Rickettsialpox is caused by Rickettsia akari, which is transmitted by the bite of the house-mouse mite Liponyssoides sanguineus [Huebner, Stamps and Armstrong, 1946; Huebner et al., 1947; Huebner, Jellison and Pomerantz., 1946]. The disease was named rickettsialpox because of its resemblance to chickenpox [Huebner, Stampls and Armstrong, 1946]. It occurs primarily in urban areas, where the density of mites, mice, and humans is high [Koss et al., 2003]. Huebner and his collaborators first isolated Rickettsia akari from a patient, mites, and a naturally infected house mouse in Queens, New York in 1946 [Huebner, Stamps and Armstrong, 1946; Huebner et al., 1947; Huebner, Jellison and Pomerantz., 1946].
Rickettsialpox is almost certainly under-recognized and under-reported [Koss et al., 2003]. The bioterrorism attacks of October 2001 may have led to increased awareness and detection of this disease [Koss et al., 2003]. Prior to that time, these clinical syndromes may have been misdiagnosed, or perhaps the infected persons did not seek medical attention. Since the 1960s, only single case reports and small case series have been published, and most of these cases have occurred in New York City [Huebner, Stamps and Armstrong, 1946; Huebner et al., 1947; Huebner, Jellison and Pomerantz., 1946; Koss et al., 2003; Kass et al., 1994], but the disease has also been reported in other large cities in the eastern United States [Koss et al., 2003; Kass et al., 1994] as well as in Europe, South Africa and Latin America [Parola et al., 2013]. The presence of an eschar is a key clinical feature of rickettsialpox [Huebner, Stamps and Armstrong, 1946; Huebner et al., 1947]. This develops at the location of a mite bite, followed by the onset of systemic symptoms and a more generalized papulovesicular rash [Huebner, Stamps and Armstrong, 1946; Huebner et al., 1947; Huebner, Jellison and Pomerantz., 1946].
The most common disease that mimics rickettsialpox is chickenpox [Huebner, Stamps and Armstrong, 1946]. However, rickettsialpox characteristically has an eschar whereas chickenpox does not. In addition, in rickettsialpox, the rash consists of papulovesicles whereas in chickenpox the rash is vesicular and appears in crops [Heininger et al., 2006]. Finally, chickenpox usually presents with many more skin lesions than rickettsialpox.
Rickettsialpox has also been confused with cutaneous anthrax. This underscores the importance of clinicians' ability to promptly recognize and definitively diagnose rickettsialpox [Koss et al., 2003]. Patients with cutaneous anthrax characteristically have local edema out of proportion to the size of the lesions and gram stain of these lesions should reveal nonsporulating gram-positive rods [CDC 2001]. Rickettsialpox can also be confused with other rickettsial diseases, including Mediterranean spotted fever caused by Rickettsia conorii [Raoult et al., 1986], African tick bite fever [Owen et al., 2006], Rickettsia parkeri infection [Parola et al., 2013], and scrub typhus [Paddock et al., 2006]. All of these infections may be associated with eschars, but only African tick bite fever has rash that is typically or occasionally vesicular [Owen et al., 2006; Parola et al., 2013]. Rickettsia africae, the agent of African tick bite fever, is endemic in Africa - including Madagascar where our patient had recently travelled [Parola et al., 2013] - which made the diagnosis of our patient challenging.
The diagnosis of rickettsialpox is mainly a clinical one based on characteristic symptoms and signs [Huebner, Stamps and Armstrong, 1946; Huebner et al., 1947; Huebner, Jellison and Pomerantz., 1946; Koss et al., 2003]. It can be established retrospectively by documenting a fourfold rise in convalescent titers of complement fixation or indirect fluorescent antibodies using spotted fever group antigens [Koss et al., 2003]. Direct immunofluorescence can be used to identify rickettsial organisms in paraffin-embedded biopsy tissue from patients with rickettsialpox [Kass et al., 1994]. A definitive diagnosis can be made by isolation of Rickettsia akari from skin eschars [Paddock et al., 2006], or by a real-time multiplex polymerase chain reaction (PCR) that can specifically identify Rickettsia akari in formalin-fixed paraffin-embedded skin biopsy specimens [Denison et al., 2014], as in our case. Such tests are available through most state health departments and the Centers for Disease Control and Prevention [Koss et al., 2003].
Most patients with rickettsialpox have a mild illness and full recovery can be expected even without treatment [Kass et al., 1994]. The treatment of choice for rickettsialpox is doxycycline (100 mg orally every 12 hours) until the patient has been afebrile and clinically well for 48 to 72 hours [Kass et al., 1994].
In conclusion, rickettsialpox should be considered as a differential diagnosis in the setting of an eschar and a papulovesicular rash. Clinicians should be familiar with the clinical presentation and diagnostic features of rickettsialpox because it may be confused with more serious diseases, such as cutaneous anthrax [Koss et al., 2003] or chickenpox [Huebner, Stamps and Armstrong, 1946]. It is a self-limited disease; however, antibiotics hasten defervescence and provide relief of other systemic symptoms.