Veterinary Cooperative Oncology Group-Common Terminology Criteria for Adverse Events (VCOG-CTCAE v2) following investigational therapy in dogs and cats.

The updated VCOG-CTCAE v2 guidelines contain several important updates and additions since the last update (v1.1) was released in 2011 and published within Veterinary and Comparative Oncology in 2016. As the Veterinary Cooperative Oncology Group (VCOG) is no longer an active entity, the original authors and contributors to the VCOG-CTCAE v1.0 and v1.1 were consulted for input, and additional co-authors sought for expansion and refinement of the adverse event (AE) categories. VCOG-CTCAE v2 includes expanded neurology, cardiac and immunologic AE sections, and the addition of procedural-specific AEs. It is our intent that, through inclusion of additional authors from ACVIM subspecialties and the American College of Veterinary Surgery, that we can more comprehensively capture AEs that are observed during clinical studies conducted across a variety of disease states, clinical scenarios, and body systems. It is also our intent that these updated veterinary CTCAE guidelines will offer improved application and ease of use within veterinary practice in general, as well as within clinical trials that assess new therapeutic strategies for animals with a variety of diseases. Throughout the revision process, we strived to ensure the grading structure for each AE category was reflective of the decision-making process applied to determination of dose-limiting events. As phase I trial decisions are based on these criteria and ultimately determine the maximally tolerated dose, there is impact on standard dosing recommendations for any new drug registration or application. This document should be updated regularly to reflect ongoing application to clinical studies carried out in veterinary patients.

: The VCOG‐CTCAE is a descriptive terminology, which can be used for adverse event (AE) reporting in dogs and cats. A grading (severity) scale is provided for each AE term.

:

AE and grades apply to both cats and dogs unless otherwise stated.

CATEGORY

A CATEGORY is a broad classification of AEs based on anatomy and/or pathophysiology. Within each CATEGORY, AEs are listed accompanied by their descriptions of severity (Grade).

Adverse Event Terms

An AE is any unfavourable and unintended sign (including an abnormal clinicopathologic finding), clinical sign, or disease temporally associated with the use of a medical treatment that may or may be considered related to the medical treatment (see ATTRIBUTION below). An AE is a term that is a unique representation of a specific event used for medical documentation and scientific analyses. AEs are listed alphabetically within CATEGORIES. For several AEs, a definition is provided and highlighted in grey within the tables.

Grades

Grade refers to the severity of the AE. The VCOG‐CTCAE displays Grades 1 through 5 with unique clinical description of severity for each AE based on this general guideline:

Further comments

A Semi‐colon indicates “or” within the description of the grade. When items within the description of the grade are separated by a comma, the “,” means “and.” All items separated by a comma are necessary to establish that grade level.

An “—“indicates a grade is not available.

Not all Grades are appropriate for all AEs. Therefore, some AEs are listed with fewer than five options for grade selection.

Grade 5 (Death) is not appropriate for some AEs and therefore is not listed as an option.

Dose‐limiting toxicities (DLTs) are defined a priori by study investigators on a per‐protocol basis

CTCAE definitions and criteria for hypothermia, fever, cardiac arrhythmias and bradycardia can also be applied to anaesthetized patients as appropriate for recording of events that occur under anaesthesia.

Abbreviations used

ADL = activities of daily living (eating, drinking, sleeping, defecating and urinating)

BSA = body surface area

CHF = congestive heart failure

LLN = lower limit of normal

ULN = upper limit of normal

There exist several potential causes of AEs, including the protocol intervention under assessment, pre‐existing conditions (eg, liver disease with associated liver enzyme abnormalities, diabetes), progression of disease being treated, concomitant medications (eg, steroids) and other causes (eg, transfusion reactions, accidental injuries). Documenting and grading an AE simply reports that an event has occurred and the seriousness of the event. To be complete the clinician should assign attribution of the AE, either to the intervention or something else. Attribution of an event can be possibly due to one or more concomitant disease process. Designating an event as treatment related (or not) can be done in two ways:

By the treating clinician at the time of clinical evaluation.

