15 - Drug Allergies Flashcards
Pseudoallergic Reaction
Adverse DRUG reaction
with
Similar CLINICAL presentation to ALLERGIC reaction
but without involvement of the immune system
Which TYPE of Allergic Reaction?
Antibody Mediated Reaction
MOST COMMON
Requires a previous exposure = INDUCTION
Occurs immediately upon re-exposure = Elicitation
TYPE 1
Mediated by:
IgE & Mast Cells
Based on CLINICAL FEATURES, Which TYPE of Allergic Reaction?
URTICARIAL RASH (hives) = most common
NO FEVER IS SEEN
Pruritis / Flushing / Wheezing
ANGIOEDEMA of
face/extremities / tissues
GI Symptoms / Hypotension / ANAPHYLAXIS
TYPE 1
Immediate Onset & mediated by IgE / Mast cells
What type of Rash?
characteristic central blanching & red rims
described as WHEALS
URTICARIAL rash = HIVES
most common feature of
Type 1 Allergic Reaction
What type of Rash?
Most Common Drug-Induced Rash
Small / well demarcated lesions
that are
FLAT (macule) or RAISED (papule)
MACULOPAPULAR RASH
Anaphylaxis Manifestations
ANY DRUG CAN CAUSE ANAPHYLAXIS
SKIN = 80-90%
Anaphylaxis generally needs SKIN involvement
Flushing / Pruritus / Uticaria /Angioedema
Respiratory Tract = 70%
Nasal congestion / cough / hoarseness / SOB / wheezing
GI = 40%
Nausea / ab pain / vomiting / diarrhea
CV = 35%
hypotension / dizziness / tachycardia
Biphasic Anaphylaxis** vs **Protracted Anaphylaxis
Time Coarse of Anaphylaxis
Biphasic Anaphylaxis
After apparent recovery,
RECURRENCE within 6-10 hours is possible
Protracted Anaphylaxis
Rare, Symptoms PRESIST >24 hours
Mast Cell-Mediated vs Bradykinin-Mediated
ANGIOEDEMA
Mast Cell-Mediated Angioedema
TYPE 1 - occurs IMMEDIATELY after exposure
associated w/ uticaria / pruritis / bronchospasm
Bradykinin-Mediated Angioedema
most commonly associated with ACE-Inhibitors
NOT an ALLERGIC RXN
DELAYED onset ~can be years
Angioedema of Bowel Wall
present as colicky ab-pain / vomiting / diarrhea
Criteria for DIAGNOSING ANAPHYLAXIS
when exposure to allergen is
LIKELY
NEED 2+ of these SYMPTOMS –> TREAT IMMEDIATELY
Sudden SKIN + MUCOSAL S/sx
hives / itch-flush / swollen
Sudden RESPIRATORY s/sx
SOB / wheeze / cough
Sudden *REDUCED* BP or Symptoms of END-ORGAN dysfxn
COLLAPSE / incontinence
Sudden GASTROINTESTINAL symptoms
cramps / ab pain / Vomiting
Criteria for DIAGNOSING ANAPHYLAXIS
when exposure to allergen is
KNOWN
Exposed to a drug they are allergic to
If the allergen is KNOWN:
- *Just need**
- *REDUCED BP**
Infants & children:
low systolic BP or >30% decrease in systolic BP
Adults:
Systolic BP <90mmHg or >30% decrease from baseline
Criteria for DIAGNOSING ANAPHYLAXIS
when exposure to allergen is
UNKNOWN
involvement of skin/mucosal tissue or both
SUDDEN ONSET OF ILLNESS
ALONG WITH 1 or more of:
Sudden Respiratory Symptoms & signs
SOB / Wheeze / Cough
Sudden reduced BP or Symptoms of END-ORGAN dysfxn
Hypotonia = COLLAPSE / incontinence
Pitfalls to DIAGNOSING ANAPHYLAXIS
Signs are NON-SPECIFIC
Skin Manifestations are ABSENT in 10-20%
&
MAY BE ABSENT if H1 Antihistamine taken
Sedated / confused / demented patients
are unable to voice s/sx
What TYPE of ALLERGIC REACTION?
