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Follow-up Pictures BibliographyAuthor: Kerrie J Spoonemore, MD, PharmD, Resident Physician, Department of
Dermatology, University of Oklahoma
Coauthor(s): Gregory J Raugi, MD, PhD , Chief, Veterans Administration Medical
Center of Seattle; Program Director, Associate Professor, Department of Internal
Medicine, Division of Dermatology, University of Washington at Seattle
Kerrie J Spoonemore, MD, PharmD, is a member of the following medical societies:
American Academy of Dermatology
Editor(s): Julia R Nunley, MD, Program Director, Associate Professor, Department of
Dermatology, Medical College of Virginia; Michael J Wells, MD, Staff Physician,
Department of Dermatology, Texas Tech University Health Sciences Center; Van Perry,
MD, Assistant Professor, Department of Medicine, Division of Dermatology, University
of Texas Health Science Center; Joel M Gelfand, MD, Instructor, Department of
Dermatology, Center for Clinical Epidemiology and Biostatistics, University of
Pennsylvania Hospital; and Dirk M Elston, MD, Consulting Staff, Department of
Dermatology, Geisinger Medical Center
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Background: Catscratch disease (CSD), also known as catscratch fever or subacute
regional lymphadenitis, is caused by infection with the bacillus Bartonella henselae .
Typically, a benign and self-limited disease in patients who are immunocompetent, only
a small percentage of patients have complications involving the skin, eye, liver, or
nervous system. Infection of immunocompromised patients with the same organism leads
to a very different disease, bacillary angiomatosis-peliosis (BA/BP), which is
characterized by angioproliferative lesions resembling those of Kaposi sarcoma in the
skin, liver, spleen, bone, and other organs.
Henri Parinaud sometimes is given credit for the first description of CSD in 1889.
However, his oculoglandular syndrome of conjunctivitis with an enlarged preauricular
lymph node ultimately was shown to be only a small subset of the possible clinical
presentations of CSD, the result of inoculation of the CSD agent into the conjunctivae.
Parinaud did not make the association with cat exposure; thus, his contribution is of
limited scope.
The history of CSD has been reviewed comprehensively by Carithers in 1970 and by
Margileth in 1987 and is summarized here.
Debre and a colleague, Semelaigne, observed an unusual case of suppurating epitrochlear
adenitis in a 10-year-old boy at the University of Paris and noted a number of cat
scratches on the affected side. These were believed to be portals of entry for tubercle
bacilli. When the tuberculin skin tests turned out to be negative, the investigators pursued
an infectious cause of feline origin. While bacteriologic investigations yielded no clues,
the physicians continued to observe similar cases of spontaneously remitting regional
lymphadenitis associated with cat scratches in their pediatric population. Debre
postulated tularemia, pasteurellosis, infectious mononucleosis, or tuberculosis as possible
etiologic agents but with no convincing proof.
Foshay, a microbiologist at the University of Cincinnati, suspected CSD to be a possible
manifestation of tularemia. On meeting Debre in 1947, the 2 investigators compared
notes on ``catscratch disease" (Debre) and "cat fever" (Foshay). Foshay had produced an
antigen from the pus of affected patients and achieved what was believed to be a
diagnostic reaction after intradermal injection. Debre and his colleagues subsequently
developed a similar antigen and demonstrated reactions in both old and new cases of
CSD. These results were presented and published in 1950. These investigators also
recorded failure of transmission of CSD to 15 different species of animals and the
possible human-to-human transmission in 1 of 4 cases.
In 1951, Greer and Keefer published the first report of CSD in American literature, in
which they described a broader spectrum of CSD manifestations. In the late 1950s,
William Warwick of the University of Minnesota collaborated with Robert Good, MD, in
an attempt to transmit CSD to "every variety of lab animal from the monkey to the
mouse." Their only positive result was the development of cutaneous lymphadenopathy
in a monkey given intracerebral injections of ground lymph nodes and pus. The first
thorough review of the world's literature, published in 1967, included 567 references and
detailed the manifold clinical presentations. The landmark publication of a series of 1200
cases evaluated by one observer put the varied clinical presentations into perspective and
provided the first realistic analysis of the spectrum of disease.
Discovery and classification of the etiologic agent for CSD is one of the triumphs of
modern microbiology. The elegance and power of molecular taxonomy applied to the
CSD agent revealed unexpected connections with other well-recognized infectious
diseases and a deeper understanding of the pathogenesis of CSD.
Both viruses and Chlamydia had been proposed as possible etiologic agents for CSD,
until a small gram-negative motile coccobacillus was observed in infected lymphatic
tissue using a Warthin-Starry stain and Brown-Hopp tissue Gram stain in 1983 at the
Armed Forces Institute of Pathology. In 1984, Margileth et al, using the same staining
technique, demonstrated identical organisms in biopsy specimens taken from CSD
inoculation papules. The first successful isolation and culture of the CSD organism was
performed by English et al in 1988. Their further studies fulfilled Koch's postulates, and
the organism was determined to be the cause of CSD.
