Clinical Q+A in Oral Medicine

A case of sudden oral dryness

Dr Lalima Tiwari

Oral Medicine Specialist

Private practice, Perth Oral Medicine and Dental Sleep Centre, West Leederville

Adjunct Senior Lecturer, The University of Western Australia, Dental School, Nedlands

History

An 82-year-old male was referred to Oral Medicine for severe dry mouth that he noted about 1 year (May 2022) prior to his presentation. The onset of his symptoms was sudden and progressive, and he now reports reduced saliva and difficulty in swallowing food. Upon further questioning, he also reports dry and irritated eyes noted at the same time as his dry mouth. His medical history is significant for hyperlipidaemia, type II diabetes and stage IIIc melanoma, managed with surgery and adjuvant pembrolizumab infusions (commenced in April 2022). His other medications include 10mg rosuvastatin and 500mg metformin.

Clinical findings

My examination revealed the presence of moderate salivary gland hypofunction including frothy saliva, a lack of pooling of saliva in the floor of mouth, and a lobulated, fissured tongue (Figure 1). The intra oral mirrors were noted to stick to the buccal mucosa and there was lack of saliva secretions upon palpation of the submandibular glands. No regional lymphadenopathy was palpable extraorally. Temporomandibular joints and muscles of mastication were within normal limits. Normal mouth opening and mandibular range of motion was noted. No other oral mucosal swellings or lesions were noted. MRI imaging of the major salivary glands were unremarkable.

Based on the history and clinical findings, what is the most likely cause for the patient’s salivary gland dysfunction?

a) Salivary gland neoplasm b) Dehydration c) Type II diabetes d) Pembrolizumab

Answer: d

Cancer immunotherapy is quickly becoming a central pillar of cancer therapy. The first series of cancer immunotherapy constituted the immune check point inhibitors (ICIs). ICIs are monoclonal antibodies that work by blocking immune checkpoints, negative regulators of T cells that are co-designated by tumours to induce T-cell exhaustion and suppress anti-tumour immune activity. As these drugs increase immune activity, ICIs can induce a wide variety of inflammatory side effects known as immune-related adverse events (IRAEs). IRAEs typically develop within the first few weeks to months after initiating treatment, but can occur anytime, even after treatment has been discontinued. The most common organ systems affected include the gastrointestinal tract, endocrine glands, skin and liver, however evidence on the effects on oral mucosa and salivary glands are emerging, with an estimated incidence of 7% in patients treated with ICIs.

This case is an example of ICI – induced Sjögren's syndrome-like reaction. Sjögren's syndrome – like reactions, have been reported in patients treated with durvalumab, avelumab, pembrolizumab, nivolumab and ipilimumab. Clinical features include abrupt onset of severe xerostomia, salivary gland hypofunction, ocular dryness, and rarely bilateral parotid swelling. Patients may demonstrate reduced whole unstimulated salivary flow rate, or visible signs of oral mucosal dryness. Additional systemic features of Sjögren's syndrome (e.g., cutaneous, articular) can be present. A small proportion of patients may demonstrate positive serology (6% - 14%), while histopathological features of minor salivary gland biopsies in affected patients have ranged from mild non-specific chronic sialadenitis (50%) to focal lymphocytic sialadenitis of varying severity.

Management varies from lifestyle changes (e.g., increased hydration, avoidance of caffeine), saliva replacements (e.g., Biotene®, Oral 7®, Xylimelts®, sugar-free gum), and systemic sialagogues such as pilocarpine. In severe cases, discontinuation of ICI therapy and initiating systemic steroids with or without additional immunosuppressive agents (e.g., hydroxychloroquine) have been utilised. Caries prevention must be considered given the increased risk of dental caries in the setting of hyposalivation.

As immunotherapy continues to evolve, the rate of IRAEs will likely follow. As such, it is important for oral health practitioners to be aware of IRAEs and associated oral mucosal and salivary manifestations.

For further reading

Klein, B. A., Alves, F. A., de Santana Rodrigues Velho, J., Vacharotayangul, P., Hanna, G. J., LeBoeuf, N. R., Shazib, M. A., Villa, A., Woo, S.-B., Sroussi, H., Sonis, S., & Treister, N. S. (2021). Oral manifestations of immune-related adverse events in cancer patients treated with immune checkpoint inhibitors. Oral Diseases, 28, 9– 22.