Case Conference

K. Myra LalasPGY 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 WNLGen awake, alert, no acute distressHEENT PERRL, oropharynx clear, no LAD, TM’s normalLungs clear to auscultationHeart Normal S1/S2, no murmursAbdomen soft, nontender, no organomegaly

Ext L knee: (+) effusion, limited ROM secondary to painR knee: limited ROM secondary to painB/L ankles: erythema over lateral malleoli, no swelling, FROMNo nail changesSkin multiple erythematous, pruritic papules on back, buttocks with some excoriations

What are your differentials?

 

Differential Diagnoses

Viral ExanthemsUrticarial VasculitisMeningococcemiaReactive ArthritisOther drug reactionsErythema MultiformeSteven Johnson's SydromeKawasaki's disease

Serum Sickness Rash

SJS rash

 Meningococcemia Rash

Kawasaki

Labs

Parvovirus B19 IgG and IgM (normal)ASLO normal (25)Streptozyme negativeC4 28  C3 148Lyme Ab titer 0.2 (normal)CBC WBC 13.9 Hgb 12 Hct 35.4 platelets 429 N 52 L 43Blood Culture negativeESR 40CRP 3.5ua normalUrine culture negative

Labs

Na 136 K hemolyzed Cl 102 HCO3 20 BUN 9 Creatinine 0.6glucose 117 Ca 9.8albumin 4.1 TP 6.7 ALT hemolyzed AST 11Alk phos 145TB 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 formation2. Complement activation 3. Complement- independent mechanismsImmune 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 anti-CD20) 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. 

PenicillinMay 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.

TreatmentDiscontinuation 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.comwww.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.