Cutaneous drug, chemical and vaccine reactions

At a glance

• Drug rashes affect a few per cent of inpatients. Most (roughly 75 to 95%) are benign maculopapular exanthems that settle after the drug is stopped, and sometimes even while it continues.
• The job is to spot the severe cutaneous adverse reactions (SCAR): SJS/TEN, DRESS, AGEP and generalised bullous fixed drug eruption. These are T-cell mediated, delayed, and can kill.
• Timing is the best clue. Draw a drug timeline for the previous 8 weeks and line it up against rash onset.
• Severe reactions mean stopping the culprit and every non-essential drug, then getting dermatology (and burns or ICU for SJS/TEN) involved the same day.
• Record the reaction accurately. Most penicillin labels are wrong, and the ASCIA 2026 adult guideline now lets low-risk labels be removed in the community.

Causes

Reaction	Onset after starting	Features	Typical drugs
Urticaria, angioedema, anaphylaxis	Minutes to 1 hour (IgE)	Wheals, swelling, hypotension	Beta-lactams, NSAIDs, contrast, neuromuscular blockers
Maculopapular exanthem (MPE)	4 to 14 days	Symmetric pink macules and papules, trunk first, itch, no mucosal disease	Aminopenicillins, sulfonamides, anticonvulsants, allopurinol
SJS/TEN	4 to 28 days	Fever and malaise, then painful dusky or atypical target lesions, blisters, erosions at 2 or more mucosal sites	Allopurinol, carbamazepine, lamotrigine, phenytoin, sulfonamides, nevirapine, oxicam NSAIDs
DRESS	2 to 8 weeks	Fever, widespread rash, facial oedema, lymphadenopathy, eosinophilia, atypical lymphocytes, hepatitis, nephritis	Allopurinol, aromatic anticonvulsants, vancomycin, sulfonamides, dapsone, minocycline
AGEP	Hours to 2 days	Hundreds of tiny sterile pustules on red skin, flexures first, fever, neutrophilia	Beta-lactams, macrolides, diltiazem, terbinafine, hydroxychloroquine (slower)
Fixed drug eruption	30 minutes to 48 hours on re-exposure	One or a few round dusky plaques at the same site each time, often lips, genitals, hands; heals with pigmentation	NSAIDs, trimethoprim-sulfamethoxazole, tetracyclines, paracetamol
Serum sickness-like reaction	1 to 3 weeks	Fever, urticarial rash, arthralgia; normal complement, no immune complexes	Cefaclor, amoxicillin, trimethoprim-sulfamethoxazole
True serum sickness (type III)	1 to 2 weeks	As above, often with purpura and proteinuria; low C3 and C4	Rituximab and other chimeric antibodies, antithymocyte globulin, antivenom
Vasculitis	1 to 3 weeks	Palpable purpura on the legs	Beta-lactams, propylthiouracil (ANCA), hydralazine

Other patterns worth naming:

• Photosensitivity: doxycycline, amiodarone (slate-grey pigment), thiazides, quinolones, voriconazole (which also drives squamous cell carcinoma in transplant patients).
• Drug-induced subacute cutaneous lupus (anti-Ro positive): PPIs, terbinafine, thiazides, calcium channel blockers, TNF inhibitors.
• Cancer therapy: EGFR inhibitors cause an acneiform papulopustular rash without comedones that tracks with tumour response. Checkpoint inhibitors cause itch, MPE, lichenoid eruptions, bullous pemphigoid, vitiligo and, rarely, SJS/TEN.
• Anticoagulant necrosis: warfarin necrosis on days 3 to 5 in fatty areas (protein C deficiency); heparin necrosis at injection sites signals HIT.
• Vancomycin: the infusion reaction (flushing from direct histamine release, managed by slowing the rate) isn't allergy. Vancomycin is also a common cause of DRESS, typically weeks into a prolonged course for bone, joint or line infection.

Focused history

• Every drug in the last 8 weeks, including over-the-counter, complementary, contrast, vaccines and drugs already stopped. Note start dates, dose changes and whether a drug was recently restarted.
• Prodrome: fever, sore throat or sore eyes before the rash suggests SJS/TEN.
• Skin pain (rather than itch) and blistering are SCAR features.
• Past reactions to the same or a related drug (aromatic anticonvulsants cross-react: carbamazepine, oxcarbazepine, phenytoin, phenobarbital, lamotrigine).
• Infection: EBV, HIV, mycoplasma, HHV-6. Pitfall: the amoxicillin rash in glandular fever is usually not allergy (see EBV).
• Ancestry (HLA risk), HIV, CKD (allopurinol), and whether a high starting dose was used.

