Transcript Tick-borne Diseases and Cardiomyopathy

Tick-borne Diseases and
Cardiomyopathy
Presentation of 3 Cases with Discussion
Kenneth B. Liegner, M.D.
ILADS Conference
Newton, MA
October 28, 2007
Background
• Substantial literature exists for carditis from Lyme disease
including cardiomyopathy.
• Fatal case of pancarditis with Lyme and babesiosis co-infection
reported by Marcus et. al. 1985.
• Bartonellae, rickettsiae, piroplasms and mycoplasms also have
been reported to cause carditis
• Besides Babesia microti, WA-1, and MO-1 a wide range of
piroplasms/theileri exist in wildlife and ticks in nature.
• Test methods to detect the full diversity of piroplasms found
within ticks are not clinically available.
• The extent of human disease caused by diverse piroplasms
almost certainly remains incompletely defined at present.
Case 1 Slide 1
• First seen by me, 7/05.
• 58 y.o. Maine Army National Guard, previously
healthy.
• 8/01 On training maneuvers in coastal New
Brunswick, Canada, camping in field with high
grasses X 2 ½ weeks. Deer in vicinity. Tents had no
“floor” canvas.
• Noted circular bruise-like area left shin, orange to
grapefruit-sized – no known history of trauma, no
known tick attachments while on maneuvers.
• 6+ weeks later, flu-like symptoms, back pain, chills,
night sweats, joint pain, limping, numbness in legs;
later fatigue, cognitive problems, decreased stamina
& endurance.
Case 1 Slide 2
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Summer ’02 – Felt unwell. EKG: Complete heart block – pacemaker
placed.
Lyme suspected but tests negative.
Dyspnea developed with impairment on PFTs
Coronary angiography: virtually normal coronary arteries & normal EF.
No CHF.
Chest CT prominent mediastinal LN; sarcoid considered; Paratracheal & cervical LN Bx: non-necrotizing granulomas.
? Consistent with sarcoid but not felt definitely diagnostic.
A physician felt Lyme plausible (30 kDa band on Lyme Western blot) –
tetracycline applied 2/04-7/04 with benefit; Biaxin & Plaquenil 7/046/05 – heart block did not resolve and patient remained pacemaker
dependent. Para-tracheal and mediastinal lymphadenopathy improved
following antibiotic treatment. PFTs improved with ABx.
4/05 Ventricular tachycardia on EPS – Pacemaker removed and
Defibrillator/Pacemaker inserted.
Despite maximum doses of Sotalol, recurrent VT with repeated
automatic defibrillator discharges.
Case 1 Slide 3
• 7/05 minocycline begun.
• VT episodes appeared to have subsided and VT was not
inducible with defibrillator testing/programming 2 weeks after
minocycline begun.
• Initial labs obtained at my evaluation 7/05:
ESR 45 mm/hr
IgG Lambda on Immunofixation
Coxsackie B1-B6 negative
Lyme Western blots:
Stony Brook: ELISA (-); IgM 41 (30) IgG 30
MDL: IgM 41 IgG no bands
IgeneX: IgM ++28 +++31 +39 ++41 +58 +66 IND @
18,30,34,45,93
IgG +30 ++41 ++66 IND @28,31,39,45,66
Case 1 Slide 4
(Initial labs & diagnostics,
continued)
• Bm IgG IFA 1:20 Igenex; Negative @ Quest.
Bm FISH Neg.
• Brain SPECT: severe global cortical hypopefusion with heterogeneity; white matter
involvement noted.
• Angiotensin converting enzyme 141 (ULN
67).
• Thick & thin Giemsa smears for
babesia/piroplasms negative.
Case 1 Slide 5
Subsequent Testing
• 5/06 Stony Brook ELISA Neg WB IgM (72) IgG
(29,93)
• 5/06 IgeneX
IgM +28 ++41 +45 +66 IND @ 31,39
IgG ++28 +41 +58 IND @ 31,39
• 5/06 IgeneX Bm IFA +1:20, Bm FISH neg.
