01Approach to the Critical Patient/attcp63

Triage and immediate risk stratification

›Severity triage

›Unstable vitals

›Airway compromise from angioedema or mucosal edema

›Hypotension or shock

›Altered mental status

›Extensive skin pain

›Blistering or epidermal detachment

›Mucosal involvement

›Facial edema

›Fever with systemic symptoms

›Rapid progression over hours to days

›Red flag phenotypes

›SJS or TEN phenotype

›Skin pain out of proportion to visible rash

›Dusky erythema or targetoid lesions

›Positive Nikolsky sign

›Oral ocular genital mucositis

›DRESS phenotype

›Fever

›Facial edema

›Lymphadenopathy

›Eosinophilia or atypical lymphocytosis

›Hepatitis or nephritis or pneumonitis or myocarditis concern

›AGEP phenotype

›Numerous small nonfollicular pustules on erythema

›Fever

›Neutrophilia

02History/hx66

Medication and exposure timeline

›Exposure chronology

›All prescription drugs started in prior 8 weeks

›All OTC drugs and supplements started in prior 8 weeks

›PRN exposures including NSAIDs and antibiotics

›Recent vaccines

›Contrast exposure

›Topical agents and cosmetics

›Illicit substances

›Timing patterns by phenotype

›Morbilliform exanthem

›Onset typically 4 to 14 days after start

›Faster onset with re exposure

›Urticaria

›Minutes to hours after exposure

›SJS or TEN

›Typically 1 to 3 weeks after start for high risk drugs

›DRESS

›Typically 2 to 8 weeks after start

›AGEP

›Often within 48 hours for antibiotics

Symptom pattern and system review

›Cutaneous symptoms

›Pruritus

›Skin pain

›Burning sensation

›Blistering

›Peeling

03Physical Exam/exam41

Skin and mucosa focused exam

›Morphology and distribution

›Morbilliform maculopapular eruption

›Urticarial wheals

›Fixed plaques with residual hyperpigmentation pattern

›Targetoid lesions

›Pustules nonfollicular

›Bullae

›Purpura or palpable purpura

›Necrosis

›Edema facial

›Intertriginous predominance

›Severity markers

›Body surface area involved estimate

›Epidermal detachment percent estimate

›Nikolsky sign

›Skin tenderness

›Dusky erythema

›Mucosal sites

›Oral erosions

›Lip crusting

›Conjunctivitis

›Corneal haze concern

›Genital erosions

Vital signs and organ system screening

›Hemodynamic and respiratory status

›Hypotension

›Tachycardia

04Differential Diagnosis/ddx35

Drug eruption phenotypes and SCAR

›Drug related eruptions

›Morbilliform drug eruption

›ICD 10 L27.0 generalized skin eruption due to drugs

›Urticaria and angioedema drug related

›Fixed drug eruption

›Photo toxic or photo allergic drug reaction

›Serum sickness like reaction

›Erythema multiforme

›SJS

›ICD 10 L51.1

›TEN

›ICD 10 L51.2

›DRESS

›SNOMED CT drug reaction with eosinophilia and systemic symptoms concept

›AGEP

›SNOMED CT acute generalized exanthematous pustulosis concept

Mimics and alternative causes

›Infection related rashes

›Viral exanthem

›Scarlet fever

›Meningococcemia

›Disseminated gonococcal infection

›Inflammatory dermatoses

›Atopic dermatitis flare

›Allergic contact dermatitis

›Psoriasis including pustular

›Pityriasis rosea

05Laboratory Tests/lt33

Baseline evaluation by severity

›Baseline labs for suspected SCAR

›Complete blood count with differential

›Eosinophilia support for DRESS

›Neutrophilia support for AGEP

›Atypical lymphocytes support for DRESS

›Electrolytes including sodium and potassium and bicarbonate

›Fluid shift risk in SJS or TEN

