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Clinical Characteristics and Management of Immune Checkpoint Inhibitor-Associated Sicca Syndrome
Meridith L Balbach1, Douglas B Johnson2
1Division of Rheumatology and Immunology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Cancers
|June 12, 2026
Summary
Immune checkpoint inhibitor (ICI) therapy can cause sicca syndrome, presenting as dry mouth and eyes. Management often involves steroids or supportive care, with discontinuation leading to improvement, but rechallenge risks recurrence.
Area of Science:
- Oncology
- Immunology
- Rheumatology
Background:
- Immune checkpoint inhibitors (ICIs) can induce a distinct sicca-like syndrome.
- This ICI-associated sicca syndrome differs immunopathogenetically and clinically from primary Sjögren's disease.
- Real-world data on management and outcomes, especially regarding ICI discontinuation and rechallenge, are limited.
Purpose of the Study:
- To evaluate the real-world management and outcomes of sicca syndrome associated with immune checkpoint inhibitors.
- To assess the impact of ICI discontinuation and rechallenge on sicca syndrome symptoms.
- To analyze treatment strategies and their effectiveness in managing ICI-induced sicca syndrome.
Main Methods:
- Retrospective identification and assessment of patients experiencing new-onset or exacerbated sicca symptoms after ICI therapy.
- Evaluation of diverse malignancies, ICI types (pembrolizumab, nivolumab +/- ipilimumab), and sicca symptom severity (CTCAE v6.0 grades 1-2).
- Analysis of management strategies including conservative care, sialagogues, corticosteroids, ICI de-escalation, and discontinuation.
Main Results:
- Fifty-nine patients developed ICI-associated sicca syndrome, most commonly acute-onset dry mouth.
- Conservative management and corticosteroids showed improvement in symptoms.
- ICI discontinuation led to improvement in 75% of patients; however, all four patients rechallenged experienced sicca recurrence.
Conclusions:
- This study confirms that steroids and supportive care frequently improve ICI-associated sicca syndrome.
- ICI discontinuation is an effective strategy for managing sicca syndrome.
- Rechallenging with ICIs after a period of interruption carries a high risk of sicca syndrome recurrence.
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