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Subj: MG levels Date: 11/8/2002 8:05:25 AM Eastern Standard Time From, kathynye@...Title: Magnesium deficiency in systematic lupus erythematosus.Subject(s): MAGNESIUM deficiency diseases; SYSTEMIC lupuserythematosus -- Diagnosis Source: Journal of Nutritional & Environmental Medicine, Jun97, Vol. 7Issue 2, p107, 5p, 1 chart Author(s): Romano, J. Abstract: Discusses the effects of reduced erythrocyte magnesium(Mg) deficiency in patients with systematic lupus erythematosus (SLE).Common symptom of the disorder; How to determine if SLE patients arealso prone to hypomagnesemia; Results of the study. AN: 9711141130 ISSN: 1359-0847 Full Text Word Count: 2470 Database: Academic Search Elite Section: ORIGINAL RESEARCH MAGNESIUM DEFICIENCY IN SYSTEMIC LUPUS ERYTHEMATOSUS Reduced erythrocyte magnesium (Mg) levels have been reported infibromyalgia syndrome (FS), chronic fatigue syndrome (CFS), myofascialpain syndrome (MPS) and eosinophilia myalgia syndrome (EMS). Thesedisorders have chronic pain as a common symptom. Chronic pain alsoaffects some patients with systemic lupus erythematosus (SLE). Todetermine if SLE patients are also prone to hypomagnesemia, red bloodcell (RBC) and plasma Mg levels were measured in all SLE patients seenin a general rheumatology practice in a 3-year period. There were 25such patients with a mean age of 47 years. Thirteen SLE patients had FSand 12 did not have either FS or MPS. The mean RBC Mg level for the SLEpatients was 4.60 mg dl-1, statistically significantly lower than thatof the reference controls and 12 osteoarthritis controls. It did notmatter whether the SLE patients had ES or MPS. This finding hasimplications for diagnosis and treatment. Keywords: magnesium, myalgias, lupus, pain. INTRODUCTION Reduced erythrocyte magnesium (Mg) levels have been reported infibromyalgia syndrome (FS) [ 1], chronic fatigue syndrome (CFS) [ 2],myofascial pain syndrome (MPS) [ 3] and eosinophilia myalgia syndrome(EMS) [ 4]. These four disorders have chronic pain and/or fatigue as acommon denominator. Furthermore, it has been proposed that low Mg levelspredispose patients to myalgias [ 5] and that low muscle Mg levelscorrespond to a low pain threshold [ 6]. Systemic lupus erythematosus(SLE) is also a condition that can be characterized by chronic pain insome patients. Lupus patients have often been described as havingmyalgias, arthralgias and pain resulting from inflammation of suchstructures as the lung pleura and/or pericardium [ 7-9]. If patientsexperience pain because of a flare of this systemic inflammatoryconnective tissue disease the treatment would typically be medicationssuch as glucocorticosteroids or even immunosuppressants [ 10, 11].However, if low Mg is causing or contributing to increased pain in SLEpatients without any concomitant increase in inflammatory activity, theuse of these medications would not be expected to ease the pain andcould perhaps be counterproductive because of side-effects. With this inmind the Mg levels were checked in SLE patients in a generalrheumatology practice. PATIENTS AND METHODS Patients During the period September 1992 to May 1995 inclusive, 25 SLE patientswere evaluated and treated in a general rheumatology practice. All thepatients fulfilled 1982 American College of Rheumatology (ACR) criteriafor SLE [ 12]. There were four males and 21 females with a mean age of47 years (range 18-64 years). Thirteen SLE patients (one male and 12females) fulfilled the ACR criteria for FS [ 13]. The remaining 12patients (three males and nine females) had neither FS nor MPS. During the study period, none of the SLE patients exhibited renalinsufficiency nor was there evidence of myositis. None of the SLEpatients had creatine phosphokinase (CPK) or aldolase levels outside ofthe 'normal range'. The mean CPK level for all 25 patients was 126 U 1-1(normal range 32-236 U 1-1). The mean aldolase level for the eight SLEpatients tested was 4.8 U 1[sup -1 (normal range 1-8 U 1-1). As acontrol group, 12 patients with uncomplicated