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Immunohistopathological characterization and the impact of topical immunomodulatory therapy in oral chronic graft-versus-host disease: A pilot study
Motta, A., Zhan, Q., Larson, A., Lerman, M., Woo, S. B., Soiffer, R. J., Murphy, G. F., Treister, N. S.
Oral diseases. 2018;24(4):580-590
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Abstract
OBJECTIVE To characterize the immunohistopathological features of oral chronic graft-versus-host disease (cGVHD), and the impact of topical immunomodulatory therapy on the infiltrating cells. MATERIAL AND METHODS Paired oral cGVHD biopsies obtained before (n = 12) and 1 month after treatment (n = 12) with topical dexamethasone (n = 8) or tacrolimus (n = 4) were characterized by immunohistochemistry using a panel of CD1a, CD3, CD4, CD8, CD20, CD31, CD62E, CD103, CD163, c-kit, and FoxP3. Controls included acute GVHD (aGVHD; n = 3), oral lichen planus (OLP; n = 5), and normal tissues (n = 5). RESULTS Oral cGVHD specimens prior to treatment were mainly characterized by basal cell squamatization, lichenoid inflammation, sclerosis, apoptosis, and lymphocytic exocytosis. The infiltrating cells in oral cGVHD primarily consisted of CD3(+) , CD4(+) , CD8(+) , CD103(+) , CD163(+) , and FoxP3(+) cells, which were higher than in normal tissues. Topical dexamethasone or tacrolimus reduced neutrophilic exocytosis, basal cell squamatization, and lichenoid inflammation in oral cGVHD, and dexamethasone reduced the number of CD4(+) and CD103(+) cells. CONCLUSION The high expression of CD3, CD4, CD8, CD103, CD163, and FoxP3 confirms that oral cGVHD is largely T-cell-driven with macrophage participation. The impact of topical immunomodulatory therapy was variable, reducing histological inflammatory features, but with a weak clinicopathological correlation. Topical dexamethasone reduced the expression of CD4 and CD103, which may offer novel therapeutic targets.
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Efficacy and Safety of Topical Corticosteroids for Management of Oral Chronic Graft versus Host Disease
Elsaadany, B. A., Ahmed, E. M., Aghbary, S. M. H.
International Journal of Dentistry. 2017;2017:1908768
Abstract
BACKGROUND Oral chronic graft versus host disease (cGVHD) is a major complication in transplantation community, a problem that can be addressed with topical intervention. Topical corticosteroids are the first line of treatment although the choice remains challenging as none of the available treatments is supported by strong clinical evidence. OBJECTIVE This systematic review aims to determine the clinical efficacy and safety of topical corticosteroids for the management of the mucosal alterations of oral cGVHD. DATA SOURCES Electronic search of different databases was conducted: PubMed, Cochrane library, Grey literature, WHO, and clinical trials.gov for clinical trial registration as well as hand search in the references of relevant articles up to November 2016. DATA EXTRACTION Extracted pieces of information were intervention, population, sample sizes, and outcomes. DATA SYNTHESIS Six studies were included: 2 randomized clinical trials (RCTs), 3 cohort studies, and 1 pre-post clinical trial. RESULTS There is a limited evidence concerning clinical efficacy of topical corticosteroids. Clobetasol, dexamethasone, and budesonide were the topical corticosteroid of choice. The highest level of evidence score was given to clobetasol followed by budesonide with a lower evidence level. CONCLUSION All three topical corticosteroid preparations are effective for management of oral chronic GVHD with minimal easily avoided side effects.