CAT-SCRATCH FEVER

General Goal: To know the major cause(s) of this disease, how it is transmitted, and the major manifestations of the disease.

Specific Educational Objectives: The student should be able to:

1. recite the most common causes of cat-scratch fever (shape and gram stain?).

2. describe the common means of transmission.

3. describe the major manifestations of this infection.

4. describe how you diagnose, treat and prevent this infection.

Reading: MEDICAL MICROBIOLOGY by P.R. Murray, K.S. Rosenthal, G.S. Kobayashi and M.A. Pfaller, 3rd Edition. pp. 287.

Lecture: Dr. Neal R. Chamberlain

References: 1. eMedicine: Cat Scratch Fever, Joseph R Lex, Jr, MD, Consulting Staff, Department of Emergency Medicine, Chestnut Hill Hospital. http://www.emedicine.com/cgi-bin/foxweb.exe/showsection@d:/em/ga?book=emerg&topicid=84

2. Chomel BB, Abbott RC, Kasten RW, Floyd-Hawkins KA, Kass PH, Glaser CA, Pedersen NC, Koehler JE. 1995. Bartonella henselae prevalence in domestic cats in California: risk factors and association between bacteremia and antibody titers. J Clin Microbiol Sep;33(9):2445-50

3. Bass JW, Freitas BC, Freitas AD, et al. Prospective randomized double blind placebo-controlled evaluation of azithromycin for treatment of cat-scratch disease. Pediatr Infect Dis J. 1998;17:447-452.

4. Jared M. Frandson, MPH, Julie Rawlings, MPH, Christine R. Burgess, MPH, Kate A. Hendricks, MD, MPH&TM; Texas Department of Health, Austin. Cat-Scratch Disease in Texas. 2000. Infect Med 17(10):690-694. http://id.medscape.com/SCP/IIM/2000/v17.n10/m1710.03.fran/pnt-m1710.03.fran.html

5. Jacomo V, PJ Kelly, and D Raoult, Natural History of Bartonella Infections (an Exception to Koch's Postulate), 2002. Clin Diag Lab Immun, 9:8-18. http://cdli.asm.org/cgi/content/full/9/1/8?view=full&pmid=11777823

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 accompanied 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.
• 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.
• 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. 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.

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.

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 P-2 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.

Return to syllabus