SYSTEMIC LUPUS ERYTHEMATOSUS
-SLE-
Oral Manifestations and adverse effects
of Lupus in oral cavity

Author: Dr. Boban Fidanoski, DMD
Definition

Systemic Lupus Erythematosus is chronic inflammatory multisystem disease of unknown etiology. It is an autoimmune disease where body’s immune system (antibodies in this case referred to as autoantibodies) mistakenly attacks its own tissues, causing multi-organ inflammation and diverse clinical manifestations with domination of peripheral symmetric polyarthritis of small and large joints. SLE is characterized with periods of exacerbation and remission.

Origins of the name: Systemic Lupus Erythematosus

“Lupus” is Latin for wolf, “Erythro” in Greek stands for red, and Systemic is English word meaning that multiple organs are involved. One theory explains that this disease has gotten its name because it is similar to the attacks of a wolf on humans with its severity, random spots of attack and repetitiveness.

 
 
Pathogenesis:

SLE results in tissue damage caused by attack of autoantibodies and immune complexes. It involves polyclonal and antigen-specific T and B lymphocyte hyperactivity. T cell help in production of autoantibodies is critical for development of full-blown disease.

Proposed Etiology:

Definitive etiology is still unknown. We could only hypothesize what causes this disease is: genetics, environmental factors (sun exposure to UV light), estrogen (prepubertal and postmenopausal women have similar incidence to men; men with SLE have higher concentration of estrogenic metabolites), infection (viral: non-specific stimulant of immune response, medications (Dilantin-anticonvulsant), oral contraceptive pills are associated with exacerbation (they should be avoided in SLE patients). 25% of SLE patients have experienced false-positive tests for syphilis due to circulating lupus anticoagulant in the blood.

 
Differential Diagnosis:

Diagnostic criteria updated by American College of Rheumatology in 1997 states that at least 4 or more of 11 (7 clinical and 4 laboratory) criteria must be present serially or simultaneously:

Diagnostic Criteria Description

Clinical

1. Malar rash Classic “butterfly rash”; sparing of nasolabial folds, no scarring
2. Discoid rash; May cause scarring since invasion of basement membrane
3. Photosensitivity; Skin rush in reaction to sunlight
4. Oral/nasal ulcers; Usually painless
5. Arthritis; Symmetric, involving 2 or more small or large peripheral joints, non-erosive
6. Serositis; Pleuritis or Pericarditis
7. Neurologic disorder; Seizures or Psychosis

Laboratory

8. Renal disorder; Proteinuria
9. Hematologic disorder; Hemolytic anemia, Leukopenia, Lymphopenia, Thrombocytopenia
10. Immunologic disorder; Anti-double stranded DNA Ab (50% of patients), anti-Sm Ab (25-60% of patients), anti-phospholipid Ab.
11. Antinuclear antibody –(ANA); Most sensitive test (present in 90%of the patients)

Laboratory tests that will determine diagnosis of Lupus:

• Serologic diagnosis made by high titre of ANA detected by immunofluorescence, but this test doesn’t determine diagnosis because many other autoimmune disease have positive ANA test
• Anti-dsDNA antibodies detected by Crithidia test and anti-Sm antibodies are specific for SLE (95-98% of the cases) and these tests determine the diagnosis of Lupus.

Signs and Symptoms:

1. Musculoskeletal
The most common manifestations of SLE are Arthralgias and Nonerosive Arthritis occurs in 95% of patients, it is symmetric and involves small joints of hands, wrists, and feet).There is also avascular necrosis (cause of pain, along with arthritis) and myositis.
2. Dermatologic
Abnormalities of the skin, hair or mucous membranes are second most common manifestation of SLE, occurring in 85% of patients.
The most common skin manifestation is the classic malar butterfly rash, an erythematous rash covering both cheeks and the bridge of the nose, with sparing of the nasolabial folds.
The second most common skin manifestation is maculopapular rush that can be located anywhere on the body. Also are present: nasal/genital ulcers, panniculitis, alopecia, urticaria and purpura.

 
 
3. Oral
Painless, shallow oral ulcers, most often occur on the hard and soft palate. There is also a mild involvement of mucosal ulcers as symptom of this disease.
Oral ulcers occur at onset in 11% of patients, while at any time are present in 30% of patients. The lesions appear as maculae (red patches) that will later transform into irregular erosions and ulcers which often heal with scarring. Purpuric lesion such as ecchymoses and petechiae may occur.
In 30% of the cases, pathology of major salivary glands may occur leading to secondary Sjogren’s syndrome and severe Xerostomia
 
 
 
 
4. Gastrointestinal
Renal involvement occurs in about 50% of patients, with only few % with irreversible changes. Proteinuria is the most common clinical sign. Other signs are: Pancreatitis, Lupus Enteropathy, Hepatitis and Hepatomegaly
5. Systemic
Fever, Malaise/Fatigue, Lymphadenopathy, Weight loss
6. Cardio-Vascular
Pericarditis is the most common cardiac manifestation, occurs up to 30% of patients. Raynaud’s phenomenon, Thrombosis, Vasculitis, Livedo reticularis, Hemolytic anemia (most common vascular manifestation, in almost all patients), Leukopenia (50% of patients), Lymphopenia, Thrombocytopenia.
7. Ophtalmic
Conjunctivitis, Episcleritis, Keratokonjuctivitis (occurs in 20% of patients)
8. Pulmonary
Interstitial lung disease, Pulmonary hypertension, Alveolar hemorrhage, and Pleuritis.
9. Neurological
Depression, Personality disorder, Cerebritis, Transverse myelitis, Seizures, Headache and Peripheral neuropathy

First symptoms to occur: 1. Fatigue 2. Myalgias 3. Arthtritis

Radiographic characteristics:

Radiographically, the arthritis of SLE is non-erosive. This is helpful for differential diagnosis with Rheumatoid Arthritis where there is bone erosion on radiographs.

