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Myocarditis in association with giardia intestinalis infection
International Journal of Cardiology 177 (2014) e142–e144
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Myocarditis in association with giardia intestinalis infection Daniel Robaei a,c,⁎, Linh Vo-Robaei b, Therese Bewes c, Benjamin Terkasher a, Mark Pitney a,c a b c
Sutherland Hospital, Sydney, Australia Royal North Shore Hospital, Sydney, Australia University of New South Wales, Sydney, Australia
a r t i c l e
i n f o
Article history: Received 25 August 2014 Accepted 17 September 2014 Available online 28 September 2014 Keywords: Myocarditis Giardiasis Protozoa
A 33 year old man presented with a one day history of central chest discomfort of heavy character occurring at rest. The discomfort was not pleuritic and there was no associated dyspnoea. He had been unwell for seven days prior with frequent small volume loose stools, steatorrhea, and offensive flatus. This was accompanied by nausea and abdominal distension. The patient's past medical history was limited to eczema and previous appendectomy. He was on no regular medications. Occupational history included recent occupational exposure to sewage water. There was no recent overseas travel or exposure to unwell contacts. On examination the patient was afebrile, and haemodynamically stable. Mucosae were dry. Heart sounds were normal and the chest was clear upon auscultation. Abdominal examination found mild periumbilical tenderness but no guarding. Bowel sounds were hyperactive. The initial electrocardiogram showed sinus rhythm with up to 1.5 mm ST elevation in the infero-lateral leads (Fig. 1). A transthoracic echocardiogram performed during chest discomfort and ST elevation showed normal left ventricular size and systolic function with normal contractility in all segments. There was no significant pericardial effusion. A chest X-ray was normal. Laboratory investigations revealed a mild leucocytosis, with a leucocyte count of 12.1 × 109/L. C-reactive protein was elevated at 30 mg/L. Urea, electrolytes and creatinine were normal. Initial creatine kinase and troponin T levels were elevated at 398 U/L (N b 200) and 785 ng/L (N b 14) respectively.
⁎ Corresponding author at: University of New South Wales, Sydney, Australia. E-mail address: [email protected] (D. Robaei).
http://dx.doi.org/10.1016/j.ijcard.2014.09.050 0167-5273/Crown Copyright © 2014 Published by Elsevier Ireland Ltd. All rights reserved.
The patient was given intravenous rehydration and commenced on treatment with aspirin, intravenous heparin and ciprofloxacin. A CT coronary angiogram was performed which showed normal coronary arteries, and a provisional diagnosis of myocarditis was made. The initial ST elevation evolved to T wave inversion by day three of admission (Fig. 2) at which time Troponin T levels peaked at 1767 ng/L. There were no arrhythmias recorded on inpatient telemetry. A vasculitic screen including ANA, ds DNA, ENA, ANCA and rheumatoid factor levels was negative. Viral serology was negative for enterovirus, influenza A/B, HHV6 and CMV. IgM antibodies to EBV and herpes simplex were negative. During the admission giardia intestinalis cysts were identified by stool microscopy, and giardia coproantigens were detected on stool ELISA immunoassay. PCR testing of stool was negative for common viral and bacterial pathogens including enterovirus and campylobacter. The patient was diagnosed with giardiasis likely as a consequence of occupational exposure and was treated with tinidazole. A cardiac MRI was performed on day five of admission which revealed patchy areas of oedema on T2-weighted images (Fig. 3) as well as delayed gadolinium enhancement worse within the lateral left ventricular wall and apex, with sparing of the sub-endocardium (Fig. 4). Left and right ventricular function was normal. The MRI appearance was consistent with myocarditis. The patient was discharged home following improvement of his symptoms. A transthoracic echocardiogram at three months showed normal left and right ventricular function and an exercise stress test to maximum heart rate found no inducible arrhythmias. Myocarditis refers to acute inflammation of the myocardium typically caused by an infective, toxic or autoimmune process. In the developed world it is usually caused by a viral infection, frequently an enterovirus such as coxsackie B virus. Other viral causes of myocarditis include adenovirus, parvovirus B19, Epstein-Barr virus, and cytomegalovirus [1]. The protozoa Trypanosoma cruzi is an important cause of myocarditis in endemic areas of Latin and South America as part of Chagas disease [1]. While myocarditis in the setting of an enteric infection is most commonly due to an enterovirus, isolated case reports have described its occurrence in association with campylobacter enterocolitis [2–4]. Giardia, is a flagellated enteric protozoan, and a common intestinal parasite throughout the world. Its life cycle consists of two stages: trophozoite and cyst. Giardia transmission occurs in the cyst form through contaminated water, although person-to-person transmission can also occur in instances of poor hygiene [5]. Once cysts are ingested environmental stimuli in the gut such as the presence of gastric acid and
D. Robaei et al. / International Journal of Cardiology 177 (2014) e142–e144
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Fig. 1. Electrocardiogram at time of presentation showing sinus rhythm with ST segment elevation in the infero-lateral leads (maximal 1.5 mm lead V6).