›Creatinine and urea

›Nephritis support for DRESS

›Liver panel

›ALT AST elevation support for DRESS hepatitis

›CRP as inflammatory marker

›Urinalysis

›Hematuria or proteinuria support for renal involvement

›Additional labs by clinical concern

›Venous blood gas for critical illness

›pH

›lactate mmol per L

›Coagulation studies for severe illness or liver dysfunction

›CK for myositis or severe systemic symptoms

›Troponin and ECG for myocarditis concern in DRESS

›Blood cultures for sepsis concern

Etiology and trigger workup

›Infectious tests when mimic likely

›Respiratory viral testing by local availability

›Strep testing when pharyngitis with scarlatiniform rash

›HIV testing when risk or severe drug reaction risk stratification

06Diagnostic Tests/dt42

Scoring Systems

›Clinical scoring use

›SCORTEN for SJS or TEN mortality risk

›Age threshold factor

›Malignancy factor

›Heart rate factor

›Epidermal detachment percent factor

›Urea factor

›Glucose factor

›Bicarbonate factor

›RegiSCAR scoring for DRESS

›Fever criterion

›Enlarged lymph nodes criterion

›Eosinophilia criterion

›Atypical lymphocytes criterion

›Skin involvement extent criterion

›Organ involvement criterion

›Resolution time criterion

›Alternative cause exclusion criterion

›EuroSCAR validation score for AGEP

›Pustule morphology criterion

›Fever criterion

›Clinical course criterion

›Neutrophilia criterion

›Histology criterion

MRI

›MRI use by organ involvement

›Brain MRI for neurologic deficits not explained otherwise

07Disposition/dispo24

Admit transfer discharge criteria

›Admission indications

›Suspected SJS or TEN

›ICU or burn unit level care triggers in many protocols

›Suspected DRESS with organ involvement

›AGEP with systemic instability or extensive involvement

›Inability to stop culprit drug safely without monitoring

›Severe pain requiring parenteral analgesia

›Dehydration or poor oral intake

›Significant mucosal involvement

›Transfer indications

›Burn capable center for SJS or TEN

›Need for ophthalmology subspecialty care not available locally

›Discharge criteria for uncomplicated exanthematous eruption

›Stable vitals

›No mucosal involvement

›No skin pain or blistering

›No systemic symptoms

›Reliable follow up within 24 to 72 hours

›Clear culprit medication discontinuation plan

Follow up planning

›Outpatient follow up

›Primary care within 48 to 72 hours

›Dermatology referral for uncertain diagnosis or prolonged course

›Allergy or immunology referral for selected cases

›Pharmacy or drug information service consultation for culprit identification

08Treatment/t90

General measures by severity

›Causative drug management

›Stop culprit drug

›Class I recommendation based on expert consensus

›Avoid cross reactive agents when relevant

›Substitute essential therapy with non culprit alternative when possible

›Symptom control for uncomplicated exanthem

›Topical corticosteroid medium potency

›Limited course 7 to 14 days

›Oral antihistamine for pruritus

›Cetirizine 10 mg PO daily

›Loratadine 10 mg PO daily

›Hydroxyzine 10 to 25 mg PO q6h PRN pruritus

›Emollients and gentle skin care

›Avoid NSAIDs if suspected trigger

SJS and TEN supportive care

›Level of care

›Burn unit or ICU care for significant detachment or systemic instability

›ACEP Level C recommendation for early transfer in suspected SJS or TEN based on expert consensus and institutional protocols

