Anamnesis usually reveals an immunocompromising condition such as HIV infection, leukemia or immunosuppressive therapy after organ transplantation or diagnosis of cancer. Also, a history of cat scratches or bites may point at BA. Indeed, a pyogenic granuloma-like lesion may be visible at the site of Bartonella inoculation [9].

In general, BA is characterized by red to purple nodes, distributed all over the body without any apparent preference for a certain body region. These nodes may have formed as solitary or multiple lesions and are firm and elastic. They may bleed and ulcerate upon minimal trauma. Similar lesions are often seen in mucous membranes of mouth and throat, respiratory tract and anogenital region. With regards to the oral mucosa, papillomatosis-like lesions have been described [10].

If the infection spread to other tissues, this may manifest in form of distinct symptoms. The involvement of visceral organs may result in nausea, vomiting and abdominal pain, painful defecation and hematochezia. Upon abdominal palpation, an intraabdominal mass may be detected. Such space-occupying processes may compress the bile duct and cause jaundice; other, similar conditions are conceivable. Bone involvement is indicated by bone pain, which is most often felt in forearms and lower legs. Neuro-BA may cause headaches, trigeminal neuralgia and seizures, but also psychiatric symptoms and personality changes.

In general, systemic BA may be associated with fever, chills, night sweats, weakness, loss of appetite, anorexia and subsequent weight loss.

Surprisingly, BA may manifest upon restoration of the immune system by applying highly active antiretroviral therapy.

• Soft Tissue Mass

  A man with AIDS presented with a deep soft-tissue mass involving the right thigh. Biopsy of a skin lesion on the back and culture of a specimen from this lesion showed bacillary angiomatosis due to Bartonella (formerly Rochalimaea) quintana. [ncbi.nlm.nih.gov]

  Bartonella henselae /Bacillary angiomatosis: cutaneous biopsy Bartonella henselae /Bacillary angiomatosis: cutaneous biopsy Bartonella henselae /Bacillary angiomatosis: hepatosplenomegaly in peliosis hepatis Bartonella henselae /Bacillary angiomatosis: soft-tissue [hiv.va.gov]

  It may be better outlined according to location rather than modality: Chest lung nodules mediastinal adenopathy peripheral adenopathy pleural effusions Abdomen ascites abdominal adenopathy soft-tissue masses low-attenuating lesions in the liver +/- spleen [radiopaedia.org]

• Vascular Disease

  Volume 1 covers the visual sensory system, the autonomic nervous system, the ocular motor system, the eyelid, facial pain and headache, and nonorganic disease. Volume 2 covers tumors, the phacomatoses, and vascular disease. [books.google.com]

• Suggestibility

  Kaposi's sarcoma-associated herpes virus specific DNA was not amplifiable by polymerase chain reaction (PCR) in our patient, suggesting that the lesion represented bacillary angiomatosis alone, despite clinical and histopathological features which suggested [ncbi.nlm.nih.gov]

Molecular biological approaches are the method of choice for verifying infection with B. henselae or B. quintana. PCR analysis may be carried out on tissue samples and body fluids and is a sensitive and specific test that even allows to distinguish species and genotypes.

Of note, silver staining of blood smears is the only technique for direct visualization of Bartonella, but the method is little sensitive and little specific. Similarly, blood cultures are rarely helpful to diagnose Bartonella infection [11]. They are also not used to establish an antibiogram, because experience has shown that such results poorly correlate with therapeutic success. Due to the poor performance of direct techniques, serology is sometimes applied for diagnosing BA. However, immunodeficient patients may not present a sufficient immune response for positive results, while others retain high antibody titers although the infection occurred a long time ago. Cross-reactivity with Chlamydia and Coxiella has been reported.

Imaging techniques have to be employed to assess potential involvement of internal organs. Computed tomography is most often used to this end and may also reveal osteolytic lesions due to osseous bacillary angiomatosis [12]. Magnetic resonance imaging may pose an alternative for the former, standard radiography for the latter.

If BA diagnosis is confirmed and previously, immunodeficiency had not been diagnosed, the patient should be tested for HIV infection and possibly leukemia.

