Bartonella

Keywords

• Bartonella

• B. henselae

• CSD

• encephalopathy

• endocarditis

• flea

• granuloma

• hepatosplenomegaly

• inoculation papule

• lymphadenitis

• Parinaud oculoglandular syndrome

• stellate macular retinopathy

Etiology

Bartonella henselae can be cultured from the blood of healthy cats. B. henselae organisms are the small pleomorphic gram-negative bacilli visualized with Warthin-Starry stain in affected lymph nodes from patients with CSD. Development of serologic tests that showed prevalence of antibodies in 84–100% of cases of CSD, culturing of B. henselae from CSD nodes, and detection of B. henselae by polymerase chain reaction (PCR) in the majority of lymph node samples and pus from patients with CSD, confirmed the organism as the cause of CSD. Occasional cases of CSD may be caused by other organisms, including Bartonella clarridgeiae, B. grahamii , B. alsatica, and B. quintana .

Epidemiology

CSD is common, with >24,000 estimated cases per year in the United States. It is transmitted most frequently by cutaneous inoculation through the bite or scratch of a cat. However, transmission may occur through other routes, such as flea bites. Most patients (87–99%) have had contact with cats, many of which are kittens <6 mo old, and >50% of patients have a definite history of a cat scratch or bite. Cats have high-level Bartonella bacteremia for months without any clinical symptoms; kittens are more frequently bacteremic than adult cats. Transmission between cats occurs through the cat flea, Ctenocephalides felis. In temperate zones, most cases occur between September and March, perhaps in relation to the seasonal breeding of domestic cats or to the close proximity of family pets in the fall and winter. In tropical zones, there is no seasonal prevalence. Distribution is worldwide, and infection occurs in all races.

Cat scratches appear to be more common among children, and males are affected more often than females. CSD is a sporadic illness; usually only 1 family member is affected, even though many siblings play with the same kitten. However, clusters do occur, with family cases within weeks of one another. Anecdotal reports have implicated other sources, such as dog scratches, wood splinters, fishhooks, cactus spines, and porcupine quills.

Pathogenesis

The pathologic findings in the primary inoculation papule and affected lymph nodes are similar. Both show a central avascular necrotic area with surrounding lymphocytes, giant cells, and histiocytes. Three stages of involvement occur in affected nodes, sometimes simultaneously in the same node. The 1st stage consists of generalized enlargement with thickening of the cortex and hypertrophy of the germinal center and with a predominance of lymphocytes. Epithelioid granulomas with Langerhans giant cells are scattered throughout the node. The 2nd stage is characterized by granulomas that increase in density, fuse, and become infiltrated with polymorphonuclear leukocytes, with beginning central necrosis. In the 3rd stage, necrosis progresses with formation of large, pus-filled sinuses. This purulent material may rupture into surrounding tissue. Similar granulomas have been found in the liver, spleen, and osteolytic lesions of bone when those organs are involved.

Clinical Manifestations

After an incubation period of 7-12 days (range: 3-30 days), 1 or more 3-5 mm red papules develop at the site of cutaneous inoculation, often reflecting a linear cat scratch. These lesions are often overlooked because of their small size but are found in at least 65% of patients when careful examination is performed ( Fig. 236.1 ). Lymphadenopathy is generally evident within 1-4 wk ( Fig. 236.2 ). Chronic regional lymphadenitis is the hallmark, affecting the1st or 2nd set of nodes draining the entry site. Affected lymph nodes in order of frequency include the axillary, cervical, submandibular, preauricular, epitrochlear, femoral, and inguinal nodes. Involvement of >1 group of nodes occurs in 10–20% of patients, although at a given site, half the cases involve several nodes.

Nodes involved are usually tender and have overlying erythema but without cellulitis. They usually range between 1 and 5 cm in size, although they can become much larger. From 10–40% eventually suppurate. The duration of enlargement is usually 1-2 mo, with persistence up to 1 yr in rare cases. Fever occurs in approximately 30% of patients, usually 38-39°C (100.4-102.2°F). Other nonspecific symptoms, including malaise, anorexia, fatigue, and headache, affect less than one third of patients. Transient rashes, which may occur in approximately 5% of patients, are mainly truncal maculopapular rashes. Erythema nodosum, erythema multiforme, and erythema annulare are also reported.

CSD is usually a self-limited infection that spontaneous resolves within a few weeks to months. The most common ocular presentation of CSD is Parinaud oculoglandular syndrome, which is unilateral conjunctivitis followed by preauricular lymphadenopathy and occurs in 5% of patients with CSD ( Fig. 236.3 ). Direct eye inoculation as a result of rubbing with the hands after cat contact is the presumed mode of spread. A conjunctival granuloma may be found at the inoculation site. The involved eye is usually not painful and has little or no discharge but may be quite red and swollen. Submandibular or cervical lymphadenopathy may also occur.

