Case Management

Adajar, Antonio, Balanag

Block 1
General Data
EDC, 65/F Filipino, Mormon,
Married, from Cavite

CC: Generalized rashes of 3 days

duration
Patient’s History
History of Present Illness
1 month PTA, labs done for clearance revealed hyperuricemia
● Atorvastatin 40 mg/tab 1 tab OD
● Metformin 500 mg/tab 1 tab TID
● Allopurinol 300 mg/tab, 1 tab OD

5 days PTA,
(+) intermittent fever (T > 38.0 C) - relieved by Paracetamol
(+) fatigue
(+) anorexia
(+) polyuria
(-) cough (-) colds (-) abdominal pain (-) dysuria
History of Present Illness
3 days PTA,
● rash - generalized, erythematous and pruritic macules
● (+) eye tearing with purulent yellowish discharge
● (+)lip swelling
● (+)odynophagia.
Consulted at LH, CBC and UA done
A> UTI and an allergic reaction

Prescribed with
● Acyclovir 400 mg/tab
● Ciprofloxacin 500 mg/tab
● Tobramycin
● Dexamethasone
History of Present Illness
In the interim
● Noted progression and spreading of the lesions
● Oral mucosa involvement and swelling of the lips
● Increased eye tearing, now accompanied with blurring of vision noted.
● Desquamation of the lesions were noted, associated with severe pain.
History of Present Illness
Patient sought consult to multiple nearby health institutions but due to unavailability
of rooms, they were not able to be accomodated. At the last hospital, patient was
started on an IVF, and was referred to PGH as THOC, hence admission.
Review of Systems
CVS (-) chest pain (-) PND (-) orthopnea (-)easy fatigability

Respi (-) cough (-)dyspnea (-) hemoptysis

Endo (-) polydipsia (-)polyuria (-)polyphagia

GIT (-) dysphagia (-)abdominal pain (-)BM changes (-) food intolerance

GUT (-) dysuria (-)hematuria (-)frothy urine (-)oliguria/anuria

MSK (-) muscle or joint pains (-)jaundice (-)cyanosis

Hema (-) easy bruisability (-) bleeding

Neuro/Psych (-) headache (-)dizziness (-)seizures (-) hallucinations/delusions

Past Medical History
● s/p L CVD infarct with right-sided residuals (2006)
○ maintained on Aspirin (discontinued 5 yrs ago by local doctor)
● PTB (~2009)
○ Around 10 years ago, completed 6 months treatment
● Hypertension (2012)
○ Maintained on Amlodipine 5mg OD, Metoprolol 15 mg OD
● Type II DM (2012)
○ Maintained on Metformin 500mg TID
Past Medical History

● No previous similar symptoms, no known food or drug allergy

● No prior radiation exposure or blood transfusions

● No history of herbal medications

Timeline of Medicine Intake
Sept 9 Sept 11
2009 2014 2018 July 2017
(5 days PTA) (3 days PTA)

HRZE

Aspirin
Amlodipine
Metropolol
Metformin
Atorvastatin
Allopurinol
Paracetamol
Acyclovir
Ciprofloxacin
Tobramycin
Dexamethasone
Family Medical History
● (+) T2DM, Hypertension - mother, father
● (+) Goiter - mother
● (-) CVD, asthma, cancer
● (-) History of hypersensitivity to drugs/substances
Obstetric & Menstrual History
● G6P5(5014), no history of fetomaternal complications
● Menopause at age 50
Personal/Social History
● Non-smoker, non-alcoholic beverage drinker, denies illicit drug use (NOTE:
Patient is a Mormon)

● Claims to have had only one sexual partner, monogamous/non-promiscuous

● Previously worked as a food vendor until she suffered a stroke 13 years ago

● Currently bedridden and is assisted on her ADLs

 Key Findings in the History
● Adult female
● Fever
● Generalized Rash - erythematous, pruritic, w/ progression,
desquamation
● Eye tearing w/ discharge
● Lip swelling, odynophagia
● No previous episodes of a similar event
● Multiple medications
● Possible immunocompromised state (T2DM)
Questions to ask in the history:
1. Characteristic of the initial rash → what do they look like?

