维生素B12缺乏口腔表征的研究进展
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摘要
维生素B12是一类含有咕啉环的类咕啉化合物,在维持正常造血和神经系统功能中起到关键作用。当血清维生素B12水平低于148 pmol·L~(-1)时,即可诊断为维生素B12缺乏,主要由吸收障碍导致。维生素B12缺乏的临床症状表现繁杂,严重的可表现为巨幼细胞贫血、神经系统损害、消化系统损害等症状,也有少数患者临床表现轻微而隐匿,易被忽视。由于维生素B12缺乏所造成的神经系统损害是不可逆的,因此,正确认识维生素B12缺乏症的临床表现对此病的早期诊断和正确治疗具有非常重要的意义。维生素B12缺乏的口腔损害可表现为萎缩性舌炎、复发性阿弗他溃疡、口腔扁平苔藓、灼口综合征等,多早于巨幼细胞贫血和神经系统症状出现,因此维生素B12缺乏患者大多首诊于口腔科。本文就维生素B12缺乏在口腔中的临床表征作一综述,以便于维生素B12缺乏的早发现、早诊断和早治疗。
Vitamin B12 is a cobalt-containing coordination compound and is necessary for normal hematopoiesis and nervous system function. Serum vitamin B12 lower than 148 pmol·L~(-1) would been diagnosed as vitamin B12 deficiency.Malabsorption is the common cause of vitamin B12 deficiency. The clinical features of vitamin B12 deficiency are complicated and vary greatly in severity, with symptoms such as anaemia, neurological features and digestive system damage. However, the clinical manifestations of a few patients are mild and concealed and easy to be ignored. Early diagnosis and treatment are important to prevent neurologic signs,which could be irreversible. Oral signs and symptoms include atrophic glossitis, recurrent aphthos ulcer, oral lichen planus and burning mouth syndrome, which may occur in the absence of symptomatic anaemia or neurological features. Patients with vitamin B12 deficiency maybe first visit the department of stomatology. The aim of this review is to summarize oral manifestations of vitamin B12 deficiency, so as to facilitate early detection, diagnosis and treatment of vitamin B12 deficiency.
Vitamin B12 is a cobalt-containing coordination compound and is necessary for normal hematopoiesis and nervous system function. Serum vitamin B12 lower than 148 pmol·L~(-1) would been diagnosed as vitamin B12 deficiency.Malabsorption is the common cause of vitamin B12 deficiency. The clinical features of vitamin B12 deficiency are complicated and vary greatly in severity, with symptoms such as anaemia, neurological features and digestive system damage. However, the clinical manifestations of a few patients are mild and concealed and easy to be ignored. Early diagnosis and treatment are important to prevent neurologic signs,which could be irreversible. Oral signs and symptoms include atrophic glossitis, recurrent aphthos ulcer, oral lichen planus and burning mouth syndrome, which may occur in the absence of symptomatic anaemia or neurological features. Patients with vitamin B12 deficiency maybe first visit the department of stomatology. The aim of this review is to summarize oral manifestations of vitamin B12 deficiency, so as to facilitate early detection, diagnosis and treatment of vitamin B12 deficiency.
引文
[1] Hunt A, Harrington D, Robinson S. Vitamin B12deficiency[J]. BMJ, 2014, 349:g5226.
[2] Devalia V, Hamilton MS, Molloy AM, et al. Guidelines for the diagnosis and treatment of cobalamin and folate disorders[J]. Br J Haematol,2014, 166(4):496-513.
[3]吕颖坚,黄俊明.维生素B_(12)的研究进展[J].中国食品卫生杂志,2012, 24(4):394-399.Lu YJ, Huang JM. Progress on the studies of vitamin B_(12)[J]. Chin J Food Hyg, 2012, 24(4):394-399.
[4] Hickie I,Naismith S,Ward PB, et al. Vascular risk and low serum B12 predict white matter lesions in patients with major depression[J]. J Affect Disord,2005, 85(3):327-332.
