Ipecac Myopathy and Cardiomyopathy

56050ournal of Neurology, Neurosurgery, and Psychiatry 1992;55:560-562

SHORT REPORT J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.5.560 on 1 May 1993. Downloaded from Ipecac myopathy and cardiomyopathy

Lee P Dresser, E Wayne Massey, Eric E Johnson, Edward Bossen

Abstract anorexia nervosa. At the time of her father's Two cases of ipecac myopathy, one with death, four years before evaluation, she had associated cardiomyopathy are reported. lost 18 kilograms, dropping from 61 kilograms Both patients were young women with to 43 kilograms. Since then, her weight had eating disorders who came to medical increased to 57 kilograms and remained stable attention because of diffuse muscle weak- (height 165 cm). For the six month period ness. Clinical and electromyographic data before her evaluation, she had ingested several suggested ipecac myopathy and muscle 30 ml doses of syrup of ipecac (containing biopsies confirmed this diagnosis. One approximately 21 mgs of emetine) per week to patient had associated clinical and echo- induce emesis after eating. She claimed only cardiographic evidence of significant car- occasional alcohol use. diomyopathy. The myopathy resolved and Her general physical examination revealed a the echocardiogram returned to normal well nourished, young, white woman. Her after discontinuing the use of ipecac. resting heart rate was 104 with S3 and S4 heart sounds present. Lungs were clear. Icthyosis (7 Neurol Neurosurg Psychiatryl992;55:560-562) was present on the extensor surface ofher arms and legs. Her neurological examination was remarkable for diffuse mild extremity atrophy The abuse of syrup of ipecac by patients with and moderate diffuse weakness, greater proxi- major eating disorders has been shown to have mally. Her sensory examination was normal. toxic effects on skeletal and cardiac muscle.'7 Laboratory evaluation revealed blood These effects are most likely secondary to counts, serum electrolytes, LDH, SGOT, emetine, one of the major alkaloids in syrup of SGPT, and alkaline phosphatase to all be ipecac. Emetine is well known to produce within normal limits. A rheumatoid factor and myopathy in skeletal muscle,8 and is toxic to antinuclear antibody were negative. A serum cardiac muscle,5 and may produce electrical creatinine kinase (CK) level was elevated, with disturbances and heart failure.4 Syrup of ipe- a peak at 1027 units/I. An ECG showed sinus

cac has been responsible for several deaths in tachycardia with a prolonged QT interval and http://jnnp.bmj.com/ patients with the binge-purge type eating T-wave inversion in the lateral leads. An pattern of bulimia.23 The use of syrup of echocardiogram showed left ventricular dilata- ipecac by bulimic patients to stimulate emesis tion and diffuse hypocontractility with an is now recognised to be widespread.6 It is ejection fraction of 36-5% (see table). Electro- important for. physicians to be vigilant in myography showed low-amplitude, polyphasic seeking evidence of ipecac-induced myopathy units in proximal muscles, without increased and cardiomyopathy, especially in young spontaneous activity. on September 26, 2021 by guest. Protected copyright. women, because these disorders are potentially A left deltoid biopsy showed slight variation reversible. This report describes two patients in fibre size without evidence of inflammation. with ipecac-induced myopathy and provides ArPase and NADH stains showed targetoid echocardiographic evidence of the reversibility changes in both type 1 and 2 fibres with Divisions of Neurology of an associated cardiomyopathy. and Cardiology, Department of Medicine, and the Case Table I Echocardiogram results (patient 1) Department of reports Pathology, Duke Patient 1 Study I Study 2 University Medical This was a 26 year old female admitted for (15 months after Center, Durham, NC evaluation of progressive muscle weakness. At discontinuing ipecac) 27710, USA LVIDd 5-1 cm 4-6 cm L P Dresser the time of presentation, she had a two month (short axis) E W Massey history of progressive difficulty climbing stairs, LVIDs 4-2 cm 3-4 cm E E Johnson carrying a laundry basket, and holding her (short axis) E Bossen EDV 109-4 ml 120-5 ml head up while seated at work. She admitted to (apical view) Correspondence to: ESV 69-5 ml 65-1 ml Dr Dresser, Division of mild myalgia and had noted mild atrophy of (apical view) Neurology, Duke University her and arm musculature. She had EF 36-5% 46-0% Medical Center, Box 2905, thigh Durham, NC 27710, USA occasional palpitations, increased sweating, FS 17-6% 26-1% Received 11 December 1990 and mild pedal oedema. She denied chest pain Abbreviations: LVIDd (left ventricular internal dimension, diastole), LVIDs (left ventricular internal dimension, systole), 25 February 1992. or dyspnoea on exertion. She had a history of EDV (end diastolic volume), ESV (end systolic volume), EF Accepted 2 March 1992 asthma, mild hypertension, depression and (ejection fraction), FS (fractional shortening). Ipecac myopathy and cardiomyopathy 561

