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