AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Catscratch disease is a regional lymphadenitis affecting those lymph nodes that drain the sites of inoculation. It is one of the most common causes of chronic lymphadenopathy in children and adolescents.

In most cases, the causative agent is Bartonella henselae. The initial symptom is formation of a papule at the inoculation site, followed by regional lymphadenopathy within 1-2 weeks.

Catscratch disease usually is self-limited and resolves spontaneously over 2-4 months.

Pathophysiology

Many organ systems are affected, including the lymph nodes, CNS, eyes (neuroretinitis), skin (bacillary angiomatosis, erythema nodosum, erythema multiforme), lungs, and bones (arthritis and osteomyelitis).

Lymph nodes

In general, lymph nodes become enlarged in the 1-2 weeks after exposure. They are often tender and occasionally become fluctuant.

Lymphoid hyperplasia with arteriolar proliferation and reticular cell hyperplasia is seen early in the disease. As the disease progresses, granulomas appear, with central necrosis and multinucleated giant cells. Finally, stellate microabscesses form, and nodes can become fluctuant.

Central Nervous System

Encephalopathy is the most common neurologic manifestation, occurring in 2-3% of patients. This complication may be more common in adults than in children. The onset is usually abrupt and occurs 1-6 weeks after the lymphadenopathy becomes apparent.

Patients can become confused and disoriented, and their condition can deteriorate to coma. About 50% of patients have a fever. Focal findings of hemiparesis and reflex abnormalities may be noted. Seizures, which occur in as many as 80% of patients with neurologic sequelae, are often prolonged and recurrent.

The pathogenesis of encephalopathy is unknown, but it is not likely due to direct infection, because CSF is usually normal and recovery is rapid, often without antibiotic therapy. CT scans are often normal, and CSF examination shows mononuclear pleocytosis in 20-30% of patients. Electroencephalographs (EEGs) show nonspecific slowing. Recovery is usually complete in a 1 week or longer, but persistent neurologic deficits have been reported.

Neuroretinitis

Patients with neuroretinitis generally present with painless, unilateral visual loss. Examination reveals decreased visual acuity, decreased color vision, and centrocecal scotoma. The optic disc appears edematous, and exudates frequently surround the macula.

Neuroretinitis is possibly due to a subretinal angiomatous nodule similar to that seen in bacillary angiomatosis.

Bacillary angiomatosis

Bacillary angiomatosis almost exclusively occurs in patients who are immunocompromised. Skin lesions consisting of numerous brown to violaceous or colorless vascular tumors of the skin and the subcutaneous tissue are the most common manifestation. Disseminated disease may involve bone, liver, spleen, lymph nodes, the gastrointestinal and respiratory tracts, and bone marrow.

B henselae and Bartonella quintana have been isolated from samples of cutaneous and osseous bacillary angiomatosis lesions. Histologic examination with Warthin-Starry staining reveals vascular proliferation with numerous bacillary organisms.

Pulmonary

Six cases of catscratch disease with pneumonia and 8 cases with pleural thickening and/or effusion have been reported. In these cases, pulmonary features developed 1-5 weeks after lymphadenopathy occurred. Systemic signs of infection, including fever, were present in 85%. One case in which a massive abscess involved the chest wall has been reported.

Frequency

United States

Catscratch disease is seen in all regions of the United States. Approximately 22,000 cases are diagnosed each year. Seroprevalence among cats is highest in the southeastern states, coastal California, Hawaii, and the Pacific Northwest. In temperate climates, rates of catscratch disease seem to peak between September and March (75% of cases). In warmer climates, cases are seen between July and August.

The incidence among inpatients is estimated to be 6.6 cases per 100,000 population. However, this estimate likely is low, given that most patients are not admitted to the hospital.

Only 1 genotype of B henselae has been reported in North America.

International

Catscratch disease occurs worldwide. At least 2 genotypes of B henselae have been isolated from cats in Europe. B henselae is endemic in Europe, Africa, Australia, and Japan.

