Pediatric Serum Sickness Medication: Antihistamines, Nonsteroidal anti-inflammatory drugs (NSAIDs),

Pediatric Serum Sickness Medication: Antihistamines, Nonsteroidal anti-inflammatory drugs (NSAIDs), Corticosteroids

Medication Summary

The objective of medical therapy is to ameliorate the symptoms that result from deposition of the immune complexes in the various tissues. Antihistamines are useful in controlling urticarial lesions. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat fever and minor musculoskeletal symptoms. Corticosteroids are necessary to treat the more severe symptoms.

Antihistamines

Class Summary

These agents are used to treat urticaria and pruritus. Classic H1-blocker antihistamines block the histamine-mediated increase in vascular permeability. Some second-generation antihistamines may also reduce the release of vasoactive amines.

Diphenhydramine (Benadryl, Anti-Hist, Aler-Tab, Diphen)

Diphenhydramine is an antihistamine with anticholinergic and sedative adverse effects. It is used for treatment of allergic reactions.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

Class Summary

This class of drugs acts by inhibiting cyclooxygenase, thereby blocking the production of prostaglandins, which are powerful mediators of inflammation. These drugs are useful in relieving fever and musculoskeletal pain.

Ibuprofen (Motrin, Advil, Provil)

Ibuprofen is a member of the propionic acid group of NSAIDs. It has moderate efficacy and a good safety profile and is used in children for various conditions, including fever and arthritis. To avoid gastrointestinal (GI) complications, it should be taken with food.

Corticosteroids

Class Summary

These agents elicit anti-inflammatory and immunosuppressive properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli.

Prednisone

Prednisone is a corticosteroid with salt-retention properties that is used for its potent anti-inflammatory effects. Because of its well-known adverse effects, it is used only in cases in which the systemic symptoms are severe.

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

Coauthor(s)

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

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

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

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

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.

