Drug Eruption Concern and Severe Cutaneous Reaction Red FlagsAPPROACH

ALLERGY AND DERMATOLOGY · 19 SECTIONS

⚲

500 items

☷ Legend

⚲

Resuscitation and Universal Approaches9▾

Chest and Cardiovascular12▾

Respiratory11▾

Abdominal and Gastrointestinal24▾

Renal and Urinary7▾

Neurologic11▾

Back and Neck8▾

Women's Health, Pregnancy, and GU11▾

Infectious Disease and Fever Syndromes11▾

Allergy and Dermatology7▾

Pruritus Without Rash Contact Dermatitis And Eczema Flare Herpes Zoster Concern Drug Eruption Concern And Severe Cutaneous Reaction Red Flags Urticaria Angioedema Concern Unexplained Bruising Or Bleeding Symptoms

Musculoskeletal and Extremities14▾

Trauma and Wounds14▾

ENT, Eye, Dental10▾

Endocrine, Metabolic, and Abnormal Labs9▾

Toxicology and Behavioral14▾

Pediatrics16▾

Environmental and Exposure4▾

01History/hx55

Symptom narrative

›Drug eruption history cluster

›Rash onset date and time

›Rash progression pattern

›Initial location and spread pattern

›Pruritus severity

›Skin pain severity

›Burning sensation

›Fever onset relative to rash

›Recent infection symptoms preceding rash

Medication exposure timeline

›Exposure to suspected agents

›New medication start within 0 to 2 days

›New medication start within 3 to 14 days

›New medication start within 15 to 60 days

›Dose increase within 14 days

›Intermittent medication use pattern

›Previous exposure to same medication

Morphology history

›Lesion description history

›Morbilliform maculopapular eruption pattern

›Urticarial wheals pattern

›Targetoid lesions pattern

›Dusky or violaceous lesions pattern

›Blisters pattern

›Pustules pattern

›Fixed recurrent lesion at same site pattern

Mucosal and ocular symptoms

›Mucosal involvement screen

›Oral pain

›Odynophagia

›Genital pain

›Dysuria

›Eye pain

›Photophobia

›Vision change

›Purulent eye discharge

Systemic involvement history

›Organ involvement screen

›Dyspnea

›Cough

›Wheeze

›Chest pain

›Palpitations

›Abdominal pain

›Nausea

›Vomiting

›Diarrhea

›Jaundice

›Dark urine

›Oliguria

›Myalgias

›Arthralgias

›Headache

›Confusion

Prior reactions

›Prior hypersensitivity history

›Prior drug rash

›Prior severe cutaneous adverse reaction

›Known medication allergies with reaction type

›Prior anaphylaxis history

02Alarm Features/alarm34

Severe cutaneous adverse reaction red flags

›High risk presentation features

›Skin pain out of proportion

›Dusky or purpuric lesions

›Blistering

›Epidermal detachment

›Positive Nikolsky sign

›Facial edema

›Confluent erythema with tenderness

›Rapid progression over hours

Mucosal danger features

›Mucosal involvement danger features

›Oral erosions

›Lip crusting

›Conjunctivitis with pain

›Genital erosions

›Inability to tolerate oral intake

Vital sign danger thresholds

›Physiologic instability

›Hypotension

›Tachycardia persistent

›Fever persistent

›Hypoxia

›Altered mental status

Systemic organ danger features

›End organ injury features

›Hepatitis symptoms

›Acute kidney injury symptoms

›Dyspnea with new infiltrates concern

›Chest pain with myocarditis concern

›Coagulopathy or bleeding

Immediate escalation triggers

›Time critical triggers

›Suspected Stevens Johnson syndrome or toxic epidermal necrolysis

›Suspected drug reaction with eosinophilia and systemic symptoms

›Suspected acute generalized exanthematous pustulosis with instability

›Anaphylaxis features

›Necrotizing soft tissue infection mimic concern

›Extensive body surface area involvement

03Medications/meds30

Complete medication list

›Medication reconciliation cluster

›Prescription medications

›Over the counter medications

›Supplements

›Herbal products

›Topical medications

›Recent vaccines

High risk culprit classes

›Common high risk triggers

›Antibiotics

›Sulfonamides

›Beta lactams

›Vancomycin

›Anticonvulsants

›Lamotrigine

›Carbamazepine

›Phenytoin

›Allopurinol

›Nonsteroidal anti inflammatory drugs

›Antiretrovirals

Timing and changes

›Recent changes cluster

›New starts with start dates

›Dose increases with dates

›PRN use frequency

›Missed doses

›Recent discontinuations

Interaction and contraindication traps

›Safety considerations

›Acetaminophen dosing if hepatitis concern

›Nonsteroidal anti inflammatory drugs avoidance if kidney injury concern

›Systemic steroid risks in active infection concern

