silent myocardial infarction in wegener's granulomatosis

4
British Journal of Rheumatology 1996;35:188-191 CASE REPORT SILENT MYOCARDIAL INFARCTION IN WEGENER'S GRANULOMATOSIS T. M. LAWSON and B. D. WILLIAMS Department of Rheumatology, University Hospital of Wales, Heath Park, Cardiff CF44XW SUMMARY Histological cardiac abnormalities in Wegener's granulomatosis can frequently be demonstrated at post-mortem examination, but clinically significant cardiac involvement is rare. We describe a massive silent myocardial infarction leading to intractable heart failure and death in a young man with Wegener's granulomatosis, occurring at a time when other features of the disease were responding to aggressive immunosuppression. KEY WORDS: Wegener's granulomatosis, Myocardial infarction, Vasculitis. WEGENER'S granulomatosis is an uncommon multi- system disorder characterized by necrotizing granulo- mata and vasculitis. Prior to the introduction of immunosuppressive therapy the majority of patients died within 1 yr, renal and respiratory disease being the main causes of death [1]. Currently, with treatment the majority of patients survive and even though fulminant cases still occur treatment-related mortality has now become a significant problem [2]. Significant cardiac complications occurring during the course of Wegener's granulomatosis are rare. Even though coronary vasculitis can be demonstrated at post mortem, symptoms associated with myocardial isch- aemia or heart failure are very uncommon. In this report we describe the late onset of cardiogenic shock, due to a silent myocardial infarction, in a young male whose disease was responding to immunosuppressive therapy. CASE REPORT A 23-yr-old male initially presented to his general practi- tioner with a 10-day history of left-sided earache and a bloody discharge, symptoms initially thought to be indicative of middle ear infection. When the patient failed to respond to a short course of antibiotic therapy he was referred to an ear, nose and throat (ENT) specialist who noted the presence of a left seventh lower motor neurone facial weakness. Results of investigations performed were as follows: normal blood count, liver and renal function tests, chest radiograph and an erythrocyte sedimentation rate (ESR) of 65 mm/h. An immunological screen, which included antineutrophil cyto- plasmic antibodies (ANCA), was negative and the immuno- globulin levels were normal. A computerized tomogram (CT) of the left petrous temporal bone showed soft tissue shadow- ing in the left middle ear but no bony destruction. He under- went a biopsy and mastoidectomy, histological examination of this tissue revealing chronic non-specific inflammatory change only. He was discharged, only to be readmitted 3 weeks later with a further episode of left otalgia and fever. His ESR was now 75 mm/h but all previous investigations remained normal. Nasolaryngoscopy showed rhinitis with Submitted 26 April 1995; revised version accepted 27 July 1995. Correspondence to: T. M. Lawson. inflammation of the left Eustachian cushion. He was again discharged home on symptomatic therapy. Six weeks later he was readmitted, having developed fever, fatigue, weight loss and haemoptysis. His ESR was now 122 mm/h, his full blood count remained normal, renal and hepatic screen showed no significant abnormality and the cANCA was negative. A plain radiograph and CT scan of the chest revealed mid-zone consolidation/cavitation (Fig. 1). Mantoux test was negative and the serum angiotensin con- verting enzyme (ACE) levels were within the normal range. Bronchoscopic biopsy was performed; the small amount of tissue obtained showed an acute necrotizing ulcerative process with no evidence of vasculitis or granuloma formation. The attending physician made a diagnosis of atypical sarcoidosis and initiated treatment for 2 weeks only with 20 mg of oral prednisolone. No resolution in the chest X-ray findings took place and he was subsequently referred to the thoracic surgeons for an open lung biopsy. Whilst awaiting this procedure he developed severe arthralgia, vasculitic lesions over the elbows, nose and cheeks and gangrene of several toes of the left foot. It was at this point that he was referred to the Rheumatology Department at the University Hospital of Wales, Cardiff. Physical examination revealed multiple vasculitic lesions over the hands, feet, elbows and face, the left foot was cold and the dorsalis pedis pulse was absent. There was no lymphadenopathy, hepatomegaly or splenomegaly. His pulse rate was 120/min, blood pressure (BP) 140/100 and there were normal heart sounds with no murmurs. Auscultation of the lung fields revealed normal breath sounds only. Investiga- tions at this point revealed a haemoglobin lOg/dl, white blood count 20 x 10*/l and a platelet count 872 x 10 9 /!. The urea was 14.7mmol/l and creatinine 82/imol/l. Urine testing revealed blood and protein with a creatinine clear- ance of 46ml/min. The ESR had increased to 120 mm/h and the C-reactive protein (CRP) to 180mg/l. The ANCA was now positive at a titre of 1:320 with a cytoplasmic staining pattern. The electrocardiogram (ECG) was normal and an echocardiogram revealed no abnormality other than a tachycardia. Immunosuppressive treatment was started and comprised three 1 g intravenous pulses of methylprednisolone on alternate days, followed by 60 mg of oral prednisolone and 150mg of cyclophosphamide daily. He also underwent a course of plasma exchange totalling 301 and was in addition transfused with 3 units of packed cells. His clinical state improved within 72 h. 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Page 1: silent myocardial infarction in wegener's granulomatosis

