Transcript HSVSJS presentation Updated

STEVENS-JOHNSON
SYNDROME AND HERPES
SIMPLEX VIRUS (TYPE 1)
Lindsay Waddington PharmD
PGY-1 Pharmacy Resident
St. Vincent Hospital-Indianapolis
February 16th, 2016
Objectives
• Describe the differences between erythema
multiforme, Steven Johnson Syndrome, and Toxic
Epidermal Necrolysis
• Identify causes of erythema multiforme and
Steven Johnson Syndrome
• Recognize treatment options for erythema
multiforme and Steven Johnson Syndrome
10 Year Old Male Patient (37kg)
• Monday – developed a temperature of 102°F, fatigue, no
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•
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upper respiratory symptoms
Tuesday – Temperature still elevated, mom gives
acyclovir and ibuprofen, symptoms improve
Friday – Still slight fatigue, but overall feeling better (well
enough to attend a weekend camping trip)
Saturday – starts coughing and complains of itchy eyes,
fever returns that night, lips look swollen and eyes are
increasingly red with drainage
Sunday – Temperature of 104°F and lips continuing to
swell
Sunday Night - Presents with fever, rash, and lip swelling
to Peyton Manning Children’s Hospital
Past Medical History
• Herpes simplex virus type-1 starting 2 years ago
• 2 Similar flare ups (not requiring hospitalization)
• July: received lysine and flare resolved
• September: received oral steroids and flare resolved
• Immunizations are up to date
Home Medications and Allergies
• Acyclovir 400mg (~10mg/kg) tablet orally TID
PRN HSV flare
• Ibuprofen 200mg orally (~5mg/kg) 1 tablet orally
every 6 hours
• Drug allergies
• Amoxicillin: dermatologic, sores in mouth, swelling of
mouth and gums
• Sulfamethoxazole/trimethoprim: dermatologic, sores in
mouth, and swelling of the mouth and gums
• Cefdinir: edema/swelling
10 Year Old Male Patient (37kg)
• Notable labs
• WBC 12.1 w/ 1.5 bands
• SCr 0.56
• BUN 12
• Physical exam
• conjunctiva inflamed with thick drainage
• rhinorrhea, sore throat causing poor appetite,
productive cough
• swelling of lips and oropharynx, copious drooling, skin
on lips cracking covered in greyish white membrane
• multiple erythematous macules with purpuric centers on
trunk, back, and upper extremities, non-tender to touch,
blisters
Diagnosis: Stevens-Johnson Syndrome
(SJS)
• Overnight started on
• Prednisolone 3mg/mL oral 75mg daily (2mg/kg)
• Acyclovir IVPB 370mg every 8 hours (10mg/kg)
• Dextrose 5% - 0.45% NS w/ 20mEq K at 76mL/hour
• Ibuprofen intentionally omitted
Team discussion
• Family centered rounding
• Mom believes acyclovir caused the reaction
• Attending is agreeable and wants to discontinue
acyclovir
STEVENS-JOHNSON
SYNDROME
What is Stevens-Johnson Syndrome?
• Early symptoms
• Fever and general malaise
• Cough
• Sore throat
• Itching or burning eyes
• Acute phase lasts 8 to 12 days
• Persistent fever
• Severe mucous membrane involvement
• Epidermal sloughing
Crit Care Med 2011; 39(6): 1521-1532.
Ann Pharmacother. 2015, 49(3)335-342.
Differential Diagnosis
• Erythroderma and erythematous drug eruptions
• Phototoxic eruptions
• Staphylococcal scalded skin syndrome
• Paraneoplastic pemphigus
• Linear IgA bullous dermatosis
• Erythema multiforme
• Stevens-Johnson Syndrome(SJS)
• Toxic Epidermal Necrolysis (TEN)
Drug safety 2002; 25(13):965-972.
Ann Pharmacother. 2015, 49(3)335-342.
Spectrum of Bullous Erythema Multiforme
Bullous Erythema Multiforme
<10% BSA
PLUS
Target lesions
Atypical targets
(raised)
Stevens-Johnson Syndrome
<10% BSA
PLUS
Multiple
macules
Atypical targets
(flat)
Toxic Epidermal Necrolysis
>30% BSA
PLUS
Widespread multiple
macules/atypical
targets OR epidermal
sheets
Drug safety 2002; 25(13):965-972.
Presumed Causes
• Infection
• Herpes Simplex Virus (HSV)
• Mycoplasma pneumonia
• Drugs
• Penicillins
• Sulfonamides
• Allopurinol
• Anticonvulsants
• NSAIDs
• Genetics?
