Primary Hepatic Actinomycosis

Actinomycosis is a chronic suppurative granulomatous infection of humans and animals, marked by the formation of abscesses with a tendency to form fistulas. It is caused by Gram-positive anaerobic microorganisms called actinomycetes. The usual causative agent in man is Actinomyces israeli and, less frequently, Actinomyces naeslundii and Actinomyces bovis.1 The microbe inhabits the mouth and intestinal tract as a commensal; the portal of entry appears to be a break in the integrity of the tissue or mucosa subsequent to trauma, infection or surgical intervention.1 Other coexisting anaerobic organisms are commonly found at the site of infection.2 The cervicofacial, thoracic and abdominal areas are most frequently affected, and within the gastrointestinal tract the appendiceal area is the most common site.3 Involvement of other abdominal organs such as the liver is rare.4-6 This infection occurs more rarely in children than in adults and the two largest series report only 10% of affected patients being younger than 18 years.1, 7 We describe a pediatric patient with actinomycosis without evident predisposing factors in whom the primary site was the liver, which posed considerable problems of differential diagnosis. Case report. In March, 1994, a 4-year-old boy was referred to us with a 3-month history of attacks of periumbilical abdominal pain radiating to the epigastrium and right hypochondrium with onset at varying times of There was accompanying anorexia with weight loss, asthenia, pallor and migrating joint pain. Bowel movements were formed stools without blood or mucus. There was no past history of note. The diagnosis considered most likely by the referring hospital was chronic inflammatory bowel disease. During his week long stay there, the child had frequent brief attacks of abdominal pain rarely associated with vomiting, constipation, absence of fever and weight loss of 400 g. Laboratory investigations showed positive inflammation indices: erythrocyte sedimentation rate measured by the Westergren method (92 mm/h); serum C-reactive protein (21 mg/dl) with thrombocytosis (624 000/mm3); and elevated IgG (2900 mg/dl). Abdominal ultrasound, roentgenograms of the small intestine and colonoscopy were normal. On admission the patient was pale and distressed with abdominal tenderness to deep palpation, especially around the iliac fossa and hypochondrium. The hypothesis of chronic inflammatory disease seemed the most reasonable one to investigate further, and abdominal ultrasound was repeated, showing the intestinal walls distended by fluid but having a normal thickness. A round lesion, 4 cm in diameter, was evident at the height of the right hepatic lobe under the diaphragmatic cupula. This finding was confirmed by computerized tomographic scan, which revealed a round mass with indistinct margins, less dense in the center and more dense at the edge. The possible diagnoses considered at that stage were neoplasia, chronic granulomatous disease, bacterial abscess or amebiasis, hepatic echinococcosis or tuberculosis with hepatic involvement. Chronic granulomatous disease was excluded by a negative nitroblue tetrazolium test and normal production of superoxide after leukocyte stimulation. Ultrasonographic and radiographic findings were not compatible with a diagnosis of echinococciasis. Amebiasis is usually preceded or accompained by colitis. Tuberculosis with hepatic involvement is extremely rare and the Mantoux test was negative. Bacterial abscess remained a possibility although the absence of fever was unusual. The chest radiograph revealed that the right hemidiaphragm was abnormally raised. Given the position of the mass, with possible infiltration of the diaphragm and right inferior pulmonary lobe, the thoracic route was chosen for explorative surgical intervention. An inflammatory process was revealed, involving the base of the right lung, the diaphragm and the right hepatic lobe. The partially resected hepatic mass and a waxy, purulent appearance and numerous, pale yellow granules were visible. Histologic section showed multiple sites with microabscess formation, characterized by the presence of numerous branching filaments with a pseudohyphal appearance. The diaphragm presented extensive inflammatory infiltrates composed mostly of granulocytes, whereas the pulmonary parenchyma had multiple follicular bronchiectasia with peribronchiectasic inflammation and adjacent microabscesses. There was no sign of neoplasia. Culture produced an anaerobic flora consisting of A. israeli, Bacteroides fragilis and Fusobacterium spirilli. Parenteral antibiotic therapy was commenced with penicillin G (400 mg/kg/day), chloramphenicol (80 mg/kg/day) and metronidazole (25 mg/kg/day), and maintained for 2 months. The patient's condition improved quickly, and after only 1 week of therapy the serum C-reactive protein was normal. A computerized tomography scan performed 10 days after surgery showed that the mass was smaller, and abdominal ultrasonography revealed no lesions in the appendix, small intestine, gallbladder, pancreas or spleen, whereas a roentgenogram failed to reveal abnormalities in the colon, all of which are possible sites for visceral actinomycosis. After 2 months chloramphenicol and metronidazole were suspended and the penicillin was continued but administered orally as penicillin V in a dosage of 300 mg/kg/day. An abdominal computerized tomography scan performed at that stage revealed