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Orthostatic Intolerance in Behcet's Disease
Autonomic Neuroscience: Basic and Clinical 89 Ž2001. 96–99 www.elsevier.comrlocaterautneu
Orthostatic Intolerance in Behcet’s Disease Tahir Tellioglu, David Robertson ) Autonomic Dysfunction Center, Departments of Medicine, Pharmacology, and Neurology, Vanderbilt UniÕersity Medical Center, AA 3228 MCN, NashÕille, TN 37232, USA Received 27 November 2000; accepted 23 February 2001
Abstract Neurological manifestations are known to occur in patients with Behcet’s Disease ŽBD. and significantly affect the clinical course of the disease. Nevertheless, the prevalence, pattern and severity of autonomic impairment in such patients have yet to be defined. In this paper, we presented a BD patient with orthostatic tachycardia. Non-invasive standardized autonomic function tests revealed no evidence of autonomic impairment, but profound orthostatic tachycardia accompanied by abnormal catecholamine increase was observed upon standing. The diagnosis of Orthostatic Intolerance ŽOI. was made and initial symptomatic therapy was started. The contribution of an immunological damage to components of neural pathways in the pathogenesis of the autonomic involvement can be assumed. q 2001 Elsevier Science B.V. All rights reserved. Keywords: Behcet’s Disease; Orthostatic Intolerance; Autonomic; Autoimmune; Norepinephrine
1. Introduction Behcet’s Disease ŽBD. is a multisystem disorder presenting with recurrent oral and genital ulcerations, as well as ocular involvement ŽKastner, 1997; Sakane et al., 1999.. Vasculitis is the main pathologic lesion, and circulating autoantibodies to human oral mucous membrane antigenŽs. are present in half of the cases, suggesting it as an autoimmune disease ŽEhrlich, 1997.. The neurological involvement in BD patients has been described as primary neural parenchymal lesions Žneuro-Behcet. expressing itself as a meningoencephalitis, brainstem lesion, pseudotumor cerebri, cranial nerve palsies, as well as pyramidal, extrapyramidal, and cerebellar symptoms ŽSerdaroglu, 1998.. However, there have been only a few studies in the literature about the autonomic involvement in BD. The increase in heart rate of 30 beats per minute Žbpm. or greater, usually without significant hypotension upon standing, is diagnostic for Orthostatic Intolerance ŽOI. ŽJordan et al., 1997, Robertson, 1999.. This syndrome is mainly characterized by a variety of postural symptoms upon standing Ži.e. brisk tachycardia, lightheadedness, fa-
)
Corresponding author. Tel.: q1-615-343-6499; fax: q1-615-3438649. E-mail address: [email protected] ŽD. Robertson..
tigue, altered mentation, and syncope.. OI commonly occurs in young adult females, and has been associated with autonomic or neuroendocrine dysregulation, but its cause is still unknown, and may involve a variety of genetic and environmental factors. We recently evaluated a patient with Behcet’s Disease in whom extensive autonomic investigation revealed features of Orthostatic Intolerance. The clinical consequences of autonomic involvement in this patient suggested a probable immunological damage to the components of neural pathways in the pathogenesis of both conditions.
2. Case The patient was a 19-year-old African American female with postural hypotension, tachycardia, headaches, and chest pain. Approximately 5 years ago, she presented with lesions of her oral membranes, arms, legs, back, and vaginal mucosa, and was diagnosed with Behcet’s Disease. She initially received prednisone for several months, and then colchicine. One year ago, the patient developed postural hypotension and tachycardia with standing. Her pulse went into the 160s and her blood pressure would decrease to 80r40 on occasion. This condition was attributed to Addison’s disease, evidenced by an abnormal ACTH stimulation test. The patient was experiencing fainting spells each time she stood, and was treated with fludrocortisone,
1566-0702r01r$ - see front matter q 2001 Elsevier Science B.V. All rights reserved. PII: S 1 5 6 6 - 0 7 0 2 Ž 0 1 . 0 0 2 4 3 - 0
T. Tellioglu, D. Robertsonr Autonomic Neuroscience: Basic and Clinical 89 (2001) 96–99
97
Fig. 1. The trace of blood pressure and heart rate of the patient during Valsalva maneuver Žwith 30 mm Hg pressure.. Baseline heart rate is elevated and the 4th phase was exaggerated, otherwise no abnormality was determined.