British Journal of Rheumatology 1996;35:188-191

CASE REPORT

SILENT MYOCARDIAL INFARCTION IN WEGENER'SGRANULOMATOSIS

T. M. LAWSON and B. D. WILLIAMSDepartment of Rheumatology, University Hospital of Wales, Heath Park, Cardiff CF44XW

SUMMARYHistological cardiac abnormalities in Wegener's granulomatosis can frequently be demonstrated at post-mortem examination,but clinically significant cardiac involvement is rare. We describe a massive silent myocardial infarction leading to intractableheart failure and death in a young man with Wegener's granulomatosis, occurring at a time when other features of the diseasewere responding to aggressive immunosuppression.

KEY WORDS: Wegener's granulomatosis, Myocardial infarction, Vasculitis.

WEGENER'S granulomatosis is an uncommon multi-system disorder characterized by necrotizing granulo-mata and vasculitis. Prior to the introduction ofimmunosuppressive therapy the majority of patientsdied within 1 yr, renal and respiratory disease beingthe main causes of death [1]. Currently, with treatmentthe majority of patients survive and even thoughfulminant cases still occur treatment-related mortalityhas now become a significant problem [2].

Significant cardiac complications occurring duringthe course of Wegener's granulomatosis are rare. Eventhough coronary vasculitis can be demonstrated at postmortem, symptoms associated with myocardial isch-aemia or heart failure are very uncommon. In thisreport we describe the late onset of cardiogenic shock,due to a silent myocardial infarction, in a young malewhose disease was responding to immunosuppressivetherapy.

CASE REPORTA 23-yr-old male initially presented to his general practi-

tioner with a 10-day history of left-sided earache and abloody discharge, symptoms initially thought to be indicativeof middle ear infection. When the patient failed to respondto a short course of antibiotic therapy he was referred to anear, nose and throat (ENT) specialist who noted the presenceof a left seventh lower motor neurone facial weakness.Results of investigations performed were as follows: normalblood count, liver and renal function tests, chest radiographand an erythrocyte sedimentation rate (ESR) of 65 mm/h. Animmunological screen, which included antineutrophil cyto-plasmic antibodies (ANCA), was negative and the immuno-globulin levels were normal. A computerized tomogram (CT)of the left petrous temporal bone showed soft tissue shadow-ing in the left middle ear but no bony destruction. He under-went a biopsy and mastoidectomy, histological examinationof this tissue revealing chronic non-specific inflammatorychange only. He was discharged, only to be readmitted 3weeks later with a further episode of left otalgia and fever.His ESR was now 75 mm/h but all previous investigationsremained normal. Nasolaryngoscopy showed rhinitis with

Submitted 26 April 1995; revised version accepted 27 July 1995.Correspondence to: T. M. Lawson.

inflammation of the left Eustachian cushion. He was againdischarged home on symptomatic therapy.

