Bacillary peliosis also called bacillary peliosis hepatis or Bartonella peliosis hepatis is a blood vessel condition characterized by multiple, randomly distributed, blood-filled and cyst-like cavities throughout the liver that is secondary to Gram-negative Bartonella henselae bacteria infection in immunocompromised patients, first described in human immunodeficiency virus (HIV) infected or AIDS individuals 1), 2), 3), 4). Most patients with bacillary peliosis develop symptoms such as anorexia, weight loss, enlarged tender lymph nodes (lymphadenopathy), chills, fever, headache and malaise in addition to gastrointestinal symptoms or abdominal pain 5), 6), 7), 8), 9), 10). Approximately 1% to 2% of patients with Bartonella infection develop severe systemic disease with involvement of the liver, spleen, bone, central nervous system (brain and spinal cord) or lung 11). Approximately 25% of patients have lymphadenopathy (enlarged lymph nodes), but often the classic skin papule of cat-scratch disease is absent 12), 13), 14).
Bacillary peliosis hepatis patients have enlarged liver (hepatomegaly), and some also have enlarged spleen (splenomegaly). One-quarter of the patients also had skin bacillary angiomatosis (cutaneous bacillary angiomatosis) lesions. Abdominal CT of the peliotic liver usually reveals numerous hypodense lesions, but this appearance is not specific for bacillary peliosis; therfore the diagnosis of Bartonella infection must be confirmed by histopathological evaluation. Additionally, some HIV-infected patients with hepatic Bartonella infection develop inflammatory nodules in the liver without the vascular proliferative characteristics of peliosis hepatis. Patients with splenic bacillary peliosis can have thrombocytopenia or pancytopenia and abdominal ascites.
HIV-associated bacillary peliosis hepatis is an unusual, treatable opportunistic infection that responds to antibiotics. Inadequately treated, HIV-associated bacillary peliosis can be progressive and may be fatal 15), 16).
Figure 1. Bacillary peliosis
Footnotes: Bacillary peliosis in a 32-year-old man with HIV/AIDS who presented with fever. (a) Axial in-phase T1-weighted MR image shows an ill-defined iso-to mildly hypointense nodule in the posterior segment of the right hepatic lobe (arrow). (b) Axial fat-saturated T2-weighted MR image shows moderate to high signal intensity of the nodule (arrow). Smaller similar subcapsular nodules are seen posteriorly (arrowheads). (c) Axial contrast-enhanced early phase fatsuppressed T1-weighted MR image shows the hypointense right hepatic nodule with irregular continuous peripheral enhancement (arrow). (d) Axial contrast-enhanced delayed phase T1-weighted MR image shows delayed enhancement within the nodule (arrowhead), which reaches a signal intensity similar to that of the surrounding hepatic venous structures because of contrast agent retention within dilated sinusoids in the lesion.[Source 17) ]
Figure 2. Bacillary peliosis
Footnotes: 44-year-old man with AIDS and bacillary peliosis. Transverse contrast-enhanced CT image shows large ill-defined, hypoattenuating lesion (white arrow) with heterogeneous peripheral enhancement within left liver lobe. Smaller subcapsular hypoattenuating lesion (black arrow) with ring enhancement can also be seen in right liver lobe.[Source 18) ]
Figure 3. Peliosis hepatis liver biopsy specimen
Footnote: Liver biopsy specimen with hematoxylin and eosin staining at 45x magnification showing dilated vascular spaces (peliotic spaces) filled with red blood cells are surrounded by cords of hepatocytes. Note central area of pale myxoid stroma (arrow)[Source 19) ]
Figure 4. Bacillary angiomatosis
Footnotes: Bacillary angiomatosis clinical appearance. Angiomatous papule and nodules (a) arm and (b) fingers. A 26-year-old healthy woman had developed papules and nodules on the right arm 6 months ago. Despite treatment with short course systemic antibiotics the lesions had enlarged and gradually extended to the forearm and hand and also to her fingers.[Source 20) ]
Figure 5. Bartonella bacteria
Footnote: Warthin-Starry stain demonstrating the characteristic pleomorphic bacilli of Bartonella bacteria in bone marrow core biopsy[Source 21) ]
Bacillary peliosis cause
Bartonella henselae the bacteria that cause bacillary peliosis commonly cause cat scratch disease or cat scratch fever 22), 23), 24), 25), 26), 27),28), 29). People become infected with Bartonella henselae from the scratch of domestic or feral cats, particularly kittens 30), 31), 32), 33). Cats can have fleas that carry Bartonella henselae bacteria. These bacteria can be transmitted from a cat to a person during a scratch that is contaminated with flea stool. Infected cats that lick a person’s open wound or bite can also spread Bartonella henselae bacteria. Some evidence suggests that these bacteria may spread directly to people by the bite of infected cat fleas, but this has not been proven.