marked reduction of the hepatic lesion. Six months later oral penicillin was suspended and a final computerized tomography scan of the abdomen was almost normal. One year later the patient remained well. Discussion. In cases of visceral actinomycosis the appendiceal area is by far the most common site affected. Less frequently the infection involves the colon, stomach, liver, gallbladder, pancreas, small intestine, anorectal area and pelvis and abdominal wall.3 In most cases a single organ is involved, and the disseminated form is rare. Primary hepatic localization is extremely rare. Since 1928, 21 cases have been reported,4 2 of whom were pediatric patients.8, 9 The inflammatory process is divided into three stages: in the first stage the abscess is limited to its original site in the parenchyma and clinical manifestations may be absent; in the second phase there is peritoneal involvement in the form of a localized abscess or more often with the dissemination of the infection; in the third phase fistulas form. Most cases of visceral actinomycosis have been described in patients who had gastrointestinal disease with perforation some weeks or months previously. In Putnam's series 72% of cases had previous acute appendicitis.10 Other predisposing conditions include perforated diverticulitis of the colon, perforated peptic ulcer, ulcerative colitis and abdominal traumas, especially surgical interventions. Some cases, however, such as the one described here, may not present any of these predisposing factors, although most authors seem to think actinomycosis is always subsequent to a primary pathologic process of limited duration masked by a subclinical presentation that may not be apparent.11 Because in our case the infection involved, besides the liver, the base of the right lung, we cannot exclude that the hepatic site was not a primary lesion but rather resulted from transdiaphragmatic extension of the infection from the lung. However, the clinical onset (abdominal pain) together with a chest radiograph without clear signs of infection coupled with the fact that the hepatic site was already evident suggests that the liver was the primary site of infection with a secondary extension to the thorax. The clinical manifestations of visceral actinomycosis are multiple and vary according to the site involved. However, it usually presents as a chronic inflammatory process with subsequent formation of masses that tend to cavities and fistulas. As in our own case the most frequent symptoms described in the first phase are variable low grade fever, weight loss, nausea, vomiting, abdominal pain and progressive anemia with leukocytosis and increased inflammatory indices, a clinical picture resembling the mode of presentation of inflammatory bowel diseases of the intestine, especially Crohn's disease. Differential diagnosis is made difficult also because of the rarity of the disorder. In our case the diagnosis was delayed for 4 months and the definitive diagnosis was based on inspection rather than culture or histologic section because of the evidence of the typical sulfur granules. Culture may often present problems because of the strictly anaerobic conditions and long duration required for its growth. The granules are usually around or oval and contain numerous dark blue Gram-positive bacilli, except in 2% of cases, in which only a few microorganisms are visible. All the granules contain branching filaments with between 10 and 20 microorganisms; the structure of these filaments is less complex than that of fungi. The granules protect the actinomyces from contact with oxygen, antibodies and antibiotics.3 The antibiotic of choice remains penicillin, to which the organism responds well.12-13 In cases that do not respond or are allergic to penicillin, there are various alternatives; erythromycin and rifampin are most active in vitro, and other effective drugs are cephalothin, cephaloridine and chloramphenicol.14 The frequency with which microbes other than actinomycetes are isolated from the site of infection makes combination antibiotic therapy advisable. Administration should be parenteral for the first 2 to 6 weeks, followed by oral therapy for 6 to 12 months. Surgery is necessary in some cases, and although its role is limited to resection and drainage of empyema and abscesses, a more aggressive approach can facilitate recovery.15 As in the case reported here it can also provide an opportunity for diagnosis. Our patient responded very well to antibiotic therapy. In conclusion we have described a case of actinomycosis in a young child localized to the liver, with no history that might point to a predisposing factor. Actinomycosis must be considered in the differential diagnosis of hypo/hyperechoic images of the liver, especially when inflammatory indices are elevated. Direct surgical investigation may be necessary and may hasten resolution in the case of actinomycosis. Culture and histologic section establish the diagnosis but the intra-operative finding of pale yellow granules is highly suggestive in itself. Long term therapy with penicillin is effective. Marco Rabusin, M.D.; Nicola D'Andrea, M.D.; Franca Brizzi, M.D.; Rossana Bussani, M.D.; Alessandro Ventura, M.D. Istituto di Clinica Pediatrica (MR, AV) Istituto di Anatomia Patologica (RB) Università di Trieste Divisione di Pediatria Ospedale “I mulini” Acquaviva delle Fonti (NDA) Servizio di Radiologia Istituto Infantile Burlo Garofolo Trieste (FB) Trieste, Italy