Cat-scratch STEPHEN A. KLOTZ, MD; VOICHITA IANAS, MD; and SEAN P. ELLIOTT, MD, University of Arizona, Tucson, Arizona

Cat-scratch disease is a common that usually presents as tender . It should be included in the of of unknown origin and any lymphadenopathy syndrome. Asymptomatic, bactere- mic cats with henselae in their saliva serve as vectors by biting and clawing the skin. Cat are respon- sible for horizontal transmission of the disease from cat to cat, and on occasion, arthropod vectors (fleas or ) may transmit the disease to humans. Cat-scratch disease is commonly diagnosed in children, but adults can present with it as well. The causative microorganism, B. henselae, is difficult to culture. Diagnosis is most often arrived at by obtaining a history of exposure to cats and a serologic test with high titers (greater than 1:256) of immunoglobulin G antibody to B. henselae. Most cases of cat-scratch disease are self-limited and do not require antibiotic treatment. If an antibiotic is chosen, azithromycin has been shown in one small study to speed recovery. Infrequently, cat-scratch disease may present in a more disseminated form with hepatosplenomegaly or , or with bacillary in patients with AIDS. (Am Fam Physician. 2011;83(2):152-155. Copyright © 2011 American Academy of Family Physicians.) ▲ Patient information: at-scratch disease (CSD) is the Although a history of exposure to cats is A handout on cat-scratch most common human infection important, it is not absolutely necessary to disease is available at caused by Bartonella species. make the diagnosis. http://familydoctor. 3 org/024.xml. CSD has worldwide distribution After contact with an infected kitten or C and has been described in all areas of North cat, patients can develop a primary skin America. In northern temperate zones, it lesion that starts as a vesicle at the inocu- occurs more often in August through Octo- lation site. A small number of patients do ber, usually in humid, warm locales. There not recall contact with cats or having skin are an estimated 22,000 new cases of CSD lesions. Regional lymphadenopathy develops per year in the United States.1 one to two weeks later and is usually ipsi- is the microorganism lateral. According to one study, 46 percent responsible for CSD. It is found in feline of patients develop lymphadenopathy of the erythrocytes and fleas, which can contami- upper extremities, 26 percent develop lymph- nate saliva and then be introduced into adenopathy of the and jaw, 18 percent humans through biting and clawing by cats. develop lymphadenopathy of the groin, and The cat , Ctenocephalides felis, is the vec- 10 percent develop lymphadenopathy of other tor responsible for horizontal transmission areas (pre- and postauricular, clavicular, and of the disease from cat to cat, and its bite can chest).4 In these patients, lymph nodes are also infect humans.2 In addition, bites swollen, tender, and may eventually suppu- may transmit the bacterium to humans. rate.4 Seventy-five percent of patients develop Approximately 50 percent of cats harbor aching, , and , and 9 percent B. henselae and are entirely asymptomatic.3 develop low-grade fever.4 Lymphadenopathy can persist for several months. Musculo- Clinical Presentation skeletal manifestations, especially , CSD is commonly diagnosed in children, arthralgia, and , are common and but adults may also present with the disease. occur in more than 10 percent of patients.5 It should be suspected in patients with ten- Visceral involvement has been reported6 and der regional unilateral lymphadenopathy, usually presents as hepatosplenomegaly with especially if there is a history of exposure to or without lymphadenopathy.7 Prolonged kittens or cats. CSD causes local lymphade- in children has been nopathy in 85 to 90 percent of patients.4 The described.8,9 differential diagnosis includes other causes Rare cases of meningoencephalitis, endo- of unilateral lymphadenopathy (Table 1). carditis, and eye involvement have occurred

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Cat-scratch disease should be included in the differential diagnosis in any C 2, 3 patient with lymphadenopathy. The diagnosis of cat-scratch disease is usually confirmed by a history of cat C 3, 19 exposure and antibodies to Bartonella henselae. Most cases of cat-scratch disease are self-limited and do not require B 4, 21, 23 antibiotic therapy. If an antibiotic is chosen to treat cat-scratch disease, azithromycin B 22 (Zithromax) appears to be effective at reducing the duration of lymphadenopathy.

