History
Serum sickness develops 1-3 weeks after initial administration of the causative agent (in many cases a medication) but can occur within 12-36 hours in individuals who have been previously sensitized through an antecedent exposure. [5]
Symptoms described in serum sickness include the following [5] :
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Fever/malaise - ~100%
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Cutaneous eruptions - 93%
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Arthralgias - 77%
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Gastrointestinal (GI) complaints - 67%
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Headaches - 57%
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Myalgias - 37%
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Blurred vision - 37%
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Dyspnea/wheezing - 20%
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Lymphadenopathy - 17%
Specific GI symptoms may include abdominal pain, nausea, vomiting, or diarrhea. [2] Chest pain or breathlessness due to pleuritis, pericarditis, or myocarditis is possible but rare.
Physical Examination
Fever develops in almost all patients with serum sickness, preceding skin rash in 10-20% of cases. The fever is characterized by high spikes that normalize within the same day. [8]
Most rashes associated with serum sickness are urticarial (92%) and/or serpiginous. [2] They typically start on the anterior lower trunk or the periumbilical or axillary regions and spread to the back, upper trunk, and extremities. [8] In the extremities, eruptions occur at the junction of the palmar or plantar skin with the dorsolateral surface of the hands, feet, fingers, and toes.
Morbilliform or scarlatiniform rash, palpable purpura, erythema simplex, or erythema multiforme are less common. Pruritus and erythema are possible at injection sites. Edema can be limited to site of injection but can also be observed in the face. [2]
Lymphadenopathy (10-20%) may be generalized or may involve tenderness in the nodes that drain the injection site. Splenomegaly may occur.
Arthritis (10%-50%) is usually in the metacarpophalangeal and knee joints and usually symmetrical. [4] Occasionally, small joints, joints of the spine, and the temporomandibular joint may be inflamed. Myalgias or myositis also may occur.
Edema may occur, particularly about the face and neck.
Kidney manifestations include proteinuria, microscopic hematuria, and oliguria; however, significant disease usually does not result.
Cardiovascular findings may include myocardial and pericardial inflammation. Generalized vasculitis occurs rarely.
Neurologic manifestations include the following [2, 4] :
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Peripheral neuropathy
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Brachial plexus neuritis
Pulmonary manifestations, such as pleurisy, are rare. However, dyspnea and cyanosis are not uncommon.
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A 29-year-old woman with RA presented with fever, a diffuse skin rash, and arthralgia approximately 10 days after receiving intravenous rituximab. Diagnosis was rituximab-associated serum sickness. Image courtesy of Jason Kolfenbach, MD, and Kevin Deane, MD, Division of Rheumatology, University of Colorado Denver School of Medicine.