From the Archives: Fall 2006 Issue of Lupus Now Magazine
Aggressive Periodontitis and Chronic Cutaneous Lupus Erythematosus
A Case Study
By Christina Tietmann, D.M.D., Aachen, Germany, and Nabil F. Bissada, D.D.S., M.S.D., Professor and Chair, Department of Periodontics, Case Western Reserve University, School of Dental Medicine, Cleveland, OH
INTRODUCTION
Lupus erythematosus is considered to be a high-risk factor for periodontitis. An autoimmune disease of unknown origin, cutaneous lupus erythematosus (CLE) is divided into three categories: chronic (SCLE), subacute (CCLE), and acute (ACLE). Whereas ACLE has a high prevalence of conjunctive periodontal lesions, aggressive periodontitis in patients with chronic CLE is rarely reported.
CLE is an autoimmune inflammatory disease affecting the connective tissues. Chronic LE is restricted to skin and oral mucosal lesions. Acute LE extends to multiple organs leading to nephrotic symptoms and pericarditis. Subacute LE is considered to be between CCLE and ACLE in severity with mild systemic symptoms, but pronounced cutaneous lesions.
Most affected CLE patients are women of childbearing age. Skin involvement occurs in 70 to 85 percent in a striking variety, ranging from localized discoid lesions, annular-polycyclic forms with extreme photosensitivity, to malar erythema ("butterfly rash"). Extraoral lesions may include arthritis and Raynaud's phenomenon. Mucosal intraoral lesions consist of erythematous areas, cheilitis, and mucositis. Intraoral lesions are present in 45 percent of ACLE and in 10 percent of chronic cutaneous conditions. Evidence of xerostomia may be observed in ACLE in high proportions, and tends to occur in elderly patients.
Lupus erythematosus cannot be diagnosed by a single test. Confirming the diagnosis is often difficult, particularly during early stages. Other disorders like lichen planus or leukoplakia must be ruled out by carefully assessing the morphology of cutaneous lesions, histopathologic examinations, and direct immunofluorescence (lupus band test). A positive lupus band test will reveal IGG, IGM, and complement components (mostly C3) at the dermal-epidermal junction in 90 percent of skin lesions and 10 to 12 percent of skin lesions in sun-protected CCLE patients with healthy skin. A positive lupus band test is found in most ACLE patients. Antineutrophil antibodies (antinuclear antibodies, or ANA) are detected in more than 80 percent of patients with ACLE and 35 percent with CCLE. Evidence of antineutrophil cytoplasmic antibodies (ANCA), directed against the enzymes located in the primary granules of polymorphonuclear leukocytes and lysosomes of monocytes, ranges from 25 to 60 percent in ACLE.
No correlation has been found between ANCA and lupus erythematosus in disease activity. However, as a systemic condition where neutrophil impairment is present, ACLE has been reported as a risk factor for periodontitis in 60 to 70 percent of cases. Because a high prevalence of ANCA and periodontitis has been found (7 to 83 percent), it has been proposed to use ANCA as an indicator for the presence of periodontitis in patients with lupus erythematosus. Reduced probing depths in patients with lupus erythematosus were found only when treated with immunomodulatory drugs for prolonged periods. Similar features, such as B-lymphocyte hyperactivity and increased immunoglobulin synthesis in the pathobiology of periodontitis and lupus occur as evidenced by the presence of numerous B-lymphocytes and plasma cells in periodontal lesions, as well as severe specific IgG responses against periodontopathic bacteria in inflamed gingival tissues.
The efficacy of clearing IgG-opsonized pathogens by binding phagocytes via receptors to the Fc domain of IgG (Fc_R receptor polymorphism) is important for periodontal health. The Fc_RIIa-R131 allele also is associated with the risk for periodontitis in lupus patients. Because IgG2 is known to be a predominant immunoglobulin subclass in patients with ACLE and periodontitis, it was suggested that Fc_RIIa genotypes be considered as potential risk markers for aggressive localized periodontitis.
