The initial RMSF presentation is characterized by the classical triad of fever, headache and rash, which begins to appear after 3 to 4 days from pathogen exposure. A history of tick bite is present only in two thirds of the cases, because the bite itself is painless and subjects do not even remember being bitten. The incubation period may span from 2 to 8 days, and a clear picture of the illness becomes evident only in the second week from exposure, with the appearance of other classical signs such as muscle and joint pain, lack of appetite and forgetfulness.

Most frequent are also CNS symptoms like encephalitis (which later progresses to stupor, delirium and coma) and gastrointestinal signs, like nausea, vomiting and abdominal pain. It is important to note that this clinical picture is nonspecific and the combination of symptoms varies greatly from patient to patient. Thus, Rocky Mountain spotted fever is difficult to diagnose and frequently confused with other nonspecific febrile illnesses. For this reason RMSF has also been defined as the “great imitator” of other diseases [15].

Rash is among the most important pathognomic features of Rocky Mountain spotted fever and usually appears only by the second or third day from exposure. It has a typical centripetal or “inward” diffusion pattern. It begins at the extremities and moves towards the trunk and the central parts of the body. Rash initially appears with blanching maculopapular lesions, which slowly turn in petechial lesions after 6 days on the palms of the hands and the soles of the feet. The prompt recognition of maculopapular eruption is vital for diagnosis, because the appearance of petechial spots is a clear sign of the RMSF advanced stage.

The diagnosis of Rocky Mountain spotted fever is heavily based on laboratory findings, through methods like blood count (CBC), electrolytes and renal and liver function tests. CT and MRI are strongly indicated, especially for those cases showing altered mental status, together with lumbar puncture if the presence of meningitis is suspected. Chest radiography and electrocardiography are also indicated, to reveal pulmonary and myocardial complications.

Rocky Mountain spotted fever is usually treated with doxycycline-based antibiotic therapy. Treatment should be initiated immediately, without waiting for the laboratory confirmation. Preventive treatment for patients with tick bite history is not recommended, because it might only delay the disease presentation [16] and reduce the prospect of recovery. Chloramphenicol is a valid alternative to doxycycline, even though less used because of its numerous side effects.

The vascular inflammation triggered by Rickettsia rickettsii causes the blood vessels to leak or form clots, and the loss of fluid ultimately results in loss of circulation at the extremities of the body, which may even become paralyzed or gangrenous without prompt treatment. The disease determines a series of severe long-term health problems to the organs and tissues encountered along the way, which mainly involve the following systems:

• Nervous system, like headache, confusion, seizures, delirium, and in general signs of encephalitis.
• Respiratory system, like  pneumonia, pulmonary edema and lung failure in the most severe cases.
• Gastrointestinal problems, like the loss of bowel control.
• Renal system, like loss of bladder control or kidney failure.

Mortality rate depends on a series of factors, like age [7], race [8], gender and wrong diagnosis [9] [10] due to partial or total absence of the key RMSF features [7] [11]. It also seems to have significantly declined since 1980s, from 4% in 1982 to 1,4% and less in 2002 [12] [13] [14].

Rickettsia rickettsii is an obligate intracellular parasite which thrives in the cytoplasm of its eukaryotic host cells, especially those belonging to the endothelial tissue [2]. The natural RMSP hosts are ticks of the genus Dermacentor, like Dermacentor variabilis (the American dog tick), which largely feeds on big mammals. Because of this intra-species transmission, RMSP is a classical example of zoonosis. Dog is the excellent vector for Rickettsia rickettsii, given its high susceptibility to this bacterium and its higher rate to tick exposure.

Cases of RMSF have been reported in the United States since 1920’s. According to the most recent statistical data over the last decade, RMSF prevalence has increased, from an initial rate of 2 cases per million persons in 2000 to a final one of over 6 cases per million persons in 2010 [3]. By contrast, fatality has heavily declined over the same period, arriving at the current rate of 0,5% [3], perhaps as a consequence of the positive effects of better diagnostic and surveillance practices. No RMSP case has been reported outside the Americas, even though a variety of related diseases have been described in other continents. In any case, a clear picture of RMSP incidence worldwide still remains largely unknown.

Peaks of RMSP have been observed in North Carolina, Oklahoma, Arkansas, Tennessee, and Missouri, with more than the 60% of the cases reported. The peaks mostly appear in summer, between June and July, but some cases can also spring up in other months of the year. This seasonality varies from state to state, and it is strictly linked to the life cycle of the vector involved.

The persons at risk are mostly American Indians, males and people over 70 years of age [4]. Additional factors might be the exposure to dogs and wooded areas and the state of the immune system [4]. Particularly susceptible are also children under 10 years of age [3] [4] [5].

The main site of Rickettsia rickettsii is the endothelium of blood vessels, where the bacterium easily propagates tdue to the mechanism of actin polar polymerization [6].

The endothelial cell injury triggers a series of important physiological modifications, like increased vascular permeability, edema, hypotension and hypoalbuminemia, which cause the blood vessels to become blocked and inflamed (vasculitis). This systemic vascular damage is soon followed by a series of severe complications, like interstitial pneumonia.

