Oral Complications of Chronic Graft-Versus-Host Disease

Fall‐Dickson, Jane M.; Pavletić, Steven Z.; Mays, Jacqueline W.; Schubert, Mark M.

doi:10.1093/jncimonographs/lgz007

Cited by 46 publications

(50 citation statements)

References 90 publications

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“…Recurring histological features were assessed, ranging from intraepithelial lymphocytes and band-like inflammatory infiltrate to atrophic epithelium with basal cell liquefaction degeneration including apoptosis, as well as separation of epithelium and formation of pseudo-rete ridges. Most features had been reported previously, but the pseudo-rete ridges were novel [28]. Additional features observed but not included in the scheme were leukoedema-like changes, as well as vacuolated signet ring-like cells.…”

Section: Discussionmentioning

confidence: 78%

Histopathological Grading of Oral Mucosal Chronic Graft-versus-Host Disease: Large Cohort Analysis

Tollemar

Tudzarovski

Warfvinge

et al. 2020

Biology of Blood and Marrow Transplantation

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versus-host disease (GVHD) can manifest as acute or chronic complications in patients after hematopoietic cell transplantation (HCT). Oral chronic GVHD (cGVHD) occurs in approximately 70% of HCT recipients and includes lichenoid-like mucosal reactions, restricted mouth opening, and salivary gland dysfunction. However, the underlying histopathological presentation remains to be validated in large cohorts. We characterized the histopathological features of oral mucosal cGVHD and devised a scoring model in a large patient cohort (n = 112). Oral mucosal biopsy sections (n = 303) with and without oral cGVHD were identified from archived and current HCT recipients with additional healthy controls. Histological screening was performed on hematoxylin and eosinstained and periodic acid-Schiff-stained sections. A points-based grading tool (0 to 19, grade 0 to IV) was established based on intraepithelial lymphocytes and band-like inflammatory infiltrate, atrophic epithelium with basal cell liquefaction degeneration, including apoptosis, as well as separation of epithelium and pseudo-rete ridges. Validation involved 62 biopsy specimens, including post-HCT (n = 47) and healthy (n = 15) specimens. Remaining biopsy specimens (n = 199) were blindly graded by 3 observers. Histological severity was correlated with clinical diagnostic and distinctive features, demonstrating a spectrum of individual patient severity, including frequent signs of subclinical GVHD in healthy mucosa. However, oral cGVHD presented with significantly higher (P < .001) scores compared with HCT controls, with moderate to high positive likelihood ratios for inflammatory infiltrate, exocytosis, and basal membrane alterations. The grade II-IV biopsy specimens demonstrated a histopathological diagnosis of active mucosal lichenoid-like cGVHD, highlighting the importance of correlating clinical presentation with the dynamic histopathological processes for improved patient stratification. In addition, this tool could be used for assessing treatments, pathological processes, and immune cellular content to provide further insight into this debilitating disease.

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Section: Discussionmentioning

confidence: 78%

Histopathological Grading of Oral Mucosal Chronic Graft-versus-Host Disease: Large Cohort Analysis

Tollemar

Tudzarovski

Warfvinge

et al. 2020

Biology of Blood and Marrow Transplantation

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“…According to Fall-Dickson et al [17], no reliable clinical signs or related symptoms are known to predict the clinical course of oral involvement of cGVHD. Therefore, they recommended evaluating the impact of oral cGVHD on patients experience/symptoms and (oral health related) QoL.…”

Section: Discussionmentioning

confidence: 99%

“…Up to 80% of patients with cGVHD demonstrate oral involvement at a certain time point after HSCT [15,16]. Oral manifestations can be divided into mucosal disease, and/or salivary gland dysfunction and/or, less frequently, sclerotic changes [17]. Signs and symptoms include sensitivity of the oral mucosa to foods and liquids, oral pain, xerostomia and/or hyposalivation, increased risk for dental caries, difficulty speaking, recurrent fungal infections, recurrent superficial mucoceles, and mucosal presentations such as erythema, lichenoid or ulceration, taste alterations, dysphagia, and reduced mouth opening [7,16].…”

Section: Introductionmentioning

confidence: 99%

“…Due to the increased number of HSCT's performed and the increased survival rate after treatment, the quality of life (QoL) of patients has become an important health outcome. However, to what extent oral cGVHD affects the OHRQoL of patients is still unclear [10,17]. Therefore, the aim of this study was to examine the OHRQoL of patients with oral cGVHD and to correlate it to oral mucosal cGVHD and salivary gland cGVHD.…”