Bartonella henselae infection or cat scratch disease occurs most often in children under the age of 15 (children 5 to 10 years of age) 34), 35), 36). Though more common in the southeast, cat scratch disease occurs throughout the United States. Stray cats are more likely than pets to be infected with B. henselae. In the United States, most cases of cat scratch disease occur in the fall and winter.
Bacillary peliosis symptoms
Most patients with bacillary peliosis develop symptoms such as anorexia, weight loss, enlarged tender lymph nodes, chills, headache, malaise and fever in addition to gastrointestinal symptoms or abdominal pain 37), 38), 39), 40), 41), 42), 43). Approximately 1% to 2% of patients with Bartonella infection develop severe systemic disease with involvement of the liver, spleen, bone, central nervous system (brain and spinal cord) or lung 44). Approximately 25% of patients have lymphadenopathy (enlarged lymph nodes), but often the classic skin papule of cat-scratch disease is absent 45), 46), 47).
. Bacillary peliosis can cause splenic peliosis and peliosis hepatis. Rupture with intraabdominal hemorrhage has previously been reported in both peliosis hepatis 48) and peliosis of the spleen 49), 50) and is another possible mode of presentation, underscoring the need for rapid diagnosis and therapy in these cases.
Bacillary peliosis diagnosis
Bacillary peliosis is very difficult to diagnose. Laboratory findings typically included a mild-to-moderate elevation of the serum aminotransferase level (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) and a moderate-to-severe elevation of the alkaline phosphatase (ALP) level in association with a normal or only mildly elevated bilirubin level 51). Progressive reduction in the number of blood cells (pancytopenia) occurred in some patients. Imaging studies showed enlarged abdominal lymph glands and a heterogeneous hepatic or splenic parenchyma in some cases 52).
Liver lesions are typically multiple and associated with abdominal lymphadenopathy and, in some cases, splenic lesions; many patients come to biopsy to exclude tumors 53), 54), 55). On laparotomy, the liver may be found to be studded with hard nodules of varying sizes 56).
Liver biopsy showed the presence of multiple blood-filled cystic spaces, foci of necrosis, fibromyxoid stroma, and clumps of granular purple material that correspond to organisms on Warthin-Starry stain and electron microscopy 57).
Bartonella infection may cause vascular proliferative lesions in the liver. Bacillary epithelioid angiomatosis is a vasoproliferative tissue reaction to Bartonella henselae or Bartonella quintana that usually occurs in immunocompromised hosts. Hepatic involvement shows sharply demarcated periportal areas in which the normal parenchyma is replaced by vascular tissue with extravasated erythrocytes, delicate spindle cells, neutrophils, and karyorrhexic debris, mimicking Kaposi sarcoma 58). Similar lesions have been designated as bacillary peliosis hepatis; these are characterized by the presence of multiple blood-filled cystic spaces, foci of necrosis, fibromyxoid stroma, and clumps of granular purple material that correspond to organisms on Warthin-Starry stain and electron microscopy 59). Bacillary peliosis hepatis can be mistaken for nonbacillary peliosis hepatis.
The hallmark lesion in hepatic cat-scratch disease is an irregular, stellate microabscess surrounded by a layer of palisading histiocytes, lymphocytes, and a rim of fibrous tissue 60), 61), 62). Younger lesions may show more necrosis with less organization of the inflammatory granulomatous response, whereas older lesions may show confluent granulomas with scarring and scant residual necrosis 63). These hepatic lesions are similar to the ones seen in lymph nodes in patients with cat-scratch disease, but they have also been noted in infections with Y. enterocolitica, F. tularensis, lymphogranuloma venereum, mycobacterial species, Candida, and Actinomyces 64). Other lesions may appear as small, rounded granulomas with giant cells and small foci of central necrosis, similar to caseating granulomas in mycobacterial or fungal infections. The background liver parenchyma shows sinusoidal dilatation, portal mixed but predominantly lymphocytic inflammatory infiltrates, portal fibrosis, periductal concentric fibrosis, and focal bile ductular proliferation 65). These changes are attributed to mass effect and are also seen in other infections that result in space-occupying lesions, such as pyogenic abscesses 66).
