CAT SCRATCH DISEASE

Microbiology, epidemiology, clinical manifestations, and diagnosis

Authors

David H Spach, MD

Sheldon L Kaplan, MD Section Editors

Stephen B Calderwood, MD

Morven S Edwards, MD Deputy Editor

Anna R Thorner, MD

Last literature review version 17.1: January 2009 | This topic last updated: May 30, 2008 (More)

INTRODUCTION — Cat scratch disease (CSD) is an infectious disease characterized by self-limited

regional 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. The
treatment of CSD is discussed separately. (See "Treatment of cat scratch disease").

MICROBIOLOGY — Although clinical descriptions of cat scratch disease (CSD) existed for more
than 50 years, the first convincing evidence of an infectious cause of CSD came in 1983 when
investigators 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 from
patients with CSD [4,5] . However, current serologic and culture data provide convincing evidence
that 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, available
data suggest that B. henselae is the predominant cause of CSD, while scattered, uncommon cases
of CSD may result from A. felis, B. clarridgeiae, and perhaps other, as yet unidentified, fastidious
organisms [10] .

Among HIV-infected persons (and less commonly other immunocompromised individuals), B.

henselae can cause bacillary angiomatosis (BA), peliosis hepatis, and splenitis. (See "Bartonella
infections in HIV-infected patients"). Rare reports have also documented BA among
immunocompetent individuals [11] .

Pathogenesis — The pathogenesis of CSD remains poorly understood. Disease manifestations

result from either local infection, such as lymphadenopathy, or from bloodborne disseminated
infection, such as occurs with neuroretinitis or visceral organ involvement. Cats serve as the
natural reservoir for B. henselae and the organism causes intraerythrocytic bacteremia that can
persist 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. Within
the human host, B. henselae invades endothelial cells causing an acute inflammatory reaction
associated with activation of a proinflammatory cascade [13] . It remains unknown why some
patients have infection that remains localized whereas others develop disseminated disease.

EPIDEMIOLOGY — Currently available data suggest that cat scratch disease (CSD) can result from a
cat 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 and
1993, the overall annual incidence of CSD was 3.7 per 100,000 persons; the highest age-specific
attack 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 seasonal
distribution with a peak in fall and early winter. CSD may rarely occur in family clusters with more
than one child in the family presenting simultaneously [16] . Epidemiologic studies from the United
States, Europe, Israel, Australia, and Japan, have identified that CSD has a worldwide distribution
[17] .

CSD generally occurs in young immunocompetent individuals and infrequently causes serious
illness. In one study using a United States national database, the incidence of CSD was
approximately 9 to 10 cases per 100,000 persons per year (22,000 cases per year); most cases
occurred in persons less than 21 years of age [18] . Although most commonly a disease of children
and 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 patients
who have undergone solid organ transplantation [20-22] and in a patient being treated with
pegylated interferon and ribavirin for hepatitis C virus infection [23] .

Transmission — Multiple lines of evidence have directly linked CSD to exposure to cats, especially
young cats and cats with fleas [1,7,24] . In one study of 205 cats in northern California, B. henselae
bacteremia was documented in 56 and 34 percent of cats less than one year and at least one year
of 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 56
age-matched controls, exposure to kittens (odds ratio (OR) 15), a scratch or bite by a kitten (OR
27), 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 associated
with high seroprevalence [26] .

CLINICAL MANIFESTATIONS — Cat scratch disease (CSD) presents in 85 to 90 percent of children

as a localized cutaneous and lymph node disorder near the site of organism inoculation. In some
individuals, 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 with
disseminated disease can have life-threatening complications.

Cutaneous manifestations — 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 days
after 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 primary
inoculation lesion can be pustular or nodular. One report described a patient who developed a
paronychia (painful periungual inflammation) caused by B. henselae as a manifestation of an
inoculation 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 to
ten percent of cases and include the eye (nonsuppurative conjunctivitis, ocular granuloma) and
mucous membranes (oral ulcer) [27] . The inoculation lesions usually cause minimal symptoms and
heal without scarring.

Other uncommon cutaneous manifestations of CSD include a transient macular and papular
eruption, erythema multiforme, erythema nodosum, and thrombocytopenic purpura [27] .

