Hypersentivity Type III Diseases

serum sickness is a self limited immune complex disease caused by exposure to foreign proteins or haptens.  It can occur after a person receives injections of serum from other individuals or animals, which sometimes is used for the treatment of snakebite or exposure to the rabies virus. The cardinal features of serum sickness are rash, fever, and polyarthritis, which begin one to two weeks after first exposure to the responsible agent, and resolve within a few weeks of discontinuation.  Although patients may appear very ill and uncomfortable during the acute febrile stage, the prognosis is excellent once the responsible drug is stopped.  Upon subsequent exposure, however, serum sickness develops sooner. Almost all patients diagnosed with serum sickness develop a pruritic rash, which is often the earliest clinical feature.  The mucous membranes are not involved, which can be a useful feature in distinguishing serum sickness from clinically similar conditions. Virtually all patients diagnosed with serum sickness develop fever with malaise.  Joint pain appears in approximately two thirds of patients.  The joints commonly involved include metacarpophalangeal joints, knees, wrists, ankles, and shoulders, although pain in the spine and temporomandibular joints have also been noted. Other less common features of serum sickness include headache, blurred vision, edema, and gastrointestinal problems.  The immunological interactions observed in serum sickness occur when antigens capable of remaining in the circulation for long periods incite antibody formation.  Endothelial cells increase the expression of adhesion molecules, and proinflammatory cytokines are released by monocytes and macrophages.  Subsequently, additional inflammatory cells are recruited, and necrosis of the small vessels develops.  Complement activation promotes chemotaxis and adherence of neutrophils to the site of immune complex deposition.  This may be facilitated by increased vascular permeability due to release of vasoactive amines from tissue mast cells. Management of serum sickness involves discontinuation of the offending agent.  Typically, fever and arthralgias resolve and new skin lesions stop forming within forty eight hours of this intervention.  This is often all that is required for patients with mild symptoms.  Further treatments depend upon the discomfort of the individual patient.  Antihistamines may be administered for symptomatic relief of pruritus.  Non steroidal antiinflammatory agents and analgesics may be given for symptomatic treatment of low grade fever and arthralgias.  For patients with higher fever, more severe arthritis and arthralgias, or extensive rashes, short courses of glucocorticoids are usually administered.  Once serum sickness or a serum sickness like reaction develops, the responsible drug should be avoided in the future.