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evi- dence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.xml. in immunocompetent patients.10-12 One neu- peliosis.13 is caused only by rologic manifestation of CSD is encephalop- B. henselae and involves the liver and some- athy, which manifests as severe and times the . acute confusion one to six weeks after the can be caused by B. henselae and Bartonella onset of lymphadenopathy.10 Seizures may quintana, and usually involves the skin and occur, and occasionally patients have focal lymph nodes, but can also involve bone and neurologic deficits that are self-limiting, but internal organs. Lesions consist of single or can last up to one year. Parinaud oculoglan- multiple red to purple papules.13 Bacillary dular syndrome is the most common ocular angiomatosis was first described in patients manifestation12 and consists of - with AIDS with very low CD4 cell counts.14 tous conjunctivitis and ipsilateral periauric- Evidence for previous Bartonella infection ular lymphadenopathy. Neuroretinitis can is common in patients with human immu- occur in CSD and manifests as acute unilat- nodeficiency infection living in Rio eral visual field loss secondary to optic nerve de Janeiro, Brazil,15 and Bartonella infection and star-shaped macular . was detected in 18 percent of febrile patients In immunosuppressed patients, B. hense- with human virus infec- lae can cause bacillary angiomatosis and tion living in San Francisco, Calif.16

Diagnostic Testing The Bartonella species are difficult to cul- Table 1. Select Common ture, and culture is not routinely recom- That May Be Confused with mended. Serology is the best initial test and Cat-scratch Disease Unilateral Lymphadenopathy can be performed by indirect fluorescent assay or enzyme-linked immunosorbent assay. Although more sensitive than culture, Infectious causes serologic tests lack specificity because many lymphadenopathy* asymptomatic persons have positive serology Epstein-Barr virus lymphadenopathy* because of previous (often asymptomatic) Group A streptococcal exposure.17 The percentage of the general Human immunodeficiency virus lymphadenopathy* population that has a positive serologic test Nontuberculous mycobacterial lymphadenitis varies widely, but appears to be higher in 17 Staphylococcus aureus adenitis cat owners. Immunoglobulin G titers less lymphadenopathy* than 1:64 suggest the patient does not have Noninfectious causes current Bartonella infection. Titers between Malignancy (, [in children]) 1:64 and 1:256 represent possible infec- tion; repeat testing should be performed in *—Usually diffuse lymphadenopathy. these patients in 10 to 14 days. Titers greater than 1:256 strongly suggest active or recent

January 15, 2011 ◆ Volume 83, Number 2 www.aafp.org/afp American Family Physician 153 Cat-scratch Disease