Warthin-Starry stains identify Bartonella bacteria in some cases (see Figure 5) and the organisms often cluster around vessels or along collagen fibers; the stain is not specific for the organism 67). Culture is difficult. The diagnosis can be confirmed by polymerase chain reaction (PCR) and Southern blot for Bartonella DNA on tissue, skin testing, or serology 68), 69), 70), 71).
Bacillary peliosis differential diagnosis
- Hepatic adenoma: Similar to peliosis, hepatic adenoma might also be associated with the long-term use of estrogens. In the case of diffuse peliosis hepatis, the differential diagnosis is relatively easy. In addition, the presence of fat in some adenomas is a useful sign to make a differential diagnosis. In certain instances, however, focal peliosis can be difficult to differentiate from adenomas. In these patients, biopsy is often required to reach a definitive diagnosis.
- Cavernous hemangioma: The typical enhancement pattern of hemangiomas (i.e., globular discontinuous contrast enhancement tends to be centripetal (periphery first) rather than centrifugal (center first)) is opposite of peliosis hepatis, and therefore differential diagnosis can be achieved in most patients. In addition, hemangiomas may be rather large lesions with a mass effect on the hepatic vessels, whereas peliotic lesions usually show no mass effect on hepatic vessels.
- Hepatocellular carcinoma (liver cancer): Hepatocellular carcinoma is usually hyperattenuating in the arterial phase with rapid washout in the portal venous phase and iso- or hypoattenuation in the delayed phase. Although rare, the possibility that peliosis hepatis may mimic the presence of hypervascular hepatocellular carcinoma has been reported in the literature. In these patients, biopsy is often necessary to reach a definitive diagnosis.
- Hepatic abscess (liver abscess): The differential diagnosis between peliosis hepatis and hepatic abscess is extremely important to avoid the percutaneous drainage of peliotic lesions, which can be dangerous and even fatal 72). With regard to imaging criteria, a hepatic abscess usually presents as a mass with a multiseptated or cluster-of-grapes appearance with nonenhancing contents.
- Focal nodular hyperplasia (benign tumor that forms in the liver): Focal nodular hyperplasias are typically homogeneously hyperattenuating masses on the arterial phase and isoattenuating on the portal venous and delayed phases. These lesions often have a central scar with low attenuation on the arterial and portal venous phases and enhancement on the delayed phase images. When such typical imaging characteristics of focal nodular hyperplasia are present, the differential diagnosis with peliosis hepatis can be achieved easily. Atypical forms of focal nodular hyperplasia may not show the characteristic enhancement patterns and the central scar just described, however, and thus pose some problems in the differential diagnosis with peliosis hepatis.
- Hepatic adenoma (an uncommon solid, benign liver lesion that develops in an otherwise normal-appearing liver) may contain fat
- Hypervascular metastases: Although some hypervascular metastases with fibrotic change can show mild hyperattenuation in the delayed phase, hypervascular metastases are usually totally hypoattenuating or isoattenuating in the delayed phase of contrast enhancement because of the rapid washout of contrast material. Thus, in general, peliotic lesions are rarely confused with hypervascular metastases.
- Hepatic sinusoidal dilation: usually the enhancement pattern is different on CT/MRI 73)
Bacillary peliosis treatment
Bacillary peliosis is treated with antibiotic. Azithromyin, doxycycline, and gentamicin are all considered effective against Bartonella but the regimen of azithromycin and/or doxycycline is most commonly used in solid organ recipients 74). Macrolides (e.g., clarithromycin, azithromycin, erythromycin, clarithromycin, roxithromycin) also have immunomodulatory effects, which include reducing vascular endothelial growth factor (VEGF) activity, which may have additional benefits for Bartonella vascular lesions 75). The duration of therapy is not well-defined though given the high risk for morbidity in the immunosuppressed population and the propensity for relapse of Bartonella infections, a prolonged duration of antimicrobial therapy is typically favored 76).