Lymphadenopathy — Regional lymphadenopathy is the hallmark of CSD. Enlarged lymph nodes

appear proximal to the inoculation site, about two weeks (range, seven to 60 days) after the
organism is inoculated into the skin (show picture 2). The nodes are almost always tender, often
have erythema of the overlying skin, and occasionally suppurate (10 to 15 percent). Node size
typically 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 common
locations 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. In
another 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 several
anatomic sites [27] . Generalized lymphadenopathy is rare. Lymphadenopathy associated with CSD
usually resolves in one to four months, but reports have described persistence of enlarged nodes
for one to three years.
Visceral organ involvement — Several reports have described patients with CSD who had
involvement of the liver, spleen, or both. Visceral organ involvement is one of the more common
manifestations of CSD in children after lymphadenopathy alone [30-32] . Patients may have
persistent fever of unknown origin, abdominal pain, and/or weight loss [33] . About half of
children have hepatomegaly or splenomegaly; the liver may be tender to palpation. Many of the
patients with visceral involvement have no accompanying peripheral adenopathy. In one review,
100 of 832 patients (12 percent) with CSD had splenomegaly, but these were not patients in whom
granulomatous splenitis was documented [34] .

An abdominal CT scan will typically show scattered, multiple defects in the liver and/or spleen that
if biopsied, would show necrotizing granulomas (show picture 3). Biopsies are now rarely
performed because the clinical and imaging findings are so characteristic. These are manifested as
hypoechoic areas on ultrasound.

The erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) is typically elevated and liver
function tests may be mildly abnormal.

Fever of unknown origin — B. henselae infection should be considered in the initial evaluation of
fever of unknown origin and prolonged fever in children [35,36] . A prospective analysis of 146
children with fever of unknown origin and prolonged fever found that B. henselae was the third
most common infectious disease diagnosis [37] . Although some of these patients presented with
signs and symptoms consistent with typical CSD or hepatosplenic involvement, three of seven
patients with confirmed B. henselae infection presented with fever of unknown origin and no
clinical or radiographic manifestations of typical or hepatosplenic CSD. (See "Etiologies of fever of
unknown origin in children").

Ocular manifestations — Ocular manifestations of CSD include Parinaud's oculoglandular

syndrome, neuroretinitis, papillitis, optic neuritis, and focal retinochoroiditis [38] .

Parinaud's oculoglandular syndrome — Parinaud's oculoglandular syndrome is an atypical form of

CSD, reported in from two to eight percent of patients with CSD, and can include conjunctivitis,
conjunctival granuloma, and adjacent preauricular lymphadenopathy [39,40] . The inoculation of
the organism occurs via a cat bite or lick near (or in) the eye, as well as by self-inoculation from
another site. Serious ocular, orbital, or retinal complications almost never develop as a result of
local extension of Parinaud's oculoglandular syndrome. One report described isolation of B.
henselae from a conjunctival scraping in a patient with Parinaud's oculoglandular syndrome [41] .

Neuroretinitis — Among all patients with CSD, about one to two percent develop neuroretinitis.
Neuroretinitis is a syndrome of acute visual loss from optic nerve edema associated with macular
exudates; B. henselae is believed to be one of the most common infectious cause [42] . The
frequency of CSD as a cause of neuroretinitis is illustrated by a serologic study of patients with
neuroretinitis that found 9 of 14 (64 percent) had either elevated IgM or IgG B. henselae titers [43]
.
Patients with neuroretinitis typically present with fever, malaise, and unilateral blurred vision [44]
. On examination, patients usually have unilateral involvement, with decreased visual acuity, often
associated with an afferent papillary defect. Retinal findings may include hemorrhages, cotton
wool spots, multiple discrete lesions in the deep retina, and stellate macular exudates (known as a
"macular star") (show picture 4) [44] . However, patients with B. henselae-induced neuroretinitis
may not develop a macular star until one to four weeks after initial presentation, and some
patients never develop a macular star [38] . The macular exudates in CSD can persist for months
before resolving, and some patients have residual defects that include optic disk pallor, diminished
contrast sensitivity, and altered color vision [38] . Most patients with neuroretinitis, however,
appear to have a good long-term prognosis [38,44] .