By Investigators, usually occurring later in aggregate data review and reporting by the Investigators

:

Unrelated: The Adverse Event is clearly not related to the investigational agent(s)

Unlikely: The Adverse Event is doubtfully related to the investigational agent(s)

Possible: The Adverse Event may be related to the investigational agent(s)

Probable: The Adverse Event is likely related to the investigational agent(s)

Definite: The Adverse Event is clearly related to the investigational agent(s)

Prolonged (eg, not rapidly responsive to medication and/or brief interruption of infusion); recurrence of signs following initial improvement; hospitalization indicated for clinical sequelae (eg, renal

impairment, pulmonary infiltrates or oedema)

Dog: 10 g/dL‐

Cat: 8.0 g/dL‐

Dog: <10‐8.0 g/dL

Cat: <8.0‐6.5 g/dL

Dog: <8.0‐6.5 g/dL

Cat: <6.5‐5.0

Dog: <6.5 g/dL

Cat: <5.0

>4000/μL

20 000/μL

Dog: 30%‐

Cat: 25%‐

Dog: 20‐<30%

Cat: 20‐<25%

Dog: 15‐<20%

Cat: 15‐<20%

Transfusion indicated

Dog: <15%

Cat: <15%

Life threatening; urgent medical intervention indicated

LLN, lower limit of normal.

Supraventricular and junctional arrhythmias. :

‐ Sinus tachycardia

‐ Atrial premature complexes (APCs)

‐ APCs patterns (atrial bigeminy/trigeminy)

‐ Focal atrial tachycardia

‐ Multi‐focal atrial tachycardia

‐ Atrioventricular tachycardia mediated by accessory pathways (OAVRT [orthodromic atrioventricular reciprocating tachycardia], PJRT [persistent or permanent junctional reciprocating tachycardia])

‐ Atrial flutter

‐ Atrial fibrillation

‐ Atrial parasystole

‐ Junctional premature complexes (JPCs)

‐ Junctional tachycardia

‐ Other (specify, _________)

Bradyarrhythmias.

‐ Sinus bradycardia

‐ Sinus arrest

‐ Sinus node dysfunction (sick sinus syndrome)

‐ Atrial standstill

‐ Sino‐ventricular rhythm

‐ Ventricular asystole/arrest

‐ Pulseless electrical activity; electromechanical dissociation

Conduction abnormality/atrioventricular heart block.

‐ AV block‐first degree

‐ AV block‐second degree Mobitz I

‐ AV block‐second degree Mobitz II

‐ AV block‐second degree (2:1 conduction)

‐ AV block‐second degree (advanced)

‐ AV block‐third degree (complete)

‐ Interventricular conduction disturbance (IVCD)

‐ Bundle branch block (BBB)

‐ Phasic (rate‐dependent) aberrant conduction

‐ Other (specify_________)

Ventricular arrhythmias.

‐ VPCs (ventricular premature complexes)/uniform

‐ VPCs/multiform

‐ VPC patterns (ventricular bigeminy/trigeminy)

‐ Accelerated idioventricular rhythm

‐ Monomorphic ventricular tachycardia

‐ Polymorphic ventricular tachycardia

‐ R on T ventricular tachycardia

‐ Torsade de pointes

‐ Ventricular fibrillation

‐ Ventricular parasystole

‐ Other (specify, ___________)

Dog: <60 bpm

Cat: <140 bpm

Dog: <40 bpm

Cat: <120 bpm

Dog: <30 bpm

Cat: <100 bpm

Dog: <20 bpm

Cat: <80 bpm

Dog: >140 bpm

Cat: >220 bpm

Dog: >180 bpm

Cat: >230 bpm

Dog: >200 bpm

Cat: >240 bpm

Dog: >240 bpm

Cat: >260 bpm

Severe or medically significant but not immediately life‐threatening;

hospitalization or prolongation of existing hospitalization indicated; limiting self care ADL

ULN, upper limit of normal.

ADL, activities of daily living (eating, drinking, sleeping, defecating and urinating; in cats, also includes adequate grooming).

Severe or medically significant but not immediately life‐threatening;

hospitalization or prolongation of existing hospitalization indicated; limiting self care ADL

Pancreatic lipase enzyme elevation;

imaging findings only

Dog: >ULN‐2.5 × ULN

Cat: >ULN‐1.25 × ULN

Dog: >2.5‐5.0 × ULN

Cat: >1.25‐1.5 × ULN

Dog: >5.0‐20 × ULN

Cat: >1.5‐2.0 × ULN

Dog: >20 × ULN

Cat: >2 × ULN

Dog: >ULN‐1.5 × ULN

Cat: >ULN‐1.25 × ULN

Dog: >1.5‐4.0 × ULN

Cat: >1.25‐1.5 × ULN

Dog: >4.0‐10 × ULN

Cat: >1.5‐2.0 × ULN

Dog: >10 × ULN

Cat: >2 × ULN

Ionized dog:

Ionized cat:

<8.0‐7.0 mg/dL

Ionized dog:

<1.1‐1.0 nmol/L

Ionized cat:

<0.9‐0.8 nmol/L

<7.0‐6.0 mg/dL

Ionized dog:

<1.0‐0.9 nmol/L

Ionized cat:

<0.8‐0.7 nmol/L

<6.0 mg/dL

Ionized dog:

<0.9 nmol/L

Ionized cat:

<0.7 nmol/L

>ULN‐<12.0 mg/dL

Ionized: >ULN‐1.5 nmol/L

≥12.0‐13.0 mg/dL

Ionized: >1.5‐1.6 nmol/L, mild clinical signs not requiring immediate intervention

>13.0 mg/dL

Ionized: >1.6‐1.8 nmol/L with clinical signs and/or sequela requiring medical intervention; hospitalization indicated

Dog: >ULN‐160 mg/dL

Cat: >ULN‐200 mg/dL

abnormal glucose above normal with no medical intervention needed

Dog: >160‐250 mg/dL

Cat: >200‐250 mg/dL

Dog: >250‐500 mg/dL

Cat: >250‐500 mg/dL

Dog: >500 mg/dL

Cat: >500 mg/dL

Asymptomatic or mild symptoms; clinical or diagnostic observations only;

intervention not indicated

Pain

Specify site: _____________

Present; medical intervention

Canine

USG <1.030

Feline

USG <1.035

Neoplasms benign, malignant and unspecified (including cysts and polyps)

Other (specify, _________)

Male: oligospermia/low sperm count

Female: diminished fertility/oestrus

Symptomatic;

Invasive intervention indicated (eg, surgical repair, stent, cystoscopy, cystostomy, nephrostomy or peritoneal drainage catheters)

Grade 1	Mild; asymptomatic or mild symptoms; clinical signs or diagnostic observations only; intervention not indicated.
Grade 2	Moderate; outpatient or non‐invasive intervention indicated; moderate limitation of Activities of Daily Living (ADL).
Grade 3	Severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; disabling; significantly limiting Activities of Daily Living (ADL).
Grade 4	Life‐threatening consequences; urgent interventions indicated
Grade 5	Death related to AE Death can be defined as either euthanasia or natural death, according to the investigators' discretion.

ADMINISTRATION SITE CONDITIONS
	Grade
Adverse Event	1	2	3	4	5
Infusion site extravasation/reaction	Swelling including oedema but without erythema or pain	Erythema with associated signs (eg, oedema, pain, swelling induration, phlebitis)	Ulceration or necrosis; severe tissue damage; surgical intervention indicated (such as soft tissue debridement and repair)	Life‐threatening consequences (euthanasia will be performed without intervention), primarily wound that shows no evidence of healing or improvement over 2 weeks; urgent and extreme intervention indicated (such as limb amputation)	Death
Definition: A disorder characterized by leakage of a pharmacologic or a biologic substance from the infusion site into the surrounding tissue. Signs include induration, erythema, swelling and marked discomfort at the infusion site.
Other (specify, _________)	Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated	Moderate; minimal, local or non‐invasive intervention indicated; limiting age appropriate ADL	Severe or medically significant but not immediately life‐threatening; hospitalization or prolongation of existing hospitalization indicated; limiting self care ADL	Life‐threatening consequences; urgent intervention indicated	Death

