Discovery of the cause and transmission mechanism of cat-scratch disease has been one of the fascinating recent stories in the field of infectious diseases. The initial breakthrough was the visualization of small, pleomorphic bacilli in biopsy materials obtained from nodes and primary granulomas and stained by the Warthin-Starry silver impregnation technique. In lymph nodes, the bacilli were seen intracellularly in capillaries and in macrophages lining sinuses in or near the germinal centers.

B. henselae was identified first in 1990 in patients with acquired immunodeficiency syndrome (AIDS) who had unique opportunistic infections, either bacillary angiomatosis or bacillary peliosis hepatitis. Lesions in both conditions had been noted to contain argyrophilic bacteria similar to those seen in children with cat-scratch disease. Polymerase chain reaction amplification of ribosomal RNA in biopsy specimens led to identification of bacterial genetic material most closely related to B. quintana, the rickettsia-like agent known to cause trench fever, and B. bacilliformis, the cause of bartonellosis. After successful cultivation, the new species has been named B. henselae. Frequently, children with cat-scratch disease develop specific antibodies against this organism, which now has been cultured from affected lymph nodes and also from the blood of epidemiologically related cats. In addition, B. henselae-specific DNA sequences have been amplified from cat-scratch skin test antigens.

Cat-scratch disease is transmitted by cutaneous inoculation. In the great majority of cases, a history of a cat scratch, often by a kitten younger than 6 months, can be elicited. Play may be more frequent with kittens than with older cats, and kittens are less likely to have been declawed. Interestingly, bacillary angiomatosis in adult patients with AIDS frequently is associated with a history of cat scratch.

Cat-scratch disease occurs more commonly in children than in adults, with the peak in case numbers falling in patients between the ages of 5 and 14 years. Frequently, clustering of cases within families has been noted, generally in association with the acquisition of new pets. Veterinarians as an occupational group appear to have a greater likelihood of exposure to the disease. An increased prevalence of skin test reactivity among veterinarians and asymptomatic relatives within family case clusters indicates that some infections may be subclinical.

Cats are the zoonotic reservoir of B. henselae. In one study, 81% of cat sera were positive for antibodies. In another, 41% of apparently healthy cats were bacteremic. Cat fleas (Ctenocephalides felis) appear to be the major vector for transmission among cats. Their possible role in transmission to humans is unknown.

The pathology of the primary inoculation site is similar to that of the affected regional lymph node. Both show a characteristic central avascular necrotic area surrounded by lymphocytes, with some giant cells and histiocytes. Three evolutionary stages are recognized within affected lymph nodes; all may coexist in the same node. Initially, generalized enlargement of the node with thickening of the cortex and hypertrophy of the germinal centers occurs. Lymphocytes are the predominant cell type, and epithelioid granulomas containing multinucleate giant cells may be scattered throughout the node. In the middle stage, granulomas become distributed more densely, fuse, and are infiltrated with polymorphonuclear leukocytes. Central necrosis of the epithelioid granulomas begins at this stage. Progression of the process leads to formation of large, pus-filled sinuses that are the chief late feature. The capsule of the node may rupture, allowing pus to drain into surrounding tissues, in turn resulting in a fibrotic inflammatory reaction and binding of the node to adjacent structures. The early stage of the lesion may resemble lymphoma or sarcoidosis; in later stages, the histopathology resembles tularemia, lymphogranuloma venereum, brucellosis, or infection with mycobacteria.

After an incubation period ranging from 3 to 30 days (usually between 7 and 12 days), one or more red papules measuring 2 to 5 mm in diameter develop at the site of cutaneous inoculation, often within the line of a previous cat scratch. Although often overlooked, such primary lesions were uncovered in more than 90% of affected patients after a careful search in one series. They persist until the development of lymphadenopathy, which generally occurs in 1 to 4 weeks.

Chronic lymphadenitis is the hallmark of cat-scratch disease, most frequently affecting the first or second sets of nodes draining the site of inoculation. Intervening lymphangitis does not occur. The sites affected most frequently, in decreasing order of incidence, are the axillary, cervical, submandibular, preauricular, epitrochlear, femoral, and inguinal lymph node groups. Involvement of more than one lymph node group, either within the same regional drainage or at an unrelated site, is present in 10% to 20% of cases. At a given site, approximately one-half of all cases will involve a single node, and the other half will involve multiple nodes.