Basics
Description
- Disorders caused by the Rickettsiae family of organisms including those which cause Rocky Mountain spotted fever and other similar tick-borne illnesses, the typhus group, and the organisms that cause ehrlichiosis and anaplasmosis
- All organisms are obligate intracellular gram-negative bacteria and therefore are difficult to grow in culture.
- The diseases caused by each group of organisms are similar, encompassing a syndrome including fever, rash, headache, and capillary leak; all are transmitted via an insect vector.
General Prevention
- Fleas, ticks, and mites should be controlled in endemic areas with the appropriate insecticides.
- Clothing to cover the entire body should be worn in tick-infested areas. In the case of a recognized bite, ticks should be removed from human skin properly, with care not to expel the contents of the tick 's stomach into the site of the bite.
- In areas where louse-borne typhus is epidemic, periodic delousing and dusting of insecticide into clothes are recommended.
- Paradoxic effect of rodenticides:
- Fleas and mites seek alternate hosts (i.e., humans) when mice or rats are not present.
- Therefore, rodenticides should not be the only preventive measure taken in endemic areas.
- Except for scrub typhus, all rickettsial diseases produce long-term immunity to the etiologic organisms within the same group.
Pathophysiology
Spotted fever, typhus, ehrlichiosis, and anaplasmosis groups cause vasculitis as a result of organisms invading the endothelial cells of small blood vessels or white blood cells. This manifests as rash in cutaneous tissues and systemic illness due to capillary leak throughout other organs.
Etiology
- Spotted fever group rickettsia and the agents of ehrlichiosis and anaplasmosis (Ehrlichia and Anaplasma species) are transmitted to humans by ticks.
- Rickettsialpox and scrub typhus are transmitted by mites associated with mice.
- Epidemic typhus is a louse-borne illness, and endemic typhus, also known as murine typhus, is transmitted by fleas.
- The rickettsial diseases that occur in the United States are Rocky Mountain spotted fever, murine typhus, rickettsialpox, epidemic typhus, ehrlichiosis, and anaplasmosis.
Diagnosis
History
- In general, rickettsial disease should be considered as a diagnosis in a patient with fever, headache, and rash. Progression of rash can be particularly helpful in considering the diagnosis.
- Signs and symptoms:
- Spotted fever group
- Illness often begins with fever, myalgia, and headache.
- Rash occurs 3 " 5 days following onset of symptoms and is typically described as centripetal, beginning on hands and feet and moving toward the trunk. Rash is variable and may not always follow this pattern.
- Other symptoms include headache, neurologic changes, hypotension, hyponatremia, and consumptive coagulopathy.
- Fulminant RMSF may cause cardiovascular collapse.
- Rickettsialpox
- Similar to spotted fever group, although less severe and with fewer systemic symptoms; rash often includes an inoculation eschar.
- Typhus group
- Epidemic typhus is transmitted by the human body louse and causes fever, headache, and rash that can progress to pulmonary symptoms, neurologic disease, and death.
- Endemic typhus is transmitted by fleas associated with rodents and causes symptoms similar to epidemic typhus, although with a less prevalent rash.
- Scrub typhus is also similar but causes marked neurologic symptoms including mental status changes.
- Ehrlichiosis/anaplasmosis
- Spectrum of illnesses including human monocytotropic ehrlichiosis and human granulocytotropic anaplasmosis that cause fever, headache, and myalgias similar to the spotted fever group.
- Rash is less common as compared to spotted fever and occurs in <50% of patients in ehrlichiosis and very few in anaplasmosis.
Physical Exam
- All rickettsial diseases cause fever and the majority cause rash.
- These 3 findings suggest illness caused by the spotted fever group:
- Hypotension, cardiovascular instability
- Hepatosplenomegaly
- Tache noire (French for black spot): The earliest finding in the spotted fever group, this lesion originates at the site of the infecting bite and may form eschar with regional lymphadenopathy related to the eschar. The lesion is usually found on the head in children and on the legs in adults; present in 30 " 90% of cases.
- These 3 findings suggest illness caused by the typhus group:
- Impaired level of consciousness
- Pulmonary and renal involvement
- Brill-Zinsser disease is actually a recrudescence of a previous infection with epidemic (louse-borne) typhus caused by Rickettsia prowazekii; can occur years after the initial infection and is usually less severe than the initial episode of louse-borne typhus.
- These findings suggest ehrlichiosis:
- Acute febrile illness characterized by headache and myalgia
- Rash in ¢ ¼50%; spares palms, soles, and face
- Thrombocytopenia, leukopenia (lymphopenia), hyponatremia, and elevated liver function tests
- These findings suggest anaplasmosis:
- Acute febrile illness characterized by headache and myalgia
- Thrombocytopenia, leukopenia (neutropenia), hyponatremia, and elevated liver function tests
Diagnostic Tests & Interpretation
Lab
- Serologic testing is the standard for laboratory diagnosis of rickettsial disease because the organisms are obligate intracellular bacteria and do not grow in culture.
- Serologic tests are available for all rickettsial organisms. There is some cross-reactivity among similar organisms.
- Serologic testing is often negative at the onset of illness and requires a convalescent (paired) sample done 2 " 3 weeks later for comparison. If the convalescent titer is 4-fold or greater than the acute, it is considered positive.
- Polymerase chain reaction (PCR) tests are rarely done in clinical labs and have significant inaccuracy given the similarities in genomes of these organisms.
- The Weil-Felix agglutination test has poor sensitivity and specificity and is not used in the United States.
