Mucosal graft‐vs‐host disease

Abstract

Graft‐vs‐host disease (GVHD) is a serious complication of hematopoietic stem cell transplantation (HSCT). Indications for HSCT have greatly expanded, and more patients are undergoing HSCT today than ever before. In addition, the options for immunosuppressive therapy for both prevention and treatment of GVHD have also expanded. These changes have in turn altered the landscape of this disease. We have reviewed the current literature on this subject and presented an update on this disease with a particular emphasis on mucosal manifestations.

Longitudinal Assessment of Hematopoietic Stem Cell Transplantation and Hyposalivation

“…White corresponds to prevalence of normal stimulated whole-saliva flow rate (SWSFR) defined as > 0.7 mL/min, light striping corresponds to hyposalivation (0.3 mL/min ≤ SWSFR ≤ 0.7 mL/min), and dense striping to severe hyposalivation (SFR ≤ 0.3 mL/min). Median stimulated whole SFR (mL/min), (n) 1.0 (68) 0.8 (28) 0.9 (28) 0.7 (18) Stimulated whole SFR range (mL/min) 0.1 -3.1 0.3 -1.8 0.4 -2.1 0.2 -1.6 Hyposalivation (≤ 0.7 mL/min) %, (n) 34% (23) 36% (10) 18% (5) 28% (5) Hyposalivation (≤ 0.3 mL/min) %, (n) 9% (5) 7% (2) 0% (0) 6% (1) Low-dose TBI Median stimulated whole SFR (mL/min), (n) 0.7 (49) 0.6 (23) 0.7 (25) 0.9 (19) Stimulated whole SFR range (mL/min) 0.2 -2.8 0.2 -2.4 0.4 -2.4 0.3 -1.9 Hyposalivation (≤ 0.7 mL/min) %, (n) 53% (26) 57% (13) 36% (9) 26% (5) Hyposalivation (≤ 0.3 mL/min) %, (n) 12% (6) 17% (4) 0% (0) 5% (1) High-dose TBI Median stimulated whole SFR (mL/min), (n) 0.9 (91) 0.5 (47) frequently associated with dry mouth, oral discomfort, and weight loss (Mohty et al, 2002;Lew and Smith, 2007). Since chemotherapy, head and neck irradiation, polypharmacy, and malnutrition are all well-known individual causes of hyposalivation, it was not surprising to observe a high prevalence of hyposalivation in HSCT recipients (Sreebny, 2000;Soini et al, 2006;Moore and Guggenheimer, 2008;Jensen et al, 2010).…”

International Chronic Ocular Graft-vs-Host-Disease (GVHD) Consensus Group: Proposed Diagnostic Criteria for Chronic GVHD (Part I)

“…Dry eye disease (DED) is one of the most common manifestations of chronic graft-versus-host disease (GVHD) and has been recognized as an important complication after allogeneic hematopoietic stem cell transplantation (HSCT)123456789101112. Since visual function and ocular symptoms are largely related to patient's quality of life13, ocular complications have a great impact on morbidity after successful HSCT.…”

Autoimmunity at the ocular surface: pathogenesis and regulation

“…Ocular surface manifestations of GVHD include Dry Eye, keratoconjunctivitis sicca, pseudomembranous conjunctivitis, conjunctival fibrosis, lacrimal and meibomian gland disease, and corneal epithelial sloughing. 91,92 The severity of ocular surface disease has been staged from 1 to 4 based on the extent of conjunctival inflammation, conjunctival scarring and corneal epithelial sloughing 91,92 GVHD may be acute (developing <100 days post-transplant) or chronic (> 100 days). Conjunctivitis is typically observed in acute GVHD, whereas Dry Eye and keratoconjunctivitis sicca are more commonly observed in chronic GVHD.…”

“…Conjunctival immunopathology in acute GVHD shows T-cell infiltration within the conjunctival pseudomembranes and stroma. 92,93 More specifically, conjunctival biopsies taken from patients with chronic GVHD showed a significant increase of: CD3+ and CD14+ cells in the epithelium, T lymphocytes (CD3+, CD4+, CD8+) and CD14 cells in the stroma and very late antigen-4 (VLA-4) and lymphocyte function associated antigen-1 (LFA-1) expression in the stroma. CD14+ cells were significantly increased both in the epithelium and in the stroma of patients with signs or symptoms of Dry Eye compared with patients without ocular involvement.…”