|
| |
| EDITORIAL |
|
| Ahead of print publication |
|
|
Oral health alterations: Glimpse into its connection to inflammatory rheumatic diseases
Rahnuma Ahmad1, Mainul Haque2
1 Department of Physiology, Medical College for Women and Hospital, Dhaka, Bangladesh
2 The Unit of Pharmacology, Faculty of Medicine and Defence Health, Universiti Pertahanan Nasional Malaysia (National Defence University of Malaysia), Kuala Lumpur, Malaysia
| Date of Submission | 29-Jan-2023 |
| Date of Acceptance | 31-Jan-2023 |
| Date of Web Publication | 16-Feb-2023 |
Correspondence Address:
Mainul Haque,
The Unit of Pharmacology, Faculty of Medicine and Defence Health, Universiti Pertahanan Nasional Malaysia (National Defence University of Malaysia), Kem Perdana Sungai Besi, Kuala Lumpur
Malaysia
 Source of Support: None, Conflict of Interest: None DOI: 10.4103/aihb.aihb_11_23
Chronic inflammatory rheumatic disease (IRD) is suffered by approximately 3% of global citizens and includes rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and Sjögren's syndrome.[1],[2] There are several systemic complications, including complications of cardiovascular, renal, respiratory and neurological systems. There are also oral manifestations of rheumatic disease in some patients [Figure 1].[3] Oral symptoms along with other typical clinical manifestations may lead to the suspicion of the rheumatic disease since oral changes may be one of the early signs of these systemic disorders. Condition like oral aphthous has been noted in about 50% of individuals suffering from SLE.[4],[5] About 90% of individuals with Sjögren's syndrome suffer from hyposalivation and xerostomia. Microcheilia and microstomia have been noted in those suffering from systemic sclerosis (SSc) which interferes with the opening of the mouth. Other oral manifestations in chronic IRD include strawberry-like gum disease and jaw claudication.[3] | Figure 1: The different oral complications that may result from inflammation and altered immune response in inflammatory rheumatic diseases. This figure has been drawn with the premium version of BioRender (https://biorender.com/) with license number JB24XLKAMQ. Image Credit: Rahnuma Ahmad.
Click here to view |
| Oral Changes in Rheumatic Diseases | |  |
Oral aphthous ulcer
The frequent appearance of oral aphthous ulcers has been included in the 2012 Systemic Lupus International Collaborating Clinics SLE classification criteria. This is because individuals with IRDs and SLE patients suffer from repeated oral aphthous ulcer.[6] About 50% of SLE patients suffer from aphthous ulcer, and examination shows peripheral keratotic striae and whitish plaque with central erythema.[4],[5],[7] There have also been reports of lesions in the oral cavity like discoid lesions and lichenoid mucositis in gingival and buccal mucosae and lips.[7],[8] Basement membrane with linear deposition of immunoglobulin M, G and C3 has been observed by direct immunofluorescence study. The presence of CD4+ T-lymphocytes has also been noted in the site of lesion.[7],[9]
Dysphagia
Both muscles of the oropharynx and the wall of the oesophagus are responsible for swallowing, impairment of which may result in dysphagia.[10] In about 90% of SSc cases, there is an impairment of oesophageal movement causing dysphagia as well as stricture of oesophagus, gastro-oesophageal reflux and retrosternal burn. Hypotonia of the lower sphincter of the oesophagus and reduced functioning of the lower one-third of the oesophagus have been noted in individuals with SSc.[11],[12]
Dermatomyositis and polymyositis are rare rheumatic diseases that affect the muscles of the body and are characterised by weakness of muscle and high level of creatine kinase and affect organs such as joints, skin, gastrointestinal, cardiovascular and respiratory systems. The anti-nuclear antibodies are found often in these conditions.[3],[10] The proximal one-third of oesophagus as well as the posterior wall of the pharynx muscles suffer myopathies, which is immune mediated causing dysphagia.[10],[13] There has been a report of dysphagia in 12% and 54% of individuals suffering from dermatomyositis and polymyositis.[14] The time of transit through the pharynx to the upper sphincter of the oesophagus has been observed to be raised.[15] An association between a rise in internal malignancy incidence and dysphagia in individuals having dermatomyositis has been reported.[16] Hypersalivation observed in a number cases due to impairment of swallowing as well as salivation reflex precipitated through oesophageal reflux. Systemic symptoms such as loss of weight, fever which is low grade, joint pain or arthritis and fatigue may also be present.[17],[18],[19]