monoarticularosteoarthritis (OA) (four hip, six knee and two shoulder) were alsostudied. There were three men (ages 44, 48 and 53 years) and nine women(mean age 50 years and range 42-64 years) in the OA group (see Table 1).None of the OA or SLE patients was taking diuretics or uricosuric drugs.None was bulimic, anorexic or using laxatives inappropriately. Nopatient was cachetic or on a 'crash' diet at the time of the study. Nonewas taking vitamin supplements. All had simultaneous plasma and redblood cell (RBC) Mg determinations. Methods All 25 SLE patients had venous blood drawn for both RBC and plasma Mglevels. The samples were drawn into a heparinized tube from a peripheralvein. They were immediately refrigerated and then transported to areference laboratory (National Medical Services, Willow Grove, PA, USA)where the assays were performed. The plasma and RBC Mg levels usingwashed cells were determined by using direction dilution techniques andatomic absorption [ 14, 15] and the results here reported in mg dl-1. RESULTS The mean RBC Mg level for the SLE patients without FS or MPS was 4.50 mgdl-1 with a standard deviation of 0.72 mg dl-1 whereas the mean RBC Mglevel for the SLE patients with FS was 4.63 mg dl-1 with a standarddeviation of 0.68 mg dl-1. There was no statistically significantdifference between these two groups. The mean RBC Mg level for all theSLE patients was 4.60 mg dl-1 with a standard deviation of 0.70 mg dl-1,which is statistically significantly different from that of thereference controls (5.5 mg dl-1 and standard deviation 0.65 mg dl-1) and12 osteoarthritis controls (5.30 mg dl-1 and standard deviation 0.62 mgdl-1). A comparison of the means tests showed a z score of 4.60 and p <0.001. The plasma Mg levels for the SLE patients were not significantlydifferent from the reference controls and also the osteoarthritiscontrols. The mean plasma Mg level for the SLE patients was 2.00 mgdl-1, which is not statistically significantly different from the meanplasma Mg level for the reference controls and for the 12 osteoarthritiscontrols (2.05 and 2.00 mg dl-1, respectively). Clinical Vignette A 35-year-old white female with a history of SLE for 9 years presentedwith a 3-month history of gradually increasing myalgias. There was nochange in diet or exercise nor was she taking any new medications. HerSLE had been well controlled on prednisone (5 mg/day) and azathioprine(150 mg/day). She required occasional prescriptions for non-steroidalanti-inflammatory medications such as Salsalate of up to 3 g/day forarthralgias. On physical examination the patient had normal bloodpressure. An examination of the head, ears, eyes, nose and throat wasunrevealing. In particular, there was no alopecia, oral ulcers or malarrash. A cardiopulmonary examination was unremarkable. An abdominalexamination was benign. A musculoskeletal examination revealed no signsof synovitis, bony ankylosis or joint effusions. There was fairly goodrange of motion of all the joints: however, there was some diffusetenderness on palpation of the muscles. There were only four of 18fibromyalgia tender points noted (bilateral trapezius, right second riband left gluteus medius). She did not fulfil the ACR criteria [ 13] forFS. Laboratory values revealed normal renal function and normal levelsof sodium, potassium, chloride and bicarbonate. Her erythrocytesedimentation rate (ESR) was normal (10 mm). Her CPK and aldolase werealso within the normal range (164 and 4.0 U 1-1, respectively). However,her RBC Mg level was noted to be 3.8 mg dl-1 (reference mean 5.5 mg dl-1with a range of 4.2-6.8 mg dl-1). Her plasma Mg level was 1.7 mg dl-1(reference mean 2.05 mg dl-1 with a range of 1.6-2.5 mg dl-1). Thepatient's dose of prednisone was not increased nor was there a change inthe dose or type of immunosuppressant. Rather, she was treated with sixweekly injections of magnesium sulphate (1 g intramuscularly) as hadbeen described previously in the treatment of CFS [ 2]. After the firstseries of six injections the patient's RBC Mg level increased to 4.3 