A case report described a 10-year-old girl with CSD who developed a macular hole 12 days after
presentation with neuroretinitis in association with a posterior vitreous detachment [45] .

Neurologic manifestations — A wide range of neurologic manifestations are described in patients

with CSD, including [46-48] : Encephalopathy (most common) Transverse myelitis Radiculitis
Cerebellar ataxia

Patients with encephalopathy typically develop abrupt confusion and disorientation, which may
progress to coma, approximately one to six weeks after initially presenting with adenopathy. Most
of these patients will develop seizures and some develop focal neurologic findings such as
hemiparesis as a result of cerebral vasculitis [47] .

Among patients with CSD encephalopathy, laboratory findings include [46] : A normal computed
tomography (CT) scan of the brain — most patients Mild mononuclear pleocytosis in the
cerebrospinal fluid (CSF) (usually <50 cell/mm3) — 20 to 30 percent An abnormal
electroencephalogram — most patients

Although patients typically recover from CSD encephalopathy within several weeks, some will have
residual neurologic defects.

Musculoskeletal manifestations — Severe and often disabling musculoskeletal manifestations

may occur in patients with CSD. In a surveillance study of 913 patients with CSD in Israel, 96 (10.5
percent) had musculoskeletal manifestations [49] . These included myalgia (6 percent), arthritis or
arthralgia (5.5 percent), and less commonly tendinitis, osteomyelitis, and neuralgia.

The knee, ankle, wrist, hand, and elbow joints were the most frequently affected. Although joint
complaints resolved in the majority of patients, five patients developed chronic disease [49,50] .
Multivariate analysis identified the following characteristics significantly associated with
arthropathy (arthritis or arthralgia): Female sex (relative risk [RR], 1.89; 95% CI 1.01-3.52) Age
greater than 20 years (RR, 11.0; 95% CI 4.3-28.2) Erythema nodosum (RR, 4.07; 95% CI 1.38-12.02)
A review of bone infection associated with CSD, published prior to the above study, found 47 cases
reported in the literature [51] . The median age was 9 years. Bone pain and fever were the
predominant clinical manifestations and the most commonly affected sites were the vertebral
column and pelvic girdle.

Other atypical manifestations — Scattered reports have documented rare manifestations of CSD,
including hypercalcemia, deep tissue neck infection [52] , culture-negative endocarditis [53] ,
pneumonia, pleural effusion, septic shock, and thrombocytopenic purpura. The hypercalcemia is
associated with overproduction of calcitriol, the most active form of vitamin D, and appears to be
related to granuloma formation [54] . (See "Hypercalcemia in granulomatous diseases").

Elderly patients — Elderly patients with CSD are more likely to present with atypical features. In
the surveillance study in Israel mentioned above, clinical data for patients with CSD aged ≥ 60
years (elderly group) were compared with patients with CSD aged <60 years (nonelderly group)
[19] . The elderly group was more likely to have: General malaise (71 compared to 51 percent in
the nonelderly) Atypical CSD (33 compared to 14 percent in the nonelderly); including endocarditis
(odds ratio [OR], 61.6; 95% CI, 12.4-305.1), encephalitis (OR, 6.3; 95% CI, 1.2-33.3), and fever of
unknown origin (OR, 7.3; 95% CI, 2.2-24.5)

Lymphadenitis, the hallmark of typical CSD, was less common in the elderly group (77 compared to
94 percent in the nonelderly). For these reasons, the time from onset of symptoms to diagnosis of
CSD in elderly persons was more commonly delayed for >6 weeks (30 compared to 13 percent in
the nonelderly).