Microcheilia, microstomia and inflammatory rheumatic disease
Patients with SSc may suffer from microstomia (decreased aperture of lips) and microcheilia (small lips) along with radial folds periorally, telangiectasias of body, face and mucosa, thickening of skin and Raynaud's phenomenon.[3],[20] The opening of the mouth is limited in microstomia and is suffered by 70% of individuals suffering from SSc. Microstomia results from soft tissue fibrosis periorally.[21] There is deposition of collagen subcutaneously in the skin of the face giving it an appearance of a smooth mask.[22],[23] Telangiectasias of the labia, tongue and perioral region may also be present.[3] Since the incidence of carcinoma of the tongue in individuals suffering from SSc is high, the mucosa of the oral cavity of these individuals should be examined regularly to identify any lesion at an early stage and provide treatment.[24],[25] Dentists must refer SSc patients with oral lesion to a rheumatologist as early as possible since the involvement of the organ occurs rapidly.[26] Exercises may cause an improvement of the opening of the mouth and grafting of fat may be helpful in case of microstomia.[21],[27],[28]
Xerostomia
Xerostomia or dry mouth may be complained by patients with Sjögren's syndrome along with swelling of the salivary gland due to inflammation. This syndrome is an autoimmune disorder which affects the exocrine glands giving rise to ocular and oral dryness which is accompanied by systemic signs and symptoms.[3],[29] The primary Sjögren's syndrome criteria of classification acknowledged widely are the American-European Consensus Group classification, and four or more of the mentioned criteria need to be present: (1) symptom of xerostomia, (2) symptoms of dry eye, (3) objective dryness of mouth-positive salivary sialography and scintigraphy or <0.1 mL/min unstimulated rate of flow of saliva), (4) objective dryness of eye (Schirmer's test <5 mm in 5 min), (5) biopsy of labial gland showing focal sialadenitis of lymphocyte and (6) positive anti-SSB/La or anti-SSA/Ro.[30]
Another systemic fibroinflammatory disease related often to swelling of the salivary gland and dry mouth is a disease related to immunoglobulin G4 (IgG4). There is the presence of high level of IgG4 in serum with inflammation of multiple organs, including the lacrimal gland, periorbital structures, thyroid, pancreas, lungs, pituitary gland, biliary tree, retroperitoneal cavity and salivary gland.[31]
Periodontal disease
Periodontal disease leads to the destruction of the gingiva and supporting tissue of tooth with eventual loss of tooth.[32],[33],[34] The immune system of the host often affected through genetic make-up, infectious diseases, and environmental factors results in this chronic inflammatory condition. Individuals having RA often suffer from periodontitis. Several studies have noted an association between RA and periodontitis in which a greater prevalence of periodontitis was noted in subjects with RA when compared to those without RA.[35],[36] There is raised production of inflammatory cytokines like tumour necrosis factor-alpha, interleukin (IL)-8, IL-6 and IL-1β in case of both RA and periodontal disease.[33] In about 50%–70% of patients with RA, there is the presence of anti-citrullinated peptide antibodies and rheumatic factors, which is related to symptoms and damage of joints more in severity and greater mortality rate.[37],[38] An oral microbiota commonly related to periodontitis is Porphyromonas gingivalis which may aggravate the conversion of arginine to citrulline by means of type IV peptidyl arginine deiminase with ultimate production of ACRAs [Figure 2].[33] Studies have shown a decrease in RA severity in individuals who underwent non-surgical management of periodontal disease.[39],[40] | Figure 2: The vicious cycle of chronic inflammation, citrullination, immunity dysregulation and periodontal pathogens along with genetic and environmental factors cause periodontal damage and lead to periodontitis. This figure has been drawn with the premium version of BioRender (https://biorender.com/) with license number YC24Y151CF. Image Credit: Rahnuma Ahmad.
