1. Tick-Borne Diseases
Stephen J. Gluckman, M.D.

2. Tick-Borne Diseases Lyme Disease Babesiosis Ehrlichiosis “Tick Typhus”
Rocky Mountain Spotted Fever
African Tick Typhus
Tularemia
Relapsing fever
Powassan
Tick Paralysis
STARI

3. An adult female Ixodes scapularis (blacklegged tick)
An adult female Dermacentor variabilis
(American dog tick)
An adult female Amblyomma americanum
(lone star tick)

5. Lyme Disease Clinical Presentations A few things to clarify
Erythema migrans
Carditis
Transient heart block
Myocarditis
Neurological
VII CN palsy
Aseptic meningitis
Radiculoneuritis
Lyme Encephalopathy
Rheumatologic
Acute pauci-articular arthritis

6. Where Do You See Lyme Disease?
Throughout the world

7. National Lyme Disease Risk Map with Four Categories of Risk
(CDC)

8. Borrelia Burgdorferi B. burgdorferi is not from Mars
B. Burgdorferi is not from another dimension
B. Burgdorferi is just another bug

9. How Big is the Ixodes Tick?
1-2 mm

10. Ixodes Ticks

11. Diagnosing Erythema Migrans
ANY LARGE RED PATCH WITHOUT ANOTHER EXPLANATION IS ERYTHEMA MIGRANS

14. EM or Tick Bite Reaction?
Incubation
7-10 days
Hours
Local Symptoms
Rare
Pruritus
Size
> 5 cm
Small
Expands
Over Days
Over Hours
Resolves
Over Weeks
Systemic Symptoms
Common

15. Erythema Migrans Things to remember
It is a clinical diagnosis, not a laboratory diagnosis
It is NEVER an emergency
“Target” lesion only occurs in 30%
Any big red patch is EM unless you have another explanation

16. Lyme Disease and VII CN Palsy
Differential Diagnosis
HSV (was idiopathic)
HIV
Herpes Zoster
Local Infection/Trauma/Tumor
Sarcoidosis
Lyme
More likely with: preceding or present erythema migrans

17. Lyme Disease and VII CN Palsy
Should you treat empirically?
Tick time of year
Potential tick exposure
Bilateral
“Diagnosis”
Lyme Serology
Lumbar Puncture?

18. Lyme Radiculoneuropathy
Differential Diagnosis
Diabetes
Herpes zoster (sine herpete)
Herniated disc
Collapsed Vertebral body
Syphilis

19. Case
45 year old who has had several years of “low grade” fevers, painful lymph nodes, scratchy throat, and mental cloudiness
He has been treated with oral doxycycline, azithromycin, and paromomycin.
He has also been treated with three courses of IV ceftriaxone totaling 5 months
He has had line related of Staphylococcus aureus bacteremia and ceftriaxone induced acute cholecystitis
Is this resistant neuroborreliosis?

20. LYME ENECEPHALOPATHY TO DIAGNOSE NEED BOTH
Objective evidence of neurological disease
Objective evidence of B. burgdorferi in the CNS
Lack of response related to:
Incorrect diagnosis
Impatience
Permanent damage

21. When Should One Think of Lyme Arthritis?
Monoarticular or pauciarticular
Typically knee
Differential Diagnosis: septic, crystal, rheumatoid, Reiter’s
Class II fluid
Arthralgias can be part of early Lyme Disease, but they are usually associated with EM and do not become chronic

22. Major Clinical Error
Chronic fatigue, chronic diffuse aching, recurrent sore throats, lymphadynia, and “low grade” fevers are not symptoms of active Lyme disease.

23. Lyme Serology
Misunderstandings about the use of serological testing for Lyme disease is the primary reason for the misunderstanding of this relatively uncomplicated infectious disease.
“Real” Lyme disease is generally easy to diagnose and treat
Diseases misdiagnosed as Lyme disease are not

24. There is NO TEST for Lyme Disease

25. Interpreting Lyme Serology
What is a positive test?
Positive screening by ELISA or IFA plus a positive western blot
What is a negative test?
Negative screening or positive screening with a negative Western Blot
(2nd National Conf. on Serol Dx of LD MMWR 1995;4:590)

26. What is a positive western blot?
An IGM Western Blot is considered positive if 2 of 3 specific bands are present.
An IGG Western Blot is considered positive if 5 of 10 specific bands are present.
Otherwise they are negative AND a positive screening serology with a negative WB is a negative test.

