Unusual presentation of Sjogren syndrome.

Abstract: This case report describes a patient with Sjogren syndrome (SS) whose sole presenting feature was bilateral and painful submandibular gland enlargement. Extensive workup for alternate etiologies was negative and while serologies specific for SS were unremarkable, the diagnosis was eventually suggested by excisional biopsy. This case highlights the difficulty in making an early diagnosis of SS and demonstrates the important role of excisional biopsy in that diagnosis.

Key Words: Sjogren syndrome, submandibular gland, autoantibodies, excisional biopsy

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Sjogren syndrome is a chronic autoimmune condition characterized by exocrine gland dysfunction that presents with a variety of clinical symptoms, including keratoconjunctivitis sicca, xerostomia, and salivary gland swelling typically involving the parotid gland. There is much controversy, however, regarding the criteria used to diagnosis Sjogren syndrome. (1) Most criteria rely on the presence of autoantibodies and the objective demonstration of salivary gland involvement through biopsy or imaging studies. In many instances, the diagnosis can be difficult, and biopsy is essential. A case in which the sole presenting feature of this disorder was bilateral submandibular gland swelling is presented. The diagnosis was confirmed by excisional biopsy. This case emphasizes the importance of biopsy of major salivary glands in the diagnosis of Sjogren syndrome.

Case Report

A 24-year-old woman presented with painful bilateral submandibular swelling that had increased progressively over a period of 1 month. The symptoms were not exacerbated by eating. She reported no night sweats, sore throat, fevers, chills, skin rashes, or arthralgias. No unusual exposures or recent travel was noted, and she was otherwise healthy, with no significant family history.

Her physical examination was significant for bilateral submandibular fullness, approximately 5 cm in size, with tenderness to palpation. On manipulation of the submandibular glands, there was salivary flow and no palpable stones. No cervical, supraclavicular, axillary, or inguinal lymphadenopathy was detected, and the remainder of her examination was normal. Her chest radiograph was unremarkable, and subsequent CAT scan of the neck and chest confirmed bilateral diffuse swelling of the submandibular glands.

Blood tests showed a normal white cell count of 10.1 X [10.sup.9]/L, an elevated erythrocyte sedimentation rate of 24 mm/h, positive antinuclear antibodies in a dilution of 1:1,280 and a positive rheumatoid factor. Subsequent studies revealed a normal angiotensin-converting enzyme level, and there was no evidence of the autoantibodies anti-double stranded DNA, anti-Ro/SS-A, anti-La/SS-B, or anti-Smith. The patient was negative for HIV as tested by an enzyme-linked immunosorbent assay. A labial gland biopsy was pursued that was ultimately nondiagnostic, so an excisional biopsy of the right submandibular gland was undertaken. The submandibular tissue showed florid lymphoid follicular hyperplasia without evidence of granulomas or malignant cells. Flow cytometry of the tissue demonstrated a predominance of T-cell lymphocytes with an elevated CD4 to CD8 ratio. Tissue evaluated by acid-fast smear and culture did not reveal any acid-fast bacilli.

Further history revealed that the patient had no ocular or oral complaints. She had no alopecia, arthralgias, shortness of breath, or hematuria. To her knowledge, no members of her family had ever been diagnosed with a rheumatologic condition. Given the laboratory and biopsy findings, a diagnosis of Sjogren syndrome was made.

Discussion

The differential diagnosis of a submandibular mass includes a wide variety of conditions, including sialolithiasis, metastatic or primary malignancy, sarcoidosis, HIV infection, bacterial infection, hypertrophy related to underlying diabetes mellitus or vitamin deficiencies, and Sjogren syndrome.

Sjogren syndrome can have multiple systemic manifestations, including musculoskeletal, pulmonary, renal, and hematologic involvement. The syndrome may be primary or secondary, occurring with another rheumatic disease. A number of autoantibodies are associated with Sjogren syndrome, with the presence of certain autoantibodies being associated with the severity of disease. (1-3)