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of cat scratch disease (CSD) primarily
includes other infectious and malignant causes of lymphadenopathy [27,55] . The importance of
excluding mycobacterial disease and malignancy by analysis of a lymph node biopsy specimen is
illustrated by the analysis of 786 lymph node specimens from patients with suspected CSD [56] .
The following findings were noted: Infectious agents were identified in 391 of 786 (50 percent) of
patients. The most commonly identified infectious agent was B. henselae (245 patients, 31
percent). Mycobacterial infection was diagnosed in 54 patients (7 percent) Malignancy was
diagnosed in 47 of 181 patients in whom specimens suitable for histologic analysis were available
(26 percent of those analyzed, 6 percent of total). Concurrent disease was diagnosed in 13
patients; CSD and either mycobacterial disease (10 patients) or malignancy (3 patients) No
diagnosis was obtained in 350 patients (45 percent)

The presence of tender lymph nodes suggests an infectious cause. The most common infectious
causes are: Bacterial adenitis (caused by Staphylococcus aureus or group A beta-hemolytic
streptococci) Lymphadenopathy accompanied by a cutaneous inoculation lesion (caused by
atypical mycobacteria, Nocardia species, Francisella tularensis, Erysipelothrix rhusiopathiae,
Bacillus anthracis, Yersinia pestis, or Borrelia burgdorferi) (See "Causes of peripheral
lymphadenopathy in children" and see "Evaluation of peripheral lymphadenopathy in adults").
Viral-associated lymphadenopathy (caused by cytomegalovirus, HIV, or Epstein-Barr virus)
Toxoplasmosis (See "Toxoplasmosis in immunocompetent hosts").
Rare infectious causes include histoplasmosis and sporotrichosis.

Lymphoma is the most common malignancy that can be confused with CSD. In some
circumstances, a lymph node biopsy may need to be performed to exclude lymphoma, especially
in those patients who have an atypical presentation or who have delayed resolution of systemic
symptoms. Other noninfectious causes include congenital and acquired cysts, Kawasaki's disease,
and sarcoidosis.

DIAGNOSIS — The diagnosis of CSD may be suspected from the typical clinical findings, but
laboratory evaluation is required to confirm the clinical impression [57] . A laboratory diagnosis of
CSD is often made on the basis of a positive serologic test (ie, a positive B. henselae antibody
titer). However, serologic testing has serious shortcomings. (See "Serology" below).

It has been suggested that at least three of four of the following criteria be present to establish
the diagnosis of CSD in patients with typical findings [58] : Cat or flea contact regardless of the
presence of an inoculation site lesion Negative serology for other causes of adenopathy; sterile
pus aspirated from a node; a positive Bartonella PCR assay; and/or liver or spleen lesions seen on
CT scan Positive serology for B. henselae (enzyme immunoassay [EIA] or indirect fluorescence
assay *IFA+) with a titer ratio of ≥ 1:64 Biopsy showing granulomatous inflammation consistent
with CSD or a positive Warthin-Starry silver stain

In contrast, some experts suggest that a positive serologic test is generally adequate for diagnosis
in patients with typical clinical manifestations of CSD. In patients with atypical findings, a tissue
biopsy is often performed to investigate a number of potential causes. When a biopsy is
performed, PCR and culture of the tissue should be obtained in addition to routine histopathologic
studies. Although isolation of B. henselae by culture provides a definitive diagnosis, B. henselae is
difficult to isolate from tissue specimens.

Serology — Two serologic methods, the indirect fluorescence assay (IFA) and enzyme
immunosorbent assay (EIA) have been evaluated for diagnosis. One study found a higher
proportion of patients with presumed CSD had an indirect IFA B. henselae IgG titers of ≥ 1:64
compared to healthy controls (88 versus 3 percent) [6] . However, four subsequent studies from
Europe reported problems with B. henselae IFA tests including poor sensitivity [59,60] and
specificity [61,62] . The reported problems with the B. henselae IFA serology tests include:
Significant cross-reactivity at the species level between B. henselae and B. quintana, especially for
IgG assays Sensitivity of the test does not appear to be optimal, especially with IgG assays
Prevalence of positive Bartonella serology in the general population is four to six percent, which
creates false positive tests

Although both the IFA and EIA tests have undergone study, commercially available assays use the
IFA test. In the United States, three references labs are commonly used for Bartonella serology
testing: Associated Regional University Pathologists (Salt Lake City Utah):
www.aruplab.com/guides/ug/tests/0050108.jsp, phone: 800-522-2787 Focus Diagnostics (Cypress,
California): www.focusdx.com, phone: 714-220-1900 or 800-445-0185 Specialty Laboratories, Inc.
(Santa Monica, California): http://specialtylabs.com; phone number for client services: 800-421-
4449. This laboratory has very poor correlation with Centers for Disease Control and Prevention
(CDC) results for Bartonella serology (Kaplan, SL, Baylor College of Medicine, 2006, personal
communication).