mgdl-1, barely within the normal reference range. However, the patient'smyalgias improved significantly but did not completely subside. It wasnot until a second course of six weekly injections of magnesium sulphate(1 g intramuscularly) that the patient's myalgias almost disappeared.Her RBC Mg level increased to 5.4 mg dl-1. The patient was treatedcontinuously with an oral magnesium supplement (magnesium chloride(Slow-Mag) 64 ma, one tablet, three times a day with food). Thesubsequent RBC Mg level 6 months after the initiation of the oralmagnesium supplementation was 5.2 mg dl-1. The patient remains free ofmyalgias. DISCUSSION As in the case of other painful conditions [ 1-3], statisticallysignificant differences in Mg levels between SLE patients and controlstended to be seen much more readily using RBC Mg levels as the measureof total body Mg stores as opposed to the plasma Mg level. Mostclinicians tend to use either serum or plasma Mg levels and in doing somay overlook Mg deficiency in some patients, a potentially reversibleproblem. It can be very dangerous to treat symptoms such as myalgias inSLE patients with an increase of corticosteroids and/orimmunosuppressants without checking the RBC Mg level first. If an SLEpatient's myalgias are due to a flare of this inflammatory connectivetissue disease, it is certainly prudent to treat with medication gearedtowards controlling the inflammation. However, if the patient's myalgiasare due to Mg deficiency, treatment with an increased dose ofcorticosteroids would likely be ineffective. In fact, the literaturesuggests that corticosteroid treatment may even intensify the Mgdeficiency [ 16-21]. It could also cause complications such as avascularnecrosis of the bone [ 22], osteoporosis [ 23], a hastening of thedevelopment of cataracts [ 24] and other side-effects [ 25]. The use ofimmunosuppressants is also not without risk. They can cause bone marrowsuppression [ 26], liver toxicity [ 27] and other side-effects [ 28].These potential problems may be acceptable if one is treating a flare ofSLE. However, if the myalgias are due to hypomagnesemia, an increase incorticosteroids and/or a modification of immunosuppressants therapycould expose the patient to needless risk. Since the pain threshold tends to decrease as the total Mg levelsdecrease [ 5], it seems only reasonable to check for hypomagnesemia inpatients with an unexplained increase in chronic pain. This includes SLEpatients whose myalgias may be due to different causes on differentoccasions. Oral Mg products suitable for supplementation are availableover the counter, are relatively inexpensive and the Mg levels can bemonitored to avoid potential toxicity particularly in those SLE patientswith renal insufficiency. It is not known why Mg levels tend to drop in patients with chronic painproblems such as FS, MPS, EMS and SLE. It has been suggested [ 3] thatthere may be a problem with Mg availability and/or utilization at thetissue level as opposed to a suboptimal dietary intake or an increasedexcretion of Mg. Whatever the mechanism, Mg deficiency should not gounnoticed. To fail to consider Mg deficiency in the differentialdiagnosis of neuromuscular problems in SLE might expose such patients toundue risk and expense particularly if myalgias are mistakenlyattributed to inflammation. TABLE 1. Individual RBC determination (mg dl-1) SLE patients (n = 25) OA controls (n = 12)(a) 6.8 6.25.65.4. 5.4 5.4, 5.45.3 5.3©5.2 5.25.1 5.15.04.9, 4.9, 4.9 4.94.8, 4.8 4.84.7, 4.7 4.74.6, 4.6, 4.6( 4.64.54.34.03.93.83.03.02.8(a) Twelve osteoarthrities patients with monoarticular disease.( Mean = 4.6 mg dl-1 and standard deviation = 0.65mg dl-1.