication
Treatment should be initiated based on clinical and epidemiologic information, as laboratory confirmation may not be available during acute illness. All agents are rickettsiostatic (hinder replication), not rickettsicidal, so host can eradicate disease. Treat until there is evidence of clinical improvement and at least 3 days without fever; standard duration is 5 " 10 days.
First Line
- Doxycycline (usual tetracycline antibiotic) is the drug of choice at any age:
- Adults: 100 mg q12h PO/IV
- Children under 45 kg (100 lb): 4.4 mg/kg/24 h PO/IV divided b.i.d.
- Also treats ehrlichiosis (similar presentation)
- Side effects: less likely to stain teeth than tetracycline; contraindicated for pregnancy, although can be considered even in pregnancy if the mother 's life is in danger and the theoretical concerns on the fetus is discussed
- Chloramphenicol (alternative during pregnancy)
- Adult: 50 " 100 mg/kg/24 h IV divided q6h (max 4 g/24 h)
- Child >1 month of age: 50 " 100 mg/kg/24 h IV divided q6h (max 4 g/24 h)
- Side effects: peripheral neuropathy, aplastic anemia, "gray baby syndrome " with high dosage, possible association with leukemia, hemolytic anemia with G6PD
- Not as effective as tetracyclines, or against ehrlichiosis; higher mortality rate in those treated with chloramphenicol than tetracyclines; consider only rarely such as during pregnancy.
Second Line
- Quinolones (ciprofloxacin, pefloxacin), macrolide (clarithromycin) with in vitro effect, no clinical evidence of efficacy
- Corticosteroids
- May be helpful in severe cases, although no controlled studies published
- Not advised for mild or moderately ill patients
Additional Treatment
General Measures
- Treat empirically if clinical suspicion.
- Platelets as indicated for thrombocytopenia
- Vitamin K (IM) for prolonged clotting time
- Manage hyponatremia with fluid restriction; avoid sodium supplements.
- Albumin if indicated
- Report to state health department.
Inpatient Considerations
Initial Stabilization
Volume, electrolyte support as indicated
Ongoing Care
Follow-up Recommendations
Expect improvement in 24 " 36 hours and defervescence in 2 " 3 days with treatment, especially if initiated <5 days after onset of symptoms.
Prognosis
- Related to early recognition of disease and initiation of appropriate therapy
- Case fatality 2 " 4% if treated <6 days from onset of symptoms
- Case fatality 15 " 22.9% if treated >6 days from onset of symptoms
- Higher mortality if <4 years, G6PD deficiency, CNS involvement, renal failure, jaundice, cardiovascular collapse, hepatomegaly, thrombocytopenia, DIC, GI symptoms, inappropriate antibiotics, late rash, absence of headache, or male gender
- Death usually between 8th and 15th days (fulminant cases with death in 5 " 6 days)
Complications
- Uncommon with early, appropriate treatment
- Neurologic sequelae
- Behavioral disturbances, learning disabilities (more common), emotional lability, hyperactivity, memory loss, seizures
- Dermatologic sequelae
- Gangrene of extremities, end organs, skin necrosis
- Skin rash usually heals without sequelae.
- Hematologic sequelae: DIC
- GI sequelae
- Hepatic dysfunction
- Hypoalbuminemia from hepatic dysfunction, protein loss from damaged vessels
- Cardiac sequelae: can have persistent cardiac findings, CHF, cardiovascular collapse
- Metabolic sequelae: hyponatremia from water shift to intracellular spaces, sodium loss in urine
- Renal sequelae: acute tubular necrosis
Additional Reading
- Akgoz A, Mukundan S, Lee TC. Imaging of rickettsial, spirochetal, and parasitic infections. Neuroimaging Clin N Am. 2012;22(4):633 " 657. [View Abstract]
- Buckingham SC, Marshal GS, Schutze GE, et al. Clinical and laboratory features, hospital course, and outcomes of Rocky Mountain spotted fever in children. J Pediatr. 2007;150(2):180 " 184, 184.e1. [View Abstract]
- Centers for Disease Control and Prevention. Rocky Mountain spotted fever (RMSF). http://www.cdc.gov/ncidod/dvrd/rmsf/index.htm. Accessed March 27, 2015.
- Chen LF, Sexton DJ. What 's new in Rocky Mountain spotted fever? Infect Dis Clin North Am. 2008;22(3):415 " 432, vii " viii. [View Abstract]
- Dantas-Torres F. Rocky Mountain spotted fever. Lancet Infect Dis. 2007;7(11):724 " 732. [View Abstract]
- Openshaw JJ, Swerdlow DL, Krebs JW, et al. Rocky Mountain spotted fever in the United States, 2000 " 2007: interpreting contemporary increases in incidence. Am J Trop Med Hyg. 2010;83(1):174 " 182. [View Abstract]
- Shapiro R. Prevention of vector transmitted diseases with clove oil insect repellent. J Pediatr Nurs. 2012;27(4):346 " 349. [View Abstract]
- Walker DH. The realities of biodefense vaccines against Rickettsia. Vaccine. 2009;27(Suppl 4):D52 " D55. [View Abstract]
Codes
ICD09
ICD10
- A77.0 Spotted fever due to Rickettsia rickettsii
SNOMED
- 186772009 Rocky Mountain spotted fever (disorder)
- 240616003 Eastern Rocky Mountain spotted fever
- 240615004 Western Rocky Mountain spotted fever
FAQ
- Q: In which patients should Rocky Mountain spotted fever be considered in the differential diagnosis?
- A: Anyone with a fever during the spring and summer who has been in an endemic area, regardless of presence of rash or history of tick bite. Nonspecific symptoms (e.g., GI, respiratory, rashes) may lead to misdiagnosis and thus delay therapy.
- Q: Should a child with a tick bite receive antibiotic prophylaxis when a tick is discovered?
- A: There is no evidence that prophylaxis is necessary or efficacious in preventing disease. To contract disease, one must be bitten by a tick that carries the disease (low risk), the tick must transmit the Rickettsia (low risk, usually requires >6 hours of attachment), and the Rickettsia must be pathogenic if inoculated (low risk).