Good Morning!Happy Friday!

Friday, July 26th 2013

HPI9yo M w/ dev delay, epilepsy p/w increasing

seizure activity despite recent medication changes Seizures range from partial to tonic clonic with a

majority being focal with eye movements. Mom denies URI symptoms, fevers, rashes,

changes in urine, diarrhea, vomiting or sick contacts.

HPI continuedBHx: born premature at 24weeks, NICUx3 months,

mom with viral infectionPMH: developmental delay, ambulates and feeds with

help, left sided weakness, minimally verbal, epilepsy since 4y/o

PHS: VNS placed 3/2013. VP shunt placed 2007 then removed shortly after

Allergy: Vancomycin Red mans.Home Medications:Topamax, Keppra, Clonazepam,

Lamictal, Clonidine, MelatoninFMH: diabetes and hypertension

HPIInfectious work up initiated, no abx startedPt admitted and loaded with Depakote IV on HD#1

HD#2 pt developed progressive facial flushing and repetitive sneezing and emesis x 2. Erythematous macular rash erupted on his arms and trunk.

PEPE: VS: HR: 90 RR: 14 BP: 100/67 Temp:

98.8 weight: 28kgGen: Awake NAD, flushed cheeks, lying in bedHEENT: Throat clear, TMs clearCV: RRR no murmurResp: CTA b/lAbdomen: soft NTND bowel sounds presentSkin: erythematous diffuse macular rash on arms

and trunk

Semantic Qualifiers

Symptoms

Acute /subacute ChronicLocalized Diffuse

Single Multiple

Static ProgressiveConstant Intermittent

Single Episode RecurrentAbrupt GradualSevere MildPainful NonpainfulBilious Nonbilious

Sharp/Stabbing Dull/Vague

Problem Characteristics

Ill-appearing/Toxic

Well-appearing/Non-toxic

Localized problem

Systemic problem

Acquired Congenital

New problem Recurrence of old problem

HPIProblem Definition 9 yo M with developmental delay and epilepsy,

admitted with progressive seizure activity refractory to home medications, now with acute onset of flushing, macular rash on trunk and upper extremities and emesis

Differential Diagnosis

Drug Reactions

Types of Drug ReactionsType A: Can affect any

individual given a sufficient dose and exposurePredictable reactions based

on the pharmacologic principles of the drugs

Examples:• Diarrhea from antibiotics• Gastritis from NSAIDs• Nephrotoxicity from

aminoglycosides

Type B: Hypersensitivity reactions that occur in a subgroup of susceptible patientsSymptoms are different

from the pharmacologic actions of the drugs

Usually cannot be predicted‘Drug Allergies’

• 4 types

PREP Question

Prep QuestionA 14yo boy who w/ CF p/w fever, cough, and

respiratory distress. On PE, his temp is 38.9°C, RR 28, HR 90 bpm, BP 116/74, and pox 91% on RA. CXR reveals bilateral infiltrates. After collecting blood and sputum specimens for culture, you initiate treatment with IV ceftazidime and tobramycin. Of the following, the MOST likely adverse effect that can occur with this treatment regimen is

A. Achiles tendonitis D .interstitial pneumonitisB. Aplastic anemia E. ototoxicityC. gallbladder sludge

Prep QuestionA 14yo boy who w/ CF p/w fever, cough, and

respiratory distress. On PE, his temp is 38.9°C, RR 28, HR 90 bpm, BP 116/74, and pox 91% on RA. CXR reveals bilateral infiltrates. After collecting blood and sputum specimens for culture, you initiate treatment with IV ceftazidime and tobramycin. Of the following, the MOST likely adverse effect that can occur with this treatment regimen is

A. Achiles tendonitis D .interstitial pneumonitisB. Aplastic anemia E. ototoxicityC. gallbladder sludge

Type I Hypersensitivity ReactionsImmediate in onset

Typically within 1 hour of administrationMediators?

IgE, mast cells, basophils• Release vasoactive mediators

Clinical Features:Urticarial rashPruritis, flushing, angioedema,

wheezing, GI upset, hypotensionMost severe presentation?

• Anaphylaxis

Prep Question The parents of a 10-yo boy who has a peanut allergy ask your advice on

treatment of food allergy reactions at school. Last year, their son started itching diffusely and had difficulty breathing during lunchtime after accidentally eating some of his friend's chocolate candy bar that contained peanuts. The child is allowed to carry his own self-injectable epinephrine at school. His current weight is 90 lb (41 kg). Of the following, the BEST advice for the child, if a similar situation occurs, is to

A. Have the school call emergency services (911), who should evaluate and administer epinephrine if needed

B. Have the school nurse observe the child for 10 to 15 minutes while calling his parents

C. Immediately administer 0.15 mg of self-injectable epinephrine D. Immediately administer 0.30 mg of self-injectable epinephrine E. Take an oral antihistamine immediately

Prep Question The parents of a 10-yo boy who has a peanut allergy ask your advice on

treatment of food allergy reactions at school. Last year, their son started itching diffusely and had difficulty breathing during lunchtime after accidentally eating some of his friend's chocolate candy bar that contained peanuts. The child is allowed to carry his own self-injectable epinephrine at school. His current weight is 90 lb (41 kg). Of the following, the BEST advice for the child, if a similar situation occurs, is to

A. Have the school call emergency services (911), who should evaluate and administer epinephrine if needed

B. Have the school nurse observe the child for 10 to 15 minutes while calling his parents

C. Immediately administer 0.15 mg of self-injectable epinephrine D. Immediately administer 0.30 mg of self-injectable epinephrine E. Take an oral antihistamine immediately

Type I Hypersensitivity ReactionsCommonly-implicated drugs

Beta lactamsNeuromuscular blocking agentsQuinolonesPlatinum containing chemotherapyForeign proteins

• Cetuximab, rituximab

Type II Hypersensitivity ReactionsUncommonInvolve antibody-mediated cell destruction

Drug binds to surfaces of certain cell types and act as antigens• Subsequent binding of antibodies results in the cell being targeted for

clearance by macrophagesVariable involvement of complement activation

Requires the presence of high titers of preformed drug-specific IgG (or IgM) antibodiesMade by only a small percentage of individualsUsually in the setting of high-dose, long-term or recurrent

drug exposure

Type II Hypersensitivity ReactionsCell types most commonly affected?