• 8/06 Stony Brook ELISA Neg WB: IgM 41 IgG
41,93
• 8/06 IgeneX: IgM +41, +58 IND @23,31,34,39
IgG +30 +41 +58 IND @ 31,39
• 8/06 Bm IFAs @ Quest & IgeneX neg
Case 1 Slide 6
Treatment Interventions and
Outcome
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Minocycline 7/05-present
Plaquenil added 1/06-5/06 (arguably therapeutic both for Lyme and Sarcoid)
Prednisone by pulmonologist for possibility of sarcoid late Winter/early Spring ‘064/06 Repeat echocardiogram: decreased EF to 30-35% with moderately severe global hypo-kinesis –
worsening occurred after Prednisone added. LVEF had never been impaired until prednisone utilized.
Discussion held with patient by his pulmonologist regarding consideration of cardiac transplantation
as a possibly necessary contingency.
Empiric addition of malarone for possibility of babesiosis/piroplasmosis 5/06-11/06.
8/06 Repeat Echo 60%.
Repeat Echo 11/06 still satisfactory @ 60%
One episode of VT 1/07 felt related to hypokalemia.
Patient has strong sense that mino & malarone was responsible for dramatic turn-around in status
and feels that Prednisone did not improve his condition (and resulted in impaired LVEF).
Complication of anti-microbial Rx: grey-blue skin pigmentation lower extremities secondary to
minocycline.
CHB never reversed despite antimicrobial Tx; unusual for Lyme disease alone.
Global status substantially recovered and satisfactory quality of life.
Case 1 Slide 7
Considerations & Discussion
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Did this patient have Lyme disease?
Did this patient have babesiosis/piroplasmosis???
Did he have sarcoidoisis?
Did he have two or three of these conditions?
Did Lyme disease trigger sarcoid or a sarcoid-like
illness?
Did he require anti-borrelial and anti-piroplasm/antibabesia treatment???
Did he require Prednisone application?
Was combined Prednisone and anti-microbial
therapy necessary and beneficial in his case?
Would he have recovered without some or all of the
applied treatments?
Case 2 Slide 1
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(First seen 12/05) 54 y.o. WM; extensive epidemiologic risk for tick exposures in
MA, Pacific NW, Virginia, Minnesota, Maine. At least 12 known tick
attachments; no known EM rashes.
11/03 CHF develops. Non-smoker. Previously physically fit and active. Normal
coronary arteries on angiography, but dilated cardimyopathy. Developed
syncope secondary to VT which was recurrent which co-incided with onset of
CHF. Pacer/defibrillator placed. Recurrent bouts of paroxysmal AF as well
which have triggered defibrillator.
Medical/cardiologic treatment: Coreg (carvedilol), aldactone, Diovan(valsartan),
digoxin, Coumadin, furosemide prn.
Sarcoid r/o’d. + history of Ehler-Danlos syndrome
7/05 a prior physician found suspicious bands on Lyme WB and + anti-bodies
against WA-l babesiosis; Rx by prior physician included Ketek, Doryx, Omnicef,
Flagyl. On Ketek and Mepron developed AF and was cardioverted.
10/05 increasing dyspnea and decreasing exercise tolerance. Fevers and night
sweats. Igenex Lyme WB 6 bands
IV Rocephin X 28 days Nov/Dec 2005 with some benefit. Increased exercise
tolerance.
Case 2 Slide 2
• 11/03 EF when CHF first diagnosed: 20%;
LV ED diameter 7.3 cm.
