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Case Conference K. Myra Lalas PGY 3 CC: rash and joint pain History of Present Illness • 2 days PTA, (+) itchy, reddish wheals on back then spread to torso, chest, and extremities • Went to PMD and was prescribed Benadryl and Hydrocortisone, which gave some relief • On the day of admission, (+) swelling, redness, warmth, and pain of both knees ( R > L), ankles (R > L), L elbow • No morning stiffness, nails don’t turn funny colors when cold Review of Systems • • • • • • • • No fever No cough or runny nose No vomiting No diarrhea Good PO No sick contacts No recent travel 1st episode Past Medical History • Staghorn calculus s/p removal of stones in the right kidney 3/2010 Family History • Osteoarthritis- grandfather • No lupus, no JIA, no scleroderma • No childhood leukemia Social History • Lives with both parents • No pets or smokers at home Physical Exam VS WNL Gen awake, alert, no acute distress HEENT PERRL, oropharynx clear, no LAD, TM’s normal Lungs clear to auscultation Heart Normal S1/S2, no murmurs Abdomen soft, nontender, no organomegaly Ext L knee: (+) effusion, limited ROM secondary to pain R knee: limited ROM secondary to pain B/L ankles: erythema over lateral malleoli, no swelling, FROM No nail changes Skin multiple erythematous, pruritic papules on back, buttocks with some excoriations What are your differentials? Differential Diagnoses Viral Exanthems Urticarial Vasculitis Meningococcemia Reactive Arthritis Other drug reactions Erythema Multiforme Steven Johnson's Sydrome Kawasaki's disease Serum Sickness Rash SJS rash Meningococcemia Rash Kawasaki Labs Parvovirus B19 IgG and IgM (normal) ASLO normal (25) Streptozyme negative C4 28 C3 148 Lyme Ab titer 0.2 (normal) CBC WBC 13.9 Hgb 12 Hct 35.4 platelets 429 N 52 L 43 Blood Culture negative ESR 40 CRP 3.5 ua normal Urine culture negative Labs Na 136 K hemolyzed Cl 102 HCO3 20 BUN 9 Creatinine 0.6 glucose 117 Ca 9.8 albumin 4.1 TP 6.7 ALT hemolyzed AST 11 Alk phos 145 TB 0.2 DB 0 Serum Sickness First described by von Pirquet and Schick. They described an illness that developed in some patients after they were given horse serum antitoxin for diphtheria and Scarlet fever. The illness developed a few weeks after administration of horse serum antitoxin. Cardinal features: rash, fever, and polyarthralgias or polyarthritis, which begin 1-2 weeks after exposure to the responsible agent. Pathophysiology Type III Hypersensitivity Reaction 1. Immune complex formation 2. Complement activation 3. Complement- independent mechanisms Immune complexes in tissues can react directly with Fc gamma receptors on neutrophils, mast cells, and phagocytes, leading to release of cytokines, histamine, and other inflammatory mediators even without complement. Precipitin Curve Serum-like sickness May be caused by drugs, viral infections Has different pathophysiology than serum sickness Levels of circulating immune complexes and serum complement are often unaffected Commonly implicated drugs: Cefaclor Penicillin (amoxicillin) Trimethoprim-sulfamethoxazole Heterologous Proteins Causing Serum Sickness Microbial antitoxins • Equine anti-diphtheria • Equine or ovine anti-rabies • Equine anti-botulinin toxin Venom anti-toxins • Equine, rabbit, ovine anti-snake venom (crotalidae (pit vipers, rattlesnakes) antivenin, micrurus (coral snake) antivenin) • Equine anti-spider venom (lactrodectus) antivenin Heterologous Proteins Causing Serum Sickness Immunomodulators • Equine or rabbit antithymocyte globulin Murine antiCD3 (OKT3) • Rituximab (murine/human chimeric antiCD20) Infliximab • (murine/human chimeric anti-TNF alpha) Alemtuzumab (humanized anti-CD52, Campath) Immunizations • Rabies antigens (human diploid cell rabies vaccine) Cefaclor and Bactrim Metabolites toxic to lymphocytes. The predisposing drug metabolism is genetically influenced. Penicillin May be caused by drug-specific immune complexes, not complexes with heterologous serum proteins. Signs and Symptoms Arthralgias Lymphadenopathy Urticarial rash Fever, when present, is typically low-grade. Acute onset of joint pain, often leading to inability to walk Labs • • • • • CBC ESR, CRP Urinalysis Complement levels If infectious etiology is to be ruled out, cultures, titers should be obtained. Treatment Discontinuation of the offending agent Supportive care Antihistamines for urticaria Nonsteroidal anti-inflammatory drugs (NSAIDs) for arthritis, arthralgia, or both Steroids (Prednisone or Methylprednisolone)- Patients with higher fever (eg, temperature >38.5ºC), more severe arthritis and arthralgias, or more extensive rashes including extensive vasculitic rashes may be treated with short courses of glucocorticoids. References Brucculeri, M. et al. Serum sickness-like reaction associated with cefazolin. BMC Clin Pharmacol. 2006; 6: 3. Hay Jr., W. et al. Current Pediatric Diagnosis and Treatment, 15th ed. McGraw-Hill. 2001: pp. 958-960. www.emedicine.com www.uptodate.com PREP Questions • You have been asked by a local school to provide recommendations about the use of self-injectable epinephrine for anaphylaxis. The school supervisor is concerned about the increased incidence of peanut and tree nut food allergy. School officials have requested that each child who has a diagnosis of "food allergy" have two self-injectable epinephrine devices at the school nurse's office. Of the following, the BEST response regarding anaphylaxis is that A. A patient should not receive a second dose of epinephrine unless a clinician is present B. Epinephrine reaches higher peak plasma concentrations if injected into the thigh rather than the arm C. Families should keep one epinephrine autoinjector in the car in case a reaction occurs after school D. Skin manifestations (eg, flushing, itching, urticaria) are rare in severe anaphylaxis E. Subcutaneous injection of epinephrine is preferable to intramuscular injection In the past, outpatient administration of epinephrine was subcutaneous, but research has demonstrated that intramuscular injection, specifically in the thigh, is the preferred route and location due to higher and faster peak plasma concentration. If epinephrine is administered, parents or school should call emergency services to evaluate the child and transport him or her to the ER for further evaluation. The effects of a single dose of epinephrine typically last for 5 to 15 minutes; up to 20% of individuals experiencing anaphylaxis may require a second epinephrine dose. When symptoms persist, a second (or third) dose should be administered, even if the parent or school professional still is awaiting the ambulance.