Guest tearose Posted March 7, 2005 Report Share Posted March 7, 2005 The abstract is free and I have the full text from the library but this is a "must read"!When I can find a way to scan it in I will post the text or if anyone has a way to link to the free full text please do!abstract link: http://hyper.ahajournals.org/cgi/content/abstract/45/3/385I am so excited about this research...it seems to get closer to what causes the "autonomic storm".Now we know to ask about having urine methylhistamine levels tested!tearose Quote Link to comment Share on other sites More sharing options...
Jersey Girl Posted March 7, 2005 Report Share Posted March 7, 2005 Thanks for posting this great information. I have yet to have my urine methylhistamine levels tested and think that I should. I definitely reacted very poorly to beta-blockers. Martha Quote Link to comment Share on other sites More sharing options...
geneva Posted March 7, 2005 Report Share Posted March 7, 2005 I only read the abstract but found the article interesting. Hope you can post the entire article when you are up to it. Here's the question....if the urine methlhistamine levels are too high or low, is there somehting they can do to correct the situation? Is this something that is a simple urine test or one of the things you would have tested in the 24 hour test? thanks Tearose for finding the article. Quote Link to comment Share on other sites More sharing options...
MomtoGiuliana Posted March 8, 2005 Report Share Posted March 8, 2005 Thanks so much tearose.geneva--it looks like the only benefit of this urine test at this time is to predict how you might respond to a beta blocker regime? Certainly very useful information--but still no insight on how to correct or treat the mast cell activation problem? I sent an e-mail to the author asking about this. If I get a response from him, I will post it.Katherine Quote Link to comment Share on other sites More sharing options...
geneva Posted March 8, 2005 Report Share Posted March 8, 2005 Katherine, thanks for the information. The abstract referenced "treatment directed against mast cell mediators may be required" which is what made me think maybe they had something specific in mind. What a good idea to write the author. Quote Link to comment Share on other sites More sharing options...
Guest tearose Posted March 8, 2005 Report Share Posted March 8, 2005 I'm trying to find a way to scan the full article into the computer...can I fax it to someone who can scan it in?The article will answer a lot of your questions! The treatment for Mast Cell Activation to keep from triggering the hyperadrenergic reaction is of all things...something like an antihistamine!!!Whoever knows where I can fax this to let me know!!!tearose Quote Link to comment Share on other sites More sharing options...
MomtoGiuliana Posted March 8, 2005 Report Share Posted March 8, 2005 I got a very prompt response to my e-mail to Dr. Biaggioni. What a kind soul.Here is his response. He also sent me the entire article that I will also post next(hopefully that is ok for copyright reasons.)This is his reply to me:Many patients do not respond well to a regular dose of beta blockers anddo better with a low dose.Lack of response to beta blockers, therefore, is not an indicator ofmast cell activation.The patients we described had episodes of obvious severe flushing in theface and neck. Even in these patients, only half had documented mastcell activation (with elevated urine methylhistamines immediately aftera spell).Depending on the patient, we have bee successful in treatinghyperadrenergic POTS with aldomet alone or in combination withfludrocortisone. Only some patients require more targeted therapyagainst mast cell activation, which requires medical supervision.I hope you understand that these are only general comments. I cannotmake more specific recommendations over the internet.Hope this helps.Italo Biaggioni Quote Link to comment Share on other sites More sharing options...
MomtoGiuliana Posted March 8, 2005 Report Share Posted March 8, 2005 Here is the text of the article. It is minus the tables of course (except one that I attempted to paste in--but I am afraid it is confusing due to lack of formatting), but perhaps this will be helpful to peruse, regardless!I didn't include the abstract since that is already available at the link above.It is six pages, plus a 5-page supplemental and I would be glad to copy and snail mail it to anyone who needs it for $1.75 for the whole thing (enough to cover postage and copying costs! ).