Cat scratch disease

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Diagnosis and reasoning

The pediatric patient who presents with lymphadenopathy is a common clinical problem with a wide differential diagnosis. When evaluating these patients, the first point to keep in mind is that lymph nodes can be palpated in many healthy children (especially between the ages of 8 to 12). Thus, it is only nodes which are >1 cm in size (or >1.5 cm in the case of inguinal lymph nodes) which are considered to be enlarged (as in this child's case). Where lymphadenopathy is definitely present, a good next step is to determine if this is generalized or localized, based on the regions involved; the former is said to be present if two or more nodal groups are involved. Examination of this child shows that the right axilla, right posterior cervical chain, and right supraclavicular region are involved; thus, this is generalized lymphadenopathy indeed. Generalized lymphadenopathy is most often either infectious or neoplastic in origin, although certain autoimmune conditions and granulomatous diseases can also manifest in this manner. The age of the patient is a useful guide in this respect; in children under 10 years of age, infections are more often a cause of generalized lymphadenopathy than malignancies. Further analysis depends on the physical characteristics of the enlarged nodes, such as their size, consistency, mobility, and tenderness. In this patient, all the lymph nodes are painless and non-tender; this is a point against infection. However, they are also well-defined, mobile, and not possessed of a hard or firm consistency, which argue against neoplastic enlargement. That said, the single palpable axillary lymph node is significantly enlarged, being 4 cm in diameter; when combined with the history of progressive enlargement over time, this is highly concerning. Thus, his further evaluation should include imaging of the neck and axilla, as well as a biopsy of the axillary lymph node. The first of these confirms the clinical findings, and also shows the axillary node to be hypoechoic and lobular; these sonographic features are suspicious of malignancy (particularly lymphoma). However, the biopsy reveals a surprising and somewhat unexpected finding: granulomatous lymphadenitis. In patients of this age, the differential diagnosis of granulomatous lymphadenitis includes infections such as tuberculosis, toxoplasmosis, cat scratch disease (CSD), tularemia, and brucellosis, as well as non-infectious causes such as Kawasaki disease or even Kikuchi disease. The presence of stellate microabscesses helps us narrow down the possibilities; in this patient's context, it is only CSD and tularemia which could manifest this histological finding. That said, tularemia is almost always associated with fever, which is often very high; neither are there other supportive clinical features. Note that while CSD is often associated with a history of contact with cats, this is not essential, as arthropods such as ticks and fleas can harbor the organism and transmit it to a human host. Although application of the Warthin-Starry silver stain may reveal intracellular Bartonella bacilli in CSD, this stain is technically challenging and the tiny bacilli are easy to miss; thus, a negative result does not exclude this condition either. Thus, CSD does appear to be the most likely diagnosis so far; however, serological confirmation is essential. Simultaneously, the opportunity should be taken to definitively exclude the other key infectious causes of granulomatous lymphadenitis. Serology does turn out to be positive for Bartonella, with a very strong titer of 1:512. When combined with the biopsy findings, this is sufficient to establish the diagnosis. Note that the CSD skin test is no longer recommended, owing to its low accuracy. CSD is benign and self-limiting; symptomatic management (such as applying warm compresses) is key. Given the presence of significant lymphadenopathy, antibiotic therapy may help shorten the course of the disease. Note that there is absolutely no need for hospitalization; nor is there any rationale for corticosteroid therapy.


Cat scratch disease (CSD) is a zoonotic infection caused by the intracellular gram-negative bacillus Bartonella henselae; it is globally prevalent, with ~22,000 cases reported each year in the United States alone Cats are the major reservoir of Bartonella, with about 50% harboring the pathogen. Kittens and strays are more likely to be bacteremic than adult or domestic cats. Humans contract the infection via cat bites or scratches, or flea or tick bites. This is possibly why CSD is mainly encountered in children (due to the higher likelihood of rough contact with cats); however, all age groups can be affected. Initially, infected persons manifest a primary skin vesicle at the inoculation site. This primary lesion may later become erythematous, vesicular, papular, or crusted. A regional, unilateral, tender lymphadenopathy develops a week or two later. The most commonly affected lymph node groups are those of the upper extremities, neck and jaw, groin, chest, and the pre- or postauricular and clavicular nodes. The lymphadenopathy may persist for several months; in some individuals, the enlarged nodes may suppurate. The majority of patients also complain of body aches, malaise and anorexia. A few develop low-grade fever. Musculoskeletal manifestations such as myalgia, arthralgia and arthritis are also seen. Hepatosplenomegaly with or without lymphadenopathy is an important sign which suggests visceral involvement. Note that CSD can result in several important complications; these largely depend on the immune status of the affected individual. Immunocompetent persons may develop encephalitis or ocular manifestations such as Parinaud oculoglandular syndrome and neuro-retinitis; the latter may lead to acute unilateral visual field loss. In contrast, immunocompromised patients develop more severe complications such as bacillary angiomatosis and bacillary peliosis; the latter involves the parenchymal vasculature, resulting in the formation of blood-filled, cystic spaces in the liver, spleen, bone marrow, and lymph nodes. Where CSD is suspected, serology plays a key role in establishing the diagnosis; assessment of anti-Bartonella henselae immunoglobulin-G (IgG) titers via an indirect fluorescent assay (IFA) or enzyme-linked immunosorbent assay (ELISA) is the most common test performed in this respect. An IgG titer of less than 1:64 suggests no ongoing infection; titers between 1:64 and 1:256 suggest possible infection, in which case it is advisable to repeat the test in 10 to 14 days; titers above 1:256 strongly suggest an ongoing or recent infection. Note that the above tests lack specificity; asymptomatic persons (especially those who domesticate cats), may be falsely positive as a result of previous bacterial exposure. Polymerase chain reaction (PCR) is more specific than serology, but is also less sensitive. Cultures are not very useful, as B. henselae is highly fastidious and thus not easily cultured. A lymph node biopsy is extremely useful in situations where the diagnosis cannot be established otherwise. Lymphoid hyperplasia, multiple granulomas, and stellate microabscesses are seen on histopathological examination. The choice of treatment depends on the clinical presentation and immune status of the patient. Immunocompetent patients with mild-to-moderate infections may be simply managed with analgesia, reassurance, and regular follow-up; the lymphadenopathy usually resolves spontaneously within two to eight weeks of onset. Antibiotic therapy is indicated if there is significant lymphadenopathy, or in the presence of disease progression to the liver, spleen, eye, or central nervous system. Azithromycin, rifampicin, ciprofloxacin or trimethoprim-sulfamethoxazole can be used in this regard. Incision and drainage of the affected lymph nodes is not recommended, as this can lead to chronic sinus tract formation. Overall, immunocompetent patients with CSD have an excellent prognosis, with complications being uncommon. Even immunocompromised individuals tend to recover completely, following appropriate antibiotic therapy. Note also that a single episode of CSD is adequate to provide lifelong immunity to the affected individual.

Take home messages

  1. Cat scratch disease (CSD) is a zoonotic infection caused by Bartonella henselae; affected individuals usually have a history of recent contact with cats.
  2. These patients commonly present with a tender, regional, unilateral lymphadenopathy. A skin papule may be seen at the site of inoculation.
  3. In most cases, positive serological studies are key to establishing the diagnosis; PCR and lymph node biopsy may be useful in equivocal instances.
  4. CSD is usually self-limiting, and thus does not require specific treatment. However, significant lymphadenopathy, or the presence of complications mandates antibiotic therapy.

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