• 2/06 EF following antibiotic and antibabesia Rx increased to 35% & LV ED
diameter 6.3 cm (decreased by 13.6 %)
global hypokinesis; LV moderately dilated;
RV mildly dilated & decreased systolic
function
Case 2 Slide 3
Pertinent labs/diagnostics
• 11/03 Coxsackie AB B1-B6 neg
• 10/05 IgeneX Lyme WB: IgG ++18 +28 +++31 +34 ++41 ++58 IgM
++31 IND 23
• 10/05 Quest WA-1 1:128 (NL< 1:64); Bm IFA negative
• 7/05 MDL Lyme WB IgG 31 Lyme C6 Neg Lyme ELISA neg
• 7/05 Stony Brook ELISA neg WB IgG 30 kDa
• 8/05 Bartonella henselae IFA neg
• Heavy metals neg
• 12/05: IgM 308 (ULN 271)
• 12/05 Stony Brook: ELISA neg WB IgG 30 kDa
• 12/05 MDL: Mycoplasma fermentans PCR + @ 24,900 copies /ml
• Sonoma Co.DOH WA-1 IFA + @ 1:640
Case 2 Slide 4
Treatment and Course
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12/05 after sequeing off 28 days course of IV CFTRX, oral minocycline begun.
Malarone added after one month for combined Rx vs. Lyme and WA-l
babesiosis.
Remained on mino & malarone 12/05 at least through 10/06 when patient was
“lost to follow-up”.
Progressively improving sense of well-being and exercise capacity.
Dysrhythmias become a “non-issue” since 10/05. Atrial-ventricular dyssynchrony resolves. Patient avers addition of Malarone conferred most
dramatic symptomatic improvement; sweats resolved with Malarone. Able to
walk 4 miles @ 4 MPH and play basketball X 40 minutes, able to bike 10 miles.
Repeat Mycoplasma fermentans PCR @ MDL negative.
Last labs 9/06: Quest WA-l 1:256 (NL < 1:64)
Quest Bm IFA Neg
Stony Brook Lyme ELISA neg WB:IgM neg IgG 30,41 (34)
MDL Lyme WB IgG 31, 41 IgM No bands
IgeneX: IgM IND @ 23,31,39,41
IgG Positive ++18 +28 +++31 +++41 +58 IND @ 23, 34, 39
(negative by CDC criteria)
Case 3 Slide 1
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49 y.o. WM, resident of a southwestern U.S. state. Previously healthy,
physically active, hiker, camper, runner in mountainous and wooded regions of
the West and the Pacific Northwest. One probable engorged tick attachment
1984 without obvious illness. No history of ECM.
12/04 “heart irregularity” noted on insurance physical; advised to follow-up
with personal physician but did not do so. Retrospective review showed AF.
Spring ’06 noted “heart flutter” while back-packing. Cardiologist found atrial
fibrillation and echo with markedly reduced EF @ 25% (NL 55%) with dilated LV.
Coumadin started.
Fall ’06 cardiac cath: normal coronary arteries. LV enlarged; EF 20%.
Coxsackie viral titers NEG. Echoviral titers NEG. EBV IgG AB+; CMV AB +;
RMSF AB NEG; PCRS Bb, Bh, NEG;
11/06 Lyme WB @ MDL: IgG 39,41 (faint 28, 60) IgM faint 41.
11/06 Lyme WB @ Stony Brook: IgM 41 (18,62) IgG (37)
11/06 Lyme WB @ Igenex: IgM ++41 IgG +41 +58 faint 23,31,39
11/06 WA-l AB NEG; Bm FISH NEG
11/06 AB and PCR’s NEG Bh; AB HME/HGE NEG.
CASE 3 Slide 2
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1/07 Lyme ELISA Stony Brook POSITIVE
Stony Brook WB: IgM 41 (18,64)
IgG (37)
1/07 WB @ MDL: IgG 39,41 and faint
23,28,30,60
faint 41
1/07 WB @ IgeneX: IgM +30 +41 + 58
IND 34,39
IgG +30 ++41 +58
IND 39
ANA + 1:80 homogeneous
ACE NORMAL
C3/C4 & C1Q IMMUNE COMPLEXES NORMAL
HANTAVIRUS AB NEG
1/07 Bm IFA’s, FISH, PCR @ IgeneX NEG
IgM
CASE 3 Slide 3
• Despite severely compromised cardiac
function patient has minimal symptoms
and does not endorse shortness of breath
on exertion.
