Download SJS and TEN : Prevention, treatment and prognosis

SJS and TEN : Prevention, treatment
and prognosis
Eun-So Lee
Department of Dermatology, Ajou University School of Medicine
Contents
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Early evaluation of severity
Supportive Management
Topical Treatment
Specific Treatment
Prevention
Prognosis and Clinical Course
Early Evaluation of Severity
Bastuji-Garin S, Fouchard N, Bertocchi M, Roujeau JC, Revuz J, Wolkenstein P. SCORTEN: a severity-of-illness score
for toxic epidermal necrolysis. J Invest Dermatol 2000;115:149-53.
SCORTEN: A Prognostic Scoring System for
Patients with Toxic Epidermal Necrolysis
Guegan S, Bastuji-Garin S, Poszepczynska-Guigne E, Roujeau JC, Revuz J. Performance of the SCORTEN during the
first five days of hospitalization to predict the prognosis of epidermal necrolysis. J Invest Dermatol 2006;126:272-6.
Supportive Management
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The main principles are the same as for major
burns.
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Maintenance of fluid and electrolyte balance
Anti-infectious therapy
Nutritional support
Warming of environmental temperature
Skin care with appropriate dressings
Supportive Management
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Air-fluidized bed
Analgesia
Maintain fluid and electrolyte balance (replace up to 5 L/day)
Maintain body temperature
Maintain nutrition; oral hygiene
Frequent ophthalmological assessment
Disrupt synechiae frequently
Limitation of infection
Neutropenia: reverse barrier nursing
Frequent cultures of erosions, and blood cultures
Culture tips of Foley catheters and intravenous lines
Prophylactic broad-spectrum systemic antibiotics
(controversial)
Breathnach S. Stevens–Johnson syndrome and toxic epidermal necrolysis. In: Burns T, Breathnach S, Cox N, Griffiths
C, editors. Rook's Textbook of Dermatology. 8th ed. West Sussex, U.K.: Blackwell Publishing; 2010. p. 76.8-.22.
Topical Treatment
To prevent infection and further damage to viable
subepidermal tissue
 The blisters should be left in place or only be punctured.
 Biological or synthetic dressings → eroded areas
 Silver nitrate impregnated dressings → recommended
 Trauma(adhesive dressings or ECG electrode attachment
pads) → minimized.
 Frequent dressing changes with topical antimicrobial
ointments or solutions → not recommended
Topical Treatment
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Antiseptic/antibiotic eye drops 2-hourly
Topical cleansing/antibacterial agents
0.5% silver nitrate solution on gauze or 10% chlorhexidine
gluconate washes or saline washes or polymixin/bacitracin
or 2% mupirocin
Avoid silver sulfadiazine
Wound care
Remove necrotic epidermis (controversial)
Paraffin gauze or hydrogel dressings
Biological dressings (xenografts, allografts, skin substitutes)
For affected mucosal areas
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Overlooked mucosal lesions can lead to life-long sequelae.
Disinfectant mouth wash → oral erosions
Mild ointment → erosions and bloody crusts of the lips
Regular ophthalmologic consultation is crucial in the case
of eye involvement.
Specialized lid care daily basis
Anti-inflammatory eye drops → several times per day
Regular vaginal examination
Wet dressings or sitz baths → to avoid adhesions or
strictures of genital erosions in women
Topical Treatment
Edwards K, Stokes H, Suttle K, Potts C, Coles K. Topical treatment protocol for Stevens-Johnson syndrome and
toxic epidermal necrolysis. J Wound Ostomy Continence Nurs 2009;36:330-4.
Specific Treatment
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Corticosteroids
Cyclosporin A
Plasmapheresis
Anti–tumor necrosis factor agents
Intravenous immunoglobulin
Corticosteroids
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The use of systemic corticosteroids is still controversial.
Corticosteroids given 48 hours or more prior to
admission are associated with
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Increased rate of infections
Risk of masking septicemia
Delay of re-epithelialization
Prolonged duration of hospitalization
Higher mortality
Steroid pulse therapy (e.g., with dexamethasone) has
been proposed in the acute stage of SJS/TEN
Not recommended as the mainstay treatment of TEN
Cyclosporin A
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Activation of T helper 2 cytokines
Inhibition of CD8+ cytotoxic mechanisms
Anti-apoptotic effect through inhibition of Fas-L, nuclear
factor B, and TNF- alpha
Prospective studies are needed to confirm its benefits and
the absence of significant adverse effects.
Plasmapheresis
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To prompt the removal of the offending medication, its
metabolites, or inflammatory mediators
Beneficial use of plasmapheresis has been questioned.
Anti–Tumor Necrosis Factor Agents
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Anti-TNF-α antibodies : single case reports
Thalidomide : randomized controlled trial interrupted due
to significantly increased mortality
Pentoxifylline : a few patients
Intravenous Immunoglobulin
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Potential Fas (CD95)-mediated keratinocyte death in TEN
might be blocked by naturally occurring Fas-blocking
antibodies included in human immunoglobulin
preparations.
Fas-mediated cell death can be abrogated by the anti-Fas
activity present in commercial batches of normal human
immunoglobulins.
Tha-In T, Bayry J, Metselaar HJ, Kaveri SV, Kwekkeboom J. Modulation of the cellular immune system by
intravenous immunoglobulin.Trends Immunol 2008;29:608-15.
Summary of Studies Concerning IVIG for
TEN
Analysis of studies published, suggests that total IVIG doses of more
than 2 g/kg may be of greater benefit than doses of 2 g/Kg or less .
