Medical history. Examination and treatment

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1 31 CLINICAL B " REPORTS Systemic lupus erythematosus Steven J. Sam uelson, DDS Arthur H. Friedlander, DDS M ark Sw erdloff, DDS A case of osteomyelitis of the mandible in a patient with systemic lupus erythematosus is described. Both the disease process and the treatment modalities must be understood for correct management. s W-Jystemic lupus erythematosus is one of a spectrum of disorders of unknown origin which have been classified under such synonymous titles as collagen, connective tissue, or an autoimmune disease. The disease process and the therapy used to control the disease have a significant deleterious effect on the healing process. Before instituting dental therapy for such patients, the dentist should be familiar with the disease and the therapeutic modalities. Report of case A 33-year-old white man was referred to the dental service from the ambulatory internal medicine clinic of the Northport Veterans Administration Medical Center for evaluation and treatment of an infected pericoronal flap in the region of the mandibular right third molar. The patient had had intermittent pain and swelling of the overlying gingiva for the past three months. Medical history The medical history disclosed that the patient had been well until eight months before his referral. At that time, he began to experience intermittent numbness in the joints of both hands. On occasion, the joints became hot, erythematous, swollen, and painful. Two months after the onset of musculoarticular symptoms, a severe rash developed on both forearms, and the patient was admitted to the medical center for further evaluation and treatment. The results of the physical examination were normal except for the articular and cutaneous findings. The complete blood count and differential blood count were within normal limits. The platelet count was 100,000/cu mm.1 Results of the Sequential Multiple Analysis (SMA) 6, SMA 12, and urinalysis were within normal lim its. Radiographs showed that both hands were also normal. Serum was negative for rheumatoid factor but positive for antibodies to nuclear antigen. The patient was discharged to the ambulatory medical clinic with a diagnosis of systemic lupus erythematosus. A maintenance dose of prednisone, 25 mg/day, appeared to control his symptoms adequately. Examination and treatment Findings of the clinical and radiographic examination of the orofacial region were consistent with a pericoronal infection of an unerupted third molar (Fig 1). The patient was afebrile, and there was no associated cervical lymphadenopathy. A current complete blood count and differential blood count were within normal limits. In consultation with a medical service, it was determined that the third molar could be extracted without hospitalization of the patient. The patient said he was allergic to penicillin, and erythromycin, 1 gm/day in divided doses, was administered for ten days; this eliminated all clinical signs of infection. According to a recommendation of the medical service, a supplement of 200 mg hydrocortisone was administered intravenously during surgery and the impacted tooth was extracted with the patient under a local anesthetic. Erythromycin, 1 gm/day in four divided doses, was continued for ten days. Postoperative course The patient returned to the dental clinic a week after surgery. At the time the sutures were removed, the surgical site appeared to be healing norm ally. Another appointment was made to check the surgical site on the 21st postoperative day, but the patient did not return to the clinic. The patient did not keep any further medical or dental appointments. Three months after the tooth was extracted, the patient came to the dental clinic with severe pain at the right angle of the mandible; the pain radiated to the right ear. Clinical examination of the surgical area showed a partially healed extraction site, no swelling, JADA, Vol. 100, April

2 C L IN IC A L REPO RTS Fig 1 Panoramic radiograph shows embedded mandibular third mo Fig 2 Radiograph obtained three months after removal of impacted lar. tooth shows massive osteolysis. Fig 3 Fracture was disclosed approximately four months after removal Fig 4 Panoramic radiograph obtained year after closed reduction of impacted tooth. shows early osseous union. no purulent drainage, and no cervical lymphadenopathy. A radiograph showed massive osteolysis in the region of the ex traction (Fig 2). Although informed of the need for hos pitalization so that the jaws could be im mobilized and antibiotics could be ad ministered parenterally because of the possibility of a fracture, the patient re fused. He consented to debridement