Sarcoidosis is a multifocal, immune-mediated, systemic inflammatory disorder characterized by many potential signs and symptoms.

Our initial impression was that the patient had either Sjögren’s syndrome (despite previous negative evaluation findings for the disease) or sarcoidosis. We repeated the serologic workup and performed a biopsy of the labial minor salivary gland to rule out Sjögren’s syndrome. We also considered medication-induced xerostomia as a contributing factor to her oral dryness. Although the patient was taking several medications with significant xerostomia-inducing effects, including methylphenidate, zaleplon, lorazepam, doxepin and venlafaxine, she did not correlate the onset of xerostomia with the initiation of any specific drug therapy.

Test results. The results of the serologic workup for Sjögren’s syndrome antibodies (SS-A, SS-B), antinuclear antibody and rheumatoid factor were negative. Histologic examination of the biopsy specimen demonstrated replacement of minor salivary gland tissue with noncaseating granulomas suggestive of foreign-body implantation or a systemic granulomatous disease. One of us (J.R.) inspected the tissue under polarized light, which did not reveal the presence of a foreign substance. A Ziehl-Neelsen stain was negative for mycobacteria, and periodic acid–Schiff and Gomori’s methenamine-silver stains were negative for fungi (Figure 2A, B).

View larger version (79K): [in this window] [in a new window]   Figure 2. A. A biopsy of the labial minor salivary glands revealed partial effacement of the salivary gland parenchyma by a granulomatous inflammatory process consisting of focal accumulations of multinucleated giant cells, histiocytes and lymphocytes. There were no regions of necrosis (hematoxylin-eosin stain, x100 magnification). B. Histochemical stains for fungi were negative. The photomicrograph represents periodic acid–Schiff stain (x400 magnification).

We instructed the patient to use sugarless candy, artificial saliva and cevimeline salivary stimulants, as well as to take frequent sips of water for symptomatic relief of xerostomia, oral burning sensation and dysphagia. A staff dietician recommended appropriate dietary modifications to help with her oral dryness and dysphagia. In addition, we stressed the importance of daily application of neutral 1.1 percent sodium fluoride gel in custom-made trays for caries prevention and the use of a desensitizing toothpaste. We advised the patient to brush the dorsum of the tongue and to visit her general dentist and us frequently for monitoring of her dental status and oral symptoms, respectively.

On a recall visit to the oral medicine clinic seven months later, the patient reported experiencing an improvement of her oral dryness and that taste sensation had returned to normal. She had no residual oral burning or tooth sensitivity. On clinical examination, the bilateral parotid swellings had resolved (Figure 1B), and the salivary glands were nontender and secretory. The mucosa was moist intraorally. The patient’s rheumatologist obtained follow-up chest radiographs and performed blood chemistry studies, which revealed partial resolution of the pulmonary infiltrates and a return of SACE to normal levels. The clinical findings suggested spontaneous remission of sarcoidosis. The patient reported that having a specific diagnosis had significantly alleviated her anxiety, and she expressed her appreciation for our contribution to the diagnosis of her underlying systemic condition.

	DISCUSSION

TOP ABSTRACT CASE REPORT DISCUSSION CONCLUSION REFERENCES

 
A differential diagnosis for bilateral parotid swellings, with or without xerostomia, includes immunologic conditions (such as Sjögren’s syndrome and benign lymphoepithelial lesion), granulomatous disorders (such as sarcoidosis), salivary gland neoplasms (such as Warthin’s tumor), metabolic disorders (such as diabetes), viral conditions (such as mumps or HIV parotitis), sialadenosis (due to malnutrition or alcoholism), sialadenitis (bacterial or obstructive), lymphoma and medication-induced hypertrophy.

In our patient, bilateral lymphoma was unlikely, particularly in view of the relatively rapid onset reported by the patient. Bilateral swellings, absence of pain (particularly at mealtimes) and lack of pus excluded both obstructive (sialithiasis, ductal stricture) and bacterial sialadenitis as the underlying disease. The patient denied abusing alcohol and did not fit the profile of a malnourished person. Also, the relatively rapid onset of parotid swellings and the firmness of the parotid glands on palpation contradicted the insidious onset and normal texture of the enlarged parotid glands seen in sialadenosis.⁴ The patient did not have diabetes, had no risk factors for HIV disease and reported a distant history of childhood mumps. Therefore, we considered Sjögren’s syndrome, sarcoidosis and medication-induced xerostomia to be the potential causes of the patient’s symptoms.

