Psoriasis
Psoriasis/psoriasiform rashes are skin reactions that cause red, itchy
scaly patches, present most commonly on the knees, elbows, trunk, and
scalp. Most commonly these itchy scaly patches occur in a patient with a
former history of psoriasis before starting the immunotherapy, but few
cases show the new onset of psoriasis 63, 64. Plaque
psoriasis is one of the most common forms of psoriasiform rashes, but
the occurrence of other forms has also been reported, including pustular
psoriasis, palmoplantar psoriasis, guttate psoriasis, nail psoriasis,
inverse psoriasis, erythrodermic psoriasis. Clinical description of the
disease includes well-demarcated, erythematous, scaly papules and
plaques. Importantly, cases of exacerbation or de-novo incidence of
psoriatic arthritis with cutaneous psoriasis, have also been reported65, 66.
Pathogenesis: PD-1/PD-L1 blockade activates the T-cell
which stimulates an inflammatory state and leads to the development of
psoriasiform lesions. Psoriasis is T-cell and dendritic cell
(DCs)-mediated disease generally mediated by Type 1 and 17 helper T
cells (Th1/Th17). In psoriatic patients, dendritic-cell (DCs) of skin
secretes IL-23 that induces the production of pro-inflammatory cytokines
released by Th-17 mainly IL-17A, IL-17F, and IL-22. Dermal Th-1
lymphocytes are also activated by dermal DCs to produce interferon-gamma
(IFN- γ), tumor necrosis factor (TNF)-alpha. PD-1/PD-L1 signaling
pathway causes down-regulation of Th1/Th17 cells, whereas inhibition of
this pathway causes an up-regulation of Th-1/Th17 cells stimulating
overexpression of pro-inflammatory cytokines IL-17 and IL-22. These
inflammatory mediators cause the stimulation and hyperproliferation of
keratinocytes on the skin surface. Activated keratinocytes produce key
pro-inflammatory cytokines, chemokines, and antimicrobial peptides,
which can recruit and activate immune cells in the inflamed skin,
leading to epidermal hyperplasia, acanthosis, and hyperparakeratosis.
Since Th17 is an important factor for the development of psoriasis,
checkpoint inhibitors initiate new psoriasis or cause exacerbation of
existing diseases 64, 67.
Clinical incidence : A total of twenty-one cases of psoriasiform
rashes were found including psoriasis and psoriasis induced psoriatic
arthritis with PD-1/PD-L1 inhibitors. Whereas, twenty cases were
reported with anti-PD-1 which includes nine cases with
pembrolizumab68-72, eleven cases with nivolumab
therapies 64-66, 72-80 while one case was reported
with the PD-L1 inhibitor atezolizumab81 therapy. In
reported cases, the median age was 68 years. The occurrence of psoriasis
ranges from 12%% in patients with anti-PD-1/PD-L1 immune therapy. The
time from initiation of anti-PD-1/PD-L1 treatment to the development of
psoriasis ranges from 2 to 14 months and psoriasis cases were found more
in males as compared to females. Clinical psoriasis is reported as an
adverse event that extends from guttate psoriasis to plaque psoriasis,
inverse psoriasis, palmoplantar psoriasis, and nail psoriasis to
erythrodermic psoriasis. The patients that developed concurrent
psoriasis involved psoriatic arthritis of several joints.
Treatment: The first-line treatment of psoriasis was topical
corticosteroids 64 and systematic steroids like oral
prednisone 70 or methylprednisolone therapy at doses
of 16 mg (n=1) 69, 1000 mg (n=1) 65.
One patient was prescribed triamcinolone ointment 0.1%, hydrocortisone
cream 2.5%, and methylprednisolone, further the eruption was controlled
with the combination of topical and oral
steroids.80Other treatments include clobetasol
propionate 0.05% ointment 68, 78 applied on both
nails and skin, 50% urea gel on nails 74. A case has
been reported with nivolumab immunotherapy in which skin lesions were
treated with the combination of psoralen and long-wave ultraviolet
radiation (PUVA) 75. Two patients with immune-mediated
psoriasiform reactions from anti-PD-1 inhibitor had been treated with
UVB-NB light therapy also known as UV7001K phototherapy.72. Treatment with intravenous fluconazole,
apremilast76, acitretin71,
subcutaneous injections of secukinumab (300 mg once every two weeks) had
also been introduced. In one case, a patient with widespread
psoriasiform lesions responded well to anti-interleukin 17A treatment71. In the case of nivolumab immunotherapy, a patient
with drug-induced psoriasis was treated well with
risankizumab-rzaa79. A patient with psoriasis-induced
psoriatic arthritis was treated well with apremilast at a dose of 30 mg
BID66.