CYTOTOXIC reaction
Drug binds to surface of certain cell types
–> act as antigens
cell is then targeted for lysis by macrophage
Symptoms appear
- *1 week +** after exposure
- can be within HOURS if previously exposed*
TYPE 2
Delayed onset & caused by IgG mediated Cell destruction
CELL LINE DIES
Hemolytic Anemia
Thrombocytopenia
Leukopenia / Neutropenia
Pancytopenia / Agranulocytosis
HEPARIN INDUCED THROMBOCYTOPENIA
HIT
Type 2 Allergic Reaction
Causes:
Paradoxical INCREASED RISK for CLOTTING
- *AB –> HYPERACTIVE PLATELETS**
but. .. - *AB initiates CLEARANCE –> LOW PLATELETS**
Life + Limb threatening clots
Which TYPE of ALLERGIC REACTION?
IMMUNE-COMPLEX hypersensitivity
Timing:
Occurs with HIGH DOSE / long term / recurrent drug exposure
DELAYED by 1week+ after drug exposure
needs significant titers of AB to generate symptoms
TYPE 3
- *Delayed onset** and caused by IgG
- *immune-complex desposition –> complement activation**
FREE IgG or IgM –> binds drug
VVV
forms a free/soluble circulating immune comlex
VV
Precipitates in TISSUES –> INFLAMMATORY RESPONSE
Based on CLINICAL FEATURES, Which TYPE of Allergic Reaction?
DRUG FEVER
also seen with type 4 reactions
- *Vasculitis**
- *Purpura** (larger) / Petechiae (smaller) = bleeding into skin
- may also be seen in THROMBOCYTOPENIA in Type 2*
Serum Sickness
TYPE 3
Immune-Complex
delayed
Free IgG / IgM binds drug –> complex
What DRUGS are implicated with VASCULITIS?
Vasculitis common with TYPE 3
Pupura / Petechiae / Fever / Uticaria
PROPYLTHIOURACIL = PTU
MOST COMMON
- *Beta Lactams** / Sulfonamides / Phenytoin / Allopurinol
- may take weeks for resolving after D/C*
How to DISCRIMINATE
DRUG FEVER vs Infectious Fever
Drug fever common with Type 3 Reactions
but also with Type 4
Most commonly caused by Antibiotics
fever will stop after D/C of drug, recurs within hours of re-challenge
- *COMMONLY HIGH_ = _102-104***F
- BUT*
- *Patient DOES NOT KNOW they have Fever**
Presense of EOSINOPHILIA
correlated well with drug fever
What TYPE of ALLERGIC REACTION?
- *CELL-MEDIATED**
- *T-Cell**, not antibodies
Typically present as SKIN REACTIONS
DELAYED –> occur after 1-3 weeks of treatment
TYPE 4
Aka = Delayed Hypersnsitivity Reaction
Based on CLINICAL FEATURES, Which TYPE of Allergic Reaction?
Maculopapular Eruptions
SJS = Steven Johnsons Syndrome
TEN = Toxic Epidermal Necrolysis
DRESS = Drug rash with eosinophilia and Systemic Symptoms
Contact dermatitis
TYPE 4
Generally involve the skin, since skin is repository for a LARGE # of T-CELLS
Presentation of SJS & TENs
Commonly seen with:
Type 4 Delayed Hypersensitivity
Begins with FEVER & MALAISE
VVV
Followed rapidly by ERythmatous / purpuric macules+plaques
VVV
Progress to EPIDERMAL NECROSIS / SLOUGHING
SJS = LESS severe = <10% BSA slough
TEN = >30% BSA slough
SJS-TEN mix = 10-30%
MOST COMMONLY IMPLICATED DRUG
for
SJS & TENS
Type 4
ANTIBIOTIC SULFONAMIDES
beta lactams
Anticonvulsants
Allopurinol / Abacavir / Nevirapne
NSAIDs
Presentation of
DRESS
Drug Rash with Eosinophilia and Systemic Symptoms
SEVERE, involves:
Widespread Rash / FEVER >38.5
+
SINGLE or MULTI-ORGAN FAILURE
Liver = most common involved organ
- NOT all cases are associated with EOSINOPHILIA*
- *DiHS** is new name
Commonly caused by:
Anti-Epileptics
Most commonly implicated drug cause for
DRESS
ANTICONVULSANTS
Unique symptom = Organ Failure
Phenytoin / Phenobarbital / Lamotrigine –> hepatitis
Allopurinol / Sulfonamades -> nephritis
Abacavir –> pneumonitis
Olanzapine
What UNCLASSIFIED Drug Allergy?
