MORNING MEETING

DR. HASAN ALBANNAY

KBIM R5
17/01/2023
Do you know them?
 CASE 1
• 37 YEARS OLD MALE
PRESENTED TO ER WITH 5 DAYS HX OF
1) BURNING SENSATION IN MOUTH
2) DIFFICULTY SWALLOWING
3) GENERALASIED ERYTHEMATOUS RASH
• RECEIVED AMOXICILLIN FOR DENTAL ABSCESS
 CASE 2
• 40 YEARS OLD FEMALE
PRESENTED TO ER WITH 3 DAYS HX OF
1) MACULOPAPULAR RASH
2) OROMUCUTANOUS EROSION
3) FEVER
• RECEIVED UDA FOR RECENT DIAGNOSIS OF
AUTOIMMUNE HEPATITIS.
 CASE 3
• 50 YEARS OLD MALE
PRESENTED TO ER WITH 3 DAYS HX OF
1) BLURRED VISION
2) GENERALISED NON-BLANCHING RASH
3) FEVER 39
• TEGRETOL TO TREAT POST HERPATIC
NEURALAGIA
 CASE 4
• 29 YEARS OLD MALE
PRESENTED TO ER WITH 5 DAYS HX OF
1) GENERALISED MACULOPAPULAR RASH
2) FEVER 39
3) DYSPHAGIA AND VOMITING
• PHENYTOIN FOR NEW DIAGNOSIS FITS
 CAUSE
• CONNECTION BETWEEN ALL CASES?
DDX ?
DRUG HYPERSENSITIVITY REACTION
• Group of reactions mediated by the
immune system after exposure to a drug.
• The mechanisms are complex and not
always fully characterised.
• Multiple systems have been developed to characterize
and classify different reactions to drugs

• The Gell and Coombs classification divides

immunologic DHRs into 4 major pathophysiologic
categories based on the immunologic mechanism
 Type 4 DHR
• SJS AND TEN ARE SEVERE CUTANOUS HYPERSENSITIVITY
REACTIONS
• DRUGS ARE THE MOST COMMON CAUSES
• MACULES RAPIDLY SPREAD LEADING TO NECROSIS
• DIAGNOSIS IS USUALLY CLINICAL
• TREATMENT IS SUPPORTIVE
• MORTALITY TEND TO BE LOWER WITH EARLY TREATMENT
• Stevens-Johnson syndrome (SJS) and toxic
epidermal necrolysis (TEN) are clinically similar
except for their distribution.
• By one commonly accepted definition,
changes affect < 10% of body surface area in
SJS and > 30% of body surface area in TEN
• Involvement of 10 to 30% of body surface
area is considered SJS/TEN overlap.
 Etiology
• Sulfa drugs (sulfasalazine)
• Ampicillin or amoxicillin, fluoroquinolones,
cephalosporins
• Phenytoin, carbamazepine, phenobarbital, valproic acid
and lamotrigine
• NSAID drugs (piroxicam, meloxicam)
• Antiretroviral drugs (nevirapine)
• Miscellaneous (allopurinol, chlormezanone)
• Infection (Mycoplasma pneumoniae)
• Vaccination
 Pathophysiology
• The exact mechanism is unknown.
• Theory 1 : altered drug metabolism (eg, failure to clear reactive
metabolites) in some patients triggers a T-cell–mediated cytotoxic
reaction to drug antigens in keratinocytes. CD8+ T cells have been
identified as important mediators of blister formation. Interleukin-
15 has also been found to be increased in patients with SJS/TEN
and has been found to increase granulysin production.
• Theory 2 : interactions between Fas (a cell-surface receptor that
induces apoptosis) and its ligand, particularly a soluble form of Fas
ligand released from mononuclear cells, lead to cell death and
blister formation.
• A genetic predisposition for SJS/TEN has been suggested.
 Symptoms and Signs
• Within 1 to 3 weeks after the start of the offending
drug, patients develop a prodrome of malaise, fever,
headache, cough and keratoconjunctivitis.
• Macules appear suddenly usually on the face, neck,
and upper trunk, coalesce into large flaccid bullae
and slough over a period of 1 to 3 days.
• Nails and eyebrows may be lost along with
epithelium.
• The palms and soles may be involved. Skin, mucosal
and eye pain are common.
• In severe cases of toxic epidermal necrolysis, large sheets
of epithelium slide off the entire body at pressure points
(Nikolsky sign), exposing weepy, painful, and
erythematous skin.
• Painful oral crusts and erosions, keratoconjunctivitis, and
genital problems (eg, urethritis) accompany skin
sloughing in up to 90% of cases.
• Bronchial epithelium may also slough, causing cough,
dyspnea, pneumonia, pulmonary edema, and hypoxemia.
• Glomerulonephritis and hepatitis may develop.
 Diagnosis
• Clinical evaluation
- Lesion
- rapid progression of symptoms
- examination
• Often skin biopsy
 DDX
• STEVEN JOHNSON SYNDROME (SJS)
• TOXIC EPIDERMAL NECROLYSIS (TEN)
• SJS-TEN OVERLAP
• ERYTHEMA MULTIFORME
• DRUG RASH WITH EOISONPHILIA AND SYSTEMIC
SYMPTOMS (DRESS)
• STAPHYLOCOCCAL SCALDED SKIN SYNDROME
• PEMPHGOID VULGARIS
• BULLOUS BEMPHIGOID
 SJS VS TEN
SJS TEN
BSA % <10% >30%
PRIMARY LESION FLAT DUSKY RED LESION POORLY DELINEATED
WITH ATYPICAL TARGET ERYTHEMATOUS PLAQUE.
WITH FLAT DUSKY LESION

