History
Bartonella species cause several clinical syndromes, including cat scratch disease (with enlarged nodes and other organ involvement), bacteremia, endocarditis, bacillary angiomatosis, peliosis hepatis, Oroya fever, and verruga peruana. The inability to mount an immune response contributes to manifestations observed in immunosuppressed individuals with advanced AIDS and other diseases.
Cat scratch disease
Most affected individuals have typical cat scratch disease symptoms and present with an enlarged lymph node.
A primary inoculation lesion often develops at the site of a bite or scratch.
A papule or pustule develops 5-10 days after exposure. This lesion may persist for a few weeks.
B henselae DNA may be chronically shed into peripheral blood during the natural course of cat scratch disease. [21]
Bacteremia and systemic illnesses
Trench fever was described in military personnel during World War I. Urban trench fever is now observed in homeless persons in the United States and Europe.
Symptoms of trench fever begin with chills and fever after an incubation period of a few days to a month. Occasionally, the patient experiences only a single febrile episode that lasts 4 or 5 days. More commonly, several episodes of fever occur. Each episode lasts about 5 days, which is the origin of the designation quintana. The patient cycles between severe chills and profuse sweating. In other patients, continuous fever lasts 2-6 weeks.
Associated symptoms include joint and muscle aches, injected conjunctivae, headache, dizziness, and pain behind the eyes. Some patients have diffuse symptoms without fever.
Some cases of trench fever become chronic with debility, with or without fever or aching, and occasionally with hyperexcitability.
In patients with HIV, infection with either B henselae or B quintana causes gradual onset of aching, headache, fatigue, and weight loss. Fever begins later. Persistent bacteremia with B henselae may develop in people with AIDS.
Encephalopathy has been associated mostly with B henselae. Guillain-Barré syndrome, hydrocephalus, and encephalopathy were associated with B quintana acute infection in one case report. [22]
Meningitis due to a "Bartonella washoensis"-like human pathogen was isolated from the blood of a patient with meningitis in California, the patient owned cats and dogs, and had contact with squirrels. [23]
Bacillary angiomatosis and peliosis hepatitis
Bacillary angiomatosis was initially described in persons infected with HIV. It typically involved the skin and was believed to resemble Kaposi sarcoma but can affect other organs such as the respiratory tract, bone, lymph nodes, gastrointestinal tract, and brain. When the liver or spleen was involved, bacillary peliosis or peliosis hepatis was diagnosed before Bartonella infection was discovered to be the cause.
Symptoms depend on the anatomic site involved and may include fever, tender lymphadenopathy, and skin lesions.
Oroya fever and verruga peruana
Over a century ago, a medical student named Daniel Carrión injected himself with blood from the skin lesion of a patient who had verruga peruana. He developed Oroya fever. Today, Oroya fever and verruga peruana are called Carrión disease. Before that time, the relationship between the diseases was unknown.
Bacteremia of Oroya fever begins 3-12 weeks after a bite from an infected sand fly. The illness may range from mild to very severe. In severe cases, fever, chills, headache, sweating, aches, dyspnea, mental status changes, and seizure may occur. Severe disease has an abrupt onset.
Transplant patients
Infection with B henselae is rare but has diverse manifestations. A review of 29 cases found that disseminated disease is common (72%). Fever was reported in 27 patients (93%), lymphadenopathy in 12 patients (41%), and skin lesions in seven patients (24%). [24]
Physical
Cat scratch disease
Enlarged lymph glands develop 1 week to 2 months after exposure. Swollen tender nodes are the usual presenting symptom.
Careful examination of the interdigital spaces, skin creases, and scalp increases the chance of finding the primary inoculation lesion. Inoculation sites other than the skin include the eye and mucous membranes (oral ulcer).
One third to two thirds of patients develop low-grade fever that lasts several days.
B henselae infection is one of the common causes of fever of unknown origin and prolonged fever in children. One study showed that the absence of lymphadenopathy in patients with cat scratch disease was closely related to the presence of prolonged fever or systemic complications. Another study of 186 patients with a serological diagnosis of cat scratch disease showed that 30 (16.1%) patients had no regional lymphadenopathy. These patients had persistent fever and more frequent systemic complications than patients with lymphadenopathy. [25, 26, 27]
Malaise and fatigue are common. Many patients feel healthy except for the enlarged node or nodes. Patients occasionally have multifocal lymphadenopathy.
Laboratory studies include the following:
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Diagnosis should be confirmed with demonstration of a fourfold rise in antibody levels, initially immunoglobulin M (IgM) followed by immunoglobulin G (IgG).
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Culture confirmation is difficult; PCR is more sensitive. [28]
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In some patients, hypercalcemia complicates cat scratch disease lymphadenopathy via overproduction of vitamin D due to granuloma formation.
Other morbidities include the following:
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Rarely, cat scratch disease spreads and causes granulomatous hepatitis or granulomas in the spleen or bones. Granulomas in the liver or spleen do not enhance with contrast on computed tomography (CT) scanning.
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Parinaud oculoglandular syndrome follows contamination of the eye, often from the patient's own hand. A granulomatous conjunctivitis follows and is associated with enlarged preauricular nodes.
