Cardiac Manifestations of Rocky Mountain Spotted Fever

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Cardiac

Manifestations

of Rocky

Mountain

Spotted

Fever

Jos#{233}

Mann-Garcia,

MD, W. M. Gooch

III, MD, and

Daniel L. Coury, MD

From the Department of Pediatrics and Pathology, University of Tennessee Center for the Health Sciences and LeBonheur Children ‘s Medical Center, Memphis

ABSTRACT. An increasing incidence of Rocky Mountain

spotted fever is being noted across the United States.

From 1955 to 1978 80 children with this disease were seen in a children’s hospital. Autopsies were performed in six

of the nine fatal cases, and cardiac lesions were seen in

each. Multifocal myocarditis with petechiae was present

in four cases, and in two of them there were areas of

myocardial necrosis. In four of the necropsied cases there were electrocardiographic changes and cardiac

enlarge-ment on chest roentgenogram. Among survivors five pa-tients manifested at least one cardiac abnormality. ST-T

changes were noted in two patients, atrioventricular

con-duction disturbance in two, and severe left ventricular hypertrophy in one patient. Cardiomegaly was observed

in three patients, and one had severe cardiac failure that responded to medical management. Cardiac involvement is frequently present in Rocky Mountain spotted fever,

and close observation seems to be warranted. Pediatrics 67:358-361, 1981; Rocky Mountain spottedfever, myocar-ditis.

Rocky Mountain spotted fever is an acute,

poten-tially lethal febrile illness in which cardiac

involve-ment has been sporadically reported.’5 The disease

is endemic in the South Central and Atlantic States,

and during the last two decades an increasing mci-dence has been noted across the United States.6 The disease involves many organs and systems and

is characterized by generalized vasculitis involving

primarily the endothelial cells of small blood vessels initially and the smooth muscle cells of larger ar-teries later. Although focal myocarditis and myo-cardial necrosis frequently have been found at

post-Received for publication April 24, 1980; accepted Aug 4, 1980. Presented in part at the 48th Annual Meeting of the American Academy of Pediatrics, San Francisco, October 1979. Reprint requests to (J.M.) Department of Pediatrics, University of Tennessee Center for the Health Sciences, 848 Adams Aye,

Memphis, TN 38103.

mortem examination, the clinical manifestations of

the cardiac involvement and its possible pathogenic role in some of the fatal cases has not been empha-sized.

This paper presents the physical manifestations and the radiographic and electrocardiographic fea-tures in 14 cases of Rocky Mountain spotted fever. The results of anatomic examination of six cases

also are presented.

MATERIALS AND METHODS

The clinical and pathologic records of LeBonheur Children’s Medical Center in Memphis from 1952 to 1978 were reviewed for cases of Rocky Mountain spotted fever. Eighty cases of the disease were confirmed based upon the presence of at least two of the following criteria: (1) history of exposure to ticks or a tick bite; (2) typical clinical picture and course (fever and rash that progresses from macu-lopapular to hemorrhagic); (3) Weil-Felix aggluti-nation titer of 1:320 or fourfold rise between acute

and convalescent sera. In 66 cases there was no

clinical evidence of cardiac involvement

(noncar-diac group). Cases with cardiac involvement are designated the cardiac group. There were nine deaths (fatal group) and autopsy was available in six of these. There was no attempt to grade the severity of anatomic lesions because of the unsys-tematic sampling of tissues inherent in a retrospec-tive analysis. In all cases from the fatal group and five cases of the survival group (cardiac survival

group) there were clinical manifestations of cardiac

involvement. Clinical and electrocardiographic data were available for study in each of the 14 cases and radiologic data were available in 13 cases.

