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