BODY CAVITY
	Grade
Adverse Event	1	2	3	4	5
Abdominal pain	Mild pain	Moderate pain; limiting ADL	Severe pain; limiting ADL	—	—
Definition: A sensation of marked discomfort in the abdominal region.
Ascites	Clinical or diagnostic observations only; intervention not indicated	Symptomatic; medical intervention indicated	Severe symptoms; invasive intervention indicated	Life‐threatening consequences; urgent operative intervention indicated	Death
Definition: A disorder characterized by accumulation of serous or haemorrhagic fluid in the peritoneal cavity.
Hernia, non‐diaphragmatic	Clinical or diagnostic observation only; intervention not indicated	Reducible, non‐strangulating; elective intervention indicated	Incarcerated, symptomatic; operative intervention indicated	Life‐threatening consequences; strangulating or necrotic; urgent intervention indicated	Death
Definition: Organ or tissue displacement through an opening in muscle or fascia of the body wall, scrotum, or inguinal, femoral or pelvic canals
Hernia, hiatal	Clinical or diagnostic observation only; intervention not indicated	Symptomatic; medical management indicated	Symptomatic; operative intervention indicated	Severe symptoms; urgent intervention indicated	Death
Definition: Displacement of abdominal contents into the thorax through the oesophageal hiatus
Hernia, diaphragmatic	—	Clinical or diagnostic observation with minimal or absent symptoms; incidental finding without recent history of trauma; elective intervention indicated	Symptomatic; operative intervention indicated	Life‐threatening consequences; urgent operative intervention indicated	Death
Definition: Displacement of abdominal contents into the thorax through an abnormal opening in the diaphragm muscle, fascia, or attachments to the body wall.
Peritonitis (septic)	—	Symptomatic; medical management indicated	Hospitalization, IV antimicrobials indicated; invasive intervention indicated (eg, tube feeding, abdominal drainage, surgery)	Life‐threatening consequences including organ system dysfunction; urgent operative intervention indicated	Death
Definition: Focal or generalized inflammation of the peritoneum attributed to microbial contamination.
Peritonitis (non‐septic)	Asymptomatic diagnostic finding; intervention not indicated	Symptomatic; medical management indicated	Hospitalization, invasive intervention indicated (eg, tube feeding, abdominal drainage, surgery)	Life‐threatening consequences including organ system dysfunction; urgent intervention indicated	Death
Definition: Focal of generalized inflammation of the peritoneum attributed to non‐microbial (sterile) aetiologies.
Pleural effusion (non‐malignant)	Asymptomatic	Symptomatic, intervention with diuretics or single thoracocentesis indicated	Symptomatic and supplemental oxygen, >1 thoracocenteses, continuous tube drainage or pleurodesis indicated	Life‐threatening (eg, haemodynamic instability or ventilatory support)	Death
Definition: A disorder characterized by an increase in amounts of fluid within the pleural cavity. Symptoms include shortness of breath, cough and marked chest discomfort.
Pleuritis (septic)	—	Symptomatic; medical management indicated	Hospitalization, IV antimicrobials indicated; invasive intervention indicated (eg, thoracic drainage or lavage, surgery)	Life‐threatening consequences including organ system dysfunction; urgent operative intervention indicated	Death
Definition: Focal or generalized inflammation of the pleural cavity attributed to microbial contamination.
Pneumothorax	Asymptomatic, radiographic findings only	Symptomatic; non‐operative intervention indicated	Sclerosis and/or operative intervention indicated	Life‐threatening, haemodynamic instability; ventilatory support	Death
Definition: A disorder characterized by abnormal presence of air in the pleural cavity resulting in the collapse of the lung.
Other (specify, _________)	Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated	Moderate; minimal, local or non‐invasive intervention indicated; limiting age appropriate ADL	Severe or medically significant but not immediately life‐threatening; hospitalization or prolongation of existing hospitalization indicated; limiting self care ADL	Life‐threatening consequences; urgent intervention indicated	Death

CONSTITUTIONAL CLINICAL SIGNS
	Grade
Adverse Event	1	2	3	4	5
Lethargy/fatigue	Mild lethargy over baseline; diminished activity from pre‐disease level, but able to function as an acceptable pet	Moderate lethargy causing some difficulty with performing ADL; ambulatory only to the point of eating, sleeping, and consistently defecating and urinating in acceptable area; Decreased grooming habits	Compromised, severely restricted in ADL; will ambulate if assisted; unable to confine urinations and defecation to acceptable areas unless assisted; absent grooming habits	Disabled, fully recumbent posture; reliant on urinary catheter and/or bladder expression; has no control over bowel movements	Death
Definition: Disorders characterized by a state of generalized weakness with a pronounced inability to summon sufficient energy to accomplish daily activities.
Fever	39.5‐40.0°C (103.5‐104°F)	>40.0‐40.8°C (>104‐105.5°F)	>40.9‐41.7°C (>105.6‐107.6°F)	>41.8°C (>107.6°F)	Death
Hypothermia	—	36.1‐>34.4°C (97.0‐>94.0°F)	34.4‐>32.2°C (93.9‐>90.0°F)	<32.1°C (<89.9°F) or life‐threatening consequences (eg, coma, hypotension, pulmonary oedema)	Death
Weight loss	>5% but <10% from baseline	10%‐15% from baseline	>15% but <20% of baseline	>20% of baseline	Death
Other (specify, _________)	Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated	Moderate; minimal, local or non‐invasive intervention indicated; limiting age appropriate ADL	Severe or medically significant but not immediately life‐threatening; hospitalization or prolongation of existing hospitalization indicated; limiting self care ADL	Life‐threatening consequences; urgent intervention indicated	Death