________________________________________________________Postural tachycardia syndrome (POTS) is a disablingcondition that commonly affects otherwise normal youngfemales. This disorder is characterized by symptoms offatigue, tachycardia, shortness of breath, and even syncope onstanding. The etiology is not clear, but 2 possibilities havebeen proposed previously. In the neuropathic variant, theprimary defect is thought to be a partial autonomic denerva-tionthat compromises lower limbs with exaggerated ortho-staticvenous pooling,1 and perhaps the kidneys with lowlevels of plasma renin activity.2 Patients with the hyperadren-ergicvariant are thought to have centrally driven sympatheticactivation.3A circulating vasodilator could produce reflex sympatheticactivation, presenting clinically as ?hyperadrenergic? POTS.In our evaluation of patients with POTS, some describedflushing episodes associated with orthostatic intolerance. Onthe basis of this observation, also reported by others, wehypothesized that activated mast cells may provide a sourceof circulating vasodilators in a subset of patients withhyperadrenergic POTS. If true, histamine and other mast cellmediators could play an important role in the pathogenesis ofthis syndrome.There is a wide spectrum of disorders associated with mastcell pathology. Mastocytosis is a common term used to defineabnormal proliferation and accumulation of mast cells in 1 ormore body tissues. The clinical manifestation is produced byepisodic release of mast cell mediators in response to specificstimuli 8 and can follow either an indolent or aggressivecourse ranging from circumscribed cutaneous involvement tolife-threatening mast cell leukemia. In 1991, Roberts andOates described the clinical syndrome of idiopathic mast cellactivation (MCA).9 In this condition, there is no evidence ofmast cell proliferation, but patients are disabled by episodicMCA, documented by accumulation of mediators in plasmaor urine. Patients with this syndrome typically present epi-sodesor ?attacks? of flushing accompanied by palpitations,lightheadedness, dizziness, shortness of breath, occasionalnausea and diarrhea, headache, and syncope.Here we describe patients disabled by persistent orthostaticintolerance and evidence of MCA. These patients oftenpresent with a typical hyperadrenergic variant of POTS andbiochemical evidence of MCA. _-Blockers should be usedwith great caution in these patients, if at all, and treatmentdirected against mast cell mediators may be required.MethodsSubjectsWe evaluated 177 subjects referred to the Vanderbilt AutonomicDysfunction Clinic for disabling orthostatic intolerance who werestudied as inpatients from January 1995 to January 2004. A patientwas considered to have an MCA disorder and POTS (also known asorthostatic intolerance) if they met the following criteria. (1) Long-standing(_6 months) disabling orthostatic intolerance; (2) anincrease in heart rate of _30 bpm within 5 minutes after assuming astanding position; (3) absence of an underlying cause (debilitatingdisease, substantial weight loss, prolonged bed rest, previous historyof any disease producing peripheral neuropathy, or any medicationimpairing autonomic reflexes); (4) a history of facial or upper trunkflushing (defined as objective and intense facial redness witnessed bya physician or caregiver); and (5) urine methylhistamine _230 _g/gcreatinine associated with a flushing episode.9 Patients were classi-fiedinto 3 separate groups. Eight young female subjects met thecriteria of MCA and POTS (MCA_POTS). An additional 5 patientswere identified as having similar characteristics, with the exceptionthat they presented with orthostatic hypotension (OH; identified by adecrease in systolic blood pressure of _20 mm Hg or in diastolicblood pressure of _10 mm Hg; MCA_OH). We thought it impor-tantto include a group of 16 patients with a history of POTS withfacial flushing but no evidence of MCA (documented by absence ofincreased urine methylhistamine, POTS). This provides a compari-songroup to determine whether the presence of MCA modifies theclinical presentation of POTS. We also include a fourth controlgroup of 12 normal, healthy, age-matched females.ProceduresAll subjects were admitted to the Vanderbilt General ClinicalResearch Center and were fed a low-monoamine, caffeine-free dietcontaining 150 mEq sodium and 70 mEq potassium per day for atleast 3 days before evaluation. Medications affecting the autonomicnervous system were withheld for at least 3 days before admission.Autonomic function tests were used to evaluate the integrity of thedifferent reflex arcs. These included Valsalva maneuver, the coldpressor and handgrip tests to assess cardiovascular autonomic function,and the sinus arrhythmia ratio (change in heart rate in response tocontrolled breathing) to assess cardiac parasympathetic activity.10 Alltests were standardized previously in our laboratory.11 An orthostatictest was performed to evaluate hemodynamic and hormonal changes onstanding. An indwelling catheter was placed in an antecubital vein toobtain blood samples while patients remained supine after an overnightrest. Subjects were encouraged to stand as long as possible or up to 30minutes. During this period, they were allowed to sit at intervals ifpresyncopal symptoms developed. Blood samples were obtained forcatecholamines, aldosterone, and renin measurements. Brachial bloodpressure and heart rate were obtained using an automated sphygmoma-nometer(Dinamap; GE Medical Systems Information Technologies)during supine and standing test