2. Distribution and pattern of spread of initial rash → how did they progress?

3. Sexual history
Differential Diagnoses
Differentials for Fever and Rash
Too many to mention . . .
Considerations
● Acute

● Progressive, desquamating skin lesions

● Systemic symptoms
Considerations:
● Drug-induced
○ Culprits: Allopurinol, Atorvastatin

● Autoimmune

● Immunocompromised
Differential Diagnoses
AUTOIMMUNE or POST-INFECTIOUS DISORDERS:

1. Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis

OR

Erythema Multiforme Majus (Fuch’s Syndrome)

2. Exfoliative Erythroderma
3. Drug-induced hypersensitivity syndrome
4. Systemic Lupus Erythematosus
Top Differential Diagnoses
FOR
Stevens-Johnson Syndrome
Toxic Epidermal Necrolysis
Erythema Multiforme Majus
(Fuch’s Syndrome)
AGAINST
● Fever
● Adult Female
● Erythematous rash, w/
spreading, progression, and
desquamation
● Eye and oral mucosa
involvement
● Drug intake involvement
● Fever
● Adult Female
● Erythematous rash, w/
spreading, progression, and
desquamation
● Eye and oral mucosa
involvement
● Drug intake involvement
● Possible
Immunocompromised state
Other Differential Diagnoses
FOR
Exfoliative Erythroderma ● Fever
● Adult Female
● Generalized erythema,
w/ desquamation
● Drug-intake involvement
Drug-Induced ● Fever
Hypersensitivity Syndrome ● Erythematous rash, w/
(DRESS) spreading to extremities
● Drug intake involvement
AGAINST
● Eye and oral mucosa
involvement
● No significant swelling of
face and extremities
● Prominent
desquamation of lesions
● Eye and oral mucosa
involvement
Differential Diagnoses
FOR AGAINST

Staphylococcal Scalded ● Fever ● Adult Female

Skin Syndrome ● Diffuse central erythema ●
spreading to extremities
● Prominent
desquamation of lesions
● Conjunctival
involvement
● Possible
immunocompromised
state

Systemic Lupus ● Fever ● Prominent

Erythematosus ● Adult female desquamation of lesions
● Erythematous rash ● No significant swelling of
● Mucosal involvement face and extremities
● No joint or MSK pains
WHICH ONE IS IT?
Physical Examination
Systemic Physical Examination
Awake, alert, not in cardiorespiratory distress

BP 144/69 HR 81 bpm RR 15 cpm T 36.7

Anicteric sclera, pink palpebral conjunctiva, (+) hyperpigmented plaques on the oral surrounding and
other areas of the face (+)blisters on the vermilion of upper and lower lip (+) blisters at tongue and
buccal mucosa (-)CLADS/ANM/NVE

Equal chest expansion, clear breath sounds, (-)crackles/wheezes/rhonchi

Adynamic precordium, distinct heart sounds, normal rate and regular rhythm, (-)murmurs/heaves/thrills

Full equal pulses, brisk capillary refill

Eye Physical Examination
VA not assessed

Pupil size is 3mm and equally briskly reactive to light on both eyes. (+) eye
redness, (+) matting of eyelashes, (+) mucoid discharge

EOMs intact

Both eyes are soft upon digital tonometry

On fundoscopy, OD: partial ROR, hazy media OS: (+)ROR, hazy media. No noted
hemorrhages or exudates.
Dermatology Physical Examination
HEAD AND NECK:

● Multiple erythematous to brownish macules

and coalescing patches
● Distributed on the forehead, neck, nasolabial
folds, labial, and mental areas.
● There is epithelial desquamation of the upper
and lower lips with associated crusting.
Dermatology Physical Examination
BODY:

● Multiple
erythematous to
brownish macules
and patches 1 x 1 cm
in size
● Distributed to the
arms, legs, chest
and abdomen
● With associated
desquamation of the
epithelium.
Gynecologic Physical Examination
● External genitalia: Normal external genitalia (+) hyperpigmented tender
patches (-) masses (-) discharge

● Speculum: Smooth vagina and cervix (-) mass (-) dicharge (-) bleeding

● IE: (+) hyperpigmented tender patches on labia majora, smooth pink vagina,
cervix 2x2 cm, small carpus, bilateral parametria smooth and pliable
Body Map
● Extent of skin
erythema (in pink) =
30-40% body surface
area (BSA)

● Extent of epidermal
detachment (in red) =
10-15% BSA
 FOR AGAINST

Toxic Epidermal Necrolysis ● History of Fever ● (-) CLADs

● Adult Female
● Multiple erythematous to
brownish macules on body
and face
● Desquamation and crusting
● (+) Bullae & Blisters
● Eye and oral mucosa
involvement
● Body > Extremities
● 30 - 40% of BSA
● Drug intake involvement

