CAT SCRATCH DISEASE

Microbiology, epidemiology, clinical manifestations, and diagnosis

AuthorsDavid H Spach, MDSheldon L Kaplan, MD Section EditorsStephen B Calderwood, MDMorven S Edwards, MD Deputy EditorAnna R Thorner, MDLast literature review version 17.1: January 2009 | This topic last updated: May 30, 2008 (More)

INTRODUCTION

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Cat scratch disease (CSD) is an infectious disease characterized by self-limitedregional lymphadenopathy. The manifestations of CSD, however, can include visceral organ,neurologic, and ocular involvement [1,2] .The microbiology, epidemiology, clinical features, and diagnosis of CSD will be reviewed here. Thetreatment of CSD is discussed separately. (See "Treatment of cat scratch disease").

MICROBIOLOGY

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Although clinical descriptions of cat scratch disease (CSD) existed for morethan 50 years, the first convincing evidence of an infectious cause of CSD came in 1983 wheninvestigators at the Armed Forces Institute of Pathology, using a Warthin-Starry stain,demonstrated small, pleomorphic organisms in the lymph nodes of 29 of 34 patients with CSD [3] .Afipia felis first was believed to be the cause of CSD after investigators isolated this organism frompatients with CSD [4,5] . However, current serologic and culture data provide convincing evidencethat Bartonella (formerly Rochalimaea) henselae is the etiologic agent in most cases of CSD [6-8] .One report also described a case of CSD caused by B. clarridgeiae [9] . Taken together, availabledata suggest that B. henselae is the predominant cause of CSD, while scattered, uncommon casesof CSD may result from A. felis, B. clarridgeiae, and perhaps other, as yet unidentified, fastidiousorganisms [10] .Among HIV-infected persons (and less commonly other immunocompromised individuals), B.henselae can cause bacillary angiomatosis (BA), peliosis hepatis, and splenitis. (See "Bartonellainfections in HIV-infected patients"). Rare reports have also documented BA amongimmunocompetent individuals [11] .

Pathogenesis

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The pathogenesis of CSD remains poorly understood. Disease manifestationsresult from either local infection, such as lymphadenopathy, or from bloodborne disseminated

infection, such as occurs with neuroretinitis or visceral organ involvement. Cats serve as thenatural reservoir for B. henselae and the organism causes intraerythrocytic bacteremia that canpersist for a year or longer in some cats [12] . Following inoculation of B. henselae into humans,the organism typically causes a local infection that manifests as regional lymphadenopathy. Withinthe human host, B. henselae invades endothelial cells causing an acute inflammatory reactionassociated with activation of a proinflammatory cascade [13] . It remains unknown why somepatients have infection that remains localized whereas others develop disseminated disease.

EPIDEMIOLOGY

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Currently available data suggest that cat scratch disease (CSD) can result from acat scratch or bite, as well as from a flea bite. Rare cases of CSD occur after exposure to a dog,presumably resulting from flea bites.In a prospective, population-based study performed in Connecticut during the years 1992 and1993, the overall annual incidence of CSD was 3.7 per 100,000 persons; the highest age-specificattack rate occurred in those under the age of 10, 9.3 per 100,000 per year [14] . In another study,CSD was identified in 61 of 454 patients (13 percent) with primary head and neck masses [15] .CSD appears to occur in a broad geographic distribution in North America. Cases have a seasonaldistribution with a peak in fall and early winter. CSD may rarely occur in family clusters with morethan one child in the family presenting simultaneously [16] . Epidemiologic studies from the UnitedStates, Europe, Israel, Australia, and Japan, have identified that CSD has a worldwide distribution[17] .CSD generally occurs in young immunocompetent individuals and infrequently causes seriousillness. In one study using a United States national database, the incidence of CSD wasapproximately 9 to 10 cases per 100,000 persons per year (22,000 cases per year); most casesoccurred in persons less than 21 years of age [18] . Although most commonly a disease of childrenand young adults, a surveillance study conducted in Israel found that 52 of 846 (6 percent)immunocompetent patients with

CSD were ≥ 60 years of age *19+ .

CSD can also occur in immunocompromised patients. Systemic CSD has been described in patientswho have undergone solid organ transplantation [20-22] and in a patient being treated withpegylated interferon and ribavirin for hepatitis C virus infection [23] .

Transmission

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Multiple lines of evidence have directly linked CSD to exposure to cats, especiallyyoung cats and cats with fleas [1,7,24] . In one study of 205 cats in northern California, B. henselaebacteremia was documented in 56 and 34 percent of cats less than one year and at least one yearof age, respectively [25] . Moreover, 90 and 77 percent of cats less than one and one year or older,respectively, had positive B. henselae serology.Fleas have also been implicated in the transmission of CSD. In one study of 60 CSD patients and 56age-matched controls, exposure to kittens (odds ratio (OR) 15), a scratch or bite by a kitten (OR27), and having a kitten with fleas (OR 29) were more common among cases than controls [7] . In a

study of B. henselae antibodies in catteries, flea infestation was the risk factor most associatedwith high seroprevalence [26] .

CLINICAL MANIFESTATIONS

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Cat scratch disease (CSD) presents in 85 to 90 percent of childrenas a localized cutaneous and lymph node disorder near the site of organism inoculation. In someindividuals, the organisms disseminate and infect the liver, spleen, eye, or central nervous system.Patients with localized disease generally have a self-limited illness, whereas those withdisseminated disease can have life-threatening complications.

Cutaneous manifestations

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CSD typically begins with a cutaneous lesion at the site of inoculation, the so-called primary inoculation lesion. This lesion usually develops three to ten daysafter the introduction of the organism into the skin and generally evolves through vesicular,erythematous, and papular phases [27,28] (show picture 1). Less commonly the primaryinoculation lesion can be pustular or nodular. One report described a patient who developed aparonychia (painful periungual inflammation) caused by B. henselae as a manifestation of aninoculation site lesion [29] . The primary inoculation lesion typically persists for one to three weeks(range several days to several months).Careful examination of the interdigital spaces, skin creases, and scalp increases the chance of finding the primary inoculation lesion. Inoculation sites other than the skin occur in about five toten percent of cases and include the eye (nonsuppurative conjunctivitis, ocular granuloma) andmucous membranes (oral ulcer) [27] . The inoculation lesions usually cause minimal symptoms andheal without scarring.Other uncommon cutaneous manifestations of CSD include a transient macular and papulareruption, erythema multiforme, erythema nodosum, and thrombocytopenic purpura [27] .

Lymphadenopathy

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Regional lymphadenopathy is the hallmark of CSD. Enlarged lymph nodesappear proximal to the inoculation site, about two weeks (range, seven to 60 days) after theorganism is inoculated into the skin (show picture 2). The nodes are almost always tender, oftenhave erythema of the overlying skin, and occasionally suppurate (10 to 15 percent). Node sizetypically ranges from one to five cm, but may enlarge to eight to 10 cm.The location of the lymphadenopathy depends on the site of the inoculation; the most commonlocations are the axillary, epitrochlear, cervical, supraclavicular, and submandibular lymph nodes.In one study, solitary lymphadenopathy occurred in approximately 85 percent of patients [28] .Less commonly, patients presented with several enlarged nodes in the same anatomic region. Inanother study, regional adenopathy (single or multiple nodes) occurred in approximately two-thirds of cases, with the remaining one-third of patients having enlarged nodes in severalanatomic sites [27] . Generalized lymphadenopathy is rare. Lymphadenopathy associated with CSDusually resolves in one to four months, but reports have described persistence of enlarged nodesfor one to three years.