References

1. von Pirquet CF, Schick B (Translator). Serum Sickness. Baltimore: Williams & Wilkins Co; 1951.
2. Gamarra RM, McGraw SD, Drelichman VS, Maas LC. Serum sickness-like reactions in patients receiving intravenous infliximab. J Emerg Med. 2006 Jan. 30(1):41-4. [Medline].
3. Brucculeri M, Charlton M, Serur D. Serum sickness-like reaction associated with cefazolin. BMC Clin Pharmacol. 2006 Feb 23. 6:3. [Medline]. [Full Text].
4. Colton RL, Amir J, Mimouni M, Zeharia A. Serum sickness-like reaction associated with griseofulvin. Ann Pharmacother. 2004 Apr. 38(4):609-11. [Medline].
5. Creamer JD, McGrath JA, Webb-Peploe M, Smith NP. Serum sickness-like illness following streptokinase therapy. A case report. Clin Exp Dermatol. 1995 Nov. 20(6):468-70. [Medline].
6. Heckbert SR, Stryker WS, Coltin KL, Manson JE, Platt R. Serum sickness in children after antibiotic exposure: estimates of occurrence and morbidity in a health maintenance organization population. Am J Epidemiol. 1990 Aug. 132(2):336-42. [Medline].
7. Hosoda N, Sunaoshi W, Shirai H, Bando Y, Miura H, Igarashi M. Anticarbamazepine antibody induced by carbamazepine in a patient with severe serum sickness. Arch Dis Child. 1991 Jun. 66(6):722-3. [Medline]. [Full Text].
8. King BA, Geelhoed GC. Adverse skin and joint reactions associated with oral antibiotics in children: the role of cefaclor in serum sickness-like reactions. J Paediatr Child Health. 2003 Dec. 39(9):677-81. [Medline].
9. Kunnamo I, Kallio P, Pelkonen P, Viander M. Serum-sickness-like disease is a common cause of acute arthritis in children. Acta Paediatr Scand. 1986 Nov. 75(6):964-9. [Medline].
10. Platt R, Dreis MW, Kennedy DL, Kuritsky JN. Serum sickness-like reactions to amoxicillin, cefaclor, cephalexin, and trimethoprim-sulfamethoxazole. J Infect Dis. 1988 Aug. 158(2):474-7. [Medline].
11. Segal AR, Doherty KM, Leggott J, Zlotoff B. Cutaneous reactions to drugs in children. Pediatrics. 2007 Oct. 120(4):e1082-96. [Medline].
12. Vial T, Pont J, Pham E, et al. Cefaclor-associated serum sickness-like disease: eight cases and review of the literature. Ann Pharmacother. 1992 Jul-Aug. 26(7-8):910-4. [Medline].
13. Lawley TJ, Bielory L, Gascon P, et al. A prospective clinical and immunologic analysis of patients with serum sickness. N Engl J Med. 1984 Nov 29. 311(22):1407-13. [Medline].
14. Knowles S, Shapiro L, Shear NH. Serious dermatologic reactions in children. Curr Opin Pediatr. 1997 Aug. 9(4):388-95. [Medline].
15. Kearns GL, Wheeler JG, Childress SH, Letzig LG. Serum sickness-like reactions to cefaclor: role of hepatic metabolism and individual susceptibility. J Pediatr. 1994 Nov. 125(5 Pt 1):805-11. [Medline].
16. Black RE, Gunn RA. Hypersensitivity reactions associated with botulinal antitoxin. Am J Med. 1980 Oct. 69(4):567-70. [Medline].
17. Jurkovich GJ, Luterman A, McCullar K, et al. Complications of Crotalidae antivenin therapy. J Trauma. 1988 Jul. 28(7):1032-7. [Medline].
18. Shemesh IY, Kristal C, Langerman L, Bourvin A. Preliminary evaluation of Vipera palaestinae snake bite treatment in accordance to the severity of the clinical syndrome. Toxicon. 1998 Jun. 36(6):867-73. [Medline].
19. Lavonas EJ, Kokko J, Schaeffer TH, Mlynarchek SL, Bogdan GM, Dart RC. Short-term outcomes after Fab antivenom therapy for severe crotaline snakebite. Ann Emerg Med. 2011 Feb. 57(2):128-137.e3. [Medline].
20. Offerman SR, Bush SP, Moynihan JA, Clark RF. Crotaline Fab antivenom for the treatment of children with rattlesnake envenomation. Pediatrics. 2002 Nov. 110(5):968-71. [Medline]. [Full Text].
21. LoVecchio F, McBride C. Scorpion envenomations in young children in central Arizona. J Toxicol Clin Toxicol. 2003. 41(7):937-40. [Medline].
22. Isbister GK. Safety of i.v. administration of redback spider antivenom. Intern Med J. 2007 Dec. 37(12):820-2. [Medline].
23. Bielory L, Gascon P, Lawley TJ, et al. Human serum sickness: a prospective analysis of 35 patients treated with equine anti-thymocyte globulin for bone marrow failure. Medicine (Baltimore). 1988 Jan. 67(1):40-57. [Medline].
24. da Silva PS, Passos RM, Waisberg DR, Park MV. Serum sickness and severe acute renal failure after rabbit antithymocyte globulin treatment in aplastic anemia: a case report. J Pediatr Hematol Oncol. 2011 Jan. 33(1):43-6. [Medline].
25. Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet. 2002 May 4. 359(9317):1541-9. [Medline].
26. Colombel JF, Loftus EV Jr, Tremaine WJ, et al. The safety profile of infliximab in patients with Crohn's disease: the Mayo clinic experience in 500 patients. Gastroenterology. 2004 Jan. 126(1):19-31. [Medline].
