Phenotype |
Incidence |
Clinical description |
Average latency |
Mortality |
Skin biopsy |
Common drugs 64 |
Clinical |
scores |
AGEP 1-5 / million / year 48 |
Non-follicular sterile pustular rash over widespread erythema ( flexural predisposition ), fever and / or biological abnormalities 64 |
|
Antibiotics ( penicillins , cephalosporins ), antimycotics ; other ( diltiazem , oxicam , analgesics ) |
Naranjo score AGEP validation score |
FBC and differential count ( neutrophils ) |
Drug withdrawal Symptomatic treatment # |
|
DRESS 0.9-2 / 100,000 /
67 , 68 year
|
Erythematous urticaria-like or violaceous skin eruption , facial and extremity oedema , lymphadenopathy , fever , biological abnormalities and internal organ involvement 51 |
2-8 weeks ( less than two weeks with antibiotics and contrast product 69 ) |
3 -10 % 70 , 71 Interface dermatitis with basal vacuolization |
Anticonvulsants , antibiotics ( sulfonamides , vancomycin , minocycline ), allopurinol |
Naranjo score RegiSCAR score |
FBC and differential count ( eosinophils ) LFTs Renal function |
Drug withdrawal Symptomatic treatment # Systemic glucocorticoids , 72 cyclosporine 73 |
SJS / TEN 2-7 / million / year 74 |
Skin necrosis , skin detachment ( Nikolsky sign ) and blistering of the mucous membranes accompanied by serious systemic manifestations |
|
Allopurinol , anticonvulsants , antibacterial sulfonamides , nevirapine , NSAIDs , antituberculosis agents |
Naranjo score SCORTEN ALDEN |
FBC and differential count LFTs Renal function |
Drug withdrawal
76 , 77
Supportive wound care , IvIg , 78 systemic glucocorticoids and IvIg , 79 cyclosporine , 80 , 81 TNF inhibitor 82
|
|
with the implicated drug ( s ) at the recommended concentrations . 59 As disease reactivation has been described following skin testing , it is recommended to wait at least 6-8 weeks after skin resolution or after stopping the systemic immunosuppressive treatment . PT ( see figure 8 ) involves applying the drug allergen to intact skin under occlusion to reproduce the original delayed reaction . The major advantage of PT is the ability to use non-sterile and oral drug formulations . There is no positive control available , and the sensitivity is very poor , varying depending on the phenotype and the drug tested . This remains the major diagnostic tool in patients with SJS / TEN .
IDT involves injecting a small quantity of a drug under the skin with a reading performed after 24-48 hours . A positive reaction is indicated by local erythema and infiltration compared with the negative control , usually saline . There is no positive control for delayed reactions . Evidence indicates that IDT is safe in the severe delayed phenotypes , with sensitivity of non-SJS / TEN delayed reactions ranging from 40 % to 56 %, with unknown specificity . 60-63
Most ex vivo diagnostic testing , including lymphocyte transformation , ELISpot or flow-cytometric analy sis is unavailable for routine testing . The utility of these ex vivo assays in immunophenotype reactions has been established , but their use as diagnostic assays in clinical practice and their durability remains under investigation .
NSAIDs
NON-steroidal anti-inflammatory drug ( NSAID ) induced hypersensitivity is estimated to occur in 1.6 % of the population . 83 Hypersensitivity occurs via allergic ( typically IgE-mediated , rarely T-cell-mediated ), or cyclooxygenase ( COX ) enzyme inhibition mechanisms . 84 COX-inhibition blocks the conversion of arachidonic acid to prostaglandins and thromboxane ; this increases arachidonic acid that can then be converted into leukotrienes . 84 The enzyme has two isoforms , COX-1 and COX-2 . COX-1 inhibition can increase leukotriene formation resulting in bronchospasm , angioedema and urticaria . COX-2 inhibition preferentially blocks production of inflammatory prostaglandins and results in the anti-inflammatory effects of NSAIDs . 84
|
None
R 1
R 1
O
C
Penicillins
H
N
O
Monobactams †
O
C
H
N
O
Figure 4 . Cross-reactivity between beta-lactams .