CASE HISTORY
A 38-year-old Moroccan female was referred by her general dentist to the author's private practice for regenerative periodontal therapy. Two years ago, the patient was diagnosed with chronic periodontitis and was treated by scaling/root planing. For the past year she noticed a loosening of her upper and lower incisors. Her general dentist performed DNA testing of the plaque, which revealed the presence of high counts of Actinomyces actinomycetemcomitans, low numbers of Tannerella forsythensis, Porphyromonas gingivalis, and Treponema denticola-bacteria found in the dental plaque that are associated with chronic periodontitis. (In particular, A. actinomycemcomitans is more prevalent in the dental plaque associated with aggressive periodontitis.) Systemic antibiotics were not administered. An initial review of the patient's medical history revealed no systemic disease condition, no medication, and no history of smoking.
Clinical Examination
An intraoral clinical exam presented no missing teeth and multiple well-functioning amalgam restorations. All teeth but the left maxillary second premolar (due to failed root canal treatment) showed positive vitality reactions to thermal tests.
Periodontal examination revealed probing depths ranging from 2 mm to 8 mm, and increased tooth mobility of the maxillary and mandibular incisors, and first left maxillary molar. Involvement of the buccal (surface) furcation of both maxillary first molars was present. A minimum amount of dental plaque was detected. An interleukin genotype test was negative.
Radiographic Findings
Radiographic examination revealed severe horizontal bone loss around the anterior teeth, especially the mandibular incisors. There was vertical bone loss around the maxillary first molars and mandibular left first and second molars. There was furcation involvement of the first maxillary molars. Based on clinical and radiographic findings, the aggressive periodontitis was diagnosed as the periodontal condition.
After initial therapy (root planing and occlusal adjustment) and reevaluation, a treatment plan for surgical regenerative therapy was set up. Despite the patient's excellent oral hygiene compliance, acute periodontal abscesses of the right maxillary and left mandibular lateral incisors developed two months after initial therapy.
Extraoral Findings
Although the patient was generally healthy, whitish skin hypopigmentations around the left eye and left angle of the mouth were noted. This discoloration lasted more than 10 years, but the patient received no treatment because dermatologists had reached no diagnosis. The patient experienced advanced hair loss two months after initially visiting our office. The patient was diagnosed with acute periodontal abscesses despite excellent compliance and successful initial therapy. She was treated in the Department of Dermatology at the University of Aachen, Germany. Also noted were pale fingers and toes (Raynaud's phenomenon) as well as edema in the legs and around the eyes. The patient was extremely fatigued. Parts of her lips were swollen. No intraoral changes of the buccal (cheek) mucosa or tongue were present. No associated systemic diseases were diagnosed.
Laboratory tests showed an increased erythrocyte sedimentation rate and lymphocytosis. Diabetes was ruled out because the patient's blood glucose level was normal. No antinuclear and antineutrophil cytoplasmic antibodies were present.
Histologic Examination
A biopsy of the forehead skin was obtained. Histopathologic examination showed follicular keratosis with mononuclear cell infiltrate. Also found were vacuolar degeneration of the basal keratinocytes and thickening of the basement membrane. A lupus band test of the biopsy was positive.
DIAGNOSIS AND TREATMENT
Based on clinical and histological findings, the patient was diagnosed as having CCLE. Antimalarial drugs were administered systemically and corticosteroid ointments were applied locally for the alopecia. When the patient presented herself three months later, her periodontal condition was stable with no further progression of the existing periodontitis. Probing depths ranged from 2 mm to 6 mm.
Since lupus erythematosus appeared to be well under control, a definitive periodontal treatment was performed. The patient had a full-mouth scaling/root planing with open flap of mandibular and maxillary incisors. Emdogain(r) was used for better wound healing. The mandibular and maxillary incisors were splinted with a semi-permanent splint. The patient refused further regenerative procedures for financial reasons. She was placed on a three-month recall basis for maintenance therapy.
The 11-month postoperative control showed stable general medical and periodontal conditions. Antimalarial drugs were still administered systemically; corticoid ointments were stopped. Alopecia and the extraoral hypopigmentations were less apparent. The periodontal examination revealed shallow probing depths ranging from 1 mm to 4 mm, no bleeding on probing, slight loss of interdental papilla height in the anterior mandibular region, and reduced tooth mobility. The radiographic examination showed a stable bone level and no further progression of bone loss.
