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Serum Sickness

para>If rash is atypical or does not abate after withdrawing suspected drug, consider obtaining

  • Antinuclear antibodies
  • Antineutrophil cytoplasmic antibodies
  • Rheumatoid factor (RF)
  • Cryoglobulins
  • Skin biopsy with immunofluorescence

Diagnostic Procedures/Other

Patch testing may be useful for anticonvulsants and antibiotics but does not work consistently with all medications (6)[C].

TREATMENT

GENERAL MEASURES

  • Mainstay of treatment is to remove the offending agent.
  • Reticuloendothelial system removes immune complexes, leading to improvement within 48 to 72 hours.
  • Complete resolution of rash may take days to weeks.
  • Time frame of improvement largely depends on half-life of antigen.
  • Symptoms usually resolve within 4 to 14 days after stopping the offending agent.In case reports, use of prednisone 60 mg/day along with high doses of antihistamines can help resolve pruritus and skin rash.

MEDICATION

First Line

  • Diphenhydramine or hydroxyzine: 25 to 50 mg IV/PO q4 " 6h for urticaria and generalized pruritus (2)
  • Long-acting H1 antihistamines, such as cetirizine or loratadine, which are less sedating, can also control urticaria and are recommended to be continued for 1 week after resolution of symptoms and then gradually discontinued.
  • Topical corticosteroids for skin manifestations (2)
  • NSAIDs may offer relief of arthralgia/myalgia (2).

Second Line

Prednisone: 0.5 to 1 mg/kg/day PO or methylprednisolone 1 to 2 mg/kg IV divided QID or BID for 5 to 7 days if inflammation is severe or first-line drugs fail (2)

ISSUES FOR REFERRAL

  • Consider allergy referral to identify inciting agent.
  • Consider rheumatology referral if autoimmune disorder suspected.

ADDITIONAL THERAPIES

  • IVIG is not routinely recommended. May have a role if other therapies are ineffective or contraindicated
  • Premedicating rituximab infusions with IV corticosteroids may reduce incidence of infusion-associated reactions (3)[C].

INPATIENT CONSIDERATIONS

Admission Criteria/Initial Stabilization

  • Most patients with acute SS or SSLR require admission for observation, supportive care, and to exclude other diagnoses.
  • Recognition and treatment of hypersensitivity reactions occurring in the ICU can be challenging given the number of medications frequently prescribed. Cab mimic other diagnoses, including septic shock (7)[C].
  • Basic life support and advanced cardiac life support, as needed

IV Fluids

As indicated for hydration

Nursing

As clinically indicated

Discharge Criteria

  • When significant reduction in inflammation occurs after stopping suspected drug
  • When ambulatory and tolerating PO

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

  • Bed rest during acute illness if severe arthralgia/myalgia
  • No indication for skin testing for ²-lactam antibiotics because severe non " IgE-mediated reactions are drug-specific, and reexposure should be avoided.

Patient Monitoring

As clinically indicated

DIET

Routine

PATIENT EDUCATION

Counsel patient to avoid offending agent and document allergy.

PROGNOSIS

Favorable

  • Self-limiting with improvement in 48 to 72 hours after offending antigen is removed.
  • If reexposed to antigen, SS can develop more rapidly and with more severe symptoms.

COMPLICATIONS

  • Vasculitis
  • Neuropathy
  • Hepatitis
  • Glomerulonephritis
  • Anaphylaxis
  • Shock
  • Death

REFERENCES

11 Butt A, Rashid D, Fox R, et al. Urticaria and arthralgias in a nine-year-old with recurrent urinary tract infections. World Allergy Organ J. 2012;5(Suppl 2):S139.22 Knowles SR, Shear NH. Recognition and management of severe cutaneous drug reactions. Dermatol Clin. 2007;25(2):245 " 253.33 Brown BA, Torabi M. Incidence of infusion-associated reactions with rituximab for treating multiple sclerosis: a retrospective analysis of patients treated at a US centre. Drug Saf. 2011;34(2):117 " 123.44 Alvares ML, Warrier I. Pneumococcal vaccine after IVIG treatment causing serum sickness. In: 2010 Annual Meeting of the American College of Allergy, Asthma and Immunology; November 11, 2010. Abstract P106.55 Aujero MP, Brooks S, Li N, et al. Severe serum sickness-like type III reaction to insulin detemir. J Am Acad Dermatol. 2011;64(6):e127 " e128.66 Friedmann PS, Ardern-Jones M. Patch testing in drug allergy. Curr Opin Allergy Clin Immunol. 2010;10(4):291 " 296.77 Kanji S, Chant C. Allergic and hypersensitivity reactions in the intensive care unit. Crit Care Med. 2010;38(6 Suppl):S162 " S168.

ADDITIONAL READING

  • Bonds RS, Kelly BC. Severe serum sickness after H1N1 influenza vaccination. Am J Med Sci. 2013;345(5):412 " 413.
  • Hempel C, Martin C. Getting under the skin of adverse drug reactions. Orthopedics. 2012;35(10):872 " 876.
  • Khan DA, Solensky R. Drug allergy. J Allergy Clin Immunol. 2010;125(2 Suppl 2):S126 " S137.
  • Tisdale J, Miller D. Drug Induced Disease: Prevention, Detection, Management. Bethesda, MD: American Society of Health System Pharmacists; 2010.

CODES

ICD10

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

ICD9

  • 999.59 Other serum reaction
  • 999.52 Other serum reaction due to vaccination
  • 999.51 Other serum reaction due to administration of blood and blood products

SNOMED

  • Serum sickness due to drug
  • Serum rash (disorder)
  • transfusion reaction due to serum protein reaction (disorder)
  • Serum sickness type vasculitis (disorder)

CLINICAL PEARLS

  • Consider serum sickness when patients present with symptoms and recent exposure to a foreign antigen.
  • Cutaneous drug reactions are among the most commonly reported adverse drug reactions (ADRs).
  • Specific medications causing a SSLR should be identified as allergens, listed as a medication allergy in the patient problem list, and avoided in the future.
  • Premedication does not prevent SS or SSLR.
  • Serpiginous rash on lateral borders of hands and feet is a classic physical finding in SS and SSLR.