›QT prolonging agents if myocarditis concern

04Diet/diet10

Exposure and intake context

›Intake and exposures

›Reduced oral intake

›Dehydration risk

›New foods or additives temporal association

›Alcohol exposure temporal association

›Caffeine exposure temporal association

Trigger pattern

›Diet related triggers

›Histamine rich food exposure with urticaria concern

›Hot spicy foods worsening flushing or pruritus

›Supplement or protein powder exposure timing

05Review of Systems/ros32

Dermatologic and allergic

›Skin and allergy symptoms

›Pruritus

›Skin pain

›Burning

›Angioedema

›Urticaria

›New photosensitivity

Infectious and constitutional

›Systemic symptoms

›Fever

›Chills

›Malaise

›Sore throat

›Sick contacts

Cardiopulmonary

›Cardiopulmonary symptoms

›Dyspnea

›Wheeze

›Chest pain

›Palpitations

Gastrointestinal and hepatic

›Gastrointestinal symptoms

›Abdominal pain

›Nausea

›Vomiting

›Diarrhea

›Jaundice

Genitourinary and renal

›Renal and urinary symptoms

›Dysuria

›Hematuria

›Reduced urine output

Neurologic

›Neurologic symptoms

›Headache

›Confusion

›Weakness

06Collateral History and Family History/chafh12

Collateral source

›Source reliability

›Caregiver history available

›Pharmacy fill history available

›Photos of early rash available

Family history

›Genetic and atopy context

›Atopic disease family history

›Severe drug reaction family history

›Autoimmune disease family history

Exposure context

›Household and community context

›New household products exposure

›Recent viral illness in household

›Travel exposures within 30 days

07Risk Factors/rf22

Patient factors for severe reactions

›Host risk factors

›Immunocompromised state

›HIV

›Malignancy

›Chronic kidney disease (N18.9)

›Chronic liver disease (K76.9)

›Older age

›Prior severe cutaneous adverse reaction

Medication specific risks

›Known higher risk medication contexts

›Allopurinol with kidney disease

›High initial dose of lamotrigine

›Rapid titration of anticonvulsants

Exposure risks and mimics

›Non drug causes to consider

›Recent viral infection

›Mycoplasma infection risk

›New topical exposure

›Arthropod exposure

Special populations

›Population specific considerations

›Pregnancy

›Postpartum

›Pediatrics

›Older adults with frailty

08Differential Diagnosis/ddx66

Life threatening

›Life threatening causes

›Stevens Johnson syndrome toxic epidermal necrolysis (L51.1)

›Mucosal involvement

›Skin pain

›Dusky lesions

›Epidermal detachment

›Drug reaction with eosinophilia and systemic symptoms (DRESS)

›Facial edema

›Lymphadenopathy

›Hepatitis

›Eosinophilia

›Acute generalized exanthematous pustulosis

›Numerous sterile pustules

›Fever

›Neutrophilia

›Anaphylaxis (T78.2)

›Hypotension

›Bronchospasm

›Angioedema

›Meningococcemia mimic (A39.9)

›Petechiae

›Purpura

›Shock

›Staphylococcal scalded skin syndrome

›Superficial desquamation

›Periorificial crusting

Common

›Common causes

›Morbilliform drug eruption

›Symmetric trunk predominant eruption

›Pruritus

›Minimal systemic symptoms

›Urticaria and angioedema (L50.9)

›Transient wheals

›Migratory pattern

›Fixed drug eruption

›Recurrent same site lesion

›Post inflammatory hyperpigmentation

›Contact dermatitis (L23.9)

›Geometric distribution

›Exposure pattern

›Viral exanthem

›URI symptoms

›Exposure clusters

Less common

›Less common causes

›Serum sickness like reaction

›Fever

›Arthralgias

›Urticarial eruption

›Cutaneous small vessel vasculitis (L95.9)

›Palpable purpura

›Dependent distribution

›Phototoxic drug reaction

›Sun exposed distribution

›Sharp clothing lines

›Symmetric drug related intertriginous and flexural exanthema

›Flexural involvement

›Symmetry

›Erythema multiforme

›Target lesions

›Herpes simplex association

Key distinguishing clues

›Differentiating features

›Wheals that resolve within 24 hours favor urticaria

›Fixed same site recurrence favors fixed drug eruption

›Pustules with neutrophilia favor acute generalized exanthematous pustulosis

›Facial edema with hepatitis favors DRESS

›Skin pain with mucosal erosions favors Stevens Johnson syndrome toxic epidermal necrolysis

09Past Medical History/pmh14

Relevant conditions

›Comorbidities influencing risk

›Chronic kidney disease (N18.9)

›Chronic liver disease (K76.9)

›HIV (B20)

›Autoimmune disease

›Atopic dermatitis (L20.9)