Sarcoidosis is a multifocal, immune-mediated, systemic inflammatory disorder characterized by many potential signs and symptoms, as well as by the presence of noncaseating granulomas in the involved organs.^5–8 The disease occurs worldwide and may affect people of either sex, as well as those from any ethnic or age group.^7,9–12 It usually arises in the second to fourth decades of life,^6,10,12 with women being somewhat more frequently affected and at a greater risk than men of developing serious complications.^9,13,14

In the United States, sarcoidosis primarily affects African-Americans, who tend to have more acute symptoms, extrapulmonary manifestations and a higher mortality rate at an earlier age compared with whites, who often are asymptomatic and have a better prognosis.^6,13,15,16 Several authors^17–21 have reported a familial, spatial (for example, among people in the same household), seasonal and occupational clustering of the disease, suggesting a multifactorial origin that includes genetic predisposition, infectious organisms and environmental exposures as probable underlying mechanisms.^5,10

Sarcoidosis is known to affect a wide array of organs and tissues, including the lung, heart, liver, spleen, bones, skin, eyes, lymph nodes, parotid glands and, on occasion, the oral cavity.^22,23 The extent of the disease and its complications vary, ranging from mild symptoms in some patients to major incapacitation in others.^13,23 Many patients experience no symptoms and are identified incidentally.^6,7 The most prominent manifestations of the disease involve the lungs, as evidenced clinically by the presence of dyspnea in patients.^7,12–14,24 Lung volumes and diffusing capacity often are reduced, and chest radiographs reveal bilateral hilar lymphadenopathy, diffuse parenchymal infiltrates or both.^7,24

The pattern of onset in sarcoidosis determines the course and prognosis of the disease.

Skin, eyes and lymph nodes are the most frequent sites of extrapulmonary involvement.⁹ Cutaneous sarcoidosis has been reported to occur in 25 percent of patients, and it may suggest chronicity and poor prognosis.^6,7,14 Similarly, one of four patients is affected with ocular sarcoidosis with the potential for progression to blindness.^6,7,13 Cardiac sarcoidosis and neurosarcoidosis are uncommon, but they may lead to fatal complications such as dysrhythmias and conduction block, as well as seizures and encephalopathy.^6,10 Other possible systemic effects include liver and spleen enlargement, thrombocytopenia, abnormal calcium metabolism, renal dysfunction, arthropathy and skeletal deformities.^{6,12,13,25,26}

Diagnosis of exclusion. Owing to the absence of a diagnostic gold standard, sarcoidosis is a diagnosis of exclusion.^6,11,14,24 First, the clinician establishes a compatible clinical picture based on symptomatology and physical and radiologic findings.^6,7,12 Next, the clinician performs a biopsy of the most accessible organ, such as skin or lymph nodes, to obtain histologic evidence of noncaseating granulomas.^6,12,13,27 These structures are composed of focal aggregates of lymphocytes, macrophages and multinucleated giant cells, but they are not unique to this disease. Therefore, it is necessary to exclude other sources of granulomatous inflammation, such as foreign-body implantation, tuberculosis, Crohn’s disease and deep fungal infections, although such diseases often exhibit necrotizing granulomas.^6,10,12,13

Comprehensive assessment. Clinicians must perform a comprehensive assessment of potential target organs in patients suspected of having sarcoidosis, with special attention paid to the lungs, heart, central nervous system (CNS), eyes, skin and lymph nodes.^9,10,11 A chest radiograph and a thorough ophthalmic evaluation are required, even for patients without specific pulmonary or ocular complaints.^9,10 Baseline laboratory tests include complete blood cell counts, erythrocyte sedimentation rate, liver and renal function tests, serum calcium and SACE levels, pulmonary function tests, electrocardiography and tuberculin testing.^9–13 Periodic follow-up is essential for the clinician to evaluate the progression of the disease and to detect new organ involvement.^9,11

The SACE level has been studied extensively as a laboratory marker in sarcoidosis. Secretion of ACE by granuloma-forming epithelioid cells results in high serum levels in 80 to 90 percent of patients with sarcoidosis.^11,28 However, because of the lack of specificity, an elevated SACE level is only suggestive of, rather than diagnostic for, sarcoidosis.^11,28 The reported false-positive and false-negative rates for the SACE level as a laboratory marker of sarcoidosis are 10 and 40 percent, respectively.^29,30

The pattern of onset in sarcoidosis determines the course and prognosis of the disease, as well as the patient’s therapeutic response.^8,12 Although spontaneous resolution is common in cases of acute sarcoidosis, chronic disease often is associated with a gradual onset, a progressive course and many potential complications.^8,12 Poor prognostic indicators include older age at onset, black race, hypersplenism and advanced pulmonary involvement.^10,31 It is uncommon for patients to die of sarcoidosis,^13,24 and death often is attributed to terminal fibrosis of critical organs such as the lungs, heart or CNS.^10,13,32

Orofacial manifestations of sarcoidosis are uncommon, and the disease typically is diagnosed before orofacial sequelae appear.^14,33,34 Sarcoidosis may affect the head and neck lymph nodes, osseous and soft oral tissues, as well as the major and minor salivary glands.^13,14,26,34 Mandel and Kaynar² reported observing enlargement of the major salivary glands as the first sign of sarcoidosis in asymptomatic patients. Parotid glands are affected in 4 to 6 percent of cases of sarcoidosis, with a self-limiting or permanent enlargement as the outward presentation.^6,13,34–36 Enlargements often are bilateral, asymptomatic, firm and smooth on palpation, with no changes in size when eating.^2,4 Associated xerostomia may or may not be present.^2,6,13 These clinical features are characteristic of Sjögren’s syndrome, but occasionally they may be associated with sarcoidosis.^36–39 A labial gland biopsy is a highly sensitive and specific diagnostic test in the histologic assessment of Sjögren’s syndrome,^37,40 but it also can assist in the differentiation of Sjögren’s syndrome from sarcoidosis when clinical presentations are similar.⁴⁰

Sarcoid lesions of the jaw bones may appear as diffuse, poorly defined radiolucencies on dental radiographs, and they can result in tooth mobility on clinical examination.