One of the isolates from English's study was investigated at the Centers for Disease
Control, along with additional specimens from Tripler Army Medical Center in
Honolulu. From these specimens, the CSD organism was determined to be a new entity
and given the name Afipia (from Armed Forces Institute of Pathology) felis.
Reports associating another agent (Rochalimaea henselae) with CSD began appearing in
1992. Although they are not closely related, R henselae and A felis are members of the
alpha2 subclass of Proteobacteria and share a similar microscopic appearance and
affinity for the Warthin-Starry stain. R henselae already had been implicated in the
pathogenesis of bacillary angiomatosis (BA), an angioproliferative condition observed in
patients who are immunocompromised. Reports of R henselae-associated CSD appeared,
and new immunological data subsequently supported a major role for R henselae as the
etiologic agent in CSD. Although R henselae now is believed to be the principal
pathogen in CSD, both organisms have been reported in some patients with CSD.
When the sequences of 16S bacterial ribosomal RNA (rRNA) from R henselae and
Bartonella were compared, it became clear that these organisms were so closely related
that they belonged in the same genus. Since Bartonella had historical precedence, R
henselae was renamed Bartonella henselae.
Pathophysiology: Feline infection with B henselae is common and asymptomatic. In the
United States, 28% of surveyed cats had antibodies against the organism. In California,
blood cultures were positive in 56% of domestic cats younger than 1 year and in 34% of
cats older than 1 year. More than three fourths of all cats in California had antibodies to
B henselae as evidence of prior infection; however, only 21% of pet cats were bacteremic
compared to 61% of stray cats.
A similar survey of cats in the Baltimore area found seropositivity in 12-14% of domestic
cats versus 44% of feral animals. Cats can be asymptomatically bacteremic for months,
even while antibody titers are developing. The organism has been isolated from fleas
residing on infected cats. Studies have shown that flea-vectored transmission of infection
among cats occurs with high efficiency and that in the absence of fleas, infected cats do
not transmit the infection to uninfected cats. Although flea-vectored transmission to
humans has not been documented, it could explain some cases in which no history of
exposure to cats exists. Treatment of cats with doxycycline is associated with a reduction
of bacteremia, but whether such treatment prevents relapse or reinfection is unknown.
Familial and household clustering of cases of CSD have been reported. However, only
one member of a family in contact with an infected cat usually is affected. Zangwill et al
found an 18% prevalence of seropositivity to B henselae among family members of
patients with CSD. On further questioning, 43% of these individuals reported symptoms
consistent with CSD during the previous 2 months. In the same study, matched control
subjects not exposed to cats exhibited a 3.6% seropositivity. Carithers found similar
results in a series of 1200 patients; 18.5% of asymptomatic family members had positive
CSD antigen skin tests.
Frequency:
* In the US: CSD is not a reportable infection. Approximately 22,000 cases occur
annually in the United States. The incidence is estimated to be 9.3 cases per 100,000.
Cases of CSD occur throughout the United States. The incidence is greater in regions
with higher temperature and humidity (eg, Hawaii, Pacific Northwest, southeastern
states, coastal California). Regions of lower incidence include Alaska, the Rocky
Mountains, and midwestern states. Incidence peaks in the fall and winter months. These
trends parallel the feline flea population density.
Mortality/Morbidity: CSD generally is a self-limited infection. No deaths from CSD have
been reported in individuals who are immunocompetent. However, significant morbidity
occurs in 5-10% of cases, usually because of involvement of the central or peripheral
nervous system or to multisystem disseminated disease.
Race: No racial predisposition to CSD appears to exist.
Sex: In some case series, a slightly higher incidence of CSD appears to occur in male
patients, while others show equal rates among males and females. One hypothesis to
explain a greater incidence among males is the tendency toward rougher play with kittens
and cats.
Age: CSD affects all age groups, but most patients are younger than 21 years.
* The younger age of individuals most likely to acquire CSD reflects their likelihood
of exposure to the major risk factor, ie, kittens.
* A bias may exist in the literature because pediatricians collected many of the large
case series.
* Adults are more likely to manifest atypical features of CSD.
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History:
* Margileth et al studied a series of 1312 patients referred for chronic
lymphadenopathy. The diagnosis of CSD was confirmed in 1174 patients via catscratch
antigen (CSA) testing, similar to the tuberculosis purified protein derivative (PPD) test.
Of this cohort, 88% exhibited a typical course characterized by lymphadenopathy lasting
an average of 3 months.
* Fever and malaise/fatigue were described in approximately one third of patients,
none of whom were symptomatic for greater than 1 month.