Serologic testing is also performed by the CDC through the Viral and Rickettsial Diseases Branch
[63] . The disadvantage to the CDC laboratory is that the turn-around time is longer than for
commercial laboratories; however, physicians may be able to expedite the process by calling 404-
639-1075 to discuss urgent specimens.

In general, IFA IgG titers <1:64 suggest the patient does not have a current Bartonella infection; a
low positive titer may represent past infection. Titers between 1:64 and 1:256 represent possible
Bartonella infection; repeat testing in 10 to 14 days is recommended. Titers >1:256 strongly
suggest active or recent infection.

Culture — B. henselae is a fastidious, slow-growing, gram-negative bacterium that requires

specific laboratory conditions for optimal growth. Blood culture samples should be incubated in
pediatric or adult isolator tubes (Wampole, Cranbury, NJ) or in blood tubes containing
ethylenediaminetetraacetic acid (EDTA) to increase the probability of isolating B. henselae.

Plating samples onto either chocolate agar or heart infusion agar supplemented with five percent
rabbit blood enhances isolation of organisms from subcultures. Optimally, the microbiology lab
should use fresh agar plates and incubate them in five percent CO2 at 35 to 37ºC for a minimum of
21 days. Even employing the optimal techniques, most patients with CSD do not have B. henselae
isolated from blood cultures.

Isolation of B. henselae from tissue samples remains very difficult, but a successful isolation in HIV-
infected patients has been reported by directly plating tissue homogenates onto agar and co-
cultivating with a bovine endothelial cell monolayer [64] .

Histopathology — Histopathologic examination of the primary inoculation lesion site reveals

acellular areas of necrosis in the dermis. Histiocytes and epithelioid cells surround the areas of
necrosis in multiple layers, with the innermost layer often showing a palisading arrangement. A
zone of lymphocytes surrounds the histiocytes; multinucleated giant cells are variably present.
Although these findings support a diagnosis of CSD, they should not be considered definitive.

The histopathologic findings in involved lymph nodes are nonspecific and depend upon the stage
of the disease. Lymphoid hyperplasia is present initially, followed by the development of stellate
granulomas. The centers are acellular and necrotic; histiocytes and peripheral lymphocytes
surround these areas, similar to findings in skin samples. Microabscesses develop and may
become confluent at a later stage.
Warthin-Starry stain may demonstrate delicate pleomorphic B. henselae bacilli in chains, clumps,
or filaments within areas of necrosis of involved lymph nodes and in the primary inoculation site of
the skin. Although a positive Warthin-Starry stain does not provide a definitive diagnosis of CSD, it
would strongly suggest a diagnosis of CSD if observed in conjunction with compatible clinical
findings.

Polymerase chain reaction — PCR based tests have predominantly been used in research settings.
One PCR assay amplifies a 296 base pair fragment of the 16S ribosomal RNA (rRNA) of B. henselae
species. The PCR test can distinguish among the different Bartonella species.

The PCR test on tissue or blood is available commercially through either Focus Technologies or
Specialty Laboratories, Inc. A rapid single-step PCR assay for Bartonella that amplifies the 16S-23S
rRNA intergenic regions has shown promise [65] .

The timing of biopsy may influence whether or not PCR from tissue is positive in CSD. In a study of
61 patients with CSD cited above, PCR was positive in only 10 of the 212 lymph node specimens on
which this test was performed; 9 of the 10 positive patients had a duration of illness of less than
six weeks [15] . Patients with a compatible clinical presentation and serologic evidence of B.
henselae infection (single IgG titer ≥ 1:512, four-fold increase in titer between paired serum
specimens, or IgG titer between 1:64 and 1:256 accompanied by a positive IgM) were considered
to have CSD in this study.