Patient 2 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.5.560 on 1 May 1993. Downloaded from ,-. I. -, WkI This was a 29 year old, white female who was f evaluated for muscle weakness during a psy- chiatric admission for an eating disorder. She had a several month history of progressive generalised weakness, exercise intolerance and amenorrhea. For the six months before evaluation, she drank approximately one bottle of wine per day. During this period, she had a pattern ofminimal food intake alternating with binge eating, always followed by ipecac- induced emesis. General physical examination showed a thin white female with dry skin. Heart and lungs examination were normal. Diffuse moderate muscle atrophy and weakness were present, more prominent proximally. Sensory examination was normal. Laboratory evaluation showed blood counts, L~~~~~~ serum chemistries, thyroid function test, and serum CK to be within normal limits. An ECG showed nonspecific T-wave abnormalities. Electromyography showed long, polyphasic motor units with no increased insertional or Figure 1 Electron micrograph shows !electron-dense< s | l .~~~~~A aggregates within fibres, which spontaneous activity. apparently correspond to degenerating Z-band materiaL (Magnification x 6,600). A biopsy of the left vastus laterlis muscle showed foci of fibres with increased numbers of internal nuclei with minimal atrophy. Tri- chrome staining showed focal groups of fibres with blurring of the myofibrillar network and aggregations of dense staining material (fig 2). These aggregates were seen by electron microscopy to represent Z-band streaming. NADH staining also showed loss of the myofibrillar network in many fibres, resulting in a targetoid appearance similar to that seen in patient 1. There was no evidence of inflammation, and phosphorylase and myoadenylate 4i staining showed normal activity.

Discussion

.I $ Ipecac is isolated from the root of Cephalis http://jnnp.bmj.com/ - ipecacuanha. It contains two major alkaloids, emetine and cephaeline. Cephaeline is prima- rily responsible for producing nausea and v-- As.. emesis, whereas emetine is more toxic to skeletal muscle and the heart.4 Ipecac has long been used by natives of Brazil to treat diar- 11.- x / rhoea and has had widespread use in the treatment of amebiasis.4 It has also been used on September 26, 2021 by guest. Protected copyright. A in aversive therapy for alcoholism9 and has Figure 2 Trichome stain of muscle biopsy from patient 2 shows aggregationIs of been employed experimentally as an antineo- dense-staining bodies within fibres (arrows). (Magnification x 400). plastic agent. In the USA, the only official use of ipecac is as an emetic to treat accidental poisoning. It is available without prescription only in syrup form. Through experiences with its use as a treatment for amebiasis, ipecac has been shown to cause a myopathy.'0 normal fibre distribution. Phosphorylase, In one study, nearly 5% of high school age myoadenylate deaminase, congo rec1, and lipid females admitted to bulimic activity.5 They stains were normal. Electron imicroscopy may resort to ipecac abuse if they cannot showed extensive disorganisation offmyofibrils effectively induce mechanical emesis. It is with extreme smudging of Z-band nnaterial (fig estimated that there are one million bulimic 1). The patient stopped using ipecalc and after women in America and that 35 000 abuse three months her strength returned to near ipecac.6' normal and she had no further coimplaints of Ipecac myopathy should be considered in all palpitations or ankle oedema. A repeat echo- young women with progressive proximal mus- cardiogram performed 15 month!s after the cle weakness, atrophy, or stiffness, especially first study demonstrated normal left ven- when there is any suggestion of an eating tricular function (see table). disorder. Both of our patients had dry skin, 562 Dresser, Massey, J7ohnson, Bossen

