Intraosseous Sarcoidosis of the Jaws Mimicking Aggressive ...

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Case Report Intraosseous Sarcoidosis of the Jaws Mimicking Aggressive Periodontitis: A Case Report and Literature Review Lakshmanan Suresh,* Alfredo Aguirre,* Robert J. Buhite,† and Lida Radfar*

Background: Sarcoidosis is a relatively common systemic granulomatous disease of unknown etiology. The skeletal system is affected in up to 39% of patients, but intraosseous sarcoidosis affecting the maxilla and mandible is rare. Only 20 cases have been reported previously in the English literature. This paper presents a case of generalized intraosseous sarcoidosis of the jaw bones that mimicked rapidly progressive periodontitis. Methods: A 46-year-old male patient presented with loose teeth for assessment of implants. He had been gradually losing his teeth since 1999. His past medical history was significant, with sarcoidosis diagnosed in 1998. A panoramic radiograph showed a bilateral cotton-wool appearance of the mandible. A soft tissue and bone biopsy was performed and sent for histological examination. Results: Microscopic examination of hematoxylin and eosin-stained sections revealed non-caseating granulomatous inflammation consistent with skeletal sarcoidosis. Conclusions: Intraosseous sarcoidosis of the jaw bones is rare and presents commonly as progressive and rapid alveolar bone loss similar to periodontitis. Therefore, it is important for periodontists to be knowledgeable and able to diagnose this condition, as rapid alveolar bone loss may be the first sign of sarcoidosis. J Periodontol 2004;75:478-482. KEY WORDS Alveolar bone loss/diagnosis; periodontitis/ diagnosis; sarcoidosis/diagnosis.

* Department of Oral Diagnostic Sciences, School of Dental Medicine, University at Buffalo, Buffalo, NY. † Department of Restorative Dentistry, School of Dental Medicine, University at Buffalo.

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Sarcoidosis is a systemic, non-caseating granulomatous disease of unknown etiology. Jonathan Hutchinson, an English surgeon-dermatologist, reported the first case of sarcoidosis in 1875, but the term “sarcoidosis” was introduced by Boeck in 1899.1 In Greek, sarcoidosis means a “flesh-like condition.”2 Sarcoidosis affects individuals regardless of race, gender, or age and exhibits a worldwide prevalence rate of 20/100,000.3 In the United States, the prevalence is 35.5 to 64/100,000 for African Americans and 10 to 14/100,000 for Caucasians.4 The disease exhibits a female predominance and a bimodal distribution. The first peak is between the ages of 25 to 35 years, and the second peak at 45 to 65 years.2,5 Sarcoidosis may affect any organ, including the skeleton. The most common clinical presentation of sarcoidosis consists of hilar lymphadenopathy, pulmonary infiltration, dermal, and ocular lesions.6 Skeletal involvement varies widely and ranges from 1% to 39%.7-9 The reason for bone involvement in sarcoidosis is not clear.7 Although any bone may be affected, the small bones of the hands and feet are the most commonly involved.10 Sarcoidosis affecting the maxillary or mandibular bone is rare. Poe11 reported the first case of intraosseous sarcoidosis affecting the jaws in 1943. Since then, including our case, there have been only 21 cases documented in the English literature (Table 1).11-30 When intraosseous sarcoidosis affects the jaws, it is usually localized. To the best of our knowledge, only three cases of sarcoidosis have been published in the English-language literature where jaw involvement resulted in generalized and rapid loss of teeth (Table 1).28-30 The purpose of this paper is to report an unusual case of maxillary and mandibular sarcoidosis that mimicked generalized aggressive periodontitis. CASE REPORT A 46-year-old Caucasian male was referred to the Oral Medicine Clinic, School of Dental Medicine, University at Buffalo, in December 2002 for an assessment of his suitability to receive dental implants. The patient’s chief complaint was “loose teeth.” History revealed that the patient had noticed progressive mobility of his teeth since early 1999, which was evaluated by his primary dentist. His condition was

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Table 1.

Intraosseous Jaw Sarcoidosis Reference

Age

Race/Gender

Chief Complaint

Location

Management

Localized bone loss Poe, 194311 Kalman et al., 195412 MacDonald et al., 198513 Thomas et al., 197614 Hillerup., 197615 Betten et al., 197616 Schwartz, 198117 Aragon et al., 198218 Cohen et al., 198219 Verheijen-Breemhaar et al., 198720 Hildebrand et al., 199021 Rubin et al., 199122 Klesper et al., 199423 Clayman et al., 199824 Hong et al., 200025 White et al., 200026 Krajekian et al., 200227

41 54 45 30 22 49 29 25 59 28 41 25 16 35 40 37 31

B/F W/F W/F B/M NA W/M W/F B/F W/F NA/F B/M B/F W/F B/F B/M W/M W/M

Pain left ear Pain/lump Dull pain Pain right TMJ Mandibular lesion None TMJ pain Painful gums Non-healing socket Loose teeth Nasal obstruction None Loose teeth Loose teeth Loose teeth Maxillary bone loss Loose teeth