27. Lees CW, Ali AI, Thompson AI, et al. The safety profile of anti-tumour necrosis factor therapy in inflammatory bowel disease in clinical practice: analysis of 620 patient-years follow-up. Aliment Pharmacol Ther. 2009 Feb 1. 29(3):286-97. [Medline].
28. Zabana Y, Domènech E, Mañosa M, et al. Infliximab safety profile and long-term applicability in inflammatory bowel disease: 9-year experience in clinical practice. Aliment Pharmacol Ther. 2010 Mar. 31(5):553-60. [Medline].
29. Wang J, Wiley JM, Luddy R, et al. Chronic immune thrombocytopenic purpura in children: assessment of rituximab treatment. J Pediatr. 2005 Feb. 146(2):217-21. [Medline].
30. Bennett CM, Rogers ZR, Kinnamon DD, et al. Prospective phase 1/2 study of rituximab in childhood and adolescent chronic immune thrombocytopenic purpura. Blood. 2006 Apr 1. 107(7):2639-42. [Medline].
31. Sailler L. Rituximab off label use for difficult-to-treat auto-immune diseases: reappraisal of benefits and risks. Clin Rev Allergy Immunol. 2008 Feb. 34(1):103-10. [Medline].
32. Kumar A, Khamkar K, Gopal H. Serum sickness and severe angioedema following rituximab therapy in RA. Int J Rheum Dis. 2012 Feb. 15(1):e6-7. [Medline].
33. Ungprasert P, Srivali N, Kittanamongkolchai W, Leeaphorn N, Griger DT. Rituximab-induced serum sickness in overlapping syndrome between sjögren syndrome and systemic lupus erythematosus. J Clin Rheumatol. 2013 Sep. 19(6):360. [Medline].
34. Goto S, Goto H, Tanoshima R, et al. Serum sickness with an elevated level of human anti-chimeric antibody following treatment with rituximab in a child with chronic immune thrombocytopenic purpura. Int J Hematol. 2009 Apr. 89(3):305-9. [Medline].
35. Hellwig K, Schimrigk S, Fischer M, et al. Allergic and nonallergic delayed infusion reactions during natalizumab therapy. Arch Neurol. 2008 May. 65(5):656-8. [Medline].
36. Pilette C, Coppens N, Houssiau FA, Rodenstein DO. Severe serum sickness-like syndrome after omalizumab therapy for asthma. J Allergy Clin Immunol. 2007 Oct. 120(4):972-3. [Medline].
37. Russo EA, Iacucci M, Lindsay JO, et al. Survey on the use of adalimumab as maintenance therapy in Crohn's disease in England and Ireland. Eur J Gastroenterol Hepatol. 2010 Mar. 22(3):334-9. [Medline].
38. Comenzo RL, Malachowski ME, Meissner HC, Fulton DR, Berkman EM. Immune hemolysis, disseminated intravascular coagulation, and serum sickness after large doses of immune globulin given intravenously for Kawasaki disease. J Pediatr. 1992 Jun. 120(6):926-8. [Medline].
39. Azik FM, Kanmaz G, Ileri T. Serum sickness-like syndrome after immunoglobulin M-enriched polyclonal immunoglobulin. Drug Metabol Drug Interact. 2010. 25(1-4):49-50. [Medline].
40. Wise RP, Iskander J, Pratt RD, et al. Postlicensure safety surveillance for 7-valent pneumococcal conjugate vaccine. JAMA. 2004 Oct 13. 292(14):1702-10. [Medline].
41. Bonds RS, Kelly BC. Severe serum sickness after H1N1 influenza vaccination. Am J Med Sci. 2013 May. 345(5):412-3. [Medline].
42. Aujero MP, Brooks S, Li N, Venna S. Severe serum sickness-like type III reaction to insulin detemir. J Am Acad Dermatol. 2011 Jun. 64(6):e127-8. [Medline].
43. Zhang Z, Xiang Y, Wang B, Chen H, Cai X, Wang X, et al. Intestinal mucosal permeability of children with cefaclor-associated serum sickness-like reactions. Eur J Pediatr. 2013 Apr. 172(4):537-43. [Medline].
44. Suwansrinon K, Jaijareonsup W, Wilde H, Benjavongkulchai M, Sriaroon C, Sitprija V. Sex- and age-related differences in rabies immunoglobulin hypersensitivity. Trans R Soc Trop Med Hyg. 2007 Feb. 101(2):206-8. [Medline].
45. Bielory L, Yancey KB, Young NS, Frank MM, Lawley TJ. Cutaneous manifestations of serum sickness in patients receiving antithymocyte globulin. J Am Acad Dermatol. 1985 Sep. 13(3):411-7. [Medline].
46. Biuk D, Jukic T, Vukojevic N, Kalauz M. Serum sickness and uveitis. Coll Antropol. 2005. 29 Suppl 1:127-8. [Medline].
47. Tolpinrud WL, Bunick CG, King BA. Serum sickness-like reaction: histopathology and case report. J Am Acad Dermatol. 2011 Sep. 65(3):e83-5. [Medline].
48. Nangaku M, Couser WG. Mechanisms of immune-deposit formation and the mediation of immune renal injury. Clin Exp Nephrol. 2005 Sep. 9(3):183-91. [Medline].
49. Tanriover B, Chuang P, Fishbach B, et al. Polyclonal antibody-induced serum sickness in renal transplant recipients: treatment with therapeutic plasma exchange. Transplantation. 2005 Jul 27. 80(2):279-81. [Medline].

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.