N
O
N
Various NSAIDs inhibit COX-1 and COX-2 isoenzymes by differing amounts . Non-selective NSAIDs ( aspirin , ibuprofen , naproxen , mefenamic acid , diclofenac , indomethacin ) inhibit both ; celecoxib is highly selective for COX-2 . Paracetamol is a weak COX-1 inhibitor . 18
Allergy-mediated NSAID hypersensitivity presents with the typical symptoms of IgE-mediated allergy , varying from mild urticaria to severe anaphylaxis . T-cell-mediated reactions are beyond the scope of this How to Treat . Differentiating allergy-mediated from COX-inhibition mediated hypersensitivity is important . Allergy-mediated hypersensitivity is typically limited to a single NSAID , and patients will tolerate other NSAIDs . Conversely , in COX-inhibition mediated hypersensitivity , all medications that inhibit COX-1 will cross-react ( see box 4 ). 18
Respiratory symptoms are typically rhinitis and bronchospasm , cutaneous symptoms are urticaria and angioedema typically in the facial area . Symptoms occur immediately after administration , usually in less than one hour . 18
S
S
|
Dr Thomas Habif / CC BY-SA 3.0 / bit . ly / 43lhP0J
H O
O
OH
|
CH 3
CH 3
O
< 2 %*
None
Figure 5 . Stevens- Johnson syndrome .
|
< 1 %
R 1
O
C
|
In addition , those with NSAID-exacerbated respiratory disease tend to develop refractory chronic rhinosinusitis with polyposis and may benefit from |
H N
S
N O
R 1
R 2
Cephalosporins
Carbapenems
R 3
R 2
|
N O
O
H O
< 1 %
aspirin desensitisation to reduce symptoms . 85
Substantial overlap exists in the symptomatology and timing of allergic and COX-mediated NSAID
|
hypersensitivity . A history of tolerance to other NSAIDs that inhibit COX-1 following the index reaction indicates allergy-mediated hypersensitivity . Underlying asthma , rhinosinusitis or chronic urticaria may suggest a COX-mediated hypersensitivity but does not exclude allergy . Diagnostic testing performs poorly and graded provocation testing , usually to an alternative NSAID , is often required to confirm diagnosis .
Specialists can undertake supervised provocation challenge to both celecoxib and / or paracetamol ( if uncertain ) to confirm tolerance . In adult patients , specialists often perform an aspirin challenge to differentiate between allergy and COX-mediated hypersensitivity . In the interim , the authors recommend NSAID avoidance , except celecoxib ( if tolerated in provocation challenge ) and paracetamol . These should adequately cover simple analgesic needs .
LOCAL ANAESTHETIC
LOCAL anaesthetic ( LA ) hypersensitivity
is rare , occurring at an estimated rate of 0.0261 anaphylactic episodes per million LA vials used . 86 Complicating identification of these is the range of adverse reactions local anaesthetics can cause , as well as the other agents used at the same time , such as antibiotics , skin washes like chlorhexidine , or latex gloves .
Traditional IgE-mediated allergy can occur with typical symptoms but can be delayed because of the effects of adrenaline , a tourniquet , or the location of administration ( epidural or spinal ). Contact reactions ( see figure 9 ) can occur to topical preparations of local anaesthetics . T-cell-mediated reactions may occur days after use . A variety of non-allergic adverse reactions may occur because of the pharmacological properties of the LA or the adrenaline that is often co-administered with the LA . Most adverse reactions to LA are non-allergic . 87
Evaluation of LA allergies relies on skin testing , followed by subcutaneous provocation challenge .
88 , 89
Cross-reactivity between LAs has been documented in case reports , particularly within certain LA classes , but the true incidence is unknown . 89 Additives or preservatives packaged with the LA may drive cross-reactivity , rather than the LA itself . 89
The authors ’ practice is to assess
|