Understanding Sjögren’s syndrome

Sjögren syndrome is a systemic multi-organ autoimmune disease that results in chronic inflammation. Progressive B-cell and T-cell infiltration of the exocrine organs primarily targets the lacrimal and salivary glands. This results in the classic presentation of dry eye and dry mouth symptoms. Eyecare providers and oral care providers are in a distinctive situation in which we may be the first to identify Sjögren patients.

Early diagnosis is important-coordination of care can begin with primary care, eye care, oral care, and rheumatology. Most clinicians see only a small part of the full picture of Sjögren, making the diagnosis difficult. This article gives an overview of systemic manifestations and complications. Knowing that it is not just a dry eye problem will stress the importance of identifying these patients early on.

Sjögren overview

Primary Sjögren syndrome is found in isolation while secondary Sjögren syndrome is in association with another systemic autoimmune disease. The most commonly associated autoimmune diseases are rheumatoid arthritis and systemic lupus erythematosus.¹

Related: Diagnosing and treating Sjögren's syndrome

The exact pathogenesis of Sjögren still remains unknown, but multiple theories have been proposed. Viruses have been implicated as triggers, particularly Epstein-Barr, Coxsackie, hepatitis C, and HIV.² Other potential etiologies include genetics, environment, and hormones-all resulting in chronic hyperactive stimulation of the immune system.

Sjögren syndrome is the second most common rheumatic disease after rheumatoid arthritis.³ About 2 to 4 million Americans have Sjögren. Most cases are undiagnosed because the clinical findings are nonspecific and span across many different specialties. The condition targets women more than men with a female-to-male ratio of 9:1, primarily affecting middle-aged women.⁴

Diagnosing the disease

The diagnosis of primary Sjögren can be made with different classification criteria. The most commonly used criteria is the American-European Consensus Group (AECG) classification (see Table 1). This classification system requires at least four of the signs and symptoms in addition to biopsy or antibody findings. If the patient has no symptoms, three out of four objective criteria must be met.

Related: Identify Sjögren’s patients with Sjö test

Secondary Sjögren is diagnosed when a symptom criteria is accompanied by one of the sign criteria in the presence of a connective tissue disease (see Table 2).⁵

The Sjögren International Collaborative Clinical Alliance (SICCA) classification requires two out of three criteria be met (see Table 3). This system attempts to eliminate subjectivity by removing any symptom criteria and using only objective tests.⁶

Both classification schemes rely on traditional biomarkers for anti-Ro/SSA and anti-La/SSB. New antibodies have been identified to occur earlier and even in the absence of traditional biomarkers anti-Ro/SSA and anti-La/SSB. Salivary gland protein 1 (SP-1), carbonic anhydrase 6 (CA6), and parotid secretory protein (PSP) antibodies may identify Sjögren earlier and even without anti-Ro/SSA and anti-La/SSB.⁷

Sjögren as a systemic disease

Along with the classic lacrimal and salivary gland involvement, Sjögren can commonly affect the parotid gland and many extraglandular tissues and organs. Musculoskeletal joint disease is typical. Primary Sjögren can be misdiagnosed as rheumatoid arthritis while secondary Sjögren patients may have underlying rheumatoid arthritis.

Related: Sjögren's requires an understanding beyond traditional symptoms

Other organs involved include the skin, lungs, and kidneys. Dry skin is found in more than half of Sjögren patients. Other cutaneous findings include rash, burning, vasculitis, ulcers, and discoloration.⁸ These findings can also be found in lupus and scleroderma, so they must be carefully differentiated.

Dry cough is common, but clinically significant respiratory manifestations affect only 10 percent of patients.⁹ The common symptoms of nasal crusting, epistaxis, recurrent sinusitis, dry cough, and dyspnea are caused by dry nose, dry trachea, small airway obstruction, and/or interstitial lung disease. These are likely caused by decreased mucous gland secretions.

The kidneys are often involved, with distal renal acidosis being the most frequent clinical presentation, but interstitial nephritis is the most damaging and may occur prior to any symptoms of dryness. Obvious clinical renal disease is detectable in approximately 5 percent of patients.¹⁰ Interstitial inflammation is caused by lymphocytic infiltration and leads to fibrosis and atrophy.

Approximately 70 percent of patients exhibit symptoms of fatigue. In primary Sjögren, the physical more than mental aspects of fatigue are more severe and frequent.¹¹ Fatigue and depression are found to be associated, possibly due to shared common underlying biological mechanisms. For some patients, the fatigue may be more bothersome than the drying symptoms. The thyroid is a plausible cause or contributor. Autoimmune thyroiditis occurs in about 20 percent of Sjögren patients,  including Hashimoto and Graves. Subclinical hypothyroidism is present greater than 50 percent of the time.¹²

Gastrointestinal manifestations can involve the entire tract. Dryness of the pharynx and esophagus with esophageal dysmotility, and gastritis can cause symptoms of nausea, dysphagia, or epigastric pains. Lymphoid infiltration results in chronic atrophic gastritis. Lab testing frequently shows mild autoimmune hepatitis and pancreatitis.¹³