atenolol, and midodrine. Approximately 3 months ago, she was diagnosed with Cushing’s syndrome, fludrocortisone was stopped, and she was started on furosemide. The patient has had multiple tests at several hospitals to evaluate her postural hypotension and tachycardia. Her
ECHO was reported to be normal. A Holter monitor showed a pulse range from 62 to 162 bpm primarily with tachycardia on standing, but she was often noted to be tachycardic to 120 bpm even at rest. A thallium study was also reported to be normal. The coronary flow was found normal by a coronary angiogram. A tilt test was performed and reported as positive. The patient was admitted to the General Clinical Research Center at Vanderbilt University Medical Center. All medications were discontinued, and she was placed on caffeine-free, sodium and potassium controlled diet. Her physical and neurological examinations were unremarkable. The autonomic function tests revealed orthostatic tachycardia on standing, and were otherwise intact ŽFig. 1.. Upon standing from a supine position, she experienced nausea, chest discomfort, and her heart rate increased 44 bpm with a decrease of 10 mm Hg in systolic blood pressure ŽFig. 2.. Her basal norepinephrine level was 550 pgrml in supine position for 30 min, and increased to 1053 pgrml after standing for 3 min ŽFig. 2.. Addison’s disease was ruled out by ACTH stimulation test. Based upon her history and laboratory testing, a diagnosis of Orthostatic Intolerance was made, and symptomatic treatment for her orthostatic tachycardia was initiated. 3. Discussion
Fig. 2. Hemodynamic and humoral effects of posture in normal controls Žwhite bars, ns 25., in patients with Orthostatic Intolerance ŽOI; black bars, ns 34., and the patient Žshaded bars.. Upper panel shows the changes in heart rate ŽHR., and lower panel shows the changes in plasma norepinephrine ŽNE. taken from an antecubital vein.
In this paper, we present a patient who has been suffering from Behcet’s Disease with recent development of an autonomic disorder, Orthostatic Intolerance. Although several other studies have reported a possible correlation between BD and autonomic insufficiency, to our knowledge, this is the first to suggest the pathophysiology of BD as a potential cause of autonomic dysregulation resulting in OI.
98
T. Tellioglu, D. Robertsonr Autonomic Neuroscience: Basic and Clinical 89 (2001) 96–99
The autonomic nervous system involvement is not uncommon in BD. The iris, which is innervated by the autonomic nervous system, was shown to have significant differences in sensitivity in pupillometric tests between patients and controls ŽBayramlar et al., 1998.. Presence of cardiac abnormalities including left ventricular diastolic dysfunction, a high incidence of positive late potentials, and more complex ventricular arrhythmias ŽKirimli et al., 2000. may be related to autonomic impairment. The power spectrum analysis of heart rate has been used as the main non-invasive diagnostic tool in identifying patients with autonomic nervous system disorders, and BD patients have been found to have increased sympathetic and decreased parasympathetic modulation, suggesting an asymptomatic autonomic nervous system dysfunction ŽAksoyek et al., 1999.. Urodynamic studies have revealed micturitional disturbances, such as post-micturation residuals, detrussor hyperreflexia, increased bladder capacity, decreased bladder sensation, detrusor-sphincter dyssynergia, etc. ŽSakakibara et al., 2000.. Although cases are rarely seen outside the endemic areas Žeastern Asia through the Mediterranean region; Japan, Korea, and Turkey. ŽKaklamani et al., 1998; Mizuki et al., 1997., there are several reports of African and Arab patients with BD in the medical literature ŽJacyk, 1994; Bethea and Khan, 1999.. It is more common among females in Asia, whereas males are more frequently and severely affected in Middle Eastern countries ŽNakae et al., 1993; Kaklamani et al., 1998., and the onset is typically in the third or fourth decade of life ŽKastner, 1997.. On the other hand, OI commonly occurs in young adult females. The age of presentation is between 15 and 50 years ŽJordan et al., 1997.. Unfortunately, we