Oral mucosal toxicities induced by immune checkpoint inhibitors: Clinical features and algorithm management.

Immune checkpoint inhibitors (ICIs) have emerged as standard therapies for an increasing number of advanced cancers. Nonspecific immune activation may lead to immune-related adverse events among which dermatological reactions are one of the most prevalent (all-grade incidence ranging from 30 to 60%). Oral mucosal adverse reactions to ICIs are far less common than cutaneous adverse events. However, a spectrum of oral changes with characteristic features has recently emerged, including lichenoid reactions, sicca syndrome, and even autoimmune bullous disorders with oral involvement. Oral changes mainly occur during the first year of treatment, often concurrently with other dermatological changes, and may involve up to 10% of patients under ICI therapies. This article provides a systematic review of the oral changes reported with these therapies based on a rich iconography.

European recommendations for management of immune checkpoint inhibitors-derived dermatologic adverse events. The EADV task force 'Dermatology for cancer patients' position statement.

The introduction of immune checkpoint inhibitors (ICIs) opened a new era in oncologic therapy. The favourable profile of ICIs in terms of efficacy and safety can be overshadowed by the development of immune-related adverse events (irAEs). Dermatologic irAEs (dirAEs) appear in about 40% of patients undergoing immunotherapy and mainly include maculopapular, psoriasiform, lichenoid and eczematous rashes, auto-immune bullous disorders, pigmentary disorders, pruritus, oral mucosal lesions, hair and nail changes, as well as a few rare and potentially life-threatening toxicities. The EADV task force Dermatology for Cancer Patients merged the clinical experience of the so-far published data, incorporated the quantitative and qualitative characteristics of each specific dirAEs, and released dermatology-derived, phenotype-specific treatment recommendations for cutaneous toxicities (including levels of evidence and grades of recommendation). The basic principle of management is that the interventions should be tailored to serve the equilibrium between patients' relief from the symptoms and signs of skin toxicity and the preservation of an unimpeded oncologic treatment.

[Green tongue phenomenon, or diagnosis via Google]. / Le phénomène de la langue verte, ou le diagnostic par Google.

BACKGROUND: Regular cannabis use may be associated with several oral changes not usually identified by dermatologists: xerostomia, increased risk of caries, periodontitis, leukoedema, gingival hyperplasia, and higher prevalence and density of Candida albicans, leukoplakia or gingivitis. PATIENTS AND METHODS: We report herein the appearance of a characteristic green tongue in a patient following intensive marijuana inhalation. DISCUSSION: This complication has rarely been reported in the medical literature. Paradoxically, it is clearly described in different Internet search engines, particularly Google.

[Dermatologic toxicities of immune checkpoint inhibitors]. / Toxicités dermatologiques des inhibiteurs de checkpoint immunologiques.

The development of immune checkpoint inhibitors (monoclonal antibodies targeting PD-1/PD-L1 or CTLA-4) represents a significant advance in the treatment of multiple cancers. Given their particular mechanism of action, which involves triggering CD4+/CD8+ T-cell activation and proliferation, they are associated with a specific safety profile. Their adverse events are primarily immune-related, and can affect practically all organs. In this context, dermatological toxicity is the most common, though it mostly remains mild to moderate and does not require discontinuation of treatment. More than a third of patients are faced with cutaneous adverse events, usually in the form of a maculopapular rash, pruritus or vitiligo (only in patients treated for melanoma). Much more specific dermatologic disorders, however, may occur such as lichenoid reactions, induced psoriasis, sarcoidosis, auto-immune diseases (bullous pemphigoid, dermatomyositis, alopecia areata), acne-like rash, xerostomia, etc. Rigorous dermatological evaluation is thus mandatory in the case of atypical, persistent/recurrent or severe lesions. In this article, we review the incidence and spectrum of dermatologic adverse events reported with immune checkpoint inhibitors. Finally, a management algorithm is proposed.

[Oral hairy leukoplakia induced by topical steroids]. / Leucoplasie orale chevelue induite par une corticothérapie locale.

BACKGROUND: Oral hairy leukoplakia (OHL) is an EBV-associated condition of the oral mucosa, which is often painless. It is found predominantly in HIV-positive patients and is considered a clinical indicator of immunosuppression. OHL has rarely been described in HIV-negative patients, being found most often in association with iatrogenic immunosuppression. OHL induced by topical steroids remains extremely rare. PATIENTS AND METHODS: An 81-year-old HIV-negative woman, treated for 3 months with topical steroids for oral lichen planus, developed an asymptomatic white, corrugated, non-removable plaque with vertical folds on the lateral edge of the tongue. Associated oral candidiasis was noted. Based upon histological findings and in situ hybridisation showing numerous EBV-infected epithelial cells, a diagnosis of oral hairy leucoplakia was made. DISCUSSION AND CONCLUSION: To our knowledge, we report herein only the second recorded case of OHL induced strictly by topical steroids. Self-medication and poor adherence to dosage recommendations were noted in the patient's medical history. Physicians must be aware of the rare but nevertheless possible adverse events associated with topical steroid use, particularly when such medication is prescribed over a long period for inflammatory diseases of the oral mucosa.

[Oral toxicity of targeted anticancer therapies]. / Toxicité endobuccale des thérapies ciblées anticancéreuses.

While toxicity of targeted anticancer therapies on the oral mucosa seems relatively frequent in clinical practice, it has not been properly characterized to date, apart from aphthous-like lesions due to mTOR inhibitors. Herein, we report the main oral lesions associated with these new therapies, with a description of the most frequent but also the most characteristic clinical manifestations of these drugs, such as anti-EGFR-induced mucositis, BRAF-inhibitor-associated hyperkeratosis, benign migratory glossitis and osteonecrosis of the jaw observed with angiogenesis inhibitors, as well as lesions more specifically linked with imatinib.