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Postural orthostatic tachycardia
syndrome following Lyme disease
Khalil Kanjwal, Beverly Karabin, Yousuf Kanjwal, Blair P. Grubb
Section of Electrophysiology, Division of Cardiology, Department of Medicine,
The University of Toledo Medical Center, Toledo, USA
Background: A subgroup of patients suffering from Lyme disease (LD) may initially respond
to antibiotics only to later develop a syndrome of fatigue, joint pain and cognitive dysfunction
referred to as ‘post treatment LD syndrome’. We report on a series of patients who developed
autonomic dysfunction in the form of postural orthostatic tachycardia syndrome (POTS).
Methods: Al of the patients in this report had suffered from LD in the past and were successful y
treated with antibiotics. All patients were apparently well, until years later when they presented
with fatigue, cognitive dysfunction and orthostatic intolerance. These patients were diagnosed
with POTS on the basis of clinical features and results of the tilt table (HUTT) testing.
Results: Five patients (all women), aged 22–44 years, were identified for inclusion in this
study. These patients developed symptoms of fatigue, cognitive dysfunction, orthostatic palpita-
tions and either near syncope or frank syncope. The debilitating nature of these symptoms had
resulted in lost of the employment or inability to attend school. Three patients were also
suffering from migraine, two from anxiety and depression and one from hypertension. All
patients demonstrated a good response to the employed treatment. Four of the five were able to
engage in their activities of daily living and either resumed employment or returned to school.
Conclusions: In an appropriate clinical setting, evaluation for POTS in patients suffering
from post LD syndrome may lead to early recognition and treatment, with subsequent improve-
ment in symptoms of orthostatic intolerance.
(Cardiol J 2011; 18, 1: 63–66)Key words: postural tachycardia, orthostatic intolerance, Lyme disease
pains and cognitive dysfunction known as ‘post treat-ment LD syndrome’ [3–5]. The post treatment LD
Lyme disease (LD), a tick-borne illness caused
syndrome has been reported to result in a substan-
by the spirochete borellia burgdorferi, is the multi-
tial decline in the quality of life in affected patients
-system disorder that begins with erythema migrans
. We present a series of patients who suffered from
and may later be followed by widespread complica-
LD and were successfully treated initially with anti-
tions which may involve the nervous system, cardio-
biotics, but who later developed a syndrome of fa-
vascular system and musculoskeletal system [1, 2].
tigue, cognitive dysfunction and symptoms of ortho-
While most of these manifestations usually respond
static intolerance (OI). Further investigation re-
to antibiotic treatment, there is a subgroup of pa-
vealed that each of these patients was suffering from
tients who later develop a syndrome of fatigue, joint
postural orthostatic tachycardia syndrome (POTS).
Address for correspondence: Blair P. Grubb, MD, FACC, Professor of Medicine Director Electrophysiology Services Divisionof Cardiology, Department of Medicine Health Sciences Campus,The University of Toledo Medical Center, Mail Stop 1118,3000 Arlington Ave, Toledo, Ohio 43614, USA, tel: 419 383 3778, fax: 419 383 3041, e-mail: firstname.lastname@example.orgReceived: 16.06.2010
Cardiology Journal 2011, Vol. 18, No. 1
uptake inhibitors, pyridostigmine, and erythropoi-etin, either alone or in combination. The rationale
This was a single center report on a series of
for this sequence and the doses employed are de-
five patients who followed our clinic for orthostatic
scribed in detail elsewhere. A treatment was con-
intolerance. This study was approved by our local
sidered successful if it provided symptomatic relief.
Institutional Review Board. All of these patients had
Not all drugs were used in every patient.
suffered from LD in the past and were successfullytreated with antibiotics. All of these patients were
apparently well, until years later when they startedwith fatigue, cognitive dysfunction and OI. In
Five patients (all women), aged 22–44 years,
a retrospective chart review, we collected data in-
were identified for inclusion in this study. All these
cluding demographic information, presenting symp-
patients had suffered from LD and were apparently
toms, laboratory data, tilt-table response, and treat-
cured with antibiotics and were asymptomatic for
ment outcomes. OI refers to a heterogeneous group
periods ranging from two to 12 years. Table 1 sum-
of disorders of hemodynamic regulation character-
marizes the clinical features of these patients.
ized by insufficient cerebral perfusion resulting insymptoms during upright posture relieved by recum-
Diagnosis of Lyme disease
bency. Symptoms included syncope, near syncope,
LD was diagnosed in each patient based on the
fatigue, palpitations, exercise intolerance, lighthead-
combined clinical criteria and immunological respons-
edness, diminished concentration, and headache .
es seen against borrelia burgdorferi. Each patient hadan acute episode of LD. None presented with any car-
Head up tilt test (HUTT) protocol
diac complications. The acute episode presented mainly
The protocol used for tilt table testing has been
as skin rash with a prior history of tick bite. All these
described elsewhere, but basically consisted of a 70-
patients had suffered from LD and were apparently
-degree baseline upright tilt for a period of 30 min,
cured with antibiotics and were asymptomatic for pe-
during which time heart rate and blood pressure
riods ranging from two to 12 years (Table 1).
were monitored continually . If symptomatichypotension and bradycardia occurred, reproducing
Symptoms of orthostatic intolerance
the patient’s symptoms, the test was ended. If no
After the quiescent period of two to 12 years
symptoms occurred, the patient was lowered to the
following their initial infection with LD, all these
supine position and an intravenous infusion of iso-
patients developed symptoms of fatigue, cognitive
proterenol started with a dose sufficient to raise the
dysfunction, orthostatic palpitations and either near
heart rate to 20–25% above the resting value. Up-
syncope or frank syncope. These symptoms had
right tilt was then repeated for a period of 15 min.