do not have sufficient data about the prevalence of OI in the world or in the black population. It has been reported that susceptibility to Behcet’s Disease is strongly associated with the presence of the HLA-B51 allele ŽOhno et al., 1982; Mizuki et al., 1997.. A similar familial tendency has been observed in patients with OI. Symptoms may occur at different levels, but present in the members of a family. Our group has showed similar hemodynamic and autonomic abnormalities on two twin pairs of OI patients, supporting a genetic predisposition in OI ŽJordan et al., 1999.. The pathophysiology of OI and BD are not well understood, but a common theory for each is a previous viral infection. Herpes simplex virus DNA and serum antibodies against the virus have been found in a higher percentage of patients with BD ŽKaklamani et al., 1998; Lehner, 1997.. Other viruses, including hepatitis C virus and parvovirus B19, may also have some role. However, none of these infectious agents have been proved to cause BD, but their existence might trigger cross-reactive autoimmune responses. Similarly, 50% of OI patients state that they have had a recent viral illness such as a common cold, prior to the onset of their symptoms ŽJordan et al., 1999; Jacob et
al., 2000.. Presence of antibodies specific for nicotinic acetylcholine receptors in the autonomic ganglia has been identified in the blood samples of patients with OI, and the positive correlation between high levels of antibodies and the severity of autonomic dysfunction has been suggested that the antibodies may have a pathogenic role in these types of neuropathy ŽVernino et al., 2000.. Another possible target of this Avirus-triggeredB reaction would be the norepinephrine transport system ŽNET. in presynaptic sympathetic neurons, but we have not yet detected such antibodies. The decreased norepinephrine reuptake may result in an increase of circulating norepinephrine, as was shown in our previous study, in which a genetic defect of NET protein was found to contribute to OI symptoms ŽShannon et al., 2000.. The treatment of patients with OI can be a challenge. Indeed, medications that are useful in some patients may have no effect in others. Acute saline administration Že.g. 1 l intravenously over 1 h. is well known to improve the symptoms. Fludrocortisone Ž0.1 to 0.4 mgrday, orally. can be tried with increased salt intake. The exaggerated sympathetic activation can be reduced by central sympatholytic agents such as clonidine or methyldopa. Beta-blockers have also been used. Vasoconstrictor agents, such as midodrine and phenylpropranolamine can be used to increase peripheral vascular resistance and venous return. Several non-pharmacological approaches, e.g. fitted stockings and short-term exercise may provide some benefits ŽJacob and Biaggioni, 1999.. The role of immunological damage cannot be overlooked in the pathophysiology of BD and OI, but the current data is lacking to provide us a comprehensive understanding. Clinical comparison of autonomic impairment in patients with BD along with other autoimmune diseases warrants further studies.
References Aksoyek, S., Aytemir, K., Ozer, N., Ozcebe, O., Oto, A., 1999. Assessment of autonomic nervous system function in patients with Behcet’ s disease by spectral analysis of heart rate variability. J. Auton. Nerv. Syst. 77, 190–194. Bayramlar, H., Hepsen, I.F., Uguralp, M., Boluk, A., Ozcan, C., 1998. Autonomic nervous system involvement in Behcet’s disease: a pupillometric study. J. Neuroophthalmol. 18, 182–186. Bethea, L., Khan, S., 1999. Behcet’s disease and pheochromocytoma. J. S. C. Med. Assoc. 95, 295–298. Ehrlich, G.E., 1997. Vasculitis in Behcet’s disease. Int. Rev. Immunol. 14, 81–88. Jacob, G., Biaggioni, I., 1999. Idiopathic orthostatic intolerance and postural tachycardia syndromes. Am. J. Med. Sci. 317, 88–101. Jacob, G., Costa, F., Shannon, J.R., Robertson, R.M., Wathen, M., Stein, M., Biaggioni, I., Ertl, A., Black, B., Robertson, D., 2000. The neuropathic postural tachycardia syndrome. N. Engl. J. Med. 343, 1008–1014. Jacyk, W.K., 1994. Behcet’s disease in South African blacks: report of five cases. J. Am. Acad. Dermatol. 30, 869–873.
