Disseminated Actinomycosis: Multisystem Mimicry in Primary Care

Michael W. Felz, MD, Michael R. Smith, MD


South Med J. 2003;96(3) 

In This Article


Our patient's findings are consistent with other published reports in which organisms invade tissues, produce a granular discharge, extend to contiguous structures across anatomic boundaries, and form indurated lesions with burrowing sinus tracts and fistulas. Several members of the order Actinomycetales can cause infection, most commonly Actinomyces israelii, a Gram-positive rod colonizing the mouth, gastrointestinal tract, and vagina in healthy individuals. Other agents causing identical disease include A. odontolyticus, A. naeslundii, A. meyeri, A. viscosus, Rothia dentocariosa, and Propionibacterium propionicus (formerly Arachnia propionica).[2] Although A. israelii can be isolated from the oral cavity, gastrointestinal tract, female genital tract, and occasionally the bronchi of healthy persons, it has never been cultured from nonhuman sources, and no instance of direct person-to-person spread has been proven. Although infection may occur in individuals of any age, actinomycosis is more common in middle decades of life and in men by a 3:1 ratio. Traumatic disruption of oral, pulmonary, enteral, or genital mucosa enables penetration of organisms into deeper tissues following surgical procedures or destructive conditions, such as infection or trauma (eg, fish bones, intrauterine devices). Solitary or multiple abscesses develop, with slowly progressive induration, fluctuation, central suppuration, and a fibrotic "wooden" texture easily mistaken for carcinoma.[2] Fistula formation across normal tissue planes accompanies chronic draining lesions, and may lead to invasion of viscera, joints, or the central nervous system (CNS). Recurrent or persistent draining abscesses of the mouth and neck are the most frequently reported manifestations of actinomycosis. Pulmonary involvement, with parenchymal masses, pleural thickening, and cavitation or empyema, can be mistaken for malignancy or tuberculosis, although extension across fissures or into mediastinum or bone should lead to consideration of actinomycosis. Abdominal, pelvic, CNS, and musculoskeletal manifestations are myriad due to indolent progression of disease and multifocal involvement through hematogenous or fistulous invasion. Disseminated infection is, therefore, a clinician's challenge, for the panorama of findings often eludes noninvasive diagnosis and may lead to unnecessary surgical intervention.

At times, the diagnosis of actinomycosis is first established, not by the attending physician, but by the pathologist, after biopsy or resection for suspected malignancy. Demonstration of grains (granules) in purulent discharge or biopsy specimens has been emphasized as the crucial diagnostic maneuver in early recognition of actinomycotic infection.[2] Gram's and modified acid-fast stains, culture, and histologic examination differentiate actinomycosis from similar infections, such as nocardiosis and botryomycosis.[3] Prolonged antibiotic therapy for 6 to 12 months, usually with penicillin or amoxicillin, is required due to poor drug penetration into fibrotic lesions, rather than organism resistance.

Our patient is unique because certain features of his illness have received only scarce attention in the literature. Fifty years ago, Weed and Baggenstross[4] analyzed 21 cases of actinomycosis with fatal outcomes and autopsy evidence of lung, liver, kidney, ovarian, CNS, and bone involvement with suppuration, sinus formation, and scarring. None of their patients, however, had the degree of multisystem involvement evident in our case. Brown[5] reviewed the records of 181 patients with actinomycosis on file at the Armed Forces Institute of Pathology, 41 of whom were autopsied, and documented disease of orofacial and neck structures, lungs, pelvis, intestine, and kidney in 33, 27, 9, 8, and 6% of patients, respectively. Of the 18 instances of disseminated disease, 10 involved liver and lung only, in contrast to the dermal, pulmonary, mediastinal, renal, nodal, and musculoskeletal invasion in our patient. Weese and Smith[6] reviewed 57 cases from the University of Iowa, documenting cervicofacial, thoracic, and abdominal infection in 50, 18, and 23% of the patients, respectively. Interestingly, hip involvement occurred in 4 cases (3%), and mediastinal spread was evident in 3 (2%), consistent with what we observed. Only 1 of 57 cases (0.5%) was described as having disseminated disease, and that patient already had metastatic renal carcinoma. The authors emphasized the difficulty of early diagnosis, in that only 4 (3%) of 57 cases were correctly diagnosed at hospital admission, while carcinoma, cellulitis, osteomyelitis, and tuberculosis were more commonly suspected, as was the situation in our patient. Six of their severely infected patients died, however, in contrast to the favorable outcome in our patient.