Mortality/Morbidity

No deaths due to catscratch disease in immunocompetent patients have been reported. Most patients with typical catscratch disease remain afebrile and do not have constitutional symptoms.

• Lymphadenopathy occurs in the nodal regions draining the inoculation site. These include the upper extremities (46%) and the cervical and submandibular (26%), inguinal (17%), preauricular (6%), and clavicular (2%) regions.
• Patients with atypical catscratch disease can present with prolonged fever, malaise, fatigue, myalgia, weight loss, and hepatosplenomegaly. Patients presenting with disseminated catscratch disease involving the liver and spleen without associated lymphadenitis have been reported.

Race

No racial predilection exists.

Sex

Catscratch disease occurs more frequently in males than in females, with a ratio of 3:2.

Age

• More than 80% of cases occur in persons younger than 21 years.
• Only 10-20% of cases occur in adults.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• History of exposure to cats is a key feature in making the diagnosis.
• Patients often present with chronic (>2-wk) history of tender regional lymphadenopathy. The location of enlarged nodes depends on the site of inoculation, which is usually in the extremities.

Physical

• Physical examination reveals tender lymphadenopathy, often with overlying erythema. About 80% of patients present with tender lymphadenopathy within 1-2 weeks of their exposure.
• • The inoculation site can be identified in up to 65% of patients on careful examination of the skin. The site appears as a macule, papule, or vesicle. The lesion can appear 3-10 days after inoculation and lasts for several days to months.
  • More than 80% of involved lymph nodes occur in the head and neck region, arms, and axillae. In 44-85% of patients, a solitary enlarged node may be present. In 20% of patients, multiple nodes in a single region are involved.
  • Approximately 30% of patients have involved nodes at multiple sites. Examine these patients for multiple inoculation sites. The involved lymph nodes are 1-5 cm, with some nodes as large as 8-10 cm.
  • Suppuration of the involved nodes occurs in 8.5-30% of patients, and the risk of suppuration is proportionate to the size of the lymphadenopathy. In general, lymphadenopathy diminishes over 2-6 weeks, but it can persist for as long as 2 years.
• Fever is present in only 30-50% of patients and generally lasts for 1-7 days. About 32% of patients have prolonged fever, or one lasting up to 3 weeks. Such fever suggests progression to suppurative lymphadenitis.
• Malaise, fatigue, and other constitutional symptoms occur in up to 30% of patients.
• Headache, sore throat, and anorexia are noted in approximately 13% of patients.
• Less common symptoms are splenomegaly (11%), exanthems (4.5%), conjunctivitis (4.3%), and parotid swelling (1.4%). Although erythema nodosum, erythema marginatum, erythema multiforme, and erythema annulare have been associated with catscratch disease, exanthems consist of a truncal maculopapular rash.
• Atypical findings occur in 10-14% of patients. Parinaud oculoglandular syndrome, found in 2-17% of patients, consists of conjunctival granuloma at the inoculation site and preauricular adenopathy.
• Submandibular and cervical adenopathy also may occur. Etiology of this syndrome probably involves rubbing of the eyes after contact with a cat.
• Other atypical manifestations are thrombocytopenic purpura; osteitis resembling bacterial osteomyelitis; hepatosplenomegaly; and CNS involvement, including transverse myelitis, radiculitis, cerebral arteritis, polyneuritis, and meningitis.
• Patients with AIDS have an increased risk of catscratch disease.
• • The inoculation sites may be difficult to distinguish from Kaposi sarcoma.
  • The normally benign course of catscratch disease may be life threatening to an immunocompromised host.

