The editors and current author would like to thank and acknowledge the significant contribution of the previous author of this chapter from the 2004 first edition, Dr. Judy Makowski Vincent. This current second edition chapter is a revision and update of the original author's work.
A 4-year-old girl presents to the pediatric clinic with a chief complaint of a slowly enlarging mass in her right axilla for the past two weeks. She has had no fever, but has had some loss of appetite. The mass was initially small and did not hurt; however, it has now grown to the size of a tennis ball and has become painful. She cannot lower her arm due to the pain from the mass, and she carries her arm extended at 90 degrees to her body. Movement of her arm exacerbates the pain. She does have a 3-month-old kitten at home that she "rescued from a sewer". It was covered with fleas when she found it. It playfully bites and scratches her. Three weeks ago it scratched her right thumb. The scratch healed, but a small "wart" has developed in the line of the scratch. There is a scab on the wart and her mother has tried to squeeze the wart, but no pus has come out.
Exam: VS T 37.2C, RR 18, P 102, BP 100/60. She is alert and very cooperative. HEENT is negative. Neck is supple without adenopathy. Chest is clear. Heart regular without murmur. Abdomen exam is normal without hepatosplenomegaly. Neurologic exam is normal (mental status, gait, strength, and reflexes). Her right axilla reveals an 7 X 7 cm firm, tender, mobile, warm, non-erythematous, non-fluctuant mass that is consistent with an enlarged axillary lymph node. Her right thumb has a 1 cm linear, non-inflamed, healing scar that is consistent with a kitten scratch. In the middle of the linear scar, there is a 3 mm brownish-red papule with a small central crust.
Lab: CBC WBC 8.0, 62% segs, 10% bands. Ultrasonography of the mass reveals that it is a matted group of about 5 lymph nodes, which are mostly solid in appearance. There is evidence of a small amount of necrosis at the periphery of one of the lymph nodes.
Impression: Lymphadenopathy due to cat scratch disease.
Clinical course: Because the axillary node is enlarged and painful, you elect to treat her with oral azithromycin at a dose of 10 mg/kg/day for the first day and 5 mg/kg/day for the next 4 days. Serology for Bartonella henselae is obtained, and the result returns one week later with an IgG of 1:512 (a positive result is a value greater than 1:64). The node remains the same size for a week and then begins to get smaller. The adenopathy resolves in one month.
Cat Scratch Disease (CSD) is a multisystem disease caused by Bartonella henselae, a small, intracellular, anaerobic gram-negative bacillus. The organism was first identified in lymph nodes of patients with CSD in 1983 at the Walter Reed Army Medical Center in Washington, DC. Overall, the incidence of CSD in the US is about 9.3 cases per 100,000 population per year. It is also more commonly seen in the fall and winter. Seroprevalence is highest in regions with warm, humid climates, which also have a higher prevalence and degree of cat flea infestation. The southeastern United States, Hawaii, California, the Pacific Northwest, and the south central plains have the highest average B. henselae antibody prevalences. Alaska, the Rocky Mountains-Great Plains region, and the Midwest have the lowest average B. henselae antibody prevalences.
Although cats are the typical host of the bacteria and up to 75% of pet cats are seropositive, B. henselae has not been found to cause disease in cats. B. henselae bacteremia can occur in flea-infested kittens and strays, but is less common in pet cats after one year of age. The organism is transmitted among cats by the cat flea, Ctenocephalides felis. The flea is not responsible for cat to human transmission. B. henselae is transmitted to humans by a cat scratch or bites, which are typically thought of as minor wounds upon initial medical evaluation. Human to human transmission has not been found to occur.
In the early stages of immunocompetent patients with CSD, biopsies of lymph nodes and involved skin areas may reveal lymphoid hyperplasia and arteriolar proliferation. As it progresses, granulomas develop and may contain multinucleated giant cells, in addition to microabscesses due to necrosis and infiltrating neutrophils. In immunocompromised patients, the response is vasculoproliferative with neutrophilic infiltration. A Warthin-Starry silver stain can help to diagnose patients with CSD with the presence of bacilli, as B. henselae is known to be argyrophilic and takes up the silver stain. Bacilli are most commonly found as single organisms, as chains, or also in clumps in the walls of blood vessels, in red blood cells, in macrophages lining the sinuses, or in areas of necrosis. However, the absence of bacilli on the silver stain does not rule out CSD, as it is difficult to visualize the small B. henselae. B. henselae may also be grown by plating the patient’s lymph node aspirate or blood from the infected kitten directly onto chocolate agar and incubating it with 6% carbon dioxide at 35°C for 60 days. After 14 days, B. henselae may appear as grayish-yellow, pinpoint colonies on the plate. If no growth occurs within 60 days, the results may be interpreted as negative.