DISCUSSION
The case presented describes a patient with aggressive periodontitis who is diagnosed as having CCLE. The extraoral findings of lupus-i.e., alopecia, whitish discolorations, and Raynaud's phenomenon-were present, whereas intraoral mucosal lesions were not apparent. The CCLE diagnosis was based on the biopsy report, a positive lupus band test, negative tests on antinuclear antibodies and antineutrophil cytoplasmic antibodies (ANCA), and the exclusion of systemic involvement. Only the acute systemic type of cutaneous lupus (ACLE) is considered a risk factor for periodontitis. Because the clinical signs and symptoms vary in both the chronic and the systemic forms of lupus, diagnosis is mainly made by excluding systemic involvement and by histopathological and immunologic examination.
Autoimmunity is expected to play a considerable role in the pathogenesis of periodontal disease as well as in lupus erythematosus. However, ANCA are not considered to be specific markers for aggressive periodontitis, although a high prevalence of ANCA-75 percent in patients with periodontitis and ACLE-has been reported, and their role as markers for periodontitis is suspect.
This case describes a patient who tested negative for antinuclear antibodies and ANCA in spite of aggressive periodontitis and chronic cutaneous lupus erythematosus. Antinuclear antibodies are only found in about 10 to 35 percent of CCLE patients and are more common in older patients and those with generalized skin involvement who have had the disease for a long time. The first signs of progression of CCLE occurred 10 years after this patient first developed facial hypopigmentations. However, skin involvement is still localized in this rather young patient, which may be a reason for the non-presence of antinuclear antibodies.
Although the patient was diagnosed with periodontitis only two years before her referral, the clinical and radiographic findings support an early onset of the disease, probably starting with puberty. The first signs of lupus erythematosus were observed by the patient while in her mid-20s, years after the suspected onset of aggressive periodontitis. Therefore, the recurrent acute periodontal abscesses after initial therapy, despite high compliance, should be considered a consequence of greater probing depths as well as a consequence of coexisting, but undiagnosed, lupus erythematosus. Once lupus erythematosus was controlled, there was no further periodontal exacerbation. This is underlined by the 11-month postoperative control, which showed stable clinical and radiographic conditions.
SUMMARY
Three months after the diagnosis of periodontitis, the patient experienced advanced hair loss (alopecia), pale fingers and toes, and edema in the legs and around the eyes. A skin biopsy showed follicular hyperkeratosis with perivascular mononuclear cell infiltrate. Also found were colliquation of the basal cells, thickening of the basal lamina, and vacuolar degeneration of basal keratinocytes. A lupus band test was positive. Diagnosis of CCLE was established. Three months following the treatment of lupus by antimalarial agents, the periodontal condition stabilized with no further exacerbation or progression of the existing periodontitis. An 11-month post-surgical follow-up revealed stable periodontal and general medical conditions.
CONCLUSIONS
We will reevaluate the patient's medical history should there be a recurrence of periodontal lesions refractory to periodontal treatment. Controlling a systemic condition like lupus erythematosus is essential for a good prognosis in treating periodontitis, as well as the patient's general health.
GLOSSARY
cheilitis - inflammation and cracking of the lips
colliquation - degeneration of tissue to a liquid state
edema - the presence of abnormally large amounts of fluid in the body's intercellular tissue spaces
furcation - the region of a multirooted tooth where the roots divide
hyperkeratosis - thickened horny layer covering the surface of the skin or oral mucosa
hypopigmentations - a deficiency in melanin (pigment) formation or a loss of pre-existing melanin
keratosis - excessive growth of horny tissue of the skin or oral mucous membrane
leukoplakia - localized, thick white patches on the tongue and other mucous membranes that develop in response to chronic irritation (for example, ill-fitting dentures, smoking, chewing tobacco)
lichen planus - a skin or oral disorder of unknown cause that causes bluish-purple, flat lesions that are often itchy; involvement of the scalp may lead to hair loss
lymphocytosis - an unusually high number of normal lymphocytes in the blood
mucositis - inflammation of a mucous membrane
neutrophil - a type of white blood cell
periodontitis - inflammation of the gums and abnormal loss of bone that surrounds the teeth and holds them in place
xerostomia - dryness of the mouth from salivary gland dysfunction, often seen with Sjogren's syndrome