Causes

• B henselae and B quintana most often are implicated in catscratch disease.
• Other possible causes are Bartonella clarridgeiae and Afipia felis.
• More than 90% of patients with catscratch disease report an exposure to cats.
• • About 75% of these patients give a history of cat scratch or bite.
  • B henselae has been isolated from fleas from infected cats.
  • Cats that transmit the illness do not show signs of the disease.
• Cases occurring after scratches from thorns, wood splinters, and crab claws have occurred. However, in each of these cases, the patient recalled that a cat licked the abrasion.
• Dogs have been implicated in 5% of cases.
• Familial outbreaks have been documented and have usually involved siblings, or in rare instances parents.
• • Symptoms among siblings often appear within 3 weeks of the index case.
  • In approximately 1% of diagnosed cases, no animal scratch is implicated.
• Person-to-person transmission has not been documented.
• • The infectious agent is transmitted only from cat to human for a period of 3 weeks.
  • The mode of transmission is direct contact from a scratch, bite, or lick of an infected animal.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

AIDS
Brucellosis
Coccidioidomycosis
Cytomegalovirus infection
Herpes simplex infection
Histoplasmosis
Hodgkin disease
Infectious mononucleosis
Kawasaki disease
Leukemia
Lymphogranuloma venereum
Lymphoproliferative disease
Metastatic carcinoma
Mycobacterial lymphadenitis
Mycoplasma hominis
Nocardia infection
Non-infectious causes cysts or dermoids
Reactive hyperplasia
Sarcoidosis
Sporotrichosis
Staphylococcus aureus infection
Streptococcal infection
Syphilis
Toxoplasmosis
Tularemia infection
Yersinia infection

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Culturing Bartonella species is difficult, as the ideal medium has not been established. Blood agar often is used, and incubation for up to 6 weeks is frequently necessary.
• Various serologic tests have been used to confirm catscratch disease.
• • A standard course of anti-B henselae immunoglobulin G (IgG) and immunoglobulin M (IgM) production does not seem to exist. Some patients with catscratch disease have high levels of both IgG and IgM, some have high levels of only IgM, and others have low levels of both.
  • Indirect fluorescence assay (IFA) has a sensitivity of up to 100% in some series and a specificity of 98%. About 84% of patients have positive titers within 1-2 weeks of clinical catscratch disease, and 16% develop positive titers 4-8 weeks later.
  • Enzyme-linked immunoassay (ELISA) testing for IgM has a sensitivity of 95% and a specificity of 77%. ELISA for IgG has a sensitivity of only 18%. Genotypic and phenotypic differences between B henselae strains are widely encountered and lead to antigenic variation and difficulty in interpreting the results of serologic tests.
  • The sensitivity of polymerase chain reaction (PCR) with samples of lymph node tissue or aspirates is 30-60% for catscratch disease. If histologic and serologic tests are coupled with PCR analysis, the sensitivity increases to 87%. PCR can be used to differentiate species, subspecies, and strains of Bartonella organisms.
• Results of CSF examination are usually normal, despite involvement of the CNS. However, CSF testing may show minimal pleocytosis or elevated protein levels.
• Skin tests have also been performed.
• • Because the antigen is prepared by heating pus aspirated from suppurative nodes from patients with catscratch disease, skin testing is controversial because of the risk of transmission.
  • A positive result is at least 5 mm of induration at 48-72 hours after an inoculation with 0.1 mL of test material. As many as 90% of patients with suspected catscratch disease have positive skin test results. The result may remain positive for as long as 28 years after the initial episode of catscratch disease.
  • False-negative tests may occur in patients who have had symptoms for less than 3-4 weeks. Patients with positive skin test results for B henselae have antibody titers to B henselae that are higher than those of controls.
  • Up to 15% of patients with chronic lymphadenitis have mycobacterial infection. Therefore, a purified protein derivative (PPD) test should be performed to rule out tuberculous and nontuberculous lymphadenitis.

Imaging Studies

• Ultrasonography may be performed to determine if a lymph node is fluctuant and amenable to needle aspiration.
• In patients with CNS involvement, imaging studies are often nondiagnostic.
• Chest radiograph should be considered to rule out tuberculosis, sarcoidosis, and mycoses.
• CT scanning of the abdomen may be helpful in patients with hepatosplenomegaly, in whom they may reveal multiple granulomata.
• On bone scintigraphy, bone lesions of catscratch disease show increased radionuclide uptake.

Other Tests

• EEG may show abnormal activity in patients with seizures or encephalopathy.
• EEG findings usually return to normal after several months.

