CAT-SCRATCH FEVERCAT-SCRATCH FEVER

OverviewOverview Cat-scratch disease is a slowly Cat-scratch disease is a slowly

progressive, self-limiting, chronic progressive, self-limiting, chronic lymphadenopathy that usually occurs in lymphadenopathy that usually occurs in children. children.

Cat-scratch disease, as its name implies, Cat-scratch disease, as its name implies, is transmitted to humans by the scratch is transmitted to humans by the scratch or bite of a cat that has or bite of a cat that has BartonellaBartonella henselae henselae in its saliva and on its nails.in its saliva and on its nails.

Etiology

Bartonella henselae is a rod-shaped gram-negative organism that causes

cat-scratch disease.

Manifestations

B henselae can cause several different diseases depending on the status of a person’s immune system.

However, individuals with a normally functioning immune system who acquire this organism usually manifest classic cat-scratch disease with fever and a regional lymphadenopathy.

Occasionally, the organism can cause symptoms associated with its ability to infect the brain and retina.

Immunocompromised hosts can develop the diseases illustrated in the figure below as well as bacillary angiomatosis and peliosis hepatica.

Classic cat-scratch disease has an incubation period of 1–2 weeks.

In 50–90% of cases, a 0.5- to 1-cm brownish papule or pustule forms at the site of the scratch or bite and is considered an indicator of cat -scratch disease.

Regional lymphadenopathy follows within 3–10 days and is often accom-panied by fever, malaise, and anorexia.

Generally, the lymph nodes are 1–5 cm in diameter and proximal to the site of B henselae inoculation.

The most commonly involved nodes are in the axillary, epitrochlear, cervical, and supraclavicular areas.

Over a period of weeks to months, lymph nodes may become fluctuant or suppurative or may spontaneously regress.

Full resolution generally occurs within 1 month, with or without treatment. A biopsy of lymph nodes will reveal hyperplasia, granuloma formation, and suppuration.

An increasing number of atypical manifestations of B henselae infections are now being recognized as atypical cat-scratch disease.

These include complications in the retina (e.g., Parinaud oculoglandular syndrome and Leber neuroretinitis), central nervous system (e.g., cat-scratch disease encephalopathy and neuropathy), heart (e.g., endocarditis), and skin (e.g., erythema nodosum).

Leber neuroretinitis is also known as idiopathic stellate neuroretinitis results in a loss of visual acuity and a macular star.

Patients with Parinaud oculoglandular syndrome have conjunctival inflammation with preauricular adenopathy and a characteristic granulomatous lesion in the conjunctiva.

The most serious complication of classic catch-scratch disease is cat-scratch encephalopathy, with manifestations of headache, tonic-clonic seizures, combative behavior, and coma.

These symptoms typically occur suddenly, 1–8 weeks after the onset of lymphadenopathy.

Recovery is usually complete.

There have been no deaths from cat-scratch disease encephalopathy confirmed at this time.

Cat-scratch disease encephalopathy occurs in a small number of patients who have cat-scratch disease.

Immunocompromised patients are not able to keep the Bartonella henselae in the regional lymph nodes.

The bacteria can then spread to other parts of the body via the bloodstream, resulting in bacillary angiomatosis and peliosis hepatica.

Liver biopsies reveal cystic blood filled spaces in patient with peliosis hepatica.

Epidemiology There are about 25,000 cases of cat-scratch

disease diagnosed each year. Most cases of cat-scratch disease occur

during the late summer and early winter months.

About 80–90% of cases of cat-scratch disease occur in patients younger than 21 years of age.

B henselae infects kittens and can remain in the bloodstream for up to 1 year. Bacteremic cats are more likely to infect their owners following bites or scratches.

EpidemiologyCats living in the warmer humid climates

of the United States (i.e., the southeast) are more likely to be infected with Bartonella henselae.

Fleas (Ctenocephalides felis) carry B henselae and can transmit the bacterium from cat to cat.

