drug allergy Flashcards
pseudoallergic (anaphylactoid):
immediate systemic rxn that mimic anaphylaxis but non IgE mediated - release mediator from mast and basophil
Drug intolerance vs
drug idiosyncrasy
: undesriable pharma effect - occur at low/usual dose - no underlying abn in metbaolism, excretion or bioavail - T and B cell not involved and cant understand mechanism - ie) tinnitus with aspirin
Drug idiosyncrasy: abn and unexpected effect unrelated t drug, and uknown why, not T or B cell mediated but is repdocuble - could be due to metabolism or bioavail - ie) fever from quinidine or g6pd and hemolytic anemia with dapsone
name gel and coombs types and subtype of 4
1-ige
2-igg or igm directed at hapten coated _ autoimm anemia
3- tissue deposited of drug ab complex with complement activation and inflm (serum sickness, vasculitis)
4: T cell medaited MCH presentinh drtug
METN
(1a - macro, 1b, eo, 4c T cell, iv d neotrphil)
type 4 reactions for gel coombs, subtypes and ex
4a- Macrophage, Infn gamma, TNFalpha Th1 medaited, APC presented ie) TB
4b: Eo, il5,/23, Eo and chronic AR and athma, dress?
4c: T cell perforin granzyme, contact dermatitis, and macolpop bullous
4d- No, ILbeta GMCSf
AGEP and bechets
what is pi concept
Pharmacologic interaction with immune receptors
Drug binds non covalantly to the TCR and this leads to immune rxn via interaction with major histocombatability receptor
No sensitization needed as its direct stimulation of the memory and effector T cell (like a superantigen)
name RF for drug allergy
patient: middle age adult more then infant, women more then men, genetic polymorphihsm , HIV herpeps, and prev rxn
Drug: HMW compound, topical>iv>oral, dose frequnt>single dose
give examples of drugs causing
1) Type 2 cytotoxic
2) serum sickness
3) type 4 contact dermatitis
hyoersensitivty vasculitis
pulm DRUG hypersensitve
SYSTEMIC sle
CUTANEOUS sle
granuloma
blistering
neophropathy
1) Type 2 cytotoxic
penicilline, sulga
2) serum sickness
penicillin, thymo, inflixmab
3) type 4 contact dermatitis
0 neomycin, pen, sulfonamide
hypersensitivty vasculitis: hydralazine
pulm DRUG hypersensitve: bleo, MTX, nitrofuranton
SYSTEMIC sle: hydralazine, procainamde, isonazid
CUTANEOUS sle: HZT, CCB, AE inh
granuloma: PTU
blistering
: NSAID, sulfonamide,
anticonvulsant
neophropathy: gold, penicillin, sulfonamide
Contraindications for drug desensitization
SJS, TEN, interstitial nephritits, hepatitis and hemolytic anemia
what is in pen testing
major determinant (PRE-penicilloylpolylysine)
MINOR
- pen G
- penicilloate and penilloate
List 4 types of reactions to NSAIDS
AERD, worsening of CSU, IgE mediated anaphylaxis/urticarial,
urticarial/angioedema to all cox-1 inhibitors (no hx of CSU)
Underlying mechanism of AERD?
aberrant arachidonic acid metabolism. Before administration of
aspirin, compared with non–aspirin-sensitive asthmatic patients,
patients with AERD have higher levels of both COX and 5-
lipoxygenase products, such as increased urinary leukotriene E4 and
throm- boxane B2, and increased leukotriene E4 and thromboxane B2
in bronchoalveolar lavage fluid.602-604 Patients with AERD also have
increased respiratory tract expression of the cystei- nyl leukotriene 1
receptor and heightened responsiveness to inhaled leukotriene
E A number of genetic polymor- phisms involving the
leukotriene pathway have been reported to be associated with
AERD, including the leukotriene C4 promotor, cysteinyl
leukotriene receptor 1 promotor,606 prostanoid receptor related
genes,607 and thromboxane A2 receptor genes. Administration of
aspirin leads to inhibition of COX-1 with resultant decrease in
prostaglandin E2. Prostaglandin E2 normally inhibits 5-lipoxygenase,
but with a loss of this modifying effect, arachidonic acid molecules
are preferen- tially metabolized in the 5-lipoxygenase pathway,
resulting in increased production of cysteinyl leukotrienes.
