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.