Treatment of cat scratch disease

INTRODUCTION — Cat scratch disease (CSD) is an infectious disease usually characterized by self-limited regional lymphadenopathy. The manifestations of CSD, however, can include visceral organ, neurologic, and ocular involvement [1,2]. Bartonella henselae is the etiologic agent in most cases of CSD.

The treatment of CSD will be reviewed here. The microbiology, epidemiology, and clinical features of CSD, Bartonella endocarditis, and other Bartonella infections, as well as the evaluation and management of cat bites, are discussed separately. (See "Microbiology, epidemiology, clinical manifestations, and diagnosis of cat scratch disease" and "Endocarditis caused by Bartonella" and "Bartonella infections in people with HIV" and "Bartonella quintana infections: Clinical features, diagnosis, and treatment" and "South American bartonellosis: Oroya fever and verruga peruana" and "Animal bites (dogs, cats, and other mammals): Evaluation and management".)

APPROACH TO TREATMENT — We suggest antimicrobial therapy be administered to all patients with CSD.

●For patients with lymphadenitis as the only manifestation, we suggest single-drug therapy. (See 'Lymphadenitis' below.)

●For those with more serious infections (eg, hepatosplenic disease, neurologic and ocular disease), we suggest combination therapy that includes rifampin. (See 'Hepatosplenic disease/fever of unknown origin' below and 'Neurologic and ocular manifestations' below.)

In certain settings, such as the treatment neuroretinitis and refractory lymphadenitis, adjunctive therapies (eg, corticosteroids and/or lymph node aspiration) may be warranted. (See 'Neuroretinitis' below and 'Adjunctive treatments' below and 'Role of corticosteroids' below.)

The approach to treatment of CSD primarily derives from case reports, small series, and personal experience. In vitro susceptibility testing often does not correlate with a clinical response and should not be considered in the choice of antibiotics [3-5].

LYMPHADENITIS

Whom to treat — We suggest antimicrobial treatment for all patients with CSD who have lymphadenitis, even immunocompetent patients with mild to moderate disease. This includes patients with presumed CSD based upon epidemiologic risk factors and typical clinical manifestations. (See "Microbiology, epidemiology, clinical manifestations, and diagnosis of cat scratch disease", section on 'Approach to diagnosis'.)

Although many patients with lymphadenitis have gradual resolution of symptoms without specific antibiotic therapy [3-5], we treat patients in an effort to prevent serious complications, since up to 14 percent of patients will have dissemination of the organisms, with potential infection of the liver, spleen, eye, or central nervous system [6-8].

In addition, available data suggest that antibiotic treatment of CSD can shorten the duration of symptoms [9,10]. In a randomized, placebo-controlled trial in 29 children and adults with CSD manifested as regional lymphadenopathy, 7 of the 14 patients who received azithromycin achieved an 80 percent decrease of lymph node volume in the first 30 days post-treatment compared with only 1 of 15 patients who received placebo (odds ratio 17; 95% CI 1.5 to 196) [10]. Similarly, in a large retrospective study that included 268 persons with CSD (age range 6 months to 72 years), the mean duration of illness was 2.8 weeks for the 89 patients treated with rifampin, ciprofloxacin, trimethoprim-sulfamethoxazole, or gentamicin versus 14.5 weeks for those who were not treated or were treated with antibiotics thought to be ineffective [9].

However, some experts do not recommend treating CSD that manifests as uncomplicated lymphangitis [11]. The major rationale for not treating is that most persons have self-resolution of the illness without complications, and the available data suggesting benefit of antimicrobial therapy are very limited.

Antimicrobial regimens — For patients with lymphadenitis, we suggest a five-day course of azithromycin (table 1). As discussed above, 7 of 14 patients who received azithromycin had a decrease of 80 percent or more in lymph node volume during a 30-day follow-up period compared with only one of fifteen placebo recipients [10]. (See 'Whom to treat' above.)

In patients intolerant to azithromycin, we suggest a 7- to 10-day course of clarithromycin, rifampin, or trimethoprim-sulfamethoxazole. Specific dosing recommendations are found in the table (table 1). The use of these alternative regimens for the treatment of CSD has only been evaluated in small case series [9,12,13]. For adults, ciprofloxacin may also be an option as an alternative agent since it has been used with apparent clinical success in immunocompetent patients [14].

For patients with lymphadenitis that does not respond to therapy after three to four weeks, we re-evaluate the patient in an effort to find an alternative diagnosis. If CSD is still the most likely diagnosis, we repeat treatment with a five-day course of azithromycin, as dosed above, and add rifampin for five days as well.

Adjunctive treatments — In addition to antibiotics, adjunctive therapies may be warranted in severe or refractory cases. Needle aspiration of painful suppurative lymph nodes may hasten the relief of symptoms (picture 1). On rare occasion, we administer corticosteroids to patients with severe or persistent disease. (See 'Role of corticosteroids' below.)