Prior similar episodes

›Prior rash episodes

›Prior drug eruption with culprit and outcome

›Prior hospital admission for rash

›Prior mucosal involvement history

Procedures and devices

›Recent procedures and exposures

›Recent surgery with perioperative antibiotics

›Implanted devices

›Recent contrast exposure

10Physical Exam/exam44

General and vitals

›General severity assessment

›Ill appearing

›Toxic appearance

›Hydration status

›Fever

›Hypotension

›Tachycardia

›Hypoxia

Skin morphology and distribution

›Skin exam core elements

›Morphology type

›Macules and papules

›Urticarial wheals

›Targetoid lesions

›Vesicles and bullae

›Pustules

›Purpura

›Dusky discoloration

›Distribution pattern

›Flexural predominance

›Photodistribution

Skin severity markers

›Severe reaction markers

›Skin tenderness

›Positive Nikolsky sign

›Epidermal detachment estimate

›Body surface area percentage estimate

Mucosal and ocular exam

›Mucosal assessment

›Oral erosions

›Lip crusting

›Conjunctival injection

›Corneal involvement concern

›Genital erosions

Lymph nodes and edema

›Systemic inflammatory clues

›Lymphadenopathy

›Facial edema

›Peripheral edema

Cardiopulmonary exam

›Cardiopulmonary findings

›Wheeze

›Stridor

›Crackles

›Signs of myocarditis

Abdominal and neurologic

›Other system findings

›Hepatomegaly

›Right upper quadrant tenderness

›Encephalopathy signs

11Lab Studies/labs26

Baseline evaluation for suspected drug eruption

›Screening labs

›Complete blood count with differential

›Comprehensive metabolic panel

›Creatinine trend

›Liver enzymes trend

›Bilirubin

›Urinalysis

Severe cutaneous adverse reaction workup

›Organ involvement assessment labs

›Absolute eosinophil count

›C reactive protein

›Creatine kinase

›Coagulation studies if liver injury concern

›Lactate if shock concern

Infection evaluation when febrile

›Infectious evaluation

›Blood cultures

›Urine culture if urinary symptoms

›Respiratory viral testing local protocol dependent

Interpretation pearls

›Lab interpretation guidance

›Eosinophilia supports DRESS but absence does not exclude

›Neutrophilia supports acute generalized exanthematous pustulosis

›Transaminitis supports DRESS severity stratification

›Rising creatinine suggests renal involvement

Limitations and pitfalls

›Common pitfalls

›Early normal labs do not exclude evolving severe cutaneous adverse reaction

›Steroid exposure may blunt eosinophilia

›Viral exanthem can mimic morbilliform drug eruption

12Imaging/img16

Scoring Systems

›Risk scoring and severity tools

›SCORTEN for Stevens Johnson syndrome toxic epidermal necrolysis

›Higher score correlates with higher mortality risk

›Use within first 24 hours and repeat as clinical course evolves

›RegiSCAR criteria for DRESS

›Supports standardized diagnosis classification

›Not a stand alone rule out tool

MRI

›MRI role in complications

›Brain MRI if encephalitis concern

›Cardiac MRI if myocarditis concern

›CT role in complications

›CT chest if hypoxia or pneumonitis concern

›CT abdomen if severe abdominal pain or hepatitis complication concern

Ultrasound

›Ultrasound role in complications

›Right upper quadrant ultrasound if cholestasis concern

›Renal ultrasound if obstructive uropathy concern

13Special Tests/spec10

Dermatology directed testing

›Skin targeted diagnostics

›Skin biopsy for Stevens Johnson syndrome toxic epidermal necrolysis confirmation

›Skin biopsy for vasculitis evaluation

›Direct immunofluorescence if autoimmune blistering concern

Infectious and trigger testing

›Trigger evaluation tests

›Mycoplasma testing in compatible clinical syndrome

›Herpes simplex evaluation if erythema multiforme concern

Allergy and causality assessment

›Causality tools and allergy considerations

›ALDEN algorithm for suspected Stevens Johnson syndrome toxic epidermal necrolysis culprit support