Crit Care Med 2011; 39(6): 1521-1532
Complications
• Fingernail and Toenail loss
• Vision loss
• Permanent pigment changes
• Other infections/Sepsis
• Altered pulmonary function
• Pulmonary edema
• Epithelial necrosis of bronchial epithelium
Crit Care Med 2011; 39(6): 1521-1532
How do we treat EM/SJS?
• Removal of offending agent (if applicable)
• No standard consensus
• Supportive care Pain
• Nutrition
• Fluids
• Steroids
• Acyclovir if infection mediated
• IV Immune globulin (consider for SJS/TEN)
J Am Acad Dermatol. 1988; 18(1): 197-199.
J Am Acad Dermatol. 1986; 15(1): 50-54.
Allergy Asthma Proc. 1996 Mar-Apr;17(2):71-3.
Allergy Proc. 1995 Jul-Aug;16(4):157-61.
Pediatrics. 2003 Dec;112(6 Pt 1):1430-6.
Tatnall et al. Acyclovir in REM
Design
Primary
outcome
Double-blind, placebo controlled RCT
Population
>18yo adult patients who suffered at least 4
episodes of EM/year (excluding pregnancy
Intervention
11 received 6 months of acyclovir 400mg BID
Efficacy of acyclovir in recurrent erythema
multiforme
9 received 6 months of placebo
Findings
15 patients had clinical evidence of HSV
precipitated episodes 6 in placebo and 9 in
acyclovir
EM attacks placebo 3 acyclovir 0 p <0.0005
HSV attacks placebo 1 acyclovir 0 p=0.04
3 patients in the acyclovir group did not respond
to therapy
Brit J Dermatol 1955;132:267-270
Schneck et al. IVIG in SJS and TEN
Design
Primary
outcome
Population
Case-control
Death during hospitalization
Intervention
87 received supportive care
35 received IVIG only
Findings
379 patients with confirmed SJS and/or TEN
40 received IVIG + steroids
119 received steroids only
OR 0.4 steroids vs. no steroids
95% CI 0.2-0.9
Trend for possible benefit with steroids
No statistically significant findings
J Am Acad Dermatol 2008;58:33-40
ADVERSE DRUG
REACTION?
Naranjo Algorithm
Criteria
Previous reports of this reaction?
AMR after drug administered?
Score
DON’T KNOW +0
YES +2
AMR worsened with dose increase or decrease with
discontinuation
NO +0
Reappear when drug re-administered
N/A +0
Potential alternative causes
YES -1
Toxic levels of drug
Similar reaction previously
DON’T KNOW +0
YES +1
Objective evidence confirming AMR?
TOTAL
1-4 POSSIBLE Adverse Medication Reaction
NO +0
2
RECOMMENDATION
Recommendation
• Continue on acyclovir, steroids, and fluids
• Acyclovir most likely a confounder
• RCT and case reports of acyclovir treating REM
• Received acyclovir previously with no reported issues
• Case reports of HSV induced REM
• Potential alternatives to acyclovir
• Avoid IVIG unless develops into SJS or TEN then
reevaluate
• Monotherapy with steroids
Clinical Course
• Managed pain with acetaminophen and morphine
• Avoided ibuprofen
• Steroids methylprednisolone IV 37mg (1mg/kg)
Q12
• Maintenance IVF (D5-1/2NS +20meq K)
• Acyclovir IVPB 370mg every 8 hours (10mg/kg)
• Ophthalmology consult – no acute vision changes
follow up outpatient
• Philadelphia mouthwash 5mL swish and swallow
PRN
Clinical Course
• Diagnosis changed from SJS to Erythema
Multiforme
• Desaturated overnight with respiratory symptoms
(required oxygen), negative chest X-ray
• Rash began blistering, no new lesions appeared
• Continued/increased eye itching and irritation; no
visual deficiencies
• Mucosal inflammation stable to slightly improved
• Discharghed home
Take Aways
• Erythema multiforme, Stevens Johnson
Syndrome, and Toxic Epidermal Necrolysis have
similar presentations with increasing severity
• Drugs most likely to cause SJS are sulfa
antibiotics, NSAIDs, anticonvulsants, penicillin
antibiotics, and allopurinol
• Treatment of SJS consists of steroids +/- IVIG
• Herpes simplex virus has been associated with
recurrent erythema multiforme
STEVENS-JOHNSON
SYNDROME AND HERPES
SIMPLEX VIRUS (TYPE 1)
Lindsay Waddington PharmD
PGY-1 Pharmacy Resident
St. Vincent Hospital-Indianapolis
February 16th, 2016