T. Tellioglu, D. Robertsonr Autonomic Neuroscience: Basic and Clinical 89 (2001) 96–99 Jordan, J., Shannon, J.R., Robertson, D., 1997. The physiological conundrum of hyperadrenergic orthostatic intolerance. Chin. J. Physiol. 40, 1–8. Jordan, J., Shannon, J.R., Jacob, G., Pohar, B., Robertson, D., 1999. Interaction of genetic predisposition and environmental factors in the pathogenesis of idiopathic orthostatic intolerance. Am. J. Med. Sci. 318, 298–303. Kaklamani, V.G., Variopoulos, G., Kaklamanis, P.G., 1998. Behcet’s disease. Semin. Arthritis Rheum. 27, 197–217. Kastner, D.L., 1997. Intermittent and periodic arthritic syndromes. In: Koopman, W.J. ŽEd.., Arthritis and Allied Conditions: A Textbook of Rheumatology. Williams & Wilkins, Baltimore, pp. 1279–1306. Kirimli, O., Aslan, O., Goldeli, O., Guneri, S., Badak, O., Fetil, E., Ozkan, S., 2000. Heart rate variability, late potentials and QT dispersion as markers of myocardial involvement in patients with Behcet’s disease. Can. J. Cardiol. 16, 345–351. Lehner, T., 1997. The role of heat shock protein, microbial and autoimmune agents in the etiology of Behcet’s disease. Int. Rev. Immunol. 14, 21–32. Mizuki, N., Inoko, H., Ohno, S., 1997. Pathogenic gene responsible for the predisposition to Behcet’s disease. Int. Rev. Immunol. 14, 33–48. Nakae, K., Masaki, F., Hashimoto, T., Inaba, G., Mochizuki, M., Sakane,
99
T., 1993. Recent epidemiological features of Behcet’s disease in Japan. In: Wechsler, B., Godeau, P. ŽEds.., Behcet’s Disease. Excerpta Medica, Amsterdam, pp. 145–151. Ohno, S., Ohguchi, M., Hirose, S., Matsuda, H., Wakisaka, A., Aizawa, M., 1982. Close association of HLA-Bw51 with Behcet’s disease. Arch. Ophthalmol. 100, 1455–1458. Robertson, D., 1999. The epidemic of orthostatic tachycardia and orthostatic intolerance. Am. J. Med. Sci. 317, 75–77. Sakakibara, R., Hattori, T., Boku, K., Uchiyama, T., Yamanshi, T., 2000. Micturitional disturbance in neuro-Behcet’s syndrome. Aut. Neurosci. 83, 86–89. Sakane, T., Takeno, M., Suzuki, N., Inaba, G., 1999. Current concepts: Behcet’s disease. N. Engl. J. Med. 341, 17. Serdaroglu, P., 1998. Behcet’s disease and the nervous system. J. Neurol. 245, 197–205. Shannon, J.R., Flattem, N.L., Jordan, J., Jacob, G., Black, B.K., Biaggioni, I., Blakely, R.D., Robertson, D., 2000. Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency. N. Engl. J. Med. 342, 541–549. Vernino, S., Low, P.A., Fealey, R.D., Stewart, J.D., Farrugia, G., Lennon, V.A., 2000. Autoantibodies to ganglionic acetylcholine receptors in autoimmune autonomic neuropathies. N. Engl. J. Med. 343, 847–855.
