Rickettsialpox is a mild, self-limited, zoonotic febrile illness characterized by eschar formation at the location of a mite bite, followed by the onset of systemic symptoms and a more generalized papulovesicular rash. The causative agent is Rickettsia akari, a member of the spotted-fever group of rickettsiae. [12]


R akari is an obligate intracellular gram-negative coccobacillus. Its vector is the colorless mite Liponyssoides sanguineus (formerly Allodermanyssus sanguineus), which is found on mice (most commonly the house mouse [Mus musculus]) and other rodents. These hosts serve as the reservoir for the disease. A sanguineus will bite humans when murine hosts are scarce. About 7-10 days after the painless bite, a papular skin lesion appears at the bite location and becomes vesicular with a surrounding area of erythema. An eschar forms and slowly heals. About 3-7 days after the initial skin lesion develops, patients may suddenly develop high-grade fever, chills, headaches, and myalgias with subsequent development of a sparse generalized papulovesicular rash.

Rickettsialpox is mild and self-limited and usually persists for about a week.



United States

Rickettsialpox occurs primarily in urban areas, where the density of mites, mice, and humans is high. Huebner et al first isolated and named rickettsialpox in 1946 in New York City. [3]

Rickettsialpox has been reported primarily in the northeastern and midwest United States (Boston, Mass; West Hartford, Conn; Philadelphia, Pa; Pittsburgh, Pa; and Cleveland, Ohio). Cases have also been reported in North Carolina, Arkansas, and Utah. [456R akari–like organisms have also been identified in wild rodents in Orange County, California. [7]

Although the prevalence of confirmed cases is very low, several reports suggest the disease is more common than previously thought. Serologic evidence of rickettsialpox exposure was found in 16% of 631 intravenous drug users in inner-city Baltimore, MD, and in 9% of 204 intravenous drug users in Harlem, NY. [89In addition, between 2001 and 2003, the number of clinical samples submitted to the Centers for Disease Control and Prevention (CDC) increased following the anthrax bioterror attack, reflecting an increased awareness of eschar-associated febrile illness. [10Prior to this, these clinical syndromes may have been misdiagnosed, or perhaps the infected persons did not seek medical attention. Consequently, rickettsialpox is widely believed to be an underrecognized and underreported clinical entity.

In 2007, about 14 cases of rickettsialpox were reported New York City (a rate of approximately 1.7 cases per 1,000,000 persons). Case reports increased in of 2001 and continued in 2002, following the anthrax attacks in New York City, New Jersey, Washington, D.C., and Florida. [11]


Internationally, rickettsialpox has been described in South Africa, Costa Rica, France, Italy, Turkey, Croatia, the Ukraine, Russia, and Korea. [41213]

A case report from 2012 described the first case of rickettsialpox in the Netherlands wherein the patient did not have any contact with mice or other animals and the cause of transmission unclear. [14There have been case reports of rickettsialpox in Mexico and suspected cases identified by serologic assays in Albania, Bosnia Herzegovina, Central African Republic, France, Germany, and Turkey. [15]


Rickettsialpox is a benign, self-limited disease. No fatalities have been reported. The incubation period varies from 10-21 days. Rickettsialpox usually resolves within 14-21 days; however, headache and lassitude may persist for another 1-2 weeks.


Rickettsialpox has no sexual predilection.


Rickettsialpox has no age predilection. It has been reported in patients aged 6 months to 72 years.



Following a mite bite, R akari proliferates locally in the skin. After 7-10 days, a firm, red papule 1-1.5 cm in diameter appears; in a few days, it vesiculates with a surrounding area of erythema. The lesion then ulcerates, forms an eschar, and slowly heals.

About 3-7 days after the appearance of the skin lesion, rickettsialpox may manifest as a sudden onset of high fever, chills, sore throat, rigor and profuse sweating, myalgias (especially backache), anorexia, and photophobia. Untreated, fever may last a week. Vertigo, conjunctival injection, cough, rhinorrhea, nausea, and vomiting sometimes occur. Headaches and neck stiffness may be severe. Regional lymphadenopathy at the draining site of the eschar is common, and generalized lymphadenopathy has also been reported. Lymphangitis is not a feature of rickettsialpox.

Approximately 2-3 days after the onset of systemic symptoms, the generalized papulovesicular rash of rickettsialpox erupts. This can involves palms and soles and is occasionally accompanied by an oropharyngeal enanthem. This rash typically lasts a week.