phases.Plasma catecholamine levels were determined by high-performanceliquid chromatography with electrochemical detection.12 Plasma reninenzymatic activity was assessed by the conversion of angiotensinogen toangiotensin I and expressed as nanograms of angiotensin I produced permilliliter of plasma per hour. Plasma aldosterone was measured byradioimmunoassay.13 Urine samples were obtained in patients with ahistory of flushing in the face or upper trunk. Patients were asked tocollect urine for 4 hours immediately after a spontaneous severe flushingepisode, defined by a subjective intensity of symptoms of ?7 to 8? on ascale of ?0? (no symptoms) to ?10? (the worst symptoms ever). Thiswas done during the inpatient or outpatient evaluation. Samples wereobtained within 4 hours after a spontaneous episode. Methylhistaminelevels were measured by gas chromatography negative ion chemicalionization mass spectrometry.14 In no case was there any abnormality inhematologic laboratory results consistent with systemic mastocytosis.To determine the response to treatment, a research nurse contacted thepatients 3 months after discharge and obtained information aboutthe medication, the frequency of mast cell episodes with flushing, andthe intensity of orthostatic tachycardia. We were able to obtain infor-mation on 6 patients with MCA_POTS and in 3 patients withMCA_OH.Statistical AnalysisData were analyzed using SPSS version 11 (SPSS). Frequency tableswere generated for categorical variables. Continuous variables areexpressed as mean_SEM. Group comparisons were made using thenonparametric Kruskal?Wallis test. Post hoc analysis between 2groups was made using the nonparametric Mann?Whitney test.Criterion for significance was P_0.05.ResultsClinical Characteristics and Autonomic Responseto PostureClinical characteristics of patients and controls are presentedin Tables 1 and 2. All patients except 1 were female, and allwere white, non-Hispanic, with an age range between 18 and50 years. There was no significant difference in age, weight,and body mass index between groups. Symptoms duringepisodes included flushing, palpitations, lightheadedness withsevere orthostatic intolerance, nausea, diarrhea, abdominalcramping, and polyuria. Blood pressure increased acutely insome cases. Patients often exhibited hypersomnia, sleepingfor hours after these episodes.Hemodynamic and humoral responses to posture are shown inFigures 1 and 2. As expected by the selection of subjects,standing heart rate was significantly higher in the MCA_POTS,POTS, and MCA_OH groups compared with normal subjects(P_0.001). Mean supine diastolic blood pressure was signifi-cantlydifferent between groups (P_0.005); MCA_OH patientshad higher values compared with MCA_POTS, POTS, andnormal subjects. Upright systolic blood pressure was signifi-cantlyincreased in the MCA_POTS group compared withnormal subjects (Table 1; Figure 2; P_0.013). We identified 5patients who presented with orthostatic hypertension, defined byan increase in systolic blood pressure on standing of_20 mm Hg. Furthermore, 4 patients presented with episodes ofsudden onset of hypertension and palpitations. There were noobvious triggering events, and these episodes resolved sponta-neously.The supine and upright blood pressure obtained fromthese patients as well as the blood pressure values during thehypertensive crisis are presented in supplemental Table I andsupplemental Figure Ia and Ib (available online athttp://www.hypertensionaha.org).Mean supine plasma norepinephrine levels were significantlydifferent between groups: MCA_OH was higher thanMCA_POTS, POTS, and normal subjects (Table 1; Figure 2;P_0.004). Supine plasma norepinephrine was also significantlyhigher in MCA_POTS patients compared with controls(269_41 and 129_22 pg/mL, respectively; P_0.05; Figure 2)but not compared with POTS patients. No differences wereobserved in supine and upright epinephrine, renin activity, oraldosterone.As expected, the methylhistamine levels were different be-tweenpatients with MCA_POTS and MCA_OH comparedwith POTS controls (P_0.001). Although not statistically sig-nificant,patients with MCA_OH tended to have higher levelsof urinary methylhistamine compared with MCA_POTS pa-tients(Table 1).Characterization of Autonomic FunctionAutonomic function tests are presented in Table 3 and Figure3. No significant differences in systolic blood pressure wereobserved between groups at baseline for Valsalva maneuver,the hyperventilation test, the cold pressor test, and thehandgrip test. There was a difference in systolic bloodpressure during phase IILate of the Valsalva maneuver(P_0.048; Table 3; Figure 3). The MCA_POTS group had asignificantly higher systolic blood pressure compared withPOTS and normal controls (P_0.023 and P_0.027, respec-tively).During phase IV of the Valsalva maneuver, weobserved that groups with MCA_POTS and POTS presentedan excessive increase in systolic blood pressure (hypertensiveovershoot) compared with normal controls (Figure 3). Thechange in systolic blood pressure between baseline