The hands, feet, ankles, knees, and shoulders are most commonly affected. Arthralgias are more common than frank arthritis, butВ either may occur. The rash typically takes days to weeks to resolve once the offending agent is discontinued. If associated with subcutaneous injection, the rash may first appear around the site of the injection. Importantly, the mucous membranes are not involved and can be helpful in distinguishing serum sickness from Stevens-Johnson syndrome or toxic epidermal necrolysis. The physical exam should be carefully undertaken to determine the severity of symptoms and signs of systemic illness.В A close inspection of the rash may reveal an urticarial, maculopapular or vasculitic (purpuric) eruption.

Also, a complete review of systems, with a focus on each organ system and severity of symptoms, should be performed to evaluate for otherВ potential causes of the patient'sВ presentation. The history should focus on identification of an offending agent within the two weeks before the onset of symptoms, or, in the case of potential repeat exposure, within the few days before presentation. Note that in patients previously sensitized to the antigen, symptoms may develop within a few days of re-exposure to the causative agent.ДЄ thorough history and physical exam are essential in the evaluation of suspected serum sickness. It is the process of clearing these immune complexes and the subsequent inflammatory reaction thatВ coincides with the onset of clinical symptoms. Also, the activation of the complement system will trigger histamine release and increase vascular permeability, whichВ leads to an inflammatory response in the tissues and joints. These levels can be used to differentiate serum sickness from a serum sickness-like reaction, which will have normal complement levels. The deposition of immune complexes may also activate the classical complement pathway, leading to lower levels of circulating C3 and C4. If the macrophage activating system is not functioning properly, these complexes will become saturated in the circulation, leading to immune complex deposition, most commonly in parenchymal tissues and synovial joint fluid. When a patient is exposed to a foreign serum protein, it takes approximately 6-10 days for antibodies to develop and form antigen-antibody complexes andВ is considered a Type III immune-mediated hypersensitivity reaction.

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