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.