The differential diagnosis of CSD can include virtually all known causes of lymphadenopathy. As a general rule the diagnosis is favored by chronicity, unilateral occurrence, tenderness, and characteristic sites of involvement, such as the axillary, epitrochlear and preauricular nodes. Cervical, femoral, inguinal, and generalized lymph node involvement is less specific for CSD and necessitates more care in differential diagnosis. The most common diagnoses in a series of patients with adenopathy and negative CSD skin test were pyogenic lymphadenitis or abscess, lymphogranuloma venereum, benign or malignant neoplasms, and cervical adenitis caused by typical or atypical mycobacteria. Tularemia, toxoplasmosis, plague, and Kawasaki disease must be considered because of the need for specific therapy. In addition, brucellosis, syphilis, sporotrichosis, histoplasmosis, toxoplasmosis, infectious mononucleosis syndromes, lymphoma, and other neoplasms must also be included in the differential diagnosis.

The clinical diagnosis of CSD depended for many years on a patient meeting three of the following four criteria: (i) history of traumatic cat contact; (ii) positive skin-test response to CSD skin-test antigen; (iii) characteristic lymph node lesions; and (iv) negative laboratory investigation for unexplained lymphadenopathy (7). Biopsy is rarely required, due to the development of reliable serologic testing. A pathologic feature of CSD-affected tissues has been the formation of granulomas, ringed by lymphocytic infiltrates and multinucleated giant cells in affected lymph nodes. In the primary inoculation site, the tissue demonstrates small areas of frank necrosis surrounded by concentric layers of histiocytes and lymphocytes with nucleated giant cells.

Current diagnostic options include the Bartonella serology, the B. henselae indirect fluorescence antibody test utilizing fluid aspirated or tissue from an affected lymph node, a lymph node biopsy, or a CSD skin test. Current tests under investigation are DNA amplification (highly selective) and PCR (highly specific).

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