The Kaposi’s Sarcoma Mimic – Cats, Peliosis, and Cat-Scratch Disease

Literature review on any “old timey” organism can be kind of a pain since I am convinced microbiologists get drunk every so often to reclassify clinically relevant organisms. This is the case for Bartonella. Originally described as bartonia, which is an erythrocyte-adherent organism similar to organisms of the genus of Rochalimacae, including Rickettsia quintana, was described by Dr A. L. Barton (of course, 1). Other organisms include B. quintana (aka trench fever) and B. henselae. Most of these are non-human pathogens with only B. quintana believed to be the mammalian reservoir for humans. Body lice is typically the reservoir and the vector by which disease spreads through. A similar disease is that of Bartonella bacilliformis, which is endemic to the Andes Mountains of Peru, Ecuador, and Colombia (2). Oroya fever is a fascinating disease because of the history of how it was discovered and its pattern of disease, but not the topic of this post. Acutely, oroya fever is an acute hematologic disease that develops anywhere from 3 to 12 weeks after inoculation and erythrocyte invasion by the organism. This leads to rapid hemolysis and profound anemia, jaundice, lymphadenopathy, thrombocytopenia, and hepatic dysfunction. This can be followed by the more “mundane” presentation, which is the “verruga peruana” which is similar to cat-scratch disease (2). It should be no surprised that HIV-infected patients, especially those with CD4 <100 cells/mm3, have odd manifestations: cutaneous bacillary angiomatosis, hepatic and splenic bacillary peliosis, granulomatous hepatitis, and endocarditis (1). Of course, it has been demonstrated in other internal organs including spleen, bone, liver, brain, and cervix. The most common presentation, however, is cat-scratch disease with an estimated prevalence of 25k in the US (3).

Starting Stuff:

 If you try to read about cat-scratch disease, then you’ll realize 2 things: one is that this is a mainly pediatric, self limited disease, as seen by this database study showing most cases are in patients under the age of 18 (4).

Second, is that cats are usually involved, as you can infer from the name. Indeed, it seems the prevalence amongst cats is actually high. A retrospective cohort of 628 feline serum samples in North America found an overall prevalence of 27.9%, predominantly in the South and Southeast area of the US (5):

In a 72 case cohort, matched cases were found to have a higher incidence and risk of CSD based on cat-related risk factors (6):

Moreover, bivariate analysis found that cat ownership is associated with higher incidence of CSD:

The most intense study came out of a study of 48 patients (42 with HIV) and 94 controls (7). Recent exposures, such as owning a cat, sending a minimum of 1 hour per day in contact with a cat, and various types of cat contact (including recently being licked, scratch, or bitten by a cat) were associated with higher likelihood of disseminated CSD:

Indeed, in bivariate analysis it seems that any type of physical contact with a cat is associated with higher risk of disease:

Typical Manifestations:

Bartonella spp are intracellular, gram-negative rods that typically take anywhere from 7 to 10 days of incubation in a high CO2 environment to grow (8). Transmission via an arthropod vector such as flies, fleas, lice, ticks, and sandflies is the rule, with infection being established within erythrocytes. Common systemic symptoms include fever, malaise, headache, splenomegaly, and arthralgia:

Primary pustule develops 3 to 10 days after animal contact, followed by regional ipsilateral lymphadenopathy that can last from 1 to 3 weeks (2). Low-grade fever can be seen in 60% and a transient rash is seen in 5% of patients. Myalgia occurs in around 5 to 6% of patients, with 11 to 12% being cases of atypical CSD, with the most common being Parinaud’s oculoglandular syndrome (aka granulomatous conjunctivitis and preauricular lymphadenopathy).   Another review highlights the pattern of disease which is typically inoculation followed by regional lymphadenopathy in areas such as the cervical, axillary, epitrochlear, and supraclavicular regions with one third having generalized lymphadenopathy (9).

A case series of 1174 patients with CSD found the most common presentation was that of typical CSD:  localized adenopathy and fevers (10). Unusual presentations were seen in at least 11% of cases:

Presentation in HIV Patients

I alluded to how HIV patients tend to be a bit different. Indeed, these folks present a bit differently from the kids with “cat-scratch disease” and may have more disseminated disease such as bacillary angiomatosis or bacillary peliosis. The reason why HIV and solid organ transplant patients are at risk for disseminated disease may stem from the fact that cell-mediated immunity plays a key role in its control. (11)  Progressive degrees of immune impairment may explain the simultaneous presentation of cutaneous bacillary angiomatosis and visceral necrotizing or granulomatous lesions in certain individuals and systemic bacillary angiomatosis in other patients:

One of the more notorious presentations is bacillary angiomatosis (12):

As seen above, the lesions from panels A and B are very similar to that of C and D. The former are BA while the latter are KS. Indeed, a case series of 3 patients from East Africa with AIDS presenting with skin lesions highlights how KS was a consideration with biopsy results showing the etiological agent to be B. hensela (14). 