Erythema Multiforme Majus (Fuch’s
Syndrome)
● History of Fever
● Adult Female
● Desquamation and crusting
● Eye and oral mucosa
involvement
● (-) CLADs
● Drug intake involvement
● Possible Immunocompromised
state
● (+) Bullae & Blisters
● Multiple erythematous to
brownish macules on body
and face (TARGETOID IN
EMM)
● Body > Extremities
(OPPOSITE IN EMM)
● 30 - 40% of BSA

Exfoliative Erythroderma
Drug-Induced Hypersensitivity
Syndrome (DRESS)
FOR
● History of Fever
● Adult Female
● Drug-intake involvement
● History of Fever
● Multiple erythematous to
brownish macules on body and
face
● Drug intake involvement
AGAINST
● Multiple erythematous to
brownish macules on body and
face
● (+) Bullae & Blisters
● Not simply generalized
erythema
● Eye and oral mucosa
involvement
● 30 - 40% of BSA
● Bullae & Blisters
● Non-morbilliform appearance of
lesions
● No significant swelling of face
and extremities
● Prominent desquamation of
lesions
● Eye and oral mucosa
involvement
● 30 - 40% of BSA
 FOR AGAINST

Staphylococcal Scalded Skin ● History of Fever ● Adult Female

Syndrome ● Diffuse central erythema spreading ● Multiple erythematous to
to extremities brownish macules on body and
● Prominent desquamation of face
lesions ● 30 - 40% BSA
● Conjunctival involvement
● Possible immunocompromised
state
● (+) Bullae & Blisters

Systemic Lupus Erythematosus ● History of Fever ● (+) Bullae & Blisters

● Adult female ● No malar or discoid rashes
● Erythematous rash ● Prominent desquamation of
lesions
● No significant swelling of face
and extremities
● No joint or MSK pains
● 30 - 40% of BSA
Primary Working Impression
Drug-induced reaction, likely:

Toxic Epidermal Necrolysis

Secondary to Allopurinol use

Diagnostics
Laboratory Tests

Lab Test Purpose Expected FIndings

Arterial Blood Gas To evaluate oxygenation HCO3 < 20mM -> poor
and predict prognosis prognosis
Respiratory alkalosis

Blood chemistry Imbalances caused by fluid Electrolyte imbalance,

loss. hypoalbuminemia,
BUM can be a marker of hypoprotenemia, mild and
severity transient renal insufficiency
and prerenal azotemia.

ESR/CRP May be elevated

Laboratory Tests

Lab Test Purpose Expected FIndings

CBC Anemia, mild leukocytosis

and thrombocytopenia

Hepatic enzymes and No impact on prognosis Slightly elevated

amylase

FBS Predict severity May lead to hyperglycemia

and occasionally overt
diabetes
Blood glucose >14mM ->
severe
Other labs to order:
● PT/PTT
● Blood CS
● Urine GS/CS
● Xray
● Skin biopsy
Laboratory Results
Serum Chemistry (09/14)

Result Result

RBS 18.8 H Mg 0.91

BUN 18.3 H Phos 1.03

Crea 119 H Alb 36

Na 132 L AST 31

K 4.7 ALT 27

Cl 93 L

Ca 2.26
Laboratory Results
CBC (09/16)

Result Result

WBC 6.30 RDW 113.7

RBC 4.04 PC 429

Hgb 118 L N 0.81 H

Hct 0.36 L L 0.08 L

MCV 89.3 M 0.11 H

MCH 29.2 E 0.00

MCHC 327 B 0.00

Laboratory Results
Urinalysis (9/14)
Result Result

Color Nitrite Negative

Transparency Hazy Leucocytes 1

Bilirubin Negative Specific Gravity 1.016

Urobilinogen Normal RBC 1

Ketone Trace WBC 26

Glucose +2 Epithelial Cells 0

Albumin +1 Bacteria 321

Blood +2 Mucus Thread 3

pH 5.0
Lab Results
Coag: PT 12.6|13.4|91%|1.06 PTT 30.38| 22.2

ABG: FiO2 21% pH 7.395 pCO2 23.2 pO2 83.7 HCO3 14.4 BE-8.2 O2St 96.7

● Normal Anion Gap, Metabolic Acidosis. Primary Metabolic Acidosis with

Secondary Respiratory Alkalosis

FBS/LP FBS 15.8 Chol 130mg/dL HDL 27.80 mg/dL LDL 72.38 mg/dL
TG 152.21 mg/dL VLDL 30.12 mg/dL