CSD can be diagnosed with serologic testing, including an immunofluorescent antibody (IFA) or enzyme immunoassay (EIA) test. The IFA test can be obtained from the CDC and measures IgG to B. henselae with a high sensitivity (88-100%) and specificity (92-98%). The EIA measures both IgG and IgM, is also highly specific (98-99%), but is less sensitive (82%) than the IFA. The problem with serologic testing is that the timing of the antibodies varies between patients and in relation to the clinical course of CSD. For example, in a recent study of 98 confirmed CSD patients, only 53% were found to be positive for IgM with EIA testing, and 92% of them were negative for IgM after 3 months. In addition, 92% were positive for IgG, but only 25% were still positive for IgG after 2 years. DNA polymerase chain reaction has also recently become an available method to detect B. henselae DNA, and can be used in combination with serology to diagnose CSD. However, this is not as useful since the organism needs to be incubated for up to 6 weeks, which may delay treatment and not be as efficient as using serologic testing for the diagnosis.
Up to 90% of patients found to have CSD develop typical CSD, which has a very predictable clinical course. Within a few days after a cat scratch or bite occurs, 2-3mm nontender, red-brown papules are found over, or in line with, the wound site. These progressively redden and form vesicles that crust over with time. About 1 to 2 weeks later, one or more regional lymph nodes gradually enlarge, becoming tender, warm and erythematous. Between 10% to 30% of lymph nodes will also eventually suppurate and the accumulated pus may need to be drained. Needle aspiration can be used to drain the pus; however if the pus is found to reaccumulate, the patient may need to undergo surgical incision of the node. It is not recommended to use incision and drainage for these nodes since this increases the risk of prolonged drainage and formation of sinus tracts.
The involved lymph nodes are typically found in the path of lymphatic drainage from the wound site, and most commonly affect the anterior cervical and axillary lymph nodes; however the inguinal, femoral, preauricular, supraclavicular, and epitrochlear nodes may also be involved. CSD lymph nodes tend to be rather large with an average diameter of 4 to 6 cm, but can be as large as 10 to 13 cm. After 1 to 2 weeks of growth, the lymph nodes tend to remain the same size for 2 to 3 weeks and then gradually resolve over a few additional weeks. Patients may also experience headaches, fever (30% to 50%, can be as high as 104°F, 40°C), malaise, anorexia, arthralgias, sore throat, and abdominal, neck, back or extremity pain. The disease is self-limited and usually resolves within 4 months, although some cases may last as long as 7 months.
Atypical CSD can also present with lymphadenopathy; however about 20% to 25% of cases present due to other reasons. One manifestation of atypical CSD is Parinaud Oculoglandular Syndrome (POGS). This syndrome consists of unilateral, non-suppurative, painless conjunctivitis and lymphadenopathy in the preauricular and submandibular areas. The site of inoculation with B. henselae is the affected eye, as opposed to a scratch or bite wound in typical CSS. The palpebral conjunctivae displays a characteristic granulomatous lesion that measures 2 mm to more than one cm in diameter. The conjunctivitis is non-suppurative and painless. POGS can also be caused by tuberculosis, tularemia, and syphilis. POGS is a predictable self-limited infection and typically has a good outcome in most cases.
About 10% to 30% of patients have also been found to present with fever without lymphadenopathy. Some of these patients are determined to have hepatosplenic microabscesses or osteolytic bone lesions. These patients tend to have daily fevers, which can be as high as 104°F (40°C), in addition to abdominal pain. In many cases, the physician neglects to ask about cat exposure until the patient had been febrile for several weeks. In a study of 146 patients presenting with fever of unknown origin (FUO), approximately 5% had CSD. Physical examination is usually only significant for a few cat scratch scars that may be overlooked without a known history of exposure. These patients do not typically have hepatosplenomegaly and their liver function tests are usually normal. The ESR may be moderately elevated (40 to 70 mm/hr). To diagnose hepatosplenic CSD, an ultrasound or CT scan is used which may reveal the presence of lytic lesions in the liver and spleen. In addition, B. henselae titers will be positive. Treatment involves giving the patient an IV aminoglycoside. However, the fever may not resolve for a few weeks. CSD has also been associated with the development of Henoch-Schonlein Purpura, as patients with HSP have been found to have significantly elevated levels of B. henselae antibody titers.
Atypical CSD is also associated with a range of neurologic complications, including headaches, cranial and peripheral nerve abnormalities, transverse myelitis, and encephalopathy. CSD encephalopathy has been associated with seizures, which occur in about half of cases and can lead to status epilepticus. Atypical CSD is also associated with Leber's stellate neuroretinitis. This neuroretinitis presents with painless unilateral loss of vision with central scotomata, optic disc swelling, macular star formation and complete recovery of vision within 1 to 3 months.
In immunocompromised hosts, B. henselae has been associated with bacillary angiomatosis and bacillary peliosis. Bacillary angiomatosis, also known as epithelioidangiomatosis, presents with firm, non-tender,skin-colored to reddish-purple papular or nodular lesions that can be up to a few centimeters in diameter. Bacillary peliosis involves vasoproliferation in the liver and spleen, with histological evaluation revealing blood-filled cysts.
