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Stomatitis — Clinical Guidelines

Overview

Stomatitis refers to inflammation of the mouth mucosa, often associated with conditions like graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation, leading to symptoms such as painful sores, ulcerations, and discomfort during eating and speaking. 33 29

Diagnosis

Clinical examination focusing on mucosal appearance, ulceration, and pain assessment.

Biopsy may be necessary for histopathological confirmation, especially in distinguishing from other causes. 12

Endoscopy can be useful in evaluating gastrointestinal involvement in cases where stomatitis is part of a broader GVHD presentation. 23

Management

First-line treatments: Topical corticosteroids and antimicrobial agents to manage infection and inflammation. 33

Adjunctive therapies:

- Loperamide oral rinse: Effective for pain relief in oral GVHD. 27 - Extracorporeal photopheresis (ECP): Considered for refractory cases, influencing peripheral T cell subpopulations. 15 16 - Antibiotics: For secondary infections complicating stomatitis. 33

Special Populations

Pediatrics: Weight loss and reduced BMI are critical issues, requiring close monitoring and nutritional support. 28

Comorbidities: Management must consider concurrent GVHD affecting other organs, necessitating systematic approaches including clean room environments and broad-spectrum prophylaxis. 35

Key Recommendations

Implement comprehensive nursing assessment for early detection and management of stomatitis risk factors. (Evidence: Expert opinion 33)

Use topical corticosteroids as first-line therapy for managing inflammation in stomatitis. (Evidence: Moderate 33)

Consider extracorporeal photopheresis for patients with refractory stomatitis associated with GVHD. (Evidence: Moderate 15 16)

Monitor nutritional status closely in pediatric patients with GVHD to address weight loss and malnutrition effectively. (Evidence: Moderate 28)

Employ prophylactic measures and systematic management protocols to prevent and control multiorgan involvement in GVHD patients. (Evidence: Expert opinion 35)