* An unusual presentation was experienced by 11.6% of the cohort. Of these,
Parinaud oculoglandular syndrome (POS) was found in one half of patients, followed in
decreasing order of frequency by encephalopathy (2.3%), systemic disease (2%),
erythema nodosum (0.6%), atypical pneumonia (0.2%), breast tumor (0.2%), and
thrombocytopenic purpura (0.1%).
* A subset of patients with severe systemic disease was observed for 7 years.
* Differences between the group with severe disease and those patients with typical
CSD included more frequent primary skin or mucous membrane lesions, fewer animal
contacts and cat scratches, greater frequency and duration of fevers, and other
constitutional symptoms.
* Skin eruptions (eg, urticaria, vesiculopapular lesions, erythema nodosum)
occurred 4 times more often in the severe CSD group. Demographics of the severe
disease group included a greater percentage of adult males, who tended to have larger
and multiple affected lymph nodes. Fortunately, all patients fully recovered. The greatest
period of recuperation was 4.5 years.
* Another interesting finding from this series was evidence of recurrent CSD.
Three of the patients in the severe disease category experienced recurrences at 4- to
20-month intervals. One patient presented with recurrent cervical lymphadenitis, whereas
the other 2 patients experienced systemic symptoms with periodic fever, malaise,
headache, and weight loss. In one patient, the episodes lasted 1-3 months, with a
20-month interval, while the second patient experienced similar episodes with a
10-month interval.
* The incubation period ranges from 3-30 days.
* Patients may remember a self-healing lesion resembling an insect bite on the
hand, arm, face, or neck.
* The most common presenting complaint of patients seeking medical care is
tender regional lymphadenopathy.
* When questioned, patients may recall being scratched, licked, or bitten by a cat
in the previous 2-8 weeks.
* The scratch is not mandatory since transmission can occur by petting alone with
subsequent self-inoculation via a mucous membrane, skin break, or conjunctiva.
* Approximately 50% of patients experience systemic symptoms (eg, fever,
headache, malaise, myalgias, arthralgias, exanthemas).
* Chronic fluctuant lymphadenitis develops in about 1 month and usually occurs in a
single node or group of regional nodes draining the inoculation site.
* More than 65% of cases involve the nodes in the axillae or anterior or posterior
triangles of the neck. Lymphadenopathy at multiple sites occurs in 37% of cases.
Lymphadenopathy remains regional and regresses over a period of 2-4 months. Rarely, it
may persist for a year or more. Approximately 10-15% of nodes suppurate.
* Table 1. Clinical Manifestations (from Moriarty & Margileth, 1987)
Sign or Symptom Percentage (%) Average Duration (d)
Adenopathy 100 14-180
Adenopathy only 52 14-180
Inoculation site 59-93 7
Fever >101�F 32-60 6
Malaise/fatigue 29 13
Headache 13 4
Anorexia, weight loss, emesis 14 5
Splenomegaly 12 11
Sore throat 5 2
Rash 5 8.5
Parotid swelling 2 --
Conjunctivitis 4.5 --
* Other problems: Atypical CSD occurs in approximately 10% of cases. The following
are considered atypical manifestations of CSD:
* POS is the most common atypical presentation of CSD and is characterized by
unilateral conjunctivitis with adjacent preauricular lymphadenopathy. Examination of the
palpebral conjunctiva on the involved side reveals either a characteristic granulomatous
lesion 2-4 mm in diameter or a frank scratch. While POS has been associated with other
infections (eg, tuberculosis, tularemia, lymphogranuloma venereum), it most commonly
is associated with CSD. Prognosis is identical to that of typical CSD.
* Central nervous system
* Encephalopathy is an uncommon complication of CSD occurring 1-6 weeks
after typical CSD. Most patients are young, in parallel to the spectrum of patients
diagnosed with CSD. Symptoms usually begin with confusion or combative behavior
rapidly progressing within hours to seizures and coma. Seizures occur in one half to three
fourths of patients and may be self-limited or progress to status epilepticus. Coma
complicated by respiratory depression requiring intubation and ventilatory assistance
often is reported. Laboratory examination of cerebrospinal fluid (CSF) is often normal.
However, when CSF studies are abnormal, no consistent patterns emerge. Abnormal
findings in the EEG, when observed, are nonspecific and transient. Recovery is usually
complete in 2-10 days, with no sequelae. Computerized tomographic or magnetic
resonance imaging study findings of the brain are usually normal or reveal transient
abnormalities.
* Transverse myelitis presenting as Brown-Sequard syndrome occurred in a
44-year-old man. The patient experienced rapid resolution of symptoms in a few days
and was asymptomatic within 3 months.
* Cranial or peripheral nerve involvement may occur. Two children with
oculoglandular CSD were reported to have developed transient facial nerve paresis.
