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Acute Myopericarditis Associated with Cat Scratch Disease in an Adolescent

Barson, William J. MD*; Honegger, J. Robert MD*; Texter, Karen MD

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The Pediatric Infectious Disease Journal: September 2014 - Volume 33 - Issue 9 - p 982-984
doi: 10.1097/INF.0000000000000352
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Abstract

A 16-year-old male was admitted to Nationwide Children’s Hospital for evaluation/treatment of an enlarging mass in the left inguinal region that had developed during the preceding week. He had been evaluated by his pediatrician 4 days earlier and treated with cephalexin (500 mg qid). In the previous 24 hours, the skin overlying the mass became erythematous. He reportedly had only 1 temperature elevation of 101°F 2 days before admission. In the local emergency room, an ultrasound examination of the left inguinal area demonstrated numerous enlarged lymph nodes the largest being 4.5 cm in maximal dimension. Parenteral clindamycin (300 mg) was begun. Of epidemiologic note, the patient was exposed to turkeys, chickens and rabbits through 4H activities and had been scratched by his 8-month-old kitten on his left mid-abdomen 1 month earlier.

The young man appeared to be healthy and in no distress: body temperature 99.8°F, pulse rate 109 beats/min, respiratory rate 20 breaths/min and blood pressure 132/70 mm Hg. The examination was normal except for a 10 × 5 cm area of erythema in the superior medial aspect of the left thigh overlying a 5 × 3.5 cm area of induration without associated fluctuance. A healed scratch lesion was present on the left abdomen.

The complete blood count showed a hemoglobin/hematocrit of 15.4 g/dL/44.8%, white blood cell count of 11,800/cu mm with 12% bands, 48% segmented neutrophils, 27% lymphocytes, 10% monocytes and 4% eosinophils; platelet count was 132,000/cu mm. The inflammatory markers were elevated with an erythrocyte sedimentation rate of 30 mm/h and C-reactive protein of 9.9 mg/dL.

Oral therapy with azithromycin (250 mg daily after a 500 mg load) was begun for the presumptive diagnosis of cat scratch lymphadenitis. Parenteral clindamycin (900 mg every 8 hours) was continued for Staphylococcus aureus and group A Streptococcus coverage until the results of the Bartonella henselae serology testing were available.

The patient remained afebrile except for a 1 time low grade temperature of 100.4°F and the area of erythema improved. During the night of his first hospital day, he experienced a 20-minute period of chest pain described as “tightness” across his upper chest and appeared to be improved after a dose of pantoprazole. A similar, but much shorter, self-limited episode occurred again the following morning. Laboratory evaluation documented an elevated aspartate aminotransferase of 291 (5–60 U/L), creatine kinase of 1105 (37–289 U/L; creatine kinase-MB isoenzyme primarily of myocardial origin was not measured) and troponin I value of 38.4 (< 0.3 nanograms/mL) ~ 20 hours after the start of his chest pain. Cardiology consultation documented normal perfusion/pulses, regular rate and rhythm, normal heart tones and no murmur, gallop or rub. The electrocardiogram (ECG) demonstrated normal sinus rhythm with diffuse ST segment elevation and subtle PR depression. Echocardiography demonstrated normal chamber sizes, normal right and left ventricular (LV) systolic/diastolic function, no regional wall motion abnormalities, no valvular abnormalities or vegetation, and no pericardial effusion. The combination of a normal physical examination, ECG findings of pericarditis and an elevated serum troponin I value led to a diagnosis of myopericarditis. The patient remained clinically well with normal serial physical examinations, stable ECGs and the troponin I value fell from the high of 38.4 to 0.8 nanograms/mL over 64 hours. Cardiac magnetic resonance imaging (MRI) obtained on day 4 demonstrated abnormal delayed myocardial enhancement in a mid-myocardial to epicardial distribution along the lateral and inferolateral walls consistent with myocardial necrosis and regional myocarditis. LV functional analysis was normal with a measured LV ejection fraction of 68%. The proximal coronary artery anatomy was also normal. Acute B. henselae serology testing, performed by the Clinical Microbiology and Immunoserology Laboratory of Nationwide Children’s Hospital using an immunofluorescence technique and Focus Diagnostics, Inc. (Cypress, CA) reagents, was positive with an IgM of > 1:32 and IgG of > 1:128. B. henselae molecular diagnostic testing by polymerase chain reaction (PCR) of plasma was negative and testing for other potential viral pathogens responsible for myocarditis was likewise negative [plasma PCRs for CMV, adenovirus, parvovirus B19 and enterovirus, throat/anal swab PCR for enterovirus, Epstein-Barr virus serology (indicated a past infection) and acute arbovirus (West Nile virus, St. Louis Encephalitis virus, California Encephalitis virus, Eastern and Western Equine Encephalitis viruses) serologies]. The patient was discharged to complete a 10-day course of azithromycin. During an 18 month follow-up period, the patient remained clinically well with normal cardiac function although the ECG transiently demonstrated ST-T inversion in the inferolateral leads as well as a right bundle branch block at the 1 month follow-up visit which subsequently resolved. Although improved, the delayed myocardial enhancement persisted on MRI examination with normal LV function.