Six weeks later he was readmitted, having developed fever,fatigue, weight loss and haemoptysis. His ESR was now122 mm/h, his full blood count remained normal, renal andhepatic screen showed no significant abnormality and thecANCA was negative. A plain radiograph and CT scan of thechest revealed mid-zone consolidation/cavitation (Fig. 1).Mantoux test was negative and the serum angiotensin con-verting enzyme (ACE) levels were within the normal range.Bronchoscopic biopsy was performed; the small amount oftissue obtained showed an acute necrotizing ulcerative processwith no evidence of vasculitis or granuloma formation. Theattending physician made a diagnosis of atypical sarcoidosisand initiated treatment for 2 weeks only with 20 mg oforal prednisolone. No resolution in the chest X-ray findingstook place and he was subsequently referred to the thoracicsurgeons for an open lung biopsy. Whilst awaiting thisprocedure he developed severe arthralgia, vasculitic lesionsover the elbows, nose and cheeks and gangrene of several toesof the left foot. It was at this point that he was referred tothe Rheumatology Department at the University Hospital ofWales, Cardiff.

Physical examination revealed multiple vasculitic lesionsover the hands, feet, elbows and face, the left foot was coldand the dorsalis pedis pulse was absent. There was nolymphadenopathy, hepatomegaly or splenomegaly. His pulserate was 120/min, blood pressure (BP) 140/100 and there werenormal heart sounds with no murmurs. Auscultation of thelung fields revealed normal breath sounds only. Investiga-tions at this point revealed a haemoglobin lOg/dl, whiteblood count 20 x 10*/l and a platelet count 872 x 109/!.The urea was 14.7mmol/l and creatinine 82/imol/l. Urinetesting revealed blood and protein with a creatinine clear-ance of 46ml/min. The ESR had increased to 120 mm/hand the C-reactive protein (CRP) to 180mg/l. The ANCAwas now positive at a titre of 1:320 with a cytoplasmicstaining pattern. The electrocardiogram (ECG) was normaland an echocardiogram revealed no abnormality other thana tachycardia.

Immunosuppressive treatment was started and comprisedthree 1 g intravenous pulses of methylprednisolone onalternate days, followed by 60 mg of oral prednisolone and150mg of cyclophosphamide daily. He also underwent acourse of plasma exchange totalling 301 and was in additiontransfused with 3 units of packed cells. His clinical stateimproved within 72 h. The vasculitic skin lesions on the

© 1996 British Society for Rheumatology188

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LAWSON AND WILLIAMS: MYOCARDIAL INFARCTION IN WEGENER'S GRANULOMATOSIS 189

elbows, nose and cheeks began to resolve and no new lesionsappeared. The ESR fell to 50 mm/h after 2 days and continuedto fall. After 1 week of treamcnt the CRP was 13 mg/1. Heremained mildly hypertensive, BP 145/100 and in view of thepersisting tachycardia a cardiological opinion was soughtThis confirmed the presence of a sinus tachycardia with anotherwise normal ECG and no additional evidence of cardiacdisease.

Clinical improvement was sustained until 5 days aftercommencing treatment he suddenly developed abdominalpain with rebound tenderness and guarding. Bowel perfor-ation was suspected clinically and at laparotomy perforationof an infarcted area of the caecum was identified. A righthemicolectomy was subsequently performed. Histologicalexamination of this tissue revealed infarction with granulo-matous vasculitis. Post-operatively the lung cavities becamecolonized by Staphylococcus aureus and he required antibiotictreatment with cefuroxime 1.5 g t.d.s., metronidazole 500 mgt.d.s. and flucloxacillin 1 g q.d.s. He made a slow clinicalresponse. Two weeks after initiation of immunosuppressivetherapy his condition deteriorated suddenly, his pulse rateincreased to 150/min and was associated with hypotensionand a gallop rhythm. A repeat ECG showed the changes ofa recent extensive anteroseptal myocardial infarct with estab-lished Q waves (Fig. 2). A review of the ECG carried out onadmission confirmed that this trace was normal. A creatinekinase level carried out some 4 days earlier as part of aroutine biochemical screen was 908 IU. At the time this wasattributed to skeletal muscle damage, but subsequent analysis