Posterior mandible Anterior maxilla Anterior mandible Right TMJ Posterior mandible Posterior mandible Mandible condyle Anterior maxilla Posterior mandible Anterior maxilla Anterior maxilla Anterior maxilla Posterior maxilla Anterior maxilla Anterior maxilla Posterior maxilla Posterior mandible

NA Curettage Exploration Steroids Curettage Curettage Condylectomy Extraction Curettage Extraction Steroids NA Steroids NA Steroids Remission Surgery and steroids

Generalized bone loss Van Swol, 197328 Cohen et al., 198129 Makris et al., 198330

22 35 27

B/F W/F B/F

Tooth mobility Swollen mandible None

Maxilla/mandible Maxilla/mandible Maxilla/mandible

NA Remission NA

NA = not available; B = black; W = white; F = female; M = male; TMJ = temporomandibular joint.

Figure 1. Panoramic radiograph taken in 2000 showing generalized severe alveolar bone resorption in the maxilla and mandible.

diagnosed as generalized periodontitis. Despite good oral hygiene, alveolar bone loss continued, and the mobility progressively worsened. Teeth #16, 19, 20, 21, 29, 30, and 31 were extracted at various times between 1999 and 2002 because they became grossly mobile due to the lack of bone support (Fig. 1). A computerized tomogram (CT) was done in 2002 for implant assessment, which showed tunneling of the cortex and replacement of the bone marrow by soft tissue in the mandible (Fig. 2). There was no other bone involvement.

Figure 2. Axial view of the CT scan done in 2002 showing bone loss in the maxilla and tunneling of the cortical bone in the posterior region of the mandible. 479

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Past medical history revealed that the patient was diagnosed with stage IV pulmonary sarcoidosis in August 1998. The chest radiograph showed bilateral hilar lymphadenopathy, end-stage fibrosis, bullae, honeycombing, and cavities in the lungs (Fig. 3). Wrist radiographs were negative. Treatment with prednisone (20 mg/daily) was initiated in July 2000, and a tapering course was completed in July 2001. Skin involvement (lupus pernio) of the chin and right shoulder developed after discontinuation of the treatment. A biopsy of the chin was taken in October 2001 and revealed non-caseating chronic granulomatous dermatitis. The rest of the medical history was non-contributory. Our physical examination revealed a pinkish skin patch on the right shoulder measuring 3.0 × 2.0 cm. Intraoral examination revealed severe gingival recession and mobility of all remaining teeth. A panoramic film showed severe alveolar bone loss and a bilateral cotton-wool appearance of the mandible. Hematology and biochemistry including alkaline phosphatase, calcium, and serum angiotensin-converting enzyme levels were requested. All of the test results were within the normal limits. A bone biopsy from the left mandibular alveolar region distal to tooth #18 was obtained and submitted for microscopic examination. The specimen revealed non-caseating granulomatous inflammation consistent with skeletal sarcoidosis (Figs. 4A and 4B).


The patient was referred to his pulmonologist for further treatment. A full-body computerized tomography (CT) scan showed involvement of the mid and distal humerus and proximal radius. Repeat hematology and biochemical tests (alkaline phosphatase, calcium, and serum angiotensin-converting enzyme levels) were within the normal range. Corticosteroid therapy was reinitiated (prednisone 80 mg/day for 2 weeks and tapered down to 40 mg/day). In addition, infliximab, a tumor necrosis factor-α receptor antagonist (5 mg/kg), was prescribed. CT scans were repeated 3 months after the initiation of therapy and showed no additional bone resorption in the maxilla or mandible. DISCUSSION Sarcoidosis of the bone was first recognized by Besnier31 in 1889, before the introduction of x-rays. In 1904, soon after the introduction of x-rays, Karl Kreibich presented an excellent radiographic reproduction and histology of patients who had lupus pernio of the fingers, showing cystic changes in the bones and non-caseating granulomas.32 Since then, there have been several published reports of sarcoidosis affecting other bones.7-9,11,12,23 Skeletal lesions of sarcoidosis have a predilection for the hands and feet, where they are usually asymptomatic and bilateral.7 There is increased bone resorption and osteolysis, with preservation of the cortical borders of the affected bones. This is evident in imaging studies as lytic, permeative, or destructive lesions.33 In a majority of cases, the bone and skin lesions occur together.33 Our patient had permeative and lytic bone

Figure 4.

Figure 3. Posterior-anterior view of the chest x-ray showing bilateral hilar lymphadenopathy and cavities. 480

Biopsy taken from the crest of the left mandibular alveolar bone. A) Three non-caseating granulomas with typical epithelioid macrophages and multinucleated giant cells are seen among a dense fibrous connective tissue stroma containing interspersed fibroblasts and scattered lymphocytes. In addition, a fragment of vital trabecular woven bone is seen (hematoxylin and eosin stain; original magnification ×200). B) Higher magnification of another microscopic field shows the presence of multinucleated giant cells exhibiting Schumann’s bodies (altered lysosomes).This cluster of giant cells and epithelioid macrophages constitute the typical non-caseating granulomas observed in sarcoidosis (hematoxylin and eosin stain; original magnification ×400).

