Clinical manifestations of cutaneous drug hypersensitivity reactions

	Primary lesion and typical features	Distribution	Other important symptoms/findings/complications	Diagnostic tests
Urticaria	Wheals (hives)	Single or widespread wheals	Eventually concomitant angioedema, beware of anaphylaxis	Clinical, duration of a wheal
Angioedema	Deep swelling	Usually face (eyelids, lips), less often extremities and genitals Often asymmetric	Eventually concomitant urticaria, beware of anaphylaxis, involvement of larynx, epiglottis → upper airway obstruction (stridor)	Clinical
SJS/TEN*	Dusky red macules and flat, atypical target lesions with blisters on top	Isolated lesions/confluence of lesions	Prodromal fever, upper respiratory tract symptoms Mucosal involvement Usually systemic symptoms	Clinical, histology (subepidermal blisters, full thickness necrosis, immunofluorescence negative)
GBFDE	Erythematous, well-demarcated patches/plaques with blisters	Widespread lesions with large areas of uninvolved skin	Mucous membranes may be involved No systemic symptoms	Clinical (often no mucosal involvement, patients are well)
AGEP	Pustules on edematous erythema	Begins typically on face or intertriginous area, dissemination within hours	Fever Leucocytosis, neutrophilia, transient renal failure can occur	Clinical, bacterial swab (sterile pustules)
Vasculitis	Purpuric papules	Lower extremities primarily	Systemic organ involvement may be present, hemorrhagic and/or necrotic lesions	Clinical (purpura), histology (leucocytoclasia)
DRESS	Variable: macules; papules; small, superficial pustules or vesicles; eczema-like, target-like lesions; purpura	Face, upper trunk, extremities, widespread	Fever Eosinophilia Lymphadenopathy Hepatitis, myocarditis, interstitial pneumonitis and nephritis, thyroiditis, arthritis	Clinical, differential blood count and organ function abnormalities, lymphadenitis
SDRIFE	Sharply delineated erythema	Flexural and intertriginous areas	Usually no systemic involvement	Clinical (involvement of body folds)
MPE	Macules, papules	Trunk > extremities	May be accompanied by low-grade fever, pruritus and eosinophilia	Clinical, blood tests (lack of systemic involvement)
FDE	Erythematous macule(s), plaque(s)	Solitary lesion(s)	By readministration recurrence at the same sites	Clinical (typical elicitor)
Systemic photoallergic reactions	Dermatitis	Sun-exposed areas, may spread	Does not arise immediately on sun exposure (delay)	Clinical (sun-exposed sites), Photopatch test
Injection site reaction	Erythematous plaque	Drug injection site	No systemic symptoms In extreme cases can spread into MPE	Clinical (history of injection)

SJS: Stevens-Johnson syndrome; TEN: toxic epidermal necrolysis; GBFDE: generalized bullous fixed drug eruption; AGEP: acute generalized exanthematous pustulosis; DRESS: drug reaction with eosinophilia and systemic symptoms; SDRIFE: symmetrical drug-related intertriginous and flexural exanthema; MPE: maculopapular exanthem; FDE: fixed drug eruption.

* Detachment SJS <10%, SJS/TEN overlap 10 to 30%, TEN >30%.

From: Brockow K, Ardern-Jones MR, Mockenhaupt M, et al. EAACI position paper on how to classify cutaneous manifestations of drug hypersensitivity. Allergy 2019; 74:14. https://onlinelibrary.wiley.com/doi/10.1111/all.13562. Copyright © 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons, Ltd. Reproduced with permission of John Wiley & Sons Inc. This image has been provided by or is owned by Wiley. Further permission is needed before it can be downloaded to PowerPoint, printed, shared or emailed. Please contact Wiley's permissions department either via email: [email protected] or use the RightsLink service by clicking on the 'Request Permission' link accompanying this article on Wiley Online Library (https://onlinelibrary.wiley.com/).

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Clinical manifestations of cutaneous drug hypersensitivity reactions