›Referral for delayed hypersensitivity testing after recovery

14ECG/ecg10

Cardiac involvement screening

›ECG indications in drug reactions

›Chest pain

›Palpitations

›Syncope

›Suspected myocarditis in DRESS

High risk patterns

›ECG danger findings

›New conduction abnormalities

›ST segment changes

›Ventricular ectopy

›QT prolongation with high risk medications

15Assessment/ax28

Working diagnosis framework

›Syndrome classification

›Simple exanthematous drug eruption likelihood

›Urticaria and angioedema likelihood

›Fixed drug eruption likelihood

›DRESS likelihood

›Stevens Johnson syndrome toxic epidermal necrolysis likelihood

›Acute generalized exanthematous pustulosis likelihood

Severity stratification

›Severity tiers

›Mild limited rash without systemic symptoms

›Moderate diffuse rash with stable vitals

›Severe cutaneous adverse reaction suspected

›Mucosal involvement

›Skin pain

›Blistering

›Organ injury labs

Culprit medication likelihood

›Causality weighting

›Timing compatible with suspected phenotype

›Known high risk medication exposure

›Alternative diagnoses less likely

›Improvement after discontinuation

Complications to rule out

›Time sensitive complications

›Dehydration and electrolyte abnormalities

›Sepsis mimic

›Ocular injury risk

›Airway compromise with angioedema

›Hepatitis progression

›Acute kidney injury progression

›Myocarditis in DRESS

16Plan/plan38

First 5 minutes workflow

›Immediate stabilization priorities

›If airway compromise then airway management escalation

›If hypotension then IV fluids and shock pathway

›If anaphylaxis concern then epinephrine IM 0.3 mg to 0.5 mg adult

›Continuous monitoring for unstable patients

›Two large bore IV access if extensive skin involvement or shock concern

Remove the trigger

›Medication discontinuation plan

›Stop suspected culprit medications immediately

›Stop non essential medications

›Avoid re challenge with suspected culprit

Symptomatic treatment for mild to moderate eruptions

›Symptom control

›Oral antihistamine example cetirizine 10 mg daily adult

›Breakthrough pruritus example hydroxyzine 25 mg at bedtime adult

›Topical corticosteroid medium potency for trunk and extremities

›Emollients and gentle skin care

Severe cutaneous adverse reaction management

›Severe reaction pathway

›Dermatology consult

›Ophthalmology consult if any ocular symptoms

›Burn unit consult for suspected Stevens Johnson syndrome toxic epidermal necrolysis

›Fluid and electrolyte management

›Wound care with non adherent dressings

›Temperature management

›Pain control with careful renal hepatic consideration

DRESS specific therapy

›DRESS management

›Systemic corticosteroid example prednisone 0.5 mg per kg per day adult for organ involvement

›Taper plan over weeks to prevent relapse

›Monitor liver enzymes and creatinine serially

›Avoid empiric antibiotics unless infection evidence

Stevens Johnson syndrome toxic epidermal necrolysis adjuncts

›Adjunctive therapies local protocol dependent

›Cyclosporine consideration in selected patients

›Etanercept consideration in selected patients

›IVIG consideration in selected patients

›Systemic corticosteroids risk benefit case based

Monitoring and reassessment loop

›Reassessment cycle

›Repeat vital signs frequency based on severity

›Repeat skin exam for new blistering or detachment

›Repeat labs within 12 to 24 hours if severe concern

›Escalate level of care if progression despite trigger removal

17Disposition/dispo25

ICU and resuscitation level care

›ICU criteria

›Hemodynamic instability

›Hypoxia requiring high flow oxygen or ventilation

›Rapidly progressive skin detachment

›Severe electrolyte derangements

›Suspected myocarditis with instability

Inpatient admission

›Admission criteria

›Suspected Stevens Johnson syndrome toxic epidermal necrolysis

›Suspected DRESS with organ involvement

›Extensive rash with inability to maintain hydration

›Severe pain requiring parenteral analgesia

›Significant mucosal involvement

›High risk comorbidities with evolving course

Observation pathway

›Observation criteria

›Diffuse rash with stable vitals

›Mild lab abnormalities requiring repeat testing

›Uncertain culprit requiring medication reconciliation

Discharge criteria

›Discharge criteria

›Stable vital signs

›No mucosal involvement

›No skin pain

›No blistering

›Labs without organ injury concern when indicated

›Reliable follow up within 24 to 72 hours

›Clear culprit discontinuation plan documented

18Discharge Instructions/di21

Copy discharge instructions

›Patient instructions

›Rash likely related to a medication or exposure

›Do not take the suspected medication again

›Bring a list of all medications to follow up visit

›Take antihistamine as directed for itching

›Use topical steroid as directed for itchy inflamed areas

›Avoid new non essential medications until cleared

›Drink fluids to maintain hydration

›Follow up with primary care within 24 to 72 hours

›Follow up with dermatology if arranged

›Return to emergency care for fever

›Return to emergency care for skin pain

›Return to emergency care for blisters

›Return to emergency care for peeling skin

›Return to emergency care for mouth sores

›Return to emergency care for eye pain or vision change

›Return to emergency care for trouble breathing

›Return to emergency care for swelling of lips or tongue

›Return to emergency care for dark urine or yellow skin

›Return to emergency care for decreased urination

›Return to emergency care for chest pain or fainting

19References/r7

Guidelines and key sources

›Core references

›Bastuji Garin S and SCORTEN development study 2000

›RegiSCAR group diagnostic criteria for DRESS 2007

›British Association of Dermatologists guideline for Stevens Johnson syndrome and toxic epidermal necrolysis 2016

›American Academy of Dermatology clinical guidance on drug eruptions and severe cutaneous adverse reactions 2020

›European Dermatology Forum guidance on severe cutaneous adverse reactions 2022

›World Allergy Organization anaphylaxis guidance 2020

Evidence & Review

Reviewed by SymptomDx Medical Team · Last reviewed February 24, 2026

SymptomDx is an educational tool for medical professionals. It does not replace clinical judgment. Verify all clinical data and drug dosages with authoritative sources.