and phaseIV of the Valsalva maneuver was significantly higher in theMCA_POTS group (50_10 mm Hg) compared with thePOTS group (31_5 mm Hg) and controls (17_3 mm Hg). Ina post hoc analysis, no differences were found betweenpatients with MCA_POTS and POTS (P_0.168). The sys-tolic blood pressure and diastolic blood pressure after 1minute of the cold pressor test and after 3 minutes of thehandgrip test were different between groups. In MCA_POTSpatients, systolic blood pressure increased 35_12 mm Hgduring the cold pressor test, whereas the response in normalcontrols averaged 20_5 mm Hg.Triggering of MCA With ExerciseBecause patients often referred to episodes of flushing trig-geredby exercise, we performed treadmill exercise on 3subjects. Flushing was triggered in these patients, and thiswas associated with an increased in urinary methylhistamine(supplemental Figure II). In 1 patient, we documented anincrease in plasma histamine, indicative of mast cell degran-ulationbut not of plasma prostaglandin D2 (PGD2), a markerof newly formed mast cell mediator release (supplementalFigure II).Response to TreatmentThe response to treatment in patients in whom follow-up wasavailable is shown in supplemental Table II. Because of thenumber of patients, we did not attempt to perform acontrolled study, and these observations remain anecdotal.However, it is noteworthy that patients improved clinicallywhen treated with H1 and H2 histamine receptor blockers withthe sympatholytic _-methyldopa, or with a combination ofboth. Of note, _-blockers triggered episodes consistent withacute MCA in 2 patients, and 4 patients had allergic reactionsto aspirin, ranging from bronchoconstriction to anaphylaxis.DiscussionWe describe here a novel syndrome characterized by chronicdisabling orthostatic tachycardia associated with episodes of sys-temicMCA. It affects otherwise normal young subjects, typicallywomen, and causes substantial disability. We found no evidence ofa primary diffuse autonomic neuropathy as the cause of thissyndrome; autonomic reflexes appeared to be intact or overactive.On the contrary, exaggerated sympathetic activation was suggestedby high plasma norepinephrine levels and increased systolic bloodpressure in the upright posture. We and others have describedpatients with orthostatic intolerance, in many ways indistinguishablefrom patients presented here, who seem to have partial sympatheticdenervation, preferentially involving lower limbs, the ?neuropathic?POTS.1 The clinical criteria that differentiate between the neuro-pathicand hyperadrenergic forms of this disease are not defined.We believe that the patients described in this report correspond tothe hyperadrenergic form of POTS because of the exaggeratedsympathetic pressor response during phase IILate and phase IV of theValsalva maneuver and the exaggerated increase in blood pressureon standing.Episodes of MCA were documented in these patients byelevated levels of urinary methylhistamine taken immediatelyafter a spontaneous event. It should be noted that urinarymethylhistamine is usually normal in between episodes inpatients with MCA disorders,9 and patients should be instructedto collect urine for a 4-hour period immediately after a severespontaneous flushing episode. Urinary histamine is often mea-suredin the evaluation of flushing, but it is less specific thanmethylhistamine and not useful in the diagnosis of MCA. Thesymptoms described during these spells are probably induced byacute release of mast cell mediators such as histamine andPGD2.15,16 Patients with isolated MCA are symptomatic onlyduring episodes, whereas our group of patients also experiencedchronic fatigue and orthostatic intolerance in between episodes,eventually leading to a disabling condition.Hypertension can be a prominent feature in some patientswith MCA and POTS. We observed 2 different clinical presen-tationsof this association. Patients may present with a consistenthypertensive response to upright posture or with acute hyperten-sivecrisis. During these hypertensive episodes, blood pressurecan increase to as high as 240/140 mm Hg, and the episodes aresimilar to the hypertensive variant of MCA disorders describedpreviously.9 These events resemble pheochromocytoma inas-muchas they are accompanied by tachycardia, nervousness,shortness of breath, and hypertension. A similar clinical presen-tation,known as pseudopheochromocytoma or diencephalichypertension, has been described by Page.17 Flushing is promi-nentin MCA disorders and in pseudopheochromocytoma and isa useful clinical distinction with pheochromocytoma, which isaccompanied by pallor. Plasma norepinephrine is increased inboth conditions, but levels are much higher in pheochromocy-tomabecause catecholamines are released directly into thecirculation, whereas in pseudopheochromocytoma, catechol-aminesare released into the synapse, and only a relatively smallproportion spills over into the circulation.We also report a group of patients with flushing and orthostaticintolerance but no evidence of MCA. The cause of flushing in