[5] Doran M, Rassam SS, Jones LM, et al. Toxicity after intermittent inhalation of nitrous oxide for analgesia[J]. BMJ, 2004, 328(7452):1364-1365.
[6] Lechner K, Fodinger M, Grisold W, et al. Vitamin B12 deficiency. New data on an old theme[J]. Wien Klin Wochenschr. 2005, 117(17):579-591.
[7] Sun A, Lin HP, Wang YP, et al. Significant association of deficiency of hemoglobin, iron and vitamin B12, high homocysteine level, and gastric parietal cell antibody positivity with atrophic glossitis[J]. J Oral Pathol Med, 2012, 41(6):500-504.
[8]朱敬慈,王宇峰,盛净,等.萎缩性舌炎与维生素B12缺乏之间的关系[J].上海口腔医学,2013, 22(1):58-62.Zhu JC, Wang YF, Sheng J, et al. Atrophic glossitis is attributed to cobalamin deficiency[J]. Shanghai J Stomatol,2013, 22(1):58-62.
[9]曹远盼.萎缩性舌炎与贫血相关因子的关系[D].青岛:青岛大学,2017.Cao YP. The relationship between atrophic glossitis and anemia factor[D]. Qingdao:Qingdao University,2017.
[10]崔鸢,代青芸,冯慧,等.萎缩性舌炎病因的研究进展[J].国际口腔医学杂志,2015, 42(4):442-445.Cui Y, Dai QY, Feng H, et al. Research progress on the etiology of atrophic glossitis[J]. Int J Stomatol,2015, 42(4):442-445.
[11] Piskin S, Sayan C,Durukan N, et al. Serum iron,ferritin, folic acid, and vitamin B12 levels in recurrent aphthous stomatitis[J]. J Eur Acad Dermatol Venereol,2002, 16(1):66-67.
[12] Koybasi S, Parlak AH, Serin E, et al. Recurrent aphthous stomatitis:investigation of possible etiologic factors[J]. Am J Otolaryngol, 2006, 27(4):229-232.
[13] Sun A, Chen HM, Cheng SJ, et al. Significant association of deficiencies of hemoglobin, iron, vitamin B12, and folic acid and high homocysteine level with recurrent aphthous stomatitis[J]. J Oral Pathol Med,2015,44(4):300-305.
[14]孟娜.成年女性维生素B12、叶酸缺乏与口腔黏膜异常的相关性分析[J].贵阳中医学院学报,2014,36(6):78-79.Meng N. Correlation analysis of vitamin B12, folate deficiency and oral mucosa abnormality in adult women[J]. J Guiyang Coll Trad Chin Med, 2014,36(6):78-79.
[15] Liu HL, Chiu SC. The effectiveness of Vitamin B12for relieving pain in Aphthous ulcers:a randomized,double-blind, placebo-controlled trial[J]. Pain Manag Nurs, 2015, 16(3):182-187.
[16]金鑫.维生素B_(12)缺乏致复发性口腔溃疡1例[J/OL].全科口腔医学电子杂志,2015, 2(10):104, 106.Jin X. Recurrent oral ulcer of vitamin B_(12)deficiency:a case report[J/OL]. Gen J Stomatol, 2015, 2(10):104, 106.
[17] Challacombe SJ. Haematological abnormalities in oral lichen planus, candidiasis, leukoplakia and nonspecific stomatitis[J]. Int J Oral Maxillofac Surg,1986, 15(1):72-80.
[18] Chen HM, Wang YP, Chang JY, et al. Significant association of deficiencies of hemoglobin, iron, folic acid, and vitamin B12 and high homocysteine level with oral lichen planus[J]. J Formos Med Assoc,2015, 114(2):124-129.
[19] Chang JY, Wang YP, Wu YC, et al. Hematinic deficiencies and anemia statuses in antigastric parietal cell antibody-positive erosive oral lichen planus patients with desquamative gingivitis[J]. J Formos Med Assoc,2016, 115(10):860-866.