Patients with rickettsialpox may have high fever fluctuating between 101-104ºF.

The maculopapulovesicular exanthema is usually composed of 20-40 lesions but may range from 5-100. Features are as follows:

  • The lesions typically begin as papules with subsequent vesiculation, but may remain avesicular.
  • Lesions are usually scattered on the face, trunk, and extremities with no particular sequence of involvement. Patients may present with lesions on the tongue, buccal mucosa, and pharynx.
  • Lesions may also be present on palms and soles.
  • The lesions are typically asymptomatic but can be pruritic.
  • Rashes last a week. Scabs form but do not leave scars.

At the time of presentation, an eschar is present in at least 95% of affected individuals. The mite bite is painless and begins as an erythematous papule, which develops into a tense vesicle that ruptures to form a dark crust with surrounding induration. More than one eschar may be present. Features are as follows:

  • Mite bites can occur on any part of the body, including the hands, feet, face, and angle of the mouth (labial commissure). They do occur in covered areas.
  • Regional adenopathy may be present and is usually tender.


Rickettsialpox is caused by R akari and was first described in 1946.

Rickettsialpox is sporadically observed in many urban centers of the United States. The bloodsucking mite L sanguineus is the vector, and mice (typically M musculus) and other rodents are the reservoir.

When murine hosts are scarce, A sanguineus will bite humans.

No human-to-human transmission occurs.


Diagnostic Considerations

Human spotted fever secondary to Rickettsia parkeri infection

African tick bite fever secondary to Rickettsia africae infection

Mediterranean Spotted Fever

Scrub Typhus [1617]



Table 1. Characteristics of Similar Conditions (Open Table in a new window)



Generalized Rash

Clinical Features


Rickettsialpox secondary to R akari infection

A red papule with a vesicle in the center dries and forms a black eschar with surrounding induration. Multiple eschars are possible.

The papulovesicular rash is usually on the trunk and extremities; the palms, soles, and oral mucosa may also be involved.

The papule precedes the febrile illness and mild systemic symptoms. Regional lymphadenopathy may develop.

See Frequency

Chickenpox secondary to varicella zoster infection

The papule turns into a vesicle on an erythematous base and resembles a "dew drop on a rose petal."

The rash begins on the head and progresses to the trunk, arms, and then legs; vesicles are present in all stages.

It is common in children. No black eschar is present.


Mediterranean spotted fever secondary to Rickettsia conorii infection

At the site of a tick bite, a single eschar with a red halo forms.

The rash is generalized, involves the palms and soles, and is often maculopapular, occasionally petechial.

Fever, headache, myalgias may develop. The onset is abrupt. The disease may be severe in context of comorbidity.

North Africa, Middle East, Southern Europe

African tick bite fever secondary to R africae infection

Single or multiple eschars with regional lymphadenopathy

A scant generalized rash, vesicular or maculopapular, may be present. Conversely, the rash may be absent.

Fever, headache, myalgias, regional lymphadenopathy; associated with reports of subacute neuropathy

Sub-Saharan Africa, Caribbean

Human spotted fever secondary to R parkeri infection

Single or multiple eschars develop from erythematous papules.

Scant nonpruritic papules

Fever, headache, myalgias, arthralgias

United States

Scrub typhus secondary to Orientia tsutsugamushi infection

A vesicle or black scab appears on an erythematous base at the bite site.

Vesicles are usually on the trunk or extremities.

The rash fades within a few days; pneumonitis is common.

Asia-Pacific rim

Differential Diagnoses


Medical Care

Rickettsialpox is a self-limited disease; however, antibiotics hasten defervescence and provide relief of other systemic symptoms. A presumptive diagnosis of rickettsialpox can be made based on high clinical suspicion in the correct geographic context, and empiric antimicrobial therapy can be appropriately prescribed. The treatment of choice is doxycycline 100 mg administered orally twice daily until the patient has clinically recovered for approximately 48 hours. Usually, 5-7 days is sufficient. Supportive and symptomatic therapy may also be provided.


If antibiotics cause no response within 48 hours, seek an alternate diagnosis.


Medication Summary

A brief course of a tetracycline antibiotic is recommended. Quinolones may also be considered. Chloramphenicol is an alternate treatment but is not usually recommended because of substantial toxicity.


Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Doxycycline (Bio-Tab, Doryx, Vibramycin, Doxy)

Inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.