Several studies have shown sarcoid infiltration of the minor salivary glands with or without clinical involvement of the major salivary glands.^{2,13,34,38,41,42} Therefore, when accessible, clinically involved tissues are not available, the clinician can perform a biopsy of normal-appearing tissue to confirm the histologic diagnosis in a patient with compatible clinical findings.^{13,26,34,42,43}

Labial minor salivary gland biopsy. Several cases of sarcoidosis-induced parotid enlargement confirmed via biopsy of the labial minor salivary gland have been reported in the literature.^41,44,45 This technique has a lower diagnostic yield in sarcoidosis compared with biopsies of the liver, lung, lymph node or parotid gland, perhaps because of the uncommon, delayed (for example, after other clinical signs develop) and less intense histologic involvement of the minor salivary glands.^46–48 On the other hand, this procedure is simple, minimally invasive and associated with significantly less morbidity than is a parotid gland biopsy.^40,42,43,45 In addition, the tissue is readily accessible from the lower labial mucosa, and the clinician can perform the procedure under local anesthesia at chairside.^42,43,45

Owing to the complexity of disease manifestation, clinicians tailor therapy to each patient.^7,9 Many patients experience temporary or long-term remission without medical therapy.^6,9,10 Therefore, treatment often is deferred for three to 12 months to assess the overall disease progression.^9,32,49 This appeared to be the case with our patient, who experienced remission without therapeutic intervention. Immediate medical treatment is reserved for patients with neurological, cardiac, severe ocular, advanced pulmonary and disfiguring cutaneous disease, as well as persistent hypercalcemia.^{5,9,10,24,32,49,50}

Clinicians focus treatment on the suppression of the immune system, and corticosteroids are the mainstay of therapy.^9,24,32,51 Topical, inhalational, intralesional or systemic steroids may be used to control the disease, depending on its severity.^6,9,52,53 Physicians closely monitor patients receiving long-term systemic steroid therapy for potential adverse effects of these medications.⁹ They also can consider steroid-sparing immunosuppressive agents for patients with critical organ involvement that is poorly controlled with systemic steroid therapy.⁵⁴ Implanted cardiac defibrillators or heart and lung transplantation may be indicated for patients with cardiac and pulmonary sarcoidosis in which the organs are not salvageable.^6,55 Splenectomy may be necessary to treat sarcoidosis-induced splenomegaly associated with a risk of rupture.⁶

Dentists need to consider a number of issues regarding the dental care of patients with sarcoidosis. Sarcoid lesions of the jaw bones may appear as diffuse, poorly defined radiolucencies on dental radiographs, and they can result in tooth mobility on clinical examination.^7,14,56 Approximately 1 to 6 percent of patients with sarcoidosis may have an obstruction of the nasal passages or chronic sinusitis.⁷ Steroid supplementation before major oral surgery may be indicated for patients with adrenal suppression secondary to long-term steroid therapy.⁷ These patients also may be susceptible to infection and require prophylactic antibiotics before undergoing invasive dental procedures.⁷

In addition, platelet retention associated with hypersplenism may lead to occasional thrombocytopenia,²⁵ necessitating preoperative blood count studies. Anemia and other hematologic changes also may result from granulomatous infiltration of bone marrow.⁵⁷ Practitioners also need to evaluate patients for leukopenia, anemia, thrombocytopenia and oral mucositis secondary to the administration of drugs that are toxic to bone marrow.^7,54 Clinicians should defer dental procedures performed in hospitals under general anesthesia until a patient’s medical status and degree of vital organ dysfunction have been evaluated.⁷

Sarcoid infiltration of major salivary glands and subsequent xerostomia predispose patients to caries, periodontal disease and candidiasis, highlighting the need for frequent recall appointments and aggressive preventive measures with salivary stimulants, topical fluoride and anti-fungal medications.^7,13

	CONCLUSION

TOP ABSTRACT CASE REPORT DISCUSSION CONCLUSION REFERENCES

 
Enlargement of the major salivary glands may be the first sign of sarcoidosis in a patient who appears healthy otherwise. This case emphasizes the importance of including sarcoidosis in the differential diagnosis of bilateral parotid swelling associated with xerostomia. It also highlights the potential role of the dentist in the diagnosis and dental treatment of patients with systemic sarcoidosis.