Fig. 2. Electrocardiogram on day 3 of admission showing sinus rhythm with T wave inversion in the infero-lateral leads.
A
B
C
D
Fig. 3. Cardiac magnetic resonance imaging (T2 weighted images) showing patchy areas of myocardial oedema (arrows) within the anterolateral, apical and inferior left ventricle. Panel A — 4 chamber view. Panel B — 3 chamber view. Panel C — 2 chamber view. Panel D — short axis view.
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D. Robaei et al. / International Journal of Cardiology 177 (2014) e142–e144
A
B
C
D
Fig. 4. Cardiac magnetic resonance imaging (T1 weighted images) showing delayed gadolinium enhancement (arrows) of the anterolateral, apical and inferior left ventricle. Panel A — 4 chamber view. Panel B — 3 chamber view. Panel C — 2 chamber view. Panel D — short axis view.
pancreatic enzymes initiate excystation and the release of a single trophozoite which divides and results in four daughter trophozoites. Trophozoites colonise the proximal small bowel and attach to the intestinal epithelium by way of a sucking disk [6]. The pathogenesis of diarrhoea in giardia infection is thought to involve direct damage to the intestinal mucosa, induction of a host immune response resulting in secretion of fluid and damage to the gut, modification of bowel flora and apoptosis of intestinal epithelium [5]. Direct invasion of intestinal mucosa is not believed to occur and no giardia enterotoxin has yet been identified. Given the failure of the giardia organism to invade the intestinal mucosa and therefore the host's bloodstream, myocarditis occurring in association with giardia may be related to autoimmune-mediated attack of the myocardium by antigen mimicry rather than direct damage to the myocardium by the organism. Giardia intestinalis is known to undergo significant antigenic variation of its cysteine-rich surface proteins, which facilitates evasion of the host's defences [7] and this wide variation may provide a theoretical mechanism by which molecular mimicry with host myocardium could occur. A study of 187 patients with biopsy-proven myocarditis aiming to investigate the association between coeliac disease and myocarditis found giardiasis as a final diagnosis in 2 patients [8]. While further clinical details were not supplied the finding of concurrent giardiasis and myocarditis in these 2 patients provides further plausibility to a link between the two conditions. To our knowledge this is the first case report of myocarditis in association with giardiasis described in the medical literature. The clinical course was benign with no haemodynamic instability, no arrhythmic
events and normal biventricular function at the time of presentation and at three month followup. Common causes of myocarditis, and in particular other known enteric causes of myocarditis were excluded, increasing the possibility of an association between the two conditions. Given the often indolent nature of giardia infection, the possibility of an association between giardia and cryptogenic myocarditis may warrant further investigation. Conflict of interest The authors report no relationships that could be construed as a conflict of interest. References [1] Cooper LT. Myocarditis. N Engl J Med 2009;360:1526–38. [2] De Cock D, Hiltrop N, Timmermans P, Dymarkowski S, Van Cleemput J. Myocarditis associated with Campylobacter enteritis: report of three cases. Circ Heart Fail 2012;5(2): e19–21. [3] Cox ID, Fluck DS, Joy MD. Campylobacter myocarditis; loose bowels and a baggy heart. Eur J Heart Fail 2001;3(1):105–7. [4] Alzand BS, Ilhan M, Heesen WF, Meeder JG. Campylobacter jejuni: enterocolitis and myopericarditis. Int J Cardiol Sep 24 2010;144(1):e14–6. [5] Huang DB, White AC. An updated review on cryptosporidium and giardia. Gastroenterol Clin N Am 2006;35(2):291–314. [6] Adam RD. Biology of giardia lamblia. Clin Microbiol Rev 2001;14:447–75. [7] Nash TE. Surface antigenic variation in giardia lamblia. Mol Microbiol 2002;45: 585–90. [8] Frustaci A, Cuoco L, Chimenti C, Pieroni M, Fioravanti G, Gentiloni N, et al. Celiac disease associated with autoimmune myocarditis. Circulation Jun 4 2002;105(22): 2611–8.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Myocarditis in association with giardia intestinalis infection Daniel Robaei a,c,⁎, Linh Vo-Robaei b, Therese Bewes c, Benjamin Terkasher a, Mark Pitney a,c a b c
Sutherland Hospital, Sydney, Australia Royal North Shore Hospital, Sydney, Australia University of New South Wales, Sydney, Australia
a r t i c l e
i n f o
Article history: Received 25 August 2014 Accepted 17 September 2014 Available online 28 September 2014 Keywords: Myocarditis Giardiasis Protozoa