Summary of Typical vs. Possible Atypical CSD Findings
Nontender, red-brown papules near wound site
Anorexia, malaise, arthralgias, sore throat, headache
Abdominal, neck, back, or extremity pain
Regional lymphadenopathy; 10% to 30% suppurate
Fever is seen in 30% to 50% of patients; may be as high as 104°F (40°C)
Atypical forms of CSD
Parinaud's Oculoglandular syndrome (POGS)
. . . Unilateral, nonsuppurative, painless conjunctivitis
. . . Lymphadenopathy in the preauricular and submandibular areas
. . . Liver and spleen microabscesses
. . . Possible abdominal pain
. . . Daily fevers
. . . Headaches, cranial and peripheral nerve abnormalities, transverse myelitis, and encephalopathy
. . . Seizures, status epilepticus
Most cases of typical CSD are self-limited. The infection usually resolves within 1 to 3 months with the use of supportive care, including warm compresses over the affected lymph nodes and antipyretics to reduce fevers. Antibiotics utilized in the treatment of B. henslae include gentamicin, azithromycin, trimethoprim-sulfamethoxazole, rifampin, ciprofloxacin, and doxycycline. However, antibiotics have been found to have little clinical significance in immunocompetent patients. The only prospective, randomized, double blind, placebo-controlled study that evaluated treating CSD lymphadenitis with a 5-day course of azithromycin found that half of the people who received azithromycin had smaller lymph node volumes by ultrasonography than those who were given the placebo with the first month after treatment. However, after 30 days there was no significant difference in lymph node improvement between the two groups (5,7). For immunocompromised patients with bacillary angiomatosis or bacilli peliosis, erythromycin, or doxycycline, with gentamicin or rifampin, should be used to treat the infection. Overall, antibiotics should be strongly considered for patients with severe or disseminated disease to help reduce recovery time and disease progression. Corticosteroids have also been found to help reduce symptoms of CSD, and may be helpful in patients with hepatosplenic disease, encephalopathy, or neuroretinitis that have not responded well to antibiotic therapy. However, more research needs to be done to confirm the effects of corticosteroids in patients with CSD (8).
Prevention of CSD is best accomplished with flea elimination in cats. There is currently no vaccine for either cats or humans to prevent CSD, and antibiotic prophylaxis is not recommended.
Although CSD may be associated with significant morbidity, it has a very good prognosis regardless of whether it was treated with antibiotics or not. As previously mentioned, most cases resolve within about 4 months with supportive care alone, although the affected lymph nodes may remain enlarged for several months. Immunocompromised patients with bacillary angiomatosis are at higher risk of death, but if treated appropriately with antibiotics the prognosis is good as well.
1. True/False: Cat scratch disease is usually transmitted by flea-infested kittens.
2. True/False: Adenopathy due to cat scratch disease usually develops rapidly, within a few hours.
3. True/False: When patients have hepatosplenic cat scratch disease, their liver function tests are always abnormal, and they always have concomitant lymphadenopathy.
4. True/False: Azithromycin is the only antibiotic that has been shown to be effective in the treatment of typical CSD lymphadenopathy in a double-blinded, placebo-controlled trial.
5. True/False: Serology is the diagnostic test of choice for cat scratch disease.
6. Which of the following statements regarding cat scratch disease is false?
. . . . . A. Kittens less than one year of age have higher antibody titers for B. henslae than older cats.
. . . . . B. Human to human transmission is the most common form of transmission.
. . . . . C. Ctenocephalidesfelis is the flea responsible for infection of the cats.
. . . . . D. Elimination of fleas is the best way to avoid cat-scratch disease.
1. Jameson P, Greene C, Regnery R, Dryden M, Marks A, Brown J, Cooper J. Prevalence of Bartonella henselae antibodies in pet cats throughout the regions of North America. J Infect Dis 1995;172:1145-1149.
2. Florin TA, Zaoutis TE, Zaoutis LB. Beyond cat scratch: widening spectrum of Bartonella henselae infection. Pediatrics 2008;121(5)e1413-25.
3. Kliegman R, Marcdante K, Jenson H, Behrman R. Nelson Essentials of Pediatrics 5th Edition, 2006
4. Guetzko L, Berman D, Chamizo, W. Index of Suspicion, Case Discussions of CSD. Pediatr Rev 2010;31(9)389-395.
5. English R. Catch Scratch Disease. Pediatr Rev 2006; 27(4): 123-128.
Answers to questions
2. False. Cat scratch disease adenopathy develops slowly, usually over 10-14 days.
3. False. With hepatosplenic CSD, LFTs are usually normal, and only 50% of patients have concomitant lymphadenopathy.
6. B. Human to human transmission does not occur. Humans are infected by cats.