Citation: Apalla Z, Papageorgiou C, Lallas A, Delli F, Fotiadou C, Kemanetzi C, Lazaridou E. Cutaneous adverse events of immune checkpoint inhibitors: a literature review. Dermatol Pract Concept. 2021;11(1):e2021155. DOI: https://doi.org/10.5826/dpc.1101a155 Accepted: September 28, 2020; Published: January 29, 2021 Copyright: ©2021 Apalla et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License BY-NC-4.0, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: None. Competing interests: The authors have no conflicts of interest to disclose. Authorship: Z.A. and C.P. contributed equally to the preparation of the manuscript. All authors have contributed significantly to this publication. Corresponding author: Zoe Apalla, MD, PhD, Second Dermatology Department, Schoo of Medicine, Aristotle University of Thessaloniki, Anatolis 5, 55535, Thessaloniki, Greece. Email: zoimd@yahoo.gr Immune checkpoint inhibitors (CPIs) are targeted molecules that modulate the immune system, assist with self-tolerance, and minimize collateral tissue damage when immune responses are activated. Although they are characterized by a favorable risk/benefit ratio, immune checkpoint blockade has been associated with a new subset of autoimmune-like toxicities, named immune-related adverse events (irAE). Dermatologic reactions are among the most prevalent irAE triggered by CPIs. In a majority of cases they are self-limiting and readily manageable. However, it is not uncommon that they result in severe skin involvement and impairment of patients’ quality of life. Awareness of the spectrum of cutaneous irAEs is mandatory for every clinician involved in the management of oncologic patients. The role of the dermatologists is essential because early recognition and appropriate management of skin toxicity may prevent dose modifications and discontinuation of CPIs. The latter is particularly relevant, considering that recent data suggest favorable oncologic response in patients developing irAEs. Keywords : immune checkpoint inhibitors, skin toxicity, adverse effects, nivolumab, pembrolizumab, ipilimumab This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Eccrine poroma (EP) is a relatively rare benign adnexal neoplasm that usually affects elderly patients. Its pathogenesis is still under investigation, but recent gene studies have revealed gene fusions as key incidences resulting in oncogenetic pathways. It often presents as a solitary, firm papule, mostly asymptomatic, located on the soles or palms. Due to its clinical and dermoscopic variability, it is characterized as the great imitator. We performed a literature review, aiming to summarize current data on the pathogenetic mechanisms, new dermoscopic features, and novel diagnostic tools that may aid in early diagnosis and proper management of this rare adnexal tumor. Furthermore, we reviewed the possible pathogenetic associations between EP and its malignant counterpart, namely eccrine porocarcinoma. This systematic approach may aid in understanding the pathogenetic mechanisms and how to use novel histopathologic markers and imaging methods to overcome the diagnostic dilemma of this rare tumor.

Uveitis, an inflammatory disorder of the mid-portion of the eye, is considered a relatively rare but very serious ocular complication of psoriasis. Data on the specific characteristics of uveitis in the background of psoriasis are extremely limited. The presence of uveitis in the context of psoriasis has been estimated to occur in 7–20% of the psoriasis cases. This incidence tends to be higher in patients suffering from psoriasis and psoriatic arthritis (PsA) or PSA alone. Psoriatic uveitis is usually bilateral, chronic, and severe. In term of pathogenesis, both psoriasis and uveitis are considered as paradigms of T-helper 1/T-helper 17 (Th1/Th17) inflammatory reactions. Certain cytokines such as tumor necrosis factor-α (TNF- α), Interleukin-17 (IL-17), IL-23, and IL-6 play a significant role in the pathogenesis of both psoriasis and uveitis. As uveitis shares common pathogenetic mechanisms with psoriasis in certain circumstances, both diseases may benefit from the same targeted biologic therapies. Undiagnosed and under-treated cases of psoriatic uveitis may cause significant morbidity and even vision loss. Larger prospective studies are needed in order to further investigate the association between these two entities.

The relationship between psoriasis and onychomycosis is controversial, and the exact nature of this association remains to be clearly elucidated. In healthy nails, the compact nail plate acts as a barrier, preventing any infection. In psoriatic nails, the nail plate involvement, together with abnormalities in the blood capillaries, may lead to decreased natural defenses against microorganisms. Moreover, onycholysis (detachment of the nail plate) induces a humid environment that may favor fungal proliferation. Treatment with immunosuppressive drugs may additionally enhance onychomycosis. In this comprehensive review, we present data regarding the incidence and pathogenic action of dermatophytes and other fungi in the development of fungal infection in psoriatic nails.

Under the umbrella of cutaneous sarcomas (CS) we include a heterogeneous group of rare, malignant, mesenchymal neoplasia, such as dermatofibrosarcoma protuberans, atypical fibroxanthoma, cutaneous undifferentiated pleomorphic sarcoma, cutaneous angiosarcoma and leiomyosarcoma. Clinical presentation and histopathological examination are the cornerstone of CS diagnosis and classification. There are scarce data in the literature in regards to the clinical and dermatoscopic characteristics of CS and the role of dermatoscopy in their early identification. We performed a literature review, aiming to summarize current data on the clinical and dermatoscopic presentation of the most common types of cutaneous sarcomas that may facilitate early diagnosis and prompt management. Based on the available published data, CS are characterized by mostly unspecific dermatoscopic patterns. Dermatofibrosarcoma protuberans, Kaposi’s sarcoma, and in a lesser degree, cutaneous angiosarcoma, may display distinct dermatoscopic features, facilitating their early clinical recognition. In conclusion, dermatoscopy, in conjunction with the overall clinical context, may aid towards suspicion of CS.