and several other cases have been reported in internal nuclei, granular breakdown of myofi- J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.56.5.560 on 1 May 1993. Downloaded from which patients were noted to have dry or laments, and central core changes or targetoid erythematous skin. ' 7 The serum CK level may changes in fibres with ATPase or NADH be elevated, but it can also be within normal stains. Electron microscopy shows Z-band limits in the presence of significant weakness. streaming and dense bodies." Inflammatory The electromyogram shows nonspecific myo- infiltrates are not seen.' These findings are pathic changes, but a muscle biopsy will help characteristic of ipecac myopathy, but are also distinguish ipecac myopathy from inflamma- seen in a variety of other conditions.'2 tory or alcohol-induced myopathy.' '3 Nerve Although patient 2 was a heavy consumer of conduction velocity is normal. alcohol, her muscle biopsy was quite similar to If ipecac abuse is suspected, an evaluation that of patient 1 and demonstrated the charac- for cardiomyopathy is warranted. Historical or teristic targetoid changes and Z-band stream- physical evidence of cardiac failure may be ing of emetine myopathy. The characteristic present. The electrocardiogram may show rest- type II fibre atrophy of chronic alcoholic ing tachycardia, prolongation of the QT and myopathy'3 was absent and therefore her PR intervals, inverted T-waves, and ST seg- myopathy was likely predominately due to ment abnormalities.4 As in the case of patient emetine toxicity. The effects on cardiac muscle 1, significant depression of left ventricular are not as well documented, but interstitial function may be detected by echocardiogram oedema, inflammation, and degenerative or radionuclide tests. The serial echocardio- change of myocardial fibres have been repor- grams performed on our patient demonstrated ted.3 that ipecac cardiomyopathy is largely reversi- Therapy consists of discontinuing ipecac use ble. and employing supportive measures. If cardio- The lethal dose of emetine has been esti- myopathy is significant, inotropic and afterload mated to be 10 to 25 mgs, or approximately reducing agents may be used. As shown in 1 25 grams for an adult.'0 Death is usually patient 1, both the cardiomyopathy and myop- caused by ventricular arrhythmias or heart athy improved after discontinuing ipecac failure.4 Emetine is so slowly excreted from the abuse. Electrical and pathological evidence of body that doses may accumulate over time to muscle recovery has also be demonstrated.9 12 approximate the lethal dose, even when emesis is stimulated.4 Syrup of ipecac is available in 30 ml doses, each dose containing approx- 1 Mateer JE, Farrell BJ, Chou SM, Gutmann L. Reversible imately 21 mgs of emetine. It is therefore ipecac myopathy. Arch Neurol 1985;42:188-90. 2 Dawson JA, Yager J. A case of syrup of ipecac resulting in possible to accumulate a lethal amount of death. JAmer Coll Health 1986;34:280.;4 emetine within the body over several months 3 Adler AG, Walinsky P, Krall RA, Cho S Death resulting from ipecac syrup poisoning. J ., Amer Med Assoc when ipecac is used daily. It has been proposed 1980;243: 1927-8. that emetine inhibits protein synthesis and 4 Manno BR, Manno JE. Toxicology of ipecac: a review. Clin Tox 1977;10:221-42. mitrochondrial oxidative phosphorylation in 5 Isner JM. Effects of ipecac on the heart. (Letter). New Engl skeletal muscle. These effects may cause J7Med 1986;313:1253-5. Hudson PL. The ATP and a 6 Pope HG, JI, Nixon RA, Herridge decreased formation subsequent epidemiology of ipecac abuse. (Letter) New Engl J Med increased release of calcium into the sarco- 1986;245-6. 7 Bennett HS, Spiro AJ, Pollock MA, Zueker P. Ipecac- plasm that, in turn, activates proteases which induced myopathy simulating dermatomyositis. Neurol http://jnnp.bmj.com/ cause Z-band lysis, granule formation, and 1982;32:91-4. 8 Bindoff L, Cullen MJ. Experimental (-) emetine myopathy. myofilament disorganisation.9 In the heart, J Neurol Sciences 1978;39:1-15. emetine is thought to depress glycolysis and 9 Sugie H, Russin R, Verity AM. Emetine myopathy: two case reports with pathobiochemical analysis. Muscle Nerve Kreb's cycle, as well as inhibit synthesis of 1984;7:54-9. contractile proteins.4 10 Anderson HH, Reed AC. Untoward affects of anti-ambeic drugs. Am J Trop Med Hygiene 1934;14:269-81. The microscopic pathological changes seen 11 Halbig L, Gutmann L, Goebel HH, Brick JF, Schochet S. in the muscle biopsies from our patients are Ultrastructural pathology in emetine-induced myopathy.

Acta Neuropath 1988;75:577-82. on September 26, 2021 by guest. Protected copyright. very similar to those reported in previous cases 12 Goebel HH. Neuropathological aspects of congenital myo- of ipecac myopathy' 7 9and experimental pathies. Prog Neuropath 1980:6:231-48. 13 Hanid A, Slavin G, Mair W et al. Fibre type changes in emetine-induced myopathy in rats.8 Light straited muscles of alcoholics. J Clin Pathol 1981;34: microscopy reveals variation in fibre size, 991-7.