Focused examination

• Percentage of BSA involved and, separately, percentage detached or detachable (Nikolsky sign: lateral pressure shears the epidermis).
• Mucosae: eyes, mouth, lips, genitals. Two or more sites with erosions points to SJS/TEN.
• Lesion morphology: typical three-ring targets favour erythema multiforme (usually HSV); flat atypical targets and dusky macules on the trunk favour SJS/TEN.
• Facial oedema, lymphadenopathy and hepatosplenomegaly in DRESS.
• Temperature, haemodynamics and fluid status.

Red flags

• Fever with a new rash on a drug started in the last 8 weeks.
• Skin pain, dusky or grey skin, blisters, erosions or a positive Nikolsky sign.
• Mucosal involvement, especially the eyes.
• Facial oedema, lymphadenopathy, eosinophilia, atypical lymphocytes.
• Abnormal liver or kidney function, cytopenias.
• Confluent erythroderma (over 90% BSA).

Investigations

• FBC with differential (eosinophilia, atypical lymphocytes, cytopenias), LFTs, urea, creatinine and electrolytes, urinalysis, CRP, glucose and bicarbonate (both in SCORTEN).
• DRESS: add troponin and ECG, TSH, lipase, and HHV-6 PCR. Reactivation of HHV-6 and other herpesviruses supports the diagnosis and tracks with relapse.
• Skin biopsy for any suspected SCAR. Full-thickness epidermal necrosis confirms SJS/TEN and separates it from staphylococcal scalded skin syndrome (a superficial split under the stratum corneum). A frozen section gives an answer within hours.
• Mycoplasma PCR or serology when mucositis dominates and skin disease is sparse (mycoplasma-induced rash and mucositis).
• Serum tryptase within 2 hours of onset where possible (no later than 4 hours) for an immediate reaction (see anaphylaxis).
• Scores: SCORTEN for SJS/TEN on days 1 and 3 (predicted mortality roughly 3% at 0 to 1 points, 12% at 2, 35% at 3, 58% at 4, and about 90% at 5 or more). RegiSCAR for DRESS: 6 or more is definite, 4 to 5 probable. ALDEN ranks drug causality in SJS/TEN.
• Later, specialist tests: patch testing or delayed intradermal testing for DRESS, AGEP and fixed drug eruption. Oral challenge is not used after a SCAR.

Management

All reactions

• Stop the suspected drug. In SCAR, stop every drug that isn't essential, and swap essential ones to structurally unrelated alternatives.
• Mild MPE: emollients, a moderate-potency topical corticosteroid and an antihistamine for itch. If the drug is essential and there are no red flags, treating through under watch is sometimes reasonable.
• Report to the TGA and document the reaction in the record, discharge summary and My Health Record.

SJS/TEN

• Transfer early to a burns unit or ICU with dermatology input, especially over 10% detachment. Mortality is roughly 10% for SJS and 30% or more for TEN.
• Barrier nursing in a warm room, non-adherent dressings, and leave detached epidermis in place as a biological dressing.
• Fluids (lower requirements than an equivalent burn), nutrition, analgesia, VTE prophylaxis. No prophylactic antibiotics; culture and treat infection.
• Ophthalmology within 24 hours and daily: lubricants, topical steroid, and amniotic membrane for severe disease. Also mouth care and urogenital care to prevent strictures and adhesions.
• Immunomodulation is unproven and varies by centre. Ciclosporin (about 3 mg/kg/day for 7 to 10 days) is the commonest choice. Etanercept compared well with corticosteroids in a 96-patient RCT (Wang, 2018), with faster healing and mortality below that predicted by SCORTEN. IVIG has weak evidence.

DRESS

• Mild disease (mild liver, kidney or blood abnormalities only): very potent topical steroid and close review, tapered over 6 weeks to 3 months.
• Severe disease (2024 Delphi consensus): systemic glucocorticoid in all, tapered over 3 to 6 months. Prednisolone 0.5 to 1 mg/kg/day is usual practice; the consensus gives no dose. Relapse with a fast taper is common. Ciclosporin is an option when steroids fail or can't be used.
• Monitor for late autoimmune disease (thyroiditis, type 1 diabetes) for months to years.
• Mortality is about 2 to 10%, higher with allopurinol and with myocarditis.