Antibiotic treatment of bacillary angiomatosis and bacillary peliosis hepatis has never been studied systematically. Two criteria must be met to achieve successful eradication of Bartonella infections in the immunocompromised patient: first, the specific strain of Bartonella henselae and Bartonella quintana infecting the patient must have excellent in vivo susceptibility to the prescribed antibiotic, and second, the treatment must be of sufficient duration to prevent relapse 77). The first patient with bacillary angiomatosis to be described was treated empirically with erythromycin, and the lesions resolved completely78). Subsequently, erythromycin has become the drug of first choice and has successfully been used to treat many patients with bacillary angiomatosis 79), 80). Treatment of bacillary angiomatosis and bacillary peliosis hepatis with oral doxycycline (100 mg twice daily) has also been consistently successful 81). Lesions resolved in several patients treated with ceftriaxone or fluoroquinolone compounds 82), 83), but the progression of bacillary angiomatosis lesions in patients has been observed during treatment with ciprofloxacin 84). Additionally, a Bartonella species has been isolated from the blood or bacillary angiomatosis lesions of patients being treated with narrow-spectrum cephalosporins 85), nafcillin, gentamicin, and trimethoprim-sulfamethoxazole (but never from patients being treated with a macrolide, rifamycin, or a tetracycline) 86). Experts therefore do not recommend fluoroquinolones, trimethoprim-sulfamethoxazole, or narrow-spectrum cephalosporins for the treatment of bacillary angiomatosis or bacillary peliosis hepatis 87). Treatment failures have been reported with many different antibiotics, and these are usually attributable to a lack of susceptibility of Bartonella in vivo and/or an insufficient duration of therapy 88), 89).
The drug of choice for the treatment of bacillary angiomatosis is erythromycin given p.o. (500 mg p.o. four times daily) for 3 months, but intravenous (IV) administration should be used in patients with severe disease 90). Patients intolerant of erythromycin can be treated with doxycycline (100 mg p.o. or i.v. twice daily) 91), 92), 93). The response to treatment appears to be equivalent whether erythromycin or doxycycline is prescribed 94). Combination therapy, with the addition of rifampin (300 mg p.o. twice daily) to either erythromycin or doxycycline, is recommended for immunocompromised patients with acute, life-threatening Bartonella infection. The intravenous route is especially important in cases of gastrointestinal intolerance or poor absorption. The combination of doxycycline and rifampin is preferred for the treatment of patients with CNS Bartonella infection because of the superior CNS penetration of doxycycline compared with those of the other first-line antibiotics.
The response to treatment can be dramatic in immunocompromised patients. In one patient who received a single 250-mg oral dose of erythromycin, blood cultures became sterile and a palpable subcutaneous lesion disappeared within hours (but recurred months later). More chronic lesions resolve more slowly, but after approximately 4 to 7 days of therapy, cutaneous bacillary angiomatosis lesions usually improve and resolve completely after 1 month of treatment 95). Bacillary bacillary peliosis hepatis responds more slowly than cutaneous bacillary angiomatosis, but hepatic lesions should improve after several months of treatment.
Relapses of bacillary peliosis hepatis and bacillary angiomatosis lesions in bone and skin have been reported frequently 96), 97), 98), 99). Relapses occur when antibiotics are given for a shorter duration (<3 months), especially in severely immunocompromised HIV-infected patients 100), 101). For this reason and from extensive experience treating patients with bacillary angiomatosis and bacillary peliosis hepatis, experts recommend that treatment be given for at least 3 months for bacillary angiomatosis and 4 months for bacillary peliosis hepatis 102), 103). All immunocompromised patients with a Bartonella infection should receive antibiotic therapy (erythromycin 500 mg p.o. four times daily or doxycycline 100 mg p.o. twice daily); patients who have relapses after the recommended treatment should then receive secondary prophylactic antibiotic treatment with erythromycin (500 mg p.o. four times daily) or doxycycline (100 mg p.o. twice daily) as long as they are immunocompromised 104). Of note, AIDS patients receiving prophylaxis with a macrolide or rifamycin antibiotic for Mycobacterium avium complex infection appear to be protected from developing infections with Bartonella species 105). Some immunocompromised patients develop a potentially life-threatening Jarisch-Herxheimer-like reaction within hours after institution of antibiotic therapy 106). Physicians should advise patients of this possible treatment complication, and patients with severe respiratory and/or cardiovascular compromise should be monitored carefully following institution of antimicrobial therapy 107).
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