thosepatients is not clear. Other entities associated with flushing andsimilar clinical characteristics are associated with dopamine release,as described by Kuchel.18 Panic attacks can also be associated withflushing and regional sympathetic activation,19 but patients usuallydo not experience orthostatic intolerance between attacks.Mast cells are localized in close proximity to blood vessels andperipheral nerves and are therefore strategically positioned tomodulate sympathetic activity, vascular tone, and angiogenesis.20Histamine is a powerful vasodilator that could explain the cutaneousvasodilatation responsible for flushing. With regard to the patho-physiologyunderlying the association between POTS and MCA,we propose a positive feedback loop by which MCA, with thesubsequent release of vasoactive mediators, may contribute tovasodilation, reflex sympathetic activation, central volume contrac-tion,norepinephrine release, and orthostatic intolerance (Figure 4).Conversely, our results indicate that exercise can lead to MCA,presumably through sympathetic activation. In this regard, neu-ropeptideY (NPY), a 36-aa neuropeptide that is coreleased withnorepinephrine from noradrenergic neurons, has been shown toinduce mast cell degranulation with the release of preformedmediators in purified rat peritoneal 21,22 and human jejunal mastcells 23 and to induce hypotension in animals secondary to MCA invivo.24 This appears to be a nonreceptor-mediated effect related tothe presence of positively charged amino acid residues of the Cterminus of NPY. Therefore, the physiological significance ofNPY-mediated MCA remains speculative.Our findings have potential implications for the treatment ofthese patients. Because of the prominent orthostatic tachycardia,_-blockers are commonly used in the treatment of POTS patients.However, these drugs should be used with great caution in thesepatients, if at all, because of possible worsening of MCA. In ourexperience, a therapeutic trial with _-methyldopa should be consid-ered,given the evidence of a hyperadrenergic state. Some patientsmay require treatment directed at controlling mast cell mediators,including H1 and H2 receptor antagonists.PerspectivesWe report a novel syndrome of chronic hyperadrenergicorthostatic intolerance associated with episodes of MCA.This syndrome should be considered in POTS patients with ahistory of flushing. This symptom is often not volunteered bypatients and may require careful questioning by the physician.Diagnosis requires biochemical documentation of MCA be-causeother causes of flushing can be associated with POTS.A correct diagnosis is important because the presence ofMCA mandates a different approach in the treatment of thesepatients. _-Blockers, a commonly used therapeutic option inPOTS patients, should be used with caution, if at all, becauseof the risk of triggering MCA. These patients can be treatedwith H1/H2 histamine antagonist and central sympatholytics.AcknowledgmentsThis research was supported in part by a general clinical researchcenter grant from National Center for Research Resources and bygrants HL56693 and HL67232 from the National Institutes ofHealth. S.R.R. is supported by a K12 grant from the NationalInstitutes of Health. C.S. is recipient of the international fellowshipin clinical pharmacology supported by Merck Foundation.References1. Jacob G, Costa F, Shannon JR, Robertson RM, Wathen M, Stein M,Biaggioni I, Ertl A, Black B, Robertson D. The neuropathic posturaltachycardia syndrome. N Engl J Med. 2000;343:1008 ?1014.2. Jacob G, Robertson D, Mosqueda-Garcia R, Ertl AC, Robertson RM,Biaggioni I. Hypovolemia in syncope and orthostatic intolerance role of therenin-angiotensin system. Am J Med. 1997;103:128 ?133.3. Jordan J, Shannon JR, Diedrich A, Black BK, Robertson D. Increasedsympathetic activation in idiopathic orthostatic intolerance: role of systemicadrenoreceptor sensitivity. Hypertension. 2002;39:173?178.4. Kuchel O, Leveille J. Idiopathic hypovolemia: a self-perpetuating autonomicdysfunction? Clin Auton Res. 1998;8:341?346.5. Biaggioni I. Orthostatic intolerance syndrome, vasoregulatory asthenia andother hyperadrenergic states. In: Robertson D, Biaggioni I, eds. Disorders ofthe Autonomic Nervous System. London, UK: Harwood Academic Pub-lishers;1995.6. Streeten DH, Kerr CB, Kerr LP, Prior JC, Dalakos TG. Hyperbradykininism:a new orthostatic syndrome. Lancet. 1972;2:1048 ?1053.7. Valent P, Akin C, Sperr WR, Horny HP, Metcalfe DD. Mast cell proliferativedisorders: current view on variants recognized by the World Health Organi-zation.Hematol Oncol Clin North Am. 2003;17:1227?1241.8. Castells M, Austen KF. Mastocytosis: mediator-related signs and symptoms.Int Arch Allergy Immunol. 2002;127:147?152.9. Roberts LJ, Oates JA. Biochemical diagnosis of systemic mast cell disorders.J Invest Dermatol. 