Lymphadenitis caused by infection by herpes simplex virus (HSV).

HSV lymphadenitis.

Herpes simplex virus has a worldwide distribution and is primarily spread person-to-person by direct contact with infected secretions (1,2,3). Both humans and animals can be infected by HSV but only humans become symptomatic. The two types of HSV, types 1 and 2, are α herpesviruses with large genomes that encode over 80 proteins. Like other herpesviruses, HSV types 1 and 2 are linear, double-stranded DNA viruses. Both types of HSV are closely related genetically, with over 50% DNA sequence homology, but they have antigenic differences in their envelope proteins.

Herpes simplex virus 1 (HSV-1) is most often spread mouth-to-mouth and can cause gingivostomatitis, orolabial lesions (lip sores), keratoconjunctivitis, and esophagitis. Herpes simplex virus 1 also can spread systemically and cause encephalitis, skin infections (e.g. herpetic whitlow, eczema herpeticum) and hepatic and adrenal necrosis in infants (4). Exposure to HSV-1 is relatively more frequent in children and adolescents. Herpes simplex virus 2 (HSV-2) is most frequently spread via sexual contact, causing genital lesions, and is relatively more common in adults. Overlap exists: HSV-1 can cause genital infections and HSV-2 can cause oral disease, and the lesions are clinically indistinguishable. Primary HSV infection of either type also is commonly asymptomatic, with first diagnosis occurring at time of reactivation and recurrence. The frequency of HSV seropositivity in the general population is high (5). Herpes simplex virus 2 seropositivity is particularly high in persons with a high number of sexual contacts.

Clinically evident herpesvirus lesions may result from either primary exposure to HSV or by reactivation (1,2,3). Following primary infection, HSV multiplies at the site of infection, usually in epithelial cells but lymphocytes also can be infected, and then travels along sensory nerves to the dorsal root ganglia. In ganglia, HSV becomes latent, but with reactivation the virus can retrace its path back to the skin or mucous membranes (2,3). The frequency of reactivation depends on the anatomic site and virus type. In the genital region, HSV-2 reactivates and causes recurrent infection more often than does HSV-1 infection. In the oral region, the converse is true. In immunosuppressed patients, particularly those with acquired immunodeficiency syndrome, herpetic infection may have a chronic and severe course.

Herpetic lymphadenitis is uncommonly diagnosed pathologically, and relatively few cases have been reported in the literature. A large subset of patients reported had a coexistent hematologic neoplasm, suggesting that patients with hematologic malignancies are at increased risk for herpetic infection, either disseminated or localized and self-limited (6). As the frequency of herpes infection is much higher in the general population than is the frequency of hematologic neoplasms, it seems likely that cases of herpes lymphadenitis associated with hematologic neoplasms are over-represented in the literature. A likely explanation is that the diagnosis of herpes infection in an otherwise healthy patient is most often made by examination of mucocutaneous lesions and viral culture, and therefore lymph nodes are rarely biopsied. In contrast, lymph node biopsy is performed in patients with known hematologic neoplasms because of the suspicion of recurrent neoplasm.

In patients with leukemia or lymphoma, HSV lymphadenitis may be superimposed upon the neoplasm, or may involve another anatomic site (7,8). Most often, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is associated with HSV lymphadenitis (7,9,10,11). Other neoplasms associated with herpetic infection include Hodgkin lymphoma, nodal marginal zone B-cell lymphoma, mantle cell lymphoma, acute lymphoblastic leukemia, acute myeloid leukemia, and chronic myelogenous leukemia (6,12). In some of these cases, both the neoplasm and evidence of herpes infection were identified within the same lymph node biopsy specimen (6,13).

Cases of HSV lymphadenitis reported in the literature can be subdivided into three groups. Some patients have localized lymphadenopathy (6,14,15,16,17,18). The latter form may be seen particularly in the inguinal region, which is tender and affected by an erythematous or vesicular rash, suggesting lymphatic spread from an infection of the urogenital tract (17). A second group of patients have generalized lymphadenopathy that may be associated with an erythematous rash and no other organ involvement (9,19,20). A last group of patients, often immunocompromised, have disseminated HSV infection involving multiple organs. In these studies, lymph node involvement is not always specified, but lymph node involvement is likely in the setting of widespread infection (12,21).