of the surgical site in the region of the mandibu lar right third molar and extraction of the m an d ibu lar righ t second molar. The m an d ib u lar rig h t seco n d m olar was mobile, and the distal root was exposed to within 3 mm of the apex and in continuity with the osteolytic process. A local anes thetic was administered and the extrac tion was performed. A dose of 200 mg hydrocortisone was administered intra venously during surgery. On recommendation of both the inter nal m edicine and infectious disease ser vices, the patient was given half a gram of oral cefalexin every six hours for six weeks and was instructed about the prep aration of a balanced soft diet. Cultures 554 a JADA, Vol. 100, April 1980 obtained at the time the tooth was extrac ted were negative. A soft tissue specimen removed from around the roots of the sec ond molar was interpreted as granulation tissue by the pathologist. The patient was asked to return to the clin ic twice a week. The patient again broke all follow-up appointments. Three weeks later he came to the emergency room of the hospital with pain and swelling on the right side of the face of two days duration. He said that his teeth did not occlude properly. Ra diographs taken at that time showed a fracture of the right angle of the mandible (Fig 3). This time the patient agreed to the rec omm endation for hospitalization. The medical service recommended continua tion of 25 mg prednisone a day. Dental therapy consisted of the application of arch bars and the placement of m axillo mandibular elastics. One gram of cefal exin was administered every six hours for nine days. The patient demanded to be discharged on the tenth postoperative day. He was given a prescription for 500 mg cefalexin to be taken every six hours. The patient was observed on a weekly basis as an out patient during the 16 weeks of immobili zation of the jaws. Antibiotics were ad ministered for this entire period. At the time of removal of the arch bars, there was union of the fractured segments and ra diographic evidence of early bone con solidation (Fig 4). The patient has been seen on a monthly basis for the past year. The fracture site has healed completely. Discussion Systemic lupus erythematosus was previously considered a rare disease. Improved methods of detection and an awareness of the many milder forms confirm an incidence of one per 1 0, Females outnumber males in a ratio of 9:1. The age of onset is typically in the second and third decades. Patients usually have a variety of abnorm alities involving several

3 organ systems. Musculoarticular manifestations, arthritis, and arthralgia occur in almost all patients during the course of the illness. Cutaneous manifestations of systemic lupus erythematosus include a characteristic facial rash with a butterfly distribution over the bridge of the nose and the malar areas in 37% of the cases.2 Similar eruptions occur on other parts of the body, particularly the extremities. The skin lesion may be precipitated or aggravated even by exposure to sunlight. Renal involvement, one of the most serious manifestations, occurs in 40% to 50% of patients.2 Clinical abnormalities range from mild proteinuria to frank nephrotic syndrome and eventual renal failure. Almost half of the patients have cardiac abnormalities; the most commonly encountered abnormalities are pericarditis, myocarditis, or a nonbacterial verrucous endocarditis (Libman- Sacks disease). Neuropsychiatric involvement is also a frequent finding, and the patient may have a convulsive disorder, psychosis, emotional instability, or organic brain syndrome.2 Oral manifestations occur in approximately 15% of patients.3 Lesions are found on both the lips and the oral mucous membranes. The lesions on the lip consist of a central atrophic area with small white dots; the area is encircled by a keratinized border of white striae. The mucosal lesions are composed of a central depressed atrophic area surrounded by a raised keratotic zone which tapers off into small white lines. The orofacial lesions usually accompany the skin lesions, but, on occasion, the orofacial lesions may precede all clinical manifestations of the disease.3 Etiologic questions Whereas the cause of systemic lupus erythematosus remains unknown, a hypothesis of an infectious component is supported by the isolation of a species of Mycoplasma and the identification of viruslike particles in the kidney and other tissues.4 As 90% of patients with systemic lupus erythematosus are women and the incidence of the condition has been reported to increase with the use of oral contraceptives, the possibility of an endocrine disturbance is suggested.5 Hypersensitivity may be considered as a cause because of the similarity