The criteria used to diagnose Sjogren syndrome has been the subject of much controversy, with as many as nine different sets of criteria having been previously proposed. Most criteria require the presence of keratoconjunctivitis sicca, xerostomia, autoantibodies, and the objective demonstration of salivary gland involvement through biopsy or imaging studies. (2,3) Salivary gland enlargement occurs in as many as 30% of patients with Sjogren syndrome during the course of their illness, although the parotid gland is most commonly involved and the glands are typically firm and nontender. On the other hand, bilateral and painful submandibular gland disease as a presenting complaint for Sjogren syndrome has been rarely described. (4) In addition, the typical features of keratoconjunctivitis sicca, xerostomia, and arthritis were absent in this case. Positive antinuclear antibody in a dilution of 1:1,280 suggested autoimmune phenomena, but the absence of anti-Ro/SS-A and anti-La/SS-B were unusual as well. Without a biopsy containing the characteristic pathologic findings and immunocytology of Sjogren syndrome, a diagnosis would not have been possible.

This case helps highlight the diagnostic quandary that is Sjogren syndrome. Although many of the current guidelines recommend the presence of anti-Ro/SS-A or anti-La/SS-B to confirm the diagnosis, these precipitins only occur in 75% and 40% of patients with primary Sjogren syndrome, respectively. (5,6) The most frequent clinical features associated with Sjogren syndrome, namely, keratoconjunctivitis sicca and xerostomia, are nonspecific and highly subjective. Although sialometry and sialochemistry are noninvasive, objective measures of salivary flow, their sensitivity and specificity in diagnosing Sjogren syndrome have yet to be properly defined. Biopsy of the labial gland has been suggested as an alternative to the more invasive biopsy of a major salivary gland, yet some patients with classic Sjogren syndrome may not show the typical histology, probably as the result of sampling error. Therefore, for younger patients in whom the diagnosis of SS is being entertained, biopsy of a major salivary gland is indicated.

Although the treatment modalities for Sjogren syndrome are largely limited to symptomatic relief of associated symptoms, diagnosis remains essential because long-term surveillance for the development of malignant lymphoma is necessary. Serology at the time of diagnosis can be useful in predicting the subsequent complications associated with Sjogren syndrome. The presence of anti-Ro/SS-A or anti-La/SS-B is more likely to suggest systemic disease and an increased risk for the development of lymphoma in the future. (2,3)

Conclusion

This case demonstrates an unusual presentation of Sjogren syndrome. In many instances, autoimmune serologies may be unremarkable, especially early in the disease, so biopsy must be pursued to make a definitive diagnosis. Early diagnosis is essential to prevent complications of Sjogren syndrome and to undertake surveillance for the development of lymphoma.

References

1. Kassan SS, Moutsopoulos MM. Clinical manifestations and early diagnosis of Sjogren syndrome. Arch Intern Med 2004;164:1275-1282.

2. Jonsson R, Moen K, Vestrheim D, et al. Current issues in Sjogren's syndrome. Oral Dis 2002;8:130-140.

3. Mahoney EJ, Spiegel JH. Sjogren's disease. Otolaryngol Clin North Am 2003;36:733-745.

4. Ahmad I, Ray J, Cullen RJ, et al. Bilateral and multicast major salivary gland disease: a rare presentation of primary Sjogren's syndrome. J Laryngology Otol 1998;112:1196-1198.

5. Reichlin JD, Scofield RH. SS-A Ro autoantibodies. In: Peter JB, Schoenfeld Y, eds. Autoantibodies. Elsevier: Amsterdam, pp. 783-788.

6. Keech CL, McCluskey J, Gordon TP. SS-B (La) autoantibodies. In: Peter JB, Schoenfeld Y, eds. Autoantibodies. Elsevier: Amsterdam, pp. 789-797.

K. Kulkarni, MD

From the Department of Internal Medicine, Columbia University Medical Center, New York, NY.

Reprint requests to Ketan Kulkarni, 400 Central Park West, 16U, New York, NY 10025. Email: [e-mail]

Accepted August 1, 2005.

RELATED ARTICLE: Key Points

* Sjogren syndrome is an autoimmune condition characterized by exocrine gland dysfunction that presents with a variety of symptoms, including keratoconjunctivitis sicca, xerostomia, and salivary gland swelling typically involving the parotid gland.

* Most diagnostic criteria rely on the presence of autoantibodies and the objective demonstration of salivary gland involvement through biopsy or imaging studies.

* Since autoantibodies may be normal early in the disease, biopsy is indicated for younger patients in whom the diagnosis is being entertained.

* Early diagnosis is essential because long-term surveillance for the development of malignant lymphoma is necessary.