RMSP prevention is very easy if a few simple precautions are followed, like wearing long pants and sleeves and using insect repellents. In the areas where RMSP cases have been reported, you are also strongly advised to tick-proof your yard and check yourself for ticks.

Rocky Mountain spotted fever (RMSP) is spread to humans by ticks. Very difficult to diagnose, especially in the early stages, its typical signs include sudden fever, headache and muscle pain. Without proper treatment, this disease may sometime be lethal [1]. Its name is a misnomer, since although very frequent in the Rocky Mountain region, where it was first recognized towards the end of the nineteenth century with the name of “black measles”, the illness has been diagnosed throughout the American continent, from as far north as Canada to as far south as Central America.

Rocky Mounatin spotted fever (RMSP) is an illness caused by Rickettsia rickettsii, a bacterium belonging to a group responsible for diseases such as typhus and rickettsialpox. Its natural hosts are the ticks of the species Dermacentor variabilis (the American dog tick), which largely feeds on big mammals. Once in the body, the bacterium infects the endothelium of blood vessels, causing vascular inflammation and thereby a series of severe complications, like interstitial pneumonia and a rash with the characteristic “inward” diffusion patters. The initial symptoms of fever, rush and headache are soon followed by muscle pain and other complications of key apparatuses such as the nervous and gastrointestinal systems. The RMSP is usually treated with doxycycline-based antibiotic therapy, but chloramphenicol can be a valid alternative.

1. Masters EJ, Olson GS, Weiner SJ, Paddock CD. Rocky Mountain spotted fever: a clinician's dilemma. Arch. Intern. Med. 2003 163 (7): 769–74
2. Walker DH. Rickettsiae. In: Barron's Medical Microbiology (4th ed.). Galveston (TX): University of Texas Medical Branch at Galveston; 1996. Chapter 38. 
3. Openshaw JJ, Swerdlow DL, Krebs JW, Holman RC et al.  Rocky Mountain spotted fever in the United States, 2000-2007: Interpreting contemporary increases in incidence. Am J Trop Med Hyg. 2010 Jul;83(1):174-82.
4. Dahlgren FS, Holman RC, Paddock CD, Callinan LS, McQuiston JH. Fatal Rocky Mountain spotted fever in the United States, 1999–2007. Am J Trop Med Hyg(86)2012, 713
5. Demma LJ, Traeger MD, Nicholson WL, Paddock CD et al. Rocky Mountain spotted fever from an unexpected tick vector in Arizona. N Engl J Med. 2005 Aug 11;353(6):587-94.
6. Carlsson F, Brown EJ. Actin-based motility of intracellular bacteria, and polarized surface distribution of the bacterial effector molecules. J Cell Physiol. 2006 Nov; 209 (2):288-96.
7. Holman RC, Paddock CD, Curns AT, Krebs JW, McQuiston JH, Childs JE. Analysis of risk factors for fatal Rocky Mountain spotted fever: evidence for superiority of tetracyclines for therapy. J Infect Dis. 2001; 184:1437-1444.
8. Helmick CG, Bernard KW, D'Angelo LJ. Rocky Mountain spotted fever: clinical, laboratory, and epidemiological features of 262 cases. J Infect Dis. 1984;150:480-488.
9. Buckingham SC, Marshall GS, Schutze GE, Woods CR et al. Clinical and laboratory features, hospital course, and outcome of Rocky Mountain spotted fever in children. J Pediatr. 2007;150:180-184.
10. Chapman AS, Bakken JS, Folk SM, Paddock et al. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever, ehrlichioses, and anaplasmosis--United States: a practical guide for physicians and other health-care and public health professionals. MMWR Recomm Rep. 2006;55:1-27.
11. Hattwick MA, Retailliau H, O'Brien RJ, Slutzker M, Fontaine RE, Hanson B.Fatal Rocky Mountain spotted fever. JAMA. 1978;240:1499-1503.
12. Treadwell TA, Holman RC, Clarke MJ, Krebs JW, Paddock CD, Childs JE. Rocky Mountain spotted fever in the United States, 1993-1996. Am J Trop Med Hyg. 2000;63:21-26.
13.  Dalton MJ, Clarke MJ, Holman RC, Krebs JW et al. National surveillance for Rocky Mountain spotted fever, 1981-1992: epidemiologic summary and evaluation of risk factors for fatal outcome. Am J Trop Med Hyg. 1995;52:405-413.
14. Chapman AS, Murphy SM, Demma LJ, Holman RC et al. Rocky Mountain spotted fever in the United States, 1997-2002. Vector Borne Zoonotic Dis. 2006;6:170-178.
15. Sexton DJ, Corey GR. Rocky Mountain "spotless" and "almost spotless" fever: a wolf in sheep's clothing.Clin Infect Dis. Sep 1992;15(3):439-48
16. Gammons M, Salam G. Tick removal. Am Fam Physician 2002 66 (4): 643–5.