• Does not endorse multi-system symptoms
as often seen in Lyme disease; has only
some mild arthralgia in knees, mild
cervicalgia, myalgia, occasional tinnitus,
questionable paresthesias.
CASE 3 Slide 4
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1/07 Cardioverted into NSR but reverted to AF within one week
Minocycline 200 mg/day begun 12/06
Malarone added 2/07 for strictly empiric therapy to cover possible
piroplasm co-infection
Repeat echo 5/07 after 6 months minocycline combined for the final 3
months with malarone: No improvement in EF @ 20 %. AF continued.
Minocycline and malarone discontinued 6/07.
Patient decides to pursue evaluation for possible trial of Valganciclovir
with Dr. Montoya @ Stanford U. Medical Center in view of strongly
elevated IgG antibody titers to CMV, EBV, and HHV6.
Meanwhile, repeat Echocardiogram 2months after discontinuing
mino/malarone shows improvement in EF to 30-35% (prior to any use
of valganciclovir); Not clear but it is possible anti-microbial treatment
might have been responsible for improvement.
Intent for patient to undergo either pharmacologic attempts to restore
sinus rhythm or catheter ablation of pulmonary vein region of left
atrium.
SUMMARY
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Carditis including cardiomyopathy can be caused by tick-borne infections.
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Patients with cardiomyopathy deserve thorough evaluation for exposure to
tick-borne diseases as possible treatable/reversible etiologies. Other causes
for cardiomyopathy must be systematically assessed as well.
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Close collaboration/cooperation with a cardiolgist is mandatory.
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If there is clinical and/or laboratory evidence of one tick-borne infection
consider the possibility that other tick-borne co-infections might be operative;
it may be prudent to cover the most likely “bases” empirically in dealing with
this potentially life-threatening illness, given the insensitivity of current test
methods and the fact that borreliae, rickettsiae/ehrlichiae, piroplasms,
bartonellae species, and mycoplasms all can cause carditis.
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Minocycline combined with malarone would seem a rational and economical
regimen that would cover most of the tick-transmissible bacterial/parasitic
infections in patients who are felt to have evidence of tick-borne etiology for
their carditis. Other regimens may be also be acceptable. Systematic
comparison of optimal regimens have not been undertaken due to the relative
rarity of cardiomyopathy as a complication of tick-borne illness.
SUMMARY (cont’d)
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General physicians, cardiologists and other health care professionals need to
be educated to consider tick-borne illness as one possible etiology of
cardiomyopathy.
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Antimicrobial treatment can sometimes reverse the myocardial dysfunction
and abolish life-threatening dysrhythmias and congestive cardiomyopathy and
can avert catastrophic outcomes. Early recognition and appropriate treatment,
as in other manifestations of Lyme disease, seem most likely to result in
optimal outcomes; late diagnosis can result in irreversible cardiac injury and
death. Late application of treatment might result less responsiveness due to
scarring of myocardium and/or conduction system.
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One might want to be circumspect about the use of azalides in patients with
carditis/cardiomyopathy because these agents can sometimes prolong the QT
interval and may be pro-arrhythmic in that setting.
SUMMARY (cont’d)
• FOOD FOR THOUGHT:
• How many cases of “idiopathic” cardiomyopathy
might result from occult TBDs?????
• What is the excess cost to society for congestive
cardiomyopathies and refractory life-threatening
dysrhythmias (e.g. Atrial fib, ventricular tachycardias
and ventricular fibrillation) requiring pacemakers,
implanted automatic defibrillators, hospitalizations
and expensive drug therapies and/or cardiac
transplantation due to missed diagnoses of tickborne carditis??? What is the extent of avoidable
personal suffering for patients and their families
consequent to failure to diagnose and treat
carditis/cardiomyopathy due to TBDs???
PERTINENT REFERENCES
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BORRELIAE
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Marcus LC, Steere AC, Duray PH, Anderson AE, Mahoney EB.
Fatal pancarditis in a patient with coexistent Lyme disease and babesiosis.
Demonstration of spirochetes in the myocardium.
Ann Intern Med. 1985 Sep;103(3):374-6.