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lesions in the mandible, humerus, and radius. He also had skin lesions under the chin and on the shoulder. There have been a total of 20 cases (17 localized and 3 generalized) reported in the English literature of sarcoidosis affecting the jaw bones (Table 1).11-30 Maxillary anterior and mandibular posterior regions were the most common regions affected. There was a slight female predominance, but no racial predilection was noted. The age of the patients ranged from 16 to 59 years (mean, 44). The most common clinical presentation was mobility of the teeth. Our patient presented with rapid bone loss leading to exfoliation of many of his teeth. There is a general lack of agreement as to the etiology and pathogenesis of sarcoidosis. Immunologic, genetic, infectious, and environmental agents have been postulated as possible etiological factors,34 but current evidence supports an immunologic pathogenesis in which T-helper 1 lymphocytes (Th1) play a central role.35 The clinical symptoms of sarcoidosis are usually non-specific. Patients may present with fever, fatigue, malaise, or weight loss.3 The lungs and lymph nodes are the most common organs involved.36 Other organ involvement and clinical features are summarized in Table 2. Our patient had non-specific constitutional symptoms, with a chest x-ray showing fibrosis, honeycombing, and cavities. Sarcoidosis is a diagnosis of exclusion as there are no absolute diagnostic tests available.3,26 The differential diagnosis for systemic sarcoidosis affecting bones includes bacterial infections (tuberculosis, syphilis, lep-

Table 2.

Organ Involvement in Sarcoidosis2,13 Organs Lungs/lymph nodes Liver/spleen

Frequency 90% 50-80%

Signs and Symptoms Dry cough, dyspnea, Lofgren’s syndrome Hepatosplenomegaly, abnormal liver function

Eyes

50%

Uveitis, iritis, photophobia

Bone and marrow

40%

Osteolytic lesions

Skin

25%

Indurated purple plaques (lupus pernio), erythema nodosum

Heart/nerves

5-10%

Cardiac arrythmias, congestive heart failure, facial nerve palsy

Parotid gland

4-6%

Parotitis, Herefordt syndrome

Lofgren’s syndrome: bilateral hilar lymphadenopathy with erythema nodosum. Herefordt’s syndrome: uveoparotitis and facial palsy.

rosy), fungal infections (histoplasmosis, coccidiodomycosis), and foreign body granulomas (berylliosis). Serum levels of calcium and angiotensin-converting enzyme (SACE) are helpful, but non-specific. Hypercalcemia occurs in about 10%8 of patients, and elevation of SACE is seen in 50% to 80% of patients with sarcoidosis.37 Our patient did not exhibit elevation of calcium or SACE. The histology of sarcoidosis shows non-caseating granulomas with occasional giant cells containing Schumann’s bodies (altered lysosomes) or stellate asteroid bodies (entrapped collagen).38 It has been speculated that sarcoidosis is the result of abnormal degradation of an antigenic material. The identity of the antigenic material is still unclear; however, the available evidence suggests that an atypical mycobacterium of limited pathogenesis establishes residency in a susceptible population and triggers the formation of noncaseating granulomas.39 While the histology is not specific, the findings should raise the suspicion of sarcoidosis. The histological sections from our patient showed non-caseating granulomas with multinucleated giant cells consistent with sarcoidosis. Sarcoidosis is a relatively common disease; however, there have been fewer than 50 reports of sarcoidosis affecting the oral cavity.40 Common oral manifestations, apart from periodontal bone loss, include gingival hyperplasia and nodules in any site of the oral mucosa.40 In our literature review, we found that seven of 21 cases (including our case) had intraosseous jaw sarcoidosis as the initial sign of the disease. Therefore, it is important for the periodontist to recognize the oral manifestations of sarcoidosis, such as rapid bone loss mimicking periodontitis or gingival hyperplasia. In such conditions, a simple soft tissue and bone biopsy of the affected sites is recommended. The patient who is suspected of having bone sarcoidosis also should be evaluated for other systemic involvement. There is a scarcity of information regarding the treatment of intraosseous jaw sarcoidosis. In the cases reported in the jaws, a variety of therapeutic approaches such as no treatment,29 simple curettage,12,15,16,19 systemic corticosteroids,14,21,23,25,27 and surgery (condylectomy)17 were used, yielding varying results.11-30 We believe that the treatment of choice for jaw sarcoidosis is curettage of the granulomas, followed by splinting of teeth. Granulomas already present within the bone should be surgically eliminated, and if dental mobility ensues, stabilization with splints should be done. Steroids are recommended if the disease is symptomatic and progressive. ACKNOWLEDGMENT The authors would like to thank Dr. Mirdza Neiders, School of Dental Medicine, University at Buffalo, for her assistance in preparation of the manuscript. 481

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