• Lymphocytic Infiltrate

  A second biopsy contained a diffuse polyclonal lymphocytic infiltrate in which large lymphocytes with irregular nuclei and mitotic figures were prominent. Systemic examination disclosed mild splenomegaly and a benign paraproteinemia. [ncbi.nlm.nih.gov]

As has been indicated in the previous paragraph, antibiograms are rarely established. According to experience, erythromycin is most effective in treating BA and virtually all patients respond to erythromycin treatment. An anti-angiogenic effect mediated by this drug has been proposed and would possibly explain part of this resounding success [13].

If erythromycin therapy is contraindicated or not well tolerated, tetracycline antibiotics are a very good second choice. Immunodeficient patients suffering from severe BA may benefit  from combined administration of doxycycline (100 mg, bid) and rifampin (300 mg, bid). Combinations with a variety of other antimicrobial agents have been reported successful in a number of cases. In this line, doxycycline may also be administered in combination with ciprofloxacin, macrolides like clarithromycin or azithromycin, chloramphenicol, gentamicin, trimethoprim-sulfamethoxazole or isoniazid.

Instead of doxycycline, ciprofloxacin may be used in combined antibiotic approaches.

The treatment of choice is erythromycin or doxycycline. With regards to the above mentioned alternatives, treatment failures have been reported [14]. Upon sole dermatological symptoms, therapeutic drugs should be applicated for at least two months, although skin lesion usually resolve much faster. Involvement of additional organ systems requires antibiotic treatment for more than three months, possibly for life if frequent relapses occur.

Of note, patients may react with fever, myalgias and malaise to antibiotic therapy.

Prognosis of BA is very good. Patients respond very well to antibiotic treatment and lesions to all organ systems resolve after cure. Only slightly hardened, hyperpigmented spots may remain on the skin. Delayed or missing therapy renders BA a life-threatening condition.

In order to avoid relapses, the immunocompromising condition should be remedied. If that is not possible, recurrences have to be expected.

Bartonella are gram-negative bacteria that are considered opportunistic pathogens. Thus, Bartonella infection and BA are almost exclusively diagnosed in immunodeficient people. HIV infection is among the most common causes of susceptibility to Bartonella infection and subsequent development of BA [2]. Similarly, certain forms of leukemia that are associated with immunosuppression may leave patients more prone for BA as well as immunosuppressive therapy administered, for instance, in the scope of chemotherapy or post-transplantational treatment. In this line, there are case reports of BA after long-term systemic application of corticosteroids [3]. Very rarely, BA is detected in immunocompetent individuals. For example, an otherwise healthy child who suffered from a facial wound developed BA due to as of yet unknown reasons [4]. Similarly, Bartonella species caused leg ulcers in an adult men without any known immunodeficiency [5].

B. henselae is also the causative agent of cat scratch fever. As this name indicates, the bacterium may be transmitted by cat scratches or bites. It has been proposed that cat fleas (Ctenocephalides felis) serve as vectors. Thus, those are at higher risk that live or work with cats. Of note, neither of the above mentioned immunocompetent child or man did have any contact to cats.

B. quintana is transmitted by lice and since those are more prevalent among the poorer population, homeless and those with a low socioeconomic status have an increased risk for B. quintana infection and development of BA.

BA incidence varies significantly between distinct countries. Europe reports less cases of BA than North America and BA was described only in individual countries of South America, the Near East and Australia. In 2008, B. henselae was first isolated in Thailand [6]. It has been suggested that Bartonella reservoirs are either very small or not present where these bacteria cannot be isolated. This hypothesis seems to be more likely than racial differences.

With regards to potential racial differences, equal numbers of US-American BA patients are Caucasian and Black. Less often, Hispanics present with BA. These numbers have to be interpreted with care, keeping the overall population shares and possible socioeconomic differences in mind.

Although men seem to be affected more often, this observation does not seem to represent a gender preference either. Most BA patients are HIV positive and most people infected with HIV are men.

People of all ages are susceptible, but the disease is rarely described in children. There may also be a correlation with HIV prevalence in distinct age groups.

Bartonella are gram-negative, facultative intracellular bacteria. After infection, they rapidly spread throughout the body by means of the blood stream. The may enter erythrocytes and replicate inside these cells [7]. It is not yet understood how Bartonella evade defense mechanisms of the host, but the fact that immunocompetent individuals only account for a very small share of BA patients may justify the hypothesis that they are unable to prevent and/or avoid an immune response in an otherwise health individual. It has been suggested that these bacteria avoid opsonization and thus phagocytosis.

