Atypical presentations of Sjogren disease.

It has been more than 70 years since Swedish ophthalmologist, Henrik Sjogren, described the triad of xerophthalmia, parotid enlargement, and arthritis. Fifty years before that, Mikulicz noted a correlation between cellular destruction in the lacrimal and salivary glands with cellular infiltrates. Over the ensuing years, literally thousands of papers have been published on Sjogren syndrome (SS) and many diagnostic algorithms have been proposed. (1)

Dr. Ketan Kulkarni's paper, "An Unusual Presentation of Sjogren Syndrome," is notable as it presents a patient with the atypical presentation of the disorder as bilateral tender submandibular gland enlargement. Perhaps an alternate title could have been, "An Astute Clinician's Diagnosis of Sjogren Disease in Its Early Phases."

SS is estimated to have a prevalence as high as 1 to 3% of the general population, with the "textbook" presentation being a woman between 40 and 60 years of age. At the time of eventual diagnosis, it is frequently recognized that symptoms first manifested 8 to 10 years earlier and commonly include dry eyes (xerophthalmia) and/or dry mouth (xerostomia).

These two primary components of the sicca syndrome, xerophthalmia and xerostomia, are the hallmarks of Sjogren disease and are prominent in all major diagnostic criteria for the disorder. To address the presence of competing diagnostic criteria, a consensus panel met and published the diagnostic criteria seen in the Table. (2)

It is important to note that the consensus group specified early in their report that clinical observation is the criterion standard in diagnosis and that no set of diagnostic criteria can replace the acumen of an expert.

In the case report by Kulkarni, a 24-year-old woman without complaints of dry eye or mouth was diagnosed with Sjogren by biopsy of one of her submandibular glands, which had been progressively enlarging and tender. Minor salivary gland biopsy was unremarkable, but submandibular gland histopathology showed lymphoid hyperplasia without granulomas or signs of malignancy. An autoimmune basis was reinforced by positive rheumatoid factor, antinuclear antibody (ANA), and erythrocyte sedimentation rate. While this presentation is decidedly atypical in that it has been only rarely reported, it may simply be unrecognized. The very early manifestations of SS, before xerostomia and xerophthalmia, can include early tooth loss, sialochemistry alterations, salivary gland swelling, and paradoxically, sialorrhea. (3) The eventual development of xerostomia in Kulkarni's reported patient is heralded by her positive ANA as reduced salivary flow in patients with SS correlates directly with positive ANA and other immunologic indicators. (4) A significant negative, not provided in the history, would be the absence of silicone breast implants. For although controversial, some authors have postulated a correlation between these implants and the development of SS. (5)

Overall, approximately one-third of patients with SS will manifest salivary gland enlargement. However, a number of other manifestations may present which could be considered unusual in that they are not commonly considered as part of the diagnostic criteria. High frequency sensorineural hearing loss, hypothyroidism (particularly Hashimoto thyroiditis), and hoarseness due to a unique type of vocal fold nodule (called the bamboo node) are all associated with SS. In addition, epistaxis, nasal dryness, dry cough with shortness of breath, esophageal dysmotility, gastritis, interstitial nephritis, and dysuria have all been reported. Musculoskeletal, vascular, hematologic, and neurologic manifestations have also been described. (1)

The primary lesson of the Kulkarni paper is to consider SS as a potential diagnosis and to use good clinical judgment as a guide. This approach permitted SS to be diagnosed at a very early stage, thus allowing for proper monitoring and care of the young woman presented.

References

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

2. Vitali C, Bombardieri S, Jonsson R, et al. and the European Study Group on Classification Criteria for Sjogren's Syndrome. Classification criteria for Sjogren's syndrome: a revised version of the European criteria proposed by the American-European consensus group. Ann Rheum Dis 2002;61:554-558.

3. Mignogna MD, Fedele S, Russo LL, et al. Sjogren's syndrome: the diagnostic potential of early oral manifestations preceding hyposalivation/xerostomia. J Oral Pathol Med. 2005 Jan;34:1-6.

4. Haga HJ. Clinical and immunological factors associated with low lacrimal and salivary flow rate in patients with primary Sjogren's syndrome. J Rheumatol. 2002 Feb;29:305-308.

5. Contant CM, Swaak AJ, Obdeign AL, et al. A prospective study on silicone breast implants and the silicone-related symptom complex. Clin Rheumatol. 200221;215-219.

Faith is the strength by which a shattered world shall emerge into the
light.
--Helen Keller

Jeffrey H. Spiegel, MD, FACS 

From Boston University School of Medicine, Boston, MA.

Reprint requests to Jeffery H. Spiegel, MD, FACS, Associate Professor, Chief of Facial Plastic and Reconstructive Surgery, Boston University School of Medicine, 88 East Newton Street, Suite D-616, Boston, MA 02118. Email: [e-mail]

Table. 2002 European-American Consensus Group Diagnostic Criteria for
Sjogren syndrome (2)

Must have four of the following, including at least one of number 4 or
  number 6:
  1. Ocular symptoms -- subjective sense of dry eyes or use of tear
  substitutes more than three times a day.
  2. Oral symptoms -- subjective sense of dry mouth, recurrent or
  persistently swollen salivary glands, or frequent use of liquids to
  assist in swallowing foods.
  3. Ocular signs
  4. Schirmer I test without anesthetic ([less than or equal to] 5mm in
  5 minutes)
  5. Rose Bengal or ocular dry score of 4 or more
  6. Histopathologic symptoms -- focus score of 1 or higher
  ([greater than or equal to] 50 lymphocytes per 4 [mm.sup.2] in minor
  salivary gland biopsy)
  7. Salivary gland involvement -- positive results in one of the
  following tests:
    a. Salivary scintigraphy
    b. Unstimulated salivary flow rate of 1.5 mL or less in 15 minutes
    c. Parotid sialography showing diffuse sialectasis
    d. Autoantibodies--presence of antibodies to Ro (SS-A) or La (SS-B)
    or both
Exclusion criteria:
  1. Past head and neck radiation treatment
  2. Hepatitis C infection
  3. Acquired immunodeficiency syndrome
  4. Pre-existing lymphoma
  5. Sarcoidosis
  6. Graft-versus-host disease
  7. Use of anticholinergic drugs (in a time frame shorter than four
  times the half life of the agent)