TABLE 3.

Nonimmediate Reactions: Clinical Features and Management

Type of Reaction	Timing	Cutaneous Symptoms	Systemic Symptoms	Possible Laboratories in Acute Setting	Differential Diagnosis	Commonly Involved Antibiotics	Testing	Management
Delayed drug reaction	7–14 d	Maculopapular exanthema	Low-grade fever	Eosinophilia (mild)	Viral exanthem	Aminopenicillins	Delayed intradermal testing	Avoidance drugs and/or cross-reactive drugs
		Urticaria	Pruritus		IgE-mediated drug allergy	Sulfonamides		Drug provocation testing
					Early DRESS syndrome or SJS and/or TEN	Clindamycin
SJS and/or TEN	4–28 d	Painful erythematous macules with purpuric or dusky centers	Prodrome	Anemia	EM	Sulfonamides	LTT and/or ELISPOT	Avoidance drug and/or drug class
		Superficial sloughing	High fever	Lymphopenia	Bullous pemphigoid	Minocycline (used for acne)	HLA screening
		Mucositis in ≥2 surfaces	Malaise		Staphylococcal scalded skin syndrome	β-lactams
			Pneumonitis (occasionally)		FDE
					DRESS syndrome
DRESS syndrome	2–8 wk	Morbilliform eruption >50% BSA	Fever	Eosinophilia	Viral or drug exanthem	Vancomycin	Patch testing	Avoidance of drugs and/or cross-reacting drugs
		Nonerosive mucositis	Lymphadenopathy	Atypical lymphocytes	Early SJS and/or TEN	β-lactams	LTT and/or ELISPOT
		≥2 facial edema, infiltrated lesions, scaling, and purpura		Hepatitis	Severe eczema or psoriasis	Tetracyclines	HLA screening
				Renal impairment		Rifampin
						Antituberculosis drugs
						Sulfonamides and/or sulfonesa,91
FDE	1–14 db	1 or more well-demarcated, round, dusky-to-violaceous macules or plaques	None	None	EM	Sulfonamides	Patch testing	Drug provocation testingc
		Blistering may occur			Bullous pemphigoid	Tetracyclines		Avoidance of drug and/or cross-reactive drug
		Mucosal predilection but limited mucositis			SJS and/or TEN	β lactams
		Postinflammatory hyperpigmentation				Quinolones
						Fluconazole
Acute generalized exanthematous pustulosis	24–48 h	Dozens to hundreds of pustules on erythematous background	High fever	Neutrophilia	Pustular psoriasis	Aminopenicillins	Patch testing	Avoidance of drugs and/or cross-reactive drugs
		Flexural accentuation	Edema	Eosinophilia	Bullous impetigo	Clindamycin
					Subcorneal pustular dermatosis	Sulfonamides
					DRESS syndrome	Quinolones
Serum-sicknesslike reaction	1–2 wk	Pruritic urticarial or serpiginous plaques (usually at injection site)	High fever	Neutropenia	Vasculitis	β lactams (especially cefaclor)	None	Avoidance of specific drugd
			Malaise	Mild eosinophilia	Rheumatic fever	Macrolides
			Polyarthralgia or polyarthritis	Mild proteinuria	Other drug reactions	Sulfonamides

BSA, Body Surface Area; EM, erythema multiforme; FDE, fixed drug eruption; HLA, human leukocyte antigen.

^aSulfonamides include trimethoprim-sulfamethazole and sulfones include dapsone. There is no cross reactivity between sulfa antimicrobials and non-antibiotic sulfonamides (such as acetazolamide, bumetanide, celecoxib, chlorothiazide, diazoxide, dorzolamide, furosemide, glyburide, hydrochlorothiazide, indapamide, metolazone, sumatriptan, torsemide and zonisamide).

^bRapid recurrence on drug re-exposure.

^cContraindicated in generalized FDE.

^dControversial. Some sources recommend avoiding drug and drug class while others (ie cefaclor) just recommend avoiding culprit drug.