More severe, disseminated illness occurs up to 14% of patients and is characterized by presentation with high fever, often persisting for several weeks. Other prominent symptoms include significant abdominal pain and weight loss. Hepatosplenomegaly may occur, although hepatic dysfunction is rare ( Fig. 236.4 ). Granulomatous changes may be seen in the liver and spleen. Another common site of dissemination is bone, with the development of multifocal granulomatous osteolytic lesions, associated with localized pain but without erythema, tenderness, or swelling. Other, uncommon manifestations are neuroretinitis with papilledema and stellate macular exudates, encephalitis, endocarditis, and atypical pneumonia.

Diagnosis

In most cases the diagnosis can be strongly suspected on clinical grounds in a patient with history of exposure to a cat. Serologic testing can be used to confirm the diagnosis. Most patients have elevated IgG antibody titers at presentation. However, the IgM response to B. henselae has frequently resolved by the time testing is considered. There is cross-reactivity among Bartonella spp., particularly B. henselae and B. quintana.

If tissue specimens are obtained, bacilli may be visualized with Warthin-Starry and Brown-Hopps tissue stains. Bartonella DNA can be identified through PCR analysis of tissue specimens. Culturing of the organism is not generally practical for clinical diagnosis.

Laboratory Findings

Routine laboratory tests are not helpful. The erythrocyte sedimentation rate is often elevated. The white blood cell count may be normal or mildly elevated. Hepatic transaminases are often normal but may be elevated in systemic disease. Ultrasonography or CT may reveal many granulomatous nodules in the liver and spleen; the nodules appear as hypodense, round, irregular lesions and are usually multiple. However, CSD presenting as a solitary splenic lesion has been reported.

Treatment

Antibiotic treatment of CSD is not always needed and is not clearly beneficial. For most patients, treatment consists of conservative symptomatic care and observation. Studies show a significant discordance between in vitro activity of antibiotics and clinical effectiveness. For many patients, diagnosis is considered in the context of failure to respond to β-lactam antibiotic treatment of presumed staphylococcal lymphadenitis.

A small prospective study of oral azithromycin (500 mg on day 1, then 250 mg on days 2-5; for smaller children, 10 mg/kg/24 hr on day 1 and 5 mg/kg/24 hr on days 2-5) showed a decrease in initial lymph node volume in 50% of patients during the 1st 30 days, but after 30 days there was no difference in lymph node volume. No other clinical benefit was found. For the majority of patients, CSD is self-limited, and resolution occurs over weeks to months without antibiotic treatment. Azithromycin, clarithromycin, trimethoprim-sulfamethoxazole (TMP-SMX), rifampin, ciprofloxacin, and gentamicin appear to be the best agents if treatment is considered.

Suppurative lymph nodes that become tense and extremely painful should be drained by needle aspiration , which may need to be repeated. Incision and drainage of nonsuppurative nodes should be avoided because chronic draining sinuses may result. Surgical excision of the node is rarely necessary.

Children with hepatosplenic CSD appear to respond well to rifampin at a dose of 20 mg/kg for 14 days, either alone or in combination with a 2nd agent such as azithromycin, gentamicin, or TMP-SMX.

Complications

Encephalopathy can occur in as many as 5% of patients with CSD and typically manifests 1-3 wk after the onset of lymphadenitis as the sudden onset of neurologic symptoms, which often include seizures, combative or bizarre behavior, and altered level of consciousness. Imaging studies are generally normal. The cerebrospinal fluid is normal or shows minimal pleocytosis and protein elevation. Recovery occurs without sequelae in almost all patients but may take place slowly over many months.

Other neurologic manifestations include peripheral facial nerve paralysis, myelitis, radiculitis, compression neuropathy, and cerebellar ataxia. One patient has been reported to have encephalopathy with persistent cognitive impairment and memory loss.

Stellate macular retinopathy is associated with several infections, including CSD. Children and young adults present with unilateral or rarely bilateral loss of vision with central scotoma, optic disc swelling, and macular star formation from exudates radiating out from the macula. The findings usually resolve completely, with recovery of vision, generally within 2-3 mo. The optimal treatment for the neuroretinitis is unknown, although treatment of adults with doxycycline and rifampin for 4-6 wk has had good results.

Hematologic manifestations include hemolytic anemia, thrombocytopenic purpura, nonthrombocytopenic purpura, and eosinophilia. Leukocytoclastic vasculitis, similar to Henoch-Schönlein purpura, has been reported in association with CSD in one child. A systemic presentation of CSD with pleurisy, arthralgia or arthritis, mediastinal masses, enlarged nodes at the head of the pancreas, and atypical pneumonia also has been reported.

Prognosis

The prognosis for CSD in a normal host is generally excellent, with resolution of clinical findings over weeks to months. Recovery is occasionally slower and may take as long as 1 yr.

Prevention

Person-to-person spread of Bartonella infections is not known. Isolation of the affected patient is not necessary. Prevention would require elimination of cats from households, which is not practical or necessarily desirable. Awareness of the risk of cat (and particularly kitten) scratches should be emphasized to parents. Cat scratches or bites should be washed immediately. Cat flea control is helpful.