Three adult women reportedly developed peripheral neuritis lasting 1-4 months
associated with the onset of lymphadenitis due to CSD.
* Neuroretinitis (Leber stellate neuroretinitis, Leber idiopathic stellate
retinopathy, Leber idiopathic stellate maculopathy) was first described in 1916. Patients
present with painless, unilateral (rarely bilateral) decreased vision associated with central
scotomata. Funduscopic examination reveals optic disc swelling and macular star
formation. Permanent loss of vision is not reported, although recovery may take 1-3
months.
* Hepatosplenic CSD is a rare form of atypical CSD found in patients who are
immunocompetent. Individuals present with daily fevers up to 104�F and no identifiable
cause. Physical examination findings are usually normal, with occasional detection of
well-healed cutaneous scars secondary to cat scratches. Abdominal discomfort is a
common complaint, without focal findings. Lymphadenopathy is present in about one
half of cases. Hepatosplenomegaly, jaundice, and elevated transaminase levels are not
associated with this condition. The diagnosis is based on characteristic filling defects in
the liver and/or spleen as detected by ultrasound or CT scan and a positive B henselae
titer. Administration of intravenous aminoglycoside antibiotics has been reported to be
helpful. Most patients become afebrile within 48 hours of initiating treatment; however,
in a few cases, fever has persisted for up to a month even with antibiotics.
* Blood culture-negative endocarditis has been reported. Bartonella species
account for about 3% of all cases of endocarditis, and, now, many cases of blood
culture-negative endocarditis are believed to be the result of infection with Bartonella
species. Some cases diagnosed as Chlamydia endocarditis also are likely to be caused by
Bartonella species because of the high prevalence of cross-reacting antibodies. Of 22
patients proven to have Bartonella endocarditis, 4 were infected with B henselae. Contact
with cats was a significant risk factor in this group.
Physical:
* Careful examination may reveal an inoculation papule in up to 90% of patients.
* Given the tendency to hold cats against one's chest, the lesion most often is
found on the head or upper extremities.
* Include the scalp, finger web spaces, eyelids, and conjunctiva in a thorough
inspection. Multiple sites may be infected.
* The initial lesion evolves from a small, 2- to 5-mm reddish brown macule or vesicle
to a papule or pustule over the course of several days. Often, it is mistaken for an insect
bite.
* Lesions typically are nonpruritic and heal in days to months without scarring.
* Conjunctival CSD may manifest as nonsuppurative conjunctivitis or ocular
granuloma.
* Lymphadenitis involving 1 or more nodes in the proximal drainage area of regional
lymphatics occurs in all CSD cases approximately 2 weeks (range 5-50 d) after initial
inoculation.
* Nodes are tender and range in size from 1-5 cm, occasionally exceeding 10 cm.
The overlying skin may be erythematous, but only rarely is an associated cellulitis
present.
* The most commonly involved nodes are in the cervical, axillary, inguinal,
femoral, preauricular, supraclavicular, and epitrochlear areas.
* Lymphadenopathy involving multiple sites occurs in about one third of patients.
* Lymphadenitis resolves over 2-4 months, rarely persisting longer than a year.
* Other dermatologic manifestations occur in about 5% of patients and are more likely
to occur in patients with more severe or atypical disease.
* These manifestations include macular, maculopapular, morbilliform, and
petechial rashes. They typically are nonpruritic and resolve in days to weeks.
* Cases of erythema multiforme, erythema nodosum, erythema annulare, and
ecchymoses associated with thrombocytopenia rarely have been reported in patients with
CSD.
* Table 2. Clinical Manifestations of Catscratch Disease (from Margileth et al,
1987 and Carithers, 1985)
Clinical Feature Margileth,
n = 1174
(Percent, %) Carithers,
n = 1200
(Percent, %)
Typical presentation 88.4 95
Inoculation lesion (skin, eye, mucous membrane) 58.6
Unusual presentation 11.6 5
Parinaud oculoglandular syndrome 6.3 4
Encephalopathy 2.3 0.25
Systemic disease, severe, chronic 2.0
Erythema nodosum 0.6 0.42
Atypical pneumonia 0.2
Breast tumor 0.2
Thrombocytopenic purpura 0.1 0.08
Causes: B henselae, the etiologic agent for CSD, is a small, fastidious, slow-growing,
gram-negative, aerobic, nonmotile, pleomorphic bacillus. Although domestic cats are the
principal reservoir for this bacterium, occasional cases of infection associated with dog
and monkey bites have been reported.
* Risk factors for acquiring CSD include ownership of a cat younger than 12 months,
having been bitten or scratched by a kitten, and owning at least 1 kitten with fleas.
* More than 90% of patients with CSD have a history of exposure to cats, and 75% of
patients have a history of a cat scratch or bite, usually from a healthy kitten.
