EM, SJS, TEN Flashcards
Most common cause of EM?
HSV (HSV1 more common)
What seperates EM minor and major?
In EM minor the target lesions are associated with minimal mucosal involvement and NO systemic symptoms
What is the most common cause of erythema multiforme (EM) major?
Mycoplasma Pneumoniae
It often has severe mucous membrane involvement (simulates SJS).
What is the major driver of prognosis in SJS and TEN
Speed at which culprit drug is identified and withdrawn.
What is the major mediator of apoptosis in SJS and TEN
Granulysin –> secreted in cytotoxic granules of CD8+ T-cells/NK-cells, directly damages keratinocytes.
What is the difference in distribution between EM and TEN/SJS?
Distal extremities are relatively spared in SJS/TEN and lesions tend to be more proximal. This is reversed in EM
What is the SCORTEN system?
For gauging prognosis in SJS/TEN: has to be done on day 1 and day 3 Tachycardia (>120bpm) Age (>40) Malignancy Epidermal loss >10% Bicarbonate Urea (>17) Glucose (>120)
What is the most important indicator of mortality within the SCORTEN scoring?
Serum bicarbonate (<20mmol/L)
Does bactrim and furosemide cross-react for SJS TEN?
NO! sulfa abx do not cross-react with other sulfa medications like furosimide
Epidemiology for EM?
Young adults; slight male predominance, 90% of cases d/t infection (HSV 1>2), drugs (<10%, NSAIDS, abx, sulfa, antiepileptics, TNF-a inhibitors), systemic dz, physical triggers.
What Infections can cause EM?
HSV, Mycoplasma pneuoniae (mucosal involvement), histoplasma capsulatum, parapoxvirus (orf)
Describe classic target lesions in EM?
<3mm, regular round shape, well-defined border, 3 distinct zones: 2 concentric rings of color change surrounding central circular zone that has evidence of damage to the epidermis (vesicles, blister, dusky appearance)
Usually palpable!
Describe atypical target lesions?
Round, edematous, macular, only 2 zones or poorly defined border
Macules are key, classic lesions tend to be palpable
Difference between SJS/TEN and EM lesions?
In SJS the lesions tend to be macular, non-palpable, non-elevated atypical targets. They also tend to be more centrally distributed with more involvement of the mucous membranes
Most common locations for EM?
Distal extremities (UE>LE), palms, neck, face and trunk are commonly involved as well.
Definition of EM minor?
Target lesions w/ minimal mucosal involvement and NO systemic sx’s.
Definition of EM major?
Mycoplasma pneumonia is most common, target lesions w/ severe mucosal involvement and systemic sx. Mucosal sx’s are severe and rapidly develop into painful erosions that involve buccal mucosa and lips. -Systemic sx’s are usually fever, asthenia, arthralgias, joint swelling, pulmonary
What cause of EM also tends to have concomitant EN?
Histoplasma capsulatum
Timeline of EM?
Almost all lesions appear within 24 hours, full development by 72 hours, pruritus and burning, individual lesions remain fixed at the same site for 7 days or longer.
Episode lasts 2 weeks and heals without sequelae in post pts.
What is the earliest histologic sign of EM?
Apoptosis of individual keratinocytes
Differential diagnosis for EM?
Giant urticaria, fixed frug eruptions (neuts, pigment incontinence), subcutaneous LE, Kawasaki disease, erythema annulare centrifugum, vasculitis
Difference between urticaria and EM?
For urticaria: central zone is clear, lesions are transient, new lesions appear daily, associated w/ swelling of face hands or feet.
Treatment for EM minor compared to major?
Minor: oral antihistamines for 3-4 days, topical therapy Major: pred 0.5-1mg/kg/day or pulsed methylprednisolone (20mg/kg/day for 3 days). May be a/w ocular complications.
Etiology of SJS/TEN?
Nearly always drug-related
Histology of SJS/TEN?
Extensive keratinocyte cell death tends to be more pauci-immune at the DEJ
Sx’s of SJS/TEN?
High fever, moderate to severe skin pain, anxiety,e and asthenia
What defines prognosis in SJS/TEN?
Speed at which culprit drug is identified and withdrawn
What are the % body surface areas that define SJS vs overlap vs TEN?
Up to 10% = SJS 10-30% = overlap >30= TEN
What is the major mediator of apoptosis in SJS/TEN?
Granulysin –> secreted in cytotoxic granules of CD8+ t-cells/ NK-cells
What are the causes of cell death in SJS/TEN?
Granulysin (major mediator of apoptosis), FasL(CD95L) activation of caspases, apoptosis; Granzyme B and perforin: Poke holes in the target cell, activate caspases
Causes besides drugs of SJS/TEN?
Mycoplasma pneumoniae, contrast media, dengue virus, CMV
Clincal presentaton of SJS/TEN?