Click here to view |
Periodontitis has also been observed in patients with SSc. In 40% of SSc patients, a typical periodontitis radiographic sign of widening of space of the periodontal ligament was noted.[41],[42] This may have resulted from raised deposition of collagen,[43] decreased vascular endothelial growth factor and lowered periodontal capillary number with eventual greater tooth loss prevalence in patients with SSc.[44],[45] Periodontitis has also been noted in about 70% of individuals with SLE.[46] A meta-analysis of eight studies observed that periodontitis risk was higher than those without SLE.[47]
Overgrowth of the gingiva
Although overgrowth of the gingiva (gingiva enlargement resulting from raised cell number and extracellular matrix accumulation) may result from gingivitis related to poor maintenance of hygiene of oral cavity, different systemic disorders may also aggravate it.[3],[48] In granulomatosis with polyangiitis, there may be an overgrowth of the gingiva that is swollen, reddened with small punctate lesions and petechia-covered granular tissue which is strawberry-like gingivitis.[49],[50] Necrotising granulomatous vasculitis affects upper respiratory tracts in 90% of cases and, if not treated, may result in mandibular and maxillary bone destruction.[3],[51] Other conditions of the oral cavity include lingual necrosis and ulceration of the mucosa.[52]
Claudication of jaw
Pain of muscle of mastication during chewing is claudication of the jaw and occurs when function is impaired due to ischaemia with lactate accumulation of lactate in skeletal muscles.[53] A common manifestation of giant cell arteritis affecting large blood vessel is claudication of the jaw in Western subjects above the age of 50 years.[54] The temporal artery is affected by giant cell arteritis which when palpated is tender.[55] Giant cell artery symptoms include low-grade fever, depression, weight loss, temporal headaches, dental pain, dysarthria, dysphagia and rare occasion lip and tongue necrosis.[53] Individuals with claudication of the jaw need to be assessed by a rheumatologist for giant cell arteritis exclusion.[56]
Involvement of temporomandibular joint
A frequent condition suffered by patients of IRD is temporomandibular joint inflammation.[57] The individual suffers from pain of the jaw, restriction of motion, malocclusion and swelling. Involvement of the temporomandibular joint may take place in 90% of cases of juvenile idiopathic arthritis.[58],[59]
Rheumatic disease is frequently associated with different manifestations of the oral cavity for which patients seek the doctor's consultation initially. There are non-specific symptoms such as xerostomia and oral ulcers while other symptoms such as microstomia and strawberry-like gingivitis are characteristic of rare IRD like SSc and granulomatosis with polyangiitis, respectively. In IRDs, there are alterations in the immunological response, and inflammation. These deleterious process often influenced by lifestyle. Additionally, with erroneous healthcare intervention. There needs to be a collaboration between physicians and dentists to help early diagnosis and management of rheumatic disease complications both systemic and that of the oral cavity.
Consent for publication
The author reviewed and approved the final version and has agreed to be accountable for all aspects of the work, including any accuracy or integrity issues.
Disclosure
The author declares that they do not have any financial involvement or affiliations with any organisation, association or entity directly or indirectly with the subject matter or materials presented in this article. This includes honoraria, expert testimony, employment, ownership of stocks or options, patents or grants received or pending or royalties.
Data availability
Information is taken from freely available sources for this editorial.
Authorship contribution
All authors contributed significantly to the work, whether it be in the conception, design, utilisation, collection, analysis and interpretation of data or in all these areas. They also participated in the article's drafting, revision or critical review, gave their final approval for the version that would be published, decided on the journal to which the article would be submitted and made the responsible decision to be held accountable for all aspects of the work.
