Background
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.
Pathophysiology
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.
The disease is mild and self-limited and usually persists for about a week.
Epidemiology
Frequency
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.[1]
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.[2, 3, 4]
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.[5, 6] In 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.[7] Prior 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.
International
Internationally, the disease has been described in South Africa, Costa Rica, France, Italy, Turkey, Croatia, the Ukraine, Russia, and Korea.[2, 8, 9]
Mortality/Morbidity
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.
Sex
Rickettsialpox has no sexual predilection.
Age
Rickettsialpox has no age predilection. It has been reported in patients aged 6 months to 72 years.
Huebner RJ, Stamps P, Armstrong C. Rickettsialpox. A newly recognized rickettsial disease. 1. isolation of the etiological agent. Public Health Report. 1946;61:1605.
Parola P. Rickettsia felis: from a rare disease in the USA to a common cause of fever in sub-Saharan Africa. Clin Microbiol Infect. Jul 2011;17(7):996-1000. [Medline].
Schulze TL, Jordan RA, White JC, Roegner VE, Healy SP. Geographical distribution and prevalence of selected Borrelia, Ehrlichia, and Rickettsia infections in Amblyomma americanum (Acari: Ixodidae) in New Jersey. J Am Mosq Control Assoc. Sep 2011;27(3):236-44. [Medline].
Breitschwerdt EB, Hegarty BC, Maggi RG, Lantos PM, Aslett DM, Bradley JM. Rickettsia rickettsii transmission by a lone star tick, North Carolina. Emerg Infect Dis. May 2011;17(5):873-5. [Medline].
Comer JA, Tzianabos T, Flynn C, Vlahov D, Childs JE. Serologic evidence of rickettsialpox (Rickettsia akari) infection among intravenous drug users in inner-city Baltimore, Maryland. Am J Trop Med Hyg. Jun 1999;60(6):894-8. [Medline].
Comer JA, Diaz T, Vlahov D, Monterroso E, Childs JE. Evidence of rodent-associated Bartonella and Rickettsia infections among intravenous drug users from Central and East Harlem, New York City. Am J Trop Med Hyg. Dec 2001;65(6):855-60. [Medline].
Paddock CD, Zaki SR, Koss T, Singleton J Jr, Sumner JW, Comer JA, et al. Rickettsialpox in New York City: a persistent urban zoonosis. Ann N Y Acad Sci. Jun 2003;990:36-44. [Medline].
Bailey MS, Trinick TR, Dunbar JA, Hatch R, Osborne JC, Brooks TJ, et al. Undifferentiated febrile illnesses amongst British troops in Helmand, Afghanistan. J R Army Med Corps. Jun 2011;157(2):150-5. [Medline].
Bolaños-Rivero M, Santana-Rodriguez E, Angel-Moreno A, Hernández-Cabrera M, Limiñana-Canal JM, Carranza-Rodríguez C, et al. Seroprevalence of Rickettsia typhi and Rickettsia conorii infections in the Canary Islands (Spain). Int J Infect Dis. Jul 2011;15(7):e481-5. [Medline].
Anderson GW Jr, Osterman JV. Host defenses in experimental rickettsialpox: resistance of C3H mouse sublines. Acta Virol. Jun 1980;24(4):294-6. [Medline].
Angeloni VL, Keller RA, Walker DH. Rickettsialpox-like illness in a traveler. Mil Med. Sep 1997;162(9):636-9. [Medline].
Boyd AS. Rickettsialpox. Dermatol Clin. Apr 1997;15(2):313-8. [Medline].
Brettman LR, Lewin S, Holzman RS, Goldman WD, Marr JS, Kechijian P, et al. Rickettsialpox: report of an outbreak and a contemporary review. Medicine (Baltimore). Sep 1981;60(5):363-72. [Medline].
Heymann WR. Rickettsialpox. Clin Dermatol. May-Jun 1996;14(3):279-82. [Medline].
