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

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

Cutaneous only

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

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

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