“…Rare cases of cutaneous squamous cell carcinoma have been reported in scleroderma patients, mostly associated with localized scleroderma (morphea, including pansclerotic morphea), (5, 54). Intriguingly, some patients with melanoma treated with interferon or immune checkpoint inhibitors have developed SSc (55–57).…”
Section: Demonstrated Associations With Specific Cancersmentioning
confidence: 99%
“…More recently, anticancer immunotherapy using immune checkpoint inhibitors has been shown to trigger autoimmunity, and a few cases of scleroderma have been reported in the literature (55–57, 140). In this context, the complexity of the interplay between anti-cancer pre-existing autoimmunity, genuine paraneoplastic syndromes and the effects of immune system stimulation by biologics is striking, and strengthens the relationships between SSc and malignancy.…”
Section: Shared Mechanisms In Cancer and Systemic Sclerosismentioning
Systemic sclerosis (SSc) is an autoimmune connective tissue disorder, characterized by multisystem involvement, vasculopathy, and fibrosis. An increased risk of malignancy is observed in SSc (including breast and lung cancers), and in a subgroup of patients with specific autoantibodies (i.e., anti-RNA polymerase III and related autoantibodies), SSc could be a paraneoplastic syndrome and might be directly related to an immune response against cancer. Herein, we reviewed the literature, focusing on the most recent articles, and shed light onto the potential relationship between cancer and scleroderma regarding temporal and immunological dimensions.
“…Rare cases of cutaneous squamous cell carcinoma have been reported in scleroderma patients, mostly associated with localized scleroderma (morphea, including pansclerotic morphea), (5, 54). Intriguingly, some patients with melanoma treated with interferon or immune checkpoint inhibitors have developed SSc (55–57).…”
Section: Demonstrated Associations With Specific Cancersmentioning
confidence: 99%
“…More recently, anticancer immunotherapy using immune checkpoint inhibitors has been shown to trigger autoimmunity, and a few cases of scleroderma have been reported in the literature (55–57, 140). In this context, the complexity of the interplay between anti-cancer pre-existing autoimmunity, genuine paraneoplastic syndromes and the effects of immune system stimulation by biologics is striking, and strengthens the relationships between SSc and malignancy.…”
Section: Shared Mechanisms In Cancer and Systemic Sclerosismentioning
Systemic sclerosis (SSc) is an autoimmune connective tissue disorder, characterized by multisystem involvement, vasculopathy, and fibrosis. An increased risk of malignancy is observed in SSc (including breast and lung cancers), and in a subgroup of patients with specific autoantibodies (i.e., anti-RNA polymerase III and related autoantibodies), SSc could be a paraneoplastic syndrome and might be directly related to an immune response against cancer. Herein, we reviewed the literature, focusing on the most recent articles, and shed light onto the potential relationship between cancer and scleroderma regarding temporal and immunological dimensions.
“…Morphea and disorders from this spectrum reported due to PD‐1 inhibitors in the literature are morphea, sclerodermoid changes, eosinophilic fasciitis, genital, and extragenital lichen sclerosis. To our knowledge, there have been four cases of nivolumab‐associated 5‐8 and six cases of pembrolizumab‐associated 9‐12 morphea, scleroderma, and scleroderma‐like changes in the English literature. Four cases were evaluated as relapse because they had the history of morphea or sclerodermoid changes previously 8,10,12 .…”
Background
Nivolumab is one of the targeted cancer therapy agent that acts to increase the immune responses by inhibition of antiprogrammed‐death‐receptor 1, which is one of the check points of the immune response. Nivolumab can be used to treat malign melanoma, lung, renal, head and neck, colorectal, hepatocellular cancers, and special cases of Hodgkin lymphoma.
Aims
We aimed to report a rarer cutaneous side effect of nivolumab because of the increasing uses of this agent in various cancer treatments.
Methods
We present a 48‐year‐old female, metastatic melanoma patient who developed plaque morphea lesion without any systemic involvement during nivolumab treatment. Plaque lesion responded well to use of topical corticosteroid and calcipotriol.
Results
Numerous cutaneous side effects associated with nivolumab have been reported in the literature. The most common cutaneous side effects are maculopapular rash, pruritus, and vitiligo. Morphea and disorders from this spectrum reported due to PD‐1 inhibitors in the literature are; morphea, sclerodermoid changes, eosinophilic fasciitis, and lichen sclerosis.
Conclusion
Patients who are treated by PD‐1 inhibitors may be examined carefully in terms of morphea and scleroderma‐like conditions although they are not as common as other cutaneous side effects.
“… 53 Although both in vitro and in vivo data on the role of IL-17A in fibrosis are still controversial, upregulation of Th17 cell activities provoked by ICIs may have a role on the development of fibrotic disorders. In addition to scleroderma, cases of scleroderma-like syndrome 54 and acral ischemia 55 induced by ICIs have been reported. Figure 8 ( A ) Scleroderma showing edematous fingers of an oral melanoma patient under nivolumab therapy.…”
Section: Various Mucocutaneous Disordersmentioning
In accordance with recent therapeutic progress of immune checkpoint inhibitors for certain cancers, various disorders are induced as immune-related adverse events (irAEs) affecting the skin, gut, thyroid gland, lung, and liver. Among such irAEs, mucocutaneous manifestation is the most common. Cutaneous manifestations are categorized into several groups, ie, inflammatory reactions, immunobullous reactions, alterations of epidermal keratinocytes, and alterations of epidermal melanocytes; however, there are additionally various cutaneous toxicities, unclassified into those groups. Blocking of programmed cell death 1 (PD-1)/programmed cell death ligand 1(PDL1) can lead to the induction of autoimmune reaction, via activation of cytotoxic T cells, inhibition of regulatory T cell function, and alteration of cytokine balance. Similarly, blockade of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) reduces the suppressive function of regulatory T cells. Due to those mechanisms, various autoimmune conditions can be induced, in addition to nonspecific drug eruptions. Dermatologists should be aware of various types of those mucocutaneous manifestations, either common or rare, as well as the management of such conditions. Herein, various mucocutaneous manifestations of irAEs and cases involving Japanese patients have been described, based on a single institute’s experience.
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