name 5 ways to prevent drug reactions
1) careful hx for host factors
2) avoid of cross reactive drugs
3) use of oral abx
4) use predictive tests when u can
5) proper prescribing of drugs when needed
6) document thr ADR in the chart
name an example of using induction of tolerance with drug in an non-Ige drug reaction
imatanib (tyrosine kinase inhibitor) for malignant tumors
gernally it is contraidncated tho - ie_ with SJS or TEN
Lupus (cutaneuso vs systemic) drug indue
Cutaneous
more freq- 4-8w in onset, no systmic signs, photsensitive ertyhema, scaly anular plaques,
drug: CCB, HZT, ACE, antifungal
vs systemic is rare and take months to get tehre with photosensitivty and erythema nodosum as skin
(procainamide, minocycline, isonaizide, methldopa)
causes of elevated tryptase
Familial tryptasemia, AML, refractory anemia’s, myelodysplastic syndrome, SCF (stem cell factor) administration, ESRD with elevated SCF
anaphylaxis
Mastyoctosis
anaphylaxis
myeloid HES
give three common drugs implicated in type 2 rxn
complement MEDIATED cytotoxi c IgM or IgG formed to drug altered cell surface membranes
pencillin, quinidine, and alpha methyl dopa - cause anemia
usu when treatment with pen for a long time
can get low plt with quinidine as well, and quinine, tylenol, PTU
low granulocyte anticonvulsant , sulfonamide
type 3 rxn example of drugs
remember from slight antigen excess
penicillin
sulfonamdie
phenytoin
mabs
name 5 common topical allergic contact dermatitis antigegns
neomycin parabens bactiracin thimerosal lanolin formaldehyde
remmeber - photoallergic ones: sulfonamide, thaizide, quinidine, and chlorporamazine and fluoroquinolones
five risk factor for radiocontrast anaphylactoid reaction
usually ionic is worst
but female asthma hx of prec fxn beta blocker - higher risk
steps for pt who has possible anaphylactoid
Management: Determine if its essential Patient understands risk Hydration Use NON ionic, iso osmolar RCM Pretreatment regime that works
Lupus (cutaneuso vs systemic) drug indue
Cutaneous
more freq- 4-8w in onset, no systmic signs, photsensitive ertyhema
causes of elevated tryptase
Familial tryptasemia, AML, refractory anemia’s, myelodysplastic syndrome, SCF (stem cell factor) administration, ESRD with elevated SCF
anaphylaxis
Mastyoctosis
AERD
anaphylaxis
myeloid HES
name high risk drugs for EM/SJS
sulfonamide. cephalosporine, imidazole and oxicam derivative
name two drugs causing bllous pemphigoid
and two causing pemphigus
furosemide and penicillin and sulfasalazine cause bullous pemphifoid
THIOL group meds like captoprile and penicillamine
chamomile tea… it cross reacts with ?
ragweed and mugwort FYI
what are screening tests for
- drug induced vasculitis
- serum sickness
- CBC CRP pANCA and cANCA and ANA
2. cryoglobylin or cold preictoable serum protein for immune complex
what is the advantage of LTA tests
also what do you look for marker wise on BAT
LTA - bypass need for knowledge of metabolic determinants as check for LTA to drug itself
CD63 for BAT
name 4 histologic findings with biosy of drug exantham
1) Eo
2) interface dermatitis
3) vacuolar alteration of keratinocyte
4) foci of spongiosis
name reasons why coombs are positive
presence of complement
drug on RBC membrane
Rh determinant autoanntibody
name 4 reasons drugs may be continued even tho you have allergy
ie) medicatl condtion
DKA Tb neurosyphllis endocarditis IBD
5 contrainidcations to inudction of tolerance?