Procedures

• Lymph node biopsy is generally not necessary, but it is useful when the diagnosis is uncertain or when atypical clinical and laboratory findings are observed.

Histologic Findings

In patients with catscratch disease, Warthin-Starry silver and Gram stains show small gram-negative pleomorphic bacilli in lymph node tissue or aspirates.

Histopathologic findings of the lymph nodes depend on the stage of infection. Lymphoid hyperplasia with arteriolar proliferation, reticulum cell hyperplasia, and widening of arteriolar walls are seen early in the disease.

Progression of the disease is manifested by granulomas with central necrosis and multinucleated giant cells. Microabscesses may be seen as the granulomas and areas of necrosis coalesce.

Lymphogranuloma inguinale, atypical mycobacteriosis, yersiniosis, tularemia, brucellosis, and chronic granulomatous disease of childhood may have histologic features similar to those of catscratch disease and should be considered in the differential diagnosis.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• Catscratch disease is usually self-limited and requires no specific treatment.
• • Antipyretics and analgesics may be required.
  • Use of antibiotics is controversial and not indicated in most patients.
• Use of trimethoprim-sulfamethoxazole, ciprofloxacin, gentamicin, and erythromycin has been associated with clinical improvement, but most reports are anecdotal.
• In cases with neurologic bacillary angiomatosis or ocular manifestations, patients have improved with antibiotic therapy and supportive care or with supportive care alone.
• Antibiotics with high intracellular concentrations, such as erythromycin, doxycycline, clarithromycin, azithromycin, rifampin, and gentamicin, appear to be effective.
• In patients with thoracic and/or pulmonary disease, especially in association with prolonged fever and systemic symptoms, a trial of oral trimethoprim-sulfamethoxazole, ciprofloxacin, or azithromycin 2-3 times daily for 7-21 days is recommended.
• In the rare case of a severely ill patient, intramuscular gentamicin 5 mg/kg/d may be effective within 72 hours.
  • In patients who are immunodeficient, treatment with erythromycin, clarithromycin, azithromycin, doxycycline, or tetracycline has been effective.
  • Continue treatment in patients who are severely ill for 6-8 weeks, and treat patients who have relapses for 4-6 months.

Surgical Care

• Needle aspiration may provide pus for the diagnosis and symptomatic relief of an enlarged gland. Repeated aspirations may be performed if pus reaccumulates and pain recurs.
• Incision and drainage is best avoided because the procedure leaves a scar and carries the risk of creating a draining fistula.
• Surgical excision of an enlarged node is indicated when the diagnosis is in question or when repeated aspirations fail to relieve the patient's pain.
• Excision of a persistent ocular granuloma may be required.

Consultations

• Consultation specialists, as indicated by the patient's clinical course.
• Consultation with a neurologist is indicated for patients with CNS involvement, and evaluation with an ophthalmologist may be needed in patients with any visual changes.

Activity

• Patients should avoid any trauma to the involved lymph node regions.
• In general, activity should be allowed as tolerated, and patients do not need to be isolated to prevent transmission.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Azithromycin may be an effective treatment for catscratch disease. It reduces the time for lymph nodes to return to normal size and decreases the constitutional symptoms. Azithromycin was beneficial in a prospective, randomized, double-blind, placebo-controlled study.

Other potentially beneficial medications have had anecdotal success; these include trimethoprim-sulfamethoxazole, ciprofloxacin, gentamicin, and erythromycin.

Drug Category: Antibiotics

These agents reduce the duration of lymphadenopathy and decrease constitutional symptoms.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Most patients can be treated on an outpatient basis.
• If admission is required, frequent monitoring of the adenitis is indicated to evaluate for suppurative complications.
• Aspiration is indicated if nodes become fluctuant and painful. Repeated needle aspiration may be required if fluctuation or pain recurs.

