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lymphadenopathy and splenomegaly Finally HIV infection causes adenopathy in the cervical, axillary, and inguinal regions, particularly during the acute phase of infection Nodes generally decrease in size after the first to weeks as the immune response to infection subsides, however a modest degree of adenopathy can persist Children with unexplained recurrent or opportunistic infections, fevers, failure to thrive, hepatosplenomegaly, and generalized adenopathy should be evaluated for HIV infection TABLE 47.2 CAUSES OF GENERALIZED LYMPHADENOPATHY Systemic infection Bacterial Bacteremia Group A streptococcus infection (pharyngitis, scarlet fever) Brucellosis Leptospirosis Tularemia Viral Epstein–Barr virus Cytomegalovirus Human immunodeficiency virus Adenovirus Varicella Rubella Rubeola (measles) Hepatitis B virus Fungal Histoplasmosis Coccidioidomycosis Blastomycosis Parasitic Toxoplasmosis Malaria Spirochete Syphilis Lyme disease Autoimmune disease Juvenile idiopathic arthritis Systemic lupus erythematosus Dermatomyositis Serum sickness Drug reaction with eosinophilia and systemic symptoms (DRESS) Autoimmune hemolytic anemia Chronic granulomatous disease (sarcoid) Malignancy Leukemia (acute lymphoblastic or acute myelogenous leukemia) Non-Hodgkin lymphoma Hodgkin lymphoma Neuroblastoma Histiocytosis Hemophagocytic lymphohistiocytosis (HLH) Langerhans cell histiocytosis (LCH) Sinus histiocytosis with massive lymphadenopathy (Rosai–Dorfman disease) Storage disease Gaucher disease Niemann–Pick disease Miscellaneous Autoimmune lymphoproliferative syndrome (ALPS) Castleman disease Hyperthyroidism Noninfectious systemic disease that also presents with generalized adenopathy includes inflammatory or autoimmune diseases, serum sickness, malignancy, histiocytosis, and genetic storage diseases More than half of patients with systemic lupus erythematosus or systemic onset juvenile idiopathic arthritis manifest generalized adenopathy during the acute phase of illness Nodes are typically soft, nontender, and located in the cervical, axillary, and inguinal regions Serum sickness is an immune complex–mediated hypersensitivity reaction to a number of drugs, with clinical manifestations including fever, rash, myalgias, and arthralgias Symptoms begin to weeks after exposure to an inciting agent, and resolve spontaneously within weeks of discontinuation Skin manifestations are variable, though typically urticarial and macular involving the lower trunk, groin, or axillary regions and spreading to the back, upper extremities, and hands Lymphadenopathy may be noted with the rash, but may be seen without the rash and may be accompanied by splenomegaly Table 47.3 lists drugs that have been implicated in serum sickness reactions Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, potentially life-threatening drug-induced hypersensitivity reaction postulated to be caused by a drugspecific immune response and reactivation of herpes virus Clinical manifestations include fever, diffuse morbilliform skin eruption, facial edema, hematologic abnormalities (eosinophilia, atypical lymphocytosis), lymphadenopathy, and visceral involvement (liver, kidney, lung, and/or bone marrow) The reaction begins to weeks after the initiation of the offending medication The aromatic antiepileptic agents and the sulfonamides are the most frequent causes of this disorder ( Table 47.3 ) Stopping the offending agent and avoiding similar cross-reacting drugs as well as supportive care are mainstay measures of treatment
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