DERMATOLOGIC/SKIN
	Grade
Adverse Event	1	2	3	4	5
Alopecia	Transient sparse thinning or denuding of hair at localized site, patchy alopecia (regrows but takes longer than 4 weeks)	Transient generalized thinning of hair coat, generalized alopecia (regrows but takes longer than 4 weeks)	Permanent sparse or generalized thinning of hair at localized site, or permanent patchy or generalized alopecia	—	—
Definition: A disorder characterized by a decrease in density of hair compared to normal for a given individual at a given age and body location.
Bruising (in absence of Grade 3 or 4 thrombocytopenia)	Localized or in a dependent area	Generalized/multi‐focal	—	—	—
Definition: A finding of injury of the soft tissues or bone characterized by leakage of blood into surrounding tissues.
Oedema, limbs	5%‐10% inter‐limb discrepancy in volume or circumference at point of greatest difference; swelling or obscuration of anatomic architecture on close inspection	>10%‐30% inter‐limb discrepancy in volume or circumference at point of greatest difference; readily apparent obscuration of anatomic architecture, deviation from normal anatomic contour	>30% inter‐limb discrepancy in volume; gross deviation from normal anatomic contour; limiting ADL	—	—
Definition: Swelling due to excessive fluid accumulation in the upper or lower extremities.
Oedema, localized	Localized to dependent areas; no disability or functional impairment	Moderate localized oedema; intervention indicated	Severe localized oedema limiting ADL; intervention indicated	—	—
Definition: Swelling due to excessive fluid accumulation at a specific anatomic site.
Erythema	Limited to localized site	Generalized	—	—	—
Definition: Superficial reddening of the skin, usually in patches, as a result of injury or irritation causing dilatation of the blood capillaries.
Erythema multiforme	Target lesions covering <10% BSA and not associated with skin tenderness	Target lesions covering 10%‐30% BSA and associated with skin tenderness	Target lesions covering >30% BSA, or any number of lesions associated with oral or genital erosions	Target lesions covering >30% BSA; associated with fluid or electrolyte abnormalities; ICU care indicated	Death
Definition: A disorder characterized by target lesions (a pink‐red ring around a pale centre).
Hyperpigmentation	Slight or moderate and confined to fewer than 3 sites (localized), or slight generalized changes	Marked localized (<3 sites), or moderate generalized changes (more than 3 sites)	Marked generalized changes	—	—
Hypopigmentation	Slight or moderate and confined to fewer than 3 sites (localized), or slight generalized changes	Marked localized (<3 sites), or moderate generalized changes (more than 3 sites)	Marked generalized changes	—	—
Nail/nailbed/claw changes	Discoloration, pitting, any number of nail(s)/claw(s)	Weakening (friable, breaks easily), no pain or changes in gait, any number of nail(s)/claw(s)	Partial or complete loss of nail(s)/claw(s) on any number of paws/feet; pain; lameness	Partial or complete loss of nail(s)/claw(s) on at least two paws/feet and significantly interfering with ADL—unwilling to ambulate	Nail/nailbed/claw changes that result in a decision for euthanasia
Palmar‐plantar erythrodysesthesia syndrome	Minimal changes or pododermatitis (eg, erythema) without pain	Skin or paw pad changes (eg, peeling/flaking, blisters, bleeding, oedema) or pain, not interfering with function, easily managed medically, resolves significantly within 1 week of drug withdrawal	Skin or paw pad changes that are painful and interfere with function (lameness, excessive licking) and include moist, ulcerative dermatitis, and return to function within 1 week of drug withdrawal	Skin or paw pad changes that are painful, interfere with function and change in function persists longer than 1 week	Skin or paw pad changes that result in a decision for euthanasia
Definition: A disorder characterized by redness, marked discomfort, swelling and possible ulceration of the palmar/plantar surfaces of the paws.
Photosensitivity	Painless erythema	Painful erythema	Erythema with dry desquamation	Erythema with moist desquamation or ulceration, life‐threatening (would result in euthanasia if not treated); disabling	Complications of photosensitivity that result in death or euthanasia
Definition: A disorder characterized by an increase in sensitivity of the skin to light.