1991;96:19S?24S.10. Mosqueda-Garcia R. Evaluation of the autonomic nervous system. In:Robertson D, Biaggioni I, eds. Disorders of the Autonomic Nervous System.London, UK: Harwood Academic Publishers; 1995.11. Robertson D. Clinical pharmacology: assessment of autonomic function. In:Clinical Diagnostic Manual for the House Officer. Baltimore, Md: Williamand Wilkins; 1981.12. Goldstein DS, Eisenhofer G, Stull R, Folio CJ, Keiser HR, Kopin IJ. Plasmadihydroxyphenylglycol and the intraneuronal disposition of norepinephrine inhumans. J Clin Invest. 1988;81:213?220.13. Workman RJ, Sussman CR, Burkitt DW, Liddle GW. Circulating levels ofangiotensin I measured by radioimmunoassay in hypertensive subjects. J LabClin Med. 1979;93:847? 856.14. Roberts LJ, Oates JA. Accurate and efficient method for quantification ofurinary histamine by gas chromatography negative ion chemical ionizationmass spectrometry. Anal Biochem. 1984;136:258 ?263.15. Morrow JD, Guzzo C, Lazarus G, Oates JA, Roberts LJ. Improved diagnosisof mastocytosis by measurement of the major urinary metabolite of prosta-glandinD2. J Invest Dermatol. 1995;104:937?940.16. Roberts LJ, Sweetman BJ, Lewis RA, Austen KF, Oates JA. Increasedproduction of prostaglandin D2 in patients with systemic mastocytosis.N Engl J Med. 1980;303:1400 ?1404.17. Page IH. A syndrome simulating diencephalic stimulation occurring inpatients with essential hypertension. Am J Med Sci. 1935;190:9 ?14.18. Kuchel O, Buu NT, Hamet P, Larochelle P, Gutkowska J, Schiffrin EL,Bourque M, Genest J. Orthostatic hypotension: a posture-induced hyperdo-paminergicstate. Am J Med Sci. 1985;289:3?11.19. Wilkinson DJ, Thompson JM, Lambert GW, Jennings GL, Schwarz RG,Jefferys D, Turner AG, Esler MD. Sympathetic activity in patients with panicdisorder at rest, under laboratory mental stress, and during panic attacks. ArchGen Psychiatry. 1998;55:511?520.20. Feoktistov I, Ryzhov S, Goldstein AE, Biaggioni I. Mast cell-mediatedstimulation of angiogenesis: cooperative interaction between A2B and A3adenosine receptors. Circ Res. 2003;92:485? 492.21. Arzubiaga C, Morrow J, Roberts LJ, Biaggioni I. Neuropeptide Y, a putativecotransmitter in noradrenergic neurons, induces mast cell degranulation butnot prostaglandin D2 release. J Allergy Clin Immunol. 1991;87:88 ?93.22. Grundemar L, Hakanson R. Neuropeptide Y, peptide YY and C-terminalfragments release histamine from rat peritoneal mast cells. Br J Pharmacol.1991;104:776 ?778.23. Santos J, Saperas E, Nogueiras C, Mourelle M, Antolin M, Cadahia A,Malagelada JR. Release of mast cell mediators into the jejunum by cold painstress in humans. Gastroenterology. 1998;114:640 ?648.24. Shen GH, Grundemar L, Zukowska-Grojec Z, Hakanson R, Wahlestedt C.C-terminal neuropeptide Y fragments are mast cell-dependent vasodepressoragents. Eur J Pharmacol. 1991;204:249 ?256._______________________________________If you can interpret this table with its lack of formatting, I thought this might be useful to include. KM________________________________________TABLE 2. Clinical Manifestation of Patients With POTS andMCA DisorderOrthostatic Symptoms?n (%)MCA_POTS MCA_OHn %n%Flushing 8 100 5 100Palpitations 8 100 5 100Lightheadedness 8 100 3 60Chronic fatigue 7 88 3 60Headache 5 63 2 40Dizziness 5 63 4 80Presyncope/syncope episodes 3 38 1 20Shortness of breath 3 38 2 40Confusion 3 38Increase in blood pressure 3 38Paresthesias 3 38Gastrointestinal symptoms (nausea and vomiting) 3 38 4 80Abdominal cramps and diarrhea 3 38 3 60Blurred vision 2 25Anxiety 2 25 1 20Excessive diuresis 5 100Orthostatic intolerance exacerbated by?n (%)After exercise 5 63 5 100Prolonged standing 3 38 1 20After meals 3 38 1 20Premenstrual 2 25 1 20Heat intolerance 2 25 5 100Emotional stress 1 13 1 20Sexual intercourse 1 13 Quote Link to comment Share on other sites More sharing options...
Ernie Posted March 8, 2005 Report Share Posted March 8, 2005 Thanks Katherine and Tearose for posting this article. I will print it and bring it to my doctors.Ernie Quote Link to comment Share on other sites More sharing options...
Guest Julia59 Posted March 9, 2005 Report Share Posted March 9, 2005 Tearose,That is a very interesting article. I think I did read the abstract at one time.It was nice to see to whole thing---thanks MomtoGiulianaI will copy and paste it to my Microsoft word. In the beginning of my POTS I was so hyper adrengic and had so many of those attacks I was not able to eat. And I had the attacks on beta-blockers! 60mg of propranolol was not enough----I was truly a mess for about 6 months until Dr. Grubb put me on the Wellbutrin. Then the attacks went away---but I still get milder ones, and unfortunately most of the other potsy symptoms. The the hyper adrengic attacks stopped me in my tracks. Crippling.I never did have any autonomic testing other then the TT test. All this blood work I read about---I've never had any of it done. I will ask Dr. Grubb why on the 22nd this month---that is my next appointment.Julie :0) Quote Link to comment Share on other sites More sharing options...
Ernie Posted March 9, 2005 Report Share Posted March 9, 2005 I just realised while I was reading this article that I was part of this research! Kind of weird.Ernie Quote Link to comment Share on other sites More sharing options...