27. Other Diagnostic Tests
Culture
Low sensitivity, high specificity
Unapproved tests
PCR on blood or urine
Urinary Antigen Testing
Borreliacidal Antibody Test (Gundersen test)
Immune Complex Disruption
T-cell Proliferative Response

28. Common Testing Errors Not establishing a true positive test
Not understanding that a positive serology does not mean disease
Treating to eliminate antibodies
Antibodies persist and vary in titer
Treating a positive IgM alone: IgM may persist and is not helpful in disease beyond 1 month
Believing that a false negative test is frequent: False negatives are very rare other than in EM
Treating on the basis of an unestablished test

29. So, what is the consequence of misunderstanding the serology?
THE CREATION OF MYTHS
An entire syndrome (disease?) has been created that does not exist
A belief that the serology is not good.
A belief that Lyme disease is difficult to treat.

30. How Good is the Treatment of Lyme Disease?
VERY GOOD
There Rarely is a Reason to Retreat a Patient

31. Lyme Disease Treatment
Oral
Doxycycline 100 mg BID
Amoxicillin 500 mg TID
Cefuroxime axetil 500 mg BID
Parenteral
Ceftriaxone 2 gm IV daily
Cefotaxime 2 gm IV Q8H

32. Lyme Disease Treatment
Erythema migrans
Oral x d
VII cranial nerve palsy
Oral x d
Acute meningitis
Parenteral x d (can finish with oral)
Cardiac
1st or 2nd degree block: Oral x d
3rd degree block or myocarditis: parenteral x d

33. Lyme Disease Treatment
Arthritis
Oral x 28 d
Encephalopathy
Parenteral x 28 d
Neuropathy
Persistent arthritis after two courses of therapy or other chronic symptoms
Symptomatic therapy

34. What About the Newer Antibiotics for Lyme Disease
There is no advantage for azithromycin, clarithromycin, cefixime, cefuroxime, etc….
Do Not Use Them!

35. LYME DISEASE Concept Summary
23 year old with 4 months of diffuse aching and fatigue.
Lyme serology: EIA (+)
IgG Western Blot: 2 bands
IgM Western Blot: 1 band
Is this Lyme disease? NO

36. LYME DISEASE Concept Summary
41 year old who has had difficulty remembering names for the past several years.
Lyme serology: EIA: (-)
Western blot IgG (-)
Western blot IgM (+)
Is this Lyme disease? NO

37. LYME DISEASE Concept Summary
35 year old who presented several months ago with typical rash of erythema migrans.
Treated with 3 weeks of doxycycline
Rash resolves after 4 days, but she continues with malaise and diffuse myalgias
Repeat testing:
Lyme serology: EIA (+)
Western blot IgG (+)
IgM (+)
Does this patient need more treatment? NO

38. LYME DISEASE Concept Summary
31 year old with the non-pruritic, non-painful skin lesions seen on the following slide.
Lyme serology: EIA (-)
Western blot IgG (-)
Western blot IgM (-)
Does this patient have Lyme disease?

39. YOU BETCHA

40. Babesiosis What is it? Where is it? What is the clinical syndrome?
An intracellular protozoan parasite
Where is it?
Northeast
(Northwest)
What is the clinical syndrome?
“FLU” – like: fever, chills, headache, fatigue
Hemolytic anemia
Serious especially in asplenic persons
Relapses can occur - especially in immunosuppressed persons

41. Babesiosis Diagnosis and Treatment
Peripheral blood smear
PCR on blood
Serology has the same problems as that for Lyme disease. A positive test does not mean disease.
Don’t treat a positive test; treat a person with a positive test an a compatible clinical syndrome
Treatment
Quinine and Clindamycin
Atovaquone and azithromycin

42. Babesiosis

43. Ehrlichiosis and Anaplasmosis
What are they?
Rickettsiaceae family
Human Monocytic Ehrlichiosis (HME)
Lone star tick
Human Granulocytic Anaplasmosis (HGA)
Ixodes ticks
Where is it?
Everywhere

44. Human Monocytic Ehrlichiosis
E. chaffeensis
First described in 1987
Primarily infects mononuclear cells
Reservoir: deer, dogs, goats
Vector: Lone star tick (Amblyomma americanum)

45. Human Granulocytic Anaplasmosis
First described in 1994
Organism recently named Anaplasma phagocytophilum.
Reservoir: deer, rodents, elk
Vector: Ixodes ticks