Drug Eruption Concern and Severe Cutaneous Reaction Red FlagsAPPROACH

ALLERGY AND DERMATOLOGY · 19 SECTIONS

⚲

500 items

☷ Legend

⚲

Resuscitation and Universal Approaches9▾

Chest and Cardiovascular12▾

Respiratory11▾

Abdominal and Gastrointestinal24▾

Renal and Urinary7▾

Neurologic11▾

Back and Neck8▾

Women's Health, Pregnancy, and GU11▾

Infectious Disease and Fever Syndromes11▾

Allergy and Dermatology7▾

Musculoskeletal and Extremities14▾

Trauma and Wounds14▾

ENT, Eye, Dental10▾

Endocrine, Metabolic, and Abnormal Labs9▾

Toxicology and Behavioral14▾

Pediatrics16▾

Environmental and Exposure4▾

01History/hx55

Symptom narrative

›Drug eruption history cluster

›Rash onset date and time

›Rash progression pattern

›Initial location and spread pattern

›Pruritus severity

›Skin pain severity

›Burning sensation

›Fever onset relative to rash

›Recent infection symptoms preceding rash

Medication exposure timeline

›Exposure to suspected agents

›New medication start within 0 to 2 days

›New medication start within 3 to 14 days

›New medication start within 15 to 60 days

›Dose increase within 14 days

›Intermittent medication use pattern

›Previous exposure to same medication

Morphology history

›Lesion description history

›Morbilliform maculopapular eruption pattern

›Urticarial wheals pattern

›Targetoid lesions pattern

›Dusky or violaceous lesions pattern

›Blisters pattern

›Pustules pattern

›Fixed recurrent lesion at same site pattern

Mucosal and ocular symptoms

›Mucosal involvement screen

›Oral pain

›Odynophagia

›Genital pain

›Dysuria

›Eye pain

›Photophobia

›Vision change

›Purulent eye discharge

Systemic involvement history

›Organ involvement screen

›Dyspnea

›Cough

›Wheeze

›Chest pain

›Palpitations

›Abdominal pain

›Nausea

›Vomiting

›Diarrhea

›Jaundice

›Dark urine

›Oliguria

›Myalgias

›Arthralgias

›Headache

›Confusion

Prior reactions

›Prior hypersensitivity history

›Prior drug rash

›Prior severe cutaneous adverse reaction

›Known medication allergies with reaction type

›Prior anaphylaxis history

02Alarm Features/alarm34

Severe cutaneous adverse reaction red flags

›High risk presentation features

›Skin pain out of proportion

›Dusky or purpuric lesions

›Blistering

›Epidermal detachment

›Positive Nikolsky sign

›Facial edema

›Confluent erythema with tenderness

›Rapid progression over hours

Mucosal danger features

›Mucosal involvement danger features

›Oral erosions

›Lip crusting

›Conjunctivitis with pain

›Genital erosions

›Inability to tolerate oral intake

Vital sign danger thresholds

›Physiologic instability

›Hypotension

›Tachycardia persistent

›Fever persistent

›Hypoxia

›Altered mental status

Systemic organ danger features

›End organ injury features

›Hepatitis symptoms

›Acute kidney injury symptoms

›Dyspnea with new infiltrates concern

›Chest pain with myocarditis concern

›Coagulopathy or bleeding

Immediate escalation triggers

›Time critical triggers

›Suspected Stevens Johnson syndrome or toxic epidermal necrolysis

›Suspected drug reaction with eosinophilia and systemic symptoms

›Suspected acute generalized exanthematous pustulosis with instability

›Anaphylaxis features

›Necrotizing soft tissue infection mimic concern

›Extensive body surface area involvement

03Medications/meds30

Complete medication list

›Medication reconciliation cluster

›Prescription medications

›Over the counter medications

›Supplements

›Herbal products

›Topical medications

›Recent vaccines

High risk culprit classes

›Common high risk triggers

›Antibiotics

›Sulfonamides

›Beta lactams

›Vancomycin

›Anticonvulsants

›Lamotrigine

›Carbamazepine

›Phenytoin

›Allopurinol

›Nonsteroidal anti inflammatory drugs

›Antiretrovirals

Timing and changes

›Recent changes cluster

›New starts with start dates

›Dose increases with dates

›PRN use frequency

›Missed doses

›Recent discontinuations

Interaction and contraindication traps

›Safety considerations

›Acetaminophen dosing if hepatitis concern

›Nonsteroidal anti inflammatory drugs avoidance if kidney injury concern

›Systemic steroid risks in active infection concern

›QT prolonging agents if myocarditis concern

04Diet/diet10

Exposure and intake context

›Intake and exposures

