Subsequently, blood cultures yielded Bacteroides thetaiotamicron, an anaerobic bacterium.
First described in 1877 by Bollinger as the cause of “lumpy jaw” in cattle, the microbial organisms causing human actinomycosis are a variety of anaerobic or microaerophilic gram-positive bacteria classified in the genus Actinomyces . The term actinomyces is a misnomer of Greek origin that means “ray fungus,” from the organism’s microscopic appearance . Prompt diagnosis of actinomycosis is difficult because of the paucity of clinical symptoms, even with extensive organ involvement. Hence, actinomycosis is designated as the “most misdiagnosed disease” .
We reviewed literature on disseminated and cardiac actinomycosis published since the first report of lumpy jaw in 1877. To our knowledge, sudden death caused by cardiac involvement by actinomycosis has not been described previously. In view of this, we believe that our case of disseminated actinomycosis is unusual and will add to our understanding and recognition of the spectrum of this rare disease. A review of the clinical aspects of disseminated and cardiac actinomycosis is presented below.
The incidence of disseminated disease reported from different case series is variable (Table 1). By reviewing medical literature published in the modern antibiotic era between 1948 and 1995, we found that only 15.9% of all cases had evidence of disseminated actinomycosis. A detailed report on actinomycosis by Bennhoff  in 1984 suggested that the incidence of all forms of actinomycosis has declined.
Disseminated actinomycosis occurs predominantly in males (male-to-female ratio = 3:1). Male predominance may be due to an increased prevalence of faciomaxillary trauma in men. The age of onset of illness is usually in the fourth to sixth decades of life. The elderly and children tend to lose teeth including the caries and hence may be at lower risk for actinomycosis .
There are no reports of contagious spread of actinomycosis from one host to another. Actinomyces is strictly endogenous to the host, where it resides in the oral cavity or gastrointestinal or genitourinary tract. Poor dental hygiene and trauma are predisposing factors for initial infection . Alcoholics have a heightened risk due to poor dentition and aspiration of oral secretions. Occasionally, invasive surgical procedures of the gastrointestinal tract pose additional risk for initial infection . Pelvic actinomycosis occurs in association with the use of intrauterine contraceptive devices . The risk of actinomycosis for immunocompromised hosts, such as those with HIV infection or diabetes and those undergoing chemotherapy or taking steroids, does not exceed that for the immunocompetent.
Most cases of disseminated actinomycosis described in the literature presented with insidious onset of constitutional symptoms such as fever, weight loss, malaise, and night sweats ranging in duration from several weeks to months or even a few years. Symptoms and signs may decrease or increase in parallel with initiation or termination of antibiotic therapy. Disseminated actinomycosis is surprisingly indolent at the time of diagnosis, and symptoms do not correlate with extent of disease. Weese et al. reported that a correct diagnosis was made for only 7% of patients at the time of admission . Although disseminated actinomycosis can involve any organ system, commonly the lungs, skin, long bones, liver, brain, and muscles are affected. Death due to actinomycosis is extremely rare. Sudden cardiac death due to actinomycosis has never been reported in the literature.
All species of Actinomyces, namely, A. israelii, A. naeslundii, A. odontolyticus, A. viscosus, and A. meyeri, can cause clinical disease. However, A. meyeri and A. israelii are common causative organisms of disseminated actinomycosis . Propionibacterium propionicus is another rare but established causative agent of actinomycosis. In addition, Eubacterium and Corynebacterium pyogenes have also been implicated as less established causes of actinomycosis.
Abnormal findings of biochemical tests are nonspecific and nondiagnostic for actinomycosis. These include mild to moderate leukocytosis with a left shift, increased ESR, and abnormally increased liver enzyme concentrations (alkaline phosphatase, AST/ALT, GGT, and LDH). Eosinophilia is not a feature of actinomycosis . Total serum protein and immunoglobulin levels may be elevated .