Orthostatic Intolerance in Behcet’s Disease Tahir Tellioglu, David Robertson ) Autonomic Dysfunction Center, Departments of Medicine, Pharmacology, and Neurology, Vanderbilt UniÕersity Medical Center, AA 3228 MCN, NashÕille, TN 37232, USA Received 27 November 2000; accepted 23 February 2001
Abstract Neurological manifestations are known to occur in patients with Behcet’s Disease ŽBD. and significantly affect the clinical course of the disease. Nevertheless, the prevalence, pattern and severity of autonomic impairment in such patients have yet to be defined. In this paper, we presented a BD patient with orthostatic tachycardia. Non-invasive standardized autonomic function tests revealed no evidence of autonomic impairment, but profound orthostatic tachycardia accompanied by abnormal catecholamine increase was observed upon standing. The diagnosis of Orthostatic Intolerance ŽOI. was made and initial symptomatic therapy was started. The contribution of an immunological damage to components of neural pathways in the pathogenesis of the autonomic involvement can be assumed. q 2001 Elsevier Science B.V. All rights reserved. Keywords: Behcet’s Disease; Orthostatic Intolerance; Autonomic; Autoimmune; Norepinephrine
1. Introduction Behcet’s Disease ŽBD. is a multisystem disorder presenting with recurrent oral and genital ulcerations, as well as ocular involvement ŽKastner, 1997; Sakane et al., 1999.. Vasculitis is the main pathologic lesion, and circulating autoantibodies to human oral mucous membrane antigenŽs. are present in half of the cases, suggesting it as an autoimmune disease ŽEhrlich, 1997.. The neurological involvement in BD patients has been described as primary neural parenchymal lesions Žneuro-Behcet. expressing itself as a meningoencephalitis, brainstem lesion, pseudotumor cerebri, cranial nerve palsies, as well as pyramidal, extrapyramidal, and cerebellar symptoms ŽSerdaroglu, 1998.. However, there have been only a few studies in the literature about the autonomic involvement in BD. The increase in heart rate of 30 beats per minute Žbpm. or greater, usually without significant hypotension upon standing, is diagnostic for Orthostatic Intolerance ŽOI. ŽJordan et al., 1997, Robertson, 1999.. This syndrome is mainly characterized by a variety of postural symptoms upon standing Ži.e. brisk tachycardia, lightheadedness, fa-
)
Corresponding author. Tel.: q1-615-343-6499; fax: q1-615-3438649. E-mail address: [email protected] ŽD. Robertson..
tigue, altered mentation, and syncope.. OI commonly occurs in young adult females, and has been associated with autonomic or neuroendocrine dysregulation, but its cause is still unknown, and may involve a variety of genetic and environmental factors. We recently evaluated a patient with Behcet’s Disease in whom extensive autonomic investigation revealed features of Orthostatic Intolerance. The clinical consequences of autonomic involvement in this patient suggested a probable immunological damage to the components of neural pathways in the pathogenesis of both conditions.
2. Case The patient was a 19-year-old African American female with postural hypotension, tachycardia, headaches, and chest pain. Approximately 5 years ago, she presented with lesions of her oral membranes, arms, legs, back, and vaginal mucosa, and was diagnosed with Behcet’s Disease. She initially received prednisone for several months, and then colchicine. One year ago, the patient developed postural hypotension and tachycardia with standing. Her pulse went into the 160s and her blood pressure would decrease to 80r40 on occasion. This condition was attributed to Addison’s disease, evidenced by an abnormal ACTH stimulation test. The patient was experiencing fainting spells each time she stood, and was treated with fludrocortisone,
1566-0702r01r$ - see front matter q 2001 Elsevier Science B.V. All rights reserved. PII: S 1 5 6 6 - 0 7 0 2 Ž 0 1 . 0 0 2 4 3 - 0
T. Tellioglu, D. Robertsonr Autonomic Neuroscience: Basic and Clinical 89 (2001) 96–99
97
Fig. 1. The trace of blood pressure and heart rate of the patient during Valsalva maneuver Žwith 30 mm Hg pressure.. Baseline heart rate is elevated and the 4th phase was exaggerated, otherwise no abnormality was determined.