Skin testing — The CSD skin test, one of the original four criteria for diagnosis of CSD, is no longer
used since other more specific and sensitive diagnostic tools are preferred [1,2,8] . In addition, the
skin test antigen is not widely available, is not standardized, and is not approved by the Food and
Drug Administration (FDA) [1] .

SUMMARY

Cat scratch disease (CSD) is an infectious disease characterized by self-limited regional

lymphadenopathy. The manifestations of CSD, however, can include visceral organ, neurologic,
and ocular involvement. (See "Introduction" above). Bartonella (formerly Rochalimaea) henselae is
the etiologic agent in most cases of CSD. (See "Microbiology" above). Multiple lines of evidence
have directly linked CSD to exposure to cats, especially young cats and cats with fleas. CSD can
result from a cat scratch or bite, as well as from a flea bite. (See "Epidemiology" above). CSD most
often (in 85 to 90 percent of children) presents as a localized cutaneous and lymph node disorder
near the site of organism inoculation. In some individuals, 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 with disseminated disease can have life-threatening
complications. (See "Clinical manifestations" above). B. henselae infection should be considered in
the initial evaluation of fever of unknown origin (FUO) and prolonged fever in children. In one
study, CSD was the third most common cause of FUO in children. (See "Fever of unknown origin"
above). Ocular manifestations of CSD include Parinaud's oculoglandular syndrome, neuroretinitis,
papillitis, optic neuritis, and focal retinochoroiditis. (See "Ocular manifestations" above). The
differential diagnosis of CSD primarily includes other infectious and malignant causes of
lymphadenopathy. (See "Differential diagnosis" above). The diagnosis of CSD is based on typical
clinical findings (ie, lymphadenopathy) associated with probable exposure to cats or fleas.
Laboratory testing that is supportive of a diagnosis includes a positive B. henselae antibody titer or
a positive Warthin Starry stain or PCR analysis of tissue. (See "Diagnosis" above). In cases of CSD
that present with atypical clinical manifestations, the diagnosis relies heavily on a positive
serologic test. However, in atypical cases, if a tissue sample is obtained, a definitive laboratory
diagnosis should be attempted by either culture or PCR. Although isolation of B. henselae by
culture provides a definitive diagnosis, B. henselae remains very difficult to isolate from tissue
specimens. (See "Diagnosis" above).

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TREATMENT OF CAT SCRATCH DISEASE

Authors

David H Spach, MD

Sheldon L Kaplan, MD Section Editors

Stephen B Calderwood, MD

Morven S Edwards, MD Deputy Editor

Anna R Thorner, MD
Last literature review version 17.1: January 2009 | This topic last updated: November 14,
2007 (More)

INTRODUCTION — Cat scratch disease (CSD) is an infectious disease characterized by self-limited

regional lymphadenopathy. The manifestations of CSD, however, can include visceral organ,
neurologic, and ocular involvement [1,2] . Bartonella (formerly Rochalimaea) henselae is the
etiologic agent in most cases of CSD.

CLINICAL STUDIES — Most patients with typical CSD have gradual resolution of symptoms, even
without specific antibiotic therapy [3] . In five to 14 percent of individuals, the organisms
disseminate and infect the liver, spleen, eye, or central nervous system [4,5] . Patients with
disseminated disease can have life-threatening complications.

In vitro susceptibility testing often does not correlate with a clinical response and should not be
considered in the choice of antibiotics [3] . The literature on the use of antibiotics in CSD primarily
derives from case reports and small series. There is one prospective, randomized trial.

Lymphadenitis

Studies A randomized prospective placebo-controlled trial of 29 immunocompetent patients

(including children and adults) with typical cat scratch disease examined the effectiveness of a
five-day course of azithromycin (10 mg/kg on day one and 5 mg/kg on the subsequent 4 days for
patients weighing less than 45.5 kg and 500 mg on day 1, followed by 250 mg on the next four
days for those weighing at least 45.5 kg) [6] . Seven of 14 patients who received azithromycin had
an 80 percent or more decrease in lymph node volume during a 30 day follow-up period compared
with only one of seven placebo recipients. This trial provides the most convincing data in favor of
antibiotic treatment. The largest therapeutic trial was an uncontrolled retrospective study of 268
persons with CSD [7] . The mean duration of illness was 14.5 weeks for 66 patients without
treatment, 14.5 weeks for 113 patients treated with antibiotics thought to be ineffective, and 2.8
weeks for 89 patients treated with rifampin, ciprofloxacin, trimethoprim-sulfamethoxazole, or
gentamicin. In one small nonrandomized series, five adults with CSD and painful lymphadenitis
received oral ciprofloxacin and had rapid clinical improvement without relapse [8] . In another
small series, four patients (three children) with localized CSD received therapy with oral
azithromycin for 5 to 10 days, and all had 50 percent reduction in lymph node size by day 5 and
complete resolution of lymphadenopathy within 14 days [9] .