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Coccidioidomycosis
Cutaneous T-Cell Lymphoma
Drug-Induced Pseudolymphoma Syndrome
Leishmaniasis
Lymphogranuloma Venereum
Mycobacterium Marinum Infection of the Skin
Nocardiosis
Sarcoidosis
Sporotrichosis
Syphilis
Other Problems to be Considered:
Consider all causes of subacute and chronic lymphadenopathy and include the following:
* Typical and atypical mycobacterial infection
* Nonspecific bacterial lymphadenitis
* Lymphogranuloma venereum
* Tularemia
* Brucellosis
* Mononucleosis
* Syphilis
* Toxoplasmosis
* Systemic mycoses
* Sarcoidosis
* Nodular lymphomas
* Drug reactions
Infection with cytomegalovirus, human immunodeficiency virus-1, or Epstein-Barr virus
usually is associated with lymphadenitis at more than one site.
Consider the following additional diagnoses with the presence of persistent skin papules
and regional lymphadenopathy: leishmaniasis, nocardiosis, and fungal infections (eg,
coccidioidomycosis, sporotrichosis, histoplasmosis).
Since the clinical manifestations of infection with B henselae are different in patients
who are immunocompromised, an entirely different differential diagnosis is appropriate.
Bartonella infection leads to vasculoproliferative lesions, namely BA (B henselae,
Bartonella quintana) and peliosis (B henselae only). The clinical differential diagnosis
includes the following: malignant neoplasms (eg, Kaposi sarcoma, angiosarcoma) and
benign reactive conditions (eg, pyogenic granuloma, angiolymphoid hyperplasia with
eosinophilia).
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Lab Studies:
* Typically, the diagnosis is based on the presence of 3 of the 4 following criteria:
* Contact with a cat in association with a scratch or lesion of the dermis, eye, or
mucous membrane
* Positive skin test for CSD
* Regional lymphadenopathy in the absence of other causes as ascertained by PPD
testing, serologic studies, and cultures of lymph node aspirates
* Characteristic histopathology in a biopsy of skin or lymph node
* CSA skin testing, which uses a preparation derived from infected lymph node tissue
of other infected humans, is similar to the intradermal tuberculin PPD procedure. The
antigen test is no longer widely available because of concern for the potential
transmission of hepatitis viruses, HIV, and prions.
* Skin testing is no longer warranted and largely has been replaced by antibody titer
testing using immunofluorescent antibody (IFA) and enzyme-linked immunosorbent
assay (EIA) techniques.
* Of patients suspected of having CSD, 88% have detectable antibody, versus 3%
of healthy controls.
* The prevalence of seropositivity in cats living in the same house as a human with
CSD is 81%, versus 14-44% in unselected households.
* Lymph node biopsy generally is not indicated in typical cases of CSD given the
associated morbidity and expense. Node aspiration in patients suspected of having CSD
traditionally has been discouraged for fear of fistula formation.
* Entertain a biopsy of skin or affected lymph node in cases of possible malignancy or
in an unclear presentation in an immunocompromised host.
* CBC findings are usually normal, although a mild leukocytosis or eosinophilia may
be present.
* Erythrocyte sedimentation rate may be mildly or moderately elevated.
* PPD should be nonreactive.
Imaging Studies:
* Imaging procedures are not diagnostic in patients with CSD but may be helpful in
excluding other conditions in the differential diagnosis. Atypical CSD may exhibit
hepatic or splenic lesions, usually round or oval, ranging from 3-30 mm. They are
hypodense on noncontrast CT scan. Injection of contrast material may yield hypodense,
isodense, or marginally enhanced lesions when compared to normal parenchyma. These
lesions have been observed to spontaneously resolve or calcify over weeks to months.
Procedures:
* Skin biopsy of the inoculation papule may be diagnostic.
* Aspiration of suppurating nodes is both a diagnostic and therapeutic procedure.
* Treat recurrence of suppuration by incision and drainage.
* The risk of fistulous sinus tract formation is small. This has been reported only in
cases of atypical mycobacterial lymphadenopathy mistaken for CSD.
* Biopsy of affected nodes is indicated only when attempting to establish a diagnosis
other than CSD.
Histologic Findings:
Skin: The dermis contains variously shaped (round, triangular, stellate) areas of necrosis
or necrobiosis surrounded by an inner zone of palisading epithelioid histiocytes with a
few multinucleated giant cells and an outer zone of lymphocytes. Organisms (visualized
with the Warthin-Starry stain or the Brown-Hopp modification of the Gram stain) appear
in the necrotic areas singly, in chains, or in clusters.
