Management of Oral Manifestations of Chronic Graft-Versus-Host-Disease
Publication Date: July 25, 2024
Last Updated: August 16, 2024
Management
- As cGVHD is a systemic disease, the overall management goal is to control the disease, to maintain optimal function, and to preserve adequate quality of life. Organ involvement with cGVHD determines the specific management goals. Below is a description of the aspects pertinent to oral cGVHD.
- The treatment goals in oral cGVHD are to relieve pain and xerostomia, improve oral function (e.g., eating, mouth opening), prevent secondary infection, prevent deterioration of the dentition, and detect malignant transformation as early as possible. Overall, this will improve quality of life and possibly life expectancy.
- Patients post allogeneic HCT, who are at risk for cGVHD, should be examined by an oral health care professional every 6–12 month for oral cGVHD manifestations, or sooner if the patient notices any changes. Biopsy and pathological examination should be performed on lesions suspicious for oral cancer [5].
- Generally, cGVHD is treated with systemic corticosteroids and steroid-sparing immunomodulators, including the classic calcineurin inhibitors as well as the more recent mechanism-based targeted agents. However, when the oral mucosa is the only site of cGVHD involvement or when the oral cGVHD is resistant to systemic treatment, topical treatment is of outmost importance. In such cases, the following treatment principles are suggested:
- When the lesions are generalized, a rinse may be more practical, whereas a gel may be more applicable for localized lesions. For gingival involvement, application in a medication tray or as a gauze occlusion may facilitate longer contact time.
- Topical corticosteroids are the first line of therapy (Table 1). The type of preparation and its concentration depend on the extent and severity of the oral lesions. When the lesions are ulcerative/erosive and symptomatic, an ultra-potent steroid is preferred. The topical steroid selection is also tailored to the patient’s tolerance of its consistency and mode of application. It is recommended to avoid long-term application of steroid on the lips. Although topical application uncommonly causes systemic adverse effects, clinicians should be aware of this potential risk [6]. This is mostly applicable for patients with ulcerative oral cGVHD who use topical steroids for longer durations. Topical application of potent steroids with lower bioavailability, such as budesonide, may be a preferred alternative.
- Topical tacrolimus or pimecrolimus (Table 1) [7] may be considered when topical steroids have an insufficient clinical effect. Patients should be informed that the medication may cause burning during initial application of tacrolimus ointment, which usually subsides with subsequent applications.
- For persistent, localized symptomatic oral lesions, intralesional steroid injections (Table 1) may be administered. Although some patients experience relief following a single injection, others need a few cycles of injections to achieve the desired outcome. Triamcinolone acetonide is the common steroid reported in the dental literature for intralesional injection in the management of inflammatory oral ulcers [8]. Additional optional steroids, side effects, complications, and pitfalls have been reported in the dermatology literature [9].
- Pain management should be considered. Topical agents for pain management include local anesthetics, local anti-histamines, or other agents that were reported to alleviate pain in oral mucositis [10]. Systemic pain management should be monitored, given the chronicity of the disease and risk for adverse effects in long-term use.
- Early evidence suggesting the benefits of phototherapy (PUVA or UVB), photobiomodulation [11, 12], and platelet gel has been published. Topical belumosudil suspension was tested for safety and tolerability in oral cGVHD patients. More research is needed about these interventions.
- Exophytic lesions, such as pyogenic granuloma and verruciform xanthoma, necessitate surgical excision followed by histopathological analysis of the excised tissue. In contrast, superficial mucoceles typically do not require a biopsy for diagnostic confirmation.
- Patients with sclerodermatous-type cGVHD are often treated systemically. In addition, these patients should be instructed to practice daily physical therapy such as active stretching of the tongue and perioral muscles, to prevent further oral and perioral fibrosis and preserve the range of motion. During follow-up appointments, the patient should be encouraged to continue performing these exercises. Other suggested treatment strategies include surgery, and intralesional corticosteroid injections.
- For detailed management protocols of hyposalivation or xerostomia, clinicians are referred to the OCSG CPS about Salivary Gland Hypofunction and Xerostomia [13]. Below are some general principles in the management of hyposalivation pertinent to cGVHD patients:
- Pharmacological sialogogues, such as pilocarpine and cevimeline, may be considered, taking into account the contraindications and possible adverse effects [14].
- Over-the-counter moistening agents may be used for palliation of dry mouth. Nonpharmacological saliva stimulants, such as sweet/sour sugar-free hard candies or chewing gums, may be used.
- In refractory cases, intraductal irrigation of the parotid glands [15] or electrostimulation therapy [16] may be considered for xerostomia relief.
- Frequent topical application of high-concentration fluoride preparation may help prevent dental caries [17]. Patient should be educated and encouraged to practice meticulous oral hygiene.
- Given that secondary oral candidiasis is relatively common in patients with hyposalivation treated with corticosteroids, antifungal treatment may be needed. Topical antifungals (e.g., nystatin, miconazole, clotrimazole) are advised for oral candidiasis. Antifungal lozenges should be avoided in cases of severe dry mouth, as such conditions do not facilitate the lozenges disintegration. Patients should be instructed to comply with the dosing protocol in order to achieve the best effect and to follow basic principles of resistance development prevention. Systemic antifungals (e.g., fluconazole) may also be considered. Denture wearers should be advised to minimize use of their prostheses (for example, removing them during sleep), and to clean, disinfect, and soak the prostheses in antifungal solution upon removal.
- The oral cGVHD manifestations may negatively impact the dentition. Hyposalivation due to cGVHD or the pretransplant high-intensity conditioning regimen may increase the risk for dental caries, and desquamative gingivitis may compromise oral hygiene practice [18, 19]. Furthermore, the limitation of mouth opening and loss of vestibular elasticity may be a barrier for oral and dental care. Therefore, the patient should be educated about the necessity of frequent dental checkups and meticulous oral hygiene tailored to their specific needs.
Recommendation Grading
Abbreviations
- cGVHD:
chronic Graft-versus-host Disease
Disclaimer
The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.
Overview
Title
Management of Oral Manifestations of Chronic Graft-Versus-Host-Disease
Authoring Organizations
Multinational Association of Supportive Care in Cancer
International Society of Oral Oncology
Publication Month/Year
July 25, 2024
Last Updated Month/Year
August 27, 2024
Document Type
Consensus
Country of Publication
Global
Document Objectives
A MASCC/ISOO Clinical Practice Statement (CPS) is aimed at generating a concise tool for clinicians, which concentrates practical information needed for the management of oral complications of cancer patients. This CPS is focused on the management of oral manifestations of chronic graft-versus-host-disease (cGVHD).
Inclusion Criteria
Male, Female, Adolescent, Adult, Child, Older adult
Health Care Settings
Ambulatory, Outpatient
Intended Users
Nurse, nurse practitioner, physician, physician assistant
Scope
Management
Diseases/Conditions (MeSH)
D006086 - Graft vs Host Disease
Keywords
graft-versus-host-disease, graft versus host disease, gvhd, graft vs host disease
Source Citation
Zadik Y, Raber-Durlacher JE, Epstein JB, Majorana A, Laheij A, Bardellini E, Blijlevens N, Elad S. MASCC/ISOO Clinical Practice Statement: Management of oral manifestations of chronic graft-versus-host-disease. Support Care Cancer. 2024 Jul 25;32(8):546. doi: 10.1007/s00520-024-08686-x. PMID: 39048807; PMCID: PMC11269426.