## 4 Discussion
In the literature, such manifestations have been described as mucositis and concomitant appearance of ulcerative lesions [12]. They generally present low severity [1,2], while cases of severe immune mucositis associated with esophagitis are rare [13]. Among the examined patients, two reported the appearance of ulcerative lesions in the context of erythemat areas on the palate. Patients reported no painful symptoms as a result of these alterations. Following the appearance of the ulcerative lesion, only one patient complained of mild burning. While no cases of candidiasis associated with patients receiving anti-PD-1 drugs are reported in the literature, candida infections were recorded in two cases, between the third and fourth infusions of the drug. In the first case, the fungal infection was not associated with other alterations in the oral mucous membranes, while in the second case, it arose in an inflammatory context. In a patient with skin cancer, the candidiasis and xerostomia could also be due to the radiation regimen. Xerostomia is reported in the literature as the second most frequent oral adverse event following treatment with ICI, described as having an incidence of 6-7.2% [14]. The present study found only one case of xerostomia associated with difficulty swallowing. Often, the dryness of the mucous membranes also causes dysgeusia. Other reported symptoms include thick or sticky saliva, dry throat with hoarseness, and sensitivity to spicy and acidic foods. Cases of dry mouth with a high degree of severity have also been reported, which required temporary or permanent discontinuation of the ICI drug [15]. The most frequent oral adverse events, following treatment with anti-PD-1 drugs, therefore include mucositis, xerostomia, dysgeusia, and lichenoid reactions. Only one study described a case of pemphigoid of mucous membranes following therapy with pembrolizumab (PD-1) [16]. In the present study, six of seven patients with cutaneous irAEs also developed oral alterations. Only in two patients was this correlation not found: in one case, the presence of erythema on the face and chest was found, without any oral manifestation, while one patient reported inflammation of the palatal mucosa in the absence of skin changes. Moreover, adverse reactions were found in four of the six patients with lung cancer and treatment with ICI drugs. It could be analyzed, with a larger number of patients, whether the type of cancer being treated could be related not only to the onset but also to the type and location of the lesions that have arisen. All patients who underwent radiotherapy developed oral lesions. Skin lesions were found in two of the three patients who received chemotherapy. The lesions found in the latter patients were always of the erythemat type, while the lesions in patients with radiotherapy were of both the erythemata and hyperkeratotic type. ICI drugs have enabled a revolution in the treatment of cancer diseases, particularly for advanced cancers that are not responsive to conventional treatments. By contrast, the introduction of such therapies has led to the appearance of a new toxicity profile. The possible correlation between the onset of irAEs and the efficacy of the ICI drug has long been studied: it has been hypothesized that patients who show a better anticancer response, following treatment with ICI, have at the same time a greater probability of autoimmune toxicity [17]. This would seem to be caused by a more competent and reactive immune system, which stops the evolution of tumor pathology but also leads to an increase in responses against self [18]. Although several studies seem to confirm this relationship, there are still several disputes: the pathogenesis of these manifestations is not entirely clear, nor how the site, severity, timing of onset, and management of irAEs can influence the effectiveness of ICI drugs.