RBCs, WBCs, plateletsSymptoms are delayed

Typically appear at least 5-8 days after exposure; can be longerClinical manifestations

Hemolytic anemia• Dyspnea, fatigue, pallor, jaundice, dark urine, hyperdynamic state (ie

bounding pulses, palpitations)Neutropenia

• Fever, stomatitis, pharyngitis, pneumonia, sepsisThrombocytopenia

• Petechiae, mucosal bleeding, splenomegaly/hepatomegaly

Type II Hypersensitivity ReactionsDrugs implicated

Hemolytic anemia• Cephalosporins, penicillins, NSAIDs, quinine/quinidine

Neutropenia• Propylthiouracil (PTU), antimalarials, flecainide

Thrombocytopenia• Heparin, abciximab, quinine, sulfonamides, vancomycin, gold, beta-

lactams, carbamazepine, NSAIDs

Type III Hypersensitivity ReactionsAlso uncommonMediated by antigen-antibody complexes

Drug acts as soluble antigen and binds to drug-specific IgG forming small immune complexes that precipitate in various tissues

Complexes bind to receptors on inflammatory cells and/or activate complement inflammatory response

Timing of response>1 week (need adequate time to develop significant quantity of

antibody)Which tissues are typically affected?

Blood vessels, joints, renal glomeruli

Type III Hypersensitivity ReactionsClinical presentation: several forms

Drug fever• Can be the sole symptom or prominent symptom• Can be accompanied by nonurticarial rash or other organ involvement• Common drugs: azathioprine, sulfasalazine, minocycline, bactrim

Vasculitis• Palpable purpura and/or petechiae, fever, urticaria, arthralgias, LAD, elevated

ESR, low complement levels• Common drugs: penicillins, cephalosporins, sulfaonamides, phenytoin, allopurinol

Serum sickness• Classic: Fever, urticarial or purpuric rash, arthralgias, and/or acute

glomerulonephritis• Can have just 1 or 2 features

• Other findings: LAD, low complement levels, elevated ESR• Common drugs: penicillin, amoxicillin, cefaclor, bactrim

Type IV Hypersensitivity ReactionsNot mediated by antibodiesInvolve the activation of what cells?

T-cellsOther cell types can be involved (macrophages,

eosinophils, neutrophils)Timing

Delayed at least 48-72 hours and up to days-weeks after exposure

Clinical presentation:Prominent skin findings!

• The skin is home to a large number of T cells

Type IV Hypersensitivity ReactionsTypes of Type IV reactions

Contact dermatitis• Topically applied drugs• Erythema, edema, vesciles or bullae (can rupture and cause crust)

Morbilliform eruptions• Generalized and symmetric maculopapular eruption• Lacks mucosal involvement

Type IV Hypersensitivity ReactionsSJS/TEN

Onset is usually 1-3 weeksFever, mucocutaneous lesions necrosis and sloughing Distinguished by the severity and percentage of body

surface involved• SJS <10% BSA• TEN >30% BSA

Drugs involved• Allopurinol, sulfonamides**, PCN, Cephalosporins,

antipsychotics, antiepileptics, NSAIDSCan also be caused by infection (mycoplasma, HSV) or

malignancy

SJS/TEN: Skin Findings

Starts as erythematous macules that develop bullous centers

“Atypical target lesions” with irregular shapes and sizes, some areas of confluence

+ Nikolsky sign

Mucosal Findings

Mucosal erosions at 2 or more sites Stomatitis Conjunctivitis Urethritis

Erythema MultiformeAcute, immune-mediated condition characterized by the

appearance of distinctive target-like lesions on the skinEM major: EM with mucosal involvementEM minor: EM without mucosal involvement

EM major and SJS are DIFFERENT diseases with distinct causes90% infectious cause: Mycoplasma pneumoniae and HSV*10% medications

Systemic symptoms uncommon in mild EM, but can include fever, malaise, myalgia, respiratory symptoms

Type IV Hypersensitivity ReactionsDrug reaction with eosinophila and systemic

symptoms (DRESS) Also known as Drug-induced Hypersensitivity SyndromeSevere drug hypersensitivity involving rash, fever, and

multi-organ failure• Liver, kidneys, heart, lungs

Drugs responsible: antiepileptics, minocycline, allopurinol, dapsone

DRESSSevere type IV hypersensitivity reactionTiming: 3-8wks after drug administrationClinical manifestations:

High feverEosinophiliaLymphocyte activationFacial edemaSkin eruption

• Maculopapular rash• Erythroderma followed by exfoliative dermatitis• Rarely, skin manifestations may be minimal

LymphadenopathyMultivisceral involvement

TreatmentGlucocorticoidsClose monitoring with slow taper

Symptoms may re-flare weeks laterIVIGantivirals

Type IV Hypersensitivity ReactionsHigher risk of some type IV drug allergy reactions

during generalized viral infectionsEBV with amoxicillinCMV with any antibioticHHV6 with antiepilepticsHIV with trimethoprim-sulfamethoxazole

Thank you!!

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