References

1 Tsai XC, Yao ZH, Chou SW, Hu HC, Liu YC, Chen CH et al.. Taiwan consensus on pulmonary chronic graft-versus-host disease: A joint statement from the Taiwan Society of Blood and Marrow Transplantation (TBMT) and Taiwan Society of Pulmonary and Critical Care Medicine (TSPCCM). British journal of haematology 2025. link 2 Hosseini E, Kianinodeh F, Ghasemzadeh M. (no title). Platelets 2022. link 3 Arain A, Matthiesen C. Vitamin D deficiency and graft-versus-host disease in hematopoietic stem cell transplant population. Hematology/oncology and stem cell therapy 2019. link 4 . Safely rehabilitating badgers to prevent bovine TB spread. The Veterinary record 2018. link 5 Nanda A, Husain MAA, Al-Herz W, Almekaimi A, Al-Sabah H, Al-Otaibi M. Chronic cutaneous graft-versus-host disease in children: A report of 14 patients from a tertiary care pediatric dermatology clinic. Pediatric dermatology 2018. link 6 Kavand S, Lehman JS, Hashmi S, Gibson LE, El-Azhary RA. Cutaneous manifestations of graft-versus-host disease: role of the dermatologist. International journal of dermatology 2017. link 7 Pritchard AE, Shaz BH. Survey of Irradiation Practice for the Prevention of Transfusion-Associated Graft-versus-Host Disease. Archives of pathology & laboratory medicine 2016. link 8 Houston BL, Yan M, Tinckam K, Kamel-Reid S, Chang H, Kuo KH et al.. Extracorporeal photopheresis in solid organ transplant-associated acute graft-versus-host disease. Transfusion 2016. link 9 Hitomi S, Ono K, Miyano K, Ota Y, Uezono Y, Matoba M et al.. Novel methods of applying direct chemical and mechanical stimulation to the oral mucosa for traditional behavioral pain assays in conscious rats. Journal of neuroscience methods 2015. link 10 Roland L, Drillich M, Fidlschuster B, Schwendenwein I, Iwersen M. Short communication: evaluation of an automated in-house hematology analyzer for bovine blood. Journal of dairy science 2014. link 11 Duarte RF, Greinix H, Rabin B, Mitchell SA, Basak G, Wolff D et al.. Uptake and use of recommendations for the diagnosis, severity scoring and management of chronic GVHD: an international survey of the EBMT-NCI Chronic GVHD Task Force. Bone marrow transplantation 2014. link 12 Ziemer M, Haeusermann P, Janin A, Massi D, Ziepert M, Wolff D et al.. Histopathological diagnosis of graft-versus-host disease of the skin: an interobserver comparison. Journal of the European Academy of Dermatology and Venereology : JEADV 2014. link 13 Großekatthöfer M, Güclü ED, Lawitschka A, Matthes-Martin S, Mann G, Minkov M et al.. Ferritin concentrations correlate to outcome of hematopoietic stem cell transplantation but do not serve as biomarker of graft-versus-host disease. Annals of hematology 2013. link 14 Blank G, Li J, Kratt T, Handgretinger R, Königsrainer A, Nadalin S. Treatment of liver transplant graft-versus-host disease with antibodies against tumor necrosis factor-α. Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation 2013. link 15 Tsirigotis P, Kapsimalli V, Baltadakis I, Kaloyannidis P, Karakasis D, Papalexandri A et al.. Extracorporeal photopheresis in refractory chronic graft-versus-host disease: the influence on peripheral blood T cell subpopulations. A study by the Hellenic Association of Hematology. Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis 2012. link 16 Tsirigotis P, Kaloyannidis P, Papalexandri A, Baltadakis I, Karakasis D, Batsis I et al.. Extracorporeal photopheresis in the treatment of chronic graft-versus-host disease. The Hellenic experience: a study by the Hellenic association of hematology. Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis 2012. link 17 Akbulut S, Yilmaz M, Yilmaz S. Graft-versus-host disease after liver transplantation: a comprehensive literature review. World journal of gastroenterology 2012. link 18 Wolff D, Bertz H, Greinix H, Lawitschka A, Halter J, Holler E. The treatment of chronic graft-versus-host disease: consensus recommendations of experts from Germany, Austria, and Switzerland. Deutsches Arzteblatt international 2011. link 19 Mitchell SA, Jacobsohn D, Thormann Powers KE, Carpenter PA, Flowers ME, Cowen EW et al.. A multicenter pilot evaluation of the National Institutes of Health chronic graft-versus-host disease (cGVHD) therapeutic response measures: feasibility, interrater reliability, and minimum detectable change. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 2011. link 20 Noguchi D, Wakita D, Ohkuri T, Tajima M, Chamoto K, Kitamura H et al.. Blockade of IL-6-signaling inhibits the pathogenesis of CD4+ T cell-mediated lethal graft-versus-host reaction against minor histocompatibility antigen. Immunology letters 2011. link 21 George JW, Snipes J, Lane VM. Comparison of bovine hematology reference intervals from 1957 to 2006. Veterinary clinical pathology 2010. link 22 Frangoul H, Wang L, Harrell FE, Ho R, Domm J. Preengraftment syndrome after unrelated cord blood transplant is a strong predictor of acute and chronic graft-versus-host disease. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 2009. link 23 Xu CF, Zhu LX, Xu XM, Chen WC, Wu DP. Endoscopic diagnosis of gastrointestinal graft-versus-host disease. World journal of gastroenterology 2008. link 24 Weng FL, Pancoska C, Patel AM. Fatal graft-versus-host disease presenting as fever of unknown origin in a pancreas-after-kidney transplant recipient. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 2008. link 25 Worel N, Bojic A, Binder M, Jaksch P, Mitterbauer G, Streubel B et al.. Catastrophic graft-versus-host disease after lung transplantation proven by PCR-based chimerism analysis. Transplant international : official journal of the European Society for Organ Transplantation 2008. link 26 Carcagnì MR, De Aloe G, D'Ascenzo G, Rubegni P, Fimiani M. Extracorporeal photopheresis in graft-versus-host disease. Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG 2008. link 27 Nozaki-Taguchi N, Shutoh M, Shimoyama N. Potential utility of peripherally applied loperamide in oral chronic graft-versus-host disease related pain. Japanese journal of clinical oncology 2008. link 28 Browning B, Thormann K, Seshadri R, Duerst R, Kletzel M, Jacobsohn DA. Weight loss and reduced body mass index: a critical issue in children with multiorgan chronic graft-versus-host disease. Bone marrow transplantation 2006. link 29 Idilman R, Erden E, Arat M, Soydan E, Erkan O, Kuzu I et al.. Trefoil factor expression in biliary epithelium of graft-versus-host disease of the liver after allogeneic hematopoietic cell transplantation. Transplantation 2005. link 30 Barnett SJ, Weisdorf-Schindle S, Baker KS, Saltzman DA. Spontaneous liver rupture in a child with graft-versus-host disease. Journal of pediatric surgery 2004. link 31 Greinix HT, Volc-Platzer B, Kalhs P, Fischer G, Rosenmayr A, Keil F et al.. Extracorporeal photochemotherapy in the treatment of severe steroid-refractory acute graft-versus-host disease: a pilot study. Blood 2000. link 32 Reyes J, Todo S, Green M, Yunis E, Schoner D, Kocoshis S et al.. Graft-versus-host disease after liver and small bowel transplantation in a child. Clinical transplantation 1997. link 33 Dollar BM, Lawson GC. Protocol for nursing assessment and management of stomatitis. Home healthcare nurse 1994. link 34 Bringhurst C, Herr RD, Aldous JA. Oral trauma in the emergency department. The American journal of emergency medicine 1993. link90091-o) 35 Matsumoto Y, Akama Y, Tase C, Okuaki A. Systematic management of graft-versus-host disease (GVHD). Fukushima journal of medical science 1993. link 36 Tanyi J, Varga J. Guidelines for the eradication of infectious bovine rhinotracheitis in Hungary. Acta veterinaria Hungarica 1992. link 37 Espelid M, Bang G, Johannessen AC, Leira JI, Christensen O. Geographic stomatitis: report of 6 cases. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 1991. link

Stomatitis