[20] Thongprasom K, Youngnak P, Aneksuk V. Folate and vitamin B12 levels in patients with oral lichen planus,stomatitis or glossitis[J]. Southeast Asian J Trop Med Public Health, 2001,32(3):643-647.
[21] Chiang CP, Yu-Fong Chang J, et al. Oral lichen planusDifferential diagnoses, serum autoantibodies, hematinic deficiencies, and management[J]. J Formos Med Assoc,2018, 117(9):756-765.
[22] Jolly M, Nobile S. Vitamin status of patients with oral lichen planus[J]. Aust Dent J, 1977, 22(6):446-450.
[23] Kleinegger CL, Krolls SO. Severe pernicious anemia presenting with burning mouth symptoms[J]. Miss Dent Assoc J, 1996, 52(1):12-14.
[24] Vucicevic-Boras V, Topic B,Cekic-Arambasin A,et al. Lack of association between burning mouth syndrome and hematinic deficiencies[J]. Eur J Med Res,2001,6(9):409-412.
[25] Lin HP, Wang YP, Chen HM, et al. Significant association of hematinic deficiencies and high blood homocysteine levels with burning mouth syndrome[J]. J Formos Med Assoc,2013, 112(6):319-325.
[26] De Giuseppe R, Novembrino C, Guzzi G, et al. Burning mouth syndrome and vitamin B12 deficiency[J]. J Eur Acad Dermatol Venereol,2011,25(7):869-870.
[27] Zong G, Holtfreter B,Scott AE,et al. Serum vitamin B12 is inversely associated with periodontal progression and risk of tooth loss:a prospective cohort study[J]. J Clin Periodontol,2016, 43(1):2-9.
[28] Neiva RF, Al-Shammari K, Nociti FH Jr, et al.Effects of vitamin-B complex supplementation on periodontal wound healing[J]. J Periodontol, 2005,76(7):1084-1091.
[29] Pontes HA, Neto NC, Ferreira KB, et al. Oral manifestations of vitamin B12 deficiency:a case report[J].J Can Dent Assoc, 2009, 75(7):533-537.
[30] Stone KL,Bauer DC,Sellmeyer D,et al. Low serum vitamin B-12 levels are associated with increased hip bone loss in older women:a prospective study[J]. J Clin Endocrinol Metab, 2004, 89(3):1217-1221.
[31] Field EA, Speechley JA, Rugman FR, et al. Oral signs and symptoms in patients with undiagnosed vitamin B12 deficiency[J]. J Oral Pathol Med, 1995,24(10):468-470.
[32] Graells J,Ojeda RM,Muniesa C,et al. Glossitis with linear lesions:an early sign of vitamin B12 deficiency[J]. J Am Acad Dermatol, 2009, 60(3):498-500.
[33] Lu SY, Wu HC. Initial diagnosis of anemia from sore mouth and improved classification of anemias by MCV and RDW in 30 patients[J]. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2004, 98(6):679-685.
[34]刘晓松,华红.口腔黏膜异常预测隐匿性维生素B12或叶酸缺乏的临床研究[A].第七次中国老年口腔医学年会暨亚洲老年口腔医学学术研讨会论文汇编[C]. 2012:160-161.Liu XS, Hua H. Clinical study on prediction of latent vitamin B12 or folic acid deficiency by abnormal oral mucosa[A]. Proceedings of the 7th Annual Meeting of Chinese Geriatric Dentistry Asian Academic Conference of Geriatric Dentistry[C]. 2012:160-161.
[2] Devalia V, Hamilton MS, Molloy AM, et al. Guidelines for the diagnosis and treatment of cobalamin and folate disorders[J]. Br J Haematol,2014, 166(4):496-513.
