Serum Sickness, Emergency Medicine

Basics

Description

Type III hypersensitivity reaction
When a foreign protein or drug (the antigen) is injected, the bodys immune system responds by forming antibodies to the foreign material and subsequently forms complexes composed of the antigen, antibody, and complement.
These complexes then deposit in tissue, inciting an inflammatory response:
- C3a and C5a act as anaphylatoxins.
- C5a is strongly chemotactic for neutrophils.
- The neutrophils then infiltrate the vessel wall at the site of the immune complex deposition and release enzymes, such as collagenase and elastase, which damage vessel walls.
Typically, symptoms arise 6 " 21 days after the primary exposure to the antigen.
Symptoms can start 1 " 4 days after exposure if there has been an initial immunizing exposure.
Symptoms typically last 1 " 2 wk before spontaneously resolving.

Etiology

Serum sickness:
- Vaccines containing foreign protein or serum such as pneumococcal vaccine or rabies.
- Antivenom and tetanus inoculations made with horse or sheep protein
- Monoclonal antibodies
Serum sickness " like reaction:
- Caused by nonprotein drugs, mostly antibiotics:
  - Penicillins, amoxicillin
  - Cephalosporins (i.e., Cefaclor)
  - Sulfonamides (i.e., Bactrim)
  - Thiazides
  - Gold
  - Thiouracils
  - Hydantoins
  - Phenylbutazone
  - Aspirin
  - Streptomycin

Diagnosis

Signs and Symptoms

Classic presentation is fever, rash, arthralgias, and lymphadenopathy.
History

Fever
Rash (urticarial, morbilliform, scarlantiniform)
Arthralgias
Myalgias
Lymphadenopathy
Facial and neck edema
Chest pain
Shortness of breath

Physical Exam

Fever
Rash
Lymphadenopathy
Arthritis
Edema
Splenomegaly
Peripheral neuritis
Myocarditis/pericarditis
Anaphylaxis

Essential Workup

History of a possible offending agent and time course of 6 " 21 days before onset of symptoms
Physical exam revealing rash as well as joint, muscular, cardiac, neurologic, or renal insult from vasculitic type process

Diagnosis Tests & Interpretation

Lab

Decreased complement levels
CBC, possible eosinophilia
Elevated ESR
Hypergammaglobulinemia
Urine with proteinuria or hematuria

Imaging
Consider CXR.
Diagnostic Procedures/Surgery
Biopsy is the only means of definitive diagnosis.

Differential Diagnosis

Vasculitides (e.g., polyarteritis nodosa, Goodpasture, Wegener)
Rashes (e.g., erythema multiforme, toxic epidermal necrolysis)
Immunologic (e.g., systematic lupus erythematosus, polymyositis, anaphylaxis)
Infectious (e.g., tick-borne disease, Rocky Mountain spotted fever, mononucleosis)

Treatment

Pre-Hospital

ABC stabilization
Anaphylaxis treatment as indicated.

Initial Stabilization/Therapy

ABCs if a severe systemic reaction is present

Ed Treatment/Procedures

Symptomatic relief until the disease spontaneously resolves in 1 " 13 wk
Antihistamines
Antipyretics
NSAIDs
Prednisone is controversial

Medication

Acetaminophen: 325 " 650 mg PO/PR (peds: 10 " 15 mg/kg) q4 " 6h
Diphenhydramine: 50 " 100 mg (peds: 5 mg/kg/d, div., max. dose 50 mg/dose or 300 mg/24h) q6 " 8h
Hydroxyzine: 25 " 50 mg (peds: 0.5 mg/kg/dose) q6 " 8h
Ibuprofen: 200 " 800 mg PO (peds >6 mo: 5 " 10 mg/kg) q6 " 8h
Prednisone: 5 " 60 mg/d PO (peds: 0.5 " 2 mg/kg/d), 2-wk taper

Follow-Up

Disposition

Admission Criteria

Involvement of the airway
Relapse of symptoms and signs after initial steroids
Immunosuppression
Concomitant serious disease
Sociologic considerations

Discharge Criteria
Stable; most cases are self-limiting.
Issues for Referral
Skin testing with heterologous antisera is performed routinely to avoid anaphylaxis to future administration of heterologous serum.

Followup Recommendations

Primary care follow-up

Pearls and Pitfalls

Identification and cessation of the offending antigen is crucial in the treatment of serum sickness.
Significant morbidity comes from a failure to diagnose when the serum sickness is not considered on the differential.

Additional Reading

Chen S. Serum sickness (emergency medicine). Emedicine. Available at Emedicine.medscape.com/article/756444-overview.
Gamarra RM,
McGraw SD, Drelichman
VS, et al. Serum sickness-like reactions in patients receiving intravenous
infliximab. J Emerg Med.
2006;30(1):41 " 44.
Piessens WF. Systemic immune complex disease. In: Ruddy S ed. Kelleys Textbook of Rheumatology. 6th ed. Philadelphia, PA: Saunders; 2001.
Pilette C, Coppens N, Houssiau FA, et al. Severe serum sickness-like syndrome after omalizumab therapy for asthma. J Allergy Clin Immunol. 2007;120(4):972 " 973.

Codes

ICD9

999.51 Other serum reaction due to administration of blood and blood products
999.52 Other serum reaction due to vaccination
999.59 Other serum reaction
999.5 Other serum reaction, not elsewhere classified

ICD10

T80.61XA Oth serum reaction due to admin blood/products, init
T80.62XA Other serum reaction due to vaccination, initial encounter
T80.69XA Other serum reaction due to other serum, initial encounter

SNOMED

72284000 transfusion reaction due to serum protein reaction (disorder)
403608009 Serum sickness due to drug

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