History

The onset of serum sickness symptoms usually occurs 1-2 weeks after administration of the offending agent and correlates with the peak of circulating immune complexes. Fever, malaise, and headache are the earliest symptoms. Rash, joint pain, edema, gastrointestinal (GI) symptoms, arthralgia, and other symptoms follow.

Physical Examination

A rash is often the first clinical symptom and is frequently pruritic. If the causal agent was injected, the rash typically starts at the site of injection. Otherwise, the rash starts on the abdomen and spreads outward. Mucous membranes are not involved. Eruption over the rest of the body is usually symmetric and may take any of the following forms:

Urticaria (see image below)
Scarlatiniform rash
Morbilliform rash
Polymorphous exanthema
Erythema, petechiae, or purpura with a serpiginous border at the margin of palmar plantar skin with the use of ATG^[13]

Urticarial rash in a child 10 days after cefaclor was administered for sore throat. Associated findings included fever, arthralgia of knees and ankles, and eosinophilia.

Approximately two thirds of patients experience joint discomfort.^[45]In order of decreasing frequency, the affected joints include the knees, ankles, shoulders, wrists, spine, and temporomandibular joint. Joint fluid usually yields a moderately high number of white cells. Myalgias in the arms and thighs may also occur.

Lymphadenopathy coincides with the onset of other symptoms of serum sickness. Lymph nodes that receive drainage from the injection site may enlarge and become tender. Other lymph nodes may also enlarge, sometimes to several centimeters in diameter.

Proteinuria, microscopic hematuria, and hyaline casts may be observed. Serum creatinine levels may transiently rise, and the creatinine clearance may decrease. Edema may be due to proteinuria or rash.

Nausea, vomiting, and abdominal pain are usually mild but may be confused with appendicitis and other GI disorders in children. Other, rare symptoms include:

Headache and blurred vision
Uveitis^[46]
Cardiovascular problems - Pericardial effusion
Respiratory problems - Dyspnea, wheezing, cyanosis

Complications

Since this condition is associated with immune complex-based bascular inflammation, in severe cases, involvement of other organs such as the kidney, brain, lung, GI tract, etc. can occur. For example, severe cases of serum sickness with sulfonamide can manifest as Stevens-Johnson syndrome.

Differential Diagnoses

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Media Gallery

Urticarial rash in a child 10 days after cefaclor was administered for sore throat. Associated findings included fever, arthralgia of knees and ankles, and eosinophilia.

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Author

Tova Ronis, MD Attending Rheumatologist, Division of Rheumatology, Children's National Medical Center; Clinical Assistant Professor of Pediatrics, George Washington University Medical Center

Tova Ronis, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Rheumatology, Childhood Arthritis and Rheumatology Research Alliance

Disclosure: Nothing to disclose.

Coauthor(s)

Hanna Kim, MD, MS Pediatric Rheumatology Fellow, AI Dupont Hospital for Children, Thomas Jefferson University, National Institutes of Health (NIH), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Hanna Kim, MD, MS is a member of the following medical societies: American Academy of Pediatrics, American College of Rheumatology, American Medical Association, Childhood Arthritis and Rheumatology Research Alliance, Rheumatism Society of the District of Columbia

Disclosure: Nothing to disclose.

Philip J Cohen, MD Chief, Section of Dermatology, New Jersey Veterans Affairs Medical Center

Disclosure: Nothing to disclose.

Lawrence K Jung, MD Chief, Division of Pediatric Rheumatology, Children's National Medical Center

Lawrence K Jung, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Rheumatology, Clinical Immunology Society, New York Academy of Sciences

Disclosure: Nothing to disclose.

Chief Editor

Harumi Jyonouchi, MD Faculty, Division of Allergy/Immunology and Infectious Diseases, Department of Pediatrics, Saint Peter's University Hospital

Harumi Jyonouchi, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association of Immunologists, American Medical Association, Clinical Immunology Society, New York Academy of Sciences, Society for Experimental Biology and Medicine, Society for Pediatric Research, Society for Mucosal Immunology

Disclosure: Nothing to disclose.

Acknowledgements

Robyn Siperstein, MD Staff Physician, Department of Dermatology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School

Robyn Siperstein, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Society for MOHS Surgery, and Sigma Xi

Disclosure: Nothing to disclose.

David J Valacer, MD Consulting Staff, Hoffman La Roche Pharmaceuticals

David J Valacer, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association for the Advancement of Science, American Thoracic Society, and New York Academy of Sciences

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.