1. CAT-SCRATCH FEVER

2. Overview  Cat-scratch disease is a slowly progressive, self-limiting, chronic lymphadenopathy that usually occurs in children.  Cat-scratch disease, as its name implies, is transmitted to humans by the scratch or bite of a cat that has Bartonella henselae in its saliva and on its nails.

3. Etiology   Bartonella henselae is a rod-shaped gram-negative organism that causes cat-scratch disease.

4. 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.

5.   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.

7.   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.

8.   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.

9.   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.

10.   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).

11.   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.

12.   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.

13.   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.

14.   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.

15. 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.

16. Epidemiology   Cats 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.

17. 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.

18. 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.

19.   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.

20.   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.

21.   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.

22.   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.

23. 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.

24.   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.

25. 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.

26. 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.

27. Recommended Treatments for Diseases Caused by Bartonella henselae DiseaseTreatment Classic cat-scratch diseaseNone If lymph node swelling is extensive; azithromycin Leber neuroretinitis, Parinaud oculoglandular syndrome Doxycycline and rifampin Cat-scratch disease encephalopathy Doxycycline and rifampin EndocarditisDoxycycline and gentamicin Other medications that have been shown effective in treating atypical cat scratch disease include ciprofloxacin and trimethoprim- sulfamethoxazole.