[3]吕颖坚,黄俊明.维生素B_(12)的研究进展[J].中国食品卫生杂志,2012, 24(4):394-399.Lu YJ, Huang JM. Progress on the studies of vitamin B_(12)[J]. Chin J Food Hyg, 2012, 24(4):394-399.
[4] Hickie I,Naismith S,Ward PB, et al. Vascular risk and low serum B12 predict white matter lesions in patients with major depression[J]. J Affect Disord,2005, 85(3):327-332.
[5] Doran M, Rassam SS, Jones LM, et al. Toxicity after intermittent inhalation of nitrous oxide for analgesia[J]. BMJ, 2004, 328(7452):1364-1365.
[6] Lechner K, Fodinger M, Grisold W, et al. Vitamin B12 deficiency. New data on an old theme[J]. Wien Klin Wochenschr. 2005, 117(17):579-591.
[7] Sun A, Lin HP, Wang YP, et al. Significant association of deficiency of hemoglobin, iron and vitamin B12, high homocysteine level, and gastric parietal cell antibody positivity with atrophic glossitis[J]. J Oral Pathol Med, 2012, 41(6):500-504.
[8]朱敬慈,王宇峰,盛净,等.萎缩性舌炎与维生素B12缺乏之间的关系[J].上海口腔医学,2013, 22(1):58-62.Zhu JC, Wang YF, Sheng J, et al. Atrophic glossitis is attributed to cobalamin deficiency[J]. Shanghai J Stomatol,2013, 22(1):58-62.
[9]曹远盼.萎缩性舌炎与贫血相关因子的关系[D].青岛:青岛大学,2017.Cao YP. The relationship between atrophic glossitis and anemia factor[D]. Qingdao:Qingdao University,2017.
[10]崔鸢,代青芸,冯慧,等.萎缩性舌炎病因的研究进展[J].国际口腔医学杂志,2015, 42(4):442-445.Cui Y, Dai QY, Feng H, et al. Research progress on the etiology of atrophic glossitis[J]. Int J Stomatol,2015, 42(4):442-445.
[11] Piskin S, Sayan C,Durukan N, et al. Serum iron,ferritin, folic acid, and vitamin B12 levels in recurrent aphthous stomatitis[J]. J Eur Acad Dermatol Venereol,2002, 16(1):66-67.
[12] Koybasi S, Parlak AH, Serin E, et al. Recurrent aphthous stomatitis:investigation of possible etiologic factors[J]. Am J Otolaryngol, 2006, 27(4):229-232.
[13] Sun A, Chen HM, Cheng SJ, et al. Significant association of deficiencies of hemoglobin, iron, vitamin B12, and folic acid and high homocysteine level with recurrent aphthous stomatitis[J]. J Oral Pathol Med,2015,44(4):300-305.
[14]孟娜.成年女性维生素B12、叶酸缺乏与口腔黏膜异常的相关性分析[J].贵阳中医学院学报,2014,36(6):78-79.Meng N. Correlation analysis of vitamin B12, folate deficiency and oral mucosa abnormality in adult women[J]. J Guiyang Coll Trad Chin Med, 2014,36(6):78-79.
[15] Liu HL, Chiu SC. The effectiveness of Vitamin B12for relieving pain in Aphthous ulcers:a randomized,double-blind, placebo-controlled trial[J]. Pain Manag Nurs, 2015, 16(3):182-187.
[16]金鑫.维生素B_(12)缺乏致复发性口腔溃疡1例[J/OL].全科口腔医学电子杂志,2015, 2(10):104, 106.Jin X. Recurrent oral ulcer of vitamin B_(12)deficiency:a case report[J/OL]. Gen J Stomatol, 2015, 2(10):104, 106.
[17] Challacombe SJ. Haematological abnormalities in oral lichen planus, candidiasis, leukoplakia and nonspecific stomatitis[J]. Int J Oral Maxillofac Surg,1986, 15(1):72-80.