resulted in substantial limitation of activities of dailyliving, to such an extent that each patient either lost
Criterion for diagnosing postural
their employment or became unable to attend
orthostatic tachycardia syndrome
school. The fear of passing out upon standing had
resulted in substantial limitation and all these pa-
greater than six months’ duration) accompanied by
tients had initially become housebound.
a heart rate increase of at least 30 bpm (or a rate thatexceeds 120 bpm) observed in the first ten minutes
of upright posture or HUTT occurring in the absence
All five patients were evaluated by a head up tilt
of other chronic debilitating disorders [6, 7].
table testing. All demonstrated a tilt pattern consis-tent with POTS (the criteria have been discussed in
the methods section above). Three patients had a tilt
The treatment protocols employed were based
table response seen within the ten minutes; the other
on our previous experiences with orthostatic dis-
two patients had to be started on an isoproterenol
orders and are described in detail elsewhere [6–11].
infusion before the test was repeated.
Briefly, a sequence of therapies is employed thatincluded physical counter maneuvers as well as in-
creased dietary fluids and sodium. If these were
Three patients complained of recurrent mi-
ineffective, pharmacotherapy was initiated in a se-
graines, two of anxiety and depression, and one of
quence generally consisting of fludrocortisone, mi-
hypertension. The patient who was suffering from
dodrine, methylphenidate, selective serotonin re-
hypertension had wide fluctuations in her blood
Khalil Kanjwal et al., Postural orthostatic tachycardia syndrome following Lyme disease
Clinical characteristics of the postural orthostatic tachycardia syndrome patients with
pre-existing post Lyme disease syndrome.
pressure, with episodes of very high blood pressure
Various treatments employed in the stu-
followed by episodes of hypotension.
The commonly used medications in this group
of patients were fludrocortisone (in two) and pyri-
dostigmine (in three). Bupropion, erythropoietin and
clonidine were used in one patient each (Table 2).
Response to treatment
All patients demonstrated a good response to
the employed treatment. The orthostatic symptoms
of patients [13–15]. In a recent report by Chandra
(especially fatigue) improved in all of them. In three
et al.  anti-neural antibody reactivity was found
patients, their syncope was completely abolished,
to be significantly higher in the patients suffering
while two patients have continued to have syncope
from post LD syndrome (49%) as compared to post
but at a much lesser frequency than before starting
Lyme healthy individuals (18.5%) or healthy indi-
treatment. All except one patient were able to en-
viduals without a history of LD (15%) with a p <
gage in their daily activities and either resume em-
< 0.01. It has been postulated that LD can trigger
‘auto antibodies’ that can bind or block post-synapticacetylcholine receptors in the autonomic ganglia.
However, due to the retrospective nature of the cur-rent study, we did not check for synaptic antibodies.
A subgroup of patients diagnosed with chronic
All our patients demonstrated a good response
LD may in fact have post LD syndrome. These pa-
to pyridostigmine. Pyridostigmine augments the
tients usually improve initially with the antibiotics
availability of acetylcholine at the synaptic cleft by
and have resolution of physical symptoms and signs
inhibiting acetylcholine esterase, an enzyme that
of LD. However, after a quiescent period, they again
causes hydrolysis of acetylcholine. Pyridostigmine
develop symptoms of fatigue, pain and cognitive
has been shown to improve symptoms in patients
dysfunction. Interestingly, these symptoms usual-
suffering from POTS or OI [17, 18]. Clinical symp-
ly develop within six months following a success-
toms of post LD syndrome are debilitating and have
ful treatment with antibiotics. The exact etiology
been reported to impair quality of life . In our
of this syndrome remains elusive. Randomized tri-
patients, symptoms of fatigue, orthostatic palpita-
als have failed to show any benefit of continued
tions, cognitive dysfunction and syncope had result-
antibiotic use in patients suffering from post LD
ed in substantial impairment of the quality of life in
syndrome, as this syndrome is not thought to be due
each patient. After diagnosis and initiation of the
to persistence of spirochete infection in this group
treatment, all but one patient reported a marked
Cardiology Journal 2011, Vol. 18, No. 1
improvement in their symptoms and quality of life.
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While there is no proven therapy for symptom con-
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Recognition of orthostatic intolerance in this subset
antibiotic treatment in patients with persistent symptoms and
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6. Grubb BP, Kanjwal Y, Kosinski DJ. The postural tachycardia
their symptoms and quality of life. Physicians need
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to have a high index of suspicion for OI in patients
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dia syndrome (POTS). J Cardiovasc Electrophysiol, 2009; 20:352–358.
Limitations of the study
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This was a retrospective report on a relatively
Olshansky B eds. Syncope: Mechanisms and management.
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why only a few patients with post LD develop POTS
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In an appropriate clinical setting, evaluation for
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a history of Lyme disease. N Engl J Med, 2001; 345: 85.
may lead to earlier recognition and treatment, with
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subsequent improvement in symptoms of OI.
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The author does not report any conflict of in-
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body reactivity in patients with a history of Lyme borreliosis andpersistent symptoms. Brain Behav Immun, 2010 [Epub ahead ofprint].
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2. Steere AC. Lymedisease. N Engl J Med, 2001; 345: 115–125.
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