| References | | |
| 1. | Arida A, Protogerou AD, Kitas GD, Sfikakis PP. Systemic inflammatory response and atherosclerosis: The paradigm of chronic inflammatory rheumatic diseases. Int J Mol Sci 2018;19:1890.  |
| 2. | Helmick CG, Felson DT, Lawrence RC, Gabriel S, Hirsch R, Kwoh CK, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum 2008;58:15-25. |
| 3. | Gualtierotti R, Marzano AV, Spadari F, Cugno M. Main oral manifestations in immune-mediated and inflammatory rheumatic diseases. J Clin Med 2018;8:21. |
| 4. | Meyer U, Kleinheinz J, Handschel J, Kruse-Lösler B, Weingart D, Joos U. Oral findings in three different groups of immunocompromised patients. J Oral Pathol Med 2000;29:153-8. |
| 5. | Khatibi M, Shakoorpour AH, Jahromi ZM, Ahmadzadeh A. The prevalence of oral mucosal lesions and related factors in 188 patients with systemic lupus erythematosus. Lupus 2012;21:1312-5. |
| 6. | Petri M, Orbai AM, Alarcón GS, Gordon C, Merrill JT, Fortin PR, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 2012;64:2677-86. |
| 7. | Lourenço SV, de Carvalho FR, Boggio P, Sotto MN, Vilela MA, Rivitti EA, et al. Lupus erythematosus: Clinical and histopathological study of oral manifestations and immunohistochemical profile of the inflammatory infiltrate. J Cutan Pathol 2007;34:558-64. |
| 8. | López-Labady J, Villarroel-Dorrego M, González N, Pérez R, Mata de Henning M. Oral manifestations of systemic and cutaneous lupus erythematosus in a Venezuelan population. J Oral Pathol Med 2007;36:524-7. |
| 9. | Sciuca AM, Toader MP, Stelea CG, Maftei GA, Ciurcanu OE, Stefanescu OM, et al. Desquamative gingivitis in the context of autoimmune bullous dermatoses and lichen planus-challenges in the diagnosis and treatment. Diagnostics (Basel) 2022;12:1754. |
| 10. | Gadiparthi C, Hans A, Potts K, Ismail MK. Gastrointestinal and hepatic disease in the inflammatory myopathies. Rheum Dis Clin North Am 2018;44:113-29. |
| 11. | Thoua NM, Bunce C, Brough G, Forbes A, Emmanuel AV, Denton CP. Assessment of gastrointestinal symptoms in patients with systemic sclerosis in a UK tertiary referral centre. Rheumatology (Oxford) 2010;49:1770-5. |
| 12. | Desbois AC, Cacoub P. Systemic sclerosis: An update in 2016. Autoimmun Rev 2016;15:417-26. |
| 13. | Stathopoulos P, Dalakas MC. Autoimmune neurogenic dysphagia. Dysphagia 2022;37:473-87. |
| 14. | Iaccarino L, Ghirardello A, Bettio S, Zen M, Gatto M, Punzi L, et al. The clinical features, diagnosis and classification of dermatomyositis. J Autoimmun 2014;48-49:122-7. |
| 15. | Ertekin C, Seçil Y, Yüceyar N, Aydoğdu I. Oropharyngeal dysphagia in polymyositis/dermatomyositis. Clin Neurol Neurosurg 2004;107:32-7. |
| 16. | Mugii N, Hasegawa M, Matsushita T, Hamaguchi Y, Oohata S, Okita H, et al. Oropharyngeal dysphagia in dermatomyositis: Associations with clinical and laboratory features including autoantibodies. PLoS One 2016;11:e0154746. |
| 17. | Lundberg IE, Dastmalchi M. Possible pathogenic mechanisms in inflammatory myopathies. Rheum Dis Clin North Am 2002;28:799-822. |
| 18. | Yazici Y, Kagen LJ. Clinical presentation of the idiopathic inflammatory myopathies. Rheum Dis Clin North Am 2002;28:823-32. |
| 19. | |
| 20. | Katada Y, Tanaka T. Images in clinical medicine. Lingual Raynaud's phenomenon. N Engl J Med 2012;366:e12. |
| 21. | Yuen HK, Marlow NM, Reed SG, Mahoney S, Summerlin LM, Leite R, et al. Effect of orofacial exercises on oral aperture in adults with systemic sclerosis. Disabil Rehabil 2012;34:84-9. |
