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Sjogren’s Syndrome: The role of the lip biopsy

Dentists are, at times, approached by rheumatologists to perform a lip biopsy on a patient with dry mouth and dry eyes to rule out Sjogren’s Syndrome. Dry mouth is a common complaint from patients of all ages. It is particularly common in the elderly because of the physiologic fatty degeneration of the salivary glands and because of the many medications that they tend to use. Dry mouth is usually an objective complaint; the typical symptom is low saliva flow. It is sometimes more of a subjective complaint without supporting evidence determined by saliva flow; this is usually the case in patients with psychological symptoms. Dry mouth with low salivary flow has two primary causes: an adverse effect of a variety of medications (the most common cause), or a disease significantly affecting the salivary gland tissue. Many drugs are known to cause dry mouth, particularly anticholinergic and sympathomimetic drugs. The diseases associated with dry mouth include Sjogren’s syndrome, uncontrolled diabetes, sarcoidosis, AIDS and several others.

Sjögren's syndrome (SS) is a chronic inflammatory and immune-mediated disorder affecting multiple organs including the eyes, mouth, and the connective tissue. It is far more common in females than males; almost 90% of SS cases occur in females with a mean age of 50, although children have also been reported to develop this disease (1-2). It has been shown to be associated with histocompatibility antigens (HLA) HLA-DRW52 and HLA-B8 (3). Almost half of the patients complain of parotid gland enlargement, usually bilateral swelling, because of the lymphocytic infiltrate and damaged ductal architecture. These types of changes lead to the classic dye-pooling effect seen in sialography images (Fig1) where a “cherry blossom” or “fruit-laden, branchless tree” effect is described. SS can be classified into two types: primary (sicca syndrome involving eyes and mouth) and secondary (involving eyes, mouth and systemic diseases). Primary SS is characterized by dry eyes and dry mouth. Dry eyes are also called keratoconjuctivitis sicca or xerophthalmia, and dry mouth is also called xerostomia(1-3). The most common systemic diseases associated with secondary SS are rheumatoid arthritis and systemic lupus erythematosus.

Several national and international groups (California, Greek, Japan, Europe) produced clinical criteria for the diagnosis of SS; some are stricter than others. The California criteria are far more stringent than the European criteria (4). These include the clinical symptoms of dry eyes, with positive Schirmer’s and/or rose Bengal tests, symptomatic with decreased basal and stimulated salivary flow, abnormal lower lip biopsy with focus score of two or greater, and positive autoantibodies including Ro/SSA and/or La/SSB. Other antibodies can be used, such as the antinuclear antibodies and rheumatoid factor antibodies at 1:160 titer. To make a definitive SS diagnosis, all four factors should be positive.

Dentists and oral surgeons are often approached to perform a lip biopsy to rule out SS. This is one of the four important criteria used to establish the diagnosis of SS. Although a lip biopsy can prove to be an important diagnostic test in patients suspected to have SS, dentists should not rush to perform a lip biopsy until they have established by the other three criteria that SS is the likely diagnosis. This is particularly true for the elderly population. A lip biopsy may be more necessary in the younger population.

An ideal biopsy for SS is an incisional biopsy of normal lower lip mucosa without any evidence of trauma or ulceration. Around 4-6 salivary gland lobules should be submitted in 10% buffered formalin. The pathologist should identify the presence of clusters of lymphocytes of 50 or more cells per 4 mm2, often found in the central portion of the lobule. California criteria require two or more of these collections per 4 mm2 for a definitive diagnosis. Care should be exercised not to misinterpret sialadentis and parenchymal atrophy and fibrosis, scattered lymphocytes and plasma cells for a positive lip biopsy. When strict histologic criteria are used, lip biopsy can be very effective in diagnosing SS. Needless to say, the diagnosis of lip biopsies should be rendered by an experienced pathologist who is familiar with the pitfalls of this diagnosis (5).

In conclusion, minor salivary gland biopsy from the lower lip plays a significant role in the diagnosis of SS and its significance should not be underestimated. However, lip biopsy should be the last test performed in rendering the SS diagnosis, not the first. Serology is very important and should be performed before the lip biopsy. Also, etiologies other than SS should be ruled out first when patients present with dry eyes and dry mouth especially in the elderly population.

References

1. Vitali C, Bombadieri S et al. Classification criteria for Sjogren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis. 2002; 6: 554-558.
2. Daniels TE, Wu AJ. Xerostomia--clinical evaluation and treatment in general practice. J Calif Dent Assoc. 2000; 28: 933-941.
3. Miyagawa S. Clinical, serological and immunogenetic features of Japanese anti-Ro/SS-A-positive patients with annular erythema. Dermatology. 1994;189:11-13.
4. Fox RI, Saito, I. Criteria for diagnosis of Sjögren's syndrome. Rheum Dis Clin North Am 1994; 20:391-407.
5. Daniels TE. Labial salivary gland biopsy in Sjogren's syndrome. Assessment as a diagnostic criterion in 362 suspected cases. Arthritis Rheum. 1984; 27:147-156.

For questions or comments, please email Dolphine Oda at doda@washington.edu