of histopathologic features between system ic lupus erythematosus and the allergic process.6 Lupuslike reactions to certain drugs, such as procainamide and hydralazine, also support this theory.7 A biochemical component is supported by the increased secretion of tyrosine and phenylalanine in patients with the disease.8 A genetic predisposition has been suggested on the basis of c lin ic a l or laboratory abnormalities which have been found in the relatives of patients with systemic lupus erythematosus.9 Pathogenesis The pathogenesis of the disease has become better understood during the past two decades. The serum of p a tie n ts w ith sy ste m ic lupus erythematosus contains many antibodies; among them are the antibodies to deoxyribonucleic acid (DNA) and nucleoprotein, and other nuclear components.10 The antinuclear antibodies alone are harmless, as they do not penetrate the membrane of living cells. However, the antinuclear antibodies participate in the pathogenesis of the disease by forming antigen-antibody complexes with their specific antigens. The interaction of the antigen with the antibody may form a soluble macromolecular complex which enters the systemic circulation. These complexes act on basophils, which in turn cause a clumping of platelets and a release of histamine and serotonin. The systemic liberation of these products increases vascular permeability.11 The complexes then begin to localize in the basement membrane of target organs, such as arteries or glomeruli of the k id n e y. C o m p le m e n t and complement-derived chemotactic factors then attract leukocytes. The polymorphonuclear leukocytes release proteolytic enzymes, causing local tissue destruction. A true inflammatory response, in which the antigen-antibody complexes become trapped, is set up in these organs. A variety of injuries, ranging from acute through chronic inflammation and finally to hyaline degeneration, is possible. Thus, the target organ is unable to function properly. The clinical correlates are a dermal or osseous vasculitis with ischemic manifestations or impairment in function of the kidney.12 Estes and Christian13 reported a 21% incidence of facial dermal vasculitis. In 14 of their patients, this progressed to chronic ulceration of the skin. Gangrene developed on the fingers of two of their patients. Avascular necrosis of bone is a rare clinical finding in some patients with systemic lupus erythematosus. The cause of this change is the progression of the underlying disease entity. Velayos and co-workers14 evaluated the histology of avascular necrosis in patients treated without steroids. His interpretation of the microscopic findings were that the vessels with the dimensions of arterioles and small arteries showed thickened walls with concentric medial and adventitious fibrosis of the type associated with previous episodes of vasculitis. These findings are significantly different from the findings in avascular necrosis secondary to embolization of fat in arteries, as caused by steroid therapy. Dubois and Cozen,15 M ilch,16 and Siemsen and others17 have reported numerous cases of avascular necrosis in the hip and knee in patients with systemic lupus erythematosus who had never been exposed to steroid therapy. These authors contend that the necrosis is caused by an ischemic vasculitis unassociated with any treatm ent m o d alities. Lanigan and others18 concur with this theory. They reported a case of bilateral mandibular condyloma in a 26- year-old woman with mixed collagen vascular disease. The clinical and laboratory findings were consistent with features of rheumatoid arthritis, systemic lupus erythematosus, and scleroderma. Diagnosis, treatment Diagnosis of systemic lupus erythematosus is made in the presence of a number of clinical signs and symptoms with corroborative laboratory data. The most important laboratory finding is the presence of antibodies to nuclear antigen; a positive test for antinuclear antibody occurs in 99% of patients and is essential for the diagnosis. The test for lupus ery Samuelson-Friedlander Swerdloff: LUPUS ERYTHEMATOSUS 555