RESULTS

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mi-Case Sex Age

(yr)

Auscultation Chest X-Ray

(Cardiomegaly)

Electrocardiogram Pathologic Findings

it F 8 Summation

gallop

Mild PAT and ST-T

changes

Subendocardial myocardial necrosis;

petechial and ecchymotic hemor-rhage of subendocardial myocardium 2t F 7 Tachycardia Not available Sinus tachycardia Arteritis and arteriolitis; myocarditis;

petechial hemorrhage of

myocar-dium; myocardial necrosis

3t M 1 1 Tachycardia Mild and

pulmo-nary edema

Sinus tachycardia Arteritis and arteriolitis; myocarditis;

epicardial, endocardial, and

myocar-dial petechiae

4t M 9 2/6 Systolic Murmur

Normal Nodal tachycardia Arteritis and arteriolitis, petechial and

ecchymotic hemorrhage of epicar-dium; ventricular dilation

St M 4 Tachycardia Mild Low voltage First

degree A-V block, Prolonged Q-T

Petechial and ecchymotic hemorrhage of mitral valve leaflets; epicardium, myocardium, and endocardium; myo-carditis; biventricular dilation

6t M 7 Normal Normal LVH Endocarditis and pericarditis;

biventri-cular dilation; petechial hemorrhages of tricuspid valve

7t

F 5 Normal Normal First degree A-V

block

Autopsy not performed

8+ F 13 Normal Mild and

pulmo-nary edema

Low voltage and ST-T changes

Autopsy not performed

9t F 10 2/6 Systolic

murmur

Normal Normal Autopsy not performed

100 M 8 Summation

gallop

Moderate PAT

1 i M 1 1 Tachycardia Moderate First degree A-V

block; LAE

12 F 5 Normal Mild Normal

13 F 9 2/6 Holosys-tolic murmur at apex

Normal First degree A-V

block

14 F 4 Tachycardia Normal IRBBB, ST-T

changes

* Abbreviations and symbols used are: , fatal cases; PAT, paroxysmal atrial tachycarclia; A-V, atrioventricular; LVH,

left ventricular hypertrophy; LAE, left atrial enlargement; IRBBB, incomplete right bundle branch block; O cardiac

TABLE. Clinical and Pathologic Cardiac Findings*

ARTICLES 359

failure.

croscopic preparations were available in six of the

fatal cases. Petechial and/or ecchymotic hemor-rhages were seen in one or more cardiac sites in all cases. Arteritis and arteriolitis were seen in three cases while myocarditis and/or myocardial necrosis was seen alone or in combination with the vasculitis in four. Myocardial necrosis was always multifocal.

The inflammatory infiltrate in cardiac lesions was

composed predominantly of lymphocytes, plasma cells, and macrophages. Lesions elsewhere, psi-tic-ularly those of the liver, kidney, and testes, were

composed predominantly of neutrophils. No signifi-cant difference in the initial mode of clinical presen-tation was noted between the cardiac and noncar-diac group, nor were differences noted in the 14 cases with cardiac involvement when comparison was made between the cardiac survival group and

the fatal group. Each of these patients had fever,

rash, and past history of tick exposure. Weil-Felix agglutination was performed in each patient and a

fourfold rise was observed in 54. In 21 cases there

was no rise in a titer already considered diagnostic. In five cases from the fatal group no convalescent titer could be obtained because death occurred

within three days of admission. In each case the

illness began eight to ten days prior to the time of

admission. One patient was seen with shortness of breath and fatigability and required digoxin, diuret-ics, and fluid restriction because of severe

conges-tive cardiac failure. Five patients had inappropriate sinus tachycardia for the degree of fever (heart rate above 150 beats per minute and temperature less than 102 F) and two had gallop rhythm. In three patients a grade 2/6 systolic murmur was heard loudest along the lower left sternal border with radiation to the apex. Thrombocytopenia was pres-ent during the course of the ifiness in eight cases of the fatal group (ranged from 8,000 to 115,000/cu

mm with a mean value of 31,000/cu mm) and in

four of the survival group, and it occurred in 81% of

the cases in the noncardiac group.

In 18 cases only the diagnosis of Rocky Mountain

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spotted fever was suspected when the patient was first seen, and the initial mode of treatment was appropriate (tetracycline and chloramphenicol) in these cases.

There was no significant difference in the time

interval between onset of symptoms and initiation of treatment when the cardiac and noncardiac groups were compared.

