Pathophysiology of Rickettsial Infection
Rickettsial infection causes systemic vasculitis through direct invasion and replication within vascular endothelial cells, leading to increased capillary permeability, microhemorrhage, and end-organ damage that manifests as the characteristic clinical syndrome of fever, headache, and rash. 1
Cellular and Molecular Mechanisms
Primary Target Cells
- Rickettsia are obligate intracellular bacteria that primarily infect vascular endothelial cells of small and medium vessels, and less commonly the underlying smooth muscle cells 1
- These organisms can only replicate within the cytoplasm of eukaryotic host cells, as they cannot be grown on artificial media 2
- The bacteria are small, Gram-negative bacilli belonging to the order Rickettsiales within the α-Proteobacteria 2
Vascular Injury Cascade
- Pathogen-mediated injury to the vascular endothelium results in increased capillary permeability, microhemorrhage, and platelet consumption 1
- The hallmark of rickettsial infection is microvasculitis causing microinfarcts in various organs throughout the body 3
- When transmitted to humans, pathogenic rickettsiae multiply in endothelial cells and cause vasculitis, leading to various clinical manifestations 2
Systemic Manifestations
Early-Stage Pathophysiology
- Infection leads to systemic vasculitis that manifests externally as characteristic petechial skin lesions 1
- The classic rash begins as small blanching macules that progress to maculopapular lesions with central petechiae, reflecting progressive vascular damage 1
Late-Stage Complications
- If disease progresses untreated, microvascular leakage results in life-threatening complications including:
Metabolic Derangements
- Hyponatremia occurs as a result of appropriate secretion of antidiuretic hormone in response to hypovolemia caused by capillary leak 1
- Laboratory abnormalities reflect the systemic nature of the vasculitis and include thrombocytopenia, leukopenia, elevated hepatic transaminases, and anemia 4, 5
Transmission and Vector Biology
Arthropod Vector Maintenance
- Rickettsia are primarily transmitted by arthropod vectors, particularly ticks, in which they can be maintained through transstadial and transovarial transmission 2
- Maintenance in vector systems is driven by both vertical and horizontal transmission strategies 6
- Humans become infected when bitten or upon contact of broken skin or mucous membranes with infected secretions from an arthropod vector 7
Clinical Pitfalls
The incubation period is generally shorter (5 days or less) in patients who develop severe disease, making early recognition critical 1. The nonspecific early presentation—fever, headache, and myalgia without rash—frequently leads to misdiagnosis even in high-awareness areas 4. Delay in recognition and treatment is the most important factor associated with risk for death from rickettsial diseases 4.