HbA1c: 8.8%
Lab Results

Punch biopsy: Site - Abdomen

● Gross: Cylindrical skin segment measuring 0.4x0.4x0.4 cm;

● Microscopic: Sections show necrotic keratinocytes at the

epidermis and vacuolar interface changes, with intraepidermal
splitting
 DISCUSSION:
Stevens-Johnson Syndrome &
Toxic Epidermal Necrolysis
Stevens-Johnson Syndrome
Toxic Epidermal Necrolysis
Acute

Life-threatening

Mucocutaneous reactions

Extensive detachment of epidermis and mucosal epithelium

Common Drugs Associated to EN
HIGH RISK LOW RISK

● Allopurinol ● Aminopenicillins
● Aromatic Anti-Epileptics ● Cephalosporins
● Sulfa Drugs ● Fluoroquinolones
● Oxicam NSAIDs ● Macrolides
● Nevirapine
Spectrum of SJS & TEN

Morales-Conde, Macarena, López-Ibáñez, Natividad, Calvete-Candenas, Julio, & Mendonça, Francisco Manuel Ildefonso. (2019). Fulvestrant-induced toxic
epidermal necrolysis. Anais Brasileiros de Dermatologia, 94(2), 218-220. Epub May 09, 2019.https://dx.doi.org/10.1590/abd1806-4841.20197964
Proposed pathogenic mechanisms in toxic epidermal necrolysis

Morales-Conde, Macarena, López-Ibáñez, Natividad, Calvete-Candenas, Julio, & Mendonça, Francisco Manuel Ildefonso. (2019). Fulvestrant-induced toxic
epidermal necrolysis. Anais Brasileiros de Dermatologia, 94(2), 218-220. Epub May 09, 2019.https://dx.doi.org/10.1590/abd1806-4841.20197964
M. Ueta, H. Sawai, C. Sotozono C, et al., 2015, J Allergy Clin Immunol, 135, p. 1538e1545. Copyright 2015
Cutaneous Presentation
EARLY RASH FULL-BLOWN LESIONS

Irregular erythematous
macules/target lesions start on
face, thorax, spread symmetrically
Histopathology

● Multiple apoptotic keratinocytes

throughout the full thickness of the
epidermis
● Subepidermal split forming a bulla
● Perivascular lymphocytic inflitrate
Other Signs & Symptoms
PRODROMAL ADVANCED

● Sore throat Mucous membrane involvement → Painful oral,

● Runny nose ocular, genital, nasal, anal, and
● Cough tracheal/bronchial mucosa
● Fever
● malaise ● dysphagia,odynophagia
● Photophobia,conjunctivitis, corneal
ulceration, uveitis
● Dysuria
● Interstitial lesions → ARDS
● Renal involvement - proteinuria,
hematuria, azotemia
Factors for Poor Prognosis
● Older Age
● Greater BSA involvement
● Gastrointestinal tract involvement
● Respiratory tract involvement
● Neutropenia
SCORTEN:
A Prognostic Scoring
System for Patients
with Epidermal
Necrolysis
Complications
● Sepsis
● Dehydration

