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Snapshot
  • A 24-year-old man presents to his primary care physician for a rash. He had been hiking in Tennessee during a retreat at his new job last week. He reports that he pulled a tick off of himself, though he did not think much of it at the time. Since then, he has had fevers and headaches daily. A few days after the onset of fever, he developed a rash that started on his wrists and ankles and now has spread to his chest. On physical exam, there are small blanching erythematous macules on his chest and petechiae on his extremities. His palms and soles are spared. He is started on empiric antibiotics. (Rocky Mountain spotted fever)
Introduction
  • Classification
    • Rickettsia
      • spotted fever group (tick-borne)
        • Rickettsia rickettsii (Rocky Mountain spotted fever)
          • most common
        • Rickettsia conorii (Mediterranean spotted fever)
        • Rickettsia akari (Rickettsialpox)
        • Rickettsia africae (African tick bite fever)
      • typhus group
        • Rickettsia prowazekii (louse-borne epidemic typhus)
        • Rickettsia typhi (flea-borne murine typhus)
    • Orientia
      • scrub typhus group
        • Orientia tsutsugumushi (mite-borne)
          • formerly Rickettsia tsutsugamushi
    • obligate intracellular gram-negative bacteria
    • transmission via blood-feeding arthropod vectors
      • ticks, lice, and flea
  • Epidemiology
    • incidence depends on geographic distribution of the vector
    • North America (R. rickettsii and R. akari)
    • Europe (R. conorii)
    • Asia (R. conorii and O. tsutsugamushi)
    • Africa (R. africae and R. conorii)
    • South America (R. prowazekii)
    • worldwide (R. typhi)
  • Pathogenesis
    • the bacteria is transmitted into the human body via arthropod saliva when bitten
    • vascular endothelial cells are targeted by the bacteria
    • replication can cause local hemorrhage
  • Prognosis
    • most resolve with treatment
    • epidemic typhus (R. prowazekii) may recur (Brill-Zinsser disease)
    • Rocky Mountain spotted fever (R. rickettsii) has highest mortality
Presentation
  • Symptoms
    • fever
    • rash
    • headache
  • Physical exam
Rickettsial Diseases
Clinical Manifestations of Rickettsial Diseases
Disease Vector Rash Eschar Regional Lymphadenopathy
Rocky Mountain spotted fever (R. rickettsii)
  • Tick
  • Macular
  • Petechial
  • Purpuric
  • Spreads centripetally (extremities to trunk)
  • No
  • No
Mediterranean spotted fever (R. conorii)
  • Tick
  • Macular
  • Papular
  • Purpuric
  • Yes
  •  No
Rickettsialpox (R. akari)
  •  Mite
  • Vascular
  • Papular
  • On trunk and extremities
  • Yes
  •  Yes
African tick bite fever (R. africae)
  •  Tick
  • Vesicular
  • Maculopapular
  • Yes, multiple
  •  Yes
Epidemic tyhpus (R. prowazekii)
  •  Louse
  • Macular
  • Papular
  • Petechial
  • Spreads centrifugally (trunk to extremities)
  • No
  • No
Murine typhus (R. typhi)
  •  Flea
  • Macular
  • Papular
  • Petechial
  • Spreads centrifugally
  • No
  •  No
Scrub typhus (O. tsutsugamushi)
  •  Mite
  • Macular
  • Pale
  •  Yes
  • Yes
 
Studies
  • Labs
    • detection of immunoglobulin G (IgG) is confirmatory
    • Weil-Felix test
      • serum cross-reacts with proteus antigens
    • may have thrombocytopenia and elevated liver function tests
  • Skin biopsy
    • visualization of infecting organism on tissue
  • Making the diagnosis
    • most cases are clinically diagnosed and confirmed with laboratory evaluation
Differential
  • Q fever
    • distinguishing factors
      • also an intracellular gram-negative bacteria
      • manifests as fever and pneumonia or endocarditis
      • does not manifest with rash
Treatment
  • Management approach
    • empiric treatment is started as soon as possible
  • Medical
    • doxycycline
      • indication
        • first-line therapy
    • chloramphenicol
      • indication
        • contraindications to doxycycline
Complications
  • Neurologic sequelae
  • Peripheral gangrene
  • Reactive arthritis
 

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Questions (1)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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