Pruritus	Mild or localized, does not result in lesions because of self‐trauma	Moderate or widespread and occurs regularly; may occur at night but not when eating or playing; would result in lesions due to self‐trauma if restraint (e‐collar or covering of affected area) is not used when unsupervised.	Licking or scratching continuously, requires restraint (e‐collar or covering of affected area) at all times to prevent self‐trauma, oral corticosteroid or immunosuppressive therapy usually prescribed unless contraindicated	Severe and prolonged; continues when eating, playing, exercising, limits sleeping and eating; oral corticosteroid or immunosuppressive therapy indicated	—
Definition: A disorder characterized by intense itching.
Purpura	Combined area of lesions covering <10% BSA	Combined area of lesions covering 10%‐30% BSA; bleeding with trauma	Combined area of lesions covering >30% BSA; spontaneous bleeding	—	—
Definition: A disorder characterized by haemorrhagic areas of the skin and mucous membrane. Newer lesions appear reddish in colour. Older lesions are usually a darker purple colour and eventually become a brownish‐yellow colour.
Rash: acne/acneiform	Macules, papules apules and/or pustules covering <10% BSA, which may or may not be associated with symptoms of pruritus or tenderness	Macules, papules apules and/or pustules covering 10%‐30% BSA, which may or may not be associated with symptoms of pruritus or tenderness	Macules, papules apules and/or pustules covering >30% BSA, which may or may not be associated with symptoms of pruritus or tenderness; limiting ADL; associated with local superinfection with oral antibiotics indicated	Macules, papules apules and/or pustules covering any % BSA, which may or may not be associated with symptoms of pruritus or tenderness and are associated with extensive superinfection with IV antibiotics indicated; life‐threatening consequences	Death
Definition: A disorder characterized by an eruption of papules and pustules or a disorder characterized by the presence of macules (flat) and papules (elevated). Also known as morbilliform rash.
Scaling	Fine scaling, noticeable only upon close examination	Scaling easily visible but not exfoliation in clumps; minimal crusting	Easily visible generalized scaling and crusting with generalized exfoliation upon examination	—	—
Definition: A disorder characterized by flaky and dull skin.
Skin atrophy	Covering <10% BSA; associated with telangiectasia or changes in skin colour	Covering 10%‐30% BSA; associated with striae or adnexal structure loss	Covering >30% BSA; associated with ulceration	—	—
Definition: A disorder characterized by the degeneration and thinning of the epidermis and dermis.
Skin ulceration	Non‐blanchable erythema of only superficially eroded intact skin with associated warmth or oedema	Combined area of ulcers ≤2 cm and partial thickness skin loss involving skin or subcutaneous fat	Combined area of ulcers >2 cm with partial thickness skin loss or full‐thickness skin loss (any size) involving damage to or necrosis of subcutaneous tissue that may extend down to fascia	Any size ulcer (full thickness) with extensive destruction, tissue necrosis, or damage to muscle, bone, or supporting structures with or without full thickness skin loss	Death
Definition: A disorder characterized by circumscribed, inflammatory and necrotic erosive lesion on the skin. If depth and size are discrepant, grade is assigned based on depth of ulceration and not size.
Toxic epidermal necrolysis	—	—	—	Skin sloughing covering ≥30% body surface area with associated symptoms (eg, erythema, purpura or epidermal detachment)	Death
Definition: A disorder characterized by greater than 30% total body skin area separation of dermis. The syndrome is thought to be a hypersensitivity complex affecting the skin and the mucous membranes.
Urticaria (hives, welts, wheals)	Transient, resolves without treatment	Some discomfort, Intervention indicated for <48 h	Moderate to marked discomfort, Intervention indicated for >48 h	—	—
Definition: A disorder characterized by a pruritic skin eruption characterized by wheals with pale interiors and well‐defined red margins.
Other (specify, _________)	Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated	Moderate; minimal, local or non‐invasive intervention indicated; limiting age appropriate ADL	Severe or medically significant but not immediately life‐threatening; hospitalization or prolongation of existing hospitalization indicated; limiting self care ADL	Life‐threatening consequences; urgent intervention indicated	Death