| 22. | Anbiaee N, Tafakhori Z. Early diagnosis of progressive systemic sclerosis (scleroderma) from a panoramic view: Report of three cases. Dentomaxillofac Radiol 2011;40:457-62. |
| 23. | Sharma ML, Mehrotra G, Sharma K, Suman S. Tail of the whale appearance: A pathognomonic feature of scleroderma. J Indian Acad Oral Med Radiol 2020;32:55-9. [Full text] |
| 24. | Alantar A, Cabane J, Hachulla E, Princ G, Ginisty D, Hassin M, et al. Recommendations for the care of oral involvement in patients with systemic sclerosis. Arthritis Care Res (Hoboken) 2011;63:1126-33. |
| 25. | Derk CT, Rasheed M, Spiegel JR, Jimenez SA. Increased incidence of carcinoma of the tongue in patients with systemic sclerosis. J Rheumatol 2005;32:637-41. |
| 26. | Allanore Y, Simms R, Distler O, Trojanowska M, Pope J, Denton CP, et al. Systemic sclerosis. Nat Rev Dis Primers 2015;1:15002. |
| 27. | Del Papa N, Caviggioli F, Sambataro D, Zaccara E, Vinci V, Di Luca G, et al. Autologous fat grafting in the treatment of fibrotic perioral changes in patients with systemic sclerosis. Cell Transplant 2015;24:63-72. |
| 28. | Maria AT, Maumus M, Le Quellec A, Jorgensen C, Noël D, Guilpain P. Adipose-derived mesenchymal stem cells in autoimmune disorders: State of the art and perspectives for systemic sclerosis. Clin Rev Allergy Immunol 2017;52:234-59. |
| 29. | Negrini S, Emmi G, Greco M, Borro M, Sardanelli F, Murdaca G, et al. Sjögren's syndrome: A systemic autoimmune disease. Clin Exp Med 2022;22:9-25. |
| 30. | Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, et al. Classification criteria for Sjögren's syndrome: A revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis 2002;61:554-8. |
| 31. | Mahajan VS, Mattoo H, Deshpande V, Pillai SS, Stone JH. IgG4-related disease. Annu Rev Pathol 2014;9:315-47. |
| 32. | Kinane DF, Stathopoulou PG, Papapanou PN. Periodontal diseases. Nat Rev Dis Primers 2017;3:17038. |
| 33. | Janssen KM, Vissink A, de Smit MJ, Westra J, Brouwer E. Lessons to be learned from periodontitis. Curr Opin Rheumatol 2013;25:241-7. |
| 34. | Ahmad R, Haque M. Oral health Messiers: Diabetes mellitus relevance. Diabetes Metab Syndr Obes 2021;14:3001-15. |
| 35. | Pischon N, Pischon T, Kröger J, Gülmez E, Kleber BM, Bernimoulin JP, et al. Association among rheumatoid arthritis, oral hygiene, and periodontitis. J Periodontol 2008;79:979-86. |
| 36. | Torkzaban P, Hjiabadi T, Basiri Z, Poorolajal J. Effect of rheumatoid arthritis on periodontitis: A historical cohort study. J Periodontal Implant Sci 2012;42:67-72. |
| 37. | Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet 2016;388:2023-38. |
| 38. | Ingegnoli F, Castelli R, Gualtierotti R. Rheumatoid factors: Clinical applications. Dis Markers 2013;35:727-34. |
| 39. | Ortiz P, Bissada NF, Palomo L, Han YW, Al-Zahrani MS, Panneerselvam A, et al. Periodontal therapy reduces the severity of active rheumatoid arthritis in patients treated with or without tumor necrosis factor inhibitors. J Periodontol 2009;80:535-40. |
| 40. | Erciyas K, Sezer U, Ustün K, Pehlivan Y, Kisacik B, Senyurt SZ, et al. Effects of periodontal therapy on disease activity and systemic inflammation in rheumatoid arthritis patients. Oral Dis 2013;19:394-400. |
| 41. | Veale BJ, Jablonski RY, Frech TM, Pauling JD. Orofacial manifestations of systemic sclerosis. Br Dent J 2016;221:305-10. |