Surgical drainage is generally not recommended; however, excision of the affected lymph nodes may be reasonable in select patients with infection unresponsive to a prolonged course of treatment. As an example, in one case report, surgical excision was required to achieve resolution of persistent infection in an immunocompromised patient with progressive symptoms despite approximately nine months of antimicrobial therapy [15]. Lymph node excision may also be indicated if a patient has failed to respond to treatment and the diagnosis of CSD is uncertain.

HEPATOSPLENIC DISEASE/FEVER OF UNKNOWN ORIGIN — There are limited data to guide the management of patients with disseminated CSD. Antimicrobial therapy alone is typically sufficient; however, on rare occasion, adjunctive corticosteroids can also be administered. (See 'Role of corticosteroids' below.)

Choice of regimen — For patients with disseminated disease, such as hepatosplenic disease and fever of unknown origin, we suggest treating with azithromycin plus rifampin. An alternative regimen is rifampin plus gentamicin. For adults who cannot receive rifampin, a higher dose of azithromycin alone can be administered. Specific dosing recommendations are found in the table (table 1).

In one report, 19 children (aged 2 to 11 years) who had hepatosplenic CSD appeared to respond well to rifampin given alone or in combination with either gentamicin or trimethoprim-sulfamethoxazole [16]. These patients most often received rifampin at a dose of 20 mg/kg per day for 14 days. Another report described three patients with CSD who responded to intravenous gentamicin; two of the patients had extensive hepatic involvement [17]. A small case series also described successful treatment of three adults with hepatosplenic disease using a five-day course of oral azithromycin 500 mg daily without rifampin [18].

Patient monitoring — There are no specific markers or titers that can be followed to ensure successful treatment. We monitor the clinical response and C-reactive protein levels. In patients with severe or persistent disease, it may be reasonable to administer adjunctive corticosteroids. (See 'Role of corticosteroids' below.)

In patients with hepatosplenic disease, some providers perform follow-up abdominal imaging approximately six months after treatment to document that the lesions are regressing. However, we believe further imaging is not necessary if the patient has experienced complete clinical resolution.

NEUROLOGIC AND OCULAR MANIFESTATIONS — Patients with CSD can develop ocular complications (eg, neuroretinitis, Parinaud oculoglandular syndrome) and neurologic manifestations (eg, encephalopathy). (See "Microbiology, epidemiology, clinical manifestations, and diagnosis of cat scratch disease", section on 'Clinical manifestations'.)

We suggest treatment of all patients with neurologic and ocular manifestations in an effort to reduce the risk of long-term sequelae, even though some reports suggest patients may improve on their own [19].

Preferred regimens — The optimal therapy for neurologic and ocular disease is unknown. Our preferred approach is summarized below and described in detail in the table (table 1):

●For adults and children ≥8 years of age, we suggest doxycycline plus rifampin.

●For children <8 years of age and those unable to take doxycycline, we administer rifampin plus either azithromycin or trimethoprim-sulfamethoxazole.

●For patients with neuroretinitis, we treat for four to six weeks. For patients with Parinaud oculoglandular disease or other neurologic involvement (including encephalitis), we treat for 10 to 14 days.

●Additional considerations for patients with neuroretinitis and young children with severe disease are discussed below. (See 'Neuroretinitis' below and 'Young children with severe disease' below.)

In general, we prefer the combination of doxycycline plus rifampin because there is the most experience with this combination. As an example, a retrospective case series of seven consecutive patients with B. henselae neuroretinitis evaluated the outcome of patients treated with doxycycline (100 mg orally twice daily) and rifampin (300 mg orally twice daily) for four to six weeks compared with historic controls [20]. Antibiotic therapy appeared to promote the resolution of retinitis. In addition, there is extensive clinical experience with the use of doxycycline for treating central nervous system infections caused by other pathogens.

Additional considerations

Neuroretinitis — For patients with neuroretinitis, we suggest adjunctive corticosteroids in addition to antimicrobial therapy. Such patients should be monitored closely by an ophthalmologist.

The optimal corticosteroid regimen is unknown. We administer a six-week course of corticosteroids using 1 mg/kg of oral prednisone for two weeks with a gradual taper over the following four weeks.

Although data are limited, the use of corticosteroids for neuroretinitis was supported in a multicenter, retrospective cohort study of 86 patients with ocular manifestations of CSD (eg, neuroretinitis, inflammatory disc edema, uveitis, or vascular occlusions) [8]. Visual improvement at follow-up was significantly better in patients who received corticosteroids plus antimicrobials versus those who were treated with antimicrobial therapy alone (88 versus 50 percent). In this study, most of the patients were adults with neuroretinitis and most received oral doxycycline plus rifampin; corticosteroids were usually administered as oral prednisone at a mean starting dose of 40 to 80 mg/day and tapered gradually for a total treatment duration of six weeks.