Chest roentgenogram abnormalities found in thoracic actinomycosis include pulmonary infiltrates and pleural disease with or without pleural effusion. Pulmonary disease frequently occurs in the lower lobes. A persistent pulmonary infiltrate not responding to antibiotic therapy, with coexistent involvement of the chest wall, is highly suggestive of thoracic actinomycosis . Pulmonary lesions in the form of mass, chronic fibrocavitary or alveolar infiltrates also occur. Hilar adenopathy, frank cavitation, and miliary involvement of lungs are rare.
Electrocardiographic abnormalities occur in cases with cardiac involvement and are discussed below. Species of bacteria such as Actinobacillus, Eikenella, Fusobacterium, Bacteroides, Capnocytophaga, Staphylococcus, Streptococcus, and Enterobacteriaceae can occasionally cause coexistent infection in patients with disseminated actinomycosis. It is postulated that they may play a role in the initiation or dissemination of actinomycosis . However, the clinical significance of this finding remains unclear.
Diagnosis is usually made by isolation of microorganisms from tissues or staining and culture of the secretions showing typical sulfur granules [12,13]. Common sites useful for biopsy include skin, lung, and liver. Identification of actinomycotic agents through microbiologic testing requires strict anaerobic processing and transport of specimens. Antibiotics should be avoided prior to specimen sampling because all agents of actinomycosis are sensitive to a variety of antibiotics. Even a single dose of antibiotic can interfere with isolation of actinomycotic agents.
Direct immunofluorescence staining of specimen samples with fluorescein isothiocyanate–labeled species-specific antiserum offers a simple and cost-effective alternative to microbiologic isolation of actinomycosis. A direct immunoperoxidase staining technique for identification of Actinomyces species in biopsy specimens is also available. Electrophoretic techniques for detection of antigen have been studied with relatively low success because of their lack of specificity. Skin hypersensitivity tests such as complement fixation and hemagglutination have not been found useful because of cross-reactions with tuberculosis .
In view of sudden cardiac death and autopsy findings of disseminated actinomycosis with unusual cardiac involvement, we also reviewed the literature on cardiac actinomycosis.
Actinomycosis rarely involves the heart. Among reports of actinomycosis published since 1891, we found evidence of cardiac actinomycosis reported in only 1.2% of all cases (Table 2). Kasper and Pinner  and Cornell and Shookhoff  have collected the largest series of cases of cardiovascular actinomycosis. We found interesting cardiac findings in our case that have never been reported.
Cardiac actinomycosis is often asymptomatic, and cases are usually diagnosed postmortem. In symptomatic cases, the average age at presentation is 30 years (range, 6–59 years), and there is a marked male preponderance . Actinomycosis can involve all layers of the heart. Clinical signs depend on the layer of involvement. According to Dutton and Inclan , cardiac involvement occurs almost always secondary to chest disease. The mode of spread is usually contiguous from adjacent structures and is reflected in the preferential involvement of the pericardium rather than the inner myocardial and endocardial layers. Primary cardiac involvement without chest disease was found to occur in only 6% of all cases .
About 70% of cases with cardiac actinomycosis present with pericardial disease. This usually occurs by contiguous spread from the adjacent mediastinum and rarely through a hematogenous route . However, few cases of primary pericardial actinomycosis have been reported . Acute purulent pericarditis is a frequent manifestation of pericardial actinomycosis [19–22]. Pericardial effusion with tamponade and constrictive pericarditis also occur [23,24]. Pericardial actinomycosis presents with the usual features of pericardial disease such as chest pain, pericardial friction rub, sinus tachycardia, distant heart sounds, and signs of pericardial tamponade [18–24].
Myocardial and endocardial involvement.
Endocardial, valvular, and myocardial involvement is extremely rare and usually secondary to pericardial disease [25–28]. In symptomatic individuals with myocardial actinomycosis, right and left heart failure is common. There is a male predominance in the incidence of endocarditis due to actinomycosis. Clinical or pathologic features of actinomycotic endocarditis are similar to other microbial endocarditis. Fever, cardiac murmurs, splenomegaly, and elevated white blood cell counts are common. Mitral valve involvement is common, followed by aortic valve involvement. Blood cultures were positive for Actinomyces in two thirds of these cases. Clinical evidence of systemic embolism occurs in 75% of such patients and predominantly affects the central nervous system . Coronary artery involvement in actinomycosis has been reported in only one case in the literature .