A case series of 4 HIV-infected patients highlighted the nonspecific nature of disseminated cat-scratch disease; fevers, chills, weight loss, night sweats, edema, bleeding, and pain. Moreover, many of these patients presented with skin lesions that were similar to that of Kaposi’s sarcoma (15):

Another cohort of 7 patients with HIV with lesions resembling KS were found to have histology similar to that of KS, however most resolved after a few weeks of therapy (16).  This was the same in another study of 5 HIV patients, which found that their vascular neoplasms were clinically and histologically unique, however they had some features in common with the histiocytoid hemangiomas (17). Moreover, it was found these cells had expressed markers of endothelial cells and histiocytes, suggesting another etiologic agent of the disease. The linking of both bacteria and disease was not made until the early 1980s, where a retrospective cohort of 5 patients noted that bacilli were present at the inoculation site, with papules taking anywhere from 18 days to up to 45 days to appear on the skin (18). Biopsy samples were positive for bacilli in the spot of inoculation and associated lymph nodes, suggesting both are stemming from the same pathogen. A series of 7 cases of AIDS patients who presented with subcutaneous and cutaneous nodules resembling Kaposi’s sarcoma found evidence of gram-negative rods within each vascular proliferation on electron microscopy. The bacteria had the staining profile of cat-scratch disease, which was confirmed by history and further staining results (19).

Atypical Presentation:

In HIV patients, BA usually resents during the later stages of HIV infection (3). Cutaneous lesions can be either predominantly cutaneous or subcutaneous, with them being often papular and red with a smooth or eroded surface. Other presentations include pyogenic granuloma, verruga peruana, osseous BA, splenic and hepatic,  CNS lesions, bone marrow, and bacteremia:

For instance, the above images show the presentation of bacillary peliosis, something we will talk about in a bit. It also seems the case that while many patients do not show up with symptoms, many have been at least exposed to the bacteria. A case-control study of HIV, found that 17% of a 382 cohort were previously exposed to Bartonella spp (20). Moreover, skin lesions, receipt of cat scratch or bite were associated with cases while elevated alk phos levels were also associated with the presence of Bartonella spp as etiology of fever. 

A retrospective study of 42 HIV-patients found that cutaneous vascular lesions (31%), subcutaneous nodules (24%), asymmetric lymphadenopathy (21%), abdominal symptoms (24%) were the most common types of presentation, suggesting that vague symptoms is also a typical presentation here. Further, the time from symptom development to evaluation by a physician was 4 to 5 weeks (21). Using 84 controls, multivariate models found CD4 count, hematocrit <0.36, zidovudine therapy, and elevated alk phos level were associated with the development of bacillary angiomatosis-peliosis:

A review of 29 cases of Bartonella infection occurring in solid organ transplant recipients (21) found 8 presented with typical CSD while 21 had disseminated infection, including 2 with endocarditis. Those who had liver transplantation were more likely to have patients with disseminated disease when compared to kidney transplant (87% vs 63%). The more commonly cited presenting symptoms were as follows:

This same case series also highlights 23 patients with prolonged infection, with at least 2 weeks of fever, malaise, arthralgias, and skin eruptions along with pleurisy, splenic abscess, mediastinal abscess, or recurrent CSD also being described. In two cases, disseminated infection with biopsy evidence of hepatic and splenic involvement presented with insidious symptoms in an HIV patient and a heart transplant patient (11). There has also been HIV patients with bone marrow involvement of the bacteria (22), suggesting this is a multisystem disease. 

What is a Peliosis

Peliosis is derived from the Greek “Pelios” which means black and blue and is based on the gross appearance of the liver affected from this; multiple, small, blood-filled cysts within the parenchyma (23). While many diseases can lead to this (including syphilis, steroids, alcohol), the pathophysiology is unclear however a trigger leads to the dilation of sinusoids and altered outflow, along with dilatation of the central vein as well as necrosis. I mention this since there have been several cases of granulomatous hepatitis, lesions within the GI tract, and  lymphadenopathy and lymphadenopathy associated with bartonella (24). Indeed, one patient presented with vague symptoms and imaging demonstrated mediastinal mass, numerous focal lesions in the liver and spleen, and retroperitoneal lymphadenopathy, which was reminiscent of a diagnosis of lymphoma. Indeed, despite clinicians having histopathological evidence of CSD, the patient was started on TB meds. A case series of 3 pediatric patients with granulomatous hepatitis found that neither of them had hepatomegaly or abnormal LFTs and it was a hunt for a fever of unknown origin that lead them to findings of “spots” in the liver that ended up being infectious, raising the question if liver involvement is the rule in the disease (25). A retrospective study of 8 HIV patients with bacillary angiomatosis found all presented with fever, abdominal pain, weight loss, vomiting, and biopsy findings of peliosis (26).

TL;DR

• Bacillary angiomatosis is a gram negative organism that is usually found in fleas and other arthropods. Main source tends to be cats and other mammals
• The major presentation is Cat-scratch disease, which is associated with ipsilateral lymphadenopathy and usually resolves itself; it usually seen in kids under the age of 18
• In adults, you have to be immunosuppressed (usually cancer, transplant, or HIV) to have any significant manifestations
• The presentation can range from ill-defined illness, to endocarditis, osteomyelitis, or bacillary angiomatosis or bacillary peliosis
• Bacillary peliosis refers to the gross pathological characteristics of liver on autopsy; areas of necrosis surrounded by blood-filled vessels. 

References:

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