When Ampicillin or Amoxicillin are taken
DURING INFECTION w/ Epstein-Barr Virus = MONO
- *Red/Itchy Maculopapular rash** –> upper extremeties & trunk
- can have fever / swelling of lips+eyelids / joint pain*
KEY POINT:
NOT LIKELY TO OCCUR ON RECHALLENGE
after Resolution of infection
not an allergic reaction that persisits
AMINO-PENICILLIN REACTION
What UNCLASSIFIED Drug Allergy?
Arthralgias is MOST common - 90% of cases (joint pain)
Myalgias present in 50%
Erythemia / Pericarditis / Positive ANA anti-nuclear ABs
need to differentiate from another disease
Onset can be weeks->years after starting drug
RESOLVES RAPIDLY after D/C
- *DILE**
- *Drug-Induced Lupus**
common in LUPUS but UNCOMMON in DILE:
Malar Rash / Discoid Lesions
RENAL INVOLVEMENT (only seen in LUPUS)
Positive Anti-dsDNA vs positive ANA
How to DIAGNOSE
DILE?
Drug-Induced Lupus
POSITIVE Anti-Histone AB
WITH
NEGATIVE Anti-dsDNA
anti-dS DNA is common in lupus disease
also renal involvment
What drugs are ASSOCIATED with
DILE?
Drug Induced Lupus
S H I P P
Sulfas
Hydralazine = high risk
Isoniazid
Procainamide = high risk
Phenytoin
What UNCLASSIFIED Drug Allergy?
Commonly implicated with
PPIs
Often associated with:
eosinophilia
INTERSTITIAL NEPHRITIS
What UNCLASSIFIED Drug Allergy?
and its Common drug cause
Caued by:
Ultraviolet / Visible-light ACTIVATIOn of drug
VV
Sunburn-like reaction
DRUG-INDUCED
PHOTOTOXICITY / PHOTOALLERGY
Most commonly caused by:
commonly Doxycycling
Sulfonamides / Voriconazole / Amiodarone
Which COMMON INDIVIDUAL AGENT causes this drug allergy?
All 4 types of reactions can occur
Most common is:
Uticaria / Pruritus / Angioedema
BETA LACTAMS
MOST COMMON cause of Allergic Drug Reactions
10% of patients
PCN SKIN TEST to confirm
- *PCN SKIN TESTING**
- *Penzylpenicilloyl Polylysine**
- *PRE-PEN**
Tests for IgE Reaction to PENICILLINS
(Beta Lactam allergy)
People are allergic to the METABOLITE = PRE-PEN
Start w/ EPIDERMAL inj of Pre-Pen
if NO reaction –> INTRADERMAL admin
Need to also give: Histamine & NS
Epinephrine & Diphenhydramine syringes
should be readily available
Beta Lactam
CROSS REACTIVITY
with CEPHALOSPORINS
1st Gen Cephalospirins (Cephalexin) have
HIGHER RATES OF CROSS REACTIVITY
similar side chains to PCN
Cross reactivity of
2nd / 3rd / 4th gen cephs are VERY SMALL
Beta Lactam
CROSS REACTIVITY
with CARBAPENEMS
LIKELY <1%
- *CONSIDER PCN SKIN TESTING**
- if negative, HIGHLY UNLIKELY that allergy will occur w/ carbapenem*
Beta Lactam
CROSS REACTIVITY
with AZTREONAM
NO IMMUNOLOGIC CROSS REACTIVITY
PCN allergy –> SAFELY TAKE AZTREONAM
EXCEPT FOR: CEFTAZIDIME
has identical side chain to Aztreonam
= Significant Risk of Cross-Reactivity
What to do if a patient with H/O PCN
&
requires a Cephalosporin or Carbepenem
1st, determine if patient:
- *Recieved a CEPH/CARBepenem SINCE** the time of initial PCN reaction
- if they DID w/ NO REACTION –* > can give med
2nd determine the:
SEVERITY of REACTION
Mild-Moderate & >10 years ago –> May give medication
- *Anaphylaxis / severe**
- -> DO NOT give unless test dose or desensitation in ICU
Which COMMON INDIVIDUAL AGENT causes this drug allergy?