of the cardiac isoenzyme CK-MB showed a small increase inthe proportion at 15% (normal <5%). Serial enzymes werenot investigated. Transthoracic echocardiography confirmedanteroapical akinesia. At no time had the patient complainedof chest pain. Despite maximal inotropic support thepatient's clinical course was that of worsening caidiogenicshock, which led to his death 4 days later. Permission forpost-mortem examination was refused.

DISCUSSIONThe diagnosis of Wegener's granulomatosis was

made 4 months after the initial presentation at a timewhen pulmonary inflammation, systemic vasculitis anda positive cANCA were all present. Initial diagnosticconfusion may have been due to the absence of typicalpathological features on biopsy material obtained fromthe mastoid region and the lung. However, a delay indiagnosis is not an uncommon finding in patients withthis disorder; less than 45% of patients are diagnosedwithin 3 months of the onset of symptoms [2].Although highly specific for Wegener's granulomatosis,a negative cANCA in patients with limited activedisease should not be regarded as excluding this con-dition since a positive result occurs in only 70-80%of cases [3]. Our patient improved with aggressiveimmunosuppressive therapy but succumbed to thelate vasculitic complications involving the heart.

FIG. 1.—Chest X-ray showing bilateral cavitating lesions.

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190 BRITISH JOURNAL OF RHEUMATOLOGY VOL. 35 NO. 2

FIG. 2.—ECG showing changes of a recent extensive anterolateral myocardial infarction.

Clinically significant cardiac involvement inWegener's granulomatosis is rare. A comprehensiverecent review of 158 patients reported that 10 (6%) haddeveloped pericarditis, eight of whom had typicalclinical symptoms and signs [2]. There are smallerstudies which report similar clinical and ECG findings[4]. One patient became hypotensive with a tachycardiabut echocardiography demonstrated that these signswere secondary to a large pericardial effusion, andresolved following urgent pericardectomy [5]. There isone report of constrictive pericarditis [6]. Arrhythmiasassociated with Wegener's granulomatosis are unusualbut when they do occur supraventricular arrhythmiasare the commonest. Although some arrhythmias maybe secondary to pericarditis, others have been attri-buted to vasculitis of the vessels supplying the cardiacconduction system and in some cases this has been con-firmed at post-mortem examination [7, 8]. One reportdemonstrated abnormalities of the sinoatrial and theatrioventricular node with the most extensive patho-logical changes of vasculitis and fibrosis being locatedin the sinoatrial artery. Microinfarcts were also demon-strated in the atrioventricular node [7]. Similar findingshave been reported in systemic lupus erythematosus [9],rheumatoid arthritis [10, 11] and polyarteritis nodosa[12]. Complete heart block secondary to atrioventricu-lar nodal involvement in Wegener's granulomatosishas been described in one case, the abnormality beingcorrected foUowing treatment with cyclophosphamide[13). Aortic valvulitis has also been demonstrated byechocardiography and this process also improvedfollowing the introduction of treatment [14].

Cardiac muscle and vessel involvement is much rarerclinically, occurring in less than 2% of the 158 cases

followed over a mean period of 8 yr [2]. Pathologicalexamination of tissue, however, demonstrates that car-diac abnormalities are much more common. An earlyreview of necropsy findings in Wegener's granulomato-sis reported abnormalities in 30% of cases, althoughthe majority of patients had no cardiac symptomswhilst alive and died from non-cardiac causes [13]. Thecommonest histological abnormalities were those ofcoronary arteritis and pericarditis, both occurring inapproximately 50% of cases with cardiac involvement[13]. The true frequency of these abnormalities, how-ever, is difficult to establish since the proportion ofcases undergoing detailed post-mortem histologicalexamination is variable.