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Bartonella quintana was isolated from the parotid gland of a patient with acute parotitis. [26]
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Encephalopathy is an infrequent but important manifestation that occurs in as many as 2-4% of patients with cat scratch disease. Several hundred such cases probably occur in the United States each year. Manifestations include generalized headaches, restlessness, combativeness, seizure, and neurologic defects such as aphasia, cranial nerve palsy, Brown-Sequard syndrome, and ataxia. Persistent intellectual impairment has been reported. Cerebral spinal fluid (CSF) cultures and routine studies are not helpful in diagnosis.
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The ocular manifestations of cat scratch disease are numerous. [29] Parinaud oculoglandular syndrome develops in about 2-3% of patients with cat scratch disease; posterior segment findings include optic neuropathy, neuroretinitis, and vitreitis, among others. [29] Neuroretinitis (45%) was the most common diagnosis in a study by Sulene et al (62 eyes, 53 patients); only 5 patients had significant complications. At final follow-up, there was no association between visual acuity and systemic antibiotics or steroids use. [30]
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In neuroretinitis caused by B henselae, a sudden loss of eyesight may be the presenting symptom. The patient usually has a prior flulike syndrome or enlarged nodes. A common examination finding is papilledema with a starburst appearance but the abscence doesn't exclude the diagnosis. A recent report described a 10-year-old girl with cat scratch disease who developed a macular hole 12 days after presentation with neuroretinitis in association with a posterior vitreous detachment. [31] Neuroretinitis is usually confirmed based on titers, but, on occasion, retinal biopsy with histopathology may prove helpful. Neuroretinitis usually resolves spontaneously except in immunocompromised patients. Multifocal chorioretinal lesions have also been described. [32]
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Osteomyelitis is a rare manifestation, occurring in 0.2–0.3% of patients with cat scratch disease [35] ; the most commonly involved site is the spine, but it can be multifocal. Medical therapy with antibiotics is very effective. Maman et al found that, among 913 patients with cat scratch disease, 10.5% had musculoskeletal manifestations (myalgia, arthralgia/arthritis, neuralgia, tendinitis, osteomyelitis). [36, 35]
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One study from Italy reviewed 74 cases of cat scratch disease. Atypical presentation was common (24.3%) and included ocular papillitis, maculopapular eruptions, vertebral infection, pulmonary infiltrates, and granulomatous hepatitis. [37]
Bacteremia
Findings include injected conjunctivae, nystagmus, hepatosplenomegaly, lymphadenopathy, and a maculopapular rash.
Muscles or joints may be tender.
Laboratory studies include the following:
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Patients typically exhibit increased leukocytes with occasional thrombocytopenia or albuminuria. Bacteremia is not usually detected.
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Patients with prolonged bacteremia may have culture-negative endocarditis because Bartonella species do not grow on standard blood culture media. Special media must be used. B henselae and B quintana infections can cause culture-negative endocarditis. Bartonella alsatica was isolated from the valve of a patient with endocarditis. [38] Most cases of Bartonella endocarditis involve native valves, but infection of prosthetic valves is possible. [39]
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Antibody titers are helpful in confirming the diagnosis.
As expected, persons with alcoholism and those who are homeless typically develop B quintana endocarditis (75% of cases), while persons with exposure to cats are more likely to harbor B henselae (25% of cases). Other Bartonella species are rarely implicated. Although many children are frequently exposed to cats, even those with cat scratch disease rarely develop Bartonella endocarditis.
Bacillary angiomatosis and peliosis hepatitis
Examination findings include purple to red-black, raised, palpable skin lesions.
When the liver, lymph node, or spleen is involved, it may be enlarged.
Laboratory studies include the following:
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Patients should undergo HIV antibody testing and CD4+ lymphocyte assessment.
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Patients typically have anemia and elevated levels of serum alkaline phosphatase.
Oroya fever and verruga peruana
Untreated patients have a high case-fatality rate. Survivors may be more susceptible to salmonellosis or toxoplasmosis during the convalescent period.
Verruga peruana lesions develop as crops with onset weeks to months later in untreated survivors. These lesions begin as small nodules and subsequently grow. Highly vascular mulaire lesions then form and begin to ulcerate, bleed, and heal via fibrosis over several months. Various stages of small to larger nodules, mulaire lesions, and fibrosis may occur simultaneously.
Laboratory studies include the following:
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Hemolytic anemia, thrombocytopenia, and elevated values on liver function studies are common.
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Survivors may develop persistent bacteremia.
Causes
Cat scratch disease
In the United States, cat scratch disease is the most common type of bartonellosis.
The clinical syndrome has been recognized for more than a century, but the etiology of this condition was confirmed only in the past decade. Confirmation involved isolating Bartonella species from cats and their fleas, showing an antibody titer rise in patients with the disease, and demonstrating the presence of organisms in biopsy samples through culture and PCR.
Occasional cases are negative for B henselae antibodies. In these instances, rare causes of cat scratch disease such as B clarridgeiae or Afipia felis should be considered.
Bacteremia
Bacteremia may occur with either B henselae or B quintana infection and may result in disseminated diseases. Other species of Bartonella have occasionally been associated with bacteremia.
Oroya fever and verruga peruana
Oroya fever and verruga peruana are manifestations of B bacilliformis infection. These diseases are not found in the United States, but they are common in the Peruvian Andes. Verruga peruana is characterized by subcutaneous nodules consisting of neovascularization, somewhat similar to bacillary angiomatosis.