SJS TEN hemolytic anemia interstial nephritis hepatitis
drug reactions ACE inh angioedma
name four mechainsim of asa desens
loss of tolerance ocucurs 2-4d wihtout asa
1) reduction of urinary leukotriene e4
2) intenralization of cysteinail leukotriene receptor 1 receptor
330 release of mast cell trpytase
monitor for lung issues
what is the diagnostic critetria for SWEET syndrome
most ocmmon drug GCSF
Diagnostic criteria for Sweet syndrome
Classical*
1. Abrupt onset of painful erythematous plaques or nodules
2. Histopathologic evidence of a dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis
3. Pyrexia >38°C
4. Association with an underlying hematologic or visceral malignancy, inflammatory disease, or pregnancy, or preceded by an upper respiratory or gastrointestinal infection or vaccination
5. Excellent response to treatment with systemic corticosteroids or potassium iodide
6. Abnormal laboratory values at presentation (three of four): erythrocyte sedimentation rate >20 mm/hr; positive C-reactive protein; >8,000 leukocytes; >70 percent neutrophils
Drug-induced¶
A. Abrupt onset of painful erythematous plaques or nodules
B. Histopathologic evidence of a dense neutrophilic infiltrate without evidence of leukocytoclastic vasculitis
C. Pyrexia >38°C
D. Temporal relationship between drug ingestion and clinical presentation, or temporally-related recurrence after oral challenge
E. Temporally-related resolution of lesions after drug withdrawal or treatment with systemic corticosteroids
whats SDRIFE (baboon syndrome)
symetrical drug related interginous and flexural exanthema
Tend to be near lips, hands and genitalaia - can occur with NSAID cabamazipine and tetraclcyine
Few hours to days after administration of the drug
Treat with stopping drug and then topical steroids
name 3 upper and lower resp effects of ASA desn
for acute urtcaira- 2-5 h protocol
if its CSU worsened by nsaid it dont help
1) upper
- dec nasal symptoms
- dec INCS
- less polyp
better smell
dec polpyectomy
lower - dec asth,a, dec inh steroids, dec hos and ED
four findings AFRS on CT
central hyperattenuation, heterogenous opacification with inspissated secretions in affected sinuses, nasal expansion, bony deminderalization, erosion of lamina papyacae or skull base
name 4 pre assessment and pre med before ASA desen
1-7 days before procedure
1) FEV >60 PRED
2) STARAT 10MG MONTEKULAST
3) continuse or start ICS and LABA
4) give sustemic steroid burst if feb1 low
what three cephalsopring share r1 with amox
cefprozil
cefadroxil
cefatrizine
what makes sulfonamide abx allergic in nature froma chemical structure pespective
There is NH2 S02 in sulfonamide, but the abx have aromatic amine at N4 and substituted ring at N1 which make it more allergic in nature
name 5 reasosn to stop HIV patient on septra\
dapsone cross reactiivity is LOW but avoid if severe rxn like sjs on septra
persistnt of rash and fever for more then 5 d
ANC <5000
hypotension
dspynea a
signs of blistering or desquam or mm involvement
what is IMMUNE RECONSITUTION INFLAMATORY SYNDROME
its when hiv ppl get TB and are n HAARD and anti tb drugs - causes
1) induction of p450 and recuces HAART med effeciy
2) toxic effects of drugs overlap
4) increased risk of anaphylaxis as it skews towards th2
what is IMMUNE RECONSITUTION INFLAMATORY SYNDROME
its when hiv ppl get TB and are n HAARD and anti tb drugs - causes
1) induction of p450 and recuces HAART med effeciy
2) toxic effects of drugs overlap
4) increased ris =k of anaphylaxis as it skews towards th2
what is the most common type of hypersneivity reaction inudced by steroids
contact derm allergic
IV methylprednisoline and hydrocort are most implicated in anaphylaxsi
which med can put diabetics at higher risk of anaphylaxis
protamine
from salmon testes
groups of topical anestehics?
remember when testing takng out paraben, epi and sulfites
SPT then subcut
0.1ml 1:100 and then go up every 15 min till u get 1ml of undilutes
GROUP 1: benzoic acid esters - procaine and benzocaine
GROUP 2: amides - lidocaine and mepivacaine
what do u do wiht patient prev anaphylacoitd to RCM
RF, women, asthma, prev hx, beta blocer and CVD
can try SPT if neg
then non ionic iso osmolar agent to be used and pre med with steroid and anthistamine, 13h, 7 h and 1 h before *50mg
diphenhydramine 1h before 25mg
DONT give ranitidine
can get deayed reaction 1w after in 2%
what % patients have AERD
baseline they have higher COX asnd 5 lipoxygenase products like uirintary leukotriene e4 and thromboaxane B2, with increased expression of of cysteineyl leukortirene 1 receptor.
w
ashtma 10%
AR And astham 30%
with the challemge- get dec PGE2, which inhibits 5 lipoxygnease -> hence they get more cysteinil leukotreine
what does ACE do
it breaksd down bradykinin which if its inhibitors can get angioedema and also its known bradykinin can stumulate vagal efferent nerver and produce cough as well as aa metaboites and NO wehivh can cause inflammation
name a bad reaction to the following anti TNF meds
1) inflixmab
2) humira
inflix - progressive multifocular encelopathy, if N10yoGBS peripheral neuropathy and demylinating sndorme
humira - asthma new onset (alsow ith enterncdept)
name three drugs gthat can cause cytokine storm syndorme
fever rigos chillss and ARDS
ritux
her 2 trastuzamab and \anti cll alemtuxumab
- Compare reactions between metabisulfite and ASA.
ASA
Can cause 4 types of ‘pseudoallergic reactions’, which is related to the pharmacologic ability of NSAIDs to inhibit COX-1 enzyme
(1) AERD
(2) urticaria/angioedema in patients who already have chronic urticaria
(3) urticaria/angioedema in patients without underlying disease
(4) respiratory reaction + cutaneous symptoms (either in patients with AERD or patients with no underlying disease)
NSAIDs can also cause allergic reactions (presumed to be IgE-mediated), but these are NOT reported with aspirin
metabisulfite
(1) Asthma
Sulfites are the only additives that have been convincingly demonstrated to provoke asthmatic reactions (for other additives- evidence limited to case reports)
Up to 5% of asthmatics may experience adverse reactions to sulfites
Affected patients typically have severe, steroid-dependent asthma, and sulfites can cause serious / life-threatening asthmatic reactions
(2) Anaphylaxis
Small number of cases
Epinephrine autoinjectors contain small amounts of metabisulfite, but this is not a contraindication to their use
(3) Urticaria
(4) Contact dermatitis
latex allergy
spina vs HCP
common foods
Latex allergy
Health care workers react Hev b 5, 6 and 7 - 5 and 6 are inhaled or direct contact
Spina bifida: hev b 1 and 3 are most frequent and need direct mucosal exposure
Cross reactive with BACK fruits (banana, avocado, chestnut, and kiwi) - potato, green pepper, fig, apple, cherry and some nuts → can cause anaphylaxis
patient with RCM
approach
Radiocontrast - want non ionic iso osmolar
Can be anaphylactoid, physologic (warm, chills, CP, seizure), IgE, delayed type 4 (2%)
RF for RCM rxn: female, atopy, asthma CVD, beta blocker (NOT IODINE and SEAFOOD)
JACI 2018 SPT with undilated RCM and intradermal 1:10 can be done NPV high
Treat
Prednisone 50mg - 13, 7 and 1 hour prior
Diphenhydramine 50mg - 1 hour prior
ephedrine/albuterol, H2 antagonists → controversial (as per ACAAI slides… but previous groups said to give ventolin 1 hour prior)
discuss Gel coombs and examples
Type 1: Ige mediated: anaphylaxis
Type 2: Ag:Ab mediated: hemloytic anemia (NSAID, beta lactam), thrombocytopenia (heparin) and neutropenia (PTU)
Type 3: immune complex mediated: serum sickness, vasculitis (beta lactam), arthrus reaction
Type 4: delayed T cell mediated (METN): SDRIFE, AGEP, SJS, DRESS, allergic contact
name mast cell pre formed mediators and then what is released with activation
Preformed: Histamine Tryptase Chymase Carboxypeptidase heparin
Synthesized/released after activation:
PAF
PGD2
LTB4/C4/D4
And then also cytokines/chemokines hours later
IL3/4/5/13, TNFalpha, GMCSF, RANTES
diagnostic criteria of MCAS
tryptase 1.2x + 2 from baseline
1) symptoms of mast cell activation with two organs
2) objective evidence like elevated tryptase , Elevated 24 hr urine N-methylhistamine, PGD2, or 11beta-PGF2alpha on at least two occasion
3) responds to meds that inhibit mast cell
in insulin HS rxn what are the top 3 allergens
protamine, cresol and latex, check additives if avail. Can SPT neat and use 1/100 dilution for IDT. IgE protamine, insulin and latex
findings in DRESS on bx
Considered to be type 4b. Common drug antiepileptic, septra, minocycline and alluprinol.
Reactivation of hhv6, 2-6w get rash, usu fever, skin, liver, kidney and lung. Can try for patch
Ddx: SJS, AGEP, HES, T cell lymphoma, cutaneous lymphoma, acute cutaneous lupus erythematosus
Inv: CBC, blood film, high Eo, LFTs, elevated Cr consider skin bx (mild spongiosis, perivascular infiltrate with lympcyte and Eo and dermal edema). Ebv hhv6 and 7 serology, CXR and trop for heart
Manage by stopping drug, and steroids, very slow taper
ddx for morbiliform rash
Ddx: measles, rubella, fifth disease, EBV, scarlet fever, mycplasma, JIA, acut ecutnaeous lupus erythematosus
distingush uritcaria from vasculitic urticaria
Distinguish from normal urticaria: painful, duration >48h, purpura, hyper pigm, can have EM, raynaud, livido reticularis, arthritis, renal proteinuria, hematuria, pulmonary SOB, asthma COPD, GI diarrhea or vx or pain
angiodedema, annular eryhtema
skin bx findings of UV
Skin bx: RBC extravasation, fragmented leukocyte, No predmoninance, swelling of endotheliall cellsesp post cap, fibrin deposits, leukocystoclasis and fibrinoid deposits
diagnostic criteria of HUVS
More severe and associated with COPD in 50%
Diagnostic Criteria (Schwartz)
Major: need both of Urticaria >6 months + low complement
Minor: need 2 or more
Dermal venulitis by biopsy
arthralgia/arthritis
uveitis/episcleritis
Mild GN
Recurrent abdo pain
Positive C1q precipitins test (same as antibodies to C1q) with suppressed C1q level
what would u find in bx of skin of HUV
Skin bx: RBC extravasation, fragmented leukocyte, No predmoninance, swelling of endotheliall cells esp post cap, fibrin deposits, leukocystoclasis and fibrinoid deposits
Ddx: urticaria,
HUVS mcDUffe syndrome
Diagnostic Criteria (Schwartz) Major: need both of Urticaria >6 months + low complement Minor: need 2 or more Dermal venulitis by biopsy arthralgia/arthritis uveitis/episcleritis Mild GN Recurrent abdo pain Positive C1q precipitins test (same as antibodies to C1q) with suppressed C1q level
blood findings with SSLR
Inv: CBC lymphocytosis, neutorpehnia, low plt, inc Eo, ESR CRP, urine proteinuria mild and mild hematuria, elevated Cr, low Alb. r/u HBV. C3,C4CH50 can be low. No need skin bx
ddx for extensive dermatitis
Extensive dermatitis ddx
SCALPID: seborrheic dermatitis C3: CD, CTD, cancer, AD, Lymphoma, P2 psoriasis piityriasis rubra pilaris, Infxn Idipathic, immunobulous, Drug related
list high risk and CI for desens
high risk: severe anaphlya, cardioresp disease, systemic diseas,e beta blocker, preg, ace inh
contrai
SCARS, SJS, DRESS< AGEP, Type 2 vasculitisn, SSLR
name vaccine component causing anaphylaxis
Gelatin: Flu, MMRV, zoster, rabies, yellow fever.
Egg protein (influenza, yellow fever)
Latex
Yeast (saccharomyces cerevisiae: Hep B and quadrivalent HPV)
Actual vaccine component (eg. tetanus/diphtheria)
Thimerosal: Hep B and influenza
Neomycin: Varivax and MMR
Aluminum
what are KNOWN vaccine rxns
Febrile seizure if MMRV given together at 12-15 mo
MMR can cause thrombocytopenia
Rubella acute arthritis if adult women and transient arthralgia in children
Pertussis can cause other less severe neurological events: febrile seizure, crying and hypotonic-hyporesponsive episodes
Tetanus causing arthus reaction, GBS, brachial neuritis (shoulder pain with weakness)
Varicella can cause local versicle
Absolute contraindications
Influenza vaccine causing gullain barree syndrome within 6w of vaccine
Encephalopathy with pertussis vaccine
Yellow fever can cause encephalitis and should not be given in infants
MOA of ritux
B cell-depleting monoclonal anti-CD20 antibody, comprised of both mouse and human portions.
Depletion occurs through one or more of several antibody dependant mechanisms including:
Fc receptor gamma-mediated antibody-dependent cytotoxicity and phagocytosis, complement-mediated cell lysis, growth arrest, B cell apoptosis
MOA of Cyclophoshamide
An alkylating agent, is one of the most potent immunosuppressive therapies available.
Prodrug that is converted to its active form in the liver
Alkylating agents exert their biologic activity via covalent binding and crosslinking of a variety of macromolecules including DNA, RNA, and proteins.
DNA crosslinking, probably the most important biologic action of these drugs, impairs DNA replication and transcription, ultimately leading either to cell death or to altered cellular function.
Alkylating agents are cytotoxic. Absolute lymphopenia is frequently seen following their administration, with reductions in the number of B cells and T cells of both CD4+ and CD8+ types
3 side effects
Cytopenia
Gonadal toxicity
Malignancy (leukemia and skin)
Bladder toxicity - hemorrhagic cystitis, bladder cancer
Hyponatremia due to SIADH
five causes of secondary hypogam
steroids ritux Bone marrow failure CLL, myeloma protein losing eneterophaty neprhotic sx lymphagenetiactasia
taxane reaction mgt
Taxane reactions
Paclitaxal and Docetaxel - 10-15min direct mast cell
Can pretreat and slow the infusion
If doesnt work can desnsitize
REMEMBER with platinum compound (CISplatin and carboplatin, CANNOT pre-treat and need SPT before coure) can try desensitize but does not always work
four sjs HLA risk subsyptes
Three derm features: mm erosions, target lesion and epidermal necrosis with detachment
Ill defines, coalescing, erythematous macules with itchy center, nikolsky sign, bulla spread sign, mm invovlement, urethritis ocular involvement
Drugs: sulfa, phenytoin, pb, allopruinol, carbamazepine, NSAID
Ethrnicity:
HLA b1502 - carbamaezpine ASIAN
Hla b58:01 allopriuinol in asian
HLA b57 01- abcavir
HLA b 13;01- dapsone in thai patients