Sequelae
● Ophthalmic - fibrosis, alterations of visions
● Nails - dystrophy, permanent anonychia
● Oral Mucosa - dryness, dysgeusia
● Vulvar/ Vaginal - dyspareunia, vaginal dryness, genital adhesiosn
● Other - strictures of the esophagus, intestines, urethra, and anus
U.K. Guidelines for the management of
Steven-Johnson Syndrome/Toxic Epidermal
Necrolysis in adults 2016
Initial Approach to the Patient
● Detailed history
○ Prodromal illness
○ Rash characteristis
○ Respiratory tract symptoms
○ Bowel movement
○ Index date
Initial Management and Supportive Care
● Discontinuation of the offending drug
● Inpatient care settings:
○ >10 % BSA: admit to ICU or Burn center
○ Should be managed by a team of physicians which include dermatologists/plastic surgeon and
internal medicine
○ Barrier-nursed in a room with controlled humidity, on a pressure-relieving mattress and temp
bet 25C - 28C
● Management Regimen
○ Limit trauma and avoid nosocomial infections
○ Conservative management: regular cleansing with chlorhexidine, apply greasy emollient,
topical antimicrobials, non adherent dressing
○ Surgical approach: remove necrotic/loose infected epidermis, debridement, physiologic
cl0sure (allograft/xenograft)
Initial Management and Supportive Care
● Fluid replacement
● Nutrition Regimen
○ Oral or nasogastric
○ 20-25 kcal/kg in the early, catabolic phase
○ 25-30 kcal/kg in the anabolic, recovery phase
● Analgesia
○ Mild pain: Acetaminophen
○ Moderate or severe: Opioids (morphine or fentanyl)
● Additional supportive medication
○ LMW Heparin: prophylaxis against venous thromboemolism
○ PPIs:: upper GI stress ulceration
○ Recombinant human G-CSF: neutropenia
Treatment of Eye Involvement
● Lubricant (nonpreserved hyaluronate or carmellose eye drops) Q30 minutes
● Ocular hygiene
○ Daily
○ Saline irrigation
○ Squint hook and forceps or scissors
● Establish moisture chamber
○ Polyethylene film or paper tape
● Topical antibiotic
○ Prophylaxis or treatment of corneal infection
○ (+) corneal fluorescein staining or frank ulceration
● Topical corticosteroid drops
● Amniotic Membrance Transplantation
Treatment of Mouth involvement
● Soft paraffin ointment for the lips
● Mucoprotectant mouth wash
● Warm saline mouthwash or oral sponge
● Benzydamine hydrochloride or topical anaesthetic (viscous lidocaine 2%) or
Cocaine mouthwash
● Antiseptic oral rinse
○ 1.5% hydrogen peroxide or 0.2% chlorhexidine digluconate mouthwash
● Topical corticosteroids QID
○ Betamethasone sodium phosphate
○ Clobetasol prpionate 0.05%
Treatment of Urogenital Tract Involvement
● Soft paraffin ointment
● Mepitel dressings
● Topical corticosteroid ointment
● FIC
Treatment of Airway Involvement
● Mechanical Ventilation
○ Respiratory symptoms and hypoxemia
● Fiberoptic bronchoscopy
○ Identify bronchial involvement
○ Evaluate prognosis
○ Investigate presence of pneumonitis by bacterial sampling
● Bronchoscopy
○ Mechanical removal of sloughed bronchial epithelium
● Close monitoring
○ Pulmonary function tests
○ HRCT
Active Therapy
● Intravenous immunoglobulin
○ Conflicting data
○ Huang et al: adults receiving high dose IVIg has lower mortality than those receiving low dose
IVIg
○ Firoz et al: no improved survival in patients receiving IVIg vs. supportive care alone
● Systemic corticosteroid
○ Inhibits inflammation but may increase risk of sepsis
○ Studies by Kardaun and Jonkman, and Hirahara showed decrease in mortality in patients
treated with corticosteroids
● Ciclosporin
○ Inhibition of lymphocyte function
○ Four cohort studies meet the inclusion criteria
■ Valeyrie-Allanore et al: decreased mortality
■ Singh et al: enhanced rate of epithelialization
References
● D. Creamer, S.A. Walsh, P. Dziewulski, L.S. Exton, H.Y. Lee, J.K.G. Dart, J. Setterfield, C.B. Bunker, M.R.
Ardern-Jones, K.M.T. Watson, G.A.E. Wong, M. Philippidou, A. Vercueil, R.V. Martin, G. Williams, M. Shah, D.
Brown, P. Williams, M.F. Mohd Mustapa, C.H. Smith. U.K. guidelines for the management of Stevens-Johnson
syndrome/toxic epidermal necrolysis in adults 2016. . British Journal of Dermatology, June 2016.
● Jameson, Fauci, Kasper, Hauser, Longo, Loscalzo. Harrison’s Principles of Internal Medicine (20th ed.). McGraw-Hill
Education.
● Fitzpatrick, T., & Goldsmith, L. (2012). Fitzpatrick's dermatology in general medicine. New York: McGraw-Hill Medical.
● Watanabe R, Watanabe, H, Sotozono C, Kokaze A, Iijima M. Critical factors differentiating erythema multiforme
majus from Stevens-Johnson syndrome (SJS/Toxic Epidermal NEcrolysis (TEN). European Journal of Dermatology
2011; 21(6): 889-94