EarthMother Posted March 9, 2005 Report Share Posted March 9, 2005 Big thanks to Ernie for being our famous celebrity white rat in the article!Did anyone else venture to pay for the second article in this month's journal of hypotension. The one that references this study. It looks to be an ed op piece and while it is filled with techno-jargon I can not hope to understand, it may be that the authors disagree with the findings.Snippit from:Editorial Commentaries The Causes of Postural Cardiovascular Disorders Michael G. Ziegler; Demetri P. Rizos"Mast cell disorders did not cause OH in most of Shibao?s subjects because reflex sympathetic nervous activation enhanced cardiac output enough to maintain blood pressure.9 However, a patient with a disease that alters cardiovascular physiology will eventually experience other cardiovascular stresses, such as fever, dehydration, or drugs. At that point, the mild cardiovascular disease may manifest itself as OH, often reported to a physician as "feeling too weak to get up." The most important postural cardiovascular tests described by Shibao et al1 are widely available and can often point toward cause and treatment. "I've printed out both and will review with my doctor at my next appointment. No easy answers. Many thanks to all of you for shedding light on this moving target.EM Quote Link to comment Share on other sites More sharing options...
Radha Posted March 9, 2005 Report Share Posted March 9, 2005 is there any test to confirm you have a mast cell disorder? radha Quote Link to comment Share on other sites More sharing options...
Guest tearose Posted March 9, 2005 Report Share Posted March 9, 2005 Radha, I'm still trying to understand the entire article however I do see the way to see if you have this kind of mast cell activation is by urine sample. They look for samples from people who have had an "autonomic storm" a pots diagnosis and then take the sample 4 hours after the storm and check for levels of urine methylhistimine.this is in the full article:Urine samples were obtained in patients with ahistory of flushing in the face or upper trunk. Patients were asked tocollect urine for 4 hours immediately after a spontaneous severe flushingepisode, defined by a subjective intensity of symptoms of ?7 to 8? on ascale of ?0? (no symptoms) to ?10? (the worst symptoms ever). Thiswas done during the inpatient or outpatient evaluation. Samples wereobtained within 4 hours after a spontaneous episode. Methylhistaminelevels were measured by gas chromatography negative ion chemicalionization mass spectrometry.14 In no case was there any abnormality inhematologic laboratory results consistent with systemic mastocytosis.To determine the response to treatment, a research nurse contacted thepatients 3 months after discharge and obtained information aboutthe medication, the frequency of mast cell episodes with flushing, andthe intensity of orthostatic tachycardia. We were able to obtain infor-mation on 6 patients with MCA_POTS and in 3 patients withMCA_OH.(Thank you to Katherine for getting this in full)Radha, remember that this may only explain SOME cases of those with hyperadrenergic pots. We are a loooong way from a complete picture but it helps to understand whatever we can! This field is so new. As Katherine suggests, we all fall in the category of "dysautonomia" but our types are varied and our symptoms different. The thing we all seem to share is the "dysfunction of our autonomic nervous system". I suggest if anyone fits the profile of this study, as I do, we should request a urine methylhistamine test. It can only help to further understand if the original irritant to the nervous system is an allergy like reaction; and then the treatment seems perhaps to be more of an antihistamine.the hunt for answers goes on...best regards, tearose Quote Link to comment Share on other sites More sharing options...
MomtoGiuliana Posted March 9, 2005 Report Share Posted March 9, 2005 BTW, I don't know what I was thinking yesterday when I offered to mail the article to anyone--I can also e-mail it as an attachment to you. It is in PDF format. I converted it to paste in to this thread, but that made it lose all formatting. Just send me a private message with your e-mail address, and I will e-mail the attachments to you. (there is a supplemental that I didn't paste in here, as well).Regarding diagnosis and treatment for someone with mast cell activation disorder, I would only add again what the researcher wrote to me on this yesterday:"The patients we described had episodes of obvious severe flushing in theface and neck. Even in these patients, only half had documented mastcell activation (with elevated urine methylhistamines immediately aftera spell).Depending on the patient, we have been successful in treatinghyperadrenergic POTS with aldomet alone or in combination withfludrocortisone. Only some patients require more targeted therapyagainst mast cell activation, which requires medical supervision." Quote Link to comment Share on other sites More sharing options...
Guest tearose Posted March 9, 2005 Report Share Posted March 9, 2005 Thank you Katherine. I just discovered that Aldomet is used to treat high blood pressure! Oh darn it, this is another dead end for me! I don't fit the profile!Well, maybe someone will benefit from this research but it doesn't answer my puzzle yet.best regards, tearose Quote Link to comment Share on other sites More sharing options...
Ernie Posted March 9, 2005 Report Share Posted March 9, 2005 Hi Katherine,Would you mind emailing me the whole document?ThanksErnie Quote Link to comment Share on other sites More sharing options...