infection.18,19 A positive immunoglobulin M In a study from 1985, a single inves- test suggests acute disease, but production of tigator evaluating 1,200 patients with immunoglobulin M is brief. Immunoglobu- lymphadenopathy who were believed to have lin G has significant cross-reactivity between CSD found that antibiotics were rarely used.4 B. henselae and B. quintana. Polymerase Physicians today occasionally employ antibi- chain reaction can detect different Barton- otics in CSD. The results of one randomized ella species; specificity is very trial support the use of oral azithromycin Bacillary angiomatosis and high, but the sensitivity is lower (Zithromax) for mild to moderate disease peliosis have high rates than with serology. for five days (500 mg on day 1, followed by Consequently, when a child 250 mg daily for four more days for patients of relapse and should be or adult presents with unilat- weighing more than 100 lb [45.5 kg]; or 10 treated with a prolonged eral lymphadenopathy,3 the mg per kg on day 1, followed by 5 mg per kg course of antibiotics. physician should consider the for four more days for patients weighing 100 differential diagnoses provided lb or less).22 In this small study of 29 adult in Table 1. A history of cat exposure should patients, the use of azithromycin led to a be sought and appropriate tests ordered, more rapid resolution of lymphadenopathy including serology for CSD. A history of cat than placebo; eight of 14 patients taking exposure, lymphadenopathy, and elevated azithromycin had more than 80 percent antibodies to B. henselae detected by enzyme- resolution at 30 days compared with one of linked immunosorbent assay or indirect flu- 15 patients in the control group.22 The Infec- orescent assay confirms the diagnosis. tious Diseases Society of America guidelines biopsy is not indicated for regarding CSD are equivocal about the rou- most patients; however, it is appropriate in tine use of antibiotics,23 whereas another patients whose lymph nodes fail to involute panel of authorities recommended against and in whom diagnosis is uncertain. Lymph the use of antibiotics in patients with mild node specimens in patients with CSD show or uncomplicated disease.21 Other antibi- and stellate granulo- otics that have been used in CSD include mas. B. henselae is a small, curved, aerobic rifampin, ciprofloxacin (Cipro), trime- gram-negative bacillus that stains with sil- thoprim/sulfamethoxazole (Bactrim, Sep- ver. In bacillary angiomatosis, lobular pro- tra), and gentamicin.24 liferation of small blood vessels occurs with Treatment of bacillary angiomatosis and the presence of bacilli in adjacent connec- peliosis, which have high rates of relapse, tive tissue and blood vessels. In a series of with oral or for a 786 lymph node specimens from patients prolonged course of three to four months has in whom CSD was suspected, only 245 benefited patients. Treatment with cell wall– (31.2 percent) had evidence of CSD. Thir- active antibiotics has not.13,23 Treatment of teen of the 245 patients had concurrent neurologic disease has not been evaluated, mycobacteriosis or . It is prudent but a combination of erythromycin or doxy- that physicians follow up with patients who cycline plus rifampin for four to six weeks have unilateral lymphadenopathy, even may be effective as suggested by case reports those with confirmed CSD.20 of neuroretinitis.10

Treatment The Authors Treatment of CSD depends on the disease STEPHEN A. KLOTZ, MD, is a professor of medicine and presentation. Most patients, especially chil- chief of the Section of Infectious Diseases at the University dren, have self-limited lymphadenopathy of Arizona, Tucson. lasting two to eight weeks and do not require VOICHITA IANAS, MD, is a senior fellow in adult infectious antibiotics. Up to 14 percent of persons diseases at the University of Arizona. develop dissemination to the liver, spleen, SEAN P. ELLIOTT, MD, is a professor of pediatrics in the 4 eye, or central nervous system and antibiot- Section of Pediatric Infectious Diseases at the University ics may help.21 of Arizona.