Radiographic evidence of cardiac enlargement was present in seven patients, and in two of these there was pulmonary edema. Three patients from the survival group who presented cardiac enlarge-ment initially had normal chest roentgenograms when they were discharged from the hospital.

First degree atrioventricular block was present in four cases, and in one of them there was prolonga-tion of the Q-T interval and generalized low volt-ages. Paroxysmal atrial tachycardia was observed in one case from the survival group and in another case from the necropsy group. Nonspecific ST-T changes were noted in two cases, left ventricular

hypertrophy in one, and nodal tachycardia with aberrancy in another. Inappropriate sinus

tachycar-dia was evident in the electrocardiogram of two cases and in another two cases the electrocardi-ogram was within normal limits. In each of the cardiac survival cases, the electrocardiogram was

normal when the patient was discharged from the

hospital.

DISCUSSION

Rocky Mountain spotted fever is a serious infec-tious disease that continues to occur with increasing incidence in the United States. Over 1,000 cases were reported to the Center for Disease Control in Atlanta in 1977 and again in 1978. Most cases occur between mid-April and mid-October with a peak in the summer months; however, cases have also been reported during the winter.8 A high case-fatality ratio persists despite the availability of ad-equate antibiotics (tetracycline and chlorampheni-col). Bradford and Hawkins9 reported 13% fatality rate in a large series of cases with Rocky Mountain spotted fever, but no statement was made concern-ing treatment with tetracycline or chloramphenicol. As in that study, serologic diagnosis in our series depended primarily upon either a presumptively diagnostic titer of Weil-Felix agglutinins or a

four-fold rise in agglutinins, since this is the diagnostic

test most commonly available. In our series an 11%

fatality rate was seen, and in each case appropriate antibiotic therapy was initiated upon admission to the hospital. Although delay in diagnosis and initi-ation of treatment could play a role in the deaths of some patients, in our experience there was no

ap-parent difference between the pretreatment,

syrup-tomatic interval of the fatal and survival groups. Host factors and differences in the toxicity of var-ious strains of Rickettsia rickettsii might influence the severity of disease in individual cases, but these

variable were not assessed in the current study.

Clinically, it is difficult to determine the

fre-quency of cardiac involvement in Rocky Mountain

spotted fever. A definitive diagnosis of myocardial

disease can be made only after histologic examina-tion of the myocardium. Sometimes clinical mani-festations of myocardial involvement may be very subtle or may be overshadowed by those of extra-cardiac disease. In our cases inappropriate sinus tachycardia for the degree of fever and gallop rhythm were common clinical findings, and a sys-tolic murmur suggestive of mitral insufficiency was present in three patients. Cardiac enlargement was noted on the chest roentgenogram ofseven patients.

One of them had pulmonary edema as well as

tachypnea and gallop rhythm when he was admit-ted to the hospital. The features of this latter case

may be related to myocardial impairment, although

pulmonary edema in Rocky Mountain spotted fever may be secondary to pulmonary vasculitis and sub-sequent interstitial edema.’#{176} In our group of cases with cardiac involvement the spectrum of electro-cardiographic findings included low voltages and changes in the ST-T segment compatible with

myo-cardial damage. Conduction disturbances were present in four of our cases. This incidence is similar to that reported by others.’ It seems possible for the conduction system to be involved in Rocky

Mountain spotted fever by inflammatory cells,

hem-orrhages secondary to thrombocytopenia,2 or

is-chemia due to vasculitis. Similarly arrhythmias and conduction disturbances have been reported previ-ously in adults with thrombotic thrombocytopenic purpura.” Paroxysmal atrial tachycardia was ob-served in two of our cases and nodal tachycardia in one. Atrial fibrillation and nodal tachycardia had been reported previously in adults with Rocky Mountain spotted fever,2 but to the best of our knowledge no cases have been described previously in the pediatric literature.