Lymph nodes: Focal areas of necrosis with neutrophilic infiltration occur near the
germinal centers of lymph nodes. Organisms line the vascular sinuses. When necrosis is
present, organisms may be seen within histiocytes as well as extracellularly in the
necrotic areas and in the lumina of thrombosed blood vessels. Organisms are fewer in
number in necrotic areas extensively infiltrated with neutrophils. With disease
progression, granulomas may appear with central necrosis and multinucleated giant cells.
Late findings include stellate microabscesses, which may fuse within suppurating nodes.
Liver: Hepatic parenchyma may be replaced by zones of organizing granulation tissue
containing focal areas of granulomatous inflammation with stellate areas of central
necrosis. The necrotic areas are infiltrated with neutrophils and are surrounded by
palisading fibroblasts.
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Medical Care: Margileth et al reported the results of antibiotic therapy with 18 different
antimicrobials for CSA-proven CSD in 268 adult and pediatric patients in a 1992 study.
Augmentin, amoxicillin, erythromycin, erythromycin-sulfasoxazole, dicloxacillin,
cephalexin, cefadroxil, tetracycline, doxycycline, penicillin, cephradine, cefaclor,
ceftriaxone, and cefotaxime were found to be of little or no value. Rifampin (efficacy of
87%), ciprofloxacin (efficacy of 84%), gentamicin IM (efficacy of 73%), and
trimethoprim/sulfamethoxazole (efficacy of 58%) were considered moderately to highly
effective, which was defined by 3 days or more of antibiotic treatment and patients'
improvement within 3-10 days. In conclusion, Margileth concluded that these 4
antibiotics were the most effective and should be considered for patients with severe
CSD. As for most patients with mild or moderate CSD, conservative symptomatic
treatment is recommended.
Somewhat paradoxically, patients with AIDS and BA/BP frequently respond to a variety
of commonly used antibiotics. Response to erythromycin, isoniazid, rifampin,
doxycycline, and ethambutol is reported by Koehler et al.
Table 3. Response to Medications
Ciprofloxacin
500 PO bid 5 adults ``Dramatic improvement'' in a few days Holley, 1991
Gentamicin
5 mg/kg/d IV/IM 3 febrile children, 2 with hepatitis, 1 with painful regional
lymphadenopathy Resolution of fever and systemic symptoms in 1 or 2 days Bogue et al,
1989
TMP/SMX
6-8 mg TMP/kg/d PO 60 patients with prolonged fever, systemic symptoms 58%
effective, 7-day course Margileth, 1992
Rifampin 10-20 mg/kg/d PO/IV 60 patients with prolonged fever, systemic symptoms
87% effective, 7- to 14-day course Margileth, 1992
Azithromycin
500 mg PO qd for 1 d, then 250 mg PO qd for 4 d Prospective placebo controlled double
blind study of 29 patients 80% of lymph node volume (measured by ultrasonography)
resolved in 30 days in 7 of 15 patients on azithromycin vs 1 of 15 control patients Bass et
al, 1998
* While Bartonella species are exquisitely sensitive to antibiotics in vitro, antibiotic
treatment of typical CSD is variably successful.
* Because of the potential risk of arthropathy, caution should be taken if considering
the use of fluoroquinolones in patients younger than 18 years.
* Supportive treatment includes hydration and analgesics.
* Warm moist compresses may be applied to tender nodes.
* Avoid trauma or unnecessary manipulation.
Surgical Care: Perform aspiration of suppurative nodes, as detailed in Procedures.
Activity: Bed rest or isolation is not indicated.
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Margileth et al reported the results of antibiotic therapy with 18 different antimicrobials
for CSA-proven CSD in 268 adult and pediatric patients. See Treatment for reported
efficacy and precautions.
Drug Category: Antibiotics -- Empiric antimicrobial therapy must be comprehensive and
should cover all likely pathogens in the context of the clinical setting. Antibiotic
selection should be guided by blood culture sensitivity whenever feasible.
Drug Name
Ciprofloxacin (Cipro) -- Fluoroquinolone with activity against pseudomonads,
streptococci, MSSA, Staphylococcus epidermidis, and most gram-negative organisms but
no activity against anaerobes. Inhibits bacterial DNA gyrase and consequently growth.
Continue treatment for at least 2 d after signs and symptoms have disappeared (7-14 d
typically).
Adult Dose 250-500 mg PO bid for 7-14 d
Pediatric Dose <18 years: Not recommended
Contraindications Documented hypersensitivity
Interactions Antacids, iron salts, and zinc salts may reduce serum levels; administer
antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with
metabolism of fluoroquinolones; ciprofloxacin reduces therapeutic effects of phenytoin;
probenecid may increase ciprofloxacin serum concentrations; may increase toxicity of
theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase
effects of anticoagulants (monitor PT)
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions During prolonged therapy, perform periodic evaluations of organ system
functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment;
superinfections may occur with prolonged or repeated antibiotic therapy
Drug Name
Gentamicin (Garamycin) -- Aminoglycoside antibiotic for gram-negative coverage. Binds
bacterial 30S and 50S ribosomal subunits. Used in combination with both an agent
against gram-positive organisms and an agent that covers anaerobes.