DELAYED cutaneous macupapular rash within 3 days
Most common cause of:
SJS & TENs
SULFONAMIDES
2nd most common cause
ONLY ANTIBIOTIC SULFONAMIDES
due to arylamine side chain
Non-Antibiotic sulfonamides
no significant cross reactivity, RARE to occur
Which COMMON INDIVIDUAL AGENT causes this drug allergy?
Acute Hypersensitivity Reaction
similar to TYPE 1 reaction
Samter’s Triad of Symptoms
Hypersensitivity Rxn / Asthma Exacerbation / Rhinitis + Nasal polups
ASPIRIN
Cross Rxn w/ NSAIDs are common
little to NO cross reaction with COX-2 inhibitors
Which COMMON INDIVIDUAL AGENT causes this drug allergy?
Most common cause of DRESS
Eosinophilia is common
Can develop into –> SJS or TEN
Fever / rash / internal organ involvement
onset occurs several weeks into therapy
ANTICONVULSANTS
Anticonvulsant Hypersensitivity Syndrome / DRESS
VERY COMMONLY CAUSED BY:
VALPROATE + LAMATRIGINE
valproate inhibits lamotrigine metabolism
increased risk of hypersensitivity
Drugs that REQUIRE
HLA TESTING
A-C A P
ABACAVIR
CARBAMEZAPINE
ALLOPURINOL
PHENYTOIN
drugs that require HLA TESTING
TREATMENT for Symptoms of UTICARIA
Generally self-limiting after D/C of offending agent
Treat Symptoms:
H1 / H2 Anthitamines // glucocorticoids
EPINEPHRINE if H/O of Anaphylaxis
Treatment for ANAPHYLAXIS
D/C SUSPECTED ANTIGEN/DRUG
- *IM INJECTION OF EPINEPHRINE**
- DO NOT DELAY ONCE DIAGNOSED*
Anaphylaxis –> release of histamine –> vasodilation –> drop in BP
to RAISE BP:
Lay patient Down on Back & keep Legs Raised
0.9% NaCl 1-2 L wide open
EPINEPHRINE
- NO CONTAINDICATIONS TO EPI FOR ANAPHYLAXIS*
- *DO NOT DELAY after Anapylaxis Diagnosis**
- *Alpha & Beta AGONIST**
- *Vasoconstriction –> ^BP^
- inhibits FURTHER MEDIATOR RELEASE***
- *bronchodilation**
Dosing:
IM/SC - 0.3 mg of 1mg/ml q3-5min until improvement
into mid/outer thigh for faster onset
Adjunct Therapies to EPInephrine
if Continued URTICARIA
do NOT substitute adjunct therapy for ephinephrine
- *BENADRYL**
- *25-50 mg IVP**
- *RANITIDINE**
- *50 mg IVPB**
Adjunct Therapies to EPInephrine
if Continued RESPIRATORY SYMPTOM
do NOT substitute adjunct therapy for ephinephrine
Bronchodialators
- *Albuterol Nebulized Solution**
- *2.5 - 5 mg PRN**
- *Ipratropium Nebulized Solution**
- *0.5 mg PRN**
Adjunct Therapies to EPInephrine
to PREVENT / MINIMIZE LATE-PHASE REACTION
do NOT substitute adjunct therapy for ephinephrine
Corticosteroids
do NOT reverse symptoms ACUTELY
onset of action is 4-6 hours
- *MethylPrednisolone**
- *125 - 250 mg IV q6h**
Transition to oral prednisone as pt stabilizes for 3 days of total therapy
Treatment for
REFRACTORY ANAPHYLAXIS
EPINEPHRINE INFUSION
Slow IV infusion, is mcg (not mg)
Vasopressors
dopamine / dobutamine
- *IV FLUIDS**
0. 9% saline
What to do AFTER
RECOVERY FROM ANAPHYLAXIS
Monitor for 4-6 hours
Transition to –> oral meds
- *EDUCATE** patient on:
- *causitive agent / avoid exposure / RECORD**
Consider:
Self Treatment Device = Epipen
EPI-PEN or Adrenaclick
- *Adult Version = 0.3 mg IM**
- *>30 kg**
Kids = 0.15 mg IM
Pull off blue tab –> inject –> then
HOLD IN PLACE FOR 3 SECONDS