›Wound and mucosal care

›Nonadherent dressings

›Temperature controlled environment

›Fluid resuscitation individualized to losses

›Electrolyte replacement strategy

›Pain control multimodal

›Nutrition support early

›DVT prophylaxis if no contraindication

›Ocular care

›Early ophthalmology involvement

›Lubrication and eyelid hygiene per specialist plan

›Infection management

›No prophylactic antibiotics routinely

›Targeted antibiotics for confirmed infection

SJS and TEN immunomodulating therapies

›Systemic therapy selection

›Dermatology led selection preferred

›Evidence base heterogenous with practice variation

›Corticosteroids

›Consider early short course in selected cases

›Class IIb recommendation based on mixed observational evidence

›Cyclosporine

›Cyclosporine 3 to 5 mg per kg per day PO or via NG divided BID

›Typical duration 7 to 10 days then taper per specialist

›Renal function monitoring

›Class IIa recommendation in some institutional protocols and reviews

›IVIG

›IVIG 0.4 g per kg per day for 3 to 5 days in selected cases

›Class IIb recommendation due to inconsistent outcome data

›TNF alpha inhibitor

›Etanercept single dose protocols vary by center

›Class IIb recommendation pending broader evidence

DRESS treatment

›Core management

›Stop culprit drug

›Evaluate and manage organ involvement

›Systemic corticosteroids for organ involvement

›Prednisone 0.5 to 1 mg per kg per day PO for moderate to severe DRESS

›Slow taper over weeks to months to reduce relapse risk

›Class IIa recommendation based on expert consensus and observational evidence

›IV methylprednisolone 1 to 2 mg per kg per day for severe organ involvement

›Specialist guided escalation

›Steroid sparing and refractory options

›Cyclosporine for steroid refractory DRESS in selected cases

›IVIG or other immunomodulators per specialist

›Monitoring plan

›Serial CBC with differential

›Serial ALT AST and bilirubin

›Serial creatinine and urinalysis

›Cardiac monitoring if myocarditis concern

AGEP treatment

›Core management

›Stop culprit drug

›Supportive care

›Symptom management

›Topical corticosteroids for inflammation

›Oral antihistamines for pruritus

›Antipyretics avoiding suspected class triggers

›Systemic therapy

›Systemic corticosteroids reserved for severe or persistent cases per specialist

›Class IIb recommendation based on limited evidence

Anaphylaxis and immediate hypersensitivity

›Immediate treatment when criteria met

›IM epinephrine 0.01 mg per kg up to 0.5 mg adult

›Repeat every 5 to 15 minutes if needed

›Class I recommendation

›Airway support and bronchodilator therapy as needed

›IV fluids for hypotension

›H1 antihistamine adjunct

›Corticosteroid adjunct with delayed onset

Documentation and prevention

›Allergy documentation quality

›Culprit drug name

›Reaction phenotype

›Timing from exposure

›Severity features

›Treatment required

›Cross reactivity notes

09Special Populations/sp17

Pregnancy

›Pregnancy considerations

›Maternal stabilization priority in suspected SCAR

›Medication selection safety review

›Prednisone preferred systemic steroid when needed

›Avoid teratogenic alternatives when possible

›Obstetrics involvement for fetal monitoring if systemic illness

›Differential expansion for pregnancy specific dermatoses

Geriatric

›Older adult considerations

›Polypharmacy and culprit identification complexity

›Higher baseline risk for dehydration and AKI in SJS or TEN

›Lower physiologic reserve for systemic inflammation

›Medication dose adjustment for renal or hepatic dysfunction

Pediatrics

›Pediatric considerations

›Viral exanthem mimic frequency higher

›Weight based dosing for systemic therapies

›Lower threshold for ophthalmology in SJS or TEN

›Kawasaki disease and MIS C in differential for febrile rash

10Background/b19

Epidemiology

›Frequency and spectrum

›Exanthematous drug eruption most common cutaneous adverse drug reaction

›SCAR subset includes SJS TEN DRESS AGEP

›DRESS case fatality reported around 10 to 20 percent in reviews

Pathophysiology

›Mechanisms

›Delayed type hypersensitivity common in morbilliform eruptions

›Cytotoxic T cell mediated keratinocyte death in SJS and TEN

›Eosinophil and cytokine driven systemic inflammation in DRESS

›Neutrophil rich pustular inflammation in AGEP

›Viral reactivation associations

›HHV 6 reactivation reported in DRESS pathogenesis models

Therapeutic Considerations

›Drug withdrawal impact

›Early withdrawal associated with improved outcomes in SJS and TEN literature and protocols

›Supportive care primacy

›Barrier loss drives fluid loss and infection risk in SJS and TEN

›Multidisciplinary care central in SJS and TEN protocols

›Immunomodulation uncertainty

›No universal consensus therapy for SJS and TEN beyond supportive care

›Observational evidence supports consideration of cyclosporine in selected cases

11Patient Discharge Instructions/pdi25

copy discharge instructions

›Drug eruption discharge instructions

›Stop and avoid the suspected medication and related medications as directed

›Written list of medications to avoid

›Symptom relief plan

›Moisturizer multiple times daily

›Topical steroid thin layer as prescribed

›Oral antihistamine as prescribed for itch

›Skin care precautions

›Avoid hot showers and harsh soaps

›Avoid new cosmetics or topical products until resolved

›Follow up plan

›Primary care within 48 to 72 hours

›Dermatology referral if not improving within 3 to 5 days

›Return to ED immediately for red flags

›Fever

›Facial swelling

›Blistering or skin peeling

›Mouth sores or eye pain or genital pain

›Trouble breathing or wheeze

›Dizziness or fainting

›Dark urine or yellow eyes

›Reduced urine output

›Rapid spread of rash

›Documentation reminder

›Tell every clinician and pharmacist about this drug reaction

12References/r11

Clinical guidelines and protocols

›Key guidance sources

›DermNet NZ morbilliform drug reaction overview and treatment

›DermNet NZ drug hypersensitivity syndrome DRESS overview

›VUMC burn protocol for SJS and TEN 2025

›Emergency Care BC SJS and TEN treatment summary

Evidence based sources

›Reviews and criteria

›RegiSCAR diagnostic criteria discussion for DRESS

›AGEP update and EuroSCAR validation score review

›SJS and TEN management review with emphasis on early withdrawal and supportive care

›Medscape drug eruptions treatment summary

›JACI In Practice 2025 review on diagnosing and managing DRESS

Evidence & Review

Evidence & Review