The prevalence and incidence in young children are unknown.⁴ Most cases develop in patients ranging in age from 8 to 15 years.⁵ Prevalence increases until adulthood, with the 20- to 40-year-old age group being most susceptible.⁶ Among children diagnosed with sarcoidosis, there is no established sex predilection. In adults, sarcoidosis tends to be more common in women.⁷ In addition, research has clearly established that in the United States, sarcoidosis affects African-Americans more commonly than it does whites, with a ratio varying from 10:1 to 17:1.² Furthermore, more than 70 percent of the pediatric cases in the United States have been reported from the Southeastern and South Central regions, suggesting an endemic pattern for childhood sarcoidosis.³

	CASE REPORT

TOP ABSTRACT CASE REPORT DISCUSSION CONCLUSION REFERENCES

 
A 13-year-old black girl was referred to Columbia University’s Salivary Gland Center, or SGC, New York, with a four-month history of a painless, symmetrical, bilateral, parotid swelling first noticed by her mother (Figure 1). The patient reported no history of any fluctuations in size, with or without eating.

View larger version (98K): [in this window] [in a new window]   Figure 1. Patient with sarcoidosis and bilateral parotid swelling (arrows).

Because the chest radiographs were negative and because ACE is not a specific test for sarcoidosis, the ophthalmologist could not make a firm diagnosis of a sarcoidal uveitis. Therefore, the patient’s pediatrician referred her to the SGC for evaluation of the parotid swellings.

Extraoral palpation indicated that the parotid swellings were firm and painless. They followed the anatomic configuration of both parotid glands. The overlying skin was not inflamed. We found no trismus, and palpation detected no cervical lymphadenopathy.

Stimulated salivary volume. Intraorally, the mucosa appeared moist. We used a modified Carlsen-Crittenden collector to measure stimulated salivary volume from each parotid gland individually. A smaller-than-normal volume of saliva was obtained from each gland. The right parotid produced 0.4 milliliters per minute, while the left parotid produced 0.3 mL/minute (normal, 0.5 to 1.0 mL/minute). Furthermore, the saliva was quite viscous, indicating the presence of an inflammatory process. The salivary chemistry of both glands revealed significant elevations of electrolyte and protein levels, thus substantiating the existence of a bilateral parotid inflammation.

Salivary gland biopsy. To establish a diagnosis of sarcoidosis, we performed a labial salivary gland biopsy. Histologic examination of the specimen revealed numerous noncaseating granulomas infiltrating and replacing the glandular parenchyma, a pattern associated with sarcoidosis (Figure 2). Special staining ruled out the presence of mycobacterial or fungal infections, berylliosis and a foreign body, conditions that produce similar granulomas.

View larger version (146K): [in this window] [in a new window]   Figure 2. Photomicrograph of a labial salivary gland biopsy specimen shows granuloma peripherally delineated by lymphocytes (arrows) in a bed of normal labial salivary gland tissue (A). Giant cells are present (hematoxylin-eosin stain, original magnification x125).

	DISCUSSION

TOP ABSTRACT CASE REPORT DISCUSSION CONCLUSION REFERENCES

 
Despite extensive studies, no agent has been identified as the cause of sarcoidosis. Several studies suggest that an infectious organism is the cause, particularly mycobacteria.^8–10 Sarcoidosis currently is considered a chronic inflammatory disease, distinguished by hyperimmune reactions to an unspecified agent at the lesion sites. Continuous stimulation by the antigenic agent sustains the pathological process.¹¹

The clinical presentation of sarcoidosis varies, because it is a multisystem disease and affects several organs.⁵ Organs most frequently involved include the lungs, lymph nodes, eyes, skin, liver, spleen and salivary glands. The organs may be symptomatic or silent in their presentation. In addition, most cases of childhood sarcoidosis are accompanied by nonspecific symptoms, including fever, weight loss, fatigue, cough or rashes.

Of great significance to the dental profession is the involvement of the salivary glands in this disease. Parotid gland swelling has been reported in 4 to 6 percent of patients diagnosed with sarcoidosis.^12,13 Parotid enlargement is a more frequent finding in children diagnosed with early-onset sarcoidosis.¹⁴

Clinical patterns. The salivary gland involvement may manifest itself in a variety of clinical patterns. The most common pattern is represented by major salivary gland swelling, with histologic involvement of the minor salivary glands.¹⁵ Xerostomia may be present (a decreased salivary volume was observed in our patient), and it is directly proportional to the extent of the granulomatous infiltration into the gland. Spontaneous regression of the swelling can be expected.¹⁶

A second pattern of salivary gland involvement is characterized by the absence of clinical salivary gland swelling. Regardless of whether swelling is present, however, histologic examination of minor salivary gland biopsy specimens usually will reveal the presence of noncaseating granulomas. The palatine mucous gland will demonstrate granulomas in 38 percent of patients with known sarcoidosis, while labial salivary glands that have undergone a biopsy reveal granulomas in 58 percent of patients.^17,18

A definitive diagnosis of sarcoidosis is best achieved by integrating clinical data with the presence of noncaseating granulomas.