© Mean = 5.3 mg dl-1 and standard deviation = 0.62mg dl-1.Reference range mean = 5.5 mg dl-1.REFERENCES[1]Romano TJ, Stiller, JW. Magnesium deficiency in fibromyalgiasyndrome. J Nutr Med 1994;4: 165-7. [2] IM, MJ, Dowson D. Red blood cell magnesium and chronicfatigue syndrome. Lancet 1991; 337: 757-60. [3]Romano TJ. Magnesium deficiency in patients with myofascial pain. JMyofascial Ther 1994; 1: 11-12. [4]Clauw DJ, Ward K, B, et al. Magnesium deficiency in theeosinophilia-myalgia syndrome. Arthritis Rheumat 1994; 37: 1331-4. [5]Webb WI, Gehi M. Electrolyte and fluid imbalance: neuropsychiatricmanifestations. Psychosomatics 1981; 22: 199-203. [6]Clauw D, Ward K, Katz P, et al. Muscle intracellular magnesium levelswith pain tolerance in fibromyalgia (FM) (abstract). Arthritis Rheumat1994; S213: 324. [7]Matthay RA, Schwartz ML Petty TL, et al. Pulmonary manifestations ofsystemic lupus erythematosus: review of 12 cases of acute lupuspneumonitis. Medicine 1974; 54: 397-409. [8]Haupt M, GW, Hutchins GM. The lung in systemic lupuserythematosus: analysis of the pathogenic changes in 120 patients. Am JMed 1981; 71: 791-9. [9]Brigden W, Bywaters EGL, Less of MH, et al. The heart in systemiclupus erythematosus. Br Heart J 1960; 22: 1-7. [10] RP. Steroid use in systemic lupus erythematosus in systemiclupus erythematosus. In: Lahita RG ed. New York: Wiley & Sons,1987, pp. 889-922. [11]Klippel JH. Immunosuppressive therapy in systemic lupuserythematosus. In: Lahita RG ed. New York: Wiley & Sons, 1987, pp.923-45. [12]Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for theclassification of systemic lupus erythematosus. Arthritis Rheumat 1982;25: 1271-7. [13]Wolfe F, Smythe HA, Yunus MB, et al. The American College ofRheumatology 1990 Criteria for the classification of fibromyalgia.Report of the multicenter criteria committee. Arthritis Rheumat 1990;33: 160-72. [14]Tietz NW, ed. Fundamentals of clinical chemistry, 3rd edn.Philadelphia: WB Saunders, 1987, pp. 17-18. [15]Brown SS, FL, Young DS, eds. Chemical diagnosis of disease.Amsterdam: Elsevier/North Holland, Biomedial Press, 1979, p. 440. [16]Aikawa JK, Harms DR, Reardon JZ. Effect of cortisone on magnesiummetabolism in the rabbit. Am J Physiol 1960; 199: 229-30. [17]Lutwak L, Hurt C, Reid JM. Effect of corticoids on magnesiummetabolism in man (abstract). Clin Res 1961, 9: 181. [18]Huszak I, Heiner L. Changes of the magnesium content of the serumfollowing ACTH loads in patients suffering from multiple sclerosis.Psychiat Neurol Basel 1964; 148: 245-52. [19]Massry SG, Coburn JW. The hormonal and non-hormonal control of renalexcretion of calcium and magnesium. Nephron 1973; 10: 66-112. [20]Gelach K, Morowitz DA, Kirsner JB. Symptomatic hypomagnesemiacomplicating regional enteritis. Gastroenterology 1970; 59: 567-74. [21]Mader IJ, Iseri LT. Spontaneous hypopotassemia, hypomagnesemia,alkalosis and tetany due to hypersecretion of cortisone-likemineralcorticoid. Am J Med 1955; 19: 976-88. [22]Zizic TM, Marcoux C, Hungerford DS, et al. Corticosteroid therapyassociated with ischemic necrosis of bone in systemic lupuserythematosus. Am J Med 1985; 79: 596-604. [23]Lukert BP, Raisz LG. Glucocorticoid-induced osteoporosis.Pathogenesis and management. Ann Intern Med 1990; 112: 352-64. [24]Lubkin VL. Steroid cataract: a review and a conclusion. J Asthma Res1977; 14: 55-9. [25]Axelrod L. Adrenal corticosteroids. In: RR, Green DJ, eds.Handbook of drug therapy. New York: Elsevier North-Holland, 1979, p.809. [26]Bacon BR, Treuhaft WH, Goodman AM. Azathioprine-inducedpancytopenia. Occurrence in two patients with connective tissuediseases. Arch Intern Med 1981; 141: 223-6. [27]DePinho RA, Goldberg CS, Lefkowitch JH. Azathioprine and the liver.Evidence favoring idiosyncratic mixed cholestatic-heparo cellular injuryin humans. Gastroenterology 1984; 86: 162-5. [28]Schein PS, Winokur SH. Immunosuppressive and cytotoxic therapy:long-term complications. Ann Intern Med 1975; 82: 84-95. ~~~~~~~~By THOMAS J. ROMANO MD PHD, 30 Medical Park, Wheeling, WV 26003, USA _____ Copyright of Journal of Nutritional & Environmental Medicine is theproperty of Carfax Publishing Company and its content may not be copiedor emailed to multiple sites or posted to a listserv without thecopyright holder's express written permission. However, users may print,download, or email articles for individual use.Source: Journal of Nutritional & Environmental Medicine, Jun97, Vol. 7Issue 2, p107, 5pItem: 9711141130