Type of reaction according to the Gell and Coombs classification |
Type of allergy (relative frequency) |
Mechanism |
Signs/symptoms For classification of severity of symptoms see SWAB richtlijn table 8
|
Chronology of onset |
Antibody-mediated |
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Type I |
Immediate (common) |
IgE mediated reaction based on cross linking of IgE on the surface of mast cells and subsequent degranulation. |
Urticaria, angio-edema, bronchospasm and anaphylaxis |
<1h typical, can be up to 6h post exposure |
Type II |
Delayed (rare) |
Antigen binding to IgM or IgG antibody on cell surfaces or extra cellular matrix proteins. Complement mediated phagocytosis and cytotoxicity. |
Cytopenia: hemolytic anemia, vasculitis, thrombocytopenia, probably medication induced pemphigus |
Often < 72 hours, up to 15 days |
Type III |
Delayed (rare) |
Deposition of antibody-antigen complexes in tissues and capillaries with subsequent inflammation (IgM, IgG, complement) |
Serum sickness, fever, vasculitis (purpura, petechial) arthritis, glomerulonephritis |
Days to weeks (1-3 weeks) |
Cell-mediated (type IV) = T-cell activation by specific antigens |
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Cutaneous only |
|
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Maculopapular rash (MPE) |
Delayed (common) |
Eosinophilic infiltration or infiltration of cytotoxic T cells |
Morbilliform rash, eosinophilia |
Days to weeks, typically 4-14 days |
Symmetrical drug related intertriginous and flexural exanthem (SDRIFE) |
Delayed (rare) |
Infiltration of cytotoxic T cells |
Similar to MPE, with involvement of the gluteal and intertriginous areas and symmetry of lesions. |
Up to 7 days |
Fixed drug eruption (FDE) |
Delayed (rare) |
IFN gamma and cytotoxic granules released by CD8 T cells |
Painful/ burning erythematous or edematous round plaques with gray/dusky center at same sites (lip, tongue, face, genitals) |
Days to weeks, minutes upon re-challenge
|
Contact dermatitis |
Delayed |
Monocytic inflammation |
Erythema and edema with vesicles or bullae |
Days to weeks |
Primary single organ |
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Acute interstitial nephritis |
Delayed (rare) |
CD4/ monocyte immune injury |
Rash, acute kidney injury, white cell casts in urinary sediment, eosinophilia |
3 days-4 weeks |
Liver injury |
Delayed (rare) |
CD4 then CD8 T cell activation and TNFα with perforin |
Transaminitis (cholestatic or mixed), sometimes rash, fever or eosinophilia |
5 days-12 weeks |
Severe Cutaneous Adverse Reactions (SCAR), involve systemic symptoms |
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Drug reaction eosinophilia and systemic symptoms syndrome (DRESS) |
Delayed (rare) |
CD4 and CD8 T cells implicated |
Fever, rash, peripheral blood eosinophilia, lymphadenopathy, organ involvement (liver/kidney) |
2-8 weeks |
Steven Johnson Syndrome and toxic epidermal necrolyses (SJS/TEN) |
Delayed (rare) |
CD8 cytotoxic T cells |
Rash with detachment, mucosal lesions, fever, upper respiratory tract symptoms |
4 -28 days |
Acute generalized exanthematous pustulosis (AGEP) |
Delayed (rare)
|
T cells via IL-8 and granulocyte-macrophage colony stimulating factor |
Acute pustular eruption with widespread non-follicular sterile pustules with fever, facial edema, neutropenia, oral involvement |
1-12 days
|
Other SCARs e.g. drug induced IgA dermatosis, etc. |
Delayed (rare) |
diverse |
diverse |
variable |
Bron: SWAB guideline for the approach to suspected Antibiotic Allergy, 2022. Richtlijn downloaden: 192 (swab.nl)