Hepatosplenic disease

Hepatosplenic disease in patients with CSD is uncommon as compared to localized disease and is
due to systemic dissemination of the organism. Hepatosplenic CSD should not be confused with
peliosis hepatis which is caused by either B. henselae or B. quintana and is most often diagnosed
in HIV-infected individuals, although other immunocompromised individuals, such as cancer
patients and solid organ transplant recipients, have also developed this manifestation. One report
described three patients with CSD who responded to intravenous gentamicin; two of the patients
had extensive hepatic involvement and one had regional lymphadenopathy [10] . Nineteen
children (aged 2 to 11) who had hepatosplenic CSD appeared to respond well to rifampin, either
given alone or in combination with either gentamicin or trimethoprim-sulfamethoxazole [11] .
These patients most often received rifampin at a dose of 20 mg/kg per day for 14 days.

Neuroretinitis

Studies A retrospective case series of seven consecutive patients with B. henselae neuroretinitis
evaluated the outcome of patients treated with doxycycline (100 mg PO twice daily) and rifampin
(300 mg PO twice daily) for four to six weeks compared to historic controls [12] . Antibiotic
therapy appeared to promote the resolution of retinitis. However, a case report described prompt
resolution of B. henselae-associated neuroretinitis in a patient who received no antimicrobial
therapy [13] . Thus, optimal therapy for neuroretinitis remains unknown.

ANTIMICROBIAL REGIMENS — Given the available data, we make the following treatment
regimen recommendations according to the clinical disease setting. A Jarisch-Herxheimer reaction
can occur after the first several doses of antibiotics [14,15] .

Lymphadenitis — Although some experts would suggest not treating typical CSD in
immunocompetent patients with mild to moderate illness [3] , we suggest a five-day course of
azithromycin (500 mg on day one, followed by 250 mg for four days for patients weighing more
than 45.5 kg; or 10 mg/kg on day one, followed by 5 mg/kg for four days for those weighing less
than 45.5 kg [100 lbs]).

In patients intolerant to azithromycin, we suggest one of the following alternative regimens for a
seven- to ten-day course: Clarithromycin (15 to 20 mg/kg divided in two doses for those weighing
less than 45.5 kg; or 500 mg twice daily for patients weighing more than 45.5 kg) Rifampin (in
children, 10 mg/kg every 12 hours, maximum dose 600 mg daily; in adults, 300 mg twice daily)
Trimethoprim-sulfamethoxazole (in children, trimethoprim 8 mg/kg per day, sulfamethoxazole 40
mg/kg per day, in two divided doses; in adults, one double strength tablet twice a day)
Ciprofloxacin (for patients >17 years of age, 500 mg twice a day).

Hepatosplenic disease and prolonged fever — Limited data suggest treatment in children should
consist of rifampin as a single agent for 10 to 14 days. However, given the concern for rapid
development of rifampin resistance, we along with some experts recommend adding a second
agent, such as gentamicin (loading dose 2 mg/kg then 1.5 mg/kg every 8 hours dosed based upon
normal renal function and adjusted with monitoring) or azithromycin (dosed as above) for the
entire 10 to 14 day course. As long as the patient improves, there is no need to repeat the imaging
studies of the liver or spleen to document resolution of the lesions.
Neuroretinitis — The optimal therapy for neuroretinitis is unknown. Based upon limited data, we
would suggest in adults, doxycycline (100 mg orally twice daily) plus rifampin (300 mg orally twice
daily) for four to six weeks in conjunction with close monitoring by an ophthalmologist. For
children ≤ 8 years of age, we suggest rifampin (10 mg/kg every 12 hours, maximum dose 600 mg
daily) plus either azithromycin (10 mg/kg on day one, followed by 5 mg/kg for four days for those
weighing less than 45.5 kg) or trimethoprim-sulfamethoxazole (trimethoprim 8 mg/kg per day,
sulfamethoxazole 40 mg/kg per day, in two divided doses).