Electrocardiographic findings include repolarization changes, ST elevation mimicking myocardial infarction, low voltage complexes, sinus tachycardia, and, rarely, arrhythmias. Chest roentgenogram abnormalities in cases with heart failure and pericardial effusion include an enlarged cardiac silhouette. Diagnosis of cardiac actinomycosis is usually made postmortem or incidental to thoracic disease. Sulfur granules on the valves, pericardium, and myocardium have been described.
Our patient was a middle-aged man who had normal dentition and oral hygiene and a history of occasional alcohol use. Blood sugar levels were elevated, suggesting the presence of previously undetected diabetes in our case. Whether untreated diabetes was a risk factor for actinomycosis in our patient is unclear.
Similar to other cases of disseminated actinomycosis, he presented with nonspecific symptoms such as fever, transient skin rash, and malaise and weight loss. In contrast to sinus tracts and abscesses described in the majority of cases with cutaneous actinomycosis, skin involvement occurred in the form of transient macular pruritic lesions on the extremities. The duration of symptomatic disease in our patient was brief and without features of organ-specific involvement. As in other cases, leukocytosis, elevated ESR, and abnormal liver function test findings were noted. Moreover, blood cultures yielded Bacteroides, an anaerobic bacterium that can cause coexistent infection in patients with disseminated actinomycosis.
Our patient did not have any symptoms or signs of cardiac involvement. Radiological and electrocardiographic signs of cardiac involvement were unusually absent. Acute upper back pain, dyspnea, and abnormal chest examination findings occurred only just before sudden death. On autopsy, there was no evidence to suggest contiguous spread of actinomycosis from lung to heart. Although pericardial and myocardial inflammation was noted on autopsy, usual manifestations of cardiac actinomycosis such as purulent pericarditis, pericardial effusion, and endocardial or valvular lesions were not found. However, Actinomyces filaments were found inside the coronary and pulmonary circulation, a rare phenomenon.
The initial portal of entry in this case likely was the gut, as evidenced by extensive colonization of the gastrointestinal tract on autopsy. This may have been followed by sequential spread to the liver, causing abscess formation, and to the lungs and heart, resulting in pneumonitis and myopericarditis. Identification of Actinomyces in the coronary and pulmonary microvessels is strong evidence of hematogenous spread of the disease to the lungs and heart. Concomitant bloodstream infection with Bacteroides species may have facilitated hematogenous dissemination of actinomycotic infection to the lungs and heart.
Sudden death may be related to cardiac actinomycosis resulting from hematogenous dissemination, a phenomenon that has not been reported in the literature. The cause of sudden cardiac death might be attributed to arrhythmia resulting from myocardial ischemia due to inflammation and occlusion of coronary microvasculature, or myocarditis or a combination of both.
Treatment of actinomycosis
With the advent of antibiotics, death due to actinomycosis is unusual. Prior to the advent of antibiotic therapy, irradiation, administration of iodides or thymol, and surgery were certain traditional measures used for treatment of actinomycosis. However, since 1945, penicillin has been found to be effective in all cases . Alternative choices such as erythromycin, sulfonamides, clindamycin, and tetracyclines can be used but with relatively low success rates [30,31]. The average duration of therapy recommended for disseminated actinomycosis is 6 months (range, 1–12 months), with no recurrence observed after 3–4 months of therapy. Surgical excision and drainage may be necessary in certain cases . In cases with pericardial actinomycosis, pericardial resection should be considered. Prompt diagnosis and treatment improve morbidity and mortality rates .
Our case illustrates that disseminated actinomycosis is difficult to diagnose and can be fatal. Sudden cardiac death can occur in cases of disseminated actinomycosis as a result of cardiac infection. An awareness of the full spectrum of the disease is needed to expedite diagnosis and treatment and thus to minimize morbidity and prevent death. [3–41]
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