Stevens-Johnson syndrome/toxic epidermal necrolysis (TEN):
The stevens-johnson syndrome is a mucocutaneous adverse drug reaction
recognized as a complex delayed hypersensitivity reaction characterized
by epidermal detachment. SJS is a very rare and severe disorder that
involves mucosa and cutaneous tissue. It is characterized by flu-like
symptoms including fever, anorexia, malaise followed by erythematous
eruptions that arise as dusky-red, purpuric macules symmetrically
dispersed over the neck, trunk, extremities, and proximal limbs. Soon
after they spread to all over the body surface area and develop into
flaccid blisters characterized by epidermal detachment as well as
associated with inflammation and pain of oral, ocular, and genital
mucous membrane 128. SJS is a potentially fatal
syndrome associated with anti-PD-1/PD-L1 therapy which must be
recognized and treated on time. It is an immune-mediated syndrome with
granulysin, a cytolytic protein present in drug-specific CD81 cytotoxic
granules of T lymphocytes and natural killer cells, which act as key
mediators of keratinocyte apoptosis 129. but it may
involve blocking of PD-1/PD-L1 interaction
Pathogenesis: The exact mechanism underlying stevens-johnson
syndrome and toxic epidermal necrolysis remains to be elucidated, but it
may involve blocking of PD-1/PD-L1 interaction which results in the
cessation of T-cell homeostasis within the cutaneous and mucous membrane
associated with self-directed cytotoxic and inflammatory reactions. It
is a rare and unpredictable reaction that involves the accumulation of
drug-specific CD8+ cytotoxic lymphocytes associated with keratinocyte
apoptosis129.
Clinical incidence: Eighteen cases reported stevens-johnson
syndrome/ toxic epidermal necrolysis (TEN) with anti-PD-1/PD-L1 therapy.
Eleven cases were reported with pembrolizumab128,
130-138, five cases with nivolumab139-142, and two
cases with azetolizumab137, 143. The clinical
incidence has shown erythematous eruptions to papules and plaques to
purpuric patches over the neck, trunk, and extremities, with erosions on
the lips, hemorrhagic and yellow crust on lips, an erythematous
maculopapular rash with erythema, oedema, vesicles, desquamation, or
even ulceration.
Treatment: First-line treatment included systemic high-dose
corticosteroids (methylprednisolone, prednisone) while other treatments
like intravenous fluids and silver sulfadiazine, vancomycin, intravenous
immunoglobulin (IVIG) infusion 136, lidocaine 1%
solution 139, nystatin betnovate 0.1% ointment141, infliximab 138, were initiated
for the prevention of adverse events associated with anti-PD-1/Pd-L1
therapy.
Oral mucosa involvement