4 thematosus cells is also used but is positive in only 60% to 80% of the cases. Leukopenia and anemia occur in more than half the patients with the disease.19 In the differential diagnosis, consideration must be given to other conditions that have been labeled collagen, connective tissue, or autoimmune diseases. A positive antinuclear antibody may, on o c c a s io n, be o b ta in e d in rheumatoid arthritis, scleroderma, Sjogren syndrome, and some adverse reactions to drugs. These pathologic conditions may be eliminated from the differential diagnosis by a complete history and physical examination and additional laboratory data. There is no cure for systemic lupus erythematosus. High doses of cort ic o s te r o id s are u sed w h en symptoms become severe and are then tapered to a m aintenance level.20 Immunosuppressive drugs have been effective in some patients as the prim ary th erap y.21 The symptoms of arthritis and arthralgia have responded well to salicylates and rest. Patients are advised to avoid exposure to sunlight to prevent aggravation of lesions of the skin. Current estimates indicate that more than 75% of patients with this disease have a five-year survival rate. The patient dies because of either renal failure, degeneration of the central nervous system, or'recurrent bacterial infections. Systemic lupus erythematosus compromises the ability of the body to fight infection. Patients with untreated system ic lupus eryth e matosus are highly susceptible to infections of the urinary tract or the respiratory system. This is because most of the patients afflicted with the disease have a leukocyte count which ranges between 2,000 to 4,000/cu mm.1 The mechanism for leukopenia has not been fully delineated; however, intravascular - immune complexes as'w ell as antibodies directed to leukocytes may be contributing factors. Brandt and Hedberg22 studied the increase in rate of infection and determined that the patients were more susceptible both because of leukopenia and the fact that the leukocytes present had a significantly lower capability to perform phagocytosis. Additional factors influencing the increased rate of infection among patients with the 556 JADA, Vol. 100, April 1980 disease are throm bocytopenia, anemia, and plasma protein abnormalities. Systemic steroids, which are used to treat the disease, unfortunately have increased the incidence of complications of the surgical wound site23 and delayed healing by inhibiting proliferation of fibroblast and epithelial cells.24 In studies on experimental fractures in animals, steroids have been found to affect adversely the process of bone repair by not allowing bone formation in the periosteum and by fostering the formation of an abnormal type of cartilagenous callus.25 Steroids inhibit the inflammatory response of the body by suppressing the permeability of small blood vessels during inflammation, thereby retarding the migration of polymorphonuclear leukocytes and circulating antibodies into the area of injury.26 Similarly, a focus of infection may be insulated from the full effects of antibiotics because of decreased vascular permeability. Osteomyelitis that progresses to a pathologic fracture of the mandible after removal of an impacted tooth is a rare complication. However, the possibilities become clinically significant when the patient has a catabolic disease, such as systemic lupus erythematosus with its underlying vasculitus, and when the patient is receiving steroids. Thus, the authors conclude that both the underlying disease and the therapy contributed to the initiation and progression of the infection and to the ultimate bony fracture. Dental management Correct dental management of a patient with systemic lupus erythematosus requires an understanding of both the disease process and the treatment modalities. The dentist must obtain a complete medical and dental history. Of particular concern are the drugs being used and their consequent physiologic effects. Dental treatment should not be undertaken without previous consultation with the patient s physician. Coordination of medical and dental therapy is mandatory. If a surgical procedure is planned and the patient has been receiving intensive or long-term steroid therapy, additional steroids may be required to avoid an adrenal crisis. Antibiotics may be necessary to prevent an infection of the surgical site resulting from d e cre a se d h o st r e s is ta n c e ; a prophylactic measure to prevent endocarditis in patients with Libman- Sacks disease on the cardiac valves may also be required. The exact antibiotic and its level of dosage must take into account the patient s current renal function. A bleeding and coagulation profile must be performed before any therapy in which bleeding is likely to occur. Patients with systemic lupus erythematosus frequently have a severely deficient platelet count. Periodontal surgery, endodontic surgery, or oral surgery and the adjunctive medications used during these procedures may in themselves cause an exacerbation of the disease. Thus, elective dental procedures should be undertaken with caution. After completion of therapy, close monitoring of the patient both clinically and radiographically is indicated. Summary Dentists treating patients with systemic lupus erythematosus must be familiar with the disease and the medications used to