1	Bextra & Stevens Johnson Syndrome
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3	Stevens Johnson Syndrome (SJS) Sever exfoliative disorder with superficial sloughing of skin and mucosa Involves skin and mucous membranes (i.e. oral, nasal, eye, vaginal, urethral, GI and respiratory tract). GI and respiratory involvement may progress to necrosis SJS is a serious systemic disorder with potential for severe morbidity and even death
4	SJS -- General Immune complex hypersensitivity disorder Caused by drugs, viral infections and malignancies Often times no specific etiology can be identified
5	SJS -- Causes Four etiologic categories: 1. infectious 2. drug-induced 3. malignancy related 4. idiopathic Drugs and malignancies are most often implicated 2/3 of SJS patients had previously been prescribed sulfa, phenytoin or penicillin ½ of SJS patients have recent history of URI
6	SJS -- Clinical Presentation 1-14 day prodrome: fever, sore throat, chills, headache, malaise Abrupt development of mucocutaneous lesions Outbreak clusters may continue 2-4 weeks Oral mucosal involvement may make eating and drinking difficult & genitourinary involvement may lead to dysuria
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8	Toxic Epidermal Necrolysis TENS Severe mucocutaneous exfoliative disease Distinction between SJS cloudy Leaves a denuded dermal surface -- epidermis comes off in sheets with close to total body involvement Mortality rate as high as 40%
9	SJS/TENS -- Work Up No lab work significantly helpful Skin Biopsy will show bullae are subepidermal Epidermal cell necrosis may exist Perivascular areas high in lymphocytes
10	SJS Treatment No specific drug therapy exists Use of steroids is controversial Consultants: Critical care, ophthalmologist, GI, burn or plastic surgeon Wash wounds daily and dress with saline soaks or dilute silver nitrate soaks Treat Skin Lesions As Burns
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13	SJS Complications Corneal ulcerations Esophageal strictures Penile scarring, vaginal stenosis Tracheobronchial shedding with resultant respiratory failure Cutaneous hypo and hyper pigmentation
14	Grafting with Cadaver Skin (Homograft/Allograft) Promotes and speeds healing Decreases risk of infection Reduces size of wound Decreases hyper metabolic state Decreases pain Decreases potential of scar formation
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17	Stevens - Johnson / TENS Frequency United States: 2-12 cases per 1,000,000 World Wide: 1-1.3 cases per 1,000,000
18	"Morbidity /Mortality" Morbidity /Mortality Sepsis, GI bleeding, markedly low white blood cell count, pneumonia, fluid/electrolyte imbalance and renal insufficiency are the major complications that contribute to mortality Mortality rate 15-40%
19	Stevens - Johnson / TENS Grossman Burn Center Data 1991-2004 40 patients with SJS/TENS Deaths 5 Mortality rate of 12.5%
20	Stevens - Johnson / TENS Hospital Costs Hospital charges: $90, 000 - >$1,000,000 Does not include physician charges Hospital reimbursement: 25% -70% of charges
21	Bextra & SJS Evolution of the Warnings
22	Start at the End April 7, 2005 – No advantages
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24	Introduced March 2002
25	First Problems Nov. 2002 -- Contraindication
26	Nov. 2002 -- Warning
27	Dear Dr. Letter Nov. 13, 2002
28	October 15, 2004 Dear Dr. letter
29	November 2004 Black Box – Not Bold Serious skin reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) have been reported in patients receiving Bextra. Some of these reactions have resulted in death. …. The reported rate of these serious skin events appears to be greater for Bextra as compared to other COX-2 agents.
30	Dec. 9, 2004 – Q & A
31	Dec. 23, 2004 Talk Paper
32	Begin at the End Letter re DTC Advertising
33	April 7, 2005
34	Sufficient? Should be marketed to limited patient population No more efficacious than selective or non-selective NSAIDs Similar (if not worse CV risk) Higher Incidence of horrible disease Can you have an effective warning?
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36	Causation Issues The Idiopathic Problem Lack of Viral Confounder (e.g., Ibuprofen) Class Effect? Do Damages Moot It?
37	Bextra & Stevens Johnson Syndrome