[18] Chen HM, Wang YP, Chang JY, et al. Significant association of deficiencies of hemoglobin, iron, folic acid, and vitamin B12 and high homocysteine level with oral lichen planus[J]. J Formos Med Assoc,2015, 114(2):124-129.
[19] Chang JY, Wang YP, Wu YC, et al. Hematinic deficiencies and anemia statuses in antigastric parietal cell antibody-positive erosive oral lichen planus patients with desquamative gingivitis[J]. J Formos Med Assoc,2016, 115(10):860-866.
[20] Thongprasom K, Youngnak P, Aneksuk V. Folate and vitamin B12 levels in patients with oral lichen planus,stomatitis or glossitis[J]. Southeast Asian J Trop Med Public Health, 2001,32(3):643-647.
[21] Chiang CP, Yu-Fong Chang J, et al. Oral lichen planusDifferential diagnoses, serum autoantibodies, hematinic deficiencies, and management[J]. J Formos Med Assoc,2018, 117(9):756-765.
[22] Jolly M, Nobile S. Vitamin status of patients with oral lichen planus[J]. Aust Dent J, 1977, 22(6):446-450.
[23] Kleinegger CL, Krolls SO. Severe pernicious anemia presenting with burning mouth symptoms[J]. Miss Dent Assoc J, 1996, 52(1):12-14.
[24] Vucicevic-Boras V, Topic B,Cekic-Arambasin A,et al. Lack of association between burning mouth syndrome and hematinic deficiencies[J]. Eur J Med Res,2001,6(9):409-412.
[25] Lin HP, Wang YP, Chen HM, et al. Significant association of hematinic deficiencies and high blood homocysteine levels with burning mouth syndrome[J]. J Formos Med Assoc,2013, 112(6):319-325.
[26] De Giuseppe R, Novembrino C, Guzzi G, et al. Burning mouth syndrome and vitamin B12 deficiency[J]. J Eur Acad Dermatol Venereol,2011,25(7):869-870.
[27] Zong G, Holtfreter B,Scott AE,et al. Serum vitamin B12 is inversely associated with periodontal progression and risk of tooth loss:a prospective cohort study[J]. J Clin Periodontol,2016, 43(1):2-9.
[28] Neiva RF, Al-Shammari K, Nociti FH Jr, et al.Effects of vitamin-B complex supplementation on periodontal wound healing[J]. J Periodontol, 2005,76(7):1084-1091.
[29] Pontes HA, Neto NC, Ferreira KB, et al. Oral manifestations of vitamin B12 deficiency:a case report[J].J Can Dent Assoc, 2009, 75(7):533-537.
[30] Stone KL,Bauer DC,Sellmeyer D,et al. Low serum vitamin B-12 levels are associated with increased hip bone loss in older women:a prospective study[J]. J Clin Endocrinol Metab, 2004, 89(3):1217-1221.
[31] Field EA, Speechley JA, Rugman FR, et al. Oral signs and symptoms in patients with undiagnosed vitamin B12 deficiency[J]. J Oral Pathol Med, 1995,24(10):468-470.
[32] Graells J,Ojeda RM,Muniesa C,et al. Glossitis with linear lesions:an early sign of vitamin B12 deficiency[J]. J Am Acad Dermatol, 2009, 60(3):498-500.
[33] Lu SY, Wu HC. Initial diagnosis of anemia from sore mouth and improved classification of anemias by MCV and RDW in 30 patients[J]. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 2004, 98(6):679-685.
[34]刘晓松,华红.口腔黏膜异常预测隐匿性维生素B12或叶酸缺乏的临床研究[A].第七次中国老年口腔医学年会暨亚洲老年口腔医学学术研讨会论文汇编[C]. 2012:160-161.Liu XS, Hua H. Clinical study on prediction of latent vitamin B12 or folic acid deficiency by abnormal oral mucosa[A]. Proceedings of the 7th Annual Meeting of Chinese Geriatric Dentistry Asian Academic Conference of Geriatric Dentistry[C]. 2012:160-161.