46. Ehrlichiosis and Anaplasmosis
SIGNS AND SYMPTOMS
Incubation period: days
Early symptoms are non-specific (“flu-like”)
Fever, headache, myalgias
GI symptoms can occur
Rash variable
Laboratory
Leucopenia, thrombocytopenia, abnormal liver enzymes

47. Ehrlichiosis and Anaplasmosis
COMPLICATIONS
Can be very severe
Renal failure
ARDS
DIC
Encephalitis
3% mortality
Worse in patients with impaired host defenses
Watch out for dual or triple infections with
Borrelia burgdorferi and Babesia

48. Ehrlichiosis and Anaplasmosis
DIAGNOSIS
Peripheral smear looking for morulae
Serology
PCR (state laboratories)
Culture
Treat based on epidemiologic and clinical clues. Do not delay while waiting for confirmation.

49. Ehrlichiosis and Anaplasmosis
Morulae

50. Ehrlichiosis and Anaplasmosis
TREATMENT
Treatment should not be delayed until laboratory confirmation is obtained
Doxycycline: 100 mg PO/IV
Until 3 days after fever abates
Expect response in hours
Pregnancy and children ???
Rifampin 600 mg IV/PO has been used

51. Rocky Mountain Spotted Fever
Clinical Spectrum from mild to fulminant
Throughout the Western Hemisphere
Vector: Dermacentor
Dog or Wood Ticks

52. Rocky Mountain Spotted Fever

53. Rocky Mountain Spotted Fever Clinical Manifestations
Incubation Period: days (ave 5 - 7)
Non-specific
Fever
Headache
Myalgias GI
Rash
Mortality about 25% if treatment delayed

54. Rocky Mountain Spotted Fever Rash
Begins on day 3 - 5
Only 15% have a rash on the first day
10% never get a rash
Do not wait for a rash to initiate therapy
Starts on ankles and wrists
Spreads centrally and to palms/soles

56. Rocky Mountain Spotted Fever Diagnosis
Initially made clinically on suspicion and epidemiology
Serology
Used to confirm diagnosis
Takes at least days to seroconvert
Skin biopsy
Rapid, if available (requires special stains)
70% sensitive

57. Rocky Mountain Spotted Fever Treatment
Can not overstress the importance of early therapy
Mortality related to when treatment initiated
< 5 days 6.5%
> 5 days 22.9% (most saw a physician within the first five days)
Doxycycline for adults and children
Chloramphenicol is the alternative

58. Tick Typhus Throughout the world All have rashes
Typically on trunk
Most with tick bite site eschar
All diagnosed serologically
All treated with doxycycline
Consider the diagnosis in a febrile returning traveler

59. Tick Typhus

60. STARI “Southern Tick-Associated Rash Illness”
Rash similar to erythema migrans in persons living in the SE USA
First reported in 1996 and organism identified in 2001
Different vector than Lyme disease
Amblyomma rather than Ixodes
Same life cycle and ecology
Different pathogen
Borrelia lonestari (?)

61. Amblyomma americanum “Lone Star” Tick

62. STARI “Southern Tick-Associated Rash Illness”
Distribution of Lone Star Ticks in the USA

63. STARI “Southern Tick-Associated Rash Illness”
Diagnosis
Unable to culture at this time
PCR on biopsy of rash
Lyme disease serology is negative
Treatment
? Doxycycline
Sequellae
None known to date

64. Managing a Tick Bite
You get a phone call at 5:30 on a Friday evening from a patient who says that he just found a tick behind the ear of his wife. They ask:
How should they remove it?
Should she get antibiotics?

65. Removing a Tick Do not use Vaseline, kerosene, matches, gasoline
Use a hemostat or forceps and grasp tick as close to the skin as possible
Pull back gently and firmly perpendicular to the skin
Don’t squeeze or crush
Don’t worry about residual mouth parts

66. Antibiotic ? Need to address three questions
Type of tick?
Attached or engorged?
Duration of attachment?
Prophylactic antibiotics generally not indicated

67. SINGLE DOSE DOXYCYCLINE?
If:
> 8 years old
Attached tick was nymph or adult Ixodes scapularis
Attached for at least 36 hours
Prophylaxis can be started within 72 hours of tick removal
Local prevalence of Lyme disease is > 20%
No contraindication to doxy
Otherwise observation alone is recommended

68. Questions?