Differential Diagnosis
- Before rash appears, constitutional symptoms associated with the spotted fevers result in a broad differential diagnosis. After rash appears, the diagnoses are more limited.
- Infectious:
- Measles
- Meningococcemia
- Secondary syphilis
- Coxsackievirus (e.g., hand-foot-and-mouth disease)
- Infectious mononucleosis
- Enteroviral infection
- Environmental (poisons)
- Drug hypersensitivity reaction (i.e., toxicodermatosis)
- Tumors: leukemia with thrombocytopenia
- Immunologic: idiopathic thrombocytopenia purpura
- Miscellaneous:
- Leukocytoclastic angiitis
- Erythema multiforme/Stevens-Johnson syndrome
Treatment
Medication
- The 1st-line antibiotic treatment for all rickettsial diseases is doxycycline. Therapy is most effective if instituted within the 1st week of illness.
- Antibiotics should be given for 7 " 14 days.
- Studies have shown that there is little risk of tooth staining in children <8 years old who receive doxycycline.
- In the case of rickettsial disease, the benefit of giving doxycycline far outweighs the risk of adverse effects.
Inpatient Considerations
Initial Stabilization
- Fluid resuscitation and respiratory support as indicated
- Antimicrobial therapy should be instituted as soon as the diagnosis is suspected and should not be delayed while awaiting serologic confirmation.
- Patients may require blood product transfusion in the case of consumptive coagulopathy or severe thrombocytopenia.
Ongoing Care
Prognosis
Improvement in the patient 's clinical status usually takes place within 1 " 2 weeks after therapy starts, depending on the severity of illness. This improvement may also be delayed if treatment is begun after the 1st week of illness.
Complications
- Venous thrombosis
- Disseminated intravascular coagulation
- Cardiac injury including endocarditis
- Severe disease is more common in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, cardiac insufficiency, or immunodeficiency.
Additional Reading
- Demma LJ, Holman RC, McQuiston JH, et al. Epidemiology of human ehrlichiosis and anaplasmosis in the United States, 2001 " 2002. Am J Trop Med Hyg. 2005;73(2):400 " 409. [View Abstract]
- Dumler JS, Dey C, Meier F, et al. Human monocytic ehrlichiosis: a potentially severe disease in children. Arch Pediatr Adolesc Med. 2000;154(8):847 " 849. [View Abstract]
- Pickering LK, Baker CJ, Kimberlin DW, et al, eds. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012:620 " 622.
- Purvis JJ, Edward MS. Doxycycline use for rickettsial disease in pediatric patients. Pediatr Infect Dis J. 2000;19(9):871 " 874. [View Abstract]
Codes
ICD09
- 083.9 Rickettsiosis, unspecified
- 082.0 Spotted fevers
- 081.9 Typhus, unspecified
- 082.40 Ehrlichiosis, unspecified
- 083.2 Rickettsialpox
- 082.8 Other specified tick-borne rickettsioses
- 082.3 Queensland tick typhus
- 082.49 Other ehrlichiosis
- 082.41 Ehrlichiosis chafeensis [E. chafeensis]
- 083.0 Q fever
- 082.1 Boutonneuse fever
- 081.0 Murine (endemic) typhus
- 081.2 Scrub typhus
- 083.8 Other specified rickettsioses
- 082.2 North Asian tick fever
- 082.9 Tick-borne rickettsiosis, unspecified
- 083.1 Trench fever
- 081.1 Brill 's disease
ICD10
- A79.9 Rickettsiosis, unspecified
- A77.0 Spotted fever due to Rickettsia rickettsii
- A75.9 Typhus fever, unspecified
- A77.40 Ehrlichiosis, unspecified
- A77.9 Spotted fever, unspecified
- A79.81 Rickettsiosis due to Ehrlichia sennetsu
- A77.49 Other ehrlichiosis
- A77.3 Spotted fever due to Rickettsia australis
- A77.1 Spotted fever due to Rickettsia conorii
- A77.8 Other spotted fevers
- A78 Q fever
- A79.0 Trench fever
- A77.2 Spotted fever due to Rickettsia siberica
- A79.89 Other specified rickettsioses
- A77.41 Ehrlichiosis chafeensis [E. chafeensis]
- A79.1 Rickettsialpox due to Rickettsia akari
SNOMED
- 409904000 disease due to Rickettsiales (disorder)
- 186771002 Spotted fevers
- 240613006 typhus group rickettsial disease (disorder)
- 77361002 Ehrlichiosis (disorder)
- 271425001 Scrub typhus (disorder)
- 186772009 Rocky Mountain spotted fever (disorder)
- 25668000 Murine typhus (disorder)
- 39111003 Louse-borne typhus (disorder)
- 13906002 Anaplasmosis (disorder)
- 82214002 Trench fever
- 416829003 Disease due to Rickettsia
FAQ
- Q: Should my child receive antibiotics if he is bitten by a tick in an area endemic to rickettsial disease?
- A: There is no role for prophylaxis against rickettsial diseases for patients who have suffered tick bites.
- Q: Are there differences between typhoid and typhus?
- A: Typhoid, or typhoid fever, is a separate entity from typhus. Typhoid is an enteric infection caused by Salmonella typhi and is unrelated to the rickettsial diseases.
- Q: If I contract a rickettsial illness, can I get that illness or a similar illness again?
- A: With the exception of scrub typhus, infection with a rickettsial organism confers immunity to other rickettsia within the same group.