title: [Chronic graft-versus-host-disease involving the oral mucosa: clinical presentation and treatment].
abstract: Graft versus host disease (GVHD) is an alloimmune inflammatory process, which results from a donor-origin cellular response against host tissues. The chronic syndrome of GVHD (cGVHD) occurs in approximately 50% of patients post hematopoietic stem cell transplantation (HSCT) and remains the leading cause of non-malignant mortality. Oral cavity is one of the most frequent sites involved in cGVHD, possibly only second to skin. The oral tissues targeted by cGVHD are the mucosae, the salivary glands, the musculoskeletal apparatus and the periodontal structures. The mucosal cGVHD is accompanied by pain and mucosal irritation. Patients with cGVHD present with mucosal erosion and atrophy, lichenoid-hyperkeratotic changes, pseudomembranous ulcerations and mucoceles. Dry mouth may exacerbate mucosal irritation and erosion. In addition to impaired oral functions, cGVHD may lead to secondary malignancies in the form of solid cancers, particularly squamous cell carcinomas of the oral cavity. Moreover, administration of systemic azathioprine, a commonly used immunosuppressive drug in cGVHD patients, may significantly increase the incidence of tumors of oral cavity. The increased risk of secondary malignancies indicates the need for lifelong surveillance, particularly in younger patients. Scoring of oral GVHD was first addressed by NIH only in 2005. The NIH consensus paper referred to standard criteria for diagnosis, classification, and response to treatment. These scales were introduced for clinical use, although they require prospective validation studies. In the past, other scales were suggested and may still be used for research purposes. Management of oral cGVHD is compromised of preventive protocols and when cGVHD is developed, systemic and topical treatment. Because the majority of patients with oral cGVHD will develop the extensive form of the disease, they will be treated systemically. Systemic treatment is based on steroids and immunosuppressants, and, thus, increases the frequency of opportunistic infections. Only a few well-designed controlled trials using systemic treatments for cGVHD assessed oral outcomes. When the oral mucosa is the only site resistant to high doses of systemic corticosteroids or when GVHD is manifested only in the oral mucosa, the treatment approach should be topical therapy. Topical steroid preparations are the mainstay of local treatment. Budesonide is a novel steroid preparation that is being developed in the recent years for cGVHD. Its high topical anti-inflammatory activity together with low systemic bioavailability may provide enhanced treatment effects for local oral disease while sparing the host immunity. Second line of topical therapy includes pharmacologic immunosuppressants and phototherapy, combined with palliative treatment. This article aims at presenting the novel information about the clinical presentation, scoring scales, long term complications and treatment for mucosal cGVHD.
authors.affiliation: Dept. of Oral Medicine, The Hebrew University, Hadassah School of Dental Medicine, Israel.
authors.forename: S
authors.initials: S
authors.lastname: Elad
authors.forename: M
authors.initials: M
authors.lastname: Levitt
authors.forename: Shapira
authors.initials: S
authors.lastname: M Y
mesh_terms: D000278:Administration, Buccal; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis; D002908:Chronic Disease; D005938:Glucocorticoids / Q000627:therapeutic use; D006086:Graft vs Host Disease / Q000175:diagnosis* / Q000188:drug therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D017512:Lichenoid Eruptions / Q000175:diagnosis; D009059:Mouth Diseases / Q000175:diagnosis* / Q000188:drug therapy; D009061:Mouth Mucosa / Q000473:pathology; D009062:Mouth Neoplasms / Q000175:diagnosis; D016609:Neoplasms, Second Primary / Q000175:diagnosis; D019226:Oral Ulcer / Q000175:diagnosis; D010789:Phototherapy
chemical_list: D000305:Adrenal Cortex Hormones; D005938:Glucocorticoids; D007166:Immunosuppressive Agents