Table 2.

Summary of antimicrobial associated T-cell-mediated ADRs

Characteristics	SJS/TEN	DRESS	AGEP	EM	FDE	Drug-induced linear IgA	MPE
Drug latency (days)	4–28a	14–42	1–18b	<1–10	<1 to 14c	1–18d	4–9
Prodrome	Common	Common	Uncommon – Fever with acute phase	Uncommon – Unless severe	Uncommon	Uncommon	Uncommon
Distinguishing cutaneous features	Starts face thorax. Palms, soles and scalp rarely involved. Nikolsky signe	Morbilliform +/− follicular accentuation. Usually >50% BSA involvement and >2 of (i) facial oedema (50% cases) (ii) infiltrated lesions, (iii) scaling or (iv) purpura.	Starts face thorax. Dozens to hundreds non-follicular, sterile, pin-sized pustules, generally with background erythema. Flexural accentuation.	Can involve all regions. Symmetrical target lesions, spreading in centripetal fashion. Oral involvement can be isolated finding.	Can involve all regions. Commonly lips, genitalia, perianal area, hands, feet. Well demarcated +/− vesiculation or blistering.	Sub-epidermal blisters on trunk, extensor surfaces, buttocks and face (especially perioral region).	Morbilliform eruption –macules, papules or rarely pustules/bullae. Desquamation often follows resolution.
Mucosal involvement	Yes (very common - 90%)	Yes (infrequent)	Yes (uncommon, only lips)	Yes (common, 70%)	Yes (infrequent)	Yes (common – 80%)	No
Commonly implicated antibiotics	Beta-lactams (penicillins > cephalosporins), vancomycin, sulphonamides, macrolides, quinolones, tetracycline, clindamycin	Sulphonamides, vancomycin, minocycline, dapsone ≫ beta-lactams, pristinamycin nevirapine, telaprevir, acyclovir	Vancomcyinf, amoxycillin, ciprofloxacin, gentamicin, carbapenemsg	Sulphonamides, penicillins, quinolonesh	Sulphonamides, tetracyclines, penicillins, quinolones, macrolides, metronidazole,	Vancomycin ≫ amoxycillin, ADF, quinolones, sulphonamides	Beta-lactams, (especially penicillin, amoxicillin/amoxicillin- clavulanate), sulphonamides, cephalosporins, lincosamides
Scoring Algorithmsi	ALDEN[11]	RegiSCAR[67]	EuroSCAR[68]	Nil	Nil	Nil	Nil
Preferred diagnostics (in vitro)	PT	PT> Delayed-IDT	PT	PT	PT> Delayed-IDTj	PT	Delayed-DT
Research diagnostics (ex vivo)	LTT ELISpot	LTT ELISpot	LTT ELISpot	LTT ELISpot	LTT ELISpot	LTT ELISpot	LTT ELISpot

References: [5,9,39,65,69,73–111]

Abbreviations: T-cell-mediated ADRs, delayed hypersensitivity reactions; SJS, Stevens-Johnson Syndrome; TEN, toxic epidermal necrolysis; DRESS, drug reaction with eosinophilia and systemic symptoms; AGEP, acute generalised exanthematous pustolosis; EM, erythema multiforme; FDE, fixed drug eruption; Linear IgA, linear immunoglobulin IgA disease; MPE, maculopapular examthem; TMP-SMX, trimethoprim-sulfamethoxazole; ADF, amoxicillin-clavulanate; LTT, lymphocyte transformation test; ELISpot, enzyme-linked immunospot assay; BSA, body surface area.

^aMuch shorter duration for antibiotics than other drugs (1 vs. 11)

^bCan be as early as 48 hours on drug re-exposure, median time 14 days

^cCan be as short as 30 mins to 8 hours post drug administration [69]

^dLatency periods are rarely up to 30 days.

^eNikolsky sign – The ability to extend the area of sloughing with the application of gentle lateral pressure on seemingly unaffected skin. Asboe- Hansen sign (“bullae spread”) – Lateral extension of bullae with gentle pressure

^fVancomycin most commonly implicated antibiotic

^gRare reports secondary to carbapenems (meropenem, doripenem, ertapenem) [70,71]

^hInfective causes are more common in EM than SJS (e.g. HSV1 and Mycoplasma)

ⁱIn cases where a specific scoring system has not been developed, ‘Naranjo score’ can be employed as a guide [72]

^jAt the site of previously described reaction