Clinical meaning
Rocky Mountain spotted fever is the most severe rickettsial disease in North America, caused by Rickettsia rickettsii, an obligate intracellular Gram-negative bacterium transmitted through tick bites (primarily Dermacentor variabilis — American dog tick, and Dermacentor andersoni — Rocky Mountain wood tick). After inoculation, R. rickettsii targets vascular endothelial cells, invading them through induced phagocytosis and multiplying within the cytoplasm. The organisms spread from cell to cell using actin-based motility. Endothelial infection causes widespread small vessel vasculitis: endothelial damage increases vascular permeability, leading to edema, hypovolemia, and hypotension. Damaged endothelium activates the coagulation cascade, potentially causing disseminated intravascular coagulation (DIC). Perivascular inflammation involves virtually every organ system, explaining the diverse clinical manifestations. The classic triad is fever, headache, and rash — but the rash may not appear until day 3-5 of illness, and up to 10% of cases never develop a rash ('spotless' RMSF). The characteristic rash begins on the wrists and ankles as blanching macules, then spreads centripelally (toward the trunk), becomes petechial (non-blanching), and may involve the palms and soles (a distinguishing feature). Fatality rate without treatment is 20-25%; with prompt doxycycline treatment, mortality drops to <5%. The key clinical pearl is: DO NOT WAIT for the rash to treat — empiric doxycycline should be started when RMSF is clinically suspected based on fever, headache, and tick exposure in an endemic area.