Young children with severe disease — In general, we avoid doxycycline in children <8 years old because of concerns of dental staining. However, in patients with sight-threatening neuroretinitis or severe neurologic disease, the following key points related to the risks and benefits of doxycycline should be considered and discussed.

●Although there are very limited data on the optimal treatment regimen for neurologic and ocular disease, most studies evaluating the treatment of neuroretinitis have used doxycycline in combination with rifampin. In addition, there is extensive clinical experience with the use of doxycycline to treat central nervous system infections caused by other pathogens.

●Observational studies support the relative safety of doxycycline compared with older tetracyclines when short courses are administered to children; however, the impact of longer durations is unknown.

Thus, the choice of antimicrobial regimen for young children with severe ocular or neurologic disease must be determined on a case-by-case basis.

ENDOCARDITIS — Treatment of suspected or proven Bartonella endocarditis is discussed separately. (See "Endocarditis caused by Bartonella".)

ROLE OF CORTICOSTEROIDS — We suggest administering adjunctive corticosteroids to patients with neuroretinitis. The use of corticosteroids in this setting is discussed above. (See 'Neuroretinitis' above.)

On rare occasion, adjunctive corticosteroids may also be reasonable for patients with severe or persistent disease other than neuroretinitis. For such patients, an initial dose of 1 mg/kg of prednisone (maximum daily dose 80 mg/day) can be administered for five to seven days, with a taper over the subsequent 10 to 14 days.

The use of corticosteroids in patients without neuroretinitis is based upon expert opinion since there are no controlled trials examining their efficacy in patients with CSD. The rationale for their use is based in part upon the observation that, despite an intense inflammatory response, there are very few organisms detected in the lymphoid tissue of patients with classic CSD or in the granulomatous material of patients with hepatosplenic involvement [9,21]. In addition, multiple case reports have described rapid resolution of localized and systemic symptoms following a course of corticosteroids, including reports in patients with hepatosplenic CSD [22-25]. These reports included patients who had progressive and/or persistent disease despite receiving antimicrobial therapy. Further study is needed to determine if corticosteroids should have a role in the management of CSD, and if so, what dose would provide optimal benefit.

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●Basics topics (see "Patient education: Cat scratch disease (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Clinical overview – Cat scratch disease (CSD) is an infectious disease cause by Bartonella henselae and is usually characterized by self-limited regional lymphadenopathy. However, the manifestations can include visceral organ, neurologic, and ocular involvement. (See 'Introduction' above.)

●Approach to antimicrobial therapy – We suggest antimicrobial treatment for all patients with CSD (Grade 2C). This includes immunocompetent patients with mild to moderate lymphadenitis. Although some patients may improve without therapy, treatment may shorten the duration of symptoms and reduce the risk of developing systemic disease and/or long-term sequelae. The approach to treatment of CSD primarily derives from case reports, small series, and personal experience. (See 'Approach to treatment' above and 'Whom to treat' above.)

•Lymphadenitis – For patients with lymphadenitis as the only manifestation, we suggest azithromycin (table 1) (Grade 2C). Alternative regimens include rifampin, trimethoprim-sulfamethoxazole, and, in adults, ciprofloxacin. Repeat treatment (with azithromycin plus rifampin) and adjunctive therapies, such as needle aspiration and corticosteroids, may be warranted in severe or refractory cases. (See 'Lymphadenitis' above.)

•Serious infections other than lymphadenitis – For those with more serious infections, we suggest combination therapy that includes rifampin (Grade 2C). The duration of treatment and the use of adjunctive corticosteroids depends upon the clinical manifestation (table 1):

-Hepatosplenic disease or fever of unknown origin – For these patients, we administer rifampin plus azithromycin. Alternative regimens include rifampin plus gentamicin or higher doses of azithromycin alone (for adults). (See 'Hepatosplenic disease/fever of unknown origin' above.)

-Neurologic or ocular disease – For adults and children ≥8 years of age with neurologic or ocular disease, we administer doxycycline plus rifampin. In children <8 years of age, azithromycin or trimethoprim-sulfamethoxazole should generally be substituted for doxycycline; however, for those with severe disease, the risks and benefits of using doxycycline should be discussed. (See 'Neurologic and ocular manifestations' above and 'Young children with severe disease' above.)

For patients with neuroretinitis, the usual duration of antimicrobial therapy is four to six weeks; such patients should be managed in conjunction with an ophthalmologist. The duration of treatment for patients with Parinaud oculoglandular disease and other neurologic manifestations is 10 to 14 days. (See 'Preferred regimens' above and 'Neuroretinitis' above.)

●Role of corticosteroids – For patients with neuroretinitis, we suggest adjunctive corticosteroids (Grade 2C). On rare occasion, it may also be reasonable to administer corticosteroids to patients with severe or persistent disease other than neuroretinitis. (See 'Role of corticosteroids' above.)