Lymphadenitis in the course of syphilis caused by infection with Treponema pallidum.

Luetic lymphadenitis.

The epidemiology of syphilis has radically changed with time. After high levels in the post-World War II era, the incidence of syphilis decreased dramatically owing to the successful introduction of penicillin treatment. However, after years of quiescence, during the 1980s, syphilis reemerged disproportionately among male homosexuals affected by acquired immune deficiency syndrome (AIDS) (1,2). Subsequently, the adoption of safer sex practices by this group led to a declining incidence of new cases. More recently, a shift toward heterosexual transmission has been recorded as more drug-addicted women contract the disease (3,4) and transmit it to their newborns. In developing countries, chronic lymphadenopathies are relatively common in children and are more often caused by infectious agents. Of these, tuberculosis is the most common, accounting for 332 of 1,877 cases of cervical lymphadenopathy in a South African study. Syphilis was diagnosed in four of these cases (5).

Syphilis is caused by a bacterial spirochete, T. pallidum, which can be acquired through sexual contact or intrauterine transmission from mother to fetus. T. pallidum is a slender, spiral organism, 5 to 15 μm long and 0.2 μm thick (6). In its natural form, the spirals are regular, with a depth of 0.5 to 1 μm (Fig. 20.1). The basic structure is that of a cylinder of protoplasm surrounded by a trilaminar membrane. Bundles of axial filaments stretch from one end to the other, maintaining the elasticity of the organism and making its movements possible (6). The surface consists of a phospholipid-rich layer with few exposed proteins, a strategy that prevents antibody attack from the host (7). To initiate infection, a minimum of approximately 50 organisms is necessary.

The course of the disease is divided into three stages. Primary syphilis, characterized by a chancre at the site of entry, may persist from several days to 4 weeks, although in most patients the lesion disappears in 2 weeks. The treponemes spread from the chancre through lymphatics to the regional lymph nodes, which are enlarged, hard, and painless (8). Secondary syphilis, beginning 6 to 8 weeks after the onset, is manifested by symptoms including generalized lymphadenopathy, and localized or generalized skin and mucosal eruptions (8). Rashes, in the form of macules or papules, and condylomata lata in genital and anal areas are characteristic of this stage. After a period of latency lasting as long as 2 years and interrupted by occasional relapses, tertiary syphilis develops, with the formation of nodules, ulcers, and gummata affecting various organs, notably in the cardiovascular and central nervous systems.

Luetic lymphadenitis regularly accompanies primary, secondary, and possibly latent or early tertiary stages of syphilis (9). The lymphadenopathy is caused by the persistence of spirochetes in the tissues, particularly the lymph nodes, which provide continuous antigenic stimulation. The inguinal lymph nodes are most commonly involved, especially in primary syphilis. Femoral, epitrochlear, cervical, and axillary lymph nodes are sometimes affected, and generalized lymphadenopathy is often present in secondary syphilis (10). Since the oral cavity is the most common extragenital site of syphilis, tonsils and particularly cervical lymph nodes may be involved. Anterior unilateral lymphadenopathy with spirochetes identified in the tissues have been reported in patients with or without simultaneous human immunodeficiency virus (HIV) infection (11,12,13).

Histopathologic features include marked hyperplasia of the lymphoid follicles, which sometimes assume bizarre shapes and occasionally form a second row in the deep cortex that extends to the medullary region (Fig. 20.2). The secondary follicles contain scattered macrophages and a sharply defined margin formed by small lymphocytes (9). On occasion, the excessive follicular hyperplasia resembles follicular lymphoma (14,15,16). The lymph node capsule is substantially broadened by chronic inflammation and fibrosis (Fig. 20.3). In addition, the T zones are expanded by a mixed cellular infiltrate that includes numerous immunoblasts (17) (Fig. 20.4).