atenolol, and midodrine. Approximately 3 months ago, she was diagnosed with Cushing’s syndrome, fludrocortisone was stopped, and she was started on furosemide. The patient has had multiple tests at several hospitals to evaluate her postural hypotension and tachycardia. Her
ECHO was reported to be normal. A Holter monitor showed a pulse range from 62 to 162 bpm primarily with tachycardia on standing, but she was often noted to be tachycardic to 120 bpm even at rest. A thallium study was also reported to be normal. The coronary flow was found normal by a coronary angiogram. A tilt test was performed and reported as positive. The patient was admitted to the General Clinical Research Center at Vanderbilt University Medical Center. All medications were discontinued, and she was placed on caffeine-free, sodium and potassium controlled diet. Her physical and neurological examinations were unremarkable. The autonomic function tests revealed orthostatic tachycardia on standing, and were otherwise intact ŽFig. 1.. Upon standing from a supine position, she experienced nausea, chest discomfort, and her heart rate increased 44 bpm with a decrease of 10 mm Hg in systolic blood pressure ŽFig. 2.. Her basal norepinephrine level was 550 pgrml in supine position for 30 min, and increased to 1053 pgrml after standing for 3 min ŽFig. 2.. Addison’s disease was ruled out by ACTH stimulation test. Based upon her history and laboratory testing, a diagnosis of Orthostatic Intolerance was made, and symptomatic treatment for her orthostatic tachycardia was initiated. 3. Discussion
Fig. 2. Hemodynamic and humoral effects of posture in normal controls Žwhite bars, ns 25., in patients with Orthostatic Intolerance ŽOI; black bars, ns 34., and the patient Žshaded bars.. Upper panel shows the changes in heart rate ŽHR., and lower panel shows the changes in plasma norepinephrine ŽNE. taken from an antecubital vein.
In this paper, we present a patient who has been suffering from Behcet’s Disease with recent development of an autonomic disorder, Orthostatic Intolerance. Although several other studies have reported a possible correlation between BD and autonomic insufficiency, to our knowledge, this is the first to suggest the pathophysiology of BD as a potential cause of autonomic dysregulation resulting in OI.
98
T. Tellioglu, D. Robertsonr Autonomic Neuroscience: Basic and Clinical 89 (2001) 96–99
The autonomic nervous system involvement is not uncommon in BD. The iris, which is innervated by the autonomic nervous system, was shown to have significant differences in sensitivity in pupillometric tests between patients and controls ŽBayramlar et al., 1998.. Presence of cardiac abnormalities including left ventricular diastolic dysfunction, a high incidence of positive late potentials, and more complex ventricular arrhythmias ŽKirimli et al., 2000. may be related to autonomic impairment. The power spectrum analysis of heart rate has been used as the main non-invasive diagnostic tool in identifying patients with autonomic nervous system disorders, and BD patients have been found to have increased sympathetic and decreased parasympathetic modulation, suggesting an asymptomatic autonomic nervous system dysfunction ŽAksoyek et al., 1999.. Urodynamic studies have revealed micturitional disturbances, such as post-micturation residuals, detrussor hyperreflexia, increased bladder capacity, decreased bladder sensation, detrusor-sphincter dyssynergia, etc. ŽSakakibara et al., 2000.. Although cases are rarely seen outside the endemic areas Žeastern Asia through the Mediterranean region; Japan, Korea, and Turkey. ŽKaklamani et al., 1998; Mizuki et al., 1997., there are several reports of African and Arab patients with BD in the medical literature ŽJacyk, 1994; Bethea and Khan, 1999.. It is more common among females in Asia, whereas males are more frequently and severely affected in Middle Eastern countries ŽNakae et al., 1993; Kaklamani et al., 1998., and the onset is typically in the third or fourth decade of life ŽKastner, 1997.. On the other hand, OI commonly occurs in young adult females. The age of presentation is between 15 and 50 years ŽJordan et al., 1997.. Unfortunately, we