DISCUSSION

Cat scratch disease is an infection characterized by self-limited chronic regional lymphadenopathy and caused most often by the fastidious pleomorphic Gram-negative bacillus, B. henselae. An estimated 22,000 cases of cat scratch disease are diagnosed annually in the United States, predominately in children.1 Greater than 90% of patients with cat scratch disease recall recent contact with a cat, often a kitten, and 50–87% report being scratched.1 Less common clinical manifestations include fever of unknown origin frequently associated with hepatic and splenic granulomatous inflammation; neurologic involvement including encephalopathy, transverse myelitis, radiculitis and cerebellar ataxia; ocular involvement of neuroretinitis, Parinaud’s oculoglandular syndrome, papillitis, optic neuritis and focal retinochoroiditis and musculoskeletal involvement of myalgia, arthralgia/arthritis, tendinitis and osteomyelitis. Unusual manifestations including pneumonia with pleural effusion, septic shock, dermatologic findings of transient macular and papular eruptions, erythema multiforme, erythema nodosum and thrombocytopenic purpura, and cardiac involvement in the form of culture-negative endocarditis, which is seen more commonly in adult patients, are also reported.1,2 However, myopericarditis is not mentioned as one of the cardiac manifestations in major pediatric and adult infectious diseases textbooks and reviews related to cat scratch disease.

Myocarditis associated with cat scratch disease is a known complication of Bartonella spp. infection in cats but has been rarely reported in humans (Table 1). In 1997, Holmberg et al3 presented a 60-year-old Swedish male with myocarditis and sudden death associated with Bartonella spp. infection in abstract format at the 13th Sesquiannual Meeting of the American Society for Rickettsiology. However, it was not until 2001 that the first published report of histologically confirmed myocarditis associated with acute B. henselae infection appeared.4 A 32-year-old man was presented with fever and left-sided inguinal swelling, erythema and tenderness. On the seventh day of hospitalization, he developed chest pressure and palpitations associated with orthopnea and exertional dyspnea. Echocardiography demonstrated biventricular and left atrial dilatation, an ejection fraction of 10%, severe tricuspid and moderate mitral valve regurgitation. An endomyocardial biopsy performed 33 days after recognition of the lymphadenopathy demonstrated lymphocytic infiltration with associated myocyte necrosis and replacement fibrosis consistent with chronic active myocarditis. A lymph node biopsy performed close to the same time demonstrated well-formed granulomas with central necrosis and the presence of B. henselae DNA detected by PCR technique. Serologic testing confirmed antibody titers to B. henselae at 1:2048. However, the myocardial biopsy specimen was negative for B. henselae by PCR and immunohistochemical staining. During the period of 1979–1992, an increasing number of sudden unexpected cardiac deaths occurred in elite Swedish orienteers (orienteering is a sport with the aim of finding the fastest route through unfamiliar terrain between defined checkpoints using a compass and detailed map) with myocarditis diagnosed in 75% of the 16 victims.5Bartonella spp. genomes were detected in cardiac tissue in 4 of 5 patients whose hearts were available for testing (3 B. henselae, 1 B. quintana). Most recently in 2008, a 22-year-old male presenting with axillary adenopathy and chest pain was reported with an elevated troponin level, ST segment elevation and positive B. henselae serology.6 This patient appeared to respond to a 7-day course of azithromycin.