Neurologic disease — Little is known about optimal therapy for neurologic manifestations of B.
henselae infection. In severe cases, we suggest therapy with a combination of doxycycline plus
rifampin for 10 to 14 days. Azithromycin is an alternative to doxycycline, but more experience
exists with using doxycycline to treat central nervous system infections caused by other pathogens
and we prefer treatment with this agent. In children ≤ 8 years of age, azithromycin or
trimethoprim-sulfamethoxazole (dosed as above) should be substituted for doxycycline.

Endocarditis — Treatment of suspected or proven Bartonella endocarditis is discussed separately.

(See "Endocarditis caused by Bartonella").

SUMMARY AND RECOMMENDATIONS

Cat scratch disease (CSD) is an infectious disease characterized by self-limited regional

lymphadenopathy. The manifestations of CSD, however, can include visceral organ, neurologic,
and ocular involvement. (See "Introduction" above). Bartonella (formerly Rochalimaea) henselae is
the etiologic agent in most cases of CSD. (See "Introduction" above). Most patients with typical
CSD have gradual resolution of symptoms, even without specific antibiotic therapy, however, in
five to 14 percent of individuals, the organisms disseminate and infect the liver, spleen, eye, or
central nervous system. Patients with disseminated disease can have life-threatening
complications. (See "Clinical studies" above). Although some experts would suggest not treating
typical CSD in immunocompetent patients with mild to moderate illness, we suggest treatment of
all patients with antimicrobial agents (Grade 2B). The preferred antibiotic for treatment is
azithromycin since this agent is the only one studied in a randomized controlled study. The typical
dose is a five-day course (500 mg on day one, followed by 250 mg for four days for patients
weighing more than 45.5 kg; or 10 mg/kg on day one, followed by 5 mg/kg for four days for those
weighing less than 45.5 kg [100 lbs]). (See "Lymphadenitis" above). Other regimens that appear
effective in patients with mild to moderate illness who are intolerant to azithromycin, include:
 - Clarithromycin (15 to 20 mg/kg divided in two doses for those weighing less than 45.5 kg; or
500 mg twice daily for patients weighing more than 45.5 kg)

- Rifampin (in children, 10 mg/kg every 12 hours, maximum dose 600 mg daily; in adults, 300
mg twice daily)

- Trimethoprim-sulfamethoxazole (in children, trimethoprim 8 mg/kg per day,

sulfamethoxazole 40 mg/kg per day, in two divided doses; in adults, one double strength tablet
twice a day)

- Ciprofloxacin (for patients >17 years of age, 500 mg twice a day).

(See "Lymphadenitis" above). We recommend treatment of all patients with hepatosplenic or

disseminated disease (Grade 1B). Acceptable treatment regimens include rifampin (in children, 10
mg/kg every 12 hours, maximum dose 600 mg daily; in adults, 300 mg twice daily) plus either
gentamicin (loading dose 2 mg/kg then 1.5 mg/kg every 8 hours dosed based upon normal renal
function and adjusted with monitoring) or azithromycin (dosed as above). The usual duration of
treatment is 10 to 14 days. (See "Hepatosplenic disease and prolonged fever" above). We
recommend treatment of all patients with neuroretinitis or neurologic disease (Grade 1B). An
acceptable treatment regimen in adults is doxycycline (100 mg orally twice daily) plus rifampin
(300 mg orally twice daily). In children ≤ 8 years of age, azithromycin or trimethoprim-
sulfamethoxazole (dosed as above) should substitute for doxycycline. The usual duration of
treatment is four to six weeks for neuroretinitis and 10 to 14 days for other neurologic disease.
Neuroretinitis should be managed in conjunction with close monitoring by an ophthalmologist.
(See "Neuroretinitis" above and see "Neurologic disease" above).

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