›Reduced oral intake

›Dehydration risk

›New foods or additives temporal association

›Alcohol exposure temporal association

›Caffeine exposure temporal association

Trigger pattern

›Diet related triggers

›Histamine rich food exposure with urticaria concern

›Hot spicy foods worsening flushing or pruritus

›Supplement or protein powder exposure timing

05Review of Systems/ros32

Dermatologic and allergic

›Skin and allergy symptoms

›Pruritus

›Skin pain

›Burning

›Angioedema

›Urticaria

›New photosensitivity

Infectious and constitutional

›Systemic symptoms

›Fever

›Chills

›Malaise

›Sore throat

›Sick contacts

Cardiopulmonary

›Cardiopulmonary symptoms

›Dyspnea

›Wheeze

›Chest pain

›Palpitations

Gastrointestinal and hepatic

›Gastrointestinal symptoms

›Abdominal pain

›Nausea

›Vomiting

›Diarrhea

›Jaundice

Genitourinary and renal

›Renal and urinary symptoms

›Dysuria

›Hematuria

›Reduced urine output

Neurologic

›Neurologic symptoms

›Headache

›Confusion

›Weakness

06Collateral History and Family History/chafh12

Collateral source

›Source reliability

›Caregiver history available

›Pharmacy fill history available

›Photos of early rash available

Family history

›Genetic and atopy context

›Atopic disease family history

›Severe drug reaction family history

›Autoimmune disease family history

Exposure context

›Household and community context

›New household products exposure

›Recent viral illness in household

›Travel exposures within 30 days

07Risk Factors/rf22

Patient factors for severe reactions

›Host risk factors

›Immunocompromised state

›HIV

›Malignancy

›Chronic kidney disease (N18.9)

›Chronic liver disease (K76.9)

›Older age

›Prior severe cutaneous adverse reaction

Medication specific risks

›Known higher risk medication contexts

›Allopurinol with kidney disease

›High initial dose of lamotrigine

›Rapid titration of anticonvulsants

Exposure risks and mimics

›Non drug causes to consider

›Recent viral infection

›Mycoplasma infection risk

›New topical exposure

›Arthropod exposure

Special populations

›Population specific considerations

›Pregnancy

›Postpartum

›Pediatrics

›Older adults with frailty

08Differential Diagnosis/ddx66

Life threatening

›Life threatening causes

›Stevens Johnson syndrome toxic epidermal necrolysis (L51.1)

›Mucosal involvement

›Skin pain

›Dusky lesions

›Epidermal detachment

›Drug reaction with eosinophilia and systemic symptoms (DRESS)

›Facial edema

›Lymphadenopathy

›Hepatitis

›Eosinophilia

›Acute generalized exanthematous pustulosis

›Numerous sterile pustules

›Fever

›Neutrophilia

›Anaphylaxis (T78.2)

›Hypotension

›Bronchospasm

›Angioedema

›Meningococcemia mimic (A39.9)

›Petechiae

›Purpura

›Shock

›Staphylococcal scalded skin syndrome

›Superficial desquamation

›Periorificial crusting

Common

›Common causes

›Morbilliform drug eruption

›Symmetric trunk predominant eruption

›Pruritus

›Minimal systemic symptoms

›Urticaria and angioedema (L50.9)

›Transient wheals

›Migratory pattern

›Fixed drug eruption

›Recurrent same site lesion

›Post inflammatory hyperpigmentation

›Contact dermatitis (L23.9)

›Geometric distribution

›Exposure pattern

›Viral exanthem

›URI symptoms

›Exposure clusters

Less common

›Less common causes

›Serum sickness like reaction

›Fever

›Arthralgias

›Urticarial eruption

›Cutaneous small vessel vasculitis (L95.9)

›Palpable purpura

›Dependent distribution

›Phototoxic drug reaction

›Sun exposed distribution

›Sharp clothing lines

›Symmetric drug related intertriginous and flexural exanthema

›Flexural involvement

›Symmetry

›Erythema multiforme

›Target lesions

›Herpes simplex association

Key distinguishing clues

›Differentiating features

›Wheals that resolve within 24 hours favor urticaria

›Fixed same site recurrence favors fixed drug eruption

›Pustules with neutrophilia favor acute generalized exanthematous pustulosis

›Facial edema with hepatitis favors DRESS

›Skin pain with mucosal erosions favors Stevens Johnson syndrome toxic epidermal necrolysis

09Past Medical History/pmh14

Relevant conditions

›Comorbidities influencing risk

›Chronic kidney disease (N18.9)

›Chronic liver disease (K76.9)

›HIV (B20)

›Autoimmune disease

›Atopic dermatitis (L20.9)