TABLE 1
TABLE 1:
Patients Reported With Myocarditis due toBartonella henselae

Our patient represents the youngest patient reported with myopericarditis associated with cat scratch disease. Although no myocardial biopsy was performed, the combination of chest pain with elevated serum troponin I values that followed a typical time course, abnormal delayed LV subepicardial enhancement on cardiac MRI,7,8 and ECG changes of pericarditis suggest the diagnosis of myopericarditis. The clinical presentation of regional lymphadenopathy after a kitten scratch and positive serologic testing suggest the B. henselae etiology.

Meininger et al4 suggested a post-infectious, immune-mediated myocyte injury in their patient who required heart transplantation, because B. henselae antigen was not detected in the myocardial biopsy, whereas the findings of Wesslen et al5 support direct myocardial invasion by B. henselae. Although azithromycin is known to have immunomodulatory activity, the rapid normalization of the serum troponin I values in our and Pipili et al’s6 patients after initiation of azithromycin therapy suggest the possibility of direct bacterial invasion of the myocardium that was amenable to antimicrobial therapy. Azithromycin with known immunomodulatory activity and antibacterial activity against B. henselae appears to be an appropriate treatment for this condition.

ACKNOWLEDGMENTS

The authors wish to thank Dr. Stephen Druhan of the Department of Radiology of Nationwide Children’s Hospital for his assistance in reviewing the cardiac MRI.

REFERENCES

1. Schutze GE, Jacobs RFLong SS, Pickering LK, Prober CG. Bartonella species (cat-scratch disease). Principles and Practice of Pediatric Infectious Diseases. 20124th ed. Philadelphia Elsevier:856–861 In:
2. Spach DH, Kaplan SLRose BD. Microbiology, epidemiology, clinical manifestations, and diagnosis of cat scratch disease. UpToDate. 2013 Waltham UpToDate In:
3. Holmberg M, Wesslen E, Hjelm C, et al. Bartonella spp. in a 60 year-old Swedish male with myocarditis who succumbed to sudden death [Abstract 31]. 1997Program and abstracts of the 13th Sesquiannual Meeting of the American Society for RickettsiologyChampion, PA:21–24 In: September
4. Meininger GR, Nadasdy T, Hruban RH, et al. Chronic active myocarditis following acute Bartonella henselae infection (cat scratch disease). Am J Surg Pathol.. 2001;25:1211–1214
5. Wesslen L, Ehrenborg C, Holmberg M, et al. Subacute Bartonella infection in Swedish orienteers succumbing to sudden unexpected cardiac death or having malignant arrhythmias. Scand J Infect Dis. 2001;33:429–438
6. Pipili C, Katsogridakis K, Cholongitas E. Mycocarditis due to Bartonella henselae. South Med J. 2008;101:1186
7. Skouri HN, Dec W, Friedrich MG, et al. Non-invasive imaging in myocarditis. J Am Coll Cardiol. 2006;48:2085–2093
8. Kobayashi D, Aggarwal S, Kheiwa A, et al. Myopericarditis in children: elevated troponin I level does not predict outcome. Pediatr Cardiol. 2012;33:1040–1045
9. Holmes AH, Greenough TC, Balady GJ, et al. Bartonella henselae endocarditis in an immunocompetent adult. Clin Infect Dis. 1995;21:1004–1007
Keywords:

Bartonella henselae; cat scratch disease; myopericarditis

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