Our case is unusual in that the cardiac complicationsoccurred several days after the commencement oftreatment, at a time when the patient's clinical state wasimproving. We have attributed these to the diseasesince there were no other identifiable risk factors. Theinitial presentation was that of a persistent tachycardiain the absence of fever and associated with a reductionin blood pressure. Clinically significant myocardialinfarction is extremely rare in Wegener's granulomato-sis and there is only one reported case. This was a28-yr-old male who experienced typical cardiac pain, afinding which contrasts with our patients [15]. Thereason why such an extensive anteroseptal infarct wasnot associated with symptoms is not known.

Although the acute event in this patient was notdiagnosed until the development of cardiogenic shock,it is unlikely that the clinical outcome would have beendifferent had the infarct been diagnosed earlier. How-ever, the majority of patients with myocardial infarc-tion associated with Wegener's granulomatosis could

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LAWSON AND WILLIAMS: MYOCARDLAL INFARCTION IN WEGENER'S GRANULOMATOSIS 191

benefit from early detection and appropriate therapywith ACE inhibitors. Whilst it is not feasible to admitall patients with this condition to a coronary care unitfor continuous monitoring it is important to be awarethat the potential for serious cardiac involvement ex-ists, and that it should be considered in asymptomaticpatients if there are any changes in pulse or bloodpressure recordings. More frequent ECG recordingsand a low threshold for requesting echocardiographywould appear appropriate.

REFERENCES

1. Editorial: Antimetabolities and immunoinflammatorydisease. N Engl J Med 1968;27&277-8.

2. Hoffman GS, Kerr GS, Leaitt RY et al. Wcgencr'sgranulomatosis: An analysis of 158 patients. AnnIntern Med 1992;116(6):488-98.

3. Specks U, Wheatley CL, McDonald TJ et al. Anti-cytoplasmic autoantibodies in the diagnosis and foUow-up of Wegener's granulomatosis. Mayo Clin Proc1989;64:28-36.

4. Fauci AS, Wolff SM. Wegener's granulomatosis.Medicine 1973^2:535-61.

5. Merghew NL, Bache RJL, Messner RP. Wegener'sgranulomatosis with acute pericardial tamponade.Semin Arthritis Rheum 1988;31:300-2.

6. Grant SCD, Levy RD, Yenning MC, Ward C, Brooks

NH. Wegener's granulomatosis and the heart. Br HeartJ 1994;71:82-6.

7. James TN, Birk RE. Pathology of the cardiac con-duction system in polyarthritis nodosa. Arch Intern Med1966;117:561-7.

8. Allen DC, Doherty CC, O'Reilly DPJ. Pathology of theheart and the cardiac conduction system in Wegener'sgranulomatosis. Br Heart J 1984;52:674-8.

9. James TN, Rupe CE, Monto RW. Pathology of thecardiac conduction system in systemic lupus erythemato-sus. Arm Intern Med 1965;63:402-10.

10. Harris M. Rheumatoid heart disease with complete heartblock. / Clin Pathol 1970;23:623-6.

14. James TN. De Subitaney Mortibus XXH1. Rheumatoidarthritis and ankylosing spondylitis. Circulation1977^5:669-77.

12. Thiene G, Valente M, Rossi L. Involvement of thecardiac conducting system in periarteritis nodosa. AmHeart J 1978;9S:716-24.

13. Forstot JZ, Overlie PA, Neufeld GK, Hamon CE,Forstot SL. Cardiac complications of Wegener granulo-matosis: A case report of complete heart block and reviewof the literature. Semin Arthritis Rheum 1980; 10(2): 148-54.

14. Gerbracht DD, Savage RW, Scharff N. Reversible valvu-litis in Wegener's granulomatosis. Chest 1987;92(1): 182-3.

15. Gatenby PA, Lython DG, Bulteau VG. Myocardialinfarction in Wegener's granulomatosis. Aust NZ J Med1976;6:336-40.

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