Exposure to kittens is a greater risk factor for contracting human B henselae infection than exposure to adult cats.

Epidemiology

B henselae can be transmitted to humans following contact with cats (scratches, bites) and possibly following contact with cat fleas.

Recent studies have shown that B henselae can live in ticks but as yet there have been no confirmed cases of tick transmission this organism to humans.

Pathogenesis Cats are infected with B henselae following the bite of a

flea that carries the bacteria and then transmits them to humans through a bite or a scratch. 

B henselae enters the cat’s bloodstream, where it can live in the erythrocytes for several months to a year.

The cat appears to be asymptomatic while B henselae is in the bloodstream. Researchers do not completely understand how the organism is transmitted from the cat’s bloodstream to their saliva.

It is likely that the nails are contaminated with saliva that contains B henselae after they groom themselves with their tongue.

Once in the tissue of an immunocompetent human following a cat scratch or bite, B henselae are phagocytized by macrophages but are not killed by the macrophage.

The bacteria are transported to the lymph nodes that are in the region of the bite or scratch. The macrophages produce several proinflammatory cytokines (e.g., interleukin 1, [IL-1] and tumor necrosis factor alpha [TNF-]) which recruit neutrophils and macrophages to the lymph node causing the node to swell.

The inflammatory reaction within the node is granulomatous and consists of a central zone of necrosis, an inner rim of palisading macrophages, and an outer rim of lymphocytes and nonpalisading macrophages.

IL-1 induces the fever associated with cat-scratch disease and activates T-helper lymphocytes in the node following presentation of B henselae antigens to the T-cell receptors.

B henselae occasionally can escape the lymph node of immunocompetent hosts and invade the central nervous system, heart, or skin via the bloodstream, causing the atypical manifestations mentioned above.

There is very little known about the pathogenesis of these complications; however, the complications all resolve completely with few or no sequelae following treatment.

The activated T-helper lymphocytes produce TNF-gamma, which induces the macrophages in the lymph node to produce nitric oxide.

Nitric oxide intermediates, following reaction with oxygen in the tissues, are produced, which then kill the B henselae in the lymph node and eliminate the infection.

The inflammation in the node eventually resolves and the swelling regresses.

Diagnosis

A serologic assay (indirect fluorescent antibody assay) is usually performed to confirm a diagnosis of classic cat-scratch disease.

PCR specific for B henselae from a lymph node biopsy can also be used to confirm a diagnosis of cat-scratch disease but is not always available.

Histopathological features from a lymph node biopsy can be helpful but are not pathognomonic for cat-scratch disease include granuloma formation, stellate abscesses, and lymphocytic infiltrates.

A Warthin-Starry silver stain or a Brown-Hopp tissue Gram stain of a lymph node biopsy revealing the small, curved, bacilli can aid in diagnosis.

Therapy and Prevention The efficacy of antibiotic therapy currently

has not been proven for classic cat-scratch disease in immunocompetent hosts.

Symptomatic care for most patients is indicated. Swollen lymph nodes will resolve within 1–6 months.

The infection usually will resolve in 90% of patients without treatment, however, there may be some clinical benefit to treatment with antibiotics such as azithromycin if lymph node swelling is extensive. 

Table: lists treatment recommendations for classic and atypical cat-scratch disease.

Disposal of the cat to prevent the disease is not recommended, since the cat will only carry B henselae for a limited period of time; declawing appears to make no difference. Flea control measures should be undertaken if there is a cat in the home environment.

Recommended Treatments for Diseases Caused by Bartonella henselae

DiseaseTreatment DiseaseTreatment

Classic cat-scratch disease None

If lymph node swelling is extensive; azithromycin

Leber neuroretinitis, Parinaud oculoglandular syndrome 

Doxycycline and rifampin

Cat-scratch disease encephalopathy

Doxycycline and rifampin

Endocarditis Doxycycline and gentamicin

Other medications that have been shown effective in treating atypical cat scratch disease include ciprofloxacin and trimethoprim-sulfamethoxazole.