Kass EM, Szaniawski WK, Levy H, Leach J, Srinivasan K, Rives C. Rickettsialpox in a New York City hospital, 1980 to 1989. N Engl J Med. Dec 15 1994;331(24):1612-7. [Medline].
Kass EM, Szaniawski WK, Levy H, Leach J, Srinivasan K, Rives C. Rickettsialpox in a New York City hospital, 1980 to 1989. N Engl J Med. Dec 15 1994;331(24):1612-7. [Medline].
Kemper CA, Spivack AP, Deresinski SC. Atypical papulovesicular rash due to infection with Rickettsia conorii. Clin Infect Dis. Oct 1992;15(4):591-4. [Medline].
Kenyon RH, Pedersen CE Jr. Immune responses to Rickettsia akari infection in congenitally athymic nude mice. Infect Immun. May 1980;28(2):310-3. [Medline].
Krinsky WL. Does epizootic lymphocytic choriomeningitis prime the pump for epidemic rickettsialpox?. Rev Infect Dis. Nov-Dec 1983;5(6):1118-9. [Medline].
Krusell A, Comer JA, Sexton DJ. Rickettsialpox in North Carolina: a case report. Emerg Infect Dis. Jul 2002;8(7):727-8. [Medline].
McDade JE, Black CM, Roumillat LF, Redus MA, Spruill CL. Addition of monoclonal antibodies specific for Rickettsia akari to the rickettsial diagnostic panel. J Clin Microbiol. Oct 1988;26(10):2221-3. [Medline].
Myers SA, Sexton DJ. Dermatologic manifestations of arthropod-borne diseases. Infect Dis Clin North Am. Sep 1994;8(3):689-712. [Medline].
Ozturk MK, Gunes T, Kose M, Coker C, Radulovic S. Rickettsialpox in Turkey. Emerg Infect Dis. Nov 2003;9(11):1498-9. [Medline].
Paddock CD, Koss T, Eremeeva ME, Dasch GA, Zaki SR, Sumner JW. Isolation of Rickettsia akari from eschars of patients with rickettsialpox. Am J Trop Med Hyg. Oct 2006;75(4):732-8. [Medline].
Paddock CD, Sumner JW, Comer JA, Zaki SR, Goldsmith CS, Goddard J, et al. Rickettsia parkeri: a newly recognized cause of spotted fever rickettsiosis in the United States. Clin Infect Dis. Mar 15 2004;38(6):805-11. [Medline].
Paterson PY, Taylor W. Rickettsialpox. Bull N Y Acad Med. Jul 1966;42(7):579-87. [Medline].
Radulovic S, Feng HM, Morovic M, Djelalija B, Popov V, Crocquet-Valdes P, et al. Isolation of Rickettsia akari from a patient in a region where Mediterranean spotted fever is endemic. Clin Infect Dis. Feb 1996;22(2):216-20. [Medline].
Rickettsialpox. Lancet. Jan 16 1982;1(8264):148. [Medline].
Saini R, Pui JC, Burgin S. Rickettsialpox: report of three cases and a review. J Am Acad Dermatol. Nov 2004;51(5 Suppl):S137-42. [Medline].
Walker DH. Rickettsioses of the spotted fever group around the world. J Dermatol. Jun 1989;16(3):169-77. [Medline].
Walker DH, Hudnall SD, Szaniawski WK, Feng HM. Monoclonal antibody-based immunohistochemical diagnosis of rickettsialpox: the macrophage is the principal target. Mod Pathol. May 1999;12(5):529-33. [Medline].
Wong B, Singer C, Armstrong D, Millian SJ. Rickettsialpox. Case report and epidemiologic review. JAMA. Nov 2 1979;242(18):1998-9. [Medline].
| Disease | Rash/Eschar | Generalized Rash | Clinical Features | Geography |
| 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. | Worldwide |
| 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 |

