Allergicdisorderssuchasasthma,hayfever,allergicskindiseases(e.g.,pemphigus,dermatitisherpetiformis);parasiticinfestations;drugreactions;certainmalignancies(e.g.,Hodgkinlymphomaandsomenon-Hodgkinlymphomas);collagen-vasculardisordersandsomevasculitides;atheroembolicdisease(transient)
Rare,oftenindicativeofamyeloproliferativeneoplasm(e.g.,chronicmyeloidleukemia)
Chronicinfections(e.g.,tuberculosis),bacterialendocarditis,rickettsiosis,andmalaria;collagenvasculardiseases(e.g.,systemiclupuserythematosus);andinflammatoryboweldiseases(e.g.,ulcerativecolitis)
Accompaniesmonocytosisinmanydisordersassociatedwithchronicimmunologicstimulation(e.g.,tuberculosis,brucellosis);viralinfections(e.g.,hepatitisA,cytomegalovirus,Epstein-Barrvirus);Bordetella pertussis infection from true white cell malignancies. Infectious mononucleosis merits separate consideration because it gives rise to a distinctive syndrome associated with lymphocytosis.
Infectious mononucleosis is an acute, self-limited disease of adolescents and young adults that is caused by Epstein-Barr virus (EBV), a member of the herpesvirus family. The infection is characterized by (1) fever, sore throat, and generalized lymphadenitis and (2) a lymphocytosis of activated, CD8+ T cells. Of note, cytomegalovirus infection induces a similar syndrome that can be differentiated only by serologic methods.
EBV is ubiquitous in all human populations. In the developing world, EBV infection in early childhood is nearly universal. Even though infected children mount an immune response (described later), most remain asymptomatic and more than half continue to shed virus, usually for life. By contrast, in developed countries with better standards of hygiene, infection typically is delayed until adolescence or young adulthood and symptomatic infection is much more common. For unclear reasons, only about 20% of healthy seropositive persons in developed countries shed the virus, and only about 50% of those exposed to the virus acquire the infection.
Transmission to a seronegative “kissing cousin” usually involves direct oral contact. It is hypothesized that the virus initially infects oropharyngeal epithelial cells and then spreads to underlying lymphoid tissue (tonsils and adenoids), where mature B cells are infected. The infection of B cells takes one of two forms. In a minority of cells, the infection is lytic, leading to viral replication and release of virions. More commonly, the infection is nonproductive and the virus persists in latent form as an extrachromosomal episome.
B cells that are latently infected with EBV become “activated” and proliferate as a result of the action of several viral proteins (Chapter 6). These cells disseminate in the circulation and secrete antibodies with unusual specificities, including the antibodies that recognize sheep red cells that are detected in diagnostic tests for mononucleosis. During acute infections, EBV is shed in the saliva; it is not known whether the source of these virions is oropharyngeal epithelial cells or B cells.