Not the DOC. Consider if penicillins or other less toxic drugs are contraindicated, when
clinically indicated, and in mixed infections caused by susceptible staphylococci and
gram-negative organisms. Dosing regimens are numerous; adjust dose based on CrCl and
changes in volume of distribution. May be given IV/IM.
Follow each regimen by at least a trough level drawn on the third or fourth dose (0.5 h
before dosing); may draw a peak level 0.5 h after 30-min infusion.
Adult Dose Serious infections and normal renal function: 3 mg/kg/dose IV q8h
Loading dose and maintenance dose: 1-2.5 mg/kg IV and 1-1.5 mg/kg IV, respectively,
q8h
Extended dosing regimen for life-threatening infections: 5 mg/kg/d IV/IM divided q6-8h,
usually effective within 72 h
Pediatric Dose <5 years: 2.5 mg/kg/dose IV/IM q8h
>5 years: 1.5-2.5 mg/kg/dose IV/IM q8h or 6-7.5 mg/kg/d divided q8h; not to exceed 300
mg/d; monitor as in adults
Contraindications Documented hypersensitivity; non-dialysis-dependent renal
insufficiency
Interactions Coadministration with other aminoglycosides, cephalosporins, penicillins,
and amphotericin B may increase nephrotoxicity; aminoglycosides enhance effects of
neuromuscular blocking agents, thus prolonged respiratory depression may occur;
coadministration with loop diuretics may increase auditory toxicity of aminoglycosides;
possible irreversible hearing loss of varying degrees may occur (monitor regularly)
Pregnancy D - Unsafe in pregnancy
Precautions Narrow therapeutic index (not intended for long-term therapy); congenital
deafness reported in pediatric patients exposed in utero; caution in renal failure (not on
dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular
transmission; adjust dose in renal impairment
Drug Name
Trimethoprim and sulfamethoxazole (Bactrim DS, Septra) -- Inhibits bacterial growth by
inhibiting dihydrofolate reductase, depleting folic acid. Antibacterial activity of
TMP-SMZ includes common urinary tract pathogens, except Pseudomonas aeruginosa.
Adult Dose 160 mg TMP/800 mg SMZ PO q8-12h (6-8 mg/kg/d of TMP component) for
7 d
Pediatric Dose <2 months: Do not administer
>2 months: 10-20 mg/kg/d (based on TMP) PO divided q6-8h for 14 d
Contraindications Documented hypersensitivity; megaloblastic anemia due to folate
deficiency
Interactions May increase PT when used with warfarin (perform coagulation tests, and
adjust dose accordingly); coadministration with dapsone may increase blood levels of
both drugs; coadministration of diuretics increases incidence of thrombocytopenia
purpura in elderly patients; phenytoin levels may increase with coadministration; may
potentiate effects of methotrexate in bone marrow depression; hypoglycemic response to
sulfonylureas may increase with coadministration; may increase levels of zidovudine
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Discontinue at first appearance of skin rash or sign of adverse reaction;
obtain CBCs frequently; discontinue therapy if significant hematologic changes occur;
goiter, diuresis, and hypoglycemia may occur with sulfonamides; prolonged IV infusions
or high doses may cause bone marrow suppression (if signs occur, give 5-15 mg/d
leucovorin); caution in folate deficiency (eg, long-term alcoholics, elderly patients, those
receiving anticonvulsant therapy, those with malabsorption syndrome); hemolysis may
occur in G-6-PD deficient individuals; AIDS patients may not tolerate or respond to
TMP-SMZ; caution in renal or hepatic impairment (perform urinalyses and renal
function tests during therapy); give fluids to prevent crystalluria and stone formation
Drug Name
Rifampin (Rifadin, Rimactane) -- Inhibits DNA-dependent bacterial but not mammalian
RNA polymerase.