Interestingly, an angiogenic has been identified in patients who suffer from chronic infection with Bartonella bacilliformis and who develop verruca peruana. Genetic studies have proven a close relationship between Bartonella bacilliformis and the causative agents of BA [8]. Thus, it is presumed that bacteria persist and release such an angiogenic factor, which triggers capillary proliferation.

BA is primarily associated with skin and subcutaneous lesions, sometimes mucous membranes are also affected. The infection may spread to virtually any organ system, but both species show distinct preferences for certain tissues. In this context, involvement of visceral organs is more commonly seen in B. henselae infections. Here, liver, spleen and lymph nodes most often present lesions. In contrast, spread to the subcutaneous tissue and subsequently to underlying bones is more typical for B. quintana. There seems to be a certain predilection for tibia, fibula and radius. Both species may affect the central nervous system, but such complications are more frequently caused by B. quintana than by B. henselae.

Systemic BA may lead to intrinsic organ failure and compression of adjacent structures due to the capillary nodes being space-occupying masses.

Any measures to prevent HIV infection also help to avoid BA.

HIV patients may benefit from prophylactic antibiotic therapy.

Cats, possibly cat fleas and lice may transmit B. henselae and B. quintana, respectively. Thus, contact with unknown cats should be avoided and cats should be regularly deparasited. An appropriate personal, clothing and bedding hygiene is highly recommended. If an infestation with lice is detected, it should be treated.

Angiomatosis describes a benign proliferative disorder of capillaries that may be detected in patients suffering from congenital disorders such as von Hippel-Lindau disease or Sturge-Weber syndrome, but that may also result from bacterial infection. In detail, Bartonella henselae (B. henselae), less frequently Bartonella quintana (B. quintana) may trigger this pseudo-neoplastic disease that is then called bacillary angiomatosis (BA).

BA primarily manifests with skin symptoms, but virtually any internal organ may also be compromised by the disease. The vast majority of BA patients suffers from immunodeficiency of different origin. In this context, the disease was first described in 1983 and was diagnosed in a person infected with HIV [1]. Other diseases weakening the immune system as well as iatrogenic causes may also leave individuals susceptible for BA.

The underlying disease may indeed be the greater health concern, since BA patients generally respond well to antibiotic treatment. However, BA is associated with a high mortality if left untreated. This high mortality results from systemic spread of the disease and functional impairment of the central nervous system, the bone marrow, heart, lungs and other organs.

Bacillary angiomatosis (BA) is a benign condition associated with proliferation of small blood vessels. It is not a cancerous disease but an illness triggered by infection with Bartonella henselae (B. henselae) and Bartonella quintana (B. quintana), two bacterial closely related species.

Causes

The above mentioned bacteria are facultative pathogens, i.e., they cause BA only in predisposed individuals. Here, any form of immunodeficiency leaves people more susceptible to Bartonella infection and subsequent development of BA. Most BA patients are HIV positive, but immunosuppression may also result from other diseases, notably from distinct forms of leukemia, from cancer treatment or drugs prescribed after organ transplantations.

B. henselae is transmitted by cats, through scratches and bites. It has been suggested that cat fleas serve as vectors for this bacterium.

B. quintana is transmitted by lice and is more frequently found among homeless people or those with a low socioeconomic status.

Symptoms

BA mainly manifests in form of red to purple nodes that are distributed irregularly over the whole body of the patient. Similar lesions may be observed on mucous membranes in distinct areas of the body. Upon minimal trauma, they may start bleeding.

The disease may spread to visceral organs, bones and central nervous system. A variety of symptoms may be associated with these forms of BA: vomiting, abdominal pain, painful defecation, bloody stools, bone pain, headaches, seizures, psychiatric symptoms and personality changes. Patients suffering from systemic BA often experience fever and chills, malaise, weakness and loss of appetite.

Diagnosis

Molecular biological techniques will be run on tissue samples or body fluids to detect and identify Bartonella. Computed tomography, possibly also magnetic resonance imaging or standard radiography, will be applied to confirm or rule out systemic BA and to assess potential organ damage.

Treatment

BA patients generally respond very well to antibiotic treatment. Erythromycin is the drug of choice, but tetracycline antibiotics are a good second options. In severe cases, two antimicrobials may be combined.

Drug therapy needs to be continued for several months. If the underlying immunodeficiency cannot be cured, relapses are likely. In such cases, antibiotic therapy will either be resumed or prescribed for life.

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