do not have sufficient data about the prevalence of OI in the world or in the black population. It has been reported that susceptibility to Behcet’s Disease is strongly associated with the presence of the HLA-B51 allele ŽOhno et al., 1982; Mizuki et al., 1997.. A similar familial tendency has been observed in patients with OI. Symptoms may occur at different levels, but present in the members of a family. Our group has showed similar hemodynamic and autonomic abnormalities on two twin pairs of OI patients, supporting a genetic predisposition in OI ŽJordan et al., 1999.. The pathophysiology of OI and BD are not well understood, but a common theory for each is a previous viral infection. Herpes simplex virus DNA and serum antibodies against the virus have been found in a higher percentage of patients with BD ŽKaklamani et al., 1998; Lehner, 1997.. Other viruses, including hepatitis C virus and parvovirus B19, may also have some role. However, none of these infectious agents have been proved to cause BD, but their existence might trigger cross-reactive autoimmune responses. Similarly, 50% of OI patients state that they have had a recent viral illness such as a common cold, prior to the onset of their symptoms ŽJordan et al., 1999; Jacob et
al., 2000.. Presence of antibodies specific for nicotinic acetylcholine receptors in the autonomic ganglia has been identified in the blood samples of patients with OI, and the positive correlation between high levels of antibodies and the severity of autonomic dysfunction has been suggested that the antibodies may have a pathogenic role in these types of neuropathy ŽVernino et al., 2000.. Another possible target of this Avirus-triggeredB reaction would be the norepinephrine transport system ŽNET. in presynaptic sympathetic neurons, but we have not yet detected such antibodies. The decreased norepinephrine reuptake may result in an increase of circulating norepinephrine, as was shown in our previous study, in which a genetic defect of NET protein was found to contribute to OI symptoms ŽShannon et al., 2000.. The treatment of patients with OI can be a challenge. Indeed, medications that are useful in some patients may have no effect in others. Acute saline administration Že.g. 1 l intravenously over 1 h. is well known to improve the symptoms. Fludrocortisone Ž0.1 to 0.4 mgrday, orally. can be tried with increased salt intake. The exaggerated sympathetic activation can be reduced by central sympatholytic agents such as clonidine or methyldopa. Beta-blockers have also been used. Vasoconstrictor agents, such as midodrine and phenylpropranolamine can be used to increase peripheral vascular resistance and venous return. Several non-pharmacological approaches, e.g. fitted stockings and short-term exercise may provide some benefits ŽJacob and Biaggioni, 1999.. The role of immunological damage cannot be overlooked in the pathophysiology of BD and OI, but the current data is lacking to provide us a comprehensive understanding. Clinical comparison of autonomic impairment in patients with BD along with other autoimmune diseases warrants further studies.
References Aksoyek, S., Aytemir, K., Ozer, N., Ozcebe, O., Oto, A., 1999. Assessment of autonomic nervous system function in patients with Behcet’ s disease by spectral analysis of heart rate variability. J. Auton. Nerv. Syst. 77, 190–194. Bayramlar, H., Hepsen, I.F., Uguralp, M., Boluk, A., Ozcan, C., 1998. Autonomic nervous system involvement in Behcet’s disease: a pupillometric study. J. Neuroophthalmol. 18, 182–186. Bethea, L., Khan, S., 1999. Behcet’s disease and pheochromocytoma. J. S. C. Med. Assoc. 95, 295–298. Ehrlich, G.E., 1997. Vasculitis in Behcet’s disease. Int. Rev. Immunol. 14, 81–88. Jacob, G., Biaggioni, I., 1999. Idiopathic orthostatic intolerance and postural tachycardia syndromes. Am. J. Med. Sci. 317, 88–101. Jacob, G., Costa, F., Shannon, J.R., Robertson, R.M., Wathen, M., Stein, M., Biaggioni, I., Ertl, A., Black, B., Robertson, D., 2000. The neuropathic postural tachycardia syndrome. N. Engl. J. Med. 343, 1008–1014. Jacyk, W.K., 1994. Behcet’s disease in South African blacks: report of five cases. J. Am. Acad. Dermatol. 30, 869–873.