MomtoGiuliana Posted March 9, 2005 Report Share Posted March 9, 2005 Sure Ernie--send me a personal message with your e-mail address.Yes tearose--an important symptom that appears associated with MCA disorder, besides significant flushing episodes, is high blood pressure in the upright posture. Quote Link to comment Share on other sites More sharing options...
ramakentesh Posted March 13, 2005 Report Share Posted March 13, 2005 Im not sure i see the connection with facial flushing and autonomic storms - Ive had quite severe autonomic storms/basiliar migraines that caused restlessness, mental confusion, body tremors, feeling cold, tachycardia - particularly when my POTS started shortly after a virus. I dont think i get flushing - just a surging feeling in my head and my eyes fill up with bright lights and all this weird stuff. Do you think that maybe these events are mastcell activity? Quote Link to comment Share on other sites More sharing options...
Guest tearose Posted March 13, 2005 Report Share Posted March 13, 2005 ramakentesh, if you think you "fit the profile"...flushing, high blood pressure, dx hyperadrenergic pots...then you may want your doctor to read the article and help you decide if a urine methylhistamine test is in order. This way you would see if you have elevated urine methylhistamines, after a flushing/autonomic spell.The research shows that "some" patients do have "mast cell activation" and they respond to a medicine called "Aldomet".If someone is looking for a treatment that can help them, and they fit this profile, I think it makes sense to try doing the test after a "spell"! Nothing to loose!tearose Quote Link to comment Share on other sites More sharing options...
Miriam Poorman-Knox Posted March 13, 2005 Report Share Posted March 13, 2005 This is so timely for me. I had a rah on my breast that was itchy and painful. They did a biosy on it, and the result was that my mast cells were majorly involved. I also have had other situation where i have had significant hives etc. I went to the dermatologist and he said that it was my mast cells. I have had to start antihistamines which really dont work bur I said I would gicee it 1 month till my next appt. I will have the urine test done when I have my 24 hour urin this month. It was comforting that my dermatologist knew this was due to pots and how to treat it. Thanks everyone. Miriam Quote Link to comment Share on other sites More sharing options...
calypso Posted March 14, 2005 Report Share Posted March 14, 2005 Does anyone here understand how beta blockers would trigger mast cell activation? I'm not following.Does this mean that if beta blockers help you in any way, you probably don't have mast cell activation? I am on a beta blocker and still have these episodes of flushing, shortness of breath, extreme tachycardia. They tend to come when my menstrual cycle arrives. I've had one every month for the last four months. And they are very disturbing. When the last one occurred, I told my husband to call an ambulance, because I thought I had a run of v-tac or something ... the beats were extremely chaotic for about 15 seconds. Then I had a run of tachycardia that felt like it was over 140. I felt like I was choking. And just as fast as it came on, it completely stopped. I was exhausted afterward, just like this article describes. And I felt like my head was on fire -- almost like all of the blood in my body had traveled to my head.Anyway, I am just trying to figure out whether I would even pursue looking into mast cell activation. If BBs help me even a little -- which they do by controlling my heart rate a little -- then I would think mast cell activation might be ruled out. Or maybe I am wrong.Amy Quote Link to comment Share on other sites More sharing options...
MomtoGiuliana Posted March 14, 2005 Report Share Posted March 14, 2005 calypsoI may be incorrect, but what I infer from the researcher's direct response to me was that even people with Mast Cell Activation *symptoms* may do ok with conventional treatment--only b/c you can have the symptoms (flushing spells), yet not actually have the MCA problem. Regardless, it sounds like this urine test (to be done immediately after a spell) might be in order for you. Hope you can talk to your doctor about that and figure out how to do the test.take care,Katherine Quote Link to comment Share on other sites More sharing options...
seaboardbc Posted July 18, 2005 Report Share Posted July 18, 2005 I purchased this article and I can e-mail it to anyone who would like a copy (I'm not trying to infringe on copyrights, I'm just sharing my copy with those who need to read it). I'm being tested for mastocytosis right now.Bren Quote Link to comment Share on other sites More sharing options...
Alicia479 Posted July 18, 2005 Report Share Posted July 18, 2005 Okay so I posted on the other mastocytosis thread but maybe I should have read this first. So I am kinda confused. Maybe someone can explain this for me. I have POTS. Dr. Grubb thinks it is caused by some sort of autoimmune reaction. However, I also have high N- methylhistamine levels. The allergist I saw at the Mayo was concerned about mastocytosis but said that since my POTS explained my symptoms and my GI biopsy was normal (no mast cells) that he would not pursue it further at this point. If there is a connection between the two maybe I should pursue it a little further. This is all so interesting..... Quote Link to comment Share on other sites More sharing options...
Recommended Posts
Join the conversation
You can post now and register later. If you have an account, sign in now to post with your account.