treat it. The trauma of the dental procedure, the underlying disease process, the medications used to treat the disease, and the failure of the patient to return for his follow-up examination contributed to the diseased condition. Close monitoring of the patient s healing process is mandatory. More significant is the fact that steroids, which are the main treatment modality, mask the signs of infection and thus may lull the practitioner and the patient into a false sense of security. Dr. Samuelson, formerly a resident in general dental practice at the Northport Veterans Administration Medical Center, Northport, NY, is currently a graduate student in the department of periodontology, Henry Goldman School of Graduate Dentistry, Boston University, Boston, Dr. Friedlander is chief of oral and maxillofacial surgery, Northport Veterans Administration Medical Center, and associate professor of oral and maxillofacial surgery, School of Dental Medicine, State University of New York at Stony Brook. Dr. Swerdloff is associate professor of oral and maxillofacial surgery, School of Dental Medicine, State University of New York at Stony Brook, and consultant in oral and maxillofacial surgery, Northport Veterans

5 Administration Medical Center. Address requests for reprints to Dr. Samuelson. 1. Dubois, E.L. (ed.). Lupus erythematosis, ed 2. Los Angeles, University of Southern California Press, Dubois, E.L., and Tuffanelli, D.L. Clinical manifestations of systemic lupus erythematosus: computer analysis of520 cases. JAMA 190(2): , Andreasen, J.O. Oral manifestations in discoid and systemic lupus erythematosus. Clinical investigation. Acta Odontol Scand 22(3): , Phillips, P.E. The virus hypothesis in systemic lupus erythematosus. Ann Intern Med 83(5): ,1975. '5. Bole, G.G., Jr.; Friedlaender, M.H.; and Smith, C.K. Rheumatic symptoms and serological abnormalities induced by oral contraceptives. Lancet 1: , Harvey, A.M., and others. Observations on effect of adrenocorticotropic hormone (ACTH) on disseminated lupus erythematosus, drug hypersensitivity reactions, and chronic bronchial asthma. Trans Am Clin Climatol Assoc 61: , Molina, J., and others. Procainamideinduced serologic changes in asymptomatic patients. Arthritis Rheum 12: , Nishimura, N., and others. Phenylalanine and tyrosine in collagen diseases. Urinary excretion of general intermediary metabolites liver disease. Arch Dermatol 83: , Grumet, F.C., and others. Histocompatibility (HL-A) antigens associated with systemic lupus erythematosus. A possible genetic predisposition to disease. N Engl J Med 285: , Mannik, M., and Gilliland, B.C. Systemic lupus erythematosus. In Harrison, T.R. (ed.). Principles of internal medicine, ed 8. New York, McGraw-Hill, Dixon, F.J. Immune-complex diseases. In Harrison, T.R. (ed.). Principles of internal medicine, ed 8. New York, McGraw-Hill, Pollack, V.E., and others. The clinical course of lupus nephritis: relationship to the renal histologic findings. In Pkincaid-Smith and others (eds.). Perspectives in nephrology and hypertension. New York, John Wiley and Sons, Inc., vol 1, Estes, D and Christian, C.L. The natural history of systemic lupus erythematosus by prospective analysis. Medicine 50:85-95, Velayos, E.E., and others. Arthropathy associated with steroid therapy. Ann Intern Med 64: , Dubois, E.L., and Cozen, L. Avascular (aseptic) bone necrosis associated with systemic lupus erythematosus. JAMA 174(8): , Milch, R.A. Blood supply and the localization of tetracycline fluorescence in arthritic femoral heads. Arthritis Rheum 6: , Siemsen, J.K.; Brook, J.; and Meister, L. Lupus erythematosus and avascular bone necrosis: a clinical study of three cases and review of the literature. Arthritis Rheum 5: , Lanigan, D.T., and others. Condylysis in a patient with a mixed collagen vascular disease. Oral Surg 48(3): , Berkow, R. (ed.). The Merck manual of diagnosis and therapy. Rahway, N), Merck Sharp and Dohme Research Laboratories, Ropes, M.W. Systemic lupus erythematosus. Cambridge, Mass, Harvard University Pi;ess, Fries, J.F., and Holman, H.R. Systemic lupus erythematosus: a clinical analysis. In Smith, L.H. (ed.). Major problems in internal medicine. Philadelphia, W. B. Saunders Co., Brandt, L., and Hedberg, H. Impaired phagocytosis by peripheral blood granulocytes in systemic lupus erythematosus. Scand J Haematol 6: , Schilling, J.A. Wound healing. Surg Clin North Am 56(4): , Peacock, E.E., and Van Winkle, W. Surgery and biology of wound repairs. Philadelphia, W. B. Saunders Co., Storey, E. The influences of adrenal cortical hormones on bone formation and resorption. Clin Orthop 30:197, Azamoff, D.L. Steroid therapy. Philadelphia, W. B. Saunders Co., Samuelson-Friedlandei^-Swerdloff: LUPUS ERYTHEMATOSUS 557