MUCOSAL YES YES

SYSTEMIC SYMPTOMS USUALLY ALWAYS
 SJS/TEN VS DRESS
SJS/TEN DRESS
START 4-14 DAYS ( UP TO 28) 2-8 WEEKS
MUCOSAL > 90% ( 2 OR MORE SITES) 50%
CBC LYMPHOPENIA EOISNOPHILIA
SKIN BIOPSY FULL THECKNESS NECROSIS DERMAL ODEMA WITH
INFILTRATION BY EOIN
SYSTEMIC IVOLVMENT HEPATITIS <10 % HEPATITIS >50%
PRE-RENAL AKI TIN
RASH ERYTHEMATOUS MACULE MORBILIFORM
 SJS/TEN VS EM
SJS/TEN ERYTHEMA MULTIFORME
CAUSES MEDICATIONS HSV AND MYCOPLASMA
LESION FLAT DUSKY LESION PAPULAR ERYTHEMATOUS
TARGET ATYPICAL TYPICAL
INITIAL DISTRIBUTION FACE AND PROXIMAL LIMB ACRAL DISTRIBUTION
CONSTITUTIONAL SYMP. FEVER, MYALGIA, HEADACHE ABSCENT
BSA % DEPENDS MOST <10%
RECURRENCE UNCOMMON COMMON (HSV RELATED)
 SJS/TEN VS SSSS
SJS/TEN SSSS
THICKNESS FULL THICKNESS SUPERFICIAL LAYER
ETIOLOGY T LYMPHOCYTE FAS STAPH. EXFOLIATIVE TOXIN
MUCOSAL YES NO (UNLESS TOXIC SHOCK
SYNDROME)
AGE AFFECTED OLDER CHILDREN OR ADULT
NIKOLSKY SIGN YES YES
HISTOPATHOLOGY EPIDERMAL CELL DEATH ACANTHOLYSIS
 PEMPHIGOUID VS BULLOUS
PEMPHIGUS VULGARIS BULLOUS PEMPHIGOID
AGE YOUNGER ( 40-60 ) OLDER ( >60 )
MUCOSA > 80% 10-30%
BULLAE FLACCID TENSE
NIKOLSKY SIGN POSITIVE NEGATIVE
AUTOANTIBODIES AGAINST DESMOGLEIN 3 AGAINST HEMIDESMOSOME
PROGNOSIS POOR BETTER
 Prognosis
• Severe toxic epidermal necrolysis is similar to extensive
burns; patients are acutely ill, may be unable to eat or
open their eyes, and suffer massive fluid and electrolyte
losses. They are at high risk of infection, multiorgan
failure, and death. With early therapy, survival rates
approach 90%.

• The severity of illness score for TEN

7 independent risk factors within the first 24 hours of
presentation to the hospital to determine the mortality
rate for a particular patient.
• Supportive care
• Cyclosporine, Corticosteroids, plasmapheresis, IVIG or TNF alpha
inhibitors
• Treatment is most successful when recognized early
• Ophthalmology consultation is mandatory for patients with ocular
involvement.
• Potentially causative drugs should be stopped immediately.
• Patients are isolated to minimize exposure to infection and are given
fluids, electrolytes, blood products and nutritional supplements
• Skin care includes prompt treatment of secondary bacterial
infections and daily wound care as for severe burns.
• Prophylactic systemic antibiotics are controversial and often avoided
 Key points
• Drugs cause > 50% of SJS/TEN
• Confirm the diagnosis by biopsy (showing necrotic
epithelium) if clinical characteristics (target lesions
progressing to bullae, ocular and mucous membrane
involvement, Nikolsky sign, desquamation in sheets)
are inconclusive.
• Early treatment decreases the often high mortality rate.
• Consult ophthalmology if the eyes are affected.
• Consider cyclosporine and possibly plasmapheresis for
severe cases
• THANK YOU ..