Adult Dose 10-20 mg/kg/d PO/IV divided bid/tid for 7-14 d; not to exceed 1.2 g/d
Pediatric Dose Administer as in adults
Contraindications Documented hypersensitivity
Interactions Induces microsomal enzymes, which may decrease effects of
acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, beta-blockers,
chloramphenicol, oral contraceptives, corticosteroids, mexiletine, cyclosporine,
digitoxin, disopyramide, estrogens, hydantoins, methadone, clofibrate, quinidine,
dapsone, tazobactam, sulfonylureas, theophyllines, tocainide, and digoxin; blood pressure
may increase with coadministration of enalapril; coadministration with isoniazid may
result in higher rate of hepatotoxicity than with either agent alone (discontinue one or
both agents if alterations in LFTs occur)
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Obtain CBC and baseline clinical chemistries prior to and throughout
therapy; in liver disease, weigh benefits against risk of further liver damage; interruption
of therapy and high-dose intermittent therapy are associated with thrombocytopenia that
is reversible if therapy is discontinued as soon as purpura occurs; if treatment is
continued or resumed after appearance of purpura, cerebral hemorrhage or death may
occur
FOLLOW-UP Section 8 of 10 [Click here to go to the previous section in this topic]
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topic]
Author Information Introduction Clinical Differentials Workup Treatment Medication
Follow-up Pictures Bibliography
Deterrence/Prevention:
* Pet quarantine, disposal, or euthanasia is unnecessary.
* Although doxycycline treatment of cats is associated with decreased B henselae
bacteremia, this treatment has not been shown to reduce the risk of cat-to-human
transmission.
* Feline B henselae bacteremia has been reported to last from weeks to months, with
100-fold fluctuations in bacteremic levels and intermittent negative cultures.
* The natural history of feline infection and infectivity remains unknown.
* Given the established link between flea infection and B henselae transmission,
common sense measures seem prudent (eg, avoiding stray cats, keeping pets free of
fleas).
Prognosis:
* CSD generally is a self-limited infection.
* No deaths have been reported from CSD in individuals who are immunocompetent.
However, significant morbidity occurs in 5-10% of cases, usually due to involvement of
the central or peripheral nervous system or to multisystem disseminated disease.
PICTURES Section 9 of 10 [Click here to go to the previous section in this topic]
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topic]
Author Information Introduction Clinical Differentials Workup Treatment Medication
Follow-up Pictures Bibliography
Caption: Picture 1. Papulopustular lesions of a primary inoculation site on the hand of a
16-year-old patient. These lesions had been present for about 3 weeks. A catscratch
antigen skin test was positive with 15-mm induration. No treatment was administered,
and her condition resolved spontaneously in 2.5 months. Andrew Margileth, MD,
contributed the image and history.
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Caption: Picture 2. A crusted primary inoculation papule on the neck of a 4-year-old
child. Note the adjacent lymphadenitis. This patient had contact with cats and multiple
scratches. Andrew Margileth, MD, contributed the image and history.
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Caption: Picture 3. This 10-year-old child had contact with dogs but not cats. The
impressive lymphadenitis had been present for 5 weeks and was not tender. Pathologic
examination of a biopsy of the lymph node revealed nonspecific changes. She had a
positive catscratch disease skin test and negative purified protein derivative skin tests.
Treatment with cephalexin was administered with a good response. Complete resolution
occurred in 4.5 months. Andrew Margileth, MD, contributed the image and history.
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Caption: Picture 4. This 13-year-old girl developed fatigue and malaise after being licked
and scratched by a cat. The typical conjunctival granuloma was accompanied by a
parotid mass and intraparotid adenitis. No treatment was administered, and all her signs
and symptoms resolved in 3 months. Andrew Margileth, MD, contributed the image and
history.
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Caption: Picture 5. This 9-year-old boy developed catscratch disease (CSD) encephalitis
and a papular pruritic dermatitis after sustaining cat scratches and developing regional
lymphadenitis. He was in a coma for 4 days but experienced a complete and rapid
recovery within 3 weeks. Biopsy of the skin rash revealed nonspecific changes. The CSD
antigen skin test was positive. Andrew Margileth, MD, contributed the image and history.
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Caption: Picture 6. This 2 1/2-year-old boy was recovering from catscratch disease
acquired 10 months before when he developed this neck abscess over a period of 3
weeks. Biopsy revealed caseating granulomas; acid-fast bacillus and Warthin-Starry stain
results were negative. Andrew Margileth, MD, contributed the image and history.
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Caption: Picture 7. This 22-year-old man complained of blindness in his right eye
beginning 11 days after an illness characterized by fever, malaise, chills, nausea, and
tender left femoral lymphadenopathy. He had a history of cat scratches and had 2
inoculation papules on his thigh. The image of the retina shows papilledema and stellate
retinitis. His vision returned to baseline in 3 months. He had no reoccurrence in 3 years
of follow-up care. Andrew Margileth, MD, contributed the image and history.
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Caption: Picture 8. Light micrograph of lymph node tissue showing follicular hyperplasia
and focal areas of necrosis. Andrew Margileth, MD, contributed the image.
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Caption: Picture 9. Warthin-Starry stained sections of lymph node showing chains and
clusters of organisms. Andrew Margileth, MD, contributed the image.
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BIBLIOGRAPHY Section 10 of 10 [Click here to go to the previous section in this
topic] [Click here to go to the top of this page]
Author Information Introduction Clinical Differentials Workup Treatment Medication
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