Prior similar episodes

›Prior rash episodes

›Prior drug eruption with culprit and outcome

›Prior hospital admission for rash

›Prior mucosal involvement history

Procedures and devices

›Recent procedures and exposures

›Recent surgery with perioperative antibiotics

›Implanted devices

›Recent contrast exposure

10Physical Exam/exam44

General and vitals

›General severity assessment

›Ill appearing

›Toxic appearance

›Hydration status

›Fever

›Hypotension

›Tachycardia

›Hypoxia

Skin morphology and distribution

›Skin exam core elements

›Morphology type

›Macules and papules

›Urticarial wheals

›Targetoid lesions

›Vesicles and bullae

›Pustules

›Purpura

›Dusky discoloration

›Distribution pattern

›Flexural predominance

›Photodistribution

Skin severity markers

›Severe reaction markers

›Skin tenderness

›Positive Nikolsky sign

›Epidermal detachment estimate

›Body surface area percentage estimate

Mucosal and ocular exam

›Mucosal assessment

›Oral erosions

›Lip crusting

›Conjunctival injection

›Corneal involvement concern

›Genital erosions

Lymph nodes and edema

›Systemic inflammatory clues

›Lymphadenopathy

›Facial edema

›Peripheral edema

Cardiopulmonary exam

›Cardiopulmonary findings

›Wheeze

›Stridor

›Crackles

›Signs of myocarditis

Abdominal and neurologic

›Other system findings

›Hepatomegaly

›Right upper quadrant tenderness

›Encephalopathy signs

11Lab Studies/labs26

Baseline evaluation for suspected drug eruption

›Screening labs

›Complete blood count with differential

›Comprehensive metabolic panel

›Creatinine trend

›Liver enzymes trend

›Bilirubin

›Urinalysis

Severe cutaneous adverse reaction workup

›Organ involvement assessment labs

›Absolute eosinophil count

›C reactive protein

›Creatine kinase

›Coagulation studies if liver injury concern

›Lactate if shock concern

Infection evaluation when febrile

›Infectious evaluation

›Blood cultures

›Urine culture if urinary symptoms

›Respiratory viral testing local protocol dependent

Interpretation pearls

›Lab interpretation guidance

›Eosinophilia supports DRESS but absence does not exclude

›Neutrophilia supports acute generalized exanthematous pustulosis

›Transaminitis supports DRESS severity stratification

›Rising creatinine suggests renal involvement

Limitations and pitfalls

›Common pitfalls

›Early normal labs do not exclude evolving severe cutaneous adverse reaction

›Steroid exposure may blunt eosinophilia

›Viral exanthem can mimic morbilliform drug eruption

12Imaging/img16

Scoring Systems

›Risk scoring and severity tools

›SCORTEN for Stevens Johnson syndrome toxic epidermal necrolysis

›Higher score correlates with higher mortality risk

›Use within first 24 hours and repeat as clinical course evolves

›RegiSCAR criteria for DRESS

›Supports standardized diagnosis classification

›Not a stand alone rule out tool

MRI

›MRI role in complications

›Brain MRI if encephalitis concern

›Cardiac MRI if myocarditis concern

›CT role in complications

›CT chest if hypoxia or pneumonitis concern

›CT abdomen if severe abdominal pain or hepatitis complication concern

Ultrasound

›Ultrasound role in complications

›Right upper quadrant ultrasound if cholestasis concern

›Renal ultrasound if obstructive uropathy concern

13Special Tests/spec10

Dermatology directed testing

›Skin targeted diagnostics

›Skin biopsy for Stevens Johnson syndrome toxic epidermal necrolysis confirmation

›Skin biopsy for vasculitis evaluation

›Direct immunofluorescence if autoimmune blistering concern

Infectious and trigger testing

›Trigger evaluation tests

›Mycoplasma testing in compatible clinical syndrome

›Herpes simplex evaluation if erythema multiforme concern

Allergy and causality assessment

›Causality tools and allergy considerations

›ALDEN algorithm for suspected Stevens Johnson syndrome toxic epidermal necrolysis culprit support