AGEP and fixed drug eruption

• AGEP: stop the drug, potent topical steroid, antipyretics. Pustules clear in under 2 weeks with collar-like desquamation.
• Fixed drug eruption: avoid the drug. A generalised bullous form counts as a SCAR.

Prevention

• HLA screening: HLA-B*57:01 before abacavir (routine); HLA-B*15:02 before carbamazepine in Han Chinese, Thai, Malaysian and other Southeast or South Asian ancestry (SJS/TEN); HLA-A*31:01 also predicts carbamazepine DRESS and MPE, including in European and Japanese ancestry; HLA-B*58:01 before allopurinol in Han Chinese, Korean and Thai ancestry. See epilepsy and gout.
• Start low: allopurinol 50 to 100 mg daily (50 mg in CKD) and slow lamotrigine titration (halved with valproate).

Vaccine and chemical reactions

• Local reactions (redness, swelling, pain) are common and aren't a contraindication. Extensive limb swelling after a booster dose of DTPa vaccine resolves and doesn't stop later doses.
• Delayed large local reaction to mRNA COVID-19 vaccine ("COVID arm") appears about day 7, settles in days and doesn't contraindicate further doses.
• Persistent itchy injection-site nodules after aluminium-adsorbed vaccines can last months and sometimes reflect aluminium contact allergy.
• Anaphylaxis to vaccines is rare, about 1 per million doses, which is why vaccinees wait 15 minutes. Refer to a specialist immunisation clinic or allergist before further doses.
• Report adverse events following immunisation to the state or territory service or the TGA.
• Chemical reactions: irritant contact dermatitis (detergents, wet work) is commoner than allergic contact dermatitis (nickel, fragrance, preservatives, hair dye); patch test when allergy is suspected. Chemical burns need copious irrigation. Hydrofluoric acid burns need calcium gluconate gel because pain and hypocalcaemia outstrip what the skin shows. Wet cement causes alkaline full-thickness burns under clothing.

Labelling and re-exposure

• Record the drug, reaction type, date and what to avoid. "Allergy: carbamazepine (SJS 2026). Avoid all aromatic anticonvulsants" is useful; "allergic to tablets" isn't.
• No re-challenge and no desensitisation after a SCAR. ASCIA calls desensitisation in SCAR absolutely contraindicated.
• ASCIA 2026 adult penicillin risk tiers:
  • Minimal risk (history not consistent with allergy, such as diarrhoea, headache or family history): remove the label directly.
  • Low risk (benign rash 5 or more years ago, or an unknown reaction that long ago): direct oral challenge, which can be done in general practice with trained staff, observing at least 1 hour after the last dose.
  • Intermediate risk (benign rash under 5 years ago, or a suspected mild to moderate IgE-mediated reaction other than anaphylaxis under 5 years ago): specialist assessment, with skin testing considered (optional), then a split-dose challenge. The tier text doesn't place a mild immediate reaction more than 5 years ago, so discuss it with an allergist rather than challenging directly in the community.
  • High risk (possible SCAR, anaphylaxis, single-organ disease, vasculitis, cytopenia): specialist only.
• Defer community challenges without specialist discussion in pregnancy, acute illness, unstable heart or lung disease, chronic urticaria, or within 72 hours of antihistamines or on biologics, immunosuppressants or JAK inhibitors.
• After a tolerated challenge, mark the record "confirmed not allergic" everywhere, including My Health Record.

Pitfalls

• Calling SJS "erythema multiforme". Erythema multiforme is usually HSV-triggered, acral, with typical targets and limited mucosal disease.
• Starting a slow-onset DRESS workup only when the liver fails. Check LFTs and eosinophils in anyone with fever and rash weeks into a new drug.
• Blaming the most recent drug. DRESS can follow a drug started 6 weeks ago, and the drug added yesterday is often innocent.
• Tapering DRESS steroids over 2 weeks and seeing it relapse.
• Swapping carbamazepine for phenytoin or lamotrigine after SJS. Aromatic anticonvulsants cross-react.
• Labelling a viral or amoxicillin-EBV rash as penicillin allergy, which leads to broader, costlier antibiotics and more C. difficile and MRSA.