| 42. | Dagenais M, MacDonald D, Baron M, Hudson M, Tatibouet S, Steele R, et al. The Canadian Systemic Sclerosis Oral Health Study IV: Oral radiographic manifestations in systemic sclerosis compared with the general population. Oral Surg Oral Med Oral Pathol Oral Radiol 2015;120:104-11. |
| 43. | Baron M, Hudson M, Dagenais M, Macdonald D, Gyger G, El Sayegh T, et al. Relationship between disease characteristics and oral radiologic findings in systemic sclerosis: Results from a Canadian Oral Health Study. Arthritis Care Res (Hoboken) 2016;68:673-80. |
| 44. | Ozcelik O, Haytac MC, Ergin M, Antmen B, Seydaoglu G. The immunohistochemical analysis of vascular endothelial growth factors A and C and microvessel density in gingival tissues of systemic sclerosis patients: Their possible effects on gingival inflammation. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;105:481-5. |
| 45. | Isola G, Williams RC, Lo Gullo A, Ramaglia L, Matarese M, Iorio-Siciliano V, et al. Risk association between scleroderma disease characteristics, periodontitis, and tooth loss. Clin Rheumatol 2017;36:2733-41. |
| 46. | Corrêa JD, Calderaro DC, Ferreira GA, Mendonça SM, Fernandes GR, Xiao E, et al. Subgingival microbiota dysbiosis in systemic lupus erythematosus: Association with periodontal status. Microbiome 2017;5:34. |
| 47. | Rutter-Locher Z, Smith TO, Giles I, Sofat N. Association between systemic lupus erythematosus and periodontitis: A systematic review and meta-analysis. Front Immunol 2017;8:1295. |
| 48. | Gawron K, Łazarz-Bartyzel K, Potempa J, Chomyszyn-Gajewska M. Gingival fibromatosis: Clinical, molecular and therapeutic issues. Orphanet J Rare Dis 2016;11:9. |
| 49. | Ghiasi M. Strawberry gingivitis in granulomatosis with polyangiitis. N Engl J Med 2017;377:2073. |
| 50. | Hernández G, Serrano C, Porras L, Lopez-Pintor R, Rubio L, Yanes J. Strawberry-like gingival tumor as the first clinical sign of Wegener's granulomatosis. J Periodontol 2008;79:1297-303. |
| 51. | Pagnoux C. Updates in ANCA-associated vasculitis. Eur J Rheumatol 2016;3:122-33. |
| 52. | Bachmeyer C, Petitjean B, Testart F, Richecoeur J, Ammouri W, Blum L. Lingual necrosis as the presenting sign of Wegener's granulomatosis. Clin Exp Dermatol 2006;31:321-2. |
| 53. | Paraskevas KI, Boumpas DT, Vrentzos GE, Mikhailidis DP. Oral and ocular/orbital manifestations of temporal arteritis: A disease with deceptive clinical symptoms and devastating consequences. Clin Rheumatol 2007;26:1044-8. |
| 54. | González-Gay MA, García-Porrúa C. Epidemiology of the vasculitides. Rheum Dis Clin North Am 2001;27:729-49. |
| 55. | Salvarani C, Pipitone N, Versari A, Hunder GG. Clinical features of polymyalgia rheumatica and giant cell arteritis. Nat Rev Rheumatol 2012;8:509-21. |
| 56. | Sheldon CA, White VA, Holland SP. Giant cell arteritis presenting with bilateral loss of vision and jaw pain: Reminder of a potentially devastating condition. J Can Dent Assoc 2011;77:b55. |
| 57. | Scrivani SJ, Keith DA, Kaban LB. Temporomandibular disorders. N Engl J Med 2008;359:2693-705. |
| 58. | Arabshahi B, Cron RQ. Temporomandibular joint arthritis in juvenile idiopathic arthritis: The forgotten joint. Curr Opin Rheumatol 2006;18:490-5. |
| 59. | Twilt M, Arends LR, Cate RT, van Suijlekom-Smit LW. Incidence of temporomandibular involvement in juvenile idiopathic arthritis. Scand J Rheumatol 2007;36:184-8. |
[Figure 1], [Figure 2]
|