T. Tellioglu, D. Robertsonr Autonomic Neuroscience: Basic and Clinical 89 (2001) 96–99 Jordan, J., Shannon, J.R., Robertson, D., 1997. The physiological conundrum of hyperadrenergic orthostatic intolerance. Chin. J. Physiol. 40, 1–8. Jordan, J., Shannon, J.R., Jacob, G., Pohar, B., Robertson, D., 1999. Interaction of genetic predisposition and environmental factors in the pathogenesis of idiopathic orthostatic intolerance. Am. J. Med. Sci. 318, 298–303. Kaklamani, V.G., Variopoulos, G., Kaklamanis, P.G., 1998. Behcet’s disease. Semin. Arthritis Rheum. 27, 197–217. Kastner, D.L., 1997. Intermittent and periodic arthritic syndromes. In: Koopman, W.J. ŽEd.., Arthritis and Allied Conditions: A Textbook of Rheumatology. Williams & Wilkins, Baltimore, pp. 1279–1306. Kirimli, O., Aslan, O., Goldeli, O., Guneri, S., Badak, O., Fetil, E., Ozkan, S., 2000. Heart rate variability, late potentials and QT dispersion as markers of myocardial involvement in patients with Behcet’s disease. Can. J. Cardiol. 16, 345–351. Lehner, T., 1997. The role of heat shock protein, microbial and autoimmune agents in the etiology of Behcet’s disease. Int. Rev. Immunol. 14, 21–32. Mizuki, N., Inoko, H., Ohno, S., 1997. Pathogenic gene responsible for the predisposition to Behcet’s disease. Int. Rev. Immunol. 14, 33–48. Nakae, K., Masaki, F., Hashimoto, T., Inaba, G., Mochizuki, M., Sakane,
99
T., 1993. Recent epidemiological features of Behcet’s disease in Japan. In: Wechsler, B., Godeau, P. ŽEds.., Behcet’s Disease. Excerpta Medica, Amsterdam, pp. 145–151. Ohno, S., Ohguchi, M., Hirose, S., Matsuda, H., Wakisaka, A., Aizawa, M., 1982. Close association of HLA-Bw51 with Behcet’s disease. Arch. Ophthalmol. 100, 1455–1458. Robertson, D., 1999. The epidemic of orthostatic tachycardia and orthostatic intolerance. Am. J. Med. Sci. 317, 75–77. Sakakibara, R., Hattori, T., Boku, K., Uchiyama, T., Yamanshi, T., 2000. Micturitional disturbance in neuro-Behcet’s syndrome. Aut. Neurosci. 83, 86–89. Sakane, T., Takeno, M., Suzuki, N., Inaba, G., 1999. Current concepts: Behcet’s disease. N. Engl. J. Med. 341, 17. Serdaroglu, P., 1998. Behcet’s disease and the nervous system. J. Neurol. 245, 197–205. Shannon, J.R., Flattem, N.L., Jordan, J., Jacob, G., Black, B.K., Biaggioni, I., Blakely, R.D., Robertson, D., 2000. Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency. N. Engl. J. Med. 342, 541–549. Vernino, S., Low, P.A., Fealey, R.D., Stewart, J.D., Farrugia, G., Lennon, V.A., 2000. Autoantibodies to ganglionic acetylcholine receptors in autoimmune autonomic neuropathies. N. Engl. J. Med. 343, 847–855.