Further Outpatient Care

• Closely follow up patients for 6 months or until the lymphadenopathy resolves.
• • Neurologic complications can occur up to 6 weeks after inoculation.
  • Instruct parents to seek medical attention if they notice any abnormal behavior in their children.
• If the lymphadenitis does not resolve or if it progressively enlarges, surgical biopsy may be indicated to rule out neoplastic causes and to definitively diagnose catscratch disease.

In/Out Patient Meds

• Intravenous antibiotics are not indicated.
• Use of oral antibiotics is controversial, as many cases resolve without medication.
• Antipyretics and analgesics may be necessary.

Deterrence/Prevention

• Children should be taught how to handle pets gently.
• Any scratch or bite should be brought to the attention of parents and carefully followed up.

Complications

• CNS complications include encephalopathy, encephalitis, radiculitis, polyneuritis, myelitis or neuroretinitis. Combative behavior has been reported in up to 40% of patients with catscratch disease in the recovery phase after seizures and coma.
• The onset of neurologic symptoms is often sudden and associated with a fever in 50% of cases.
• • Such symptoms can occur 1-6 weeks after adenitis appears.
  • Seizures occur in 46% of cases involving the CNS.
• Extreme lethargy and coma have been reported, often after a seizure, and usually last for 1-4 days.
• In general, all patients with CNS complications recover completely within 1 year.

Prognosis

• Lymphadenitis usually resolves spontaneously over 2-4 months, but 1-2 years may be required. One episode of catscratch disease confers lifelong immunity to children and adolescents.
• Three adults with catscratch disease have been reported to have recurrent lymphadenopathy 6-13 months after the initial diagnosis.

Patient Education

• Assure parents that the disease will resolve spontaneously and that an episode of catscratch disease probably confers long-term immunity. Although rare, adults can have recurrent illnesses.
• Teaching children how to handle pets gently and declawing pets may decrease the incidence of catscratch disease. The animal is infectious for only a short period, so removal of the pet from the home is not recommended.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Many potential diagnostic dilemmas exist because regional lymphadenopathy has several differential diagnoses.
• Be aware of the possibility of catscratch disease. Thoroughly search for other causes of lymphadenopathy when the diagnosis is doubtful, when the disease fails to resolve, or when the patient's clinical history and physical findings are not consistent with catscratch disease.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Bass JW, Vincent JM, Person DA. The expanding spectrum of Bartonella infections: II. Cat-scratch disease. Pediatr Infect Dis J. Feb 1997;16(2):163-79. [Medline].
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• Bergmans AM, Peeters MF, Schellekens JF, et al. Pitfalls and fallacies of cat scratch disease serology: evaluation of Bartonella henselae-based indirect fluorescence assay and enzyme-linked immunoassay. J Clin Microbiol. Aug 1997;35(8):1931-7. [Medline].
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• Relman DA. Are all Bartonella henselae strains created equal?. Clin Infect Dis. Jun 1998;26(6):1300-1. [Medline].
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• Sander A, Posselt M, Bohm N, et al. Detection of Bartonella henselae DNA by two different PCR assays and determination of the genotypes of strains involved in histologically defined cat scratch disease. J Clin Microbiol. Apr 1999;37(4):993-7. [Medline].
• Sander A, Ruess M, Bereswill S, et al. Comparison of different DNA fingerprinting techniques for molecular typing of Bartonella henselae isolates. J Clin Microbiol. Oct 1998;36(10):2973-81. [Medline].
• Tsukahara M, Tsuneoka H, Iino H, et al. Bartonella henselae infection from a dog. Lancet. Nov 21 1998;352(9141):1682. [Medline].
• Ziemssen F, Bartz-Schmidt KU, Gelisken F. Secondary unilateral glaucoma and neuroretinitis: atypical manifestation of cat-scratch disease. Jpn J Ophthalmol. Mar-Apr 2006;50(2):177-9. [Medline].
• de Kort JG, Robben SG, Schrander JJ, van Rhijn LW. Multifocal osteomyelitis in a child: a rare manifestation of cat scratch disease: A case report and systematic review of the literature. J Pediatr Orthop B. Jul 2006;15(4):285-8. [Medline].

Article Last Updated: Jun 12, 2006