Harr T, French LE. Toxic epidermal necrolysis and Stevens-Johnson syndrome. Orphanet J Rare Dis 2010;5:39.
Comparisons of Clinical and Therapeutic Parameters
Between Low-dose Group and High-dose Group in
The Adult Patients
Huang YC, Li YC, Chen TJ. The efficacy of intravenous immunoglobulin for the treatment of toxic epidermal
necrolysis: A systematic review and meta-analysis. Br J Dermatol 2012.
Comparisons of Clinical and Therapeutic
Parameters Between Child Group and Adult Group
Huang YC, Li YC, Chen TJ. The efficacy of intravenous immunoglobulin for the treatment of toxic epidermal
necrolysis: A systematic review and meta-analysis. Br J Dermatol 2012.
SJS/TEN Patients Admitted at Our
Department During 2002-2012
Total number of patients
Male : Female
Age (years), mean ± SD
26
8:18
45.6 ± 18.5
Treatment
Steroid
20
Cyclosporine + steroid
2
IVIG + Steroid
1
Patient characteristics admitted at our
department during 2002-2012
Total number of patients
Male : Female
Age (year, mean ±
SD)
Treatment
Steroid
Cyclosporine + steroid
IVIG + Steroid
26
8:18
45.6 ± 18.5
20
2
1
List of Causative Medications
Medication
Antibiotics
N
8
NSAIDs
URI or ENT
Ophthalmologic
7
6
4
Musculoskeletal related
Herbal medicine
Immunoglobulin
3
2
2
Anticonvulsants
Hormone
Neuralgia
1
1
1
Vitamin
Placenta product
Herbicide
Unknown
1
1
1
2
Period From the First Symptom
Development Until Hospital Visit
2 cases
0-1 days
2-5 days
15 cases
6-15 days
9 cases
16 and more days
0 cases
0
2
4
6
8
10
12
14
16
Length of Hospital Stay of Patients
With TEN/SJS
1-9 days
16 cases
10-19 days
7 cases
20 and more days
3 cases
0
2
4
6
8
10
12
14
16
18
Case Summary
F/61, duration: 7-10 days
 3 weeks prior to admission: herbal medicine, 10 days
prior to admission: URI medication
 Steroid therapy for 10 days → extended more than BSA
30% → IVIG (1 mg/kg) for 5 days → much improved with
epithelization → drowsy mental status, dyspnea,
leukopenia, metabolic acidosis, bactriuria developed →
IVIG stop → transfer to PIMD → sepsis (blood culture :
MSSA) diagnosed → ICU care with cephalosporin,
vancomycin → improved
Prevention
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Evaluate drug causality
All exposures to medications in the few weeks prior to the onset of
the reaction → identification approx. 70 %
A detailed drug history
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Duration of treatment before onset (typically 4 to 30 days)
Absence of prior intake
Use of a drug known for being associated with a high risk
In vitro tests or patch tests to medications occasionally can be
useful
Re-challenge and intradermal testing with the culprit drugs → risk
of re-inducing a second episode of SJS/TEN
Patients should be advised to avoid re-exposure to the suspect
drug(s).
No rationale to restrict the use of all classes of ‘high-risk drugs’
Spontaneous Adverse Event Reports of Stevens–Johnson
Syndrome/Toxic Epidermal Necrolysis: Detecting Associations
with Medications
Pharmacoepidemiology and drug safety 2012; 21: 289–296
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Fifty drugs were identified as
being associated with SJS/TEN.
This included 12 “highly
suspect” drugs and 36
“suspect” drugs.
Meloxicam was the only drug
that appeared on the “highly
suspect” list from EuroSCAR
that did not show a
disproportional increase in
relative reporting frequency
(EB05 = 0.734).
In addition, several drugs did
not have an association with
SJS/TEN (EB05<2).
Drugs Reported as Causing Erythema
Multiforme or SJS or TEN
Pharmacogenetic screening
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Abacavir: HLA-B*5701 allele (OR117; 95% CI 29–481)
Allopurinol : HLAB*5801 allele in South-East Asian
populations7 (OR 348.3; 95% CI 19.2–6336.9), but less so
in Europeans
Carbamazepine: HLA-B*1502 in South-East Asians of Han
Chinese descent, Asian countries including Malaysia,
Thailand and India
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estimated incidence of SJS ⁄TEN is 1–6 cases per 10 000 new
users in countries of mainly Caucasian populations, but the risk
in some Asian countries is estimated to be about 10 times
higher
Wu K, Reynolds NJ. Pharmacogenetic screening to prevent carbamazepine-induced toxic epidermal necrolysis
and Stevens-Johnson syndrome: a critical appraisal. Br J Dermatol 2012;166:7-11; discussion -4.
Prognosis and Clinical Course
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Epidermal detachment progresses for 5 to 7 days → a
plateau phase → progressive re-epithelialization for a few
days to several weeks
During this period, life-threatening complications such as
sepsis or systemic organ failure may occur.
Average reported mortality rate : SJS 1-5%, TEN 25-35%
More than 50% of patients : long-term sequelae
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Symblepharon, conjunctival synechiae, entropion, ingrowth of
eyelashes, cutaneous scarring, irregular pigmentation, eruptive
nevi, and persistent erosions of the mucous membranes,
phimosis, vaginal synechiae, nail dystrophy, and diffuse hair loss
Conclusion
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No specific treatment has been identified to be
capable of stopping the progression of skin
detachment.
Interdisciplinary care and follow-up of patients with
SJS/TEN is important.