Neurologic disease in Sjögren occurs in 2 percent to 60 percent of patients, with the most common significant presentation the peripheral nervous system with sensory involvement.¹⁴ Involvement of the peripheral nervous system includes sensorimotor polyneuropathy and polyradiculopathy, mononeuritis multiplex, autonomic neuropathy, and trigeminal and other cranial neuropathies. Central nervous system involvement is much less common-manifestations include multiple sclerosis-like changes, seizures, transverse myelitis, aseptic meningitis, optic neuritis, diffuse encephalopathy, and dementia.¹⁵

Related: Diagnosing Demodex

The main complication of Sjögren syndrome is development of lymphoma. Sjögren patients have a 10 to 50 times greater risk compared to the general population. Non-Hodgkin’s lymphoma occurs in two to 9 percent percent of Sjögren patients. The mean time from diagnosis of Sjögren to lymphoma is 7.5 years.¹⁶

Testing for Sjögren

Early diagnosis and management are important in Sjögren syndrome. A long delay may occur before diagnosis due to vagueness of symptoms, mimicking of various conditions, and symptoms being considered minor. This can lead to insidious progression and serious complications. Being aware of the disease state and its varied systemic presentations will help promote a more expansive approach to diagnosing the condition.

New diagnostics tests like Sjo (Bausch + Lomb) may help identify these patients. Like most diseases, timely treatment and management will improve quality of life and reduce complications. We started Sjo in office and trained a staff member to handle collection and paperwork. This system worked, but it would occupy staff time and the examination lane, slowing down office flow. Now both LabCorp and Quest are able to handle collection, so we send out 100 percent of test orders. These outside laboratories send results-but without detailed interpretation like Immco’s diagnostics laboratory. However, Bausch + Lomb offers a website to input test results for a more detailed explanation. I spend a little more time to interpret the results, but it saves a lot of office and staff resources.

Scott Han, OD, FAAO, is a partner and director of optometry in a multi-specialty group practice in Florida.

Dr. Han has no financial interests to disclose.

scottbhan@gmail.com

References

1. Peri Y, Agmon-Levin N, Theodor E, Shoenfeld Y: Sjögren’s syndrome, the old and the new. Best Practice and Research: Clinical Rheumatology. 2012, 26: 105-117.

2. Hansen A, Lipsky PE, Dorner T. New concepts in the pathogenesis of Sjögren syndrome: many questions, fewer answers. Current Opinion in Rheumatology. 2003; 15(5): 563–70.

3. Talal N. What is Sjögren ’s syndrome and why is it important?. Journal of Rheumatology. 2000; 27 (Suppl 61):1–2.

4. Mavragani CP, Moutsopoulos HM: The geoepidemiology of Sjögren’s syndrome. AutoimmunityRev. 2010, 9: A305-A310.

5. Tzioufas AG, Voulgarelis M. Update on Sjögren's syndrome autoimmune epithelitis: from classification to increased neoplasias. Best Practice and Research: Clinical Rheumatology. 2007 Dec. 21(6):989-1010.

6. Shiboski SC, Shiboski CH, Criswell L, Baer A, Challacombe S, Lanfranchi H, et al. American College of Rheumatology classification criteria for Sjögren's syndrome: a data-driven, expert consensus approach in the Sjögren's International Collaborative Clinical Alliance cohort. Arthritis Care and Research. 2012 Apr. 64(4):475-87.

7. Shen L, Suresh L, Lindemann M, et al. Novel autoantibodies in Sjögren’s syndrome. Clinical Immunology. 2012;145:251-255.

8. Kittridge A, Routhouska SB, Korman NJ: Dermatologic manifestations of Sjögren syndrome. Journal of Cutaneous Medicine and Surgery. 2011, 15: 8-14.

9. Hatron PY, Tillie-Leblond I, Launay D, Hachulla E, Fauchais AL, Wallaert B: Pulmonary manifestations of Sjögren’s syndrome. Presse Med. 2011, 40: e49-e64.

10. Bossini N, Savoldi S, Franceschini F, Mombelloni S, Baronio M, Cavazzana I, Viola BF, Valzorio B, Mazzucchelli C, Cattaneo R, Scolari F, Maiorca R: Clinical and morphological features of kidney involvement in primary Sjögren’s syndrome. Nephrology Dialysis Transplantation. 2001, 16: 2328-2336.

11. Ng WF, Bowman SJ: Primary Sjögren’s syndrome: too dry and too tired. Rheumatology. 2012, 49: 844-853.].

12. Mavragani CP, Fragoulis GE, Moutsopoulos HM: Endocrine alterations in primary Sjögren’s syndrome: an overview. Journal of Autoimmunity. 2012, 39: 354-358.

13.Ebert EC: Gastrointestinal and hepatic manifestations of Sjögren syndrome. Journal of Clinical Gastroenterology. 2012, 46: 25-30.

14. Garcia-Carrasco M, Ramos-Casals R, Rosas J, Pallares L, Calvo-Alen J, Cervera R, Font J, Ingelmo M: Primary Sjögren’s syndrome. Clinical and immunological disease patterns in a cohort of 400 patients. Medicine. 2002, 81: 270-280.

15.Chai J, Logigian EL: Neurological manifestations of primary Sjögren’s syndrome. Current Opinion Neurology. 2010, 23: 509-513.

16. Ramos-Casals M, Brito-Zeròn P, Sisò-Almirall A, Bosch X: Primary Sjögren syndrome. BMJ. 2012, 344: e3821.