PMID: 4040723 [PubMed - indexed for MEDLINE]
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Vlay SC, Dervan JP, Elias J, Kane PP, Dattwyler R.
Ventricular tachycardia associated with Lyme carditis.
Am Heart J. 1991 May;121(5):1558-60. No abstract available.
PMID: 2017995 [PubMed - indexed for MEDLINE]
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Stanek G, Klein J, Bittner R, Glogar D.
Borrelia burgdorferi as an etiologic agent in chronic heart failure?
Scand J Infect Dis Suppl. 1991;77:85-7.
PMID: 1947816 [PubMed - indexed for MEDLINE]
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Stanek G, Klein J, Bittner R, Glogar D.
Isolation of Borrelia burgdorferi from the myocardium of a patient with
longstanding cardiomyopathy.N Engl J Med. 1990 Jan 25;322(4):249-52. No abstract
available.
PMID: 2294450 [PubMed - indexed for MEDLINE]
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Gasser R, Lercher P, Klein W. Lyme Carditis and Borrelia-Associated Dilated
Cardiomyopathy. Heart Failure Reviews 1999, 3:241-248.
PERTINENT REFERENCES
(continued)
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BABESIOSIS/PIROPLASMS
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Armstrong PM, Katavolos P, Caporale DA, Smith RP, Spielman A, Telford SR
3rd. Diversity of Babesia infecting deer ticks (Ixodes dammini).
Am J Trop Med Hyg. 1998 Jun;58(6):739-42.
PMID: 9660456 [PubMed - indexed for MEDLINE]
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Persing DH, Conrad PA.
Babesiosis: new insights from phylogenetic analysis.
Infect Agents Dis. 1995 Dec;4(4):182-95. Review.
PMID: 8665084 [PubMed - indexed for MEDLINE]
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Persing DH, Herwaldt BL, Glaser C, Lane RS, Thomford JW, Mathiesen D,
Krause PJ, Phillip DF, Conrad PA.
Infection with a babesia-like organism in northern California.
N Engl J Med. 1995 Feb 2;332(5):298-303.
PMID: 8607592 [PubMed - indexed for MEDLINE]
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Herwaldt B, Persing DH, Precigout EA, Goff WL, Mathiesen DA, Taylor PW,
Eberhard ML, Gorenflot AF.
A fatal case of babesiosis in Missouri: identification of another piroplasm
that infects humans.
Ann Intern Med. 1996 Apr 1;124(7):643-50.
PERTINENT REFERENCES
(cont’d)
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BARTONELLA, EHRLICHEA, RICKETTSIAE, MYCOPLASMA
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Shah SS, McGowan JP. Rickettsial, ehrlichial and Bartonella infections of the myocardium and
pericardium. Front Biosci. 2003 Jan 1;8:e197-201. Review. PMID: 12456377 [PubMed - indexed for
MEDLINE]
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Paz A, Potasman I Mycoplasma-associated carditis. Case reports and review. Cardiology. 2002;97(2):83-8.
Review. PMID: 11978954 [PubMed - indexed for MEDLINE]
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Jahangir A, Kolbert C, Edwards W, Mitchell P, Dumler JS, Persing DH.
Fatal pancarditis associated with human granulocytic Ehrlichiosis in a
44-year-old man. Clin Infect Dis. 1998 Dec;27(6):1424-7.
PMID: 9868655 [PubMed - indexed for MEDLINE]
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Meininger GR, Nadasdy T, Hruban RH, Bollinger RC, Baughman KL, Hare JM.
Chronic active myocarditis following acute Bartonella henselae infection (cat
scratch disease). Am J Surg Pathol. 2001 Sep;25(9):1211-4.
PMID: 11688584 [PubMed - indexed for MEDLINE]
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Walker DH, Paletta CE, Cain BG Pathogenesis of myocarditis in Rocky Mountain spotted fever.
Arch Pathol Lab Med. 1980 Apr;104(4):171-4.PMID: 6767463 [PubMed - indexed for MEDLINE]