Bennhoff[7] compiled an extensive review of the historical aspects of actinomycotic infection in animals and people, and analyzed 32 human cases in Cleveland. The range of presumptive diagnoses was diverse: 11 malignancies, 7 dental abscesses or masses, 4 tuberculosis, 4 pneumonia, and 1 each of stroke, endometritis, pilonidal cyst, pulmonary embolus, "classical" appendicitis, and, in a 12-year-old girl, lung cancer. Frequent confusion with pulmonary infection or malignancy was further illustrated in 5 cases reviewed by Ariel et al.[8] Each patient had experienced more than 6 weeks of persistent pulmonary symptoms, infiltrates or masses on chest x-rays, and poor or no response to antibiotic therapy. Bronchoscopy was required for definitive diagnosis. Mimicry of metastatic endometrial carcinoma has been reported in a 41-year-old woman in Chicago with an IUD, weight loss, pulmonary and hepatic nodules, uterine enlargement, a large salpingo-ovarian abscess, recurrent abdominal wall masses, and a stormy surgical course.[9] Confusion with metastatic renal cell carcinoma has been documented in a cachectic 62-year-old man in Toronto with weight loss, weakness, and a 15-cm left renal mass infiltrating the psoas musculature.[10] After percutaneous biopsy revealed granules of A. israelii instead of carcinoma, he underwent 1 year of penicillin therapy and had a dramatic clinical and radiologic recovery. A similar response occurred in our patient. Nephrectomy was avoided in the Canadian patient, as was thoracotomy in our patient.

Manifestations of A. israelii dissemination can mimic metastatic lung carcinoma in convincing fashion, as in the case of a 41-year-old man in San Diego with cough, cachexia, fever, nodular pulmonary lesions, anemia, ESR of 143 mm/h, and hypodense hepatic lesions highly suggestive of metastases.[11] Fine-needle aspiration of the liver revealed yellowish granules and filamentous, branching, Gram positive bacteria, with morphology similar to organisms noted in our patient. Two patients[12] in an Illinois Veterans Affairs Hospital were thought to have colon carcinoma based on persistent abdominal pain and radiologic evidence of abdominal masses measuring 12 to 15 cm. At laparotomy, each patient was found to have "sulfur granules" and filamentous organisms on histologic examination, documenting colonic actinomycosis and not malignancy, similar to the diagnostic sequence in our patient. Younger patients thought to have hepatic malignancies warrant consideration of actinomycosis, as was the case in a 35-year-old man with weight loss, anemia, pleural rub, pulmonary nodules, mediastinal adenopathy, and a necrotic liver mass invading the right kidney.[13] Aspiration of the liver mass yielded sulfur granules and A. meyeri on culture. Marked improvement followed penicillin therapy, and no surgical intervention was required. In similar fashion, dissemination of A. meyeri in a 34-year-old man from Switzerland[14] with a pulmonary infiltrate, 10-cm paravertebral mass, thigh abscess, and ESR of 118 mm/h was attributed to invasive portals from poor oral hygiene, gingivitis, and carious teeth, as were observed in our patient. Another Swiss patient, a 47-year-old man, presented with osteomyelitis of the left knee, firm abscesses of the trunk with fistulization, an infiltrative mass in the right middle lobe of the lung, and severe anemia.[15] A. meyeri was documented by Gram stain and culture of a dermal abscess aspirate, as was performed in our patient, and clinical and radiologic resolution accompanied prolonged penicillin therapy, also as in our case.

Neurologic manifestations, while less common, may accompany actinomycotic infection, as demonstrated in a 53-year-old college professor with headaches, status epilepticus, and an enhancing 2-cm parieto-occipital brain mass suggestive of lymphoma or glioma.[16] At craniotomy, Gram positive, filamentous, branching bacteria were demonstrated, with culture confirming A. odontolyticus infection, presumably invasive from a tooth capped 3 months previously. An apical tooth abscess was detected, drained, and found to contain A. odontolyticus as well. Penicillin provided complete cure of oral and CNS disease. Finally, diagnostic delay despite longstanding purulent drainage is illustrated in the case of a 40-year-old woman in Nashville[17] with 13 years of milky drainage from the gingiva, 12 months of numerous, oozing flank nodules repeatedly incised and drained by surgeons, lung infiltrates refractory to antibiotics, and a large paraspinous mass extending from the diaphragm to the iliac crest, invading thoracic vertebrae and the left kidney. An observant physician expressed pustular material from a dermal lesion and noted yellow flecks, again similar to our patient's case. Cultures yielded A. israelii. Complete resolution of the 3 typical forms of actinomycotic illness-recurring cervicofacial, thoracic, and abdominal infection-accompanied prolonged penicillin therapy, and further surgery was unnecessary. Several features of this case are reminiscent of the protracted illness, definitive diagnostic evaluation, and response to therapy described in our patient.