Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease primarily affecting the joints, internal organs, and the skin. The inflammatory processes of SLE and the adverse effects (AEs) from the therapies used for its treatment can negatively affect collagenous tissues, resulting in dental and orofacial manifestations. The clinical consequences can range from poor quality of life (QOL) to increased risk for oral squamous cell carcinoma. Although dental and orofacial manifestations are common in patients with SLE, no guidelines are available for their management; consequently, these manifestations are often not diagnosed and frequently not addressed by rheumatologists in their daily clinical practice. Optimizing the treatment of patients with SLE while minimizing the risks for dental and orofacial complications requires rheumatologists to be cognizant of the effect of SLE and the therapies used for its treatment on oral tissues. It also requires a multidisciplinary team approach to patient care, particularly at the early stages of the disease.

Dental and Orofacial Manifestations in SLE

Between 20% and 50% of patients report oral lesions associated with SLE.1 The precise statistic varies, depending on the study and the country in which the study was conducted; lower percentages between 6.5% and 21% have been reported.2 Because of their high prevalence, oral ulcers are considered primary disease activity and are included in the diagnostic indices for the British Isles Lupus Assessment Group, Systemic Lupus Erythematosus Disease Activity Index, Safety of Estrogens in Lupus Erythematosus National Assessment, Systemic Lupus Activity Measure, and European Consensus Lupus Activity Measurement.3

Primarily, the tongue, cheek mucosa, lips, and palate are affected. The main manifestations include oral aphthous ulcers and periodontitis,4 although other manifestations include erosive lesions, scar formation, temporomandibular joint involvement with limitation of mouth opening, burning sensation in the mouth, hyposalivation, and dry mouth.5 The underlying pathophysiology, at least for periodontitis, is thought to be similar to the inflammatory cascade responsible for the SLE disease process. In fact, SLE and periodontitis share similar pathogenic manifestations, including elevated levels of proinflammatory cytokines, elevated levels of β2-glycoprotein 1–dependent anticardiolipin, and similar mechanisms of tissue destruction.1 Untreated or poorly managed SLE directly influences dental and orofacial structures. The clinical manifestation may include difficulty with oral hygiene and challenges with fitting of dentures and dental implants because of missing teeth, carious lesions, and inadequate bone quality. Some oral presentations are potentially dangerous, such as jaw claudication.5 Overall, the QOL for this patient population may be significantly compromised.


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Need for a Cautious Approach to Treatment Selection

In addition to the manifestations from SLE disease pathophysiology, the therapies used to manage SLE, including various antimalarial, immunosuppressive, and biologic agents, can also have dental and orofacial AEs. For example, as reviewed by Benli et al, methotrexate is associated with mouth ulcers, and glucocorticoids increase the risk for medication-related osteonecrosis of the jaw.5 Immunosuppressive and biologic agents are known to increase the risk for oral infection, particularly fungal and mycobacterium infections and cytomegalovirus, varicella or herpes zoster, nontyphoid salmonella, and Pneumocystis carinii pneumonia.5 Temporomandibular joint impairment, gingivitis, and systemic complications from dental infections have been linked to treatment with immunosuppressive agents in patients with SLE receiving corticosteroids. Agents that are commonly prescribed by dental practitioners carry additional risks, particularly for patients with SLE with compromised kidney function. For example, nonsteroidal anti-inflammatory drugs, penicillin tetracycline, cephalosporins, and acetylsalicylic acid are primarily eliminated via the kidneys. Unwanted toxicity may lead to nephrotic syndrome and organ damage. Among patients who are candidates for dental implants or other devices such as dental braces, rheumatologists and dental practitioners should be aware of the high risk for metal delayed-type hypersensitivity that has been observed with nickel, gold, mercury, chromium, palladium, and titanium.5 Physicians must also be aware of the increased photosensitivity during surgical procedures, which can exacerbate SLE symptoms, including cutaneous lesions, joint pain, and fatigue. It is therefore critical to carefully evaluate the treatments patients with SLE are prescribed, monitor renal function, and adjust dosage or change treatment to minimize the risks for unwanted AEs.