A 33 year old man presented with a one day history of central chest discomfort of heavy character occurring at rest. The discomfort was not pleuritic and there was no associated dyspnoea. He had been unwell for seven days prior with frequent small volume loose stools, steatorrhea, and offensive flatus. This was accompanied by nausea and abdominal distension. The patient's past medical history was limited to eczema and previous appendectomy. He was on no regular medications. Occupational history included recent occupational exposure to sewage water. There was no recent overseas travel or exposure to unwell contacts. On examination the patient was afebrile, and haemodynamically stable. Mucosae were dry. Heart sounds were normal and the chest was clear upon auscultation. Abdominal examination found mild periumbilical tenderness but no guarding. Bowel sounds were hyperactive. The initial electrocardiogram showed sinus rhythm with up to 1.5 mm ST elevation in the infero-lateral leads (Fig. 1). A transthoracic echocardiogram performed during chest discomfort and ST elevation showed normal left ventricular size and systolic function with normal contractility in all segments. There was no significant pericardial effusion. A chest X-ray was normal. Laboratory investigations revealed a mild leucocytosis, with a leucocyte count of 12.1 × 109/L. C-reactive protein was elevated at 30 mg/L. Urea, electrolytes and creatinine were normal. Initial creatine kinase and troponin T levels were elevated at 398 U/L (N b 200) and 785 ng/L (N b 14) respectively.
⁎ Corresponding author at: University of New South Wales, Sydney, Australia. E-mail address: [email protected] (D. Robaei).
http://dx.doi.org/10.1016/j.ijcard.2014.09.050 0167-5273/Crown Copyright © 2014 Published by Elsevier Ireland Ltd. All rights reserved.
The patient was given intravenous rehydration and commenced on treatment with aspirin, intravenous heparin and ciprofloxacin. A CT coronary angiogram was performed which showed normal coronary arteries, and a provisional diagnosis of myocarditis was made. The initial ST elevation evolved to T wave inversion by day three of admission (Fig. 2) at which time Troponin T levels peaked at 1767 ng/L. There were no arrhythmias recorded on inpatient telemetry. A vasculitic screen including ANA, ds DNA, ENA, ANCA and rheumatoid factor levels was negative. Viral serology was negative for enterovirus, influenza A/B, HHV6 and CMV. IgM antibodies to EBV and herpes simplex were negative. During the admission giardia intestinalis cysts were identified by stool microscopy, and giardia coproantigens were detected on stool ELISA immunoassay. PCR testing of stool was negative for common viral and bacterial pathogens including enterovirus and campylobacter. The patient was diagnosed with giardiasis likely as a consequence of occupational exposure and was treated with tinidazole. A cardiac MRI was performed on day five of admission which revealed patchy areas of oedema on T2-weighted images (Fig. 3) as well as delayed gadolinium enhancement worse within the lateral left ventricular wall and apex, with sparing of the sub-endocardium (Fig. 4). Left and right ventricular function was normal. The MRI appearance was consistent with myocarditis. The patient was discharged home following improvement of his symptoms. A transthoracic echocardiogram at three months showed normal left and right ventricular function and an exercise stress test to maximum heart rate found no inducible arrhythmias. Myocarditis refers to acute inflammation of the myocardium typically caused by an infective, toxic or autoimmune process. In the developed world it is usually caused by a viral infection, frequently an enterovirus such as coxsackie B virus. Other viral causes of myocarditis include adenovirus, parvovirus B19, Epstein-Barr virus, and cytomegalovirus [1]. The protozoa Trypanosoma cruzi is an important cause of myocarditis in endemic areas of Latin and South America as part of Chagas disease [1]. While myocarditis in the setting of an enteric infection is most commonly due to an enterovirus, isolated case reports have described its occurrence in association with campylobacter enterocolitis [2–4]. Giardia, is a flagellated enteric protozoan, and a common intestinal parasite throughout the world. Its life cycle consists of two stages: trophozoite and cyst. Giardia transmission occurs in the cyst form through contaminated water, although person-to-person transmission can also occur in instances of poor hygiene [5]. Once cysts are ingested environmental stimuli in the gut such as the presence of gastric acid and
D. Robaei et al. / International Journal of Cardiology 177 (2014) e142–e144
e143
Fig. 1. Electrocardiogram at time of presentation showing sinus rhythm with ST segment elevation in the infero-lateral leads (maximal 1.5 mm lead V6).
