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A seven-year-old boy develops a 7-mm-wide cutaneous papule on his right hand. Over the next week or so, the papule develops into a pustule and partially crusts over. At about the same time, the child starts to experience malaise, intermittent mild fever (38ºC), and mild anorexia. Many lymph nodes in the area of his right underarm become swollen and tender as well. These symptoms persist for another three weeks, at which point the boy is taken to his pediatrician. Vital signs are T = 38.2ºC, P = 80, R = 16, BP = 105/70 mm Hg. On physical examination, the right axillary lymph nodes are found to be swollen and highly tender, and one of them has become suppurative. The pustule on the boy's right hand is oozing a small amount of yellowish-white purulent fluid. The pediatrician asks the boy if his hand was injured recently in the area where the pustule has appeared. The boy remembers that the family's new kitten scratched him on that hand, but that was a week or more before the sore on his hand was first noticed. Samples of fluid from the pustule and the suppurative lymph node are sent to lab for culturing. The lab isolates Staphylococcus aureus from the pustule material, but routine bacterial cultures for the lymph node sample are negative.
Question 1.1: What is your diagnosis?
The general symptoms (fever, malaise, swollen lymph nodes) are not very helpful by themselves, as there could be many explanations for this these problems. The presence of the pustule on the patient's hand and the fact that a lymph node has suppurated imply some kind of microbial infection that has spread from the cutaneous tissue of the patient's hand to the local lymph nodes. If so, the differential could include tuberculosis, sporotrichosis and other fungal diseases, toxoplasmosis, lymphogranuloma venereum, lymphoma, and cat scratch disease (CSD). The history (of recent exposure to a kitten) and the period of time over which the symptoms developed are consistent with a diagnosis of CSD. On the other hand, the isolation of S. aureus from the pustule seems to contradict this diagnosis because S. aureus is not the causative agent of CSD.
Question 1.2: What additional tests should be performed?
Three of four criteria are required to justify a diagnosis of CSD: (1) a history of animal exposure in the presence of a scratch or dermal lesion, (2) culture of lymphatic aspirate that is negative for other causes, (3) biopsied lymph node histology that is consistent with CSD, and (4) specific serologic evidence for the presence of the causative agent. To confirm the diagnosis, then it will be necessary to carry out the lymph node biopsy and/or the serologic test. There is a CSD skin test, in which lymph node material from people diagnosed with CSD is used as an antigen. However, this test is seldom used anymore because of concerns about possible transmission of viruses from the donor (of the lymph node material) to the patient being tested.
Test Results:
The specific serologic test for antibodies against the causative agents of CSD is positive. Moreover, the lymph node biopsy reveals the characteristic granulomatous inflammation with stellate necrosis. There is no evidence of angiogenesis. Tiny bacilli in clusters can be seen in a Warthin-Starry silver stain of the biopsy specimen.
Question 1.3: What is the causative agent?
The causative agent of CSD is a small, Gram-negative, rod-shaped bacterium named Bartonella henselae. It has fastidious growth requirements and initial isolation requires prolonged culturing (1-6 weeks) on enriched blood agar, in a humid atmosphere enriched with CO2. B. henselae was formerly known as Rochalimaea henselae and considered to be a rickettsial pathogen. However, all species of Rochalimaea recently were transferred to the genus Bartonella based on (1) phylogenetic analyses of their DNA sequences and (2) definitive evidence that these organisms are not obligate intracellular parasites (as are all other members of the rickettsiae). There is no good evidence that other species of Bartonella (B. quintana, B. clarridgeiae) can also cause CSD.
Question 1.4: What is the epidemiology of this disease?
About 60% of CSD cases in the U.S. occur in children. Exposure to bacteremic young cats that either are flea-infested or have been in contact with another cat carrying fleas poses a significant risk of human infection. Most such infections are caused by scratches, although bites and licking are also known to transmit CSD. Most cases occur in the warmer months, when fleas are active. The flea might serve to transmit infection between cats, but it is not known whether humans can be infected through the bite of an infected flea.
Question 1.5: How do you explain the pustule culture?
It is not uncommon for secondary bacterial infections to occur at the site of infection, especially if the infection occurs in a young child who scratches the pustule. In this case, Staphylococcus aureus, which was present on the child's skin, entered the pustule area and started the secondary infection. The result in this case was a deceptive lab test result that could have lead to misdiagnosis of (or even failure to detect) the underlying disease.
Question 1.6: How should you treat this disease?
There is no consensus regarding treatment of CSD because it is self-limited in most cases (unless the victim is immunocompromised). Yet, the lymphadenopathy and systemic symptoms can persist for weeks or months and become somewhat debilitating. Some authorities recommend treatment (to limit the symptoms and prevent complications), but others do not. Bartonella usually is sensitive to aminoglycosides, tetracycline, erythromycin, and the quinolones.
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