 
 
Microscopic features / histoanalysis:

Three histological lesions are most characteristic of SLE:
1. Onion-skin lesions – found in arteries of the spleen, which consist of concentric layers of fibrosis surrounding the vessel
2. Libman-Sacks verrucous endocarditis: vegetations on heart valves
3. Hematoxylin bodies: globular masses of bluish, dense, homogenous material seen on hematoxylin and eosin stain.

Microscopic features of oral lesions:

Histologically, lesions reveal lichenoid mucositis with perivascular exudate and thickening of basement membrane.

Demographics/Epidemiology:

Prevalence: 0.05%, 15 to 50 per 100,000 population in USA.
female:male ratio = 10:1 (90% of cases are in women) predominantly in young women due to higher levels of estrogen, while at premenstrual and postmenopauzal women, ratio with male decreases to 3:1
More common and severe in Blacks and Asians.

Treatment:

Systemic Lupus Erythematosus is a disease without a known cure, so treatment is based on relieving symptoms, suppressing inflammation, and preventing future pathology. Symptomatic treatment is tailored for the organ involved and for severity of the disease: use of topical sunscreen, avoid UV light and estrogens, use of NSAID’s for arthritis, use of antimalarials for dermatologic manifestations, use of topical steroids for rash, use of systemic steroids for prevention of end organ damage. Calcium and Vitamin D to fight osteoporosis, use of Corticosteroids as immunosuppressant drugs for serious organ involvement (e.g. Cerebritis, nephritis). All medications used to treat SLE require periodic monitoring for potential toxicities.

Adverse effects of Lupus therapy in oral cavity:

Long term use of medications to control Lupus can induce significant intra-oral pathology.
Corticosteroids: can lead to root canal calcification, delay of tooth eruptions and root dilaceration.
Steroids: can cause necrotizing ulcerative gingivitis.
NSAID’s: can induce gingival bleeding, but because there is a possibility NSAID’s to inhibit alveolar bone resorption, periodontal health in some patients with Lupus has been found improved due to intake of these medications.
Cyclosporine: is a common cause of gingival enlargement (hyperplasia).
Immunosuppressive treatment: fights against intra-oral infections but promotes Candidiasis and Herpes Simplex Virus infections.

 
 
 
Treatment of adverse effects of Lupus therapy in oral cavity :

Preventive dental hygiene care in Lupus patients is very important. Chlorhexidine mouthwashes could help contain periodontal disease. Mucous membrane ulcers can be treated with hydrogen peroxide gargle, buttermilk gargle, or steroid impregnated gel. Intralesional injection of corticosteroids are also effective. Bacterial, viral and fungal infection should be treated with conventional, proven therapy specific for the infection present. Dental procedures should not be undertaken on patients with active Lupus, or if necessary, antibiotic premedication is advised, due to high incidence of bacterial endocarditis.

 
 
Lupus prophylaxis before dental hygiene treatment:

Lupus is considered as high-risk category of disease by The American National Guideline Clearinghouse and American Academy of Dermatology so they recommend that patients with this kind of condition require antibiotic premedication before dental treatment.
Prognosis:

Survival in patients with SLE is 90 to 95% at 2 years, 82 to 90% at 5 years, 71 to 80% at 10 years, and 63 to 75% at 20 years. Disability in SLE patients is common. 20% of patients experience remissions. Infections due to immunosuppressive therapy and renal failure are the leading causes of death in the first decade of disease. Thromboembolic events are frequent causes of death in the second decade.

Subsets of Lupus:

1. Idiopathic
2. Discoid
3. Subacute cutaneous (ANA negative)
4. Late-onset
5. Neonatal
6. Drug-induced

 

Quotes about Lupus:

"Homo homini Lupus est." – Plautus, year 254 before Christ. (Latin phrase meaning: Man is a wolf to his fellow-man)

’It’s never Lupus” – Dr. Gregory House M.D.

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Bibliography:

Written literature:

Andreoli, T.E. et al. (1997): Cecil Essentials of Medicine; (4-th ed.)-W.B.Saunders Company,U.S.A.
Fauci, A.S. et al. (1998): Harrison’s principles of internal medicine; (14-th ed.)-The McGraw-Hill Companies INC.,U.S.A.
Shiau, C.J., Toren, A.J. (2006): The Toronto Notes 2006: Comprehensive Medical References, 26-nd Ed., Canada.
Tierney, L.M. (1997): Pocket guide to the essentials of diagnosis and treatment; (1-th ed.)- Lange medical book, U.S.A.
Younger-Lewis,C.; Complete home medical guide;Canadian Medical Association (1-st ed.), Dk Publishing Inc.

Internet resources:

Long, R.G. et al. (1998): Oral manifestations of systemic diseases, The Mount Sinai Journal of Medicine(N.Y.-USA) Vol. 65, No.5-6
http://www.mssm.edu/msjournal/65/01_Long.pdf
Sultan, S.M. et al. (1999): A review of gastrointestinal manifestations of systemic lupus erythematosus, (Oxford Journal of Rheumatology, United Kingdom) Vol. 38, No.10
http://rheumatology.oxfordjournals.org/cgi/content/full/38/10/917#SEC1

Photographs:

http://www.merckmedicus.com/ppdocs/us/hcp/content/white/chapters/white-ch-010-s002.htm
Norfolk lupus group: www.norfolklupus.co.uk
www.allaboutarthritis.com
www.zhub.com/pathology/listings/16.html
http://dermatlas.med.jhmi.edu

 
author: Boban Fidanoski; researched for the purposes of the studies at the CCDH and published on-line in July-August 2007