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 Abstract
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 [5]. 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: blair.grubb@utoledo.eduReceived: 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 [6].
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 [7]. 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 Tilt testing
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 Treatment protocols
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- Comorbidity
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
Table 1. Clinical characteristics of the postural orthostatic tachycardia syndrome patients with
pre-existing post Lyme disease syndrome.
Patient #
pressure, with episodes of very high blood pressure Table 2. 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. [16] 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 [5]. 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.
3. Halperin JJ. Nervous system Lyme disease. Infect Dis Clin North While there is no proven therapy for symptom con- trol in patients suffering from post-treatment LD 4. Feder HM Jr, Johnson BJ, O’Connell S et al. A critical appraisal syndrome, it is possible that some of these patients of “chronic Lyme disease”. N Engl J Med, 2007; 357: 1422– might have OI as a contributor to their symptoms.
5. Klempner MS, Hu LT, Evans J et al. Two controlled trials of Recognition of orthostatic intolerance in this subset antibiotic treatment in patients with persistent symptoms and of patients may lead to the initiation of appropriate a history of Lyme disease. N Engl J Med, 2001;345: 85–92.
treatment earlier, with subsequent improvement in 6. Grubb BP, Kanjwal Y, Kosinski DJ. The postural tachycardia their symptoms and quality of life. Physicians need syndrome. A concise guide to diagnosis and management. J Car- to have a high index of suspicion for OI in patients diovasc Electrophysiol, 2006; 17: 108–112.
suffering from post-treatment LD syndrome.
7. Low PA, Sandroni P, Joyner M, Shen WK. Postural tachycar- dia syndrome (POTS). J Cardiovasc Electrophysiol, 2009; 20:352–358.
Limitations of the study
8. Grubb BP. Dysautonomic (orthostatic) syncope. In: Grubb BP, This was a retrospective report on a relatively Olshansky B eds. Syncope: Mechanisms and management.
small number of patients. Because of the retrospec- Blackwell Publishing, Malden, MA 2005: 72–91.
tive nature and small number we could not estimate 9. Grubb BP. Neurocardiogenic syncope. In: Grubb BP, Olshansky B any incidence of POTS in patients suffering from eds. Syncope: Mechanisms and management. Blackwell Pub- post LD syndrome. Also, some questions such as why only a few patients with post LD develop POTS 10. Grubb BP. Neurocardiogenic syncope and related disorders of orthostatic intolerance. Circulation, 2005; 111: 2997–3006.
remain unanswered from this report. A high index 11. Grubb BP. Posturalorthostatic tachycardia. Circulation, 2008; of suspicion for POTS may allow for its early rec- ognition and treatment in patients suffering from 12. Wormser GP, Dattwyler RJ, Shapiro ED et al. The clinical as- sessment, treatment, and prevention of Lyme disease, humangranulocytic anaplasmosis, and babesiosis: Clinical Practice Conclusions
Guidelines by the Infectious Diseases Society of America. ClinInfect Dis, 2006; 43: 1089.
13. Klempner MS, Hu LT, Evans J et al. Two controlled trials of In an appropriate clinical setting, evaluation for antibiotic treatment in patients with persistent symptoms and POTS in patients suffering from post LD syndrome a history of Lyme disease. N Engl J Med, 2001; 345: 85.
may lead to earlier recognition and treatment, with 14. Kaplan RF, Trevino RP, Johnson GM et al. Cognitive function in subsequent improvement in symptoms of OI.
post-treatment Lyme disease do additional antibiotics help?Neurology, 2003; 60: 1916.
15. Krupp LB, Hyman LG, Grimson R et al. Study and treatment of Acknowledgements
post Lyme disease (STOP-LD): A randomized double maskedclinical trial. Neurology, 2003; 60: 1923.
The author does not report any conflict of in- 16. Chandra A, Wormser GP, Klempner MS et al. Anti-neural anti- body reactivity in patients with a history of Lyme borreliosis andpersistent symptoms. Brain Behav Immun, 2010 [Epub ahead ofprint].
17. Raj SR, Black BK, Biaggioni I, Harris PA, Robertson D. Acetyl- cholinesterase inhibition improves tachycardia in postural ta- 1. Stanek G, Strle F. Lyme disease: European perspective. Infect chycardia syndrome. Circulation, 2005; 111: 2734–2740.
Dis Clin North Am, 2008; 22: 327–339.
18. Gales BJ, Gales MA. Pyridostigmine in the treatment of ortho- 2. Steere AC. Lymedisease. N Engl J Med, 2001; 345: 115–125.
static intolerance. Ann Pharmacother, 2007; 41: 314–318.

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