Skin sx preceded by prodrome (1-3 days before skin) Fever, stinging eyes, dysphagia, anorexia, rhinorrhea Atypical (2 rings) poorly demarcated targetoid macular (non-palpable) lesions w/ mucocutaneous erythema & skin pain -dusky plaques w/ full-thickness sloughing (grey-hue) -Flaccid blisters -Macules variable size and shape -can become confluent Atypical & macular*** differentiate from EM (papules, palpable) 1st on trunk –> neck, face and proximal upper extremities Unlike EM, distal extremities relatively spared Flaccid blisters have positive Nikolsky/Asboe-Hansen
Systemic sx’s seen in SJS/TEN
Fever, lymphadenopathy, hepatitis & cytopenias
Factors associated w/ worse survival in SJS/ TEN?
Increasing age, extent of epidermal detachment, number of medications, elvation of serum urea, creatine and glucose, neutropenia, lymphopenia, and thrombocytopenia, late wihtodrawal of causative drug
Components of the SCORTEN system?
Tachycardia (>120bpm), Age (>40), Malignancy, Epidermal loss >10%, bicarbonate, Urea (BUN> 27), Glucose (>250)
Most common cause of death in SJS/TEN?
Infection
Sequelae of SJS/TEN?
Symblepharon, entropion, cutaneous scarring, blindness, persistent erosions in eys, eruptive melanocytic nevi, persistent erosion of mucosal membranes, phimosis, vaginal synechiae, nail dystrophy, and diffuse hair loss.
SJS/TEN treatment?
Controlled pressure, thermoregulated bed and aluminum survival sheet, careful care of detached areas, especially back and pressure sites should be covered w/ vaseline gauze until re-epithelialization has occurred. -Mupirocin/antibiotic ointment should be applied around ears, nose, mouth, and silicone dressing can be used to cover erosive denuded areas of skin.
What is good about silicone dressings in the setting of SJS/TEN ?
Does not need to be changed and can be left in place until re-epithelialization occurs but the surface should be cleansed daily w/ isotonic sterile sodium chloride solution
Consults needed for SJS/TEN?
Optho and OB/GYN/Urology
Eye care in SJS/TEN?
Eyelids should be gently cleased daily wiht isotonic sterile NaCl solution + opthoalmic anitbiotic ointment applie to eyelids -antibiotic eye drops 3x daily to cornea to reduce bacterial olonization which can lead to scarring
Nostril care in SJS/TEN
Cleansed daily with a sterile cotton swab, moistened with isotonic sterile NaCl solution + antibiotic ointment (mupirocin)
Mouth care in SJS/TEN?
Should be rinsed several times a day using syringe with isotonic sterile NaCl solution then aspirated if pt unconscious
Anogenital/Interdigital care in SJS/TEN
Daily short applications of silver nitrate solution (0.5%) in case of maceration or simply sterile NaCl solution if no maceration
Pharmacologic tx for SJS/TEN?
IV/oral steroids are mainstay early in the disease course (3 days pulse) -Can also consider IVIG, Cyclosporine, and Etanercept
What serologic tests can be helpful in distinguishing morbilliform drug rash from SJS/TEN?
Granulysin (80% sensitivity), 95% specificity High mobility group protein B1 (HMGB1)
What infectious disease increases the risk of SJS/TEN?
AIDS = 1000 fold increase in risk
What important genetic groups have increased risk of SJS/TEN?
HLA-B*1502 (Asians and East Indians exposed to carbamazepine = 220-fold increase in risk)
HLA-B*3101 (Europeans exposed to carbamazepine)
HLA-B*5701 (Abacavir)
HLA-B*5801 (Han Chinese exposed to allopurinol)
HLA-DQB1*0601 (white patients wiht SJS + ocular complications
What is the relationship between the half-life of a drug and outcomes in SJS/TEN?
Drugs with longer half-lives tend to portend to worse outcomes
What are the most common medications associated with SJS/TEN?
Allopurinol, anticonvulsants (lamotrigine, carbamazepine, phenytoin, and phenobarbital)
- Valproic acid does not cross-react with these
- Lamgotrigine does not cross-react with the aromatic anticonvulsants
When is the risk for SJS/TEN highest for starting medications that can cause it?
Risk highest within the first 2 months
What screening genetic tests should be routinely performed to prevent SJS/TEN?
HLA-B*1502 in East Asian patients prior to giving carbamazepine and HLA-B*5701 prior to starting abacavir
What is the most common sequelae after SJS/TEN?
Ocular sequelae (80%) can include dry eye syndrome (most common), entropion, symblepharon, blindness, scarring, and persistent erosions
What is the most common cause of death in SJS/TEN?
Infection (S. Aureus and Pseudomonas)
Why is there an increased risk of SJS/TEN in patients with HIV?
Loss of skin-protective CD4+/CD25+ regulatory T-cells