Section: Introductionmentioning

confidence: 99%

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Oral health–related quality of life of patients with oral chronic graft-versus-host disease

Stolze

Boor

Hazenberg

et al. 2021

Support Care Cancer

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Purpose Symptoms of oral chronic graft-versus-host-disease (cGVHD) may significantly affect the oral health–related quality of life (OHRQoL). This study aimed to assess the OHRQoL in patients with oral cGVHD and to examine whether oral cGVHD symptoms, mucosal cGVHD, and salivary gland function correlated with OHRQoL. Methods Patients referred to the oral cGVHD outpatient clinic were included. Severity of oral mucosal cGVHD, oral cGVHD symptoms, and OHRQoL was assessed by the NIH OMS, NIH OSS, and OHIP-14, respectively. Unstimulated and stimulated whole salivary flow rates were determined and categorized into “hyposalivation,” “normal salivary flow,” and “hypersalivation.” Results Of 56 included patients, 80% had mild, moderate, or severe oral mucosal cGVHD. Mean total score of OHRQoL was 16.5 (±11.7), negatively affected by functional problems. Patients reported highest scores regarding oral sensitivity and xerostomia. Significant correlations were found between severity of oral pain and OHRQoL and between oral sensitivity and OHRQoL. No correlation was found between oral mucosal cGVHD and OHRQoL. Patients with hyposalivation, normal salivary flow, and hypersalivation reported equal levels of OHRQoL. Conclusion Results demonstrate that the OHRQoL was mostly negatively affected by complaints of oral pain and oral sensitivity and less by the severity of oral mucosal cGVHD assessed by the NIH OMS score. Special attention of (oral) health care professionals for patients with oral cGVHD is mandatory to alleviate their symptoms and improve OHRQoL.

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“…Oral involvement could represent the only manifestation of the cGVHD or could be comprised in a multitude of chronic symptoms. cGVHD may appear on the oral mucosa (e.g., oral verruciform xanthoma, erytroplakia), at the salivary glands (e.g., multiple mucoceles on the soft palate, hyposalivation, xerostomia, impairment in the quality of saliva, gland swelling) and in musculoskeletal apparatus disfunction [ 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Topical Corticosteroids a Viable Solution for Oral Graft versus Host Disease? A Systematic Insight on Randomized Clinical Trials

et al. 2020

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Background and Objectives: This research attempts to provide a clear view of the literature on randomized clinical trials (RCTs) concerning the efficacy of topical dexamethasone, clobetasol and budesonide in oral graft versus host disease (GVHD). Materials and Methods: An electronic search of the PubMed, Web of Science and Scopus databases was carried out for eligible RCTs. Studies were included if they had adult patients with oral GVHD treatment with topical corticosteroids, and if the RCT study was published in English. The Cochrane Risk of Bias tool was used to assess the quality of these studies. Overall, three RCTs were included (an Open, Randomized, Multicenter Trial; a Randomized Double-Blind Clinical Trial; and an Open-Label Phase II Randomized Trial). Results: The trials involved 76 patients, of which 44 patients received topical dexamethasone, 14 patients received topical clobetasol and 18 patients received topical budesonide. Topical agents were most frequently used when oral tissues were the sole site of involvement. It appears that the best overall response is present for budesonide with no difference between the four arms, followed by clobetasol, and then by dexamethasone. The limitation of the current study is mainly represented by the fact that overall response was derived in two of the studies from other parameters. Moreover, both budesonide and clobetasol were used in only one study each, while two assessed dexamethasone. Conclusions: Based on the clinical trials, all three agents seem to be effective in treating oral GVHD and had a satisfactory safety profile. There is still a need for assessing high quality RCTs to assess the efficacy of these therapies on a larger cohort.

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Oral Complications of Chronic Graft-Versus-Host Disease

Cited by 46 publications

References 90 publications

Histopathological Grading of Oral Mucosal Chronic Graft-versus-Host Disease: Large Cohort Analysis

Histopathological Grading of Oral Mucosal Chronic Graft-versus-Host Disease: Large Cohort Analysis

Oral health–related quality of life of patients with oral chronic graft-versus-host disease

Topical Corticosteroids a Viable Solution for Oral Graft versus Host Disease? A Systematic Insight on Randomized Clinical Trials

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