Lichenoid dermatitis
Lichenoid reactions are severe inflammatory reactions mediated by T cells which comprise several maculopapular rashes, with lichenoid interface dermatitis and basal vacuolar changes, and are observed with anti-PD-1/anti PDL-1 therapy. Histological and clinical features show a dense, band-like lymphocytic infiltrate beside the dermal-epidermal junction of the skin, a vacuolar interface, and co-existing spongiosis. Patients experience asymptomatic scaly, sharp bordered erythematous psoriasiform plaques and lesions on the trunk, arms, and limbs, which may be present as discrete, multiple, or confluent lesions in a generalized, inverse, localized, palmoplantar, or mucosal (i.e. oral or genital) distribution. The number of these eruptions may range from tens to hundreds8. Lichen sclerosis (LS) is an autoimmune severe inflammatory disease affecting mainly the anogenital area which is characterized by autoreactivity of T-cells, increased levels of T-helper 1-specific cytokines9.
Pathogenesis: The immunologic mechanism of lichenoid dermatitis is supposed to be a T-cell mediated response. The blocking of PD-L1 binding with PD-1 results in the increased immune response by activation of tumor-specific T-cells. Also, increased self-immunity and antigenic immune reaction occur, which leads to non-specific activation of T-cells. This results in various adverse reactions involving multiple organ systems, such as the skin10. They specifically affect PD-L1 expressing keratinocytes in the sub-epithelium, resulting in keratinocytes necrosis. Furthermore, lymphocytic infiltration of the basal membrane causes spongiotic dermatitis, acanthosis, and hypergranulosis11.
Clinical incidence: There were thirty cases involving lichenoid dermatitis reported with PD-1/PD-L1 immunotherapy. Thirteen of them were associated with nivolumab therapy 9, 12-17 and thirteen with pembrolizumab (PD-1)10,18-25. Four cases were reported with PD-L1 inhibitors like one with avelumab26 and three with duvalumab27-29 inhibitors. Lesions appear as flat-topped, erythematous, or violaceous, and pruritic papules and plaques that may coalesce over the trunk, limbs, and extremities although a spreading of the lesions is possible. Lichenoid dermatitis occurs in the age ranges from 25-87 years (mean=66). A case was reported with nivolumab therapy where the patient developed variations on fingernails leading to the rapid development of proximal or lateral onycholysis and causing detachment of nail plate, consequent loss of nails 15
Treatment: First line: The first-line treatment for lichenoid dermatitis in the reported cases were systemic treatment and systemic prednisolone was the first choice of systemic treatment(0.5-80mg/kg)14, 16, 18, 19, 21-24, 27, and methylprednisone (60 mg/kg) 12, 14 and were effective in the majority of cases.
2nd line treatment: Topical therapies including corticosteroid creams and ointments, clobetasol propionate 0.05% 9, 12-14, 18, 20, 27, 28, topical fluocinonide ointment (0.05%)25. Intralesional triamcinolone acetonide15, 25, 26were used for hypertrophic lichen planus besides acitretin (0.2mg) 25. In one case report patient was treated with promethazine 17. Lesions were also treated with topical calcineurin inhibitors e.g., tacrolimus 0.1% ointment twice daily20. One patient was treated with a short course of cyclosporine 22. Consequently, tapering systemic steroids led to the recurrence of dermatitis which was then treated with narrowband ultraviolet B (NBUVB) phototherapy thrice weekly 13, 24.