The spectrum of myocardial lesions seen in our cases was similar to that previously described5; how-ever, the pathogenesis of these lesions was rather difficult to explain. Of interest was the association of myocarditis and pericarditis with or without myocardial necrosis in the absence of the classical vasculitis of spotted fever. One possible explanation for this observation might be the retrospective na-ture of our study of tissues previously taken for

examination. Another possible explanation may be

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ARTICLES 361 cells is complex with rapid extracellular

accumula-tion of organisms and rapid spread of the organisms to all cells in the in vitro culture.’2 This is in contrast

to the behavior of the organism in plasma clot tissue

explant cultures as performed by Wolbach and

Schlesinger’3 and Pinkerton and Hass.’4 In these experiments upon which many of our current

con-cepts of the pathogenesis of Rocky Mountain spot-ted fever are based, growth occurred most often in

endothelial and fibroblastic cells. In our cases the greater predominance of lymphoctyes, plasma cells, and macrophages in cardiac inflammatory infil-trates suggests that the lesions in the heart were

initiated earlier in the evolution of the disease than those in other organs in which neutrophils

predom-mated.

It is possible that myocardial impairment in

Rocky Mountain spotted fever may account for the

death of some patients, and cardiac failure and

arrhythmias may be more common than has been previously recognized. Awareness of the cardiac

involvement is important, and close clinical and electrocardiographic monitoring during the conva-lescence of the patients seems to be warranted.

REFERENCES

1. Linnemann CC, Janson PJ: The clinical presentations of Rocky Mountain spotted fever: Comments on recognition and management based on a study of 63 patients. Clin

Pediatr 17:673, 1978

2. Atwater JS, Markie CD, Stubbs W Jr: Rocky Mountain spotted fever with thrombocytopenia and atrial fibrillation:

A case report. JMedAssoc GA 57:210, 1968

3. Woodward TE, McCrumb FR Jr, Cary TN, et al: Viral and rickettsial causes of cardiac disease, including the coxsackie

virus etiology of pericarditis and myocarditis. Ann Intern

Med 53:1130, 1960

4. Aquiina JT, Rosenberg F, Wuertz RL: Nodal tachycardia in

a case of Rocky Mountain spotted fever. Am Heart J 43:755,

1952

5. Bradford WD, Hackel DB: Myocardial involvement in

Rocky Mountain spotted fever. Arch Pathol Lab Med 102: 357, 1978

6. Hattwick MAW, Retaffliau M, O’Brien RJ, et a!: Fatal Rocky Mountain spotted fever. JAMA 240:1499, 1978

7. Summary. Cases ofspecific notifiable disease: United States.

Morbidity Mortality Weekly Rep 21:517, 1978

8. Sexton DJ, Burgdorfer W: Clinical and epidemiologic fea-tures of Rocky Mountain spotted fever in Mississippi, 1933-1973. South Med J 68:1529, 1975

9. Bradford WD, Hawkins HK: Rocky Mountain spotted fever

inchildhood. Am J Dis Child 131:1228, 1977

10. Lees RF, Harrison RB, Williamson RB, et al: Radiographic findings in Rocky Mountain spotted fever. Radiology 129: 17, 1978

11. James TN, Monto RW: Pathology of the cardiac conduction system in thrombotic thrombocytopenic purpura. Ann

In-tern Med 65:37, 1966

12. Wisseman CL Jr, Edlinger EA, Waddell AD, et al: Infection cycle of Rickettsia rickettsii in chicken embryo and L-929

cells in culture. Infect Immun 14:1052, 1976

13. Wolbach SB, Schlesinger MJ: The cultivation of the micro-organisms of Rocky Mountain spotted fever

(Dermacentrox-enus rickettsi) and of typhus (Rickettsia prowazeki) in tissue plasma cultures. J Med Res 44:231, 1923-1924

14. Pinkerton H, Ham GM; Spotted fever. I. Intranuclear rick-ettsiae in spotted fever studied in tissue culture. J Exp Med

56:151, 1932

INTERNATIONAL MEETING

VI Congress of Pediatrics and XIII Panamericano and Peruvian Congress of

Pediatrics will be held in Lima Peru in October 1981. For information, please contact:

Congresos Internacionales De Pediatria Lima, 1981 Washington 1807-Of. 401

Apartado 1786 Lima 1, Peru South America

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1981;67;358

Pediatrics

José Marin-Garcia, W. M. Gooch III and Daniel L. Coury