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Postural Tachycardia Syndrome (POTS) and Other Autonomic Disorders in Antiphospholipid (Hughes) Syndrome (APS)

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Postural Tachycardia Syndrome (POTS) and Other Autonomic Disorders in Antiphospholipid (Hughes) Syndrome (APS) XML Template (2014) [20.2.2014–12:51pm] [1–6] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/LUPJ/Vol00000/140024/APPFile/SG-LUPJ140024.3d (LUP) [PREPRINTER stage] Lupus (2014) 0, 1–6 http://lup.sagepub.com CONCISE REPORT Postural tachycardia syndrome (POTS) and other autonomic disorders in antiphospholipid (Hughes) syndrome (APS) JR Schofield1, S Blitshteyn2, Y Shoenfeld3,4 and GRV Hughes5 1Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA; 2Department of Neurology, State University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY, USA; 3Sackler Faculty in Medicine, Laura Schwarz-Kipp Chair for Research of Autoimmune Diseases, Tel-Aviv University, Israel; 4Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel; and 5The London Lupus Centre, London Bridge Hospital, London, UK Background: Antiphospholipid syndrome (APS) is an autoimmune hypercoagulable disorder that has been shown to cause a large number of cardiac and neurological manifestations. Two recent studies have demonstrated abnormalities in cardiovascular autonomic function testing in APS patients without other cardiovascular or autoimmune disease. However, an association between autonomic disorders such as postural tachycardia syndrome and APS has not previ- ously been described. Methods and results: Data were obtained by retrospective chart review. We identified 15 patients who have been diagnosed with APS and an autonomic disorder. The median age of the patients at the time of data analysis was 39 years. The autonomic disorders seen in these patients included postural tachycardia syndrome, neurocardiogenic syncope and orthostatic hypotension. The majority of patients (14/15) were female and the majority (14/15) had non-thrombotic neurological manifestations of APS, most commonly migraine, memory loss and balance disorder. Many also had livedo reticularis (11/15) and Raynaud’s phenom- enon (nine of 15). In some patients, the autonomic manifestations improved with anticoagula- tion and/or anti-platelet therapy; in others they did not. Two patients with postural tachycardia syndrome who failed to improve with the usual treatment of APS have been treated with intravenous immunoglobulin with significant improvement in their autonomic symptoms. Conclusion: We believe that autonomic disorders in APS may represent an import- ant clinical association with significant implications for treatment. Lupus (2014) 0, 1–6. Key words: Hughes syndrome; antiphospholipid syndrome (APS); postural tachycardia syn- drome (POTS); neurocardiogenic syncope (NCS); autonomic disorders; intravenous immuno- globulin (IVIG) Introduction well as a large number of neurological manifest- ations.11 Labile hypertension without associated renal disease and autonomic neuropathy were Antiphospholipid (Hughes) syndrome (APS) is a 12 hypercoagulable autoimmune disorder associated reported in early descriptions of the syndrome, with antiphospholipid antibodies that causes both and a recent study by Bilora et al. demonstrated arterial and venous thrombosis as well as preg- abnormalities in cardiovascular autonomic func- nancy morbidity. Non-thrombotic manifestations tion testing in APS patients without cardiovascular disease, cardiovascular risk factors or other auto- also occur in APS and include valvular heart dis- 13 ease,1–4 cardiac syndrome X,5 focal arterial immune disorders. Garcia et al. also recently 6 1–3 7 reported impaired aerobic exercise capacity and stenosis, cardiomyopathy, nephropathy, stress 14 fractures,8 thrombocytopenia,9 hemolytic anemia,9 cardiac autonomic control in APS patients. livedo reticularis,10 skin ulcers and necrosis,10 as However, an association between APS and auto- nomic disorders, such as postural tachycardia syn- Correspondence to: Graham R.V. Hughes, The London Lupus Centre, drome (POTS), neurocardiogenic syncope (NCS) 1st Floor, St Olaf House, London Bridge Hospital, 27 Tooley Street, and neurogenic orthostatic hypotension (OH), has London, SE1 2PR, UK. not previously been reported. We describe a series Email: [email protected] of 15 patients with APS and a disorder of the Received 12 November 2013; accepted 28 January 2014 ! The Author(s), 2014. Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav 10.1177/0961203314524468 XML Template (2014) [20.2.2014–12:51pm] [1–6] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/LUPJ/Vol00000/140024/APPFile/SG-LUPJ140024.3d (LUP) [PREPRINTER stage] Postural tachycardia syndrome and other autonomic disorders in APS JR Schofield et al. 2 autonomic nervous system and propose an associ- characteristics of the patients are shown in ation between the two. Table 1 and the frequency of their APS manifest- ations is shown in Table 2. The median age at the time of data collection was 39 years and ranged Methods from 15 to 66 years. However, the age at the time of diagnosis of APS and/or the autonomic disorder This is a retrospective chart review of 15 patients occurred at least a few years earlier in most of the who have been diagnosed with APS as well as patients and dated back to childhood (as early as POTS, NCS, and/or OH. Patients were personally age 12) in some. The dates of diagnosis were not examined and followed by one or the other of the available for all patients and the details of the authors. timing of the onset of the APS symptoms relative The diagnosis of APS was determined by the to the autonomic symptoms were not available for presence of at least one antiphospholipid antibody many of the patients, but for some the symptoms (lupus anticoagulant, anticardiolipin immuno- began concomitantly. Eight of the 15 patients had globulin IgG or IgM, or beta 2 microglobulin I POTS, eight had NCS (two of these required pace- IgG or IgM) on more than one occasion at least maker placement), three had OH, one had inappro- 12 weeks apart as well as one or more clinical mani- priate sinus tachycardia (IST) and one had complex festations of the syndrome. Not all patients met the regional pain syndrome type I (CRPD, formerly revised Sapporo classification criteria for definite known as reflex sympathetic dystrophy, RSD), which has previously been described in association APS, which requires thrombosis or specific preg- 18 nancy morbidity and medium to high titer antibody with APS. Six of the 15 patients had more than levels.15 The classification criteria were designed for one autonomic disorder. Fourteen of the 15 rigorous clinical research studies not for diagnosis, patients were female and 14/15 had non-thrombotic and patients with low titer antibody positivity were neurological manifestations of APS, which included as were patients without a history of included most commonly migraine, memory loss thrombosis who had well-described non- and imbalance. The majority (11/15) of patients thrombotic manifestations of the syndrome. had livedo reticularis and nine of 15 had All patients in the present study underwent formal Raynaud’s phenomenon. Eight of the patients tilt table testing. POTS was diagnosed as previously had at least one other autoimmune disorder and described based on the presence of clinical features three of 15 had joint hypermobility syndrome of orthostatic intolerance and an increase in heart (JHS). One patient (#13) developed APS, POTS rate of at least 30 beats per minute within 10 minutes and NCS two months after human papillomavirus of tilt table testing without evidence of OH.16,17 (HPV) vaccination, and four patients had a family Other autonomic tests including deep breathing, history of APS. Most (11/15) of the patients the Valsalva maneuver, the handgrip test and the required treatment with anticoagulation and three quantitative sudomotor axon reflex test (QSART) required both anticoagulation and an anti-platelet may provide additional information and allow agent for optimal APS symptom control. Two better characterization of the autonomic disorder. patients have not yet been treated. We did not These tests were performed in several but not all of find any pattern in terms of the titer or type of the patients included in the present study. NCS, also the antiphospholipid antibodies present. There known as neurally mediated syncope or vasovagal was a high degree of disability noted in these rela- syncope, was diagnosed during tilt table testing if tively young patients. there was a sudden fall in blood pressure, heart rate and cerebral perfusion resulting in loss of con- sciousness.17 OH was diagnosed if there was a reduc- Discussion tion in systolic blood pressure of at least 20 mm Hg or diastolic blood pressure of at least 10 mm Hg 17 APS is an autoimmune hypercoagulable disorder within three minutes of the tilt table test. best known for its tendency to cause throm- bosis—arterial, venous and placental. However, APS is a multisystem disorder19 and in the original Results description of the syndrome by Hughes in 1983, cerebral involvement was felt to play a central We identified 15 patients with APS and a disorder role.20 Indeed, since then, APS has been found to of the autonomic nervous system. The clinical cause wide-ranging neurological manifestations, Lupus XML Template (2014) [20.2.2014–12:51pm] [1–6] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/LUPJ/Vol00000/140024/APPFile/SG-LUPJ140024.3d (LUP) [PREPRINTER stage] Postural tachycardia syndrome and other autonomic disorders in APS JR Schofield et al. 3 Table 1 Clinical Characteristics of the Patients Autonomic Patient Age Gender APS Manifestations
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