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Address correspondence to Stephen A. Klotz, MD, Uni- 13. Koehler JE, Tappero JW. Bacillary angiomatosis and bac- versity of Arizona, 1501 N. Campbell Ave., Tucson, AZ illary peliosis in patients infected with human immuno- 85724 (e-mail: [email protected]). Reprints are not deficiency virus. Clin Infect Dis. 1993;17(4):612-624. available from the authors. 14. Regnery RL, Childs JE, Koehler JE. associated with Bartonella species in persons infected with human Author disclosure: Nothing to disclose. immunodeficiency virus. Clin Infect Dis. 1995;21(suppl 1):S94-S98. REFERENCES 15. Lamas CC, Mares-Guia MA, Rozental T, et al. Bartonella spp. infection in HIV positive individuals, their pets and 1. Jackson LA, Perkins BA, Wenger JD. Cat scratch disease ectoparasites in Rio de Janeiro, Brazil: serological and in the United States: an analysis of three national data- molecular study. Acta Trop. 2010;115(1-2):137-141. bases. Am J Public Health. 1993;83(12):1707-1711. 16. Koehler JE, Sanchez MA, Tye S, et al. Prevalence of 2. Zangwill KM, Hamilton DH, Perkins BA, et al. Cat Bartonella infection among human immunodeficiency scratch disease in Connecticut. Epidemiology, risk fac- virus-infected patients with fever. Clin Infect Dis. tors, and evaluation of a new diagnostic test. N Engl J 2003;37(4):559-566. Med. 1993;329(1):8-13. 17. Bergmans AM, Peeters MF, Schellekens JF, et al. Pitfalls 3. Massei F, Gori L, Macchia P, Maggiore G. The expanded and fallacies of cat scratch disease serology: evalua- spectrum of in children. Infect Dis Clin tion of Bartonella henselae-based indirect fluorescence North Am. 2005;19(3):691-711. assay and enzyme-linked immunoassay. J Clin Micro- 4. Carithers HA. Cat-scratch disease. An overview biol. 1997;35(8):1931-1937. based on a study of 1,200 patients. Am J Dis Child. 18. Sander A, Posselt M, Oberle K, Bredt W. Seroprevalence 1985;139(11):1124-1133. of antibodies to Bartonella henselae in patients with cat 5. Maman E, Bickels J, Ephros M, et al. Musculoskeletal scratch disease and in healthy controls: evaluation and manifestations of cat scratch disease. Clin Infect Dis. comparison of two commercial serological tests. Clin 2007;45(12):1535-1540. Diagn Lab Immunol. 1998;5(4):486-490. 6. Margileth AM, Wear DJ, English CK. Systemic cat 19. Spach DH, Kaplan SL. Microbiology, epidemiology, clini- scratch disease: report of 23 patients with prolonged cal manifestations, and diagnosis of cat scratch disease. or recurrent severe bacterial infection. J Infect Dis. UpToDate. http://www.uptodate.com. Accessed Sep- 1987;155(3):390-402. tember 20, 2010. 7. Lenoir AA, Storch GA, DeSchryver-Kecskemeti K, et al. Granulomatous associated with cat scratch 20. Rolain JM, Lepidi H, Zanaret M, et al. Lymph node disease. Lancet. 1988;1(8595):1132-1136. biopsy specimens and diagnosis of cat-scratch disease. Emerg Infect Dis. 2006;12(9):1338-1344. 8. Tsujino K, Tsukahara M, Tsuneoka H, et al. Clinical impli- cation of prolonged fever in children with cat scratch 21. Rolain JM, Brouqui P, Koehler JE, Maguina C, Dolan MJ, disease. J Infect Chemother. 2004;10(4):227-233. Raoult D. Recommendations for treatment of human 9. Jacobs RF, Schutze GE. Bartonella henselae as a cause infections caused by Bartonella species. Antimicrob of prolonged fever and fever of unknown origin in chil- Agents Chemother. 2004;48(6):1921-1933. dren. Clin Infect Dis. 1998;26(1):80-84. 22. Bass JW, Freitas BC, Freitas AD, et al. Prospective ran- 10. Wong MT, Dolan MJ, Lattuada CP Jr, et al. Neuroreti- domized double blind placebo-controlled evaluation of nitis, aseptic meningitis, and lymphadenitis associated azithromycin for treatment of cat-scratch disease. Pedi- with Bartonella (Rochalimaea) henselae infection in atr Infect Dis J. 1998;17(6):447-452. immunocompetent patients and patients infected with 23. Stevens DL, Bisno AL, Chambers HF, et al.; Infectious human immunodeficiency virus type 1. Clin Infect Dis. Diseases Society of America. Practice guidelines for 1995;21(2):352-360. the diagnosis and management of skin and soft-tissue 11. Baorto E, Payne RM, Slater LN, et al. Culture-negative infections. Clin Infect Dis. 2005;41(10):1373-1406. caused by Bartonella henselae. J Pediatr. 24. Margileth AM. Antibiotic therapy for cat-scratch dis- 1998;132(6):1051-1054. ease: clinical study of therapeutic outcome in 268 12. Cunningham ET, Koehler JE. Ocular bartonellosis. Am J patients and a review of the literature. Pediatr Infect Dis Ophthalmol. 2000;130(3):340-349. J. 1992;11(6):474-478.

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