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Importance of a Multidisciplinary Treatment Approach

The multisystem effect of SLE and the challenges presented by dental and orofacial manifestations call for a collaborative multidisciplinary team management approach whereby rheumatologists must carefully select treatment for patients with SLE to minimize risk for oral AEs and collaborate with dental and other practitioners for medical and oral management.5,6 Because oral manifestations is frequently one of the early signs of SLE, dental practitioners can play an important role in early disease diagnosis and potentially increase the efficiency and efficacy of the treatment strategy for both the SLE and the dental or orofacial manifestation. Ideally, “a dental referral of [SLE] patients at risk should be proposed to detect all dental diseases before the start of a treatment by the rheumatologist,” said Oliver Huck, dental surgery professor in the Department of Periodontology at the University of Strasbourg, Strasbourg, France, and a lead author on the review by Benli et al.5 Professor Huck advises that “routine dental follow-up of SLE patients (with or without rheumatoid treatment) will be of interest for early diagnosis of dental disease.”

Munthe et al reported the case of a 17-year-old female patient, with chief complaint of bleeding and blood clots on the upper lips and labial mucosa; difficulty with eating, drinking, and swallowing; and general fatigue.6 The patient was initially misdiagnosed and treated for tuberculosis, highlighting the difficulty in the differential diagnosis of early stages of SLE. The patient’s symptoms progressed and, after further examination, adhering to American College of Rheumatology criteria, and engaging a multidisciplinary team, including oral and internal medicine, dermatology, and venereology, SLE was suspected. A clinical diagnosis of oral lesions associated with SLE and angioedema was made, according to the patient’s medical history and clinical findings.6 The oral lesions associated with SLE can be differentiated from other oral lesions (eg, erythema multiforme, oral lichen planus, and erythematosus candidiasis), which can aid in the differential diagnosis of SLE.

Clinical and histopathological findings, together with the detection of cutaneous oral lesions, can play a significant role in the early definitive diagnosis of SLE and can support appropriate treatment initiation, thereby enhancing disease prognosis. A multidisciplinary team approach and appropriate referrals ensure complete dental and medical management of patients with SLE, with the potential to slow the disease course, decrease disease severity and complications, and improve the patient’s QOL.

Implications for Clinical Practice

In the absence of guidelines for the management of dental and orofacial manifestations in patients with SLE, steps can be taken to minimize risk for complications. Oral examination should be considered routine in diagnostic evaluation and clinical management of patients with SLE. Oral ulcers are common, and patients refractory to treatment should be referred for histological examination to rule out malignant transformations. It is important to carefully examine dental bone structure before a dental implant procedure because of deterioration of bone structure and the risk for osteonecrosis secondary to steroid use. Preventive dental care with antibiotic and antifungal prophylaxis should be considered early in the SLE disease process. Anticoagulants are recommended for dental treatment to reduce the high risk for thromboembolic events. The increased photosensitivity can be minimized with ultraviolet-blocking filters during lighting for oral surgical procedures.

References

1. Mangla C, Goyal P, Singh HP. Oral manifestation of systemic lupus erythematosus: a case report. Int J App Dent Sci. 2018;4(3):69-71.

2. Pandey A, Pandey M, Pandey VP, Ravindran V. Oral manifestations of autoimmune connective tissue diseases. Indian J Rheumatol 2018;13(4):264-272.

3. Abrão AL, Santana CM, Bezerra AC, et al. What rheumatologists should know about orofacial manifestations of autoimmune rheumatic diseases. Rev Bras Reumatol Engl Ed. 2016;56(5):441-450.

4. Gualtierotti R, Marzano AV, Spadari F, Cugno M. Main oral manifestations in immune-mediated and inflammatory rheumatic diseases. J Clin Med. 2018;8(1).

5. Benli M, Batool F, Stutz C, Petit C, Jung S, Huck O. Orofacial manifestations and dental management of systemic lupus erythematosus: a review [published online December 30, 2019]. Oral Dis. doi: 10.1111/odi.13271

6. Munthe EKM, Sufiawati I. Oral lesions as a clinical sign of systemic lupus erythematosus. Dent J (Majalah Kedokteran Gigi). 2018;51(3):147-152.