Fig. 2. Electrocardiogram on day 3 of admission showing sinus rhythm with T wave inversion in the infero-lateral leads.
A
B
C
D
Fig. 3. Cardiac magnetic resonance imaging (T2 weighted images) showing patchy areas of myocardial oedema (arrows) within the anterolateral, apical and inferior left ventricle. Panel A — 4 chamber view. Panel B — 3 chamber view. Panel C — 2 chamber view. Panel D — short axis view.
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D. Robaei et al. / International Journal of Cardiology 177 (2014) e142–e144
A
B
C
D
Fig. 4. Cardiac magnetic resonance imaging (T1 weighted images) showing delayed gadolinium enhancement (arrows) of the anterolateral, apical and inferior left ventricle. Panel A — 4 chamber view. Panel B — 3 chamber view. Panel C — 2 chamber view. Panel D — short axis view.
pancreatic enzymes initiate excystation and the release of a single trophozoite which divides and results in four daughter trophozoites. Trophozoites colonise the proximal small bowel and attach to the intestinal epithelium by way of a sucking disk [6]. The pathogenesis of diarrhoea in giardia infection is thought to involve direct damage to the intestinal mucosa, induction of a host immune response resulting in secretion of fluid and damage to the gut, modification of bowel flora and apoptosis of intestinal epithelium [5]. Direct invasion of intestinal mucosa is not believed to occur and no giardia enterotoxin has yet been identified. Given the failure of the giardia organism to invade the intestinal mucosa and therefore the host's bloodstream, myocarditis occurring in association with giardia may be related to autoimmune-mediated attack of the myocardium by antigen mimicry rather than direct damage to the myocardium by the organism. Giardia intestinalis is known to undergo significant antigenic variation of its cysteine-rich surface proteins, which facilitates evasion of the host's defences [7] and this wide variation may provide a theoretical mechanism by which molecular mimicry with host myocardium could occur. A study of 187 patients with biopsy-proven myocarditis aiming to investigate the association between coeliac disease and myocarditis found giardiasis as a final diagnosis in 2 patients [8]. While further clinical details were not supplied the finding of concurrent giardiasis and myocarditis in these 2 patients provides further plausibility to a link between the two conditions. To our knowledge this is the first case report of myocarditis in association with giardiasis described in the medical literature. The clinical course was benign with no haemodynamic instability, no arrhythmic
events and normal biventricular function at the time of presentation and at three month followup. Common causes of myocarditis, and in particular other known enteric causes of myocarditis were excluded, increasing the possibility of an association between the two conditions. Given the often indolent nature of giardia infection, the possibility of an association between giardia and cryptogenic myocarditis may warrant further investigation. Conflict of interest The authors report no relationships that could be construed as a conflict of interest. References [1] Cooper LT. Myocarditis. N Engl J Med 2009;360:1526–38. [2] De Cock D, Hiltrop N, Timmermans P, Dymarkowski S, Van Cleemput J. Myocarditis associated with Campylobacter enteritis: report of three cases. Circ Heart Fail 2012;5(2): e19–21. [3] Cox ID, Fluck DS, Joy MD. Campylobacter myocarditis; loose bowels and a baggy heart. Eur J Heart Fail 2001;3(1):105–7. [4] Alzand BS, Ilhan M, Heesen WF, Meeder JG. Campylobacter jejuni: enterocolitis and myopericarditis. Int J Cardiol Sep 24 2010;144(1):e14–6. [5] Huang DB, White AC. An updated review on cryptosporidium and giardia. Gastroenterol Clin N Am 2006;35(2):291–314. [6] Adam RD. Biology of giardia lamblia. Clin Microbiol Rev 2001;14:447–75. [7] Nash TE. Surface antigenic variation in giardia lamblia. Mol Microbiol 2002;45: 585–90. [8] Frustaci A, Cuoco L, Chimenti C, Pieroni M, Fioravanti G, Gentiloni N, et al. Celiac disease associated with autoimmune myocarditis. Circulation Jun 4 2002;105(22): 2611–8.