A third manifestation of salivary involvement in sarcoidosis is uveoparotid fever, or Heerfordt’s syndrome, which consists of a triad of symptoms including bilateral parotid swelling, uveitis and cranial nerve involvement. This symptom complex rarely is seen in children.

It is important for dentists to be aware that the first clinical sign of sarcoidosis may be parotid or even submandibular salivary gland involvement, with parotid sialadenopathy a frequent finding in children.^12,13 No specific laboratory tests exist for sarcoidosis. However, the ACE level typically is elevated in approximately 80 percent of children^19,20 and 60 percent of adults with late-onset sarcoidosis.²¹ The ACE test has proven to be less sensitive in patients diagnosed with early-onset sarcoidosis.²²

ACE normally is found in many organs and body fluids and is secreted by pulmonary capillary endothelial cells and alveolar macrophages, as well as by the epithelial cells of the renal proximal tubules.²³ The elevated ACE level in patients with sarcoidosis results from its production by the epithelioid cells of the granuloma.³ Although ACE test results have been shown to aid in the diagnosis of sarcoidosis and in monitoring its course and activity, many other disorders are associated with elevated ACE levels, including miliary tuberculosis, leprosy and Gaucher’s disease.²⁴ However, other investigative measures can be used to rule out these entities.

Diagnosing sarcoidosis. A definitive diagnosis of sarcoidosis is best achieved by integrating clinical data with the presence of noncaseating granulomas. Histologically, the granuloma is characterized by tightly grouped epithelioid cells interspersed with a small number of giant cells. Accumulations of lymphocytic cells may be seen at the periphery of the granuloma. To further support the diagnosis of sarcoidosis, clinicians must use special stains to rule out the aforementioned other granulomatous conditions (for example, histoplasmosis, blastomycosis, berylliosis, foreign bodies, tuberculosis, leprosy). Clinical data and negative culture results also contribute significantly to the diagnosis. Furthermore, the clinician should be aware that noncaseating granulomas occasionally are seen in cases of tuberculosis.²⁵

Because parotid swelling is not an uncommon finding in children, it is important for the dentist to consider this disease when other, more common, causes of parotid swelling in children, such as mumps or recurrent juvenile parotitis, have been ruled out. Confirmation of a clinical diagnosis of sarcoidosis can be established on the cumulative basis of the patient’s medical history, clinical examination results, chest radiographic findings, elevated serum ACE levels and the results of a microscopic examination of a labial gland biopsy specimen with the use of special stains.

Corticosteroid therapy. After we discussed the parotid swellings with the patient’s pediatrician, she initiated a regimen of corticosteroids, which is the current therapy of choice for childhood sarcoidosis. Low-dose methotrexate therapy also can be instituted because methotrexate is an effective immunosuppressive agent and has steroid-sparing properties.³ The goal of therapy is to minimize or prevent inflammation and granuloma formation, which can lead to organ system dysfunction and ultimately cause end-stage organ destruction by the development of hyaline fibrosis. If the eye is involved, blindness might result. Therefore, the presence of an uveitis demands aggressive steroid therapy.

Few studies have been conducted to examine the prognosis of sarcoidosis in children because of the small number of cases reported. However, the cases that have been reported suggest that the prognosis is good for childhood sarcoidosis.^26,27 Children diagnosed with sarcoidosis usually have a favorable outcome, with spontaneous regression. Although the condition of most children improves, a significant number experience major complications. A 3 percent mortality rate has been reported in one review.³ Patients who experience multisystem involvement often suffer from chronic disease. Early diagnosis and treatment can slow or stop the progression to organ destruction. Therein lies the need for prompt recognition of the entity by the dental practitioner.

	CONCLUSION

TOP ABSTRACT CASE REPORT DISCUSSION CONCLUSION REFERENCES

 
We have reviewed the clinical symptoms of sarcoidosis, a benign, multisystem, granulomatous disease. The roles of ACE, salivary gland swelling and histologic examination results of a labial gland biopsy specimen in the diagnosis of sarcoidosis are highlighted. The case described above illustrates the salient features of this disease of unknown etiology.

View larger version (123K): [in this window] [in a new window]   Dr. Surattanont is a research assistant and a pediatric dental resident, New York-Presbyterian Hospital (Columbia Campus), New York.

View larger version (117K): [in this window] [in a new window]   Dr. Mandel is director, Salivary Gland Center, New York-Presbyterian Hospital (Columbia Campus), New York, and assistant dean and a clinical professor, Oral and Maxillofacial Surgery, Columbia University School of Dental and Oral Surgery, 630 W. 168th St., New York, N.Y. 10032. Address reprint requests to Dr. Mandel.