›Referral for delayed hypersensitivity testing after recovery

14ECG/ecg10

Cardiac involvement screening

›ECG indications in drug reactions

›Chest pain

›Palpitations

›Syncope

›Suspected myocarditis in DRESS

High risk patterns

›ECG danger findings

›New conduction abnormalities

›ST segment changes

›Ventricular ectopy

›QT prolongation with high risk medications

15Assessment/ax28

Working diagnosis framework

›Syndrome classification

›Simple exanthematous drug eruption likelihood

›Urticaria and angioedema likelihood

›Fixed drug eruption likelihood

›DRESS likelihood

›Stevens Johnson syndrome toxic epidermal necrolysis likelihood

›Acute generalized exanthematous pustulosis likelihood

Severity stratification

›Severity tiers

›Mild limited rash without systemic symptoms

›Moderate diffuse rash with stable vitals

›Severe cutaneous adverse reaction suspected

›Mucosal involvement

›Skin pain

›Blistering

›Organ injury labs

Culprit medication likelihood

›Causality weighting

›Timing compatible with suspected phenotype

›Known high risk medication exposure

›Alternative diagnoses less likely

›Improvement after discontinuation

Complications to rule out

›Time sensitive complications

›Dehydration and electrolyte abnormalities

›Sepsis mimic

›Ocular injury risk

›Airway compromise with angioedema

›Hepatitis progression

›Acute kidney injury progression

›Myocarditis in DRESS

16Plan/plan38

First 5 minutes workflow

›Immediate stabilization priorities

›If airway compromise then airway management escalation

›If hypotension then IV fluids and shock pathway

›If anaphylaxis concern then epinephrine IM 0.3 mg to 0.5 mg adult

›Continuous monitoring for unstable patients

›Two large bore IV access if extensive skin involvement or shock concern

Remove the trigger

›Medication discontinuation plan

›Stop suspected culprit medications immediately

›Stop non essential medications

›Avoid re challenge with suspected culprit

Symptomatic treatment for mild to moderate eruptions

›Symptom control

›Oral antihistamine example cetirizine 10 mg daily adult

›Breakthrough pruritus example hydroxyzine 25 mg at bedtime adult

›Topical corticosteroid medium potency for trunk and extremities

›Emollients and gentle skin care

Severe cutaneous adverse reaction management

›Severe reaction pathway

›Dermatology consult

›Ophthalmology consult if any ocular symptoms

›Burn unit consult for suspected Stevens Johnson syndrome toxic epidermal necrolysis

›Fluid and electrolyte management

›Wound care with non adherent dressings

›Temperature management

›Pain control with careful renal hepatic consideration

DRESS specific therapy

›DRESS management

›Systemic corticosteroid example prednisone 0.5 mg per kg per day adult for organ involvement

›Taper plan over weeks to prevent relapse

›Monitor liver enzymes and creatinine serially

›Avoid empiric antibiotics unless infection evidence

Stevens Johnson syndrome toxic epidermal necrolysis adjuncts

›Adjunctive therapies local protocol dependent

›Cyclosporine consideration in selected patients

›Etanercept consideration in selected patients

›IVIG consideration in selected patients

›Systemic corticosteroids risk benefit case based

Monitoring and reassessment loop

›Reassessment cycle

›Repeat vital signs frequency based on severity

›Repeat skin exam for new blistering or detachment

›Repeat labs within 12 to 24 hours if severe concern

›Escalate level of care if progression despite trigger removal

17Disposition/dispo25

ICU and resuscitation level care

›ICU criteria

›Hemodynamic instability

›Hypoxia requiring high flow oxygen or ventilation

›Rapidly progressive skin detachment

›Severe electrolyte derangements

›Suspected myocarditis with instability

Inpatient admission

›Admission criteria

›Suspected Stevens Johnson syndrome toxic epidermal necrolysis

›Suspected DRESS with organ involvement

›Extensive rash with inability to maintain hydration

›Severe pain requiring parenteral analgesia

›Significant mucosal involvement

›High risk comorbidities with evolving course

Observation pathway

›Observation criteria

›Diffuse rash with stable vitals

›Mild lab abnormalities requiring repeat testing

›Uncertain culprit requiring medication reconciliation

Discharge criteria

›Discharge criteria

›Stable vital signs

›No mucosal involvement

›No skin pain

›No blistering

›Labs without organ injury concern when indicated

›Reliable follow up within 24 to 72 hours

›Clear culprit discontinuation plan documented

18Discharge Instructions/di21

Copy discharge instructions

›Patient instructions

›Rash likely related to a medication or exposure

›Do not take the suspected medication again

›Bring a list of all medications to follow up visit

›Take antihistamine as directed for itching

›Use topical steroid as directed for itchy inflamed areas

›Avoid new non essential medications until cleared

›Drink fluids to maintain hydration

›Follow up with primary care within 24 to 72 hours

›Follow up with dermatology if arranged

›Return to emergency care for fever

›Return to emergency care for skin pain

›Return to emergency care for blisters

›Return to emergency care for peeling skin

›Return to emergency care for mouth sores

›Return to emergency care for eye pain or vision change

›Return to emergency care for trouble breathing

›Return to emergency care for swelling of lips or tongue

›Return to emergency care for dark urine or yellow skin

›Return to emergency care for decreased urination

›Return to emergency care for chest pain or fainting

19References/r7

Guidelines and key sources

›Core references

›Bastuji Garin S and SCORTEN development study 2000

›RegiSCAR group diagnostic criteria for DRESS 2007

›British Association of Dermatologists guideline for Stevens Johnson syndrome and toxic epidermal necrolysis 2016

›American Academy of Dermatology clinical guidance on drug eruptions and severe cutaneous adverse reactions 2020

›European Dermatology Forum guidance on severe cutaneous adverse reactions 2022

›World Allergy Organization anaphylaxis guidance 2020

Evidence & Review

Reviewed by SymptomDx Medical Team · Last reviewed February 24, 2026

SymptomDx is an educational tool for medical professionals. It does not replace clinical judgment. Verify all clinical data and drug dosages with authoritative sources.