Bacillary angiomatosis is a vascular, proliferative form of Bartonella infection that primarily occurs in immunocompromised persons. Although the disorder is treatable and curable, it may be life threatening if untreated. Bacillary angiomatosis is the second-most-common cause of angiomatous skin lesions in persons infected with the human immunodeficiency virus (HIV). Multiple lesions often demonstrate more than 1 morphologic appearance. Black patients, in particular, may bear the plaque form.
Patients with bacillary angiomatosis commonly have a history of HIV infection, organ transplantation, leukemia, or chemotherapy.[1] Inoculation bartonellosis may be evident in immunocompetent individuals as a pyogenic granuloma–like nodule at the site of a cat scratch or at a burn site.[2, 3]
Cutaneous lesions due to bacillary angiomatosis may take one of the following forms:
Solitary or multiple red, purple, flesh-colored, or colorless papules (hemangiomalike lesions) varying in size from 1 mm to several centimeters
Nodules, often covered with a fine, tightly adherent scale
Large, friable, pedunculated, or polypoid exophytic masses
Hyperpigmented, hyperkeratotic, indurated plaques, typically on the extremities and often overlying osseous defects
Lesions can also occur in the oral mucosa, tongue, oropharynx, nose, penis, and anus. Bone pain, frequently in the forearms or legs, can also occur.
Visceral involvement associated with bacillary angiomatosis may be asymptomatic or may cause the following symptoms:
Fever, chills, malaise, night sweats, anorexia, and weight loss
Symptoms of peliosis hepatis: Abdominal pain, nausea, and vomiting
Jaundice secondary to biliary obstruction caused by external compression of periportal lymph nodes
Intra-abdominal mass and gastrointestinal bleeding
Symptoms of colonic bacillary angiomatosis: Abdominal cramps, tenesmus, and bloody diarrhea
Symptoms of CNS bacillary angiomatosis: Psychiatric symptoms, such as exacerbation of depression or new-onset psychosis; personality changes, including anxiety and irritability; headache; trigeminal neuralgia; seizures; and back pain
Difficulty breathing secondary to laryngeal obstruction
Lab studies
The diagnosis of cutaneous bacillary angiomatosis and extracutaneous disease is most often based on clinical features coupled with biopsies of lesions. Histology reveals vascular proliferation with the presence of neutrophils adjacent to the blood vessels and masses of bacteria, which can be demonstrated by modified silver staining (Warthin-Starry silver stain). Detection of Bartonella DNA in tissue specimens by polymerase chain reaction (PCR) assay or of Bartonella antigens by immunohistochemical methods is diagnostic.[4]
Imaging studies
Radiography can be used to find bone lesions; chest radiography can reveal pulmonary parenchymal nodules.
Computed tomography (CT) scanning of the brain can detect intracerebral bacillary angiomatosis. CT scanning and magnetic resonance imaging (MRI) can be used in the diagnosis of peliosis hepatis, while chest and abdominal CT scans may reveal mediastinal, retroperitoneal, or mesenteric lymph node enlargement.
Procedures
Biopsy: Specimens of skin, subcutaneous or mucosal lesions, or, in cases of peliosis hepatis, the liver are diagnostic
Endoscopy: With gastrointestinal involvement, may reveal ulcerated nodules of the mucosa of the stomach, small intestine, or large intestine
Bronchoscopy: With lung involvement, may reveal polypoid lesions
Bacillary angiomatosis can be cured in most patients with antibiotics. Clinical experience strongly favors the use of erythromycin or a tetracycline derivative in this disorder.
Cryotherapy, electrodesiccation and curettage, and surgical excision of solitary cutaneous lesions can be useful as adjunctive therapy.
The reader is referred to the 2014 guidelines published by the Infectious Diseases Society of America (IDSA) for the treatment of bacillary angiomatosis (see Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America).[5]
Bacillary angiomatosis is a vascular, proliferative form of Bartonella infection that occurs primarily in immunocompromised persons. It was first described in 1983 in a patient infected with the human immunodeficiency virus (HIV).[6] The disease has since been described in patients following organ transplantation[1, 7, 8] and in other individuals with a weakened immune system, although it occasionally is reported in immunocompetent patients.[9, 10, 11, 12] Initially, bacillary angiomatosis was called epithelioid angiomatosis, because of its histologic appearance. (See Pathophysiology and Etiology.)
In 1990, Relman et al identified a visible but uncultivable bacillus from affected tissues of patients with bacillary angiomatosis.[13] The gram-negative organism was later named Bartonella (formerly Rochalimaea) henselae. A similar bacterium, B quintana, has also been detected in and cultured from lesions caused by bacillary angiomatosis. Bacillary angiomatosis due to Bartonella elizabethae in an individual with HIV infection has been reported in Mexico.[14]
The systemic nature of the disease became evident when postmortem examinations showed nodules in the larynx, gastrointestinal tract, peritoneum, and diaphragm.
Bacillary angiomatosis often responds to therapy with oral erythromycin, although other oral antibiotics and antituberculosis medications, including tetracycline, other macrolides, trimethoprim-sulfamethoxazole, ciprofloxacin, and rifampin, also may be effective. While the disorder is treatable and curable, it may be life threatening if untreated. The disease is the second-most-common cause of angiomatous skin lesions in persons infected with HIV. (See Treatment and Medication.)
Immunocompromised patients and their caregivers should be advised to avoid cat contact and to control flea infestations in cats.
B henselae and B quintana are small gram-negative rods in the family Bartonellaceae. Bartonella, Rickettsia, Ehrlichia, and Afipia species all are part of the alpha-2 subgroup of the Alphaproteobacteria.
Bacillary angiomatosis can affect almost any organ system, although most commonly it affects skin and subcutaneous tissue. Subcutaneous lesions may erode into underlying bones (ie, osseous bacillary angiomatosis), especially the tibia, fibula, and radius. Involvement of ribs and vertebrae has been described. Rarely, skeletal muscles may be involved, resulting in pyomyositis. Mucous membranes of the conjunctiva, upper airway, and perineum (anus and penis) may also be affected. Bacillary angiomatosis may be accompanied by disseminated visceral disease (peliosis), mainly in the liver (peliosis hepatis), spleen, and lymph nodes.
Other internal organs that may be involved include the following:
Brain
Bone marrow
Heart
Lungs
Pleura
Larynx
Oropharynx
Tongue
Esophagus
Stomach
Duodenum
Colon
Peritoneum
Diaphragm
Kidneys
Adrenal glands
Pancreas
Uterine cervix
Vulva[15]
Extrinsic compression of the common bile duct by enlarged peripancreatic, celiac, and portohepatic nodes has been reported.
The pathogenesis of bacillary angiomatosis includes early blood-borne dissemination of organisms. Bartonella organisms readily attach to and may enter erythrocytes.[16] They avoid opsonization and host phagocytosis by unknown mechanisms and become persistent within the intravascular compartment.
An angiogenic factor may be responsible for the vascular proliferation observed in patients with bacillary angiomatosis, because a similar factor mediates vasoproliferation in verruca peruana, the second stage of Bartonella bacilliformis infection. Moreover, deoxyribonucleic acid (DNA) hybridization, 16S ribosomal ribonucleic acid (rRNA) sequence homology, cellular fatty acid profiles, and cytosine and guanine content studies have shown that B henselae and B quintana are closely related to Bartonella bacilliformis.[17]
The specific Bartonella species, B henselae or B quintana, can affect the location of bacillary angiomatosis, as follows:
Cutaneous lesions: Result almost equally from B henselae and B quintana infections
Subcutaneous lesions: Usually caused by B quintana infection
Osseous lesions: Usually caused by B quintana infection
Visceral involvement: Almost exclusively caused by B henselae infection
Neurologic disorders: Associated more frequently with B quintana infection than with B henselae
Domestic cats (Felis domesticus) are the reservoirs of B henselae, which may be transmitted via cat bites or scratches or, potentially, by bites from cat fleas (Ctenocephalides felis). Kittens are more frequently associated with transmission of B henselae than are older cats. Humans appear to be the only reservoir of B quintana; the human body louse, Pediculus humanus, is the transmission vector.
Risk factors for bacillary angiomatosis include the following:
HIV infection[18, 19]
Chronic lymphocytic leukemia
Cytotoxic chemotherapy
Organ transplantations[1, 7, 8]
Additional risk factors for bacillary angiomatosis associated with B henselae infection include the following:
Cat ownership
Cat bites
Cat scratches
Additional risk factors for bacillary angiomatosis associated with B quintana infection include the following:
Homelessness
Low socioeconomic status
Exposure to body and hair lice
Bacillary angiomatosis was reported in a patient who was HIV-seronegative but had idiopathic thrombocytopenic purpura, had undergone splenectomy, and had been administered long-term systemic prednisone.[20] Although not taken from the same patient, see the image below.
Another report described an immunocompetent child with infected facial wound, in the vicinity of which bacillary angiomatosis lesions had developed. Similar lesions also appeared at the donor site of the skin graft, which was grafted on the facial wound.[9] A case of bacillary angiomatosis presenting as a pyogenic granuloma of the hand in an otherwise apparently healthy man recently was reported from Saudi Arabia.[21]
Multiple leg ulcers caused by bacillary angiomatosis without a history of direct contact with cats in an adult immunocompetent man has also been reported.[22]
A case of bacillary angiomatosis in an HIV-negative patient who had chronic hepatitis B but no other immunosuppressive status was reported from Turkey, suggesting that immunologic differences secondary to chronic hepatitis B could have led to an increased risk for the disease.[23] Bacillary angiomatosis may be triggered by trauma and skin burns immunocompetent individuals.[24, 25]
The exact incidence of bacillary angiomatosis is not known, but the disease has been reported in almost all states. Reports have been especially high in Florida, Texas, New York, and northern California (San Francisco area), each of which has a high frequency of HIV infection.
Bacillary angiomatosis is less commonly reported in Europe than in North America, which may imply that diagnoses are missed or that Europe has a minimal reservoir of bacilli. Cases also have been reported in Africa, Peru, Argentina, Brazil,[26, 27] Turkey,[23] Saudi Arabia,[21] and Australia.[28] In 2008, Thailand reported its first case of bacillary angiomatosis associated with B henselae.[29]
An analysis of 605 healthy people in southern Spain found 13.55% IgG seropositive to B. henselae and to 11.07% B. quintana, delineating an elevated prevalence of both in this region.[30]
Approximately 40% of US patients with bacillary angiomatosis are white, 40% are Black, and 20% are of Hispanic origin.
Approximately 90% of US patients with bacillary angiomatosis are men, probably because a disproportionate number of patients infected with HIV also are men.
A wide age range exists among patients with bacillary angiomatosis, from infancy to old age. The age range was 26-52 years in one early series of patients with acquired immunodeficiency syndrome (AIDS). Although bacillary angiomatosis is extremely rare in children, it was reported in a boy aged 12 years with acute leukemia who was undergoing chemotherapy and in a 6-year-old immunocompetent girl.
The prognosis of bacillary angiomatosis is excellent; antibiotics are curative in most patients, with lesions resolving completely after treatment. Hyperpigmentation or slight induration at the site of a lesion may persist indefinitely. Relapses can occur after cessation of therapy and are common in immunocompromised hosts.
Overall prognosis depends on early detection and treatment and on the degree of immunosuppression. Treatment may be more difficult and requires a longer duration of therapy if the diagnosis is delayed. Untreated bacillary angiomatosis may be progressive and life threatening.
Bacillary angiomatosis may cause disease of many different organs, including the heart, brain, liver, and spleen, if not treated promptly. Complications include the following:
Disfigurement
Biliary obstruction and jaundice
Gastrointestinal bleeding
Encephalopathy
Laryngeal obstruction and asphyxiation
Patients with bacillary angiomatosis commonly have a history of HIV infection, organ transplantation, leukemia, or chemotherapy.[1] However, it also has been reported in immunocompetent individuals.[10] Inoculation bartonellosis may be evident in immunocompetent individuals as a pyogenic granuloma–like nodule at the site of a cat scratch.[2, 3]
Most patients with bacillary angiomatosis are infected with HIV and have CD4+ cell counts of less than 200/µL (although bacillary angiomatosis can develop prior to HIV seroconversion in some patients). The duration of symptoms before diagnosis usually is several months.
In some cases, bacillary angiomatosis becomes evident or recurs during immune restoration after initiation of highly active antiretroviral therapy (HAART).[31, 32]
Features of skin, subcutaneous, mucosal, and osseous lesions caused by bacillary angiomatosis include the following:
Bartonella-related pseudomembranous angiomatous papillomatosis of the oral cavity, seen as vegetating papillomatosis exclusively on the oral mucosa, has been described.[7, 36] Oral lesions may occur without concomitant cutaneous lesions. Oronasal fistula formation has been reported.[37]
Visceral involvement associated with bacillary angiomatosis may be asymptomatic or may cause the following symptoms:
Cutaneous lesions due to bacillary angiomatosis may take one of the following forms:
Solitary or multiple red, purple, flesh-colored, or colorless papules (hemangiomalike lesions) varying in size from 1 mm to several centimeters. An analysis of 605 healthy people in southern Spain found 13.55% IgG seropositive to B. henselae and 11.07% seropositive to B. quintana, delineating an elevated prevalence of both in this region.[30]
Nodules, often covered with a fine, tightly adherent scale
Large, friable, pedunculated, or polypoid exophytic masses
Hyperpigmented, hyperkeratotic, indurated plaques, typically on the extremities and often overlying osseous defects
Dermoscopic examination of cutaneous papules and violaceous nodules may show oval shapes with bright red areas and globular structures on a grayish background. Arborizing telangiectasia may be evident in the periphery.[38]
The number of lesions may vary from 1 to more than 1000, and they are often multiple. Multiple lesions often demonstrate more than 1 morphologic appearance. Black patients, in particular, may bear the plaque form.
Cutaneous lesions may develop ulceration, discharge, and crusting, and they often are tender. Smaller lesions tend to be covered with an attenuated epidermis, whereas larger lesions tend to erode and bleed. Most lesions are rubbery and firm upon palpation and usually are freely mobile. They may be associated with regional lymphadenopathy. In rare cases, lesions may regress spontaneously.
Subcutaneous nodules may erode through the surface and become friable and superinfected. Deep lesions are usually uncolored and either mobile or fixed to the underlying tissues. They often are tender. The overlying skin may appear normal.
Because extensive visceral bacillary angiomatosis may occur with only cutaneous disease evident, regard skin bacillary angiomatosis as a marker of possible internal involvement.
Mucosal lesions are similar to other lesions and may involve oral, conjunctival, nasal, anal, or penile mucosal surfaces.
Ocular involvement in bacillary angiomatosis has been reported in immunocompetent and immunocompromised patients. It can range from eyelid involvement to papillitis, hyalitis, and retrobulbar neuritis.[39, 40]
Visceral involvement may lead to fever, abdominal distention, hepatomegaly, and splenomegaly. This involvement eventually may progress to bacteremia and sepsis syndrome. Neurologic deficits may accompany intracranial mass lesions.
Visceral involvement may occur in the absence of cutaneous lesions. In this case, the diagnosis often is delayed, because the manifestations of visceral involvement are nonspecific.
A retrospective analysis of 37 speciated bacillary angiomatosis cases demonstrated that fever was present in two thirds of the patients and weight loss in one third of the patients, including those without extracutaneous involvement.[41]
Differential diagnosis of bacillary angiomatosis includes the following:
Common wart
Hemangioma
Angiokeratoma
Verruga peruana
Infections caused by Mycobacterium haemophilum, M kansasii, and M marinum
Bacterial abscess
Cavernous hemangioma
Nodal myofibromatosis
Kaposi sarcoma
A multiplexed 1-pot colorimetric detection system for DNA from a frequently confounding disease, Kaposi sarcoma, and from Kaposi sarcoma-associated herpesvirus has been developed using gold and silver nanoparticles.[42]
Failure to distinguish Kaposi sarcoma from bacillary angiomatosis is problematic because bacillary angiomatosis, unlike Kaposi sarcoma, responds dramatically to antibiotic therapy. Furthermore, bacillary angiomatosis may be life threatening if untreated. Because the 2 diseases may coexist, the lesions of bacillary angiomatosis may be easily overlooked.
Cat scratch disease
B henselae and B quintana may stain positively with a specific antiserum against the cat scratch bacillus. Bacillary angiomatosis, however, causes a vascular proliferation, not a formation of stellate abscesses without granuloma formation, as found in cat scratch disease. In addition, unlike patients with bacillary angiomatosis, those with cat scratch disease do not respond to antibiotics.
Verruga peruana and Oroya fever
The organisms causing bacillary angiomatosis resemble the agent of verruga peruana and Oroya fever, Bartonella bacilliformis, in producing a histologically similar vascular proliferation, in having a gram-negative wall structure (as observed using electron microscopy), and in tending to grow in clumps visible by light microscopy. Oroya fever is transmitted by an insect vector (a Peruvian sandfly) present only in a mountainous region of Peru near the city of Oroya.
Differentials
Angiosarcoma
Catscratch Disease
Cryptococcosis
Histoplasmosis
Kaposi Sarcoma
Sporotrichosis
Acneiform Eruptions
Glomus Tumor
Pyogenic granuloma
Dermatofibroma
Epithelioid angiomatous nodule
Bacillary angiomatosis in patients who also are infected with HIV most commonly causes anemia, leukopenia, and CD4+ cell counts of less than 0.2 X 109/L. In a series of 42 patients with bacillary angiomatosis, the average CD4+ cell count was 0.021 X 109/L. A rapid drop in hemoglobin level in the absence of bleeding or hemolysis has been reported in a patient with peliosis and was thought to be secondary to the sequestration of blood into pools in a liver or spleen that was massively enlarged. Thrombocytopenia with coagulopathy also may occur with peliosis.
Elevation of alkaline phosphatase, gamma-glutamyltransferase, and transaminase levels may indicate hepatic involvement. Alkaline phosphatase levels are more markedly elevated (5 times normal on average) than transaminase levels, which are usually mildly to moderately elevated or normal.
Well-circumscribed cortical or periosteal osteolytic lesions, mainly affecting the long bones, can be seen in radiographs in patients with bone involvement.[34, 37]
Biopsy
Biopsy specimens of skin, subcutaneous or mucosal lesions, or, in cases of peliosis hepatis, the liver are diagnostic.
Endoscopy
With gastrointestinal involvement, endoscopic studies may reveal ulcerated nodules of the mucosa of the stomach, small intestine, or large intestine.
Bronchoscopy
With lung involvement, bronchoscopy may reveal polypoid lesions.
The diagnosis of cutaneous bacillary angiomatosis and extracutaneous disease most often is based on clinical features coupled with biopsies of lesions and appropriate tissue staining. Detection of Bartonella DNA in tissue specimens via polymerase chain reaction (PCR) assay or of Bartonella antigens targeting the 16S-23S ribosomal RNA gene intergenic transcribed spacer via immunohistochemical methods is diagnostic.[4] Note that a negative result suggests the absence of detectable DNA but does not rule out Bartonella infection. The PCR assay does not differentiate between Bartonella henselae and Bartonella quintana.
When indirect immunofluorescent antibody testing is used to detect immunoglobulin (Ig) antibodies to B henselae, IgG titers of higher than 1:64 against B henselae suggest the presence of bacillary angiomatosis.
An enzyme immunoassay for the detection of IgG antibodies to B henselae now is available, and is reported to be 5-10 times more sensitive than the indirect fluorescent antibody test.
In addition, an immunoglobulin M–specific enzyme-linked immunosorbent assay for the detection of an early antibody response to B henselae has been developed that discriminates between B henselae–positive and B henselae–negative patient samples with impressive sensitivity (100%) and specificity (97.1%) values.[43]
Blood cultures may yield organisms in bacillary angiomatosis if they are grown at 35°C in 5% carbon dioxide for 3 weeks using a lysis centrifugation technique. B henselae colonies are rough, cauliflowerlike, and usually deeply embedded in the agar. B quintana colonies are smooth, flat, and shiny and do not pit the agar. Whole-cell fatty acid gas chromatography has been used to identify the organisms once they have been grown in culture. Culture of Bartonella from solid tissue is more difficult but possible.
Radiographs of the bones overlying the skin lesions in patients with bacillary angiomatosis may demonstrate simple cortical erosions, osteolytic lesions, extensive cortical destruction, or a periosteal reaction. Typical lytic bone lesions, which usually manifest as focal bone pain, are sometimes localized only to the area where a subcutaneous lesion is present, and can be asymptomatic.
Chest radiography may reveal pulmonary parenchymal nodules, which may have either well-defined or poorly defined borders, with no region of the lung consistently favored.
Bone scan findings always are positive at the site of osseus lesions and may help to identify the additional areas of involvement not revealed by conventional radiography.
In peliosis hepatis, a computed tomography (CT) scan of the liver may demonstrate hypodense, ringlike lesions that enhance with contrast.[44] The absence of mass effect on adjacent vasculature is characteristic. On magnetic resonance imaging (MRI), the lesions appear bright on T2-weighted images and dark on T1-weighted images. Enhancement patterns of one published MRI case study suggested centripetal enhancement similar to hemangioma, but another MRI case study suggested centrifugal enhancement.[45]
Although authors disagree on the characteristic radiologic appearance of peliosis hepatis associated with bacillary angiomatosis, the most common presentation on CT scans consists of low-density lesions, some with peripheral enhancement. Homogeneous hypervascularity and nodular peripheral enhancement are not characteristic and would suggest an alternative pathology.[44]
CT scanning of the chest and abdomen may reveal mediastinal, retroperitoneal, or mesenteric lymph node enlargement.
In intracerebral bacillary angiomatosis, CT scanning of the brain reveals a contrast-enhancing mass lesion.
Some bacillary angiomatosis lesions have 2 distinct regions of vascular proliferation, a superficial one resembling a pyogenic granuloma or a papular angiokeratoma and a deeper one resembling a histiocytoid hemangioma, with a proliferation of small blood vessels lined by protuberant endothelial cells closely adherent to one another in an epithelioid pattern. The presence of neutrophils adjacent to the blood vessels is noteworthy and may be an important diagnostic clue.
Granular material resembling fibrin may be beside the neutrophils. This is the bacterium, observed best with either Warthin-Starry silver or Grocott-silver methenamine stain. A similar histologic pattern may be evident in affected oral mucosa, lymph nodes, liver, spleen, bone marrow, larynx, gastrointestinal tract, peritoneum, diaphragm, and bronchial mucosa.[46, 47]
Some lesions only have a few solitary neutrophils and moderate numbers of bacteria, whereas others have clusters of neutrophils and numerous nearby bacteria, in some cases to the extent of mimicking a frank abscess.
Some bacillary angiomatosis nodules may histologically resemble those of histiocytoid (epithelioid) hemangioma, Kaposi sarcoma, and verruga peruana. A proliferation of both endothelial cells and factor XIIIa–positive dermal dendrocytes is observed in bacillary angiomatosis, verruga peruana, granuloma pyogenicum, and Kaposi sarcoma .
The overlying epidermis may demonstrate atrophy, ulceration, or, at times, pseudoepitheliomatous hyperplasia.[48] An epithelial collarette may be observed, particularly in those bacillary angiomatosis nodules that clinically resemble pyogenic granuloma. The dermis shows a vascular proliferation with small vessels arranged in clusters around ectatic vessels that may be markedly dilated. A lobular pattern may be observed, with varying amounts of edema and mucinous or fibrotic change between the lobules.
Histologic examination of skin lesions reveals vascular proliferation involving small blood vessels that contain plump cuboidal epithelial cells interspersed with polymorphonuclear inflammatory cell infiltrates and clumps of granular purple material. Coincidental endothelial cell necrosis and cytologic atypia may lead to a misdiagnosis of angiosarcoma. Solid areas of spindle cells may also be present; in some cases, these mimic Kaposi sarcoma or other sarcomas.
Histologic examination of liver sections in peliosis hepatis reveals dilated, blood-filled spaces in the fibromyxoid stroma that contain inflammatory cells, dilated capillaries, and clumps of granular purple material.
Histologic examination of lymph nodes reveals coalescing nodules of proliferated small blood vessels, some with prominent endothelial cells, in the cortical and paracortical areas. The uninvolved parenchyma may show follicular hyperplasia, plasmacytosis, or sinus histiocytosis.
Bacillary angiomatosis lesions of the lymph nodes, bone, and brain may demonstrate a less lobular pattern than cutaneous lesions do, and have a less prominent neutrophilic infiltrate.
Histologic examination of the bone reveals a lobular proliferation of small blood vessels with prominent endothelial cells. Neutrophils may be sparse, and their lobular nature may not be apparent in some bone biopsy findings.
Pseudoepitheliomatous hyperplasia, a histologic reaction pattern characterized by epithelial proliferation in response to various stimuli, including mycobacterial, fungal, and bacterial infections, has been described in an immunocompromised patient with AIDS and bacillary angiomatosis.[48] Histologic examination of a finger lesion from this patient demonstrated capillary proliferation with neutrophilic debris and characteristic amorphous granular deposits. Warthin-Starry and Giemsa staining revealed clumps of coccobacilli. PCR assay using cervical lymph node tissue also revealed Bartonella organisms.
The granular purple material in tissue sections stained with hematoxylin and eosin consists of masses of bacteria, which can be demonstrated by modified silver staining (Warthin-Starry silver stain) or electron microscopy.[46, 47] However, the major drawback of Warthin-Starry silver stain is lack of specificity.
Other organisms that stain positive with Warthin-Starry silver stain include the following:
Legionella species (Legionnaires pneumonia)
Nocardia species (nocardiosis)
Trophermyma whippleii (Whipple disease)
Afipia felis (catscratch disease)
Treponema pallidum (syphilis)
Borrelia burgdorferi (Lyme disease)
Helicobacter pylori (chronic active gastritis)
However, bacillary angiomatosis is clinically distinguishable from infections caused by these organisms, except for those caused by Nocardia brasiliensis.
Transmission electron microscopy reveals clumps of pleomorphic bacilli measuring 0.2-0.5 µm by 1-3 µm that have a trilaminar structure to the cell walls, which is typical of vegetative forms of gram-negative bacilli.
Bacillary angiomatosis can be cured in most patients with antibiotics, so recognition of the disease is critical. Treatment recommendations are based on retrospective studies or clinical observations. A systematic review found that current clinical practice for the treatment of bartonellosis, including bacillary angiomatosis, mostly relies on expert opinion and antimicrobial susceptibility data.[49] No antibiotics have been studied prospectively or in randomized controlled trials. Corticosteroid, cytotoxic, and radiation therapy are not effective.[49] Antiretroviral therapy is essential in HIV-infected individuals. Immune reconstitution inflammatory syndome, complicated by Jarisch-Herxheimer reaction, was reported after antiretroviral therapy and doxycycline.[32]
The reader is referred to the 2014 guidelines published by the Infectious Diseases Society of America (IDSA) for the treatment of bacillary angiomatosis (see Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections: 2014 Update by the Infectious Diseases Society of America).[5]
Cryotherapy, electrodesiccation and curettage, and surgical excision of solitary cutaneous lesions can be useful as adjunctive therapy. However, antibiotic therapy provides treatment for possible occult dissemination of bacteria, in addition to regression of the lesions.
Consultations can include the following:
Infectious diseases specialist
Dermatologist
For cutaneous lesions, the number and size of the lesions should be monitored to determine the efficacy of treatment.
For visceral involvement, imaging study findings, hepatic transaminase levels, organomegaly, and/or lymph node enlargement should be monitored to determine response to therapy.
Clinical experience strongly favors the use of erythromycin or a tetracycline derivative in the treatment of bacillary angiomatosis. Erythromycin remains the drug of choice because it yields an excellent clinical response in almost all patients. (An antiangiogenic effect by erythromycin has been postulated and tested with in vitro models of B quintana infection.[50] )
Tetracyclines are the first alternative in patients who cannot tolerate erythromycin. A combination of doxycycline (100 mg PO/IV q12h) plus rifampin (300 mg PO bid) may be used in immunocompromised patients with severe disease.
Other antibiotics display in vitro activity but are not effective against bacillary angiomatosis in vivo. Penicillins and cephalosporins have no activity against Bartonella species despite in vitro susceptibilities. The following antibiotics have produced good clinical responses when combined with either doxycycline or ciprofloxacin:
Clarithromycin
Azithromycin
Chloramphenicol
Ciprofloxacin
Trimethoprim-sulfamethoxazole
Rifampin
Isoniazid
Gentamicin
These antibiotics have been used successfully in limited numbers of patients. However, treatment failures with ciprofloxacin, trimethoprim-sulfamethoxazole, isoniazid, and rifampin have been reported.[51, 28] Doxycycline is contraindicated in pregnancy.
A reaction resembling the Jarisch-Herxheimer reaction has been described upon the initiation of appropriate antibiotic therapy. The reaction is characterized by fever, myalgias, and constitutional symptoms.
The optimal duration of therapy is not known. Recommendations are based on clinical experience rather than scientific data. Usually, recommendations indicate that skin lesions be treated for 8-12 weeks and osseous and liver lesions for at least 3 months, although these treatment periods have not been studied in prospective, randomized trials. Patients with HIV infection may require life-long therapy if relapses occur.
The cutaneous lesions resolve substantially after approximately 4-7 days of therapy, and they usually resolve completely after 1 month. In one patient with a mass as large as 12 cm in diameter, the lesion completely resolved except for mild residual scarring after 9 weeks of azithromycin, along with antiretroviral therapy for HIV infection.[52]
Prevention of bacillary angiomatosis associated with B henselae infection includes avoidance of contact with cats and control of flea infestations in cats.
Preventive measures associated with B quintana infection are as follows:
Delousing procedures, such as the use of permethrin dusting powder (1%; 30-50 g per adult)
Treatment of clothing and bedding
In addition, macrolides for Mycobacterium avium-intracellulare prophylaxis in patients infected with HIV are protective against bacillary angiomatosis.
A study by Lappin et al indicated that the risk of B henselae infection in cats via contact with the flea Ctenocephalides felis can be reduced with the use of a flea and tick collar containing 10% imidacloprid and 4.5% flumethrin. In the 8-month trial, cats infected with B henselae and exposed to C felis were housed with a group of uninfected cats who wore flea collars during the trial period and another group of uninfected cats who received no preventive treatment.[53]
The 3 groups were separated from each other by mesh, preventing the cats from having physical contact with members of the other groups but allowing the fleas to move among the groups and, potentially, transmit B henselae to the uninfected cats. Four out of 7 of the cats who received no treatment tested positive by the end of the study for B henselae, whereas none of the cats treated with flea collars were positive for the bacterium.
Oral erythromycin remains the drug of choice for bacillary angiomatosis, with skin lesions often gradually fading over a period of 4 weeks. If the lesions persist, however, even in diminished form, medication can be changed to tetracycline. If the infection appears to be serious, adding a bactericidal medication, such as a third-generation cephalosporin or an aminoglycoside, may be prudent during the initial 3 weeks of therapy. According to a report from Chile, a patient with HIV infection and bacillary angiomatosis caused by B quintana responded favorably to azithromycin plus ciprofloxacin started together with antiretroviral therapy.[54]
The Infectious Disease Society 2014 Guidelines suggest erythromycin 500 mg 4 times a day or doxycycline 100 mg twice a day to be used for at least 2 weeks and up to 2 months.[5]
Empiric antimicrobial therapy should cover all likely pathogens in the context of the clinical setting.
Tetracycline inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunits. Primarily bacteriostatic, it has anti-inflammatory activity and is active against a wide range of gram-positive and gram-negative organisms.
Erythromycin is a highly bacteriostatic macrolide antibiotic isolated from a Streptomyces strain. Its spectrum is between those of penicillin and tetracyclines. The mechanism of action involves binding to the 50S ribosomal subunit and inhibiting microbial protein synthesis.
This agent is a highly bacteriostatic, semisynthetic macrolide. A 6-methoxy erythromycin, clarithromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl transfer RNA (tRNA) from ribosomes, causing RNA-dependent protein synthesis to arrest. It has a spectrum between those of penicillin and tetracyclines.
Azithromycin is a highly bacteriostatic macrolide with a spectrum between those of penicillin and tetracyclines. Its mechanism of action involves binding to the 50S ribosomal subunit and inhibiting microbial protein synthesis.
Doxycycline is a bacteriostatic antibiotic that inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. It is an important form of tetracycline that is effective in twice-daily dosing.
This is a bactericidal antibiotic that inhibits bacterial protein synthesis by inhibiting DNA-dependent RNA polymerase. It is useful in immunocompromised patients with severe disease.
This synthetic, antibacterial combination product discourages bacterial growth by inhibiting the synthesis of dihydrofolic acid.
Overview
What is bacillary angiomatosis?
What are the signs and symptoms of bacillary angiomatosis?
What are the symptoms of visceral involvement in bacillary angiomatosis?
Which lab tests are performed in the workup of bacillary angiomatosis?
What imaging studies are performed in the workup of bacillary angiomatosis?
What is the role of biopsy in the workup of bacillary angiomatosis?
What is the role of endoscopy and bronchoscopy in the workup of bacillary angiomatosis?
How is bacillary angiomatosis treated?
When was bacillary angiomatosis originally identified?
What is the role of antibiotics in the treatment of bacillary angiomatosis?
What is included in patient education about bacillary angiomatosis?
What is the pathophysiology of bacillary angiomatosis?
What is the pathogenesis of bacillary angiomatosis?
What is the pathogenesis of bacillary angiomatosis?
What causes vascular proliferation in the pathophysiology of bacillary angiomatosis?
What are the disease reservoirs of B henselae causing bacillary angiomatosis?
What are the risk factors for bacillary angiomatosis?
What are the risk factors for bacillary angiomatosis caused by B henselae infection?
What are the risk factors for bacillary angiomatosis caused by B quintana infection?
What causes bacillary angiomatosis in HIV-negative patients?
What is the prevalence of bacillary angiomatosis in the US?
What is the global prevalence of bacillary angiomatosis?
What are the racial predilections of bacillary angiomatosis?
What is the sexual predilection of bacillary angiomatosis?
Which age groups have the highest prevalence of bacillary angiomatosis?
What is the prognosis of bacillary angiomatosis?
What are the possible complications of bacillary angiomatosis?
Presentation
Which clinical history findings are characteristic of bacillary angiomatosis?
How are the lesions of bacillary angiomatosis characterized?
Which clinical history findings are characteristic of visual involvement in bacillary angiomatosis?
Which cutaneous findings are characteristic of bacillary angiomatosis?
Which mucosal findings are characteristic of bacillary angiomatosis?
Which ocular findings are characteristic of bacillary angiomatosis?
Which visceral findings are characteristic of bacillary angiomatosis?
DDX
Which conditions are included in the differential diagnoses of bacillary angiomatosis?
How is Kaposi sarcoma differentiated from bacillary angiomatosis?
How is cat scratch disease differentiated from bacillary angiomatosis?
How is verruga peruana and Oroya fever differentiated from bacillary angiomatosis?
What are the differential diagnoses of bacillary angiomatosis?
Workup
Which lab test findings suggest bacillary angiomatosis?
Which radiology findings suggest bone involvement in bacillary angiomatosis?
Which biopsies may be performed in the workup of bacillary angiomatosis?
Which endoscopy findings suggest bacillary angiomatosis?
Which bronchoscopy findings suggest bacillary angiomatosis?
How is bacillary angiomatosis diagnosed?
What is the role of enzyme immunoassays in the workup of bacillary angiomatosis?
What is the role of blood cultures in the workup of bacillary angiomatosis?
What is the role of radiography in the workup of bacillary angiomatosis?
What is the role of CT scanning and MRI in the workup of bacillary angiomatosis?
Which histologic findings are characteristic of bacillary angiomatosis?
Which skin histologic findings are characteristic of bacillary angiomatosis?
Which liver histologic findings are characteristic of bacillary angiomatosis?
Which lymph nodes histologic findings are characteristic of bacillary angiomatosis?
Which bone histologic findings are characteristic of bacillary angiomatosis?
What is pseudoepitheliomatous hyperplasia in bacillary angiomatosis?
What is the role of Warthin-Starry silver stain in the histologic exam of bacillary angiomatosis?
Which transmission electron microscopy findings are characteristic of bacillary angiomatosis?
Treatment
What is the role of antibiotics in the treatment of bacillary angiomatosis?
Which organizations have published guidelines on bacillary angiomatosis?
What is the role of surgery in the treatment of bacillary angiomatosis?
Which specialist consultations are beneficial to patients with bacillary angiomatosis?
What is included in the long-term monitoring of bacillary angiomatosis?
Which antibiotics are used in the treatment of bacillary angiomatosis?
What is the duration of antibiotic treatment of bacillary angiomatosis?
How is bacillary angiomatosis prevented